GMP-Grade mRNA Electroporation of Dendritic Cells for Clinical Use.

PubMed

Derdelinckx, Judith; Berneman, Zwi N; Cools, Nathalie

2016-01-01

mRNA-electroporated dendritic cells (DC) are demonstrating clinical benefit in patients in many therapeutic areas, including cancer and infectious diseases. According to current good manufacturing guidelines, cell-based medicinal products have to be defined for identity, purity, potency, stability, and viability. In order to comply with the directives and guidelines defined by the regulatory authorities, we report here a standardized and reproducible method for the manufacturing of clinical-grade mRNA-transfected DC.

Applications of pharmacogenomics in regulatory science: a product life cycle review.

PubMed

Tan-Koi, W C; Leow, P C; Teo, Y Y

2018-05-22

With rapid developments of pharmacogenomics (PGx) and regulatory science, it is important to understand the current PGx integration in product life cycle, impact on clinical practice thus far and opportunities ahead. We conducted a cross-sectional review on PGx-related regulatory documents and implementation guidelines in the United States and Europe. Our review found that although PGx-related guidance in both markets span across the entire product life cycle, the scope of implementation guidelines varies across two continents. Approximately one-third of Food and Drug Administration (FDA)-approved drugs with PGx information in drug labels and half of the European labels posted on PharmGKB website contain recommendations on genetic testing. The drugs affected 19 and 15 World Health Organization Anatomical Therapeutic Chemical drug classes (fourth level) in the United States and Europe, respectively, with protein kinase inhibitors (13 drugs in the United States and 16 drugs in Europe) being most prevalent. Topics of emerging interest were novel technologies, adaptive design in clinical trial and sample collection.

[Draft of Guidelines for Human Body Dissection for Clinical Anatomy Education and Research and commentary].

PubMed

Shichinohe, Toshiaki; Kondo, Satoshi; Ide, Chizuka; Higuchi, Norio; Aiso, Sadakazu; Sakai, Tatsuo; Matsumura, George; Yoshida, Kazunari; Kobayashi, Eiji; Tatsumi, Haruyuki; Yaginuma, Hiroyuki; Hishikawa, Shuji; Sugimoto, Maki; Izawa, Yoshimitsu; Imanishi, Nobuaki

2011-07-01

This article analyses the Draft of Guidelines for Human Body Dissection for Clinical Anatomy Education and Research drawn by the Study Group for Future Training Systems of Surgical Skills and Procedures established by the Fiscal Year 2010 research program of the Ministry of Health, Labor and Welfare. The purpose of the Draft of Guidelines is: First, to lay out the required basic guidelines for human cadaver usage to allow medical and dental faculty to conduct clinical education and research in accordance with existing regulations. Second, the guidelines are expected to give physicians a regulatory framework to carry out cadaver training in accordance with the current legal framework. This article explains the Draft of Guidelines in detail, outlines the future of cadaver training, and describes issues which must still be solved.

[Draft of guidelines for human body dissection for clinical anatomy education and research and commentary].

PubMed

Shichinohe, Toshiaki; Kondo, Satoshi; Ide, Chizuka; Higuchi, Norio; Aiso, Sadakazu; Sakai, Tatsuo; Matsumura, George; Yoshida, Kazunari; Kobayashi, Eiji; Tatsumi, Haruyuki; Yaginuma, Hiroyuki; Hishikawa, Shuji; Sugimoto, Maki; Izawa, Yoshimitsu; Imanishi, Nobuaki

2011-06-01

This article analyses the Draft of Guidelines for Human Body Dissection for Clinical Anatomy Education and Research drawn by the Study Group for Future Training Systems of Surgical Skills and Procedures established by the Fiscal Year 2010 research program of the Ministry of Health, Labor and Welfare. The purpose of the Draft of Guidelines is: First, to lay out the required basic guidelines for human cadaver usage to allow medical and dental faculty to conduct clinical education and research in accordance with existing regulations. Second, the guidelines are expected to give physicians a regulatory framework to carry out cadaver training in accordance with the current legal framework. This article explains the Draft of Guidelines in detail, outlines the future of cadaver training, and describes issues which must still be solved.

European Ethnopharmaceuticals for Self-Medication in Japan: Review Experience of Vitis vinifera L., Folium Extract and Vitex agnus-castus L., Fructus Extract as OTC Drugs.

PubMed

Hoshino, Tatsuro; Muto, Nanami; Tsukada, Shinsuke; Nakamura, Takatoshi; Maegawa, Hikoichiro

2018-01-06

Since the publication of "Application Guideline for Western Traditional Herbal Medicines as OTC Drugs" in 2007, only two European ethnopharmaceuticals, Vitis vinifera L., folium extract (Antistax) and Vitex agnus-castus L., fructus extract (Prefemin), have been approved as OTC drugs in Japan. In this review, we describe the current regulation of Western ethnopharmaceuticals in Japan, summarize our regulatory experiences and discuss the scientific and regulatory issues involved.

European Ethnopharmaceuticals for Self-Medication in Japan: Review Experience of Vitis vinifera L., Folium Extract and Vitex agnus-castus L., Fructus Extract as OTC Drugs

PubMed Central

Hoshino, Tatsuro; Muto, Nanami; Tsukada, Shinsuke; Nakamura, Takatoshi; Maegawa, Hikoichiro

2018-01-01

Since the publication of “Application Guideline for Western Traditional Herbal Medicines as OTC Drugs” in 2007, only two European ethnopharmaceuticals, Vitis vinifera L., folium extract (Antistax) and Vitex agnus-castus L., fructus extract (Prefemin), have been approved as OTC drugs in Japan. In this review, we describe the current regulation of Western ethnopharmaceuticals in Japan, summarize our regulatory experiences and discuss the scientific and regulatory issues involved. PMID:29316611

ISOTONIC DOSE-RESPONSE MODELING OF THE TRANSCRIPTIONAL RESPONSE OF RAT CEREBROCORTICAL TISSUE AFTER ACUTE PYRETHROID EXPOSURE IN VIVO.

EPA Science Inventory

Pyrethroid insecticides produce neurotoxicity in mammals by disrupting ion channel function in excitable nerve membranes. Pyrethroid use has increased as regulatory guidelines have restricted the use of other pesticide classes. Currently, a sensitive, specific, and dose-responsiv...

Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement.

PubMed

Reginster, J-Y; Reiter-Niesert, S; Bruyère, O; Berenbaum, F; Brandi, M-L; Branco, J; Devogelaer, J-P; Herrero-Beaumont, G; Kanis, J; Maggi, S; Maheu, E; Richette, P; Rizzoli, R; Cooper, C

2015-12-01

The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process. It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing). This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A qualitative study of the determinants of HIV guidelines implementation in two south-eastern districts of Tanzania

PubMed Central

Geubbels, Eveline; Wringe, Alison; Todd, Jim; Klatser, Paul; Dieleman, Marjolein

2017-01-01

Abstract Current HIV policies in Tanzania have adopted the three long-term impact results of zero new infections, zero HIV deaths and zero stigma and discrimination. Strategies to reach these results include scaling-up HIV Testing and Counselling (HTC); Preventing Mother-To-Child Transmission (PMTCT); and strengthening Care and Treatment Clinic (CTC) services. Previous studies showed that HIV policy and guideline recommendations were not always implemented in rural South Tanzania. This study aims to identify the determinants of HIV guideline implementation. A qualitative study of 23 semi-structured interviews with facility in-charges; healthcare workers; district, regional and national HIV coordinators was conducted. Five health facilities were purposively selected by level, ownership and proximity to district headquarters. Interviews were analysed according to Fleuren’s five determinants of innovation uptake related to: strategies used in guideline development and dissemination; guideline characteristics; the guideline implementing organization; guideline users; and the socio-cultural and regulatory context. None of the facilities had the HTC national guideline document. Non-involvement of providers in revisions and weak planning for guideline dissemination impeded their implementation. Lengthy guidelines and those written in English were under-used, and activities perceived to be complicated, like WHO-staging, were avoided. Availability of staff and lack of supplies like test kits and medication impeded implementation. Collaboration between facilities enhanced implementation, as did peer-support among providers. Provider characteristics including education level, knowledge of, and commitment to the guideline influenced implementation. According to providers, determinants of clients’ service use included gender norms, stigma, trust and perceived benefits. The regulatory context prohibited private hospitals from buying HIV supplies. Being tools for bringing policies to practice, national guidelines are crucial in the efforts towards the three zeros. Strategies to improve providers’ adherence to guidelines should include development of clearer guideline dissemination plans, strengthening of the health system, and possibly addressing of provider-perceived patient-level barriers to utilizing HIV services. PMID:28369374

75 FR 36756 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... existing paragraph (b)(4) of the Rule, entitled ``Numerical Guidelines Applicable to Volatile Market Opens... existing paragraph (b)(2), which provides flexibility to FINRA to use different Numerical Guidelines or... of paragraph (b)(4) (``Numerical Guidelines Applicable to Volatile Market Opens'') of the existing...

Do you know the fair market value of quality?

PubMed

Johnson, Jen

2009-10-01

To develop a physician compensation package that includes fair-market-value incentive payments for their efforts to improve healthcare quality, a hospital first needs to: Evaluate current market data on quality incentive payments. Be familiar with the existing regulatory guidelines related to paying for quality. Understand the requirements for complying with the regulations.

Development of an alternative testing strategy for the fish early life-stage (FELS) test using the AOP framework

EPA Science Inventory

Currently, the fish early life-stage (FELS) test (OECD 210) is the primary guideline used to estimate chronic toxicity of regulated chemicals. Although already more cost-efficient than adult fish tests, the FELS test has some important drawbacks. Both industry and regulatory inst...

Biosafety, risk assessment and regulation of plant-made pharmaceuticals.

PubMed

Sparrow, Penelope A C; Twyman, Richard M

2009-01-01

The technology for plant-made pharmaceuticals (PMPs) has progressed significantly over the last few years, with the first commercial products for human use expected to reach the market by 2009 (see Note 1). As part of the 'next generation' of genetically modified (GM) crops, PMPs will be subject to additional biosafety considerations and are set to challenge the complex and overlapping regulations that currently govern GM plants, plant biologics (see Note 2) and 'conventional' pharmaceutical production. The areas of responsibility are being mapped out between the different regulatory agencies (Sparrow, P.A.C., Irwin, J., Dale, P., Twyman, R.M., and Ma, J.K.C. (2007) Pharma-Planta: Road testing the developing regulatory guidelines for plant-made pharmaceuticals. Transgenic Res., 2007), with specific guidelines currently being drawn up for the regulation of PMPs. In this chapter, we provide an overview of the biosafety (see Note 3), risk assessment (see Note 4) and regulation of this emerging technology. While reference will be made to EU regulations, the underlying principles of biosafety and risk assessment are generic to most countries.

Clinical development of gene therapy needs a tailored approach: a regulatory perspective from the European Union.

PubMed

Narayanan, Gopalan; Cossu, Giulio; Galli, Maria Cristina; Flory, Egbert; Ovelgonne, Hans; Salmikangas, Paula; Schneider, Christian K; Trouvin, Jean-Hugues

2014-03-01

Gene therapy is a rapidly evolving field that needs an integrated approach, as acknowledged in the concept article on the revision of the guideline on gene transfer medicinal products. The first gene therapy application for marketing authorization was approved in the International Conference on Harmonisation (ICH) region in 2012, the product being Alipogene tiparvovec. The regulatory process for this product has been commented on extensively, highlighting the challenges posed by such a novel technology. Here, as current or previous members of the Committee for Advanced Therapies, we share our perspectives and views on gene therapy as a treatment modality based on current common understanding and regulatory experience of gene therapy products in the European Union to date. It is our view that a tailored approach is needed for a given gene therapy product in order to achieve successful marketing authorization.

Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries.

PubMed

Tomlinson, Lindsay; Boone, Laura I; Ramaiah, Lila; Penraat, Kelley A; von Beust, Barbara R; Ameri, Mehrdad; Poitout-Belissent, Florence M; Weingand, Kurt; Workman, Heather C; Aulbach, Adam D; Meyer, Dennis J; Brown, Diane E; MacNeill, Amy L; Bolliger, Anne Provencher; Bounous, Denise I

2013-09-01

The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. © 2013 American Society for Veterinary Clinical Pathology.

Brownfield site development -- The Ontario context

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, D.B.

The provincial government of Ontario recently promulgated new guidelines to deal with contamination on sites. One of the purposes of the guideline was to bolster development of contaminated sites by clarifying the regulatory process for redeveloping a contaminated site and to provide several clean-up options based on newer scientific information. These clean-up options include stratified clean-ups and site specific risk based criteria. The applications of the previous guideline were at times cumbersome for industries and land developers which may have impeded development of the Brownfield. This paper compares the changes between the old and the new regulatory clean-up guidelines andmore » presents the differences in approach. This paper also presents the results from interviews with several industries and property developers and assesses their view on the regulatory change as well as their desire to develop Brownfields in Ontario. This information determines if the change in regulatory process has really encouraged development. Results from the interviews with proponents indicated that the new guidelines are a much better approach but still contain barriers such as liability issues. Furthermore, the regulatory approval process has been transferred from the provincial government to the local governments. As a result the local governments are applying the guidelines differently across the province.« less

Recommendations for harmonization of data collection and analysis of developmental neurotoxicity endpoints in regulatory guideline studies: Proceedings of workshops presented at Society of Toxicology and joint Teratology Society and Neurobehavioral Teratology Society meetings.

PubMed

Li, Abby A; Sheets, Larry P; Raffaele, Kathleen; Moser, Virginia; Hofstra, Angela; Hoberman, Alan; Makris, Susan L; Garman, Robert; Bolon, Brad; Kaufmann, Wolfgang; Auer, Roland; Lau, Edmund; Vidmar, Thomas; Bowers, Wayne J

2017-09-01

The potential for developmental neurotoxicity (DNT) of environmental chemicals may be evaluated using specific test guidelines from the US Environmental Protection Agency or the Organisation for Economic Cooperation and Development (OECD). These guidelines generate neurobehavioral, neuropathological, and morphometric data that are evaluated by regulatory agencies globally. Data from these DNT guideline studies, or the more recent OECD extended one-generation reproductive toxicity guideline, play a pivotal role in children's health risk assessment in different world areas. Data from the same study may be interpreted differently by regulatory authorities in different countries resulting in inconsistent evaluations that may lead to inconsistencies in risk assessment decisions internationally, resulting in regional differences in public health protection or in commercial trade barriers. These issues of data interpretation and reporting are also relevant to juvenile and pre-postnatal studies conducted more routinely for pharmaceuticals and veterinary medicines. There is a need for development of recommendations geared toward the operational needs of the regulatory scientific reviewers who apply these studies in risk assessments, as well as the scientists who generate DNT data sets. The workshops summarized here draw upon the experience of the authors representing government, industry, contract research organizations, and academia to discuss the scientific issues that have emerged from diverse regulatory evaluations. Although various regulatory bodies have different risk management decisions and labeling requirements that are difficult to harmonize, the workshops provided an opportunity to work toward more harmonized scientific approaches for evaluating DNT data within the context of different regulatory frameworks. Five speakers and their coauthors with neurotoxicology, neuropathology, and regulatory toxicology expertise discussed issues of variability, data reporting and analysis, and expectations in DNT data that are encountered by regulatory authorities. In addition, principles for harmonized evaluation of data were suggested using guideline DNT data as case studies. Copyright © 2017. Published by Elsevier Inc.

Good manufacturing practices for medicinal products for human use.

PubMed

Gouveia, Bruno G; Rijo, Patrícia; Gonçalo, Tânia S; Reis, Catarina P

2015-01-01

At international and national levels, there are public and private organizations, institutions and regulatory authorities, who work and cooperate between them and with Pharmaceutical Industry, in order to achieve a consensus of the guidelines and laws of the manufacturing of medicinal products for human use. This article includes an explanation of how operate and cooperate these participants, between them and expose the current regulations, following the line of European Community/European Economic Area, referencing, wherever appropriate, the practiced guidelines, outside of regulatory action of space mentioned. In this way, it is intended to achieve quality, security and effectiveness exceptional levels in the manufacturing of health products. Good Manufacturing Practice aim the promotion of the human health and consequently, to the improvement of quality of life. For achieve the proposed objectives, it is necessary to ensure the applicability of the presented concepts and show the benefits arising from this applicability.

Good manufacturing practices for medicinal products for human use

PubMed Central

Gouveia, Bruno G.; Rijo, Patrícia; Gonçalo, Tânia S.; Reis, Catarina P.

2015-01-01

At international and national levels, there are public and private organizations, institutions and regulatory authorities, who work and cooperate between them and with Pharmaceutical Industry, in order to achieve a consensus of the guidelines and laws of the manufacturing of medicinal products for human use. This article includes an explanation of how operate and cooperate these participants, between them and expose the current regulations, following the line of European Community/European Economic Area, referencing, wherever appropriate, the practiced guidelines, outside of regulatory action of space mentioned. In this way, it is intended to achieve quality, security and effectiveness exceptional levels in the manufacturing of health products. Good Manufacturing Practice aim the promotion of the human health and consequently, to the improvement of quality of life. For achieve the proposed objectives, it is necessary to ensure the applicability of the presented concepts and show the benefits arising from this applicability. PMID:25883511

[Collaborative study on regulatory science for facilitating clinical development of gene therapy products for genetic diseases].

PubMed

Uchida, Eriko; Igarashi, Yuka; Sato, Yoji

2014-01-01

Gene therapy products are expected as innovative medicinal products for intractable diseases such as life-threatening genetic diseases and cancer. Recently, clinical developments by pharmaceutical companies are accelerated in Europe and the United States, and the first gene therapy product in advanced countries was approved for marketing authorization by the European Commission in 2012. On the other hand, more than 40 clinical studies for gene therapy have been completed or ongoing in Japan, most of them are conducted as clinical researches by academic institutes, and few clinical trials have been conducted for approval of gene therapy products. In order to promote the development of gene therapy products, revision of the current guideline and/or preparation of concept paper to address the evaluation of the quality and safety of gene therapy products are necessary and desired to clearly show what data should be submitted before First-in-Human clinical trials of novel gene therapy products. We started collaborative study with academia and regulatory agency to promote regulatory science toward clinical development of gene therapy products for genetic diseases based on lentivirus and adeno-associated virus vectors; National Center for Child Health and Development (NCCHD), Nippon Medical School and PMDA have been joined in the task force. At first, we are preparing pre-draft of the revision of the current gene therapy guidelines in this project.

Development and assessment of disinfectant efficacy test methods for regulatory purposes.

PubMed

Tomasino, Stephen F

2013-05-01

The United States Environmental Protection Agency regulates pesticidal products, including products with antimicrobial activity. Test guidelines have been established to inform manufacturers of which methodology is appropriate to support a specific efficacy claim. This paper highlights efforts designed to improve current methods and the development and assessment of new test methods. Published by Mosby, Inc.

Health claims on food products in Southeast Asia: regulatory frameworks, barriers, and opportunities.

PubMed

Tan, Karin Y M; van der Beek, Eline M; Chan, M Y; Zhao, Xuejun; Stevenson, Leo

2015-09-01

The Association of Southeast Asian Nations aims to act as a single market and allow free movement of goods, services, and manpower. The purpose of this article is to present an overview of the current regulatory framework for health claims in Southeast Asia and to highlight the current barriers and opportunities in the regulatory frameworks in the Association of Southeast Asian Nations. To date, 5 countries in Southeast Asia, i.e., Indonesia, Malaysia, the Philippines, Singapore, and Thailand, have regulations and guidelines to permit the use of health claims on food products. There are inconsistencies in the regulations and the types of evidence required for health claim applications in these countries. A clear understanding of the regulatory frameworks in these countries may help to increase trade in this fast-growing region and to provide direction for the food industry and the regulatory community to develop and market food products with better nutritional quality tailored to the needs of Southeast Asian consumers. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Challenges in orphan drug development and regulatory policy in China.

PubMed

Cheng, Alice; Xie, Zhi

2017-01-18

While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

A qualitative study of the determinants of HIV guidelines implementation in two south-eastern districts of Tanzania.

PubMed

Mwangome, Mary N; Geubbels, Eveline; Wringe, Alison; Todd, Jim; Klatser, Paul; Dieleman, Marjolein

2017-07-01

Current HIV policies in Tanzania have adopted the three long-term impact results of zero new infections, zero HIV deaths and zero stigma and discrimination. Strategies to reach these results include scaling-up HIV Testing and Counselling (HTC); Preventing Mother-To-Child Transmission (PMTCT); and strengthening Care and Treatment Clinic (CTC) services. Previous studies showed that HIV policy and guideline recommendations were not always implemented in rural South Tanzania. This study aims to identify the determinants of HIV guideline implementation. A qualitative study of 23 semi-structured interviews with facility in-charges; healthcare workers; district, regional and national HIV coordinators was conducted. Five health facilities were purposively selected by level, ownership and proximity to district headquarters. Interviews were analysed according to Fleuren's five determinants of innovation uptake related to: strategies used in guideline development and dissemination; guideline characteristics; the guideline implementing organization; guideline users; and the socio-cultural and regulatory context. None of the facilities had the HTC national guideline document. Non-involvement of providers in revisions and weak planning for guideline dissemination impeded their implementation. Lengthy guidelines and those written in English were under-used, and activities perceived to be complicated, like WHO-staging, were avoided. Availability of staff and lack of supplies like test kits and medication impeded implementation. Collaboration between facilities enhanced implementation, as did peer-support among providers. Provider characteristics including education level, knowledge of, and commitment to the guideline influenced implementation. According to providers, determinants of clients' service use included gender norms, stigma, trust and perceived benefits. The regulatory context prohibited private hospitals from buying HIV supplies. Being tools for bringing policies to practice, national guidelines are crucial in the efforts towards the three zeros. Strategies to improve providers' adherence to guidelines should include development of clearer guideline dissemination plans, strengthening of the health system, and possibly addressing of provider-perceived patient-level barriers to utilizing HIV services. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

PubMed

Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

2016-03-01

Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory guidance should be reevaluated to assure consistent safety and efficacy among different strengths.

Establishing a Quality Control System for Stem Cell-Based Medicinal Products in China

PubMed Central

2015-01-01

Stem cell-based medicinal products (SCMPs) are emerging as novel therapeutic products. The success of its development depends on the existence of an effective quality control system, which is constituted by quality control technologies, standards, reference materials, guidelines, and the associated management system in accordance with regulatory requirements along product lifespan. However, a worldwide, effective quality control system specific for SCMPs is still far from established partially due to the limited understanding of stem cell sciences and lack of quality control technologies for accurately assessing the safety and biological effectiveness of SCMPs before clinical use. Even though, based on the existing regulations and current stem cell sciences and technologies, initial actions toward the goal of establishing such a system have been taken as exemplified by recent development of new “interim guidelines” for governing quality control along development of SCMPs and new development of the associated quality control technologies in China. In this review, we first briefly introduced the major institutions involved in the regulation of cell substrates and therapeutic cell products in China and the existing regulatory documents and technical guidelines used as critical references for developing the new interim guidelines. With focus only on nonhematopoietic stem cells, we then discussed the principal quality attributes of SCMPs as well as our thinking of proper testing approaches to be established with relevant evaluation technologies to ensure all quality requirements of SCMPs along different manufacturing processes and development stages. At the end, some regulatory and technical challenges were also discussed with the conclusion that combined efforts should be taken to promote stem cell regulatory sciences to establish the effective quality control system for SCMPs. PMID:25471126

75 FR 1734 - Children’s Online Privacy Protection Rule Safe Harbor Proposed Self-Regulatory Guidelines; i-SAFE...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

...The Federal Trade Commission publishes this notice and request for public comment concerning proposed self-regulatory guidelines submitted by i-SAFE, Inc. under the safe harbor provision of the Children's Online Privacy Protection Rule.

Privacy and Biobanking in China: A Case of Policy in Transition.

PubMed

Chen, Haidan; Chan, Benny; Joly, Yann

2015-01-01

Disease-based biobanks have operated in hospitals and research institutes in China for decades, and China has recently embarked on a plan to establish further biobank networks with the aim of promoting data sharing among the existing biobanks. Although the Chinese Constitution has only recently begun to recognize individual privacy as a distinct and independent constitutional right, biobanking in China has been loosely regulated under a patchwork of sometimes overlapping laws (such as the Interim Measures for the Administration of Human Genetic Resources) and regulatory instruments, as well as and the policies of individual biobanks and networks of biobanks (such as the Shanghai Biobank Network Guidelines). A Draft Ordinance on Human Genetics Resources is currently being developed that will deal in more detail than previous laws with issues such as management measures, legal liability, and punishment for violations. International data sharing will be tightly regulated under this new law, and individual biobanks' policies such as the Shanghai Guidelines may choose to regulate such sharing even more. In contrast with national regulatory instruments, the Shanghai Guidelines also contain detailed de-identification policies, and explicitly endorse broad consent. © 2015 American Society of Law, Medicine & Ethics, Inc.

Impacts on State and Local Agencies for Maintaining Traffic Signs within Minimum Retroreflectivity Guidelines

DOT National Transportation Integrated Search

1998-04-01

The Federal Highway Administration (FHWA) has developed guidelines for minimum retroreflectivity levels for four groups of signs: 1) yellow/orange-on-black warning signs, 2) black-on-white regulatory signs, 3) white-on-red regulatory signs, and 4) wh...

Wind/Tornado Guidelines Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, D.S.; Holman, G.S.

1991-10-01

This report documents the strategy employed to develop recommended wind/tornado hazard design guidelines for a New Production Reactor (NRP) currently planned for either the Idaho National Engineering Laboratory (INEL) or the Savannah River (SR) site. The Wind/Tornado Working Group (WTWG), comprising six nationally recognized experts in structural engineering, wind engineering, and meteorology, formulated an independent set of guidelines based on site-specific wind/tornado hazard curves and state-of-the-art tornado missile technology. The basic philosophy was to select realistic wind and missile load specifications, and to meet performance goals by applying conservative structural response evaluation and acceptance criteria. Simplified probabilistic risk analyses (PRAs)more » for wind speeds and missile impact were performed to estimate annual damage risk frequencies for both the INEL and SR sites. These PRAs indicate that the guidelines will lead to facilities that meet the US Department of Energy (DOE) design requirements and that the Nuclear Regulatory Commission guidelines adopted by the DOE for design are adequate to meet the NPR safety goals.« less

Effluent quality from 200 on-site sewage systems: design values for guidelines.

PubMed

Charles, K J; Ashbolt, N J; Roser, D J; McGuinness, R; Deere, D A

2005-01-01

The quality of effluent from an on-site sewage treatment system is a critical factor in designing the disposal area and, hence, ensuring the sustained performance of the system. Contaminant concentrations in effluent are typically specified in regulatory guidelines or standards; however, the accuracy of these guideline values are brought into question due to the poor performance of septic tanks and the high failure rates of disposal systems reported here and elsewhere. Results from studies of septic tank effluent quality indicated that the effluent is of poorer quality than currently suggested by guidelines. Aerated wastewater treatment systems were found to perform to accreditation guidelines; however, insufficient nutrient data is presently available to assess nutrient loads. It is proposed that the 80th percentile of system performance be adopted as the design value for sizing effluent disposal areas to minimise failure associated with overloading. For septic tanks this equates to 660 mg L(-1) SS, 330 mg L(-1) BOD, 250 mg L(-1) TN and 36 mg L(-1) TP.

In honor of the Teratology Society's 50th anniversary: The role of Teratology Society members in the development and evolution of in vivo developmental toxicity test guidelines.

PubMed

Tyl, Rochelle W

2010-06-01

Members of the Teratology Society (established in 1960) were involved in the first governmental developmental and reproductive toxicity testing guidelines (1966) by FDA following the thalidomide epidemic, followed by other national and international governmental testing guidelines. The Segment II (developmental toxicity) study design, described in rodents and rabbits, has evolved with additional enhanced endpoints and better descriptions, mechanistic insights, range-finding studies, and toxico/pharmacokinetic ADME information (especially for pharmaceuticals). Society members were also involved in the development of the current screening assays and tests for endocrine disruptors (beginning in 1996) and are now involved with developing new testing guidelines (e.g., the extended one-generation protocol), and evaluating the current test guidelines and new initiatives under ILSI/HESI sponsorship. New initiatives include ToxCast from the U.S. EPA to screen, prioritize, and predict toxic chemicals by high throughput and high-content in vitro assays, bioinformation, and modeling to reduce (or eliminate) in vivo whole animal studies. Our Society and its journal have played vital roles in the scientific and regulatory accomplishments in birth defects research over the past 50 years and will continue to do so in the future. Happy 50th anniversary! (c) 2010 Wiley-Liss, Inc.

Workshop on problem areas associated with developing carcinogen guidelines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1984-06-01

A workshop was conducted to discuss problem areas associated with developing carcinogen guidelines. Session topics included (1) definition of a carcinogen for regulatory purposes; (2) potency; (3) risk assessment; (4) uncertainties; (5) de minimis quantity; and (6) legal and regulatory issues. Separate abstracts have been prepared for individual papers. (ACR)

The Council for International Organizations and Medical Sciences (CIOMS) guidelines on ethics of clinical trials.

PubMed

Macrae, Duncan J

2007-05-01

Numerous bodies from many countries, including governments, government regulatory departments, research organizations, medical professional bodies, and health care providers, have issued guidance or legislation on the ethical conduct of clinical trials. It is possible to trace the development of current guidelines back to the post-World War II Nuremburg war crimes trials, more specifically the "Doctors' Trial." From that trial emerged the Nuremburg Code, which set out basic principles to be observed when conducting research involving human subjects and which subsequently formed the basis for comprehensive international guidelines on medical research, such as the Declaration of Helsinki. Most recently, the Council for International Organizations and Medical Sciences (CIOMS) produced detailed guidelines (originally published in 1993 and updated in 2002) on the implementation of the principles outlined in the Declaration of Helsinki. The CIOMS guidelines set in an appropriate context the challenges of present-day clinical research, by addressing complex issues including HIV/AIDS research, availability of study treatments after a study ends, women as research subjects, safeguarding confidentiality, compensation for adverse events, as well guidelines on consent.

[Regulatory requirements regarding cell-based medicinal products for human and veterinary use - a comparison].

PubMed

Kuhlmann-Gottke, Johanna; Duchow, Karin

2015-11-01

At present, there is no separate regulatory framework for cell-based medicinal products (CBMP) for veterinary use at the European or German level. Current European and national regulations exclusively apply to the corresponding medicinal products for human use. An increasing number of requests for the regulatory classification of CBMP for veterinary use, such as allogeneic stem cell preparations and dendritic cell-based autologous tumour vaccines, and a rise in scientific advice for companies developing these products, illustrate the need for adequate legislation. Currently, advice is given and decisions are made on a case-by-case basis regarding the regulatory classification and authorisation requirements.Since some of the CBMP - in particular in the area of stem-cell products - are developed in parallel for human and veterinary use, there is an urgent need to create specific legal definitions, regulations, and guidelines for these complex innovative products in the veterinary sector as well. Otherwise, there is a risk that that the current legal grey area regarding veterinary medicinal products will impede therapeutic innovations in the long run. A harmonised EU-wide approach is desirable. Currently the European legislation on veterinary medicinal products is under revision. In this context, veterinary therapeutics based on allogeneic cells and tissues will be defined and regulated. Certainly, the legal framework does not have to be as comprehensive as for human CBMP; a leaner solution is conceivable, similar to the special provisions for advanced-therapy medicinal products laid down in the German Medicines Act.

Status of market, regulation and research of genetically modified crops in Chile.

PubMed

Sánchez, Miguel A; León, Gabriel

2016-12-25

Agricultural biotechnology and genetically modified (GM) crops are effective tools to substantially increase productivity, quality, and environmental sustainability in agricultural farming. Furthermore, they may contribute to improving the nutritional content of crops, addressing needs related to public health. Chile has become one of the most important global players for GM seed production for counter-season markets and research purposes. It has a comprehensive regulatory framework to carry out this activity, while at the same time there are numerous regulations from different agencies addressing several aspects related to GM crops. Despite imports of GM food/feed or ingredients for the food industry being allowed without restrictions, Chilean farmers are not using GM seeds for farming purposes because of a lack of clear guidelines. Chile is in a rather contradictory situation about GM crops. The country has invested considerable resources to fund research and development on GM crops, but the lack of clarity in the current regulatory situation precludes the use of such research to develop new products for Chilean farmers. Meanwhile, a larger scientific capacity regarding GM crop research continues to build up in the country. The present study maps and analyses the current regulatory environment for research and production of GM crops in Chile, providing an updated overview of the current status of GM seeds production, research and regulatory issues. Copyright © 2016 Elsevier B.V. All rights reserved.

The emergence and popularisation of autologous somatic cellular therapies in Australia: therapeutic innovation or regulatory failure?

PubMed

McLean, Alison K; Stewart, Cameron; Kerridge, Ian

2014-09-01

Private stem cell clinics throughout Australia are providing autologous stem cell therapies for a range of chronic and debilitating illnesses despite the lack of published literature to support the clinical application of these therapies. The Therapeutic Goods Administration has excluded autologous stem cell therapies from its regulatory domain leaving such therapies to be regulated by the same mechanisms that regulate research, such as the National Health and Medical Research Council Research Ethics Guidelines, and clinical practice, such as the Australian Health Practitioner Regulation Agency. However, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advance--therapeutic innovation or research. The current regulatory framework is failing to achieve its aims of protecting vulnerable patients and ensuring the proper conduct of medical practitioners in the private stem cell industry.

Biosimilars for psoriasis: worldwide overview of regulatory guidelines, uptake and implications for dermatology clinical practice.

PubMed

Cohen, A D; Wu, J J; Puig, L; Chimenti, S; Vender, R; Rajagopalan, M; Romiti, R; de la Cruz, C; Skov, L; Zachariae, C; Young, H S; Foley, P; van der Walt, J M; Naldi, L; Prens, E P; Blauvelt, A

2017-12-01

The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies. © 2017 British Association of Dermatologists.

Curriculum Guidelines & Regulatory Criteria for Family Nurse Practitioners Seeking Prescriptive Authority To Manage Pharmacotherapeutics in Primary Care. Summary Report 1998.

ERIC Educational Resources Information Center

National Council of State Boards of Nursing, Chicago, IL.

This report describes a multi-organizational project to accomplish two goals: (1) to develop pharmacology/pharmacotherapeutics curriculum guidelines designed to prepare family nurse practitioners (FNPs) for full prescriptive authority; and (2) to develop regulatory criteria for evaluating the academic preparation and clinical competencies of FNPs…

The evolution and challenges for the international harmonization of the regulation of pharmaceutical excipients in Taiwan.

PubMed

Chang, Lin-Chau; Kang, Jaw-Jou; Gau, Churn-Shiouh

2015-12-01

Excipients, once considered an inert component, have been shown to greatly influence the characteristics of the drug product, such as quality and safety. Functionality-related characteristics of excipients could affect the performance of the drug product. Moreover, the impact of globalization has complicated the issue and made the supervision of supply chain highly important. Taiwan, a member of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, makes efforts to harmonize with international regulations and to strengthen the protection of patients through regulatory controls. In order to improve the harmonization and the transparency of regulatory requirements, the aim of the present study was to investigate the regulatory framework and considerations of stringent regulatory authorities and to propose the draft regulatory requirements to the Taiwan Food and Drug Administration for jurisdiction. The proposal which was extensively discussed in the expert committee includes the regulatory considerations to ensure the safety and quality of the excipients and may serve as a platform to facilitate the communication with industries about the current thinking on related issues. Moreover, through the review of the recent guidelines published by the stringent regulatory authorities, the trend of the regulatory considerations was revealed and discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Current State of the Regulatory Trajectory for Whole Slide Imaging Devices in the USA

PubMed Central

Abels, Esther; Pantanowitz, Liron

2017-01-01

The regulatory field for digital pathology (DP) has advanced significantly. A major milestone was accomplished when the FDA allowed the first vendor to market their device for primary diagnostic use in the USA and published in the classification order that this device, and substantially equivalent devices of this generic type, should be classified into class II instead of class III as previously proposed. The Digital Pathology Association (DPA) regulatory task force had a major role in the accomplishment of getting the application request for Whole Slide Imaging (WSI) Systems recommended for a de novo. This article reviews the past and emerging regulatory environment of WSI for clinical use in the USA. A WSI system with integrated subsystems is defined in the context of medical device regulations. The FDA technical performance assessment guideline is also discussed as well as parameters involved in analytical testing and clinical studies to demonstrate that WSI devices are safe and effective for clinical use. PMID:28584684

Current State of the Regulatory Trajectory for Whole Slide Imaging Devices in the USA.

PubMed

Abels, Esther; Pantanowitz, Liron

2017-01-01

The regulatory field for digital pathology (DP) has advanced significantly. A major milestone was accomplished when the FDA allowed the first vendor to market their device for primary diagnostic use in the USA and published in the classification order that this device, and substantially equivalent devices of this generic type, should be classified into class II instead of class III as previously proposed. The Digital Pathology Association (DPA) regulatory task force had a major role in the accomplishment of getting the application request for Whole Slide Imaging (WSI) Systems recommended for a de novo . This article reviews the past and emerging regulatory environment of WSI for clinical use in the USA. A WSI system with integrated subsystems is defined in the context of medical device regulations. The FDA technical performance assessment guideline is also discussed as well as parameters involved in analytical testing and clinical studies to demonstrate that WSI devices are safe and effective for clinical use.

2012 Guidelines for Water Reuse

EPA Science Inventory

This manual is a revision of the "2004 Water Reuse Guidelines." This document is a summary of reuse guidelines, with supporting information, for the benefit of utilities of utilities and regulatory agencies, particularly EPA.

Nanopharmaceuticals: Tiny challenges for the environmental risk assessment of pharmaceuticals.

PubMed

Berkner, Silvia; Schwirn, Kathrin; Voelker, Doris

2016-04-01

Many new developments and innovations in health care are based on nanotechnology. The field of nanopharmaceuticals is diverse and not as new as one might think; indeed, nanopharmaceuticals have been marketed for many years, and the future is likely to bring more nanosized compounds to the market. Therefore, it is time to examine whether the environmental risk assessment for human pharmaceuticals is prepared to assess the exposure, fate, and effects of nanopharmaceuticals in an adequate way. Challenges include the different definitions for nanomaterials and nanopharmaceuticals, different regulatory frameworks, the diversity of nanopharmaceuticals, the scope of current regulatory guidelines, and the applicability of test protocols. Based on the current environmental risk assessment for human medicinal products in the European Union, necessary adaptations for the assessment procedures and underlying study protocols are discussed and emerging solutions identified. © 2015 The Authors. Environmental Toxicology & Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

[Perception of health and safety risks among workers pathology laboratories].

PubMed

Alvarado-Cabrero, Isabel; Valencia-Cedillo, Raquel

2015-01-01

Health care workers are experiencing increasing numbers of occupational illnesses. Safety practices in anatomical pathology laboratories (APL) are crucial to prevent unnecessary exposures to both chemical and biological agents. The main goal of this study was to determine if pathologists perceptions and actual practice mirror regulatory guidelines. Current available recommendations for APL were reviewed and used to construct an online survey distributed to pathologists. The survey was completed by 121 participants. Eighty-seven (72 %) of respondents reported receiving inadequate safety training. Most pathologists (82 %) were not well-informed about biosafety practices. Sixty-three (52 %) participants felt that the risks of chemical and infectious disease exposures in the APL were low. Most respondents reported having a needle stick or cut (71 %). Eighty-six (71 %) of participants reported musculo skeletal problems. This study indicated that there is a need for improving training in anatomical pathology safety practices in Mexican laboratories as daily practices do not reflected current guidelines.

A "good practice" approach to the quality and consistency of morphological examination of the internal head structures of the term rabbit fetus.

PubMed

French, Julian M

2014-07-01

Variation in the interpretation of the regulatory guidelines has resulted in a diversity of techniques employed to examine the internal structures of the foetal rabbit head. Examination of the foetal rabbit brain, using a single transverse section as the sole technique, is considered not to be sufficiently thorough to be regarded as an adequate examination method. It is not compliant with published EPA and OECD guidelines covering required examination of the internal head structures, nor is it considered to conform to the spirit of the safety assessment required by the ICH guideline. Fixation of approximately half of the heads in each litter to allow the examination of multiple transverse sections enables the major structures within the head to be assessed effectively. This method is compliant with current guidelines, represents "good practice" and should be consistently adopted for the examination of the internal head structures of the term rabbit foetus. Copyright © 2014 Elsevier Inc. All rights reserved.

Oversight framework over oocyte procurement for somatic cell nuclear transfer: comparative analysis of the Hwang Woo Suk case under South Korean bioethics law and U.S. guidelines for human embryonic stem cell research.

PubMed

Kim, Mi-Kyung

2009-01-01

We examine whether the current regulatory regime instituted in South Korea and the United States would have prevented Hwang's potential transgressions in oocyte procurement for somatic cell nuclear transfer, we compare the general aspects and oversight framework of the Bioethics and Biosafety Act in South Korea and the US National Academies' Guidelines for Human Embryonic Stem Cell Research, and apply the relevant provisions and recommendations to each transgression. We conclude that the Act would institute centralized oversight under governmental auspices while the Guidelines recommend politically-independent, decentralized oversight bodies including a special review body for human embryonic stem cell research at an institutional level and that the Guidelines would have provided more vigorous protection for the women who had undergone oocyte procurement for Hwang's research than the Act. We also suggest additional regulations to protect those who provide oocytes for research in South Korea.

Application of SAE ARP4754A to Flight Critical Systems

NASA Technical Reports Server (NTRS)

Peterson, Eric M.

2015-01-01

This report documents applications of ARP4754A to the development of modern computer-based (i.e., digital electronics, software and network-based) aircraft systems. This study is to offer insight and provide educational value relative to the guidelines in ARP4754A and provide an assessment of the current state-of-the- practice within industry and regulatory bodies relative to development assurance for complex and safety-critical computer-based aircraft systems.

Is it ethical to prevent secondary use of stored biological samples and data derived from consenting research participants? The case of Malawi.

PubMed

Mungwira, Randy G; Nyangulu, Wongani; Misiri, James; Iphani, Steven; Ng'ong'ola, Ruby; Chirambo, Chawanangwa M; Masiye, Francis; Mfutso-Bengo, Joseph

2015-12-02

This paper discusses the contentious issue of reuse of stored biological samples and data obtained from research participants in past clinical research to answer future ethical and scientifically valid research questions. Many countries have regulations and guidelines that guide the use and exportation of stored biological samples and data. However, there are variations in regulations and guidelines governing the reuse of stored biological samples and data in Sub-Saharan Africa including Malawi. The current research ethics regulations and guidelines in Malawi do not allow indefinite storage and reuse of biological samples and data for future unspecified research. This comes even though the country has managed to answer pertinent research questions using stored biological samples and data. We acknowledge the limited technical expertise and equipment unavailable in Malawi that necessitates exportation of biological samples and data and the genuine concern raised by the regulatory authorities about the possible exploitation of biological samples and data by researchers. We also acknowledge that Malawi does not have bio-banks for storing biological samples and data for future research purposes. This creates room for possible exploitation of biological samples and data collected from research participants in primary research projects in Malawi. However, research ethics committees require completion and approval of material transfer agreements and data transfer agreements for biological samples and data collected for research purposes respectively and this requirement may partly address the concern raised by the regulatory authorities. Our concern though is that there is no such requirement for biological samples and data collected from patients for clinical or diagnostic purposes. In conclusion, we propose developing a medical data and material transfer agreement for biological samples and data collected from patients for clinical or diagnostic purposes in both public and private health facilities that may end up in research centers outside Malawi. We also propose revision of the current research ethics regulations and guidelines in Malawi in order to allow secondary use of biological samples and data collected from primary research projects as a way of maximizing the use of collected samples and data. Finally, we call for consultation of all stakeholders within the Malawi research community when regulatory authorities are developing policies that govern research in Malawi.

76 FR 63565 - Event Reporting Guidelines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-13

...-2011-0237] Event Reporting Guidelines AGENCY: Nuclear Regulatory Commission. ACTION: Draft NUREG... comments on Draft NUREG-1022, Revision 3, ``Event Reporting Guidelines: 10 CFR 50.72 and 50.73''. The NUREG-1022 contains guidelines that the NRC staff considers acceptable for use in meeting the event reporting...

Critical review on the Environmental Risk Assessment of medicinal products for human use in the centralised procedure.

PubMed

Caneva, Laura; Bonelli, Milton; Papaluca-Amati, Marisa; Vidal, Jean-Marc

2014-04-01

In this article we analyse the Environmental Risk Assessment (ERA) of 59 medicinal products for human use authorised in the EU through the centralised procedure between 2011 and 2012, to establish whether company submissions are compliant with the European Medicines Agency (EMA) guideline and complete in terms of data and study reports provided. The most frequent questions raised by EU regulatory authorities are described, together with an evaluation of the presence and quality of ERA-related information in published regulatory assessment documents. The results of this review show recent improvement in ERA-related data presented in regulatory assessment documents available to the public while also highlighting a need to develop further guidance on environmental issues in order to assist applicants improve their ERA dossiers and overcome current shortcomings. Copyright © 2014 Elsevier Inc. All rights reserved.

Updating Human Factors Engineering Guidelines for Conducting Safety Reviews of Nuclear Power Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

O, J.M.; Higgins, J.; Stephen Fleger - NRC

The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodicmore » update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool. To this end, the NRC is updating its guidance to stay current with recent research on human performance, advances in HFE methods and tools, and new technology being employed in plant and control room design. This paper describes the role of HFE guidelines in the safety review process and the content of the key HFE guidelines used. Then we will present the methodology used to develop HFE guidance and update these documents, and describe the current status of the update program.« less

Do marketing and alcohol treatment/public health experts think televised alcohol advertisements abide by regulatory guidelines?

PubMed

Lloyd, Kelly; Cameron, Elaine; Williams, Hannah; Banister, Emma; Donmall, Michael; Higgins, Alan; French, David P

2018-04-01

Televised alcohol advertisements in the United Kingdom must abide by the Broadcast Committee of Advertising Practice Code, which provides guidelines concerning advertisements not implying, condoning or encouraging immoderate, irresponsible or antisocial drinking. Previously, 75 per cent of 373 general public respondents were shown one of seven advertisements rated a breach of at least one guideline. This study assessed whether experts in marketing ( n = 25) and alcohol treatment/public health ( n = 25) perceived the same seven television alcohol advertisements as complying with the Broadcast Committee of Advertising Practice Code. Overall, 83 per cent of advertisements were rated as breaching at least one guideline. This provides further proof that self-regulatory alcohol guidelines are not fit for purpose.

Development of World Health Organization (WHO) recommendations for appropriate clinical trial endpoints for next-generation Human Papillomavirus (HPV) vaccines.

PubMed

Prabhu, Malavika; Eckert, Linda O

2016-12-01

The World Health Organization (WHO) serves as a key organization to bring together experts along the continuum of vaccine development and regulatory approval, among its other functions. Using the revision of WHO's guidelines on prophylactic human papillomavirus (HPV) vaccine as an example, we describe the process by which (1) a need to revise the guidelines was identified; (2) a group of stakeholders with complementary expertise and key questions were identified; (3) a scientific review was conducted; (4) consensus on revisions was achieved; (5) guidelines were updated, reviewed widely, and approved. This multi-year process resulted in the consensus that regulatory agencies could consider additional endpoints, such as persistent HPV infection or immune equivalence, depending on the design of the HPV vaccine trials. Updating the guidelines will now accelerate vaccine development, reduce costs of clinical trials, and lead to faster regulatory approval. Copyright © 2016. Published by Elsevier B.V.

[Convergence of healthcare regulation in the Americas: history, development, and new challenges].

PubMed

Silva, Ana Paula Jucá; Tagliari, Patrícia Oliveira Pereira

2016-05-01

The present article describes the changing relationship among healthcare regulatory authorities in various international settings, with special emphasis on the Americas. As other sectors, healthcare also faces the need to regulate international practices, while at the same time taking into consideration the specific realities of each country. Regulatory convergence - a movement towards technical alignment to enable the adoption of local regulatory mechanisms that take into account internationally recognized standards and principles to promote a single sanitary goal - has emerged as a means to address this challenge. Organizations that already use this tool, such as the International Conference of Drug Regulatory Authorities (ICDRA), Pan American Network for Drug Regulatory Harmonization (PANDRH), International Generic Drug Regulators Programme (IGDRP), and the International Medical Device Regulators Forum (IMDRF), among others, are currently working to gather knowledge, data, and specialists from different countries to build an international technical and scientific standard that can be used for decision-making by local regulators. This would ensure convergence of national regulations despite the need to adapt international standards to local needs, structure, and capacities. The most recent resolutions issued by the World Health Organization recognize the need to bring regulatory systems closer to the reality of national healthcare systems, and underscore the advantages of using existing local guidelines as input for cooperation with regulatory authorities.

Regulatory Acceptance of Alternative Methods in the Development and Approval of Pharmaceuticals.

PubMed

Beken, Sonja; Kasper, Peter; van der Laan, Jan-Willem

Animal studies may be carried out to support first administration of a new medicinal product to either humans or the target animal species, or before performing clinical trials in even larger populations, or before marketing authorisation, or to control quality during production. Ethical and animal welfare considerations require that animal use is limited as much as possible. Directive 2010/63/EU on the protection of animals used for scientific purposes unambiguously fosters the application of the principle of the 3Rs when considering the choice of methods to be used.As such, today, the 3Rs are embedded in the relevant regulatory guidance both at the European (European Medicines Agency (EMA)) and (Veterinary) International Conference on Harmonization ((V)ICH) levels. With respect to non-clinical testing requirements for human medicinal products, reduction and replacement of animal testing has been achieved by the regulatory acceptance of new in vitro methods, either as pivotal, supportive or exploratory mechanistic studies. Whilst replacement of animal studies remains the ultimate goal, approaches aimed at reducing or refining animal studies have also been routinely implemented in regulatory guidelines, where applicable. The chapter provides an overview of the implementation of 3Rs in the drafting of non-clinical testing guidelines for human medicinal products at the level of the ICH. In addition, the revision of the ICH S2 guideline on genotoxicity testing and data interpretation for pharmaceuticals intended for human use is discussed as a case study.In October 2010, the EMA established a Joint ad hoc Expert Group (JEG 3Rs) with the mandate to improve and foster the application of 3Rs principles to the regulatory testing of medicinal products throughout their lifecycle. As such, a Guideline on regulatory acceptance of 3R testing approaches was drafted that defines regulatory acceptance and provides guidance on the scientific and technical criteria for regulatory acceptance of 3R testing approaches, including a process for collection of real-life data (safe harbour). Pathways for regulatory acceptance of 3R testing approaches are depicted and a new procedure for submission and evaluation of a proposal for regulatory acceptance of 3R testing approaches is described.

36 CFR 292.42 - Management standards and guidelines.

Code of Federal Regulations, 2010 CFR

2010-07-01

... guidelines. 292.42 Section 292.42 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF... standards and guidelines. (a) In addition to existing statutory and regulatory authority governing administration of National Forest System lands and resources, the standards and guidelines in §§ 292.43 to 292.48...

Implementation guidelines for drug and alcohol regulations in mass transit

DOT National Transportation Integrated Search

2002-08-01

These guidelines will assist transit agencies in developing drug and alcohol testing programs that comply with regulations of the Federal Transit Administration (FTA). The guidelines provide a comprehensive, up-to-date summary of the regulatory requi...

The evolution of health policy guidelines for assisted reproduction in the Republic of Ireland, 2004-2009.

PubMed

Walsh, David J; Ma, Mary L; Sills, Eric Scott

2011-06-24

This analysis reports on Irish regulatory policies for in vitro fertilisation (IVF) from 2004-2009, in the context of membership changes within the Medical Council of Ireland. To achieve this, the current (2009) edition of the Guide to Professional Conduct & Ethics was compared with the immediately preceding version (2004). The statutory composition of the Medical Council from 2004-2009 was also studied. Content analysis of the two editions identified the following differences: 1) The 2004 guide states that IVF "should only be used after thorough investigation has failed to reveal a treatable cause of the infertility", while the 2009 guide indicates IVF "should only be used after thorough investigation has shown that no other treatment is likely to be effective"; 2) The 2004 stipulation stating that fertilized ovum (embryo) "must be used for normal implantation and must not be deliberately destroyed" is absent from the 2009 guidelines; 3) The option to donate "unused fertilised ova" (embryos) is omitted from the 2009 guidelines; 4) The 2009 guidelines state that ART should be offered only by "suitably qualified professionals, in appropriate facilities, and according to the international best practice"; 5) The 2009 guidelines introduce criteria that donations as part of a donor programme should be "altruistic and non-commercial". These last two points represent original regulatory efforts not appearing in the 2004 edition. The Medical Practitioners Act 2007 reduced the number of physicians on the Medical Council to 6 (of 25) members. The ethical guidelines from 2004 preceded this change, while the reconstituted Medical Council published the 2009 version. Between 2004 and 2009, substantial modifications in reproductive health policy were incorporated into the Medical Council's ethical guidelines. The absence of controlling Irish legislation means that patients and IVF providers in Ireland must rely upon these guidelines by default. Our critique traces the evolution of public policy on IVF during a time when the membership of the Medical Council changed radically; reduced physician contribution to decision-making was associated with diminished protection for IVF-derived embryos in Ireland. Considerable uncertainty on IVF practice in Ireland remains.

The regulatory framework for preventing cross-contamination of pharmaceutical products: History and considerations for the future.

PubMed

Sargent, Edward V; Flueckiger, Andreas; Barle, Ester Lovsin; Luo, Wendy; Molnar, Lance R; Sandhu, Reena; Weideman, Patricia A

2016-08-01

Cross-contamination in multi-product pharmaceutical manufacturing facilities can impact both product safety and quality. This issue has been recognized by regulators and industry for some time, leading to publication of a number of continually evolving guidelines. This manuscript provides a historical overview of the regulatory framework for managing cross-contamination in multi-product facilities to provide context for current approaches. Early guidelines focused on the types of pharmaceuticals for which dedicated facilities and control systems were needed, and stated the requirements for cleaning validation. More recent guidelines have promoted the idea of using Acceptable Daily Exposures (ADEs) to establish cleaning limits for actives and other potentially hazardous substances. The ADE approach is considered superior to previous methods for setting cleaning limits such as using a predetermined general limit (e.g., 10 ppm or a fraction of the median lethal dose (LD50) or therapeutic dose). The ADEs can be used to drive the cleaning process and as part of the overall assessment of whether dedicated production facilities are required. While great strides have been made in using the ADE approach, work remains to update good manufacturing practices (GMPs) to ensure that the approaches are clear, consistent with the state-of-the-science, and broadly applicable yet flexible enough for adaptation to unique products and situations. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of genomic and biobanking research in Africa: a content analysis of ethics guidelines, policies and procedures from 22 African countries.

PubMed

de Vries, Jantina; Munung, Syntia Nchangwi; Matimba, Alice; McCurdy, Sheryl; Ouwe Missi Oukem-Boyer, Odile; Staunton, Ciara; Yakubu, Aminu; Tindana, Paulina

2017-02-02

The introduction of genomics and biobanking methodologies to the African research context has also introduced novel ways of doing science, based on values of sharing and reuse of data and samples. This shift raises ethical challenges that need to be considered when research is reviewed by ethics committees, relating for instance to broad consent, the feedback of individual genetic findings, and regulation of secondary sample access and use. Yet existing ethics guidelines and regulations in Africa do not successfully regulate research based on sharing, causing confusion about what is allowed, where and when. In order to understand better the ethics regulatory landscape around genomic research and biobanking, we conducted a comprehensive analysis of existing ethics guidelines, policies and other similar sources. We sourced 30 ethics regulatory documents from 22 African countries. We used software that assists with qualitative data analysis to conduct a thematic analysis of these documents. Surprisingly considering how contentious broad consent is in Africa, we found that most countries allow the use of this consent model, with its use banned in only three of the countries we investigated. In a likely response to fears about exploitation, the export of samples outside of the continent is strictly regulated, sometimes in conjunction with regulations around international collaboration. We also found that whilst an essential and critical component of ensuring ethical best practice in genomics research relates to the governance framework that accompanies sample and data sharing, this was most sparingly covered in the guidelines. There is a need for ethics guidelines in African countries to be adapted to the changing science policy landscape, which increasingly supports principles of openness, storage, sharing and secondary use. Current guidelines are not pertinent to the ethical challenges that such a new orientation raises, and therefore fail to provide accurate guidance to ethics committees and researchers.

A survey of manufacturing and handling practices for monoclonal antibodies by pharmacy, nursing and medical personnel.

PubMed

Alexander, M; King, J; Lingaratnam, S; Byrne, J; MacMillan, K; Mollo, A; Kirsa, S; Green, M

2016-04-01

There is a paucity of data available to assess the occupational health and safety risk associated with exposure to monoclonal antibodies. Industry standards and published guidelines are conflicting or outdated. Guidelines offer contrary recommendations based on an array of methodological approaches. This survey aimed to describe current practices, beliefs and attitudes relating to the handling of monoclonal antibodies by Australian medical, nursing and pharmacy clinicians. An electronic survey was distributed between June and September 2013. Respondents were surveyed on three focus areas: institutional guideline availability and content, current practices and attitudes. Demographic data relating to respondent and primary place of practice were also collected. A total of 222 clinicians completed the survey, with representation from all targeted professional groups and from a variety of geographic locations. 92% of respondents reported that their institution prepared or administered monoclonal antibodies, with 87% specifically handling anti-cancer monoclonal antibodies. Monoclonal antibodies were mostly prepared onsite (84-90%) and mostly within pharmacy clean-rooms (75%) and using cytotoxic cabinets (61%). 43% of respondents reported access to institutional monoclonal antibody handling guidelines with risk reduction strategies including training and education (71%), spill and waste management (71%), procedures for transportation (57%) and restricted handling (50%). Nurses had a stronger preference towards pharmacy manufacturing than both doctors and pharmacists for a range of clinical scenarios. 95% of all respondents identified that professional or regulatory body guidelines are an important resource when considering handling practices. Monoclonal antibodies are most commonly handled according to cytotoxic drug standards and often in the absence of formal guidelines. © The Author(s) 2014.

Regulatory Considerations of Bioequivalence Studies for Oral Solid Dosage Forms in Japan.

PubMed

Kuribayashi, Ryosuke; Takishita, Tomoko; Mikami, Kenichi

2016-08-01

Bioequivalence (BE) studies are used to infer the therapeutic equivalence of generic drug products to original drug products throughout the world. In BE studies, bioavailability (BA) should be compared between the original and generic drug products, with BA defined as the rate and extent of absorption of active pharmaceutical ingredients or active metabolites from a product into the systemic circulation. For most of BE studies conducted during generic drug development, BA comparisons are performed in single-dose studies. In Japan, the revised "Guideline for Bioequivalence Studies of Generic Products" was made available in 2012 by the Ministry of Health, Labour, and Welfare, and generic drug development is currently conducted based on this guideline. Similarly, the U.S. Food and Drug Administration and European Medicines Agency have published guidance and guideline on generic drug development. This article introduces the guideline on Japanese BE studies for oral solid dosage forms and the dissolution tests for the similarity and equivalence evaluation between the original and generic drug products. Additionally, we discuss some of the similarities and differences in guideline between Japan, the United States, and the European Union. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Statistical Considerations Concerning Dissimilar Regulatory Requirements for Dissolution Similarity Assessment. The Example of Immediate-Release Dosage Forms.

PubMed

Jasińska-Stroschein, Magdalena; Kurczewska, Urszula; Orszulak-Michalak, Daria

2017-05-01

When performing in vitro dissolution testing, especially in the area of biowaivers, it is necessary to follow regulatory guidelines to minimize the risk of an unsafe or ineffective product being approved. The present study examines model-independent and model-dependent methods of comparing dissolution profiles based on various compared and contrasted international guidelines. Dissolution profiles for immediate release solid oral dosage forms were generated. The test material comprised tablets containing several substances, with at least 85% of the labeled amount dissolved within 15 min, 20-30 min, or 45 min. Dissolution profile similarity can vary with regard to the following criteria: time point selection (including the last time point), coefficient of variation, and statistical method selection. Variation between regulatory guidance and statistical methods can raise methodological questions and result potentially in a different outcome when reporting dissolution profile testing. The harmonization of existing guidelines would address existing problems concerning the interpretation of regulatory recommendations and research findings. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Prudent use guidelines: a review of existing veterinary guidelines.

PubMed

Teale, C J; Moulin, G

2012-04-01

The World Organisation for Animal Health (OIE) TerrestrialAnimal Health Code considers the prudent use of antimicrobial agents in veterinary medicine to comprise a series of practical measures and recommendations which confer benefits to animal and public health while preserving and maintaining the therapeutic efficacy of antimicrobials. This paper reviews some of the main veterinary prudent use guidelines which have been published in English and the responsibilities of those involved at all levels in the administration of antimicrobials to animals, including national regulatory authorities. The OIE guidelines are considered comprehensive and cover all of those levels, from regulatory authorities to veterinarians and food producers. Guidelines produced by national authorities, professional veterinary associations or farming associations and which are targeted at particular individuals, for example veterinarians or food animal producers, will, obviously, restrict their coverage to those aspects considered relevant for their target audience.

Regulatory assessment of proposed accessibility guidelines for pedestrians in the public right-of-way

DOT National Transportation Integrated Search

2011-06-30

This report assesses the potential costs and benefits of proposed accessibility guidelines issued by the Access Board for pedestrian facilities in the public right-of-way. The report also analyzes the potential impacts of the proposed guidelines on s...

Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma.

PubMed

Brose, Marcia S; Smit, Johannes; Capdevila, Jaume; Elisei, Rossella; Nutting, Christopher; Pitoia, Fabian; Robinson, Bruce; Schlumberger, Martin; Shong, Young Kee; Takami, Hiroshi

2012-09-01

For patients with advanced, radioactive iodine-refractory differentiated thyroid cancer, current treatment guidelines recommend clinical trial enrollment or small-molecule kinase inhibitor therapy. However, details of patient management vary between countries depending on trial availability and national regulatory policies. Insufficient clinical trial data and variable disease characteristics challenge the creation of universal guidelines, and treatment plans often reflect regional influences. A multidisciplinary, multiregional panel of experts met to discuss regional approaches to managing patients with advanced, radioactive iodine-refractory differentiated thyroid cancer and the potential impact of emerging therapies on current treatment strategies. Despite process-oriented regional differences, the decision-making strategies were similar. Multidisciplinary teams used to manage high-risk patients varied in composition across regions, particularly regarding the responsible physician's specialty. Cytotoxic chemotherapy was viewed as limited in clinical benefit, and targeted agents as attractive, based on promising data. Panel members support clinical trial enrollment as the preferred treatment strategy for managing these patients.

Wood and Paper Manufacturing Sectors

EPA Pesticide Factsheets

Find EPA regulatory information for the wood product and paper manufacturing sectors, including paper, pulp and lumber. Information includes NESHAPs and effluent guidelines for pulp and paper rulemaking, and compliance guidelines

The use and interpretation of in vitro data in regulatory toxicology: cosmetics, toiletries and household products.

PubMed

Indans, Ian

2002-02-28

There is currently a drive to eliminate animal testing for cosmetics, toiletries and household products; indeed, the European Union Cosmetics Directive aims to prohibit the use of experimental animals for the testing of finished cosmetic products after 2002. At present, national prohibitions are in place in the UK, Germany, Austria and the Netherlands, for the testing of finished cosmetic products and cosmetic ingredients. In the USA animal testing for certain types of finished products is mandatory. Against this background, the currently available regulatory in vitro tests comprise methods for eye irritation, skin corrosivity, genotoxicity, dermal penetration and photoirritation. The draft updates to the Organisation for Economic Co-operation and Development guidelines for eye and skin irritation advocate the use of in vitro or ex vivo methods prior to the commencement of animal studies. At present, testing for these endpoints cannot be completed in vitro, but potentially corrosive substances and products can be classified without the need for animal studies. Regulatory genotoxicity testing can be completed using only in vitro methods, provided that a clear negative outcome is obtained for each test. Data from dermal penetration studies may be used to refine risk assessments. Current developments in areas such as skin sensitisation and skin irritation promise that in the reasonably near future such information may be generated without the use of animals.

78 FR 1622 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-08

... Identifier No. 370 Americans With 3014-AA11 Disabilities Act (ADA) Accessibility Guidelines for Passenger... Stage 370. Americans with Disabilities Act (ADA) Accessibility Guidelines for Passenger Vessels...

Using Discrete Choice Experiments to Inform the Benefit-Risk Assessment of Medicines: Are We Ready Yet?

PubMed

Vass, Caroline M; Payne, Katherine

2017-09-01

There is emerging interest in the use of discrete choice experiments as a means of quantifying the perceived balance between benefits and risks (quantitative benefit-risk assessment) of new healthcare interventions, such as medicines, under assessment by regulatory agencies. For stated preference data on benefit-risk assessment to be used in regulatory decision making, the methods to generate these data must be valid, reliable and capable of producing meaningful estimates understood by decision makers. Some reporting guidelines exist for discrete choice experiments, and for related methods such as conjoint analysis. However, existing guidelines focus on reporting standards, are general in focus and do not consider the requirements for using discrete choice experiments specifically for quantifying benefit-risk assessments in the context of regulatory decision making. This opinion piece outlines the current state of play in using discrete choice experiments for benefit-risk assessment and proposes key areas needing to be addressed to demonstrate that discrete choice experiments are an appropriate and valid stated preference elicitation method in this context. Methodological research is required to establish: how robust the results of discrete choice experiments are to formats and methods of risk communication; how information in the discrete choice experiment can be presented effectually to respondents; whose preferences should be elicited; the correct underlying utility function and analytical model; the impact of heterogeneity in preferences; and the generalisability of the results. We believe these methodological issues should be addressed, alongside developing a 'reference case', before agencies can safely and confidently use discrete choice experiments for quantitative benefit-risk assessment in the context of regulatory decision making for new medicines and healthcare products.

75 FR 36725 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

..., entitled ``Numerical Guidelines Applicable to Volatile Market Opens'' with a new paragraph, entitled...) of Rule 2128 to eliminate the ability of the Exchange to deviate from the Numerical Guidelines... Numerical Guidelines or Reference Prices in various ``Unusual Circumstances.'' The Exchange proposes to...

Regulatory Guide on Conducting a Security Vulnerability Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ek, David R.

This document will provide guidelines on conducting a security vulnerability assessment at a facility regulated by the Radiation Protection Centre. The guidelines provide a performance approach assess security effectiveness. The guidelines provide guidance for a review following the objectives outlined in IAEA NSS#11 for Category 1, 2, & 3 sources.

Baseline Evaluations to Support Control Room Modernization at Nuclear Power Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boring, Ronald L.; Joe, Jeffrey C.

2015-02-01

For any major control room modernization activity at a commercial nuclear power plant (NPP) in the U.S., a utility should carefully follow the four phases prescribed by the U.S. Nuclear Regulatory Commission in NUREG-0711, Human Factors Engineering Program Review Model. These four phases include Planning and Analysis, Design, Verification and Validation, and Implementation and Operation. While NUREG-0711 is a useful guideline, it is written primarily from the perspective of regulatory review, and it therefore does not provide a nuanced account of many of the steps the utility might undertake as part of control room modernization. The guideline is largely summative—intendedmore » to catalog final products—rather than formative—intended to guide the overall modernization process. In this paper, we highlight two crucial formative sub-elements of the Planning and Analysis phase specific to control room modernization that are not covered in NUREG-0711. These two sub-elements are the usability and ergonomics baseline evaluations. A baseline evaluation entails evaluating the system as-built and currently in use. The usability baseline evaluation provides key insights into operator performance using the control system currently in place. The ergonomics baseline evaluation identifies possible deficiencies in the physical configuration of the control system. Both baseline evaluations feed into the design of the replacement system and subsequent summative benchmarking activities that help ensure that control room modernization represents a successful evolution of the control system.« less

End of FY10 report - used fuel disposition technical bases and lessons learned : legal and regulatory framework for high-level waste disposition in the United States.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiner, Ruth F.; Blink, James A.; Rechard, Robert Paul

This report examines the current policy, legal, and regulatory framework pertaining to used nuclear fuel and high level waste management in the United States. The goal is to identify potential changes that if made could add flexibility and possibly improve the chances of successfully implementing technical aspects of a nuclear waste policy. Experience suggests that the regulatory framework should be established prior to initiating future repository development. Concerning specifics of the regulatory framework, reasonable expectation as the standard of proof was successfully implemented and could be retained in the future; yet, the current classification system for radioactive waste, including hazardousmore » constituents, warrants reexamination. Whether or not consideration of multiple sites are considered simultaneously in the future, inclusion of mechanisms such as deliberate use of performance assessment to manage site characterization would be wise. Because of experience gained here and abroad, diversity of geologic media is not particularly necessary as a criterion in site selection guidelines for multiple sites. Stepwise development of the repository program that includes flexibility also warrants serious consideration. Furthermore, integration of the waste management system from storage, transportation, and disposition, should be examined and would be facilitated by integration of the legal and regulatory framework. Finally, in order to enhance acceptability of future repository development, the national policy should be cognizant of those policy and technical attributes that enhance initial acceptance, and those policy and technical attributes that maintain and broaden credibility.« less

Legal and regulatory aspects of prescribing and marketing emergency contraception in Nigeria.

PubMed

Adekunle, A O; Babarinsa, I A; Akinyemi, Z; Okediran, A Y

2001-01-01

Emergency contraception remains so little used or understood and the lack of its awareness can be traced to a myriad of factors including legal and regulatory obstacles. The aim of this study was to determine the legal and regulatory aspects of dispensing or marketing a contraceptive method for reasons (especially emergency purposes) other than stated by the manufacturers. The existing drugs' and devices' regulatory systems in Nigeria, especially those governing family planning methods, were reviewed. A questionnaire was administered to 363 health workers, comprising of physicians, pharmacists, nurses and midwives, to determine the implications of dispensing some currently available oral contraceptives (OCs) for emergency purposes despite the fact that there is no explicit description of emergency use in the labelling of such drugs. In addition, in-depth interviews were conducted with regulatory bodies. It was observed that, with the exception of Postinor, the drug manufacturers' leaflets did not indicate that they could be used for emergency contraceptive purposes. Although 64.5% of the healthcare providers were aware that OCs and intrauterine contraceptive devices (IUCDs) can be used for emergency purposes, 42.1% actually prescribed or recommended them. Many health workers (62.3%) were unaware of any legal implication with regards to prescribing unregistered drugs in Nigeria. The existing guidelines stipulate that a manufacturer or marketer should 're-register' a product if a new indication or use not contained in the initial application was found later. To satisfy legal requirements, it does appear that the currently available OCs and IUCDs in Nigeria must be labelled and registered for emergency contraceptive purposes.

Does GLP enhance the quality of toxicological evidence for regulatory decisions?

PubMed Central

Borgert, Christopher J.; Becker, Richard A.; Carlton, Betsy D.; Hanson, Mark; Kwiatkowski, Patricia L.; Sue Marty, Mary; McCarty, Lynn S.; Quill, Terry F.; Solomon, Keith; Van Der Kraak, Glen; Witorsch, Raphael J.; Don Yi, Kun

2016-01-01

There is debate over whether the requirements of GLP are appropriate standards for evaluating the quality of toxicological data used to formulate regulations. A group promoting the importance of non-monotonic dose responses for endocrine disruptors contend that scoring systems giving primacy to GLP are biased against non-GLP studies from the literature and are merely record-keeping exercises to prevent fraudulent reporting of data from non-published guideline toxicology studies. They argue that guideline studies often employ insensitive species and outdated methods, and ignore the perspectives of subject-matter experts in endocrine disruption, who should be the sole arbiters of data quality. We believe regulatory agencies should use both non-GLP and GLP studies, that GLP requirements assure fundamental tenets of study integrity not typically addressed by journal peer-review, and that use of standardized test guidelines and GLP promotes consistency, reliability, comparability, and harmonization of various types of studies used by regulatory agencies worldwide. This debate suffers two impediments to progress: a conflation of different phases of study interpretation and levels of data validity, and a misleading characterization of many essential components of GLP and regulatory toxicology. Herein we provide clarifications critical for removing those impediments. PMID:27208076

75 FR 36743 - Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... ``Numerical Guidelines Applicable to Volatile Market Opens'' with a new paragraph, entitled ``Individual Stock... to eliminate the ability of the Exchange to deviate from the Numerical Guidelines contained in... existing paragraph (c)(2), which provides flexibility to the Exchange to use different Numerical Guidelines...

75 FR 61802 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-06

... replacing existing paragraph (a)(2)(C)(iv) of Rule 3312, entitled ``Numerical Guidelines Applicable to... Exchange to deviate from the Numerical Guidelines contained in paragraph (a)(2)(C)(i) when deciding which... Numerical Guidelines or Reference Prices in various ``Unusual Circumstances.'' The Exchange proposes to...

75 FR 36759 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... proposes replacing existing paragraph (c)(4) of Rule 128, entitled ``Numerical Guidelines Applicable to... the Exchange to deviate from the Numerical Guidelines contained in paragraph (c)(1) (other than under...)(2), which provides flexibility to the Exchange to use different Numerical Guidelines or Reference...

75 FR 36732 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing of a Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

....'' Second, NASDAQ replacing existing paragraph (C)(4) of Rule 11890, entitled ``Numerical Guidelines... NASDAQ to deviate from the Numerical Guidelines contained in paragraph (C)(1) (other than under limited... provides flexibility to NASDAQ to use different Numerical Guidelines or Reference Prices in various...

75 FR 37494 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change, as...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

... proposes replacing existing paragraph (c)(4) of Rule 7.10, entitled ``Numerical Guidelines Applicable to... the Exchange to deviate from the Numerical Guidelines contained in paragraph (c)(1) (other than under...)(2), which provides flexibility to the Exchange to use different Numerical Guidelines or Reference...

75 FR 36749 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing of Proposed Rule Change Amending...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

..., entitled ``Numerical Guidelines Applicable to Volatile Market Opens'' with a new paragraph, entitled... (g) of Rule 128 to eliminate the ability of the Exchange to deviate from the Numerical Guidelines... flexibility to the Exchange to use different Numerical Guidelines or Reference Prices in various ``Unusual...

75 FR 36746 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... Exchange replacing existing paragraph (c)(4) of Rule 11.19, entitled ``Numerical Guidelines Applicable to... the Exchange to deviate from the Numerical Guidelines contained in paragraph (c)(1) (other than under... provides flexibility to the Exchange to use different Numerical Guidelines or Reference Prices in various...

Overview of the European Medicines Agency's Development of Product-Specific Bioequivalence Guidelines.

PubMed

Sullivan, Jane O'; Blake, Kevin; Berntgen, Michael; Salmonson, Tomas; Welink, Jan

2017-12-05

The European Medicines Agency's (EMA) product-specific bioequivalence guidelines outline harmonized regulatory requirements for studies to demonstrate bioequivalence for products that may have particular needs due to their pharmacokinetics, in addition to those outlined in general guidance. As such they are potentially very useful to the pharmaceutical industry in the development of generic medicinal products and to regulatory authorities for harmonized decision-making. Since their introduction in 2013, EMA product-specific bioequivalence guidelines continue to increase in number, and as of June 2017, encompass a number of different pharmacotherapeutic groups and pharmaceutical forms. This article further elucidates the processes involved for stakeholders and reviews the Agency's experience with the development of these guidelines, including the scientific issues witnessed with their advancement. A comparison with the United States Food and Drug Administration approach to similar guidelines is also provided. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

ICH guidelines--implementation of the 3Rs (refinement, reduction, and replacement): incorporating best scientific practices into the regulatory process.

PubMed

Ohno, Yasuo

2002-01-01

An overview of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is described. ICH was established through cooperation of the regulatory agencies and industrial parties of three main regions involved in pharmaceuticals: the European Union, the United States, and Japan. The purpose of the ICH is to make recommendations to achieve greater harmonization regarding interpretation and application of technical guidelines and requirements for product registration in an effort to reduce or obviate the need to duplicate the testing carried out during the research and development of new medicines. The main purpose of ICH was not to foster the 3Rs per se; however, harmonization of guidelines has eliminated duplications of similar tests to satisfy the specific requirements of each region. The ICH process has contributed to mutual understanding of the regulatory requirements and has decreased the number of unnecessary animal experiments. Specific examples of the contributions of ICH harmonization to the 3Rs are described.

Assuring the Quality of Next-Generation Sequencing in Clinical Microbiology and Public Health Laboratories.

PubMed

Gargis, Amy S; Kalman, Lisa; Lubin, Ira M

2016-12-01

Clinical microbiology and public health laboratories are beginning to utilize next-generation sequencing (NGS) for a range of applications. This technology has the potential to transform the field by providing approaches that will complement, or even replace, many conventional laboratory tests. While the benefits of NGS are significant, the complexities of these assays require an evolving set of standards to ensure testing quality. Regulatory and accreditation requirements, professional guidelines, and best practices that help ensure the quality of NGS-based tests are emerging. This review highlights currently available standards and guidelines for the implementation of NGS in the clinical and public health laboratory setting, and it includes considerations for NGS test validation, quality control procedures, proficiency testing, and reference materials. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

[Dissection of differences and similarities of botanical drugs in European Union, US and Canada].

PubMed

He, Yi; Zhao, Libin; Ye, Zhengliang; Guo, Zhixin; Sun, He

2011-10-01

Because of the unique nature and treatment concept of traditional Chinese medicines (TCMs), TCMs have been respected again since 70s of last century. The regulatory agencies of some developed countries (the FDA, EMA and Health Canada etc) have published new guidance/guidelines/directives in recent years, such as the botanical drug product guidance of the FDA, the evidence for quality of finished natural health products guidance of the Health Canada and the guideline on quality of herbal medicinal products/ traditional herbal medicinal products of the EMA etc. All of the regulatory agencies are willing to scientifically evaluate the herbal medicines and accept it as therapeutic product. This paper analyzed the history of herbal medicine regulation and the similarities and differences of the regulatory requirements of the European Union, the United States and Canada, proposed possible future direction of the international development of Chinese medicine from the perspective of global regulatory affairs.

Technical standards and guidelines: prenatal screening for Down syndrome that includes first-trimester biochemistry and/or ultrasound measurements.

PubMed

Palomaki, Glenn E; Lee, Jo Ellen S; Canick, Jacob A; McDowell, Geraldine A; Donnenfeld, Alan E

2009-09-01

This statement is intended to augment the current general ACMG Standards and Guidelines for Clinical Genetics Laboratories and to address guidelines specific to first-trimester screening for Down syndrome. The aim is to provide the laboratory the necessary information to ensure accurate and reliable Down syndrome screening results given a screening protocol (e.g., combined first trimester and integrated testing). Information about various test combinations and their expected performance are provided, but other issues such as availability of reagents, patient interest in early test results, access to open neural tube defect screening, and availability of chorionic villus sampling are all contextual factors in deciding which screening protocol(s) will be selected by individual health care providers. Individual laboratories are responsible for meeting the quality assurance standards described by the Clinical Laboratory Improvement Act, the College of American Pathologists, and other regulatory agencies, with respect to appropriate sample documentation, assay validation, general proficiency, and quality control measures. These guidelines address first-trimester screening that includes ultrasound measurement and interpretation of nuchal translucency thickness and protocols that combine markers from both the first and second trimesters. Laboratories can use their professional judgment to make modification or additions.

The Production of Polyclonal Antibodies in Laboratory Animals. The Report and Recommendations of ECVAM Workshop 35.

PubMed

Leenaars, P P; Hendriksen, C F; de Leeuw, W A; Carat, F; Delahaut, P; Fischer, R; Halder, M; Hanly, W C; Hartinger, J; Hau, J; Lindblad, E B; Nicklas, W; Outschoorn, I M; Stewart-Tull, D E

1999-01-01

This is the report of the thirty-fifth of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organisation of ECVAM workshops on specific topics, at which small groups of invited experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward (1). This joint ECVAM/FELASA (Federation of European Laboratory Animal Science Associations) workshop on The Immunisation of Laboratory Animals for the Production of Polyclonal Antibodies was held in Utrecht (The Netherlands), on 20-22 March 1998, under the co-chairmanship of Coenraad Hendriksen (RIVM, Bilthoven, The Netherlands) and Wim de Leeuw (Inspectorate for Health Protection, The Netherlands). The participants, all experts in the fields of immunology, laboratory animal science, or regulation, came from universities, industry and regulatory bodies. The aims of the workshop were: a) to discuss and evaluate current immunisation procedures for the production of polyclonal antibodies (including route of injection, animal species and adjuvant ); and b) to draft recommendations and guidelines to improve the immunisation procedures, with regard both to animal welfare and to the optimisation of immunisation protocols. This report summarises the outcome of the discussions and includes a number of recommendations and a set of draft guidelines (included in Appendix 1). 1999 FRAME.

Early adopters of the magical thinking cap: a study on do-it-yourself (DIY) transcranial direct current stimulation (tDCS) user community

PubMed Central

Jwa, Anita

2015-01-01

Among currently available technologies, transcranial direct current stimulation (tDCS) is one of the most promising neuroenhancements because it is relatively effective, safe, and affordable. Recently, lay people have begun to build—or purchase—the tDCS device to use it at home for treatment or as a cognitive enhancer. The tDCS device is currently not covered by the existing regulatory framework, but there are still significant potential risks of misusing this device, and its long-term effects on the brain have not been fully explored. Thus, researchers have argued the need for regulations or official guidelines for the personal use of tDCS. However, until now, no systematic research on the do-it-yourself (DIY) tDCS user community has been done. The present study explores the basic demographic characteristics of DIY tDCS users as well as why and how they are using this device through a questionnaire survey, in-depth interviews, and a content analysis of web postings on the use of tDCS. This preliminary but valuable picture of the DIY tDCS user community will shed light on future studies and policy analysis to craft sound regulations and official guidelines for the use of tDCS. PMID:27774197

Early adopters of the magical thinking cap: a study on do-it-yourself (DIY) transcranial direct current stimulation (tDCS) user community.

PubMed

Jwa, Anita

2015-07-01

Among currently available technologies, transcranial direct current stimulation (tDCS) is one of the most promising neuroenhancements because it is relatively effective, safe, and affordable. Recently, lay people have begun to build-or purchase-the tDCS device to use it at home for treatment or as a cognitive enhancer. The tDCS device is currently not covered by the existing regulatory framework, but there are still significant potential risks of misusing this device, and its long-term effects on the brain have not been fully explored. Thus, researchers have argued the need for regulations or official guidelines for the personal use of tDCS. However, until now, no systematic research on the do-it-yourself (DIY) tDCS user community has been done. The present study explores the basic demographic characteristics of DIY tDCS users as well as why and how they are using this device through a questionnaire survey, in-depth interviews, and a content analysis of web postings on the use of tDCS. This preliminary but valuable picture of the DIY tDCS user community will shed light on future studies and policy analysis to craft sound regulations and official guidelines for the use of tDCS.

REGULATORY APPLICATIONS OF POREWATER TOXICITY TESTING

EPA Science Inventory

The purpose of this chapter is to evaluate the use of porewater toxicity tests in regulatory applications, including their potential use in the development of sediment quality guideline (SQG) values. Specifically, the following discussion focuses on the appropriateness and readin...

Liver safety assessment in special populations (hepatitis B, C, and oncology trials).

PubMed

Kullak-Ublick, Gerd A; Merz, Michael; Griffel, Louis; Kaplowitz, Neil; Watkins, Paul B

2014-11-01

The FDA guidance for industry in the premarketing clinical evaluation of drug-induced liver injury (DILI) is the most specific regulatory guidance currently available and has been useful in setting standards for the great majority of clinical indications involving subjects with a low risk of liver disorders. However, liver safety assessment faces challenges in populations with underlying liver disease, such as viral hepatitis or metastatic cancer. This is an important issue because there are currently many promising anti-viral and oncologic therapies in clinical development, with a trend toward oral therapies with reduced side effects. Without clearer guidelines, questions regarding liver safety may become a major factor in regulatory approval and ultimately physician uptake of the new treatments. The lack of consensus in defining stopping rules based on serum alanine aminotransferase (ALT) levels underscores the need for precompetitive data sharing to improve our understanding of DILI in these populations and to allow evidence-based rather than empirical definition of stopping rules. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials.

Strengthening the Canadian alcohol advertising regulatory system.

PubMed

Heung, Carly M; Rempel, Benjamin; Krank, Marvin

2012-05-24

Research evidence points to harmful effects from alcohol advertising among children and youth. In particular, exposure to alcohol advertising has been associated with adolescents drinking both earlier and heavier. Although current federal and provincial guidelines have addressed advertising practices to prevent underage drinking, practice has not been supported by existing policy. While protective measures such as social marketing campaigns have the potential for counteracting the effects from alcohol advertising, the effectiveness of such measures can be easily drowned out with increasing advertising activities from the alcohol industry, especially without effective regulation. Research reviewed by the European Focus on Alcohol Safe Environment (FASE) Project has identified a set of key elements that are necessary to make alcohol advertising policy measures effective at protecting children and youth from the harmful effects of alcohol marketing. Using these key elements as an evaluation framework, there are critical components in the Canadian alcohol advertising regulatory system that clearly require strengthening. To protect impressionable children and youth against the harmful effects of alcohol advertising, 13 recommendations to strengthen current alcohol advertising regulations in Canada are provided for Canadian policy-makers, advertising standard agencies, and public health groups.

Assessment of possible allergenicity of hypothetical ORFs in common food crops using current bioinformatic guidelines and its implications for the safety assessment of GM crops.

PubMed

Young, Gregory J; Zhang, Shiping; Mirsky, Henry P; Cressman, Robert F; Cong, Bin; Ladics, Gregory S; Zhong, Cathy X

2012-10-01

Before a genetically modified (GM) crop can be commercialized it must pass through a rigorous regulatory process to verify that it is safe for human and animal consumption, and to the environment. One particular area of focus is the potential introduction of a known or cross-reactive allergen not previously present within the crop. The assessment of possible allergenicity uses the guidelines outlined by the Food and Agriculture Organization (FAO) and World Health Organization's (WHO) Codex Alimentarius Commission (Codex) to evaluate all newly expressed proteins. Some regulatory authorities have broadened the scope of the assessment to include all DNA reading frames between stop codons across the insert and spanning the insert/genomic DNA junctions. To investigate the utility of this bioinformatic assessment, all naturally occurring stop-to-stop frames in the non-transgenic genomes of maize, rice, and soybean, as well as the human genome, were compared against the AllergenOnline (www.allergenonline.org) database using the Codex criteria. We discovered thousands of frames that exceeded the Codex defined threshold for potential cross-reactivity suggesting that evaluating hypothetical ORFs (stop-to-stop frames) has questionable value for making decisions on the safety of GM crops. Copyright © 2012 Elsevier Ltd. All rights reserved.

Estimation of southern resident killer whale exposure to exhaust emissions from whale-watching vessels and potential adverse health effects and toxicity thresholds.

PubMed

Lachmuth, Cara L; Barrett-Lennard, Lance G; Steyn, D Q; Milsom, William K

2011-04-01

Southern resident killer whales in British Columbia and Washington are exposed to heavy vessel traffic. This study investigates their exposure to exhaust gases from whale-watching vessels by using a simple dispersion model incorporating data on whale and vessel behavior, atmospheric conditions, and output of airborne pollutants from the whale-watching fleet based on emissions data from regulatory agencies. Our findings suggest that current whale-watching guidelines are usually effective in limiting pollutant exposure to levels at or just below those at which measurable adverse health effects would be expected in killer whales. However, safe pollutant levels are exceeded under worst-case conditions and certain average-case conditions. To reduce killer whale exposure to exhaust we recommend: vessels position on the downwind side of whales, a maximum of 20 whale-watching vessels should be within 800 m at any given time, viewing periods should be limited, and current whale-watch guidelines and laws should be enforced. Copyright © 2011. Published by Elsevier Ltd.

Compilation of International Regulatory Guidance Documents for Neuropathology Assessment during Nonclinical Toxicity Studies

EPA Science Inventory

Neuropathology analysis as an endpoint during nonclinical efficacy and toxicity studies is a challenging prospect that requires trained personnel and particular equipment to achieve optimal results. Accordingly, many regulatory agencies have produced explicit guidelines for desig...

The local lymph node assay in practice: a current regulatory perspective.

PubMed

Cockshott, A; Evans, P; Ryan, C A; Gerberick, G F; Betts, C J; Dearman, R J; Kimber, I; Basketter, D A

2006-07-01

Following the formal acceptance of the local lymph node assay (LLNA) as an Organization for Economic Cooperation and Development (OECD) guideline in April 2002, the UK Health and Safety Executive (HSE) informed notifiers that this was now the method of choice for the assessment of skin sensitization potential under the EU notification scheme for new industrial chemicals (NONS). This paper summarizes the experience of the HSE for the 2-year period immediately following the issuing of this statement, during which 48 LLNA study reports were assessed for notification purposes. The issues discussed here include adherence to the OECD guideline, interpretation of results, and classification outcomes. Generally, notifying laboratories followed the OECD guideline successfully, with regard to the sex/ strain/numbers of mice used, the precise process used for measurement of cell proliferation, and the use of recommended vehicles and positive controls. Initially, use of the individual animal approach (measuring the cell proliferation in each animal rather than for a pooled dose group) highlighted problems caused by technical inexperience, but these were overcome by practice. Toxicity or irritation were found to be minor factors in dose selection; more important was the choice of vehicle to correctly maximize the test substance concentration, while maintaining appropriate application properties. Contrary to concerns that the LLNA would prove to be less sensitive or more sensitive than the traditionally used Guinea Pig Maximization Test (GPMT), the proportion of new substances classified as skin sensitizers was within the range observed in previous years. Although the sample size is relatively small, the experience of the HSE indicates that the LLNA is satisfactory for routine regulatory use.

Rules and Regulations: Minimum Schoolhouse Construction Standards.

ERIC Educational Resources Information Center

Arkansas State Dept. of Education, Little Rock.

Regulatory guidelines governing the minimum schoolhouse construction standards as well as rules for new construction applications, school site selection, and approval procedures are presented. Appendices (comprising 95 percent of the publication) document the following: educational space guidelines; planning for modern education; school…

Review of achievements of the OECD Working Party on Manufactured Nanomaterials' Testing and Assessment Programme. From exploratory testing to test guidelines.

PubMed

Rasmussen, Kirsten; González, Mar; Kearns, Peter; Sintes, Juan Riego; Rossi, François; Sayre, Phil

2016-02-01

This paper charts the almost ten years of history of OECD's work on nanosafety, during which the programme of the OECD on the Testing and Assessment of Manufactured Nanomaterials covered the testing of eleven nanomaterials for about 59 end-points addressing physical-chemical properties, mammalian and environmental toxicity, environmental fate and material safety. An overview of the materials tested, the test methods applied and the discussions regarding the applicability of the OECD test guidelines, which are recognised methods for regulatory testing of chemicals, are given. The results indicate that many existing OECD test guidelines are suitable for nanomaterials and consequently, hazard data collected using such guidelines will fall under OECD's system of Mutual Acceptance of Data (MAD) which is a legally binding instrument to facilitate the international acceptance of information for the regulatory safety assessment of chemicals. At the same time, some OECD test guidelines and guidance documents need to be adapted to address nanomaterials while new test guidelines and guidance documents may be needed to address endpoints that are more relevant to nanomaterials. This paper presents examples of areas where test guidelines or guidance for nanomaterials are under development. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Comparative assessment of bioanalytical method validation guidelines for pharmaceutical industry.

PubMed

Kadian, Naveen; Raju, Kanumuri Siva Rama; Rashid, Mamunur; Malik, Mohd Yaseen; Taneja, Isha; Wahajuddin, Muhammad

2016-07-15

The concepts, importance, and application of bioanalytical method validation have been discussed for a long time and validation of bioanalytical methods is widely accepted as pivotal before they are taken into routine use. United States Food and Drug Administration (USFDA) guidelines issued in 2001 have been referred for every guideline released ever since; may it be European Medical Agency (EMA) Europe, National Health Surveillance Agency (ANVISA) Brazil, Ministry of Health and Labour Welfare (MHLW) Japan or any other guideline in reference to bioanalytical method validation. After 12 years, USFDA released its new draft guideline for comments in 2013, which covers the latest parameters or topics encountered in bioanalytical method validation and approached towards the harmonization of bioanalytical method validation across the globe. Even though the regulatory agencies have general agreement, significant variations exist in acceptance criteria and methodology. The present review highlights the variations, similarities and comparison between bioanalytical method validation guidelines issued by major regulatory authorities worldwide. Additionally, other evaluation parameters such as matrix effect, incurred sample reanalysis including other stability aspects have been discussed to provide an ease of access for designing a bioanalytical method and its validation complying with the majority of drug authority guidelines. Copyright © 2016. Published by Elsevier B.V.

Underground storage tank management plan, Oak Ridge Y-12 Plant, Oak Ridge, Tennessee

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1997-09-01

The Underground Storage Tank (UST) Program at the Oak Ridge Y-12 Plant was established to locate UST systems at the facility and to ensure that all operating UST systems are free of leaks. UST systems have been removed or upgraded in accordance with Tennessee Department of Environment and Conservation (TDEC) regulations and guidance. With the closure of a significant portion of the USTs, the continuing mission of the UST Management Program is to manage the remaining active UST systems and continue corrective actions in a safe regulatory compliant manner. This Program outlines the compliance issues that must be addressed, reviewsmore » the current UST inventory and compliance approach, and presents the status and planned activities associated with each UST system. The UST Program provides guidance for implementing TDEC regulations and guidelines for petroleum UST systems. The plan is divided into three major sections: (1) regulatory requirements, (2) active UST sites, and (3) out-of-service UST sites. These sections describe in detail the applicable regulatory drivers, the UST sites addressed under the Program, and the procedures and guidance for compliance.« less

Mesenchymal Stem Cells as Therapeutics Agents: Quality and Environmental Regulatory Aspects

PubMed Central

Sabata, Roger; Verges, Josep; Zugaza, José L.; Ruiz, Adolfina; Clares, Beatriz

2016-01-01

Mesenchymal stem cells (MSCs) are one of the main stem cells that have been used for advanced therapies and regenerative medicine. To carry out the translational clinical application of MSCs, their manufacturing and administration in human must be controlled; therefore they should be considered as medicine: stem cell-based medicinal products (SCMPs). The development of MSCs as SCMPs represents complicated therapeutics due to their extreme complex nature and rigorous regulatory oversights. The manufacturing process of MSCs needs to be addressed in clean environments in compliance with requirements of Good Manufacturing Practice (GMP). Facilities should maintain these GMP conditions according to international and national medicinal regulatory frameworks that introduce a number of specifications in order to produce MSCs as safe SCMPs. One of these important and complex requirements is the environmental monitoring. Although a number of environmental requirements are clearly defined, some others are provided as recommendations. In this review we aim to outline the current issues with regard to international guidelines which impact environmental monitoring in cleanrooms and clean areas for the manufacturing of MSCs. PMID:27999600

Proceedings: international regulatory considerations on development pathways for cell therapies.

PubMed

Feigal, Ellen G; Tsokas, Katherine; Viswanathan, Sowmya; Zhang, Jiwen; Priest, Catherine; Pearce, Jonathan; Mount, Natalie

2014-08-01

Regenerative medicine is a rapidly evolving field that faces novel scientific and regulatory challenges. In September 2013, the International Workshop on Regulatory Pathways for Cell Therapies was convened to discuss the nature of these challenges and potential solutions and to highlight opportunities for potential convergence between different regulatory bodies that might assist the field's development. The workshop discussions generated potentially actionable steps in five main areas that could mitigate cell therapy development pathway risk and accelerate moving promising therapies to patients. These included the need for convergence of regulatory guidelines on donor eligibility and suitability of lines for use in clinical trials and subsequent commercialization for cell therapies to move forward on a global basis; the need to challenge and encourage investigators in the regenerative medicine field to share information and provide examples of comparability studies related to master cell banks; the need for convergence of guidelines across regulatory jurisdictions on requirements for tumorigenicity studies, based on particular cell types and on biodistribution studies; the need to increase transparency in sharing clinical trial information more broadly and disseminating results more rapidly; and the need to establish a forum for sharing the experiences of various approaches being developed to expedite regulatory approvals and access for patients to innovative cell and regenerative therapies in the different regulatory jurisdictions and to assess their potential strengths and weaknesses. ©AlphaMed Press.

Iatrogenic Hepatitis C Virus Transmission and Safe Injection Practices.

PubMed

Defendorf, Charles M; Paul, Sindy; Scott, George J

2018-05-01

Hepatitis C virus (HCV) infection poses significant adverse health effects. Improper use of vials, needles, syringes, intravenous bags, tubing, and connectors for injections and infusions is a current preventable cause of iatrogenic HCV transmission. Numerous cases have demonstrated the need for continued vigilance and the widespread nature of this iatrogenic infection risk across a variety of medical practice settings in the United States. Failure to implement the evidence-based Centers for Disease Control and Prevention (CDC) infection prevention guidelines exposes patients to preventable harm. The guidelines establish the requirement to notify patients in cases of suspected virus transmission, as well as to screen those patients who would not otherwise have been at risk for HCV seroconversion and other bloodborne pathogens. Legal and regulatory ramifications, including state, criminal, and tort laws, hold physicians and other health care professionals accountable to use safe injection practices. This article reviews the major health risks of HCV infection, significant effects of iatrogenic infection transmission, CDC guidelines for safe injection practices, and legal regulations and ramifications designed to promote safe injection practices.

Vaccines in Argentina: a regulatory view.

PubMed

Pérez, A C; Diez, R A

2003-07-28

In Argentina, vaccines for immuno-preventable diseases are regulated by the national regulatory agency, the Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (the National Administration of Drugs, Food and Medical Devices, or ANMAT) created in 1992 to ensure efficacy and safety of drugs, food and medical devices available in the country, according to Law 16,463 and Decree 150/92. ANMAT has licensed 84 out of 157 vaccines registered in Argentina. Since 1994, ANMAT evaluated, approved and inspected 20 clinical trials with vaccines (1.8% of the 1062 trials approved by the agency since that time). The National System of Pharmaco-vigilance has received 318 communications of eventual adverse post-vaccination events (0.3% of the total). In addition, ANMAT provides support to the National Immunisation Programme. The current procedure is to follow international guidelines in the field, to be prepared for new, rapidly changing scenarios.

Aquatic Animal Models – Not Just for Ecotox Anymore

EPA Science Inventory

A wide range of internationally harmonized toxicity test guidelines employing aquatic animal models have been established for regulatory use. For fish alone, there are over a dozen internationally harmonized toxicity test guidelines that have been, or are being, validated. To dat...

Guidelines on Discrimination Because of Sex.

ERIC Educational Resources Information Center

Equal Employment Opportunity Commission, Washington, DC.

This brochure presents regulatory guidelines on sex discrimination with sections devoted to: general principles; sex as a bona fide occupational qualification; separate lines of progression and seniority systems; discrimination against married women; advertising job opportunities; employment agencies; pre-employment inquiries as to sex; the…

QSAR modeling: where have you been? Where are you going to?

PubMed

Cherkasov, Artem; Muratov, Eugene N; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

2014-06-26

Quantitative structure-activity relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists toward collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making.

QSAR Modeling: Where have you been? Where are you going to?

PubMed Central

Cherkasov, Artem; Muratov, Eugene N.; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I.; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C.; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E.; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

2014-01-01

Quantitative Structure-Activity Relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss: (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists towards collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making. PMID:24351051

The Regulatory Review Process in South Africa: Challenges and Opportunities for a New Improved System.

PubMed

Keyter, Andrea; Gouws, Joey; Salek, Sam; Walker, Stuart

2018-01-01

The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.

Regulatory forum opinion piece*: supporting the need for international harmonization of safety assessments for food flavoring substances.

PubMed

Konishi, Yoichi; Hayashi, Shim-Mo; Fukushima, Shoji

2014-08-01

The advancement of technology and the growth of international commerce underscore the need for global harmonization of regulatory safety requirements and their assessment pertaining to consumer products such as drugs, medical devices, and food. This need is particularly relevant when safety requirements involve time-intensive and costly animal safety studies. Here we present the current regulatory requirements in Europe, the United States, and Japan for flavoring substances (FSs) used in foods and point out significant differences relevant to the international standardization for safety assessments that in our opinion need to be addressed and overcome. The safety assessments that are carried out for FSs in various countries are influenced by divergent definitions of FS, by the information required and available for regulatory submission, and by different regulatory procedures, including the use of decision tree approaches. The European Food Safety Authority (EFSA), the Expert Panel of the U.S. Flavor and Extract Manufacturers Association (FEMA), and the Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) are making efforts to improve and harmonize the safety assessment of FSs. The application of in silico methods such as quantitative structure-activity relationships and read-across strategies relying on expert input are useful as a first-step screening of the assessment. Application of the Threshold of Toxicological Concern (TTC) approach permits conclusions that are compatible with the risk assessment approaches currently used by international advisory committees. The Japanese Regulatory Authority, on the other hand, does not yet consider in silico methods but still requires in vivo and in vitro genotoxicity test data as well as repeat-dose 90-day toxicity data in at least one species, to be submitted as the first step in the safety assessment of FSs. With this article, we echo requests that have been made for xenobiotics by the pharmaceutical industry worldwide, extending them to food-related products, especially FSs. We encourage regulatory agencies to adopt globally harmonized safety assessment procedures, regulatory guidelines, and review practices for FSs to foster global trade and to reduce costs and laboratory animal use. © 2013 by The Author(s).

Guidelines by the AAPM and GEC-ESTRO on the use of innovative brachytherapy devices and applications: Report of Task Group 167

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nath, Ravinder; Rivard, Mark J., E-mail: mark.j.rivard@gmail.com; DeWerd, Larry A.

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used in the evaluation of innovative devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining the equivalence of the innovative treatment modality to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of innovative radiotherapy devices or applications is a critical part in which physicists should be actively involved. The physicist’s role, along with physician colleagues, in this process is highlighted for innovative brachytherapy devices and applications andmore » includes evaluation of (1) dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, (2) risks and benefits from a regulatory and safety perspective, and (3) resource assessment and preparedness. Further, it is suggested that any developed calibration methods be traceable to a primary standards dosimetry laboratory (PSDL) such as the National Institute of Standards and Technology in the U.S. or to other PSDLs located elsewhere such as in Europe. Clinical users should follow standards as approved by their country’s regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the Accredited Dosimetry Calibration Laboratories in the U.S. is encouraged before a source is introduced into widespread routine clinical use. The American Association of Physicists in Medicine and the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) have developed guidelines for the safe and consistent application of brachytherapy using innovative devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. Nuclear Regulatory Commission, U.S. Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, U.S. Food and Drug Administration, European Commission for CE Marking (Conformité Européenne), and institutional review boards and radiation safety committees.« less

Re-evaluating ethical concerns in planned emergency research involving critically ill patients: an interpretation of the guidance document from the United States Food and Drug Administration.

PubMed

Smischney, Nathan J; Onigkeit, James A; Hinds, Richard F; Nicholson, Wayne T

2015-01-01

U.S. federal regulations require that certain ethical elements be followed to protect human research subjects. The location and clinical circumstances of a proposed research study can differ substantially and can have significant implications for these ethical considerations. Both the location and clinical circumstances are particularly relevant for research in intensive care units (ICUs), where patients are often unable to provide informed consent to participate in a proposed research intervention. Our goal is to elaborate on the updated 2013 U.S. Food and Drug Administration (FDA) guidance document regarding an exemption from the requirement of obtaining informed consent from patients or their surrogates and to address certain elements within that document, thereby assisting clinicians in developing a framework for emergency research in accordance with the regulatory bodies at their own institutions and in the United States. Review of the 2011 and updated FDA guidance document on exemption from informed consent. The current process of obtaining informed consent within ICUs needs to be revisited, especially for research in which timely informed consent is not likely. In particular, the process of obtaining informed consent may not be appropriate or even ethical for critically ill patients in extremis who require an intervention for which there is no current acceptable standard of care and clinical equipoise exists. We provide clinicians with a viewpoint that further elaborates on the FDA guidance document. The viewpoints provided herein are those of the authors and are therefore inherently limited by the personal views of a selected few. Other clinicians or researchers may not interpret the FDA guidelines in a similar manner. Moreover, the discussion of a guideline document is a limitation in and of itself. The guidelines set forth by the FDA are precisely that-guidelines. Therefore, they may not be followed as outlined in the guidance document within one's own institution. Our goal is that, by elaborating on the guidelines for planned research involving human subjects in the ICU, institutional regulatory bodies may gain a better understanding in drafting their own document when faced with a clinician or a researcher who wishes to conduct planned research in an ICU. We believe that the interpretations provided will allow clinicians to safely undertake planned research in ICUs without endangering the main tenets of ethical research involving human participants. This research is needed for the advancement of care in the critically ill. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

40 CFR 256.22 - Recommendations for State regulatory powers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Recommendations for State regulatory powers. 256.22 Section 256.22 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste...

40 CFR 256.22 - Recommendations for State regulatory powers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Recommendations for State regulatory powers. 256.22 Section 256.22 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste...

40 CFR 256.21 - Requirements for State regulatory powers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Requirements for State regulatory powers. 256.21 Section 256.21 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste...

40 CFR 256.21 - Requirements for State regulatory powers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Requirements for State regulatory powers. 256.21 Section 256.21 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste...

40 CFR 256.21 - Requirements for State regulatory powers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Requirements for State regulatory powers. 256.21 Section 256.21 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste...

40 CFR 256.22 - Recommendations for State regulatory powers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Recommendations for State regulatory powers. 256.22 Section 256.22 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste...

Safety of plant-made pharmaceuticals: product development and regulatory considerations based on case studies of two autologous human cancer vaccines.

PubMed

Tusé, Daniel

2011-03-01

Guidelines issued by regulatory agencies for the development of plant-made pharmaceutical (PMP) products provide criteria for product manufacturing and characterization, safety determination, containment and mitigation of environmental risks. Features of plant-made products do not always enable an easy fit within the criteria subscribed to by regulators. The unconventional nature of plant-based manufacturing processes and peculiarities of plant biology relative to that of traditional biological production systems have led to special considerations in the regulatory scrutiny of PMP. Presented in this review are case studies of two plant-made autologous (patient-specific) cancer vaccines, the nature of which introduced challenges to conventional and standardized development and preclinical evaluation routes. The rationale presented to FDA by the sponsors of each vaccine to build consensus and obtain variances to existing guidelines is discussed. While development of many plant-made biologics can be accomplished within the existing regulatory framework, the development of specialized products can be defended with rational arguments based on strong science.

Defining the pharmaceutical system to support proactive drug safety.

PubMed

Lewis, Vicki R; Hernandez, Angelica; Meadors, Margaret

2013-02-01

The military, aviation, nuclear, and transportation industries have transformed their safety records by using a systems approach to safety and risk mitigation. This article creates a preliminary model of the U.S. pharmaceutical system using available literature including academic publications, policies, and guidelines established by regulatory bodies and drug industry trade publications. Drawing from the current literature, the goals, roles, and individualized processes of pharmaceutical subsystems will be defined. Defining the pharmaceutical system provides a vehicle to assess and address known problems within the system, and provides a means to conduct proactive risk analyses, which would create significant pharmaceutical safety advancement.

The “Health Benefit Basket” in Denmark

PubMed Central

Ankjaer-Jensen, Anni; Danneskiold-Samsøe, Bent

2005-01-01

Until 2007, when the new legislation on health care becomes effective, the right to receive free health care services in Denmark, or “health benefits,” are described in a comprehensive set of legislation, including laws, executive orders and legal guidelines. This contribution provides an overview of the current main legislation regulating the Danish “health benefit basket” and describes the regulatory mechanisms for the provision of curative care at Danish hospitals and primary health care offices. Although the services are both financed and planned by the counties, they differ substantially in the way that benefits are regulated. PMID:16270211

World association for the advancement of veterinary parasitology (WAAVP) guideline for testing the efficacy of ectoparasiticides for fish.

PubMed

Sommerville, C; Endris, R; Bell, T A; Ogawa, K; Buchmann, K; Sweeney, D

2016-03-30

This guideline is intended to assist in the planning and execution of studies designed to assess the efficacy of ectoparasiticides for fish. It is the first ectoparasite-specific guideline to deal with studies set in the aquatic environment and therefore provides details for the maintenance of environmental standards for finfish. Information is included on a range of pre-clinical study designs as well as clinical studies in commercial/production sites, set within a regulatory framework. It provides information on the study animals, their welfare, husbandry and environmental requirements during the study. The most commonly pathogenic ectoparasites are presented with relevant points regarding life history, host challenge and numeric evaluation. Preparation and presentation of both topical and oral test treatments is provided, together with guidance on data collection and analysis. The guideline provides a quality standard or efficacy studies on finfish, which will assist researchers and regulatory authorities worldwide and contribute to the wider objective of harmonisation of procedures.

Evidence-based causation in toxicology: A 10-year retrospective.

PubMed

James, R C; Britt, J K; Halmes, N C; Guzelian, P S

2015-12-01

We introduced Evidence-based Toxicology (EBT) in 2005 to address the disparities that exist between the various Weight-of-Evidence (WOE) methods typically applied in the regulatory hazard decision-making arena and urged toxicologists to adopt the evidence-based guidelines long-utilized in medicine (i.e., Evidence-Based Medicine or EBM). This review of the activities leading to the adoption of evidence-based methods and EBT during the last decade demonstrates how fundamental concepts that form EBT, such as the use of systematic reviews to capture and consider all available information, are improving toxicological evaluations performed by various groups and agencies. We reiterate how the EBT framework, a process that provides a method for performing human chemical causation analyses in an objective, transparent and reproducible manner, differs significantly from past and current regulatory WOE approaches. We also discuss why the uncertainties associated with regulatory WOE schemes lead to a definition of the term "risk" that contains unquantifiable uncertainties not present in this term as it is used in epidemiology and medicine. We believe this distinctly different meaning of "risk" should be clearly conveyed to those not familiar with this difference (e.g., the lay public), when theoretical/nomologic risks associated with chemical-induced toxicities are presented outside of regulatory and related scientific parlance. © The Author(s) 2015.

Complex mixtures in industrial workspaces: lessons for indoor air quality evaluations.

PubMed

Lippy, B E; Turner, R W

1991-11-01

Acceptable occupational exposure levels for hundreds of airborne concentrations of dusts, vapors, fumes, and gases have been set by consensus organizations and regulatory bodies for decades. These levels have established tremendous precedent and are tempting reference values in the relatively new field of indoor air quality evaluations where validated criteria are greatly needed. The American Conference of Government Industrial Hygienists (ACGIH) has been the most visible and productive group setting these guidelines for industrial exposure. The ACGIH Chemical Substances Committee has published an annual list of threshold limit values (TLVs) for more than 40 years. Currently the list covers more than 400 substances. In 1989, the Occupational Safety and Health Administration (OSHA) published updated permissible exposure limits (PELs) for approximately 600 substances. Most PELs before this update were adopted from the 1968 ACGIH list of TLVs and consensus standards of the American Standards Association. This OSHA update has resulted in reductions of 212 PELs and the addition of 164 new levels. The magnitude of the problem of protecting workers can be seen by the small fraction that the OSHA PELs represent of the more than 60,000 entries in the National Institute for Occupational Safety and Health's Registry of Toxic Effects of Chemical Substances. None of these levels, whether guidelines or regulatory requirements, are established based on any possible synergistic effect with other chemicals. The only guidance given by the ACGIH for synergistic effects is that such cases must be determined individually. Clearly, there are major drawbacks in using occupational standards and guidelines for evaluating the health effects of chemical agents that can be found in office settings, often in concentrations orders of magnitude less than what is routinely measured in the workplace. These guidelines are even less valuable when the concern is the complex mixing of chemicals in nonoccupational environments.

40 CFR 256.62 - Requirements for public participation in State regulatory development.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Requirements for public participation in State regulatory development. 256.62 Section 256.62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE...

40 CFR 256.62 - Requirements for public participation in State regulatory development.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Requirements for public participation in State regulatory development. 256.62 Section 256.62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE...

40 CFR 256.62 - Requirements for public participation in State regulatory development.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Requirements for public participation in State regulatory development. 256.62 Section 256.62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE...

40 CFR 256.62 - Requirements for public participation in State regulatory development.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Requirements for public participation in State regulatory development. 256.62 Section 256.62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE...

76 FR 65753 - Monitoring the Effectiveness of Maintenance at Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0212] Monitoring the Effectiveness of Maintenance at...) re-issued Draft Regulatory Guide, DG-1278, ``Monitoring the Effectiveness of Maintenance at Nuclear... Revision 4A to Nuclear Management and Resources Council (NUMARC) 93-01, ``Industry Guideline for Monitoring...

40 CFR 256.62 - Requirements for public participation in State regulatory development.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Requirements for public participation in State regulatory development. 256.62 Section 256.62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE...

78 FR 44311 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

... Identifier No. 235 Americans With 3014-AA11 Disabilities Act (ADA) Accessibility Guidelines for Passenger... (ATBCB) Long-Term Actions 235. Americans With Disabilities Act (Ada) Accessibility Guidelines for... vessels covered by the Americans With Disabilities Act (ADA) are accessible to and usable by individuals...

76 FR 17064 - Shared Use Path Accessibility Guidelines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... industry professionals regarding matters covered in this notice. In particular, the Board invites comments... shared use path surfaces, either light-on-dark or dark-on-light. Size. Detectable warning surfaces shall... information on any additional areas that should be addressed in the guidelines. Regulatory Process Matters The...

Addressing the regulatory and scientific challenges in multiple sclerosis--a statement from the EU regulators.

PubMed

Balabanov, Pavel; Haas, Manuel; Elferink, Andre; Bakchine, Serge; Broich, Karl

2014-09-01

Improving and facilitating the process of making new drugs available to patients with multiple sclerosis (MS) requires cooperation among the regulators and other stakeholders. This cooperation will also positively contribute towards developing guidelines of the highest quality in medical, regulatory and scientific aspects. This would be beneficial both in areas that require further guideline development, but also in fields where existing guidance should be adapted to take into account evolution in science. Considering the input from all stakeholders, the European Medicines Agency confirmed its intention to update the relevant guideline and apply a flexible approach towards new drug development strategies in MS. This article is the first official position from the EU regulators, presenting the main changes to be expected in the guidance document. © The Author(s) 2014.

Relevance and reliability of experimental data in human health risk assessment of pesticides.

PubMed

Kaltenhäuser, Johanna; Kneuer, Carsten; Marx-Stoelting, Philip; Niemann, Lars; Schubert, Jens; Stein, Bernd; Solecki, Roland

2017-08-01

Evaluation of data relevance, reliability and contribution to uncertainty is crucial in regulatory health risk assessment if robust conclusions are to be drawn. Whether a specific study is used as key study, as additional information or not accepted depends in part on the criteria according to which its relevance and reliability are judged. In addition to GLP-compliant regulatory studies following OECD Test Guidelines, data from peer-reviewed scientific literature have to be evaluated in regulatory risk assessment of pesticide active substances. Publications should be taken into account if they are of acceptable relevance and reliability. Their contribution to the overall weight of evidence is influenced by factors including test organism, study design and statistical methods, as well as test item identification, documentation and reporting of results. Various reports make recommendations for improving the quality of risk assessments and different criteria catalogues have been published to support evaluation of data relevance and reliability. Their intention was to guide transparent decision making on the integration of the respective information into the regulatory process. This article describes an approach to assess the relevance and reliability of experimental data from guideline-compliant studies as well as from non-guideline studies published in the scientific literature in the specific context of uncertainty and risk assessment of pesticides. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

What impact will EPPO's new resistance risk assessment guideline have on selection pressure in the European Union?

PubMed

Leonard, Paul K; Dutton, Robert

2002-09-01

This paper examines practical and regulatory implications, including both costs and benefits, resulting from implementation of EPPO's new resistance risk analysis guideline. Crop-protection companies operating in Europe are preparing risk analyses and management strategies, and are monitoring for resistance. However, this is a complex and expensive process involving technical, commercial and regulatory functions. The actual cost of filling these data gaps is consequently greater than many would have anticipated. The agrochemical industry has a vested interest in managing resistance and is committed to maintaining the essential contribution of crop-protection products to sustainable agriculture. However, with increasing regulatory costs, it is important that regulatory authorities concentrate requirements for resistance risk analyses, management strategies and monitoring where these are most needed. Should these requirements be applied indiscriminately, crop-protection companies will have to consider whether or not it is economically justifiable to make these investments, or whether to remove less profitable uses from product labels. In such situations, minor crops stand to be disproportionately effected. One year after publication, it is too early to measure the guideline's impact on selection pressure. It is already clear that the guideline represents an unprecedented step forward in the regulation and harmonisation of resistance management. There are, however, valid arguments against regulation of resistance management. One of the most important criticisms that is levelled against the latter approach is that, with the best motivation and with appropriate use restrictions on labels, these actions alone do not solve the problem. It is critical that all stakeholders in the crop protection process are made aware of the importance of resistance management and of complying with prescribed strategies.

2016 Guidelines of the American Society of Mammalogists for the use of wild mammals in research and education.

PubMed

Sikes, Robert S

2016-06-09

Guidelines for use of wild mammal species in research are updated from Sikes et al. (2011) . These guidelines cover current professional techniques and regulations involving the use of mammals in research and teaching; they also incorporate new resources, procedural summaries, and reporting requirements. Included are details on capturing, marking, housing, and humanely killing wild mammals. It is recommended that Institutional Animal Care and Use Committees (IACUCs), regulatory agencies, and investigators use these guidelines as a resource for protocols involving wild mammals, whether studied in the field or in captivity. These guidelines were prepared and approved by the American Society of Mammalogists (ASM), in consultation with professional veterinarians experienced in wildlife research and IACUCs, whose collective expertise provides a broad and comprehensive understanding of the biology of nondomesticated mammals. The current version of these guidelines and any subsequent modifications are available online on the Animal Care and Use Committee page of the ASM website ( http://mammalogy.org/uploads/committee_files/CurrentGuidelines.pdf ). Additional resources pertaining to the use of wild animals in research are available at: http://www.mammalsociety.org/committees/animal-care-and-use#tab3 . Los lineamientos para el uso de especies de mamíferos de vida silvestre en la investigación con base en Sikes et al. (2011) se actualizaron. Dichos lineamientos cubren técnicas y regulaciones profesionales actuales que involucran el uso de mamíferos en la investigación y enseñanza; también incorporan recursos nuevos, resúmenes de procedimientos y requisitos para reportes. Se incluyen detalles acerca de captura, marcaje, manutención en cautiverio y eutanasia de mamíferos de vida silvestre. Se recomienda que los comités institucionales de uso y cuidado animal (cifras en inglés: IACUCs), las agencias reguladoras y los investigadores se adhieran a dichos lineamientos como fuente base de protocolos que involucren mamíferos de vida silvestre, ya sea investigaciones de campo o en cautiverio. Dichos lineamientos fueron preparados y aprobados por la ASM, en consulta con profesionales veterinarios experimentados en investigaciones de vida silvestre y IACUCS, de quienes cuya experiencia colectiva provee un entendimiento amplio y exhaustivo de la biología de mamíferos no-domesticados. La presente versión de los lineamientos y modificaciones posteriores están disponibles en línea en la página web de la ASM, bajo Cuidado Animal y Comité de Uso: ( http://mammalogy.org/uploads/committee_files/CurrentGuidelines.pdf ). Recursos adicionales relacionados con el uso de animales de vida silvestre para la investigación se encuentran disponibles en ( http://www.mammalsociety.org/committees/animal-care-and-use#tab3 ).

2016 Guidelines of the American Society of Mammalogists for the use of wild mammals in research and education

PubMed Central

Sikes, Robert S.

2016-01-01

Abstract Guidelines for use of wild mammal species in research are updated from Sikes et al. (2011) . These guidelines cover current professional techniques and regulations involving the use of mammals in research and teaching; they also incorporate new resources, procedural summaries, and reporting requirements. Included are details on capturing, marking, housing, and humanely killing wild mammals. It is recommended that Institutional Animal Care and Use Committees (IACUCs), regulatory agencies, and investigators use these guidelines as a resource for protocols involving wild mammals, whether studied in the field or in captivity. These guidelines were prepared and approved by the American Society of Mammalogists (ASM), in consultation with professional veterinarians experienced in wildlife research and IACUCs, whose collective expertise provides a broad and comprehensive understanding of the biology of nondomesticated mammals. The current version of these guidelines and any subsequent modifications are available online on the Animal Care and Use Committee page of the ASM website ( http://mammalogy.org/uploads/committee_files/CurrentGuidelines.pdf ). Additional resources pertaining to the use of wild animals in research are available at: http://www.mammalsociety.org/committees/animal-care-and-use#tab3 . R esumen Los lineamientos para el uso de especies de mamíferos de vida silvestre en la investigación con base en Sikes et al. (2011) se actualizaron. Dichos lineamientos cubren técnicas y regulaciones profesionales actuales que involucran el uso de mamíferos en la investigación y enseñanza; también incorporan recursos nuevos, resúmenes de procedimientos y requisitos para reportes. Se incluyen detalles acerca de captura, marcaje, manutención en cautiverio y eutanasia de mamíferos de vida silvestre. Se recomienda que los comités institucionales de uso y cuidado animal (cifras en inglés: IACUCs), las agencias reguladoras y los investigadores se adhieran a dichos lineamientos como fuente base de protocolos que involucren mamíferos de vida silvestre, ya sea investigaciones de campo o en cautiverio. Dichos lineamientos fueron preparados y aprobados por la ASM, en consulta con profesionales veterinarios experimentados en investigaciones de vida silvestre y IACUCS, de quienes cuya experiencia colectiva provee un entendimiento amplio y exhaustivo de la biología de mamíferos no-domesticados. La presente versión de los lineamientos y modificaciones posteriores están disponibles en línea en la página web de la ASM, bajo Cuidado Animal y Comité de Uso: ( http://mammalogy.org/uploads/committee_files/CurrentGuidelines.pdf ). Recursos adicionales relacionados con el uso de animales de vida silvestre para la investigación se encuentran disponibles en ( http://www.mammalsociety.org/committees/animal-care-and-use#tab3 ). PMID:29692469

77 FR 8014 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... agenda was developed under the guidelines of Executive Order 12866 ``Regulatory Planning and Review... regulations for review to determine whether they should be modified or eliminated. Proposed rules may be... Unified Agenda will be available online at www.reginfo.gov , in a format that offers users a greatly...

78 FR 44325 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

... developed under the guidelines of Executive Order 12866 ``Regulatory Planning and Review.'' GSA's purpose in.... GSA also invites interested persons to recommend existing significant regulations for review to... available online at www.reginfo.gov , in a format that offers users a greatly enhanced ability to obtain...

75 FR 4635 - Risk-Based Capital Guidelines; Capital Adequacy Guidelines; Capital Maintenance: Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... phase-in would unfairly penalize banking organizations given their already established businesses..., will aid banking organizations with capital planning as they implement FAS 166 and FAS 167 and adjust... assets a banking organization consolidates as a result of changes to U.S. generally accepted accounting...

77 FR 58419 - Guidelines for Preparing and Reviewing Licensing Applications for Instrumentation and Control...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... Applications for Instrumentation and Control Upgrades for Non-Power Reactors AGENCY: Nuclear Regulatory...-Power Reactors: Format and Content,'' for instrumentation and control upgrades and NUREG-1537, Part 2, ``Guidelines for Preparing and Reviewing Applications for the Licensing of Non-Power Reactors: Standard Review...

77 FR 64834 - Computational Fluid Dynamics Best Practice Guidelines for Dry Cask Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-23

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0250] Computational Fluid Dynamics Best Practice... public comments on draft NUREG-2152, ``Computational Fluid Dynamics Best Practice Guidelines for Dry Cask... System (ADAMS): You may access publicly-available documents online in the NRC Library at http://www.nrc...

A review of regulations and guidelines related to winter manure application

USDA-ARS?s Scientific Manuscript database

Application of animal manure to frozen and snow-covered soils can increase the risk of nutrient losses and impairment of water quality in regions with hardy winters. In conjunction with global distributions of animal densities, we reviewed world-wide regulatory and voluntary guidelines on winter man...

SUPPRESSION OF IMMUNE FUNCTION AND SUSCEPTIBILITY TO INFECTIONS IN HUMANS: ASSOCIATION OF IMMUNE FUNCTION WITH CLINICAL DISEASE

EPA Science Inventory

ABSTRACT
A number of regulatory agencies in western Europe, Japan and the US now include guidelines for evaluating the potential immunotoxicity of chemicals, including drugs, as part of routine toxicity testing. Most testing guidelines recommend observational or functional as...

78 FR 17727 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-22

... and each Exchange Director's underlying business, ISE also stated that it believes that Exchange... Exchange to align its Board structure in accordance with corporate governance best practices guidelines... Services Proxy Voting Guidelines, the CalPERS Core Principles of Accountable Corporate Governance, the TIAA...

75 FR 19436 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

..., the Commission is not publishing it for comment.\\4\\ This order approves the proposed rule change, as... NASDAQ OMX Corporate Governance Guidelines, however, provide a different standard for uncontested... contained in the Corporate Governance Guidelines; contested elections would remain subject to the plurality...

78 FR 36698 - Microbiology Devices; Reclassification of Nucleic Acid-Based Systems for Mycobacterium tuberculosis

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

... specimens from class III (premarket approval) into class II (special controls). FDA is also issuing the draft special controls guideline entitled ``Class II Special Controls Guideline: Nucleic Acid-Based In... regulatory controls needed to provide reasonable assurance of their safety and effectiveness. The three...

Translational Challenges in Cardiovascular Tissue Engineering.

PubMed

Emmert, Maximilian Y; Fioretta, Emanuela S; Hoerstrup, Simon P

2017-04-01

Valvular heart disease and congenital heart defects represent a major cause of death around the globe. Although current therapy strategies have rapidly evolved over the decades and are nowadays safe, effective, and applicable to many affected patients, the currently used artificial prostheses are still suboptimal. They do not promote regeneration, physiological remodeling, or growth (particularly important aspects for children) as their native counterparts. This results in the continuous degeneration and subsequent failure of these prostheses which is often associated with an increased morbidity and mortality as well as the need for multiple re-interventions. To overcome this problem, the concept of tissue engineering (TE) has been repeatedly suggested as a potential technology to enable native-like cardiovascular replacements with regenerative and growth capacities, suitable for young adults and children. However, despite promising data from pre-clinical and first clinical pilot trials, the translation and clinical relevance of such TE technologies is still very limited. The reasons that currently limit broad clinical adoption are multifaceted and comprise of scientific, clinical, logistical, technical, and regulatory challenges which need to be overcome. The aim of this review is to provide an overview about the translational problems and challenges in current TE approaches. It further suggests directions and potential solutions on how these issues may be efficiently addressed in the future to accelerate clinical translation. In addition, a particular focus is put on the current regulatory guidelines and the associated challenges for these promising TE technologies.

Recommendations for safety testing with the in vivo comet assay.

PubMed

Vasquez, Marie Z

2012-08-30

While the in vivo comet assay increases its role in regulatory safety testing, deliberations about the interpretation of comet data continue. Concerns can arise regarding comet assay publications with limited data from non-blind testing of positive control compounds and using protocols (e.g. dose concentrations, sample times, and tissues) known to give an expected effect. There may be a tendency towards bias when the validation or interpretation of comet assay data is based on results generated by widely accepted but non-validated assays. The greatest advantages of the comet assay are its sensitivity and its ability to detect genotoxicity in tissues and at sample times that could not previously be evaluated. Guidelines for its use and interpretation in safety testing should take these factors into account. Guidelines should be derived from objective review of data generated by blind testing of unknown compounds dosed at non-toxic concentrations and evaluated in a true safety-testing environment, where the experimental design and conclusions must be defensible. However, positive in vivo comet findings with such compounds are rarely submitted to regulatory agencies and this data is typically unavailable for publication due to its proprietary nature. To enhance the development of guidelines for safety testing with the comet assay, and with the permission of several sponsors, this paper presents and discusses relevant data from multiple GLP comet studies conducted blind, with unknown pharmaceuticals and consumer products. Based on these data and the lessons we have learned through the course of conducting these studies, I suggest significant adjustments to the current conventions, and I provide recommendations for interpreting in vivo comet assay results in situations where risk must be evaluated in the absence of carcinogenicity or clinical data. Copyright © 2012 Elsevier B.V. All rights reserved.

Cardiovascular considerations of attention deficit hyperactivity disorder medications: a report of the European Network on Hyperactivity Disorders work group, European Attention Deficit Hyperactivity Disorder Guidelines Group on attention deficit hyperactivity disorder drug safety meeting.

PubMed

Hamilton, Robert M; Rosenthal, Eric; Hulpke-Wette, Martin; Graham, John G I; Sergeant, Joseph

2012-02-01

Regulatory decisions regarding attention deficit hyperactivity disorder drug licensing and labelling, along with recent statements from professional associations, raise questions of practice regarding the evaluation and treatment of patients with attention deficit hyperactivity disorder. To address these issues for the European community, the European Network for Hyperkinetic Disorders, through its European Attention Deficit Hyperactivity Disorder Guidelines Group, organised a meeting between attention deficit hyperactivity disorder specialists, paediatric cardiovascular specialists, and representatives of the major market authorisation holders for attention deficit hyperactivity disorder medications. This manuscript represents their consensus on cardiovascular aspects of attention deficit hyperactivity disorder medications. Although sudden death has been identified in multiple young individuals on attention deficit hyperactivity disorder medication causing regulatory concern, when analysed for exposure using currently available data, sudden death does not appear to exceed that of the general population. There is no current evidence to suggest an incremental benefit to electrocardiography assessment of the general attention deficit hyperactivity disorder patient. Congenital heart disease patients have an increased prevalence of attention deficit hyperactivity disorder, and can benefit from attention deficit hyperactivity disorder therapies, including medication. The attention deficit hyperactivity disorder specialist is the appropriate individual to evaluate benefit and risk and recommend therapy in all patients, although discussion with a heart specialist is reasonable for congenital heart disease patients. For attention deficit hyperactivity disorder patients with suspected heart disease or risk factor/s for sudden death, assessment by a heart specialist is recommended, as would also be the case for a non-attention deficit hyperactivity disorder patient. The identification of risk factors for sudden death should not automatically exclude the use of attention deficit hyperactivity disorder medication.

Human Factors Guidelines for UAS in the National Airspace System

NASA Technical Reports Server (NTRS)

Hobbs, Alan; Shively, R. Jay

2013-01-01

The ground control stations (GCS) of some UAS have been characterized by less-than-adequate human-system interfaces. In some cases this may reflect a failure to apply an existing regulation or human factors standard. In other cases, the problem may indicate a lack of suitable guidance material. NASA is leading a community effort to develop recommendations for human factors guidelines for GCS to support routine beyond-line-of-sight UAS operations in the national airspace system (NAS). In contrast to regulations, guidelines are not mandatory requirements. However, by encapsulating solutions to identified problems or areas of risk, guidelines can provide assistance to system developers, users and regulatory agencies. To be effective, guidelines must be relevant to a wide range of systems, must not be overly prescriptive, and must not impose premature standardization on evolving technologies. By assuming that a pilot will be responsible for each UAS operating in the NAS, and that the aircraft will be required to operate in a manner comparable to conventionally piloted aircraft, it is possible to identify a generic set of pilot tasks and the information, control and communication requirements needed to support these tasks. Areas where guidelines will be useful can then be identified, utilizing information from simulations, operational experience and the human factors literature. In developing guidelines, we recognize that existing regulatory and guidance material will, at times, provide adequate coverage of an area. In other cases suitable guidelines may be found in existing military or industry human factors standards. In cases where appropriate existing standards cannot be identified, original guidelines will be proposed.

What do international ethics guidelines say in terms of the scope of medical research ethics?

PubMed

Bernabe, Rosemarie D L C; van Thiel, Ghislaine J M W; van Delden, Johannes J M

2016-04-26

In research ethics, the most basic question would always be, "which is an ethical issue, which is not?" Interestingly, depending on which ethics guideline we consult, we may have various answers to this question. Though we already have several international ethics guidelines for biomedical research involving human participants, ironically, we do not have a harmonized document which tells us what these various guidelines say and shows us the areas of consensus (or lack thereof). In this manuscript, we attempted to do just that. We extracted the imperatives from five internationally-known ethics guidelines and took note where the imperatives came from. In doing so, we gathered data on how many guidelines support a specific imperative. We found that there is no consensus on the majority of the imperatives and that in only 8.2% of the imperatives were there at least moderate consensus (i.e., consensus of at least 3 of the 5 ethics guidelines). Of the 12 clusters (Basic Principles; Research Collaboration; Social Value; Scientific Validity; Participant Selection; Favorable Benefit/Risk Ratio; Independent Review; Informed Consent; Respect for Participants; Publication and Registration; Regulatory Sanctions; and Justified Research on the Vulnerable Population), Informed Consent has the highest level of consensus and Research Collaboration and Regulatory Sanctions have the least. There was a lack of consensus in the majority of imperatives from the five internationally-known ethics guidelines. This may be partly explained by the differences among the guidelines in terms of their levels of specification as well as conceptual/ideological differences.

Legal principles of confidentiality and other public interests: Part 1.

PubMed

Fullbrook, Suzanne

The principles of confidentiality are of paramount importance to nurses and all health professionals. This is explicitly so as the Common Law recognizes confidentiality and supports its importance. However, current practice must take cognizance of the realities of 21st century healthcare delivery - we live in an age of electronic data that is potentially very difficult to keep secret. New rules, protocols and guidelines are being formulated, and regulatory bodies such as the Nursing and Midwifery Council (NMC) reflect such rules in their codes of professional conduct. There is, however, a debate that is suggesting that the rules that relate to confidentiality may need to expand or even bend a little as innovate ways of obtaining, storing, utilizing and communicating data continue to occupy the minds of government and those who formulate legal principles (British Medical Association, 2005). This series of three articles will explore these issues. The first part is a review of case law that explores the fundamental legal principles that underpin confidentiality. The second will concentrate on a review of the guidelines that are to be found in professional regulatory documentation - the NMC and the General Medical Council as they relate to the legal principles. The third and last part will review and reflect on issues that relate expressly to the implementation of electronic patient records, with a review of appropriate statutory legislation and principles of common law.

Actual concept of "probiotics": is it more functional to science or business?

PubMed

Caselli, Michele; Cassol, Francesca; Calò, Girolamo; Holton, John; Zuliani, Giovanni; Gasbarrini, Antonio

2013-03-14

It is our contention that the concept of a probiotic as a living bacterium providing unspecified health benefits is inhibiting the development and establishment of an evidence base for the growing field of pharmacobiotics. We believe this is due in part to the current regulatory framework, lack of a clear definition of a probiotic, the ease with which currently defined probiotics can be positioned in the market place, and the enormous profits earned for minimum investment in research. To avoid this, we believe the following two actions are mandatory: international guidelines by a forum of stakeholders made available to scientists and clinicians, patient organizations, and governments; public research funds made available to the scientific community for performing independent rigorous studies both at the preclinical and clinical levels.

Actual concept of "probiotics": Is it more functional to science or business?

PubMed Central

Caselli, Michele; Cassol, Francesca; Calò, Girolamo; Holton, John; Zuliani, Giovanni; Gasbarrini, Antonio

2013-01-01

It is our contention that the concept of a probiotic as a living bacterium providing unspecified health benefits is inhibiting the development and establishment of an evidence base for the growing field of pharmacobiotics. We believe this is due in part to the current regulatory framework, lack of a clear definition of a probiotic, the ease with which currently defined probiotics can be positioned in the market place, and the enormous profits earned for minimum investment in research. To avoid this, we believe the following two actions are mandatory: international guidelines by a forum of stakeholders made available to scientists and clinicians, patient organizations, and governments; public research funds made available to the scientific community for performing independent rigorous studies both at the preclinical and clinical levels. PMID:23539674

Challenges in cryopreservation of regulatory T cells (Tregs) for clinical therapeutic applications.

PubMed

Golab, Karolina; Leveson-Gower, Dennis; Wang, Xiao-Jun; Grzanka, Jakub; Marek-Trzonkowska, Natalia; Krzystyniak, Adam; Millis, J Michael; Trzonkowski, Piotr; Witkowski, Piotr

2013-07-01

Promising results of initial studies applying ex-vivo expanded regulatory T cell (Treg) as a clinical intervention have increased interest in this type of the cellular therapy and several new clinical trials involving Tregs are currently on the way. Methods of isolation and expansion of Tregs have been studied and optimized to the extent that such therapy is feasible, and allows obtaining sufficient numbers of Tregs in the laboratory following Good Manufacturing Practice (GMP) guidelines. Nevertheless, Treg therapy could even more rapidly evolve if Tregs could be efficiently cryopreserved and stored for future infusion or expansions rather than utilization of only freshly isolated and expanded cells as it is preferred now. Currently, our knowledge regarding the impact of cryopreservation on Treg recovery, viability, and functionality is still limited. Based on experience with cryopreserved peripheral blood mononuclear cells (PBMCs), cryopreservation may have a detrimental effect on Tregs, can decrease Treg viability, cause abnormal cytokine secretion, and compromise expression of surface markers essential for proper Treg function and processing. Therefore, optimal strategies and conditions for Treg cryopreservation in conjunction with cell culture, expansion, and processing for clinical application still need to be investigated and defined. Copyright © 2013 Elsevier B.V. All rights reserved.

Successful validation of in vitro methods in toxicology by ZEBET, the National Centre for Alternatives in Germany at the BfR (Federal Institute for Risk Assessment).

PubMed

Spielmann, Horst; Grune, Barbara; Liebsch, Manfred; Seiler, Andrea; Vogel, Richard

2008-06-01

A short description of the history of the 3Rs concept is given, which was developed as the scientific concept to refine, reduce and replace animal experiments by Russel and Burch more than 40 years ago. In addition, the legal framework in Europe for developing alternatives to animal experiments is given and the current status of in vitro systems in pharmacology and toxicology is described including an update on metabolising systems. The decrease in experimental animal numbers during the past decade in Europe is illustrated by the situation in Germany and the contribution of international harmonisation of test guidelines on reducing animal numbers in regulatory testing is described. A review of the development of the principles of experimental validation is given and the 3T3 NRU in vitro phototoxicity test is used as an example for a successful validation study, which led to the acceptance of the first in vitro toxicity test for regulatory purposes by the OECD. Finally, the currently accepted alternative methods for standardisation and safety testing of drugs, biologicals and medical devices are summarised.

News focus: Report on state and local air toxics regulatory strategies published by STAPPA/ALAPCO (State and Territorial Air Pollution Program Administrators/Association of Local Air Pollution Control Officials)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1989-12-01

The report is entitled Toxic Air Pollutants: State and Local Regulatory Strategies - 1989. The 364-page report is the result of a survey of state and local air pollution control agencies, which solicited information on their programs to control air toxics. According to the survey, every state currently has a program to address emissions of air toxics. Additionally, 27 of the 40 local agencies that responded to the survey have, or are developing, air toxics programs. The strategies employed by state and local agencies vary widely, including control technology requirements, risk assessment, acceptable ambient guidelines, or a combination of thesemore » approaches. This is a report summarizing the air toxics control programs currently implemented (or under development) by state and local air pollution control agencies throughout the US. The report is based upon a survey of all 50 states and 220 local air pollution control agencies conducted by the State and Territorial Air Pollution Program Administrators (STAPPA) and the Association of Local Air Pollution Control Officials (ALAPCO). This survey updates one published five years earlier.« less

Biosimilars in psoriasis: Clinical practice and regulatory perspectives in Latin America.

PubMed

de la Cruz, Claudia; de Carvalho, André V E; Dorantes, Gladys L; Londoño Garcia, Angela M; Gonzalez, Cesar; Maskin, Matías; Podoswa, Nancy; Redfern, Jan S; Valenzuela, Fernando; van der Walt, Joelle; Romiti, Ricardo

2017-01-01

Latin American countries view biosimilar agents as an effective approach to curtail health-care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country-specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health-care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes. © 2016 Japanese Dermatological Association.

Teratology studies in the rat.

PubMed

Leroy, Mariline; Allais, Linda

2013-01-01

The rat is the rodent species of choice for the regulatory safety testing of xenobiotics, such as medicinal products, food additives, and other chemicals. Many decades of experience and extensive data have accumulated for both general and developmental toxicology investigations in this species. The high fertility and large litter size of the rat are advantages for teratogenicity testing. The study designs are well defined in the regulatory guidelines and are relatively standardized between testing laboratories across the world. Teratology studies address maternal- and embryo-toxicity following exposure during the period of organogenesis. This chapter describes the design and conduct of a teratology study in the rat in compliance with the regulatory guidelines. The procedures for the handling and housing of the pregnant animals, the caesarean examinations and the sampling of fetuses for morphological examinations are described. The utility and design of preliminary studies and the inclusion of satellite animals in the main study for toxicokinetic sampling are discussed.

Global bioanalytical support.

PubMed

John Lin, Zhongping; Zhang, Tianyi; Pasas-Farmer, Stephanie; Brooks, Stephen D; Moyer, Michael; Connolly, Ron

2014-05-01

With the globalization of drug development, there is an increasing need for global bioanalytical support. Bioanalysis provides pivotal data for toxicokinetic, pharmacokinetic, bioavailability and bioequivalence studies used for regional or global regulatory submission. There are many known complications in building a truly global bioanalytical operation, ranging from lack of global regulatory guidelines and global standard operating procedures to barriers in regional requirements on sample shipping, importation and exportation. The primary objective of this article is to discuss common experiences and challenges facing the biopharmaceutical industry when providing bioanalytical support in a global setting. The key components of global bioanalytical services include the supporting infrastructure, spanning project management, IT support of data management, best practices in bioanalytical method transfer and sample analysis, and comprehensive knowledge of the requirements of bioanalysis guidelines and differences in these guidelines. A case study will highlight best practices for successful management of a global project.

WHO consultation on clinical evaluation of vaccines, 17-18 July 2014, WHO Headquarters, Geneva, Switzerland.

PubMed

Knezevic, Ivana; Moorthy, Vasee; Sheets, Rebecca

2015-04-21

A World Health Organization (WHO) consultation on guidelines for National Regulatory Authorities (NRAs) and vaccine manufacturers on clinical evaluation of vaccines was held from 17 to 18 July 2014, to review key scientific challenges that regulators have been facing since the establishment of the WHO Guidelines on Clinical Evaluation of Vaccines. The guidelines, adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2001, have served as the basis for setting or updating national requirements for the evaluation and licensing of a broad range of vaccines as well as for WHO vaccine prequalification. Regulators from Australia, Brazil, China, Canada, Germany, India, Republic of Korea, South Africa, United States of America and the United Kingdom were represented. The International Federation for Pharmaceutical Manufacturers' Association (IFPMA) and the Developing Country Vaccine Manufacturers' Network (DCVMN) provided industry representation. The consultation concluded that the guidelines should be revised to address issues that were raised in the context of vaccines that were the subject of clinical development in the past decade. Although the current guidelines have served well over time, it was recognized that an update would further increase their utility and would help regulators, manufacturers, vaccine developers and academia to respond to the challenging questions regarding the safety, immunogenicity, efficacy and effectiveness of vaccines intended for global use. A summary of the main outcomes of the consultation and proposals for the next steps regarding the guidelines and beyond are provided in this report. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape.

PubMed

Arshad, Zeeshaan; Halioua-Haubold, Celine-Lea; Roberts, Mackenna; Urso-Baiarda, Fulvio; Branford, Oliver A; Brindley, David A; Davies, Benjamin M; Pettitt, David

2018-02-17

Adipose tissue, which can be readily harvested via a number of liposuction techniques, offers an easily accessible and abundant source of adipose-derived stem cells (ASCs). Consequently, ASCs have become an increasingly popular reconstructive option and a novel means of aesthetic soft tissue augmentation. This paper examines recent advances in the aesthetic surgery field, extending beyond traditional review formats to incorporate a comprehensive analysis of current clinical trials, adoption status, and the commercialization pathway. Keyword searches were carried out on clinical trial databases to search for trials using ASCs for aesthetic indications. An intellectual property landscape was created using commercial software (Thomson Reuters Thomson Innovation, New York, NY). Analysis of who is claiming what in respect of ASC use in aesthetic surgery for commercial purposes was analyzed by reviewing the patent landscape in relation to these techniques. Key international regulatory guidelines were also summarized. Completed clinical trials lacked robust controls, employed small sample sizes, and lacked long-term follow-up data. Ongoing clinical trials still do not address such issues. In recent years, claims to intellectual property ownership have increased in the "aesthetic stem cell" domain, reflecting commercial interest in the area. However, significant translational barriers remain including regulatory challenges and ethical considerations. Further rigorous randomized controlled trials are required to delineate long-term clinical efficacy and safety. Providers should consider the introduction of patient reported outcome metrics to facilitate clinical adoption. Robust regulatory and ethical policies concerning stem cells and aesthetic surgery should be devised to discourage further growth of "stem cell tourism." © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

75 FR 41914 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-19

... consolidated last sale price by the same specified percentage. The numerical percentage proposed to be used in the Trading Collar price calculations will be equal to the appropriate ``numerical guideline... Collars will automatically be adjusted to match any future changes in the numerical guidelines in NYSE...

75 FR 36739 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

....'' Second, the Exchange proposes replacing existing paragraph (c)(4) of Rule 52.4, entitled ``Numerical... eliminate the ability of the Exchange to deviate from the Numerical Guidelines contained in paragraph (c)(1... existing paragraph (c)(2), which provides flexibility to the Exchange to use different Numerical Guidelines...

76 FR 54739 - Pacific Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-02

... Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific Halibut in...) for the guided sport fishery in International Pacific Halibut Commission (IPHC) Regulatory Areas 2C... sport fishery for halibut. The GHLs are benchmark harvest levels for participants in the guided sport...

78 FR 18323 - Pacific Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... Halibut Fishery; Guideline Harvest Levels for the Guided Sport Fishery for Pacific Halibut in...) for the guided sport fishery in International Pacific Halibut Commission (IPHC) Regulatory Areas 2C... the guided sport fishery for halibut. The GHLs are benchmark harvest levels for participants in the...

Arsenic in private drinking water wells: an assessment of jurisdictional regulations and guidelines for risk remediation in North America.

PubMed

Chappells, Heather; Parker, Louise; Fernandez, Conrad V; Conrad, Cathy; Drage, John; O'Toole, Gary; Campbell, Norma; Dummer, Trevor J B

2014-09-01

Arsenic is a known carcinogen found globally in groundwater supplies due to natural geological occurrence. Levels exceeding the internationally recognized safe drinking water standard of 10 μg/L have been found in private drinking water supplies in many parts of Canada and the United States. Emerging epidemiological evidence confirms groundwater arsenic to be a significant health concern, even at the low to moderate levels typically found in this region. These findings, coupled with survey data reporting limited public adherence to testing and treatment guidelines, have prompted calls for improved protective measures for private well users. The purpose of this review is to assess current jurisdictional provisions for private well water protection in areas where arsenic is known to naturally occur in groundwater at elevated levels. Significant limitations in risk management approaches are identified, including inconsistent and uncoordinated risk communication approaches, lack of support mechanisms for routine water testing and limited government resources to check that testing and treatment guidelines are followed. Key action areas are discussed that can help to build regulatory, community and individual capacity for improved protection of private well water supplies and enhancement of public health.

Vibrio Species in Wastewater Final Effluents and Receiving Watershed in South Africa: Implications for Public Health.

PubMed

Okeyo, Allisen N; Nontongana, Nolonwabo; Fadare, Taiwo O; Okoh, Anthony I

2018-06-15

Wastewater treatment facilities in South Africa are obliged to make provision for wastewater effluent quality management, with the aim of securing the integrity of the surrounding watersheds and environments. The Department of Water Affairs has documented regulatory parameters that have, over the years, served as a guideline for quality monitoring/management purposes. However, these guidelines have not been regularly updated and this may have contributed to some of the water quality anomalies. Studies have shown that promoting the monitoring of the current routinely monitored parameters (both microbial and physicochemical) may not be sufficient. Organisms causing illnesses or even outbreaks, such as Vibrio pathogens with their characteristic environmental resilience, are not included in the guidelines. In South Africa, studies that have been conducted on the occurrence of Vibrio pathogens in domestic and wastewater effluent have made it apparent that these pathogens should also be monitored. The importance of effective wastewater management as one of the key aspects towards protecting surrounding environments and receiving watersheds, as well as protecting public health, is highlighted in this review. Emphasis on the significance of the Vibrio pathogen in wastewater is a particular focus.

Monitoring ethical, legal, and social issues in developing population genetic databases.

PubMed

Austin, Melissa A; Harding, Sarah E; McElroy, Courtney E

2003-01-01

To characterize ethical, legal, and social issues unique to population genetic database research and to determine the relevance of international recommendations and guidelines for addressing these issues in the development of "genebank" projects globally. Building on our previous description of eight international genebanks, we conducted a comprehensive electronic search and literature review of relevant publications and consulted national and international documents applicable to genebank research. We identified and characterized five categories of ethical, legal, and social issues unique to genebank development: sponsorship and benefit-sharing, neutrality and regulatory power of ethics committees, public engagement, consent, and data protection. We illustrate these issues with examples from specific genebanks. Not all of the issues are addressed in current international guidelines, many of which are nonspecific and unenforceable. The trend of genebank development promises to provide new discoveries to the field of medical science and to greatly improve public health. However, there is a growing need for more explicit, enforceable, and coordinated international guidelines relevant to the development and implementation of genebanks. By comparing ethical, legal and social issues as they arise in genebanks, researchers can better evaluate how to best use these projects to improve public health while protecting participating populations.

Canadian Association of General Surgeons position statement: recommendations for surgeons with blood-borne communicable diseases.

PubMed

Cleary, Sean; Doucette, Karen; Doig, Christopher J; Coffin, Carla; Grant, David; Dixon, Elijah

2016-04-01

The potential for transmission of hematogenously transmitted pathogens during exposure-prone procedures is a clinically important concern to both patients and surgeons. There is inconsistency among regulatory bodies in Canada regarding the management of infection risk among surgeons, particularly with regard to screening and the postexposure management of infected surgeons. The Canadian Association of General Surgeons commissioned a task force to review the evidence regarding the management of blood-borne pathogens and transmission risk during surgical procedures. The results of this review indicate a need for several jurisdictions to update their guidelines to reflect current evidence-based practices.

Bioprocessing of plant-derived virus-like particles of Norwalk virus capsid protein under current Good Manufacture Practice regulations

PubMed Central

Lai, Huafang; Chen, Qiang

2012-01-01

Despite the success in expressing a variety of subunit vaccine proteins in plants and the recent stride in improving vaccine accumulation levels by transient expression systems, there is still no plant-derived vaccine that has been licensed for human use. The lack of commercial success of plant-made vaccines lies in several technical and regulatory barriers that remain to be overcome. These challenges include the lack of scalable downstream processing procedures, the uncertainty of regulatory compliance of production processes, and the lack of demonstration of plant-derived products that meet the required standards of regulatory agencies in identity, purity, potency and safety. In this study, we addressed these remaining challenges and successfully demonstrate the ability of using plants to produce a pharmaceutical grade Norwalk virus (NV) vaccine under current Good Manufacture Practice (cGMP) guidelines at multiple gram scales. Our results demonstrate that an efficient and scalable extraction and purification scheme can established for processing virus-like particles (VLP) of NV capsid protein (NVCP). We successfully operated the upstream and downstream NVCP production processes under cGMP regulations. Furthermore, plant-derived NVCP VLP demonstrates the identity, purity, potency and safety that meet the preset release specifications. This material is being tested in a Phase I human clinical trial. This research provides the first report of producing a plant-derived vaccine at scale under cGMP regulations in an academic setting and an important step for plant-produced vaccines to become a commercial reality. PMID:22134876

Developmental immunotoxicity of chemicals in rodents and its possible regulatory impact.

PubMed

Hessel, Ellen V S; Tonk, Elisa C M; Bos, Peter M J; van Loveren, Henk; Piersma, Aldert H

2015-01-01

Around 25% of the children in developed countries are affected with immune-based diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune diseases have shown increasing prevalences in the last decades. The role of chemical exposures in these phenomena is unclear. It is thought that the developmental immune system is more susceptible to toxicants than the mature situation. Developmental immunotoxicity (DIT) testing is nowadays not or minimally included in regulatory toxicology requirements. We reviewed whether developmental immune parameters in rodents would provide relatively sensitive endpoints of toxicity, whose inclusion in regulatory toxicity testing might improve hazard identification and risk assessment of chemicals. For each of the nine reviewed toxicants, the developing immune system was found to be at least as sensitive or more sensitive than the general (developmental) toxicity parameters. Functional immune (antigen-challenged) parameters appear more affected than structural (non-challenged) immune parameters. Especially, antibody responses to immune challenges with keyhole limpet hemocyanine or sheep red blood cells and delayed-type hypersensitivity responses appear to provide sensitive parameters of developmental immune toxicity. Comparison with current tolerable daily intakes (TDI) and their underlying overall no observed adverse effect levels showed that for some of the compounds reviewed, the TDI may need reconsideration based on developmental immune parameters. From these data, it can be concluded that the developing immune system is very sensitive to the disruption of toxicants independent of study design. Consideration of including functional DIT parameters in current hazard identification guidelines and wider application of relevant study protocols is warranted.

Study of quality assurance regulations for linear accelerators in Korea: A comparison study between the current status in Korea and the international guidelines

NASA Astrophysics Data System (ADS)

Lee, Hyunho; Jeong, Seonghoon; Jo, Yunhui; Yoon, Myonggeun

2015-07-01

Quality assurance (QA) for medical linear accelerators is indispensable for appropriate cancer treatment. Some international organizations and advanced Western countries have provided QA guidelines for linear accelerators. Currently, QA regulations for linear accelerators in Korean hospitals specify a system in which each hospital stipulates its independent hospital-based protocols for QA procedures (HP_QAPs) and conducts QA based on those HP_QAPs while regulatory authorities verify whether items under those HP_QAPs have been performed. However, because this regulatory method cannot guarantee the quality of universal treatment and QA items with tolerance criteria are different in many hospitals, the presentation of standardized QA items and tolerance criteria is essential. In this study, QA items in HP_QAPs from various hospitals and those presented by international organizations, such as the International Atomic Energy Agency, the European Union, and the American Association of Physicist in Medicine, and by advanced Western countries, such as the USA, the UK, and Canada, were compared. Concordance rates between QA items for linear accelerators that were presented by the aforementioned organizations and those currently being implemented in Korean hospitals were shown to exhibit a daily QA of 50%, a weekly QA of 22%, a monthly QA of 43%, and an annual QA of 65%, and the overall concordance rates of all QA items were approximately 48%. In the comparison between QA items being implemented in Korean hospitals and those being implemented in advanced Western countries, concordance rates were shown to exhibit a daily QA of 50%, a weekly QA of 33%, a monthly QA of 60%, and an annual QA of 67%, and the overall concordance rates of all QA items were approximately 57%. The results of this study indicate that the HP_QAPs currently implemented by Korean hospitals as QA standards for linear accelerators used in radiation therapy do not meet international standards. If this problem is to be solved, national standardized QA items and procedures for linear accelerators need to be developed.

Physico-chemical properties of manufactured nanomaterials - Characterisation and relevant methods. An outlook based on the OECD Testing Programme.

PubMed

Rasmussen, Kirsten; Rauscher, Hubert; Mech, Agnieszka; Riego Sintes, Juan; Gilliland, Douglas; González, Mar; Kearns, Peter; Moss, Kenneth; Visser, Maaike; Groenewold, Monique; Bleeker, Eric A J

2018-02-01

Identifying and characterising nanomaterials require additional information on physico-chemical properties and test methods, compared to chemicals in general. Furthermore, regulatory decisions for chemicals are usually based upon certain toxicological properties, and these effects may not be equivalent to those for nanomaterials. However, regulatory agencies lack an authoritative decision framework for nanomaterials that links the relevance of certain physico-chemical endpoints to toxicological effects. This paper investigates various physico-chemical endpoints and available test methods that could be used to produce such a decision framework for nanomaterials. It presents an overview of regulatory relevance and methods used for testing fifteen proposed physico-chemical properties of eleven nanomaterials in the OECD Working Party on Manufactured Nanomaterials' Testing Programme, complemented with methods from literature, and assesses the methods' adequacy and applications limits. Most endpoints are of regulatory relevance, though the specific parameters depend on the nanomaterial and type of assessment. Size (distribution) is the common characteristic of all nanomaterials and is decisive information for classifying a material as a nanomaterial. Shape is an important particle descriptor. The octanol-water partitioning coefficient is undefined for particulate nanomaterials. Methods, including sample preparation, need to be further standardised, and some new methods are needed. The current work of OECD's Test Guidelines Programme regarding physico-chemical properties is highlighted. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Guidelines for innovation in pediatric surgery.

PubMed

Kastenberg, Zachary; Dutta, Sanjeev

2011-05-01

Surgical innovation involves the conceptualization, research, and translation of a novel idea into a viable procedure or device. The technological advancements made within the field of pediatric surgery over the last century have led to major improvements in patient care and outcomes. There has, however, been a parallel increase in the complexity of the regulatory bodies governing research and device implementation. This article briefly outlines the history of innovation in pediatric surgery, describes the existing regulatory bodies governing surgical research and device development (i.e., Department of Health and Human Services, Food and Drug Administration), and offers a set of guidelines for the pediatric surgeon planning to incorporate a new procedure or device into clinical practice.

Clinical guidelines in the European Union: mapping the regulatory basis, development, quality control, implementation and evaluation across member states.

PubMed

Legido-Quigley, Helena; Panteli, Dimitra; Brusamento, Serena; Knai, Cécile; Saliba, Vanessa; Turk, Eva; Solé, Meritxell; Augustin, Uta; Car, Josip; McKee, Martin; Busse, Reinhard

2012-10-01

Clinical guidelines are advocated to improve the quality of care, especially for chronic diseases. However, the regulatory basis of clinical guidelines, their development, quality control, implementation and use as well as evaluation within countries across the European Union is not systematically known. Using information collected from key informants in each country by means of a structured questionnaire, this mapping exercise illustrates the varied status of guideline production in European Union countries. Most European Union countries have an established national, regional or local clinical guideline programme, and a substantial proportion have developed guidelines on the prevention and management of chronic diseases. Several countries have mechanisms in place to ensure the quality of scientific evidence used for the development of guidelines is high and that the process is consistent and transparent. Others are only now taking an interest in guideline development and are taking the first steps towards establishing ways of implementing them. The majority of countries have no legal basis for the development of guidelines and those that have well established systems mostly implement them on a voluntary basis. The process of guideline development varies in its degrees of decentralisation across countries with many different types of organisations taking on this responsibility. There is general acceptance of the value of the instrument developed by the AGREE collaboration for evaluating the methodological robustness of guidelines. However, the extent to which guidelines are implemented in Europe is unknown, as there is no systematic data collection and, in most countries, no structure to enable it. There are few examples of formal evaluations of the development, quality, implementation and use of guidelines. Our findings call for renewed efforts to respond to the severe lack of standardized guideline terminology and accessibility as well as rigorous studies to evaluate the relationship between different ways to develop guidelines and their methodological quality, between their quality and the actual implementation and usage, and finally between implementation and health outcomes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[Biosimilars--opportunity or threat?].

PubMed

Swierkot, Jerzy

2013-01-01

Strong interest in biosimilars dates back several years. In the coming years the patent protection ends for subsequent biological drugs, including monoclonal antibodies. This paper organizes the most important facts related to the issue of biosimilars. A biosimilar is a biotherapeutic product which is similar in terms of quality, efficacy and safety to an already licensed reference biotherapeutic product'. It should be noted that biosimilars approved underthe current regulations of the European Medicines Agency (EMA) meet the stringent standards of safety, efficacy and immunogenicity. It is also important to realize that the biosimilar has the right to that name, if it is registered by regulatory authorities like EMA or FDA. One should not confuse biosimilar drugs with those which counterfeit or imitate. Clinical trials on the convertibility of innovative and biosimilar drugs are ongoing. Nevertheless,there is no regulatory framework and clear guidelines of conduct in this regard. In the near future, thanks to the registration of the first biosimilar monoclonal antibodies in rheumatology and gastroenterology the availability of biological treatment for patients should increase.

Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

PubMed

Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

Precision Cardiovascular Medicine: State of Genetic Testing.

PubMed

Giudicessi, John R; Kullo, Iftikhar J; Ackerman, Michael J

2017-04-01

In the 15 years following the release of the first complete human genome sequences, our understanding of rare and common genetic variation as determinants of cardiovascular disease susceptibility, prognosis, and therapeutic response has grown exponentially. As such, the use of genomics to enhance the care of patients with cardiovascular diseases has garnered increased attention from clinicians, researchers, and regulatory agencies eager to realize the promise of precision genomic medicine. However, owing to a large burden of "complex" common diseases, emphasis on evidence-based practice, and a degree of unfamiliarity/discomfort with the language of genomic medicine, the development and implementation of genomics-guided approaches designed to further individualize the clinical management of a variety of cardiovascular disorders remains a challenge. In this review, we detail a practical approach to genetic testing initiation and interpretation as well as review the current state of cardiovascular genetic and pharmacogenomic testing in the context of relevant society and regulatory agency recommendations/guidelines. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

NIEHS/FDA CLARITY-BPA research program update.

PubMed

Heindel, Jerrold J; Newbold, Retha R; Bucher, John R; Camacho, Luísa; Delclos, K Barry; Lewis, Sherry M; Vanlandingham, Michelle; Churchwell, Mona I; Twaddle, Nathan C; McLellen, Michelle; Chidambaram, Mani; Bryant, Matthew; Woodling, Kellie; Gamboa da Costa, Gonçalo; Ferguson, Sherry A; Flaws, Jodi; Howard, Paul C; Walker, Nigel J; Zoeller, R Thomas; Fostel, Jennifer; Favaro, Carolyn; Schug, Thaddeus T

2015-12-01

Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. Published by Elsevier Inc.

NIEHS/FDA CLARITY-BPA research program update

PubMed Central

Heindel, Jerrold J.; Newbold, Retha R.; Bucher, John R.; Camacho, Luísa; Delclos, K. Barry; Lewis, Sherry M.; Vanlandingham, Michelle; Churchwell, Mona I.; Twaddle, Nathan C.; McLellen, Michelle; Chidambaram, Mani; Bryant, Matthew; Woodling, Kellie; Gamboa da Costa, Gonçalo; Ferguson, Sherry A.; Flaws, Jodi; Howard, Paul C.; Walker, Nigel J.; Zoeller, R. Thomas; Fostel, Jennifer; Favaro, Carolyn; Schug, Thaddeus T.

2016-01-01

Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. PMID:26232693

Development of the risk-based, phased-in approach for the international harmonization of the regulation of container closure systems for drugs in Taiwan.

PubMed

Chang, Lin-Chau; Kang, Jaw-Jou; Gau, Churn-Shiouh

2016-06-01

The main concern for container closure systems of drugs is to ensure suitability for the intended use which is associated with issues regarding protection, compatibility, safety, and performance. Among various concerns, leachables may pose a safety hazard to patients, while risks might vary depending on the dosage form and the administration route. Stringent regulatory authorities such as the European Medicines Agency and the United States Food and Drug Administration have established risk-based regulatory requirements and published corresponding guidelines to facilitate implementation. Taiwan, a member of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, makes every effort to harmonize with international regulations and to strengthen protection of public health through regulatory controls. The aim of the present study was to investigate the regulatory framework and policies set by stringent regulatory authorities. The strategy proposed for the development of an eventual guideline was sent to the Taiwan Food and Drug Administration for decision. A risk-based, phased-in approach which was extensively discussed in the expert committee was proposed. The approach proposed herein could also serve as a starting point which is worth considered by other countries in which international harmonization is in process. Copyright © 2016 Elsevier Inc. All rights reserved.

Perspectives on Validation of High-Throughput Assays Supporting 21st Century Toxicity Testing1

PubMed Central

Judson, Richard; Kavlock, Robert; Martin, Matt; Reif, David; Houck, Keith; Knudsen, Thomas; Richard, Ann; Tice, Raymond R.; Whelan, Maurice; Xia, Menghang; Huang, Ruili; Austin, Christopher; Daston, George; Hartung, Thomas; Fowle, John R.; Wooge, William; Tong, Weida; Dix, David

2014-01-01

Summary In vitro, high-throughput screening (HTS) assays are seeing increasing use in toxicity testing. HTS assays can simultaneously test many chemicals, but have seen limited use in the regulatory arena, in part because of the need to undergo rigorous, time-consuming formal validation. Here we discuss streamlining the validation process, specifically for prioritization applications in which HTS assays are used to identify a high-concern subset of a collection of chemicals. The high-concern chemicals could then be tested sooner rather than later in standard guideline bioassays. The streamlined validation process would continue to ensure the reliability and relevance of assays for this application. We discuss the following practical guidelines: (1) follow current validation practice to the extent possible and practical; (2) make increased use of reference compounds to better demonstrate assay reliability and relevance; (3) deemphasize the need for cross-laboratory testing, and; (4) implement a web-based, transparent and expedited peer review process. PMID:23338806

WHO expert committee on specifications for pharmaceutical preparations.

PubMed

2013-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: Release procedure for International Chemical Reference Substances; WHO guidelines on quality risk management; WHO guidelines on variations to a prequalified product; and the Collaborative procedure between the World Health Organization Prequalification of Medicines Programme and national medicines regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products.

75 FR 36762 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing of Proposed Rule Change, as...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

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75 FR 36752 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing of a Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

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Occupational Safety and Health in Vocational Education: A Guide for Administrators, Faculty, and Staff.

ERIC Educational Resources Information Center

Godbey, Frank W.

This guide is intended to help administrators at schools having vocational education programs assess their occupational safety and health needs and establish a program to ensure a safer and more healthful work environment. It consists of three sections: (1) administrative guidelines, (2) technical-regulatory guidelines, and (3) a self-evaluation…

Infant Mental Health Assessment and Intervention Guidance for Service Providers and Families of Young Children. Service Guideline 4.

ERIC Educational Resources Information Center

Connecticut Birth to Three System, Hartford.

This guide offers assessment and intervention guidelines for the Connecticut Birth to Three system concerning the emotional and psychological well-being of infants and toddlers in the system. Emphasis is on infants and toddlers who exhibit symptoms of traumatic stress disorder, depression or other affective disorders, regulatory disorders, sleep…

The Dessau workshop on bioaccumulation: state of the art, challenges and regulatory implications.

PubMed

Treu, Gabriele; Drost, Wiebke; Jöhncke, Ulrich; Rauert, Caren; Schlechtriem, Christian

2015-01-01

Bioaccumulation plays a vital role in understanding the fate of a substance in the environment and is key to the regulation of chemicals in several jurisdictions. The current assessment approaches commonly use the octanol-water partition coefficient (log K OW ) as an indicator for bioaccumulation and the bioconcentration factor (BCF) as a standard criterion to identify bioaccumulative substances show limitations. The log K OW does not take into account active transport phenomena or special structural properties (e.g., amphiphilic substances or dissociating substances) and therefore additional screening criteria are required. Regulatory BCF studies are so far restricted to fish and uptake through the gills. Studies on (terrestrial) air-breathing organisms are missing. Though there are alternative tests such as the dietary exposure bioaccumulation fish test described in the recently revised OECD test guideline 305, it still remains unclear how to deal with results of alternative tests in regulatory decision-making processes. A substantial number of bioaccumulation fish tests are required in regulation. The development of improved test systems following the 3R principles, namely to replace, reduce and refine animal testing, is thus required. All these aspects stress the importance to further develop the assessment of bioaccumulation. The Dessau Workshop on Bioaccumulation which was held from June 26th to 27th 2014, in Dessau, Germany, provided a comprehensive overview of the state of the art of bioaccumulation assessment, provided insights into the problems and challenges addressed by the regulatory authorities and described new research concepts and their regulatory implications. The event was organised by UBA (Dessau, Germany) and Fraunhofer IME (Schmallenberg, Germany). About 50 participants from industry, regulatory bodies and academia listened to 14 lectures on selected topics and joined the plenary discussions.

Validation of cell-based fluorescence assays: practice guidelines from the ICSH and ICCS - part IV - postanalytic considerations.

PubMed

Barnett, David; Louzao, Raaul; Gambell, Peter; De, Jitakshi; Oldaker, Teri; Hanson, Curtis A

2013-01-01

Flow cytometry and other technologies of cell-based fluorescence assays are as a matter of good laboratory practice required to validate all assays, which when in clinical practice may pass through regulatory review processes using criteria often defined with a soluble analyte in plasma or serum samples in mind. Recently the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in the U.S. regarding their regulatory interest in laboratory developed tests (LDTs) or so-called home brew assays performed in clinical laboratories. The absence of well-defined guidelines for validation of cell-based assays using fluorescence detection has thus become a subject of concern for the International Council for Standardization of Haematology (ICSH) and International Clinical Cytometry Society (ICCS). Accordingly, a group of over 40 international experts in the areas of test development, test validation, and clinical practice of a variety of assay types using flow cytometry and/or morphologic image analysis were invited to develop a set of practical guidelines useful to in vitro diagnostic (IVD) innovators, clinical laboratories, regulatory scientists, and laboratory inspectors. The focus of the group was restricted to fluorescence reporter reagents, although some common principles are shared by immunohistochemistry or immunocytochemistry techniques and noted where appropriate. The work product of this two year effort is the content of this special issue of this journal, which is published as 5 separate articles, this being Validation of Cell-based Fluorescence Assays: Practice Guidelines from the ICSH and ICCS - Part IV - Postanalytic considerations. © 2013 International Clinical Cytometry Society.

Validation of cell-based fluorescence assays: practice guidelines from the ICSH and ICCS - part II - preanalytical issues.

PubMed

Davis, Bruce H; Dasgupta, Amar; Kussick, Steven; Han, Jin-Yeong; Estrellado, Annalee

2013-01-01

Flow cytometry and other technologies of cell-based fluorescence assays are as a matter of good laboratory practice required to validate all assays, which when in clinical practice may pass through regulatory review processes using criteria often defined with a soluble analyte in plasma or serum samples in mind. Recently the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in the U.S. regarding their regulatory interest in laboratory developed tests (LDTs) or so-called "home brew" assays performed in clinical laboratories. The absence of well-defined guidelines for validation of cell-based assays using fluorescence detection has thus become a subject of concern for the International Council for Standardization of Haematology (ICSH) and International Clinical Cytometry Society (ICCS). Accordingly, a group of over 40 international experts in the areas of test development, test validation, and clinical practice of a variety of assay types using flow cytometry and/or morphologic image analysis were invited to develop a set of practical guidelines useful to in vitro diagnostic (IVD) innovators, clinical laboratories, regulatory scientists, and laboratory inspectors. The focus of the group was restricted to fluorescence reporter reagents, although some common principles are shared by immunohistochemistry or immunocytochemistry techniques and noted where appropriate. The work product of this two year effort is the content of this special issue of this journal, which is published as 5 separate articles, this being Validation of Cell-based Fluorescence Assays: Practice Guidelines from the ICSH and ICCS - Part II - Preanalytical issues. © 2013 International Clinical Cytometry Society. © 2013 International Clinical Cytometry Society.

75 FR 69514 - Self-Regulatory Organizations; The Depository Trust Company; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

... these guidelines, DTC must, among other things, maintain a Total Risk-Based Capital Ratio of at least 10... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63254; File No. SR-DTC-2010-14] Self-Regulatory... Preferred Stock November 5, 2010. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act...

Issues in Peer Review of the Scientific Basis for Regulatory Decisions.

ERIC Educational Resources Information Center

American Chemical Society, Washington, DC.

This document is intended to provide a discussion of the issues that need to be addressed in the development of peer review guidelines, the options for addressing the issues, and a range of views about such options. The document focuses on peer review with regard to regulatory decisions and contains major sections which deal with: (1) what should…

Regulatory considerations for clinical development of cancer vaccines.

PubMed

Heelan, Bridget Theresa

2014-01-01

Cancer vaccines are aimed at stimulating an immune response to tumor tissue. There is a high level of clinical activity in this rapidly advancing field with over 1,400 trials registered on Clincaltrials.gov. The recent approval of Sipuleucel-T which is the first cancer vaccine approved in the US and EU has encouraged developers in this field. In contrast to more established approaches for treating cancer such as chemotherapy, regulatory guidelines have been developed relatively recently for cancer vaccines. These guidelines advise on general clinical requirements. As there is an increase in innovative strategies with novel products, a 2-way dialog with regulators is recommended on a case-by-case basis to justify the clinical development plan, taking into account specific quality issues related to the product(s) in development. It is important that the rationale, background and justification for the planned development is convincing when interacting with the regulatory authorities, to enable drug developers and regulators to reach agreement.

Comparing anterior and posterior Hox complex formation reveals guidelines for predicting cis-regulatory elements

PubMed Central

Uhl, Juli D.; Cook, Tiffany A.; Gebelein, Brian

2010-01-01

Hox transcription factors specify numerous cell fates along the anterior-posterior axis by regulating the expression of downstream target genes. While expression analysis has uncovered large numbers of de-regulated genes in cells with altered Hox activity, determining which are direct versus indirect targets has remained a significant challenge. Here, we characterize the DNA binding activity of Hox transcription factor complexes on eight experimentally verified cis-regulatory elements. Hox factors regulate the activity of each element by forming protein complexes with two cofactor proteins, Extradenticle (Exd) and Homothorax (Hth). Using comparative DNA binding assays, we found that a number of flexible arrangements of Hox, Exd, and Hth binding sites mediate cooperative transcription factor complexes. Moreover, analysis of a Distal-less regulatory element (DMXR) that is repressed by abdominal Hox factors revealed that suboptimal binding sites can be combined to form high affinity transcription complexes. Lastly, we determined that the anterior Hox factors are more dependent upon Exd and Hth for complex formation than posterior Hox factors. Based upon these findings, we suggest a general set of guidelines to serve as a basis for designing bioinformatics algorithms aimed at identifying Hox regulatory elements using the wealth of recently sequenced genomes. PMID:20398649

Health risk assessment procedures for endocrine disrupting compounds within different regulatory frameworks in the European Union.

PubMed

Beronius, Anna; Rudén, Christina; Hanberg, Annika; Håkansson, Helen

2009-11-01

In this study we have investigated how different regulatory frameworks in Europe cope with identification and risk assessment of endocrine disrupting compounds (EDCs). Four regulatory groups were selected for the investigation: existing industrial chemicals, environmental pollutants in food, pharmaceuticals and plant protection products. The legislation and guidelines for each of these groups were scrutinized and compared in detail. In addition, one recent European risk assessment document each for three identified EDCs, i.e. bisphenol A, dioxins and vinclozolin, were reviewed and compared. We found that the requirements for toxicity testing and availability and scope of risk assessment guidelines varied between the four regulatory frameworks. Also, the general principles regarding the human relevance of the mode of action identified in animal tests differed in the different risk assessments. In conclusion, there is little conformity in the risk assessment processes between these groups of chemicals. Because of the complicated nature of endocrine disruption, test methods, principles and criteria for data interpretation traditionally used might not be directly applicable to EDCs and further development of a transparent and reliable risk assessment process for this type of substances is needed.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2005-01-01

This report presents the recommendations of an international group of experts convened by the World Health Organization to consider matters concerning the quality assurance of pharmaceuticals and specifications for drug substances and dosage forms. Of particular relevance to drug regulatory authorities and pharmaceutical manufacturers, this report discusses the monographs on antiretrovirals proposed for inclusion in The International Pharmacopoeia and specifications for radiopharmaceuticals, quality specifications for antituberculosis drugs and the revision of the monograph on artemisinin derivatives, as well as quality control of reference materials, good manufacturing practices (GMP), inspection, distribution and trade and other aspects of quality assurance of pharmaceuticals, and regulatory issues. The report is complemented by a number of annexes, including an amendment to good manufacturing practices: main principles regarding the requirement for the sampling of starting materials, guidelines on good manufacturing practices regarding water for pharmaceutical use, guidelines on the sampling of pharmaceutical products and related materials and draft guidelines for registration of fixed-dose combination medicinal products.

The harmonization of the regulation of blood products: a European perspective.

PubMed

Seitz, R; Heiden, M; Nübling, C M; Unger, G; Löwer, J

2008-05-01

The development of blood products as medicines initially took place on the national level in various countries, which resulted in considerable diversity of mechanisms and stringency of regulatory oversight. The scenario changed dramatically with the catastrophic experience that severe virus infections had been transmitted by blood products world-wide. Blood products, which had been regulated differently in the member states, became subject to the European pharmaceutical legislation in 1989. A specialized directive regulating the blood transfusion sector and the collection of plasma for fractionation was enacted in 2002. The European Community, particularly the Commission and the European Medicines Agency, is continuously refining the requirements, providing detailed technical and scientific guidance. In addition, institutions of the Council of Europe play an important role in the transfusion sector, the elaboration of the European Pharmacopoeia prescriptions, and the co-ordination of Official Medicines Control Laboratory or Laboratories batch release. However, further and sustained efforts towards international harmonization are needed. There are already important mechanisms in place, such as the International Conference on Harmonization initiative, which is producing internationally recognized guidelines on central issues. Another important achievement is the common technical document format, which enables the use of uniform applications for marketing authorization. However, there is still room for progress, for example, questions regarding regulatory requirements for licensing of in vitro diagnostic devices, or mutual recognition of inspections. The World Health Organization continues to play an important role in harmonization, both substantially by the production of high-level guidance documents or the establishment of physical international standard preparations, and in a more general sense by providing a platform for international collaboration. A very important aspect is the transparency of the creation and refinement of regulatory requirements. It is currently the rule that draft legal texts, monographs and guidelines are published for a consultation period before adoption. Effort and attention are required to keep track of the developments. However, in the era of modern electronic communication tools, the necessary information can be found on websites and comments can easily be submitted. Networking and exchange of information will continue to be crucial for development and maintenance of sound and balanced regulatory requirements.

Metals Sector

EPA Pesticide Factsheets

Find environmental regulatory information about the metals sector (NAICS 331 & 332), including NESHAPs for metal coatings, effluent guidelines for metal products, combustion compliance assistance, and information about foundry sand recycling.

Guidelines for spaceborne microwave remote sensors

NASA Technical Reports Server (NTRS)

Litman, V.; Nicholas, J.

1982-01-01

A handbook was developed to provide information and support to the spaceborne remote sensing and frequency management communities: to guide sensor developers in the choice of frequencies; to advise regulators on sensor technology needs and sharing potential; to present sharing analysis models and, through example, methods for determining sensor sharing feasibility; to introduce developers to the regulatory process; to create awareness of proper assignment procedures; to present sensor allocations; and to provide guidelines on the use and limitations of allocated bands. Controlling physical factors and user requirements and the regulatory environment are discussed. Sensor frequency allocation achievable performance and usefulness are reviewed. Procedures for national and international registration, the use of non-allocated bands and steps for obtaining new frequency allocations, and procedures for reporting interference are also discussed.

The current role and limitations of surrogate endpoints in advanced prostate cancer.

PubMed

Gomella, Leonard G; Oliver Sartor, A

2014-01-01

The identification of appropriate surrogate endpoints for evaluating cancer therapeutics has been of ongoing interest across various tumor types. Metastatic castrate-resistant prostate cancer (mCRPC) has been a particularly challenging area. As more targeted and novel therapies are being developed in this disease space, an urgent need exists to identify surrogate endpoints in mCRPC. The ability to discern patient benefit in the absence of patient death or other complications would facilitate both drug development and more appropriate patient care. We reviewed the available literature and guidelines used in the development and approval of recent agents for mCRPC. The majority of regulatory approvals of new medications have relied on overall survival (OS) or prevention of complications such as skeletal related events (SRE's). Progression-free survival measures, such as bone scans, computed tomography scans, and prostate-specific antigen related changes, have not been validated nor uniformly accepted as outcome surrogates. All of the successful recent pivotal Phase III trials designed to achieve regulatory approval in mCRPC have used either OS or SRE's as the primary endpoint. There are significant problematic issues that exist associated with defining and implementing surrogate markers in mCRPC beyond survival and complications. Suggestions are made as to how the current situation might be improved. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessing safety of extractables from materials and leachables in pharmaceuticals and biologics - Current challenges and approaches.

PubMed

Broschard, Thomas H; Glowienke, Susanne; Bruen, Uma S; Nagao, Lee M; Teasdale, Andrew; Stults, Cheryl L M; Li, Kim L; Iciek, Laurie A; Erexson, Greg; Martin, Elizabeth A; Ball, Douglas J

2016-11-01

Leachables from pharmaceutical container closure systems can present potential safety risks to patients. Extractables studies may be performed as a risk mitigation activity to identify potential leachables for dosage forms with a high degree of concern associated with the route of administration. To address safety concerns, approaches to toxicological safety evaluation of extractables and leachables have been developed and applied by pharmaceutical and biologics manufacturers. Details of these approaches may differ depending on the nature of the final drug product. These may include application, the formulation, route of administration and length of use. Current regulatory guidelines and industry standards provide general guidance on compound specific safety assessments but do not provide a comprehensive approach to safety evaluations of leachables and/or extractables. This paper provides a perspective on approaches to safety evaluations by reviewing and applying general concepts and integrating key steps in the toxicological evaluation of individual extractables or leachables. These include application of structure activity relationship studies, development of permitted daily exposure (PDE) values, and use of safety threshold concepts. Case studies are provided. The concepts presented seek to encourage discussion in the scientific community, and are not intended to represent a final opinion or "guidelines." Copyright © 2016 Elsevier Inc. All rights reserved.

Saturday Morning Television Advertisements Aired on English and Spanish Language Networks along the Texas-Mexico Border

PubMed Central

Barroso, Cristina S.; Rodriguez, Dianeth; Camacho, Perla L.

2011-01-01

Objectives The aim of this content analysis study is to characterize the TV advertisements aired to an at-risk child population along the Texas-Mexico border. Methods We characterized the early Saturday morning TV advertisements aired by three broadcast network categories (U.S. English language, U.S. Spanish language, and Mexican Spanish language) in Spring 2010. The number, type (food related vs. non-food related), target audience, and persuasion tactics used were recorded. Advertised foods, based on nutrition content, were categorized as meeting or not meeting current dietary guidelines. Results Most commercials were non-food related (82.7%, 397 of 480). The majority of the prepared foods (e.g., cereals, snacks, and drinks) advertised did not meet the current U.S. Dietary Guidelines. Additionally, nutrition content information was not available for many of the foods advertised on the Mexican Spanish language broadcast network category. Conclusions For U.S. children at risk for obesity along the Texas-Mexico border exposure to TV food advertisements may result in the continuation of sedentary behavior as well as an increased consumption of foods of poor nutritional quality. An international regulatory effort to monitor and enforce the reduction of child-oriented food advertising is needed. PMID:22209760

Recommendations for the ethical use and design of artificial intelligent care providers.

PubMed

Luxton, David D

2014-09-01

This paper identifies and reviews ethical issues associated with artificial intelligent care providers (AICPs) in mental health care and other helping professions. Specific recommendations are made for the development of ethical codes, guidelines, and the design of AICPs. Current developments in the application of AICPs and associated technologies are reviewed and a foundational overview of applicable ethical principles in mental health care is provided. Emerging ethical issues regarding the use of AICPs are then reviewed in detail. Recommendations for ethical codes and guidelines as well as for the development of semi-autonomous and autonomous AICP systems are described. The benefits of AICPs and implications for the helping professions are discussed in order to weigh the pros and cons of their use. Existing ethics codes and practice guidelines do not presently consider the current or the future use of interactive artificial intelligent agents to assist and to potentially replace mental health care professionals. AICPs present new ethical issues that will have significant ramifications for the mental health care and other helping professions. Primary issues involve the therapeutic relationship, competence, liability, trust, privacy, and patient safety. Many of the same ethical and philosophical considerations are applicable to use and design of AICPs in medicine, nursing, social work, education, and ministry. The ethical and moral aspects regarding the use of AICP systems must be well thought-out today as this will help to guide the use and development of these systems in the future. Topics presented are relevant to end users, AI developers, and researchers, as well as policy makers and regulatory boards. Published by Elsevier B.V.

Alternative Test Methods for Developmental Neurotoxicity: A ...

EPA Pesticide Factsheets

Exposure to environmental contaminants is well documented to adversely impact the development of the nervous system. However, the time, animal and resource intensive EPA and OECD testing guideline methods for developmental neurotoxicity (DNT) are not a viable solution to characterizing potential chemical hazards for the thousands of untested chemicals currently in commerce. Thus, research efforts over the past decade have endeavored to develop cost-effective alternative DNT testing methods. These efforts have begun to generate data that can inform regulatory decisions. Yet there are major challenges to both the acceptance and use of this data. Major scientific challenges for DNT include development of new methods and models that are “fit for purpose”, development of a decision-use framework, and regulatory acceptance of the methods. It is critical to understand that use of data from these methods will be driven mainly by the regulatory problems being addressed. Some problems may be addressed with limited datasets, while others may require data for large numbers of chemicals, or require the development and use of new biological and computational models. For example mechanistic information derived from in vitro DNT assays can be used to inform weight of evidence (WoE) or integrated approaches to testing and assessment (IATA) approaches for chemical-specific assessments. Alternatively, in vitro data can be used to prioritize (for further testing) the thousands

Management of clandestine drug laboratories: need for evidence-based environmental health policies.

PubMed

Al-Obaidi, Tamara A; Fletcher, Stephanie M

2014-01-01

Clandestine drug laboratories (CDLs) have been emerging and increasing as a public health problem in Australia, with methamphetamine being the dominant illegally manufactured drug. However, management and remediation of contaminated properties are still limited in terms of regulation and direction, especially in relation to public and environmental health practice. Therefore, this review provides an update on the hazards and health effects associated with CDLs, with a specific look at the management of these labs from an Australian perspective. Particularly, the paper attempts to describe the policy landscape for management of CDLs, and identifies current gaps and how further research may be utilised to advance understanding and management of CDLs and inform public health policies. The paper highlights a significant lack of evidence-based policies and guidelines to guide regulatory authority including environmental health officers in Australia. Only recently, the national Clandestine Drug Laboratory Guidelines were developed to assist relevant authority and specialists manage and carry out investigations and remediation of contaminated sites. However, only three states have developed state-based guidelines, some of which are inadequate to meet environmental health requirements. The review recommends well-needed inter-sectoral collaborations and further research to provide an evidence base for the development of robust policies and standard operating procedures for safe and effective environmental health management and remediation of CDLs.

Chemical Manufacturing Sector (NAICS 325)

EPA Pesticide Factsheets

find EPA regulatory information for the chemical manufacturing sector, including NESHAPs, the SNAP program for ozone depleting substances,effluent guidelines, and new and existing chemicals testing requirements under TSCA.

Transportation and Warehousing Sector (NAICS 48-49)

EPA Pesticide Factsheets

Find EPA regulatory information for the transportation and warehousing, including NESHAPs for RICE and gasoline dispensing facilities, effluent guidelines, power wash discharges, and border and port compliance

Construction Sector (NAICS 23)

EPA Pesticide Factsheets

Find environmental regulatory information for the construction sector, including the construction of buildings or engineering projects. This includes RCRA information for hazardous waste, refrigeration compliance, asbestos, effluent guidelines & lead laws

Environmental Protection Agency, Protecting Children's Environmental Health

MedlinePlus

... Indicators of children's health - "America's Children and the Environment" report Scientific journal articles Standards and Regulations Regulations Regulatory development tracker Guidelines for Considering Children's Health in Economic ...

Emergency contraception supply in Australian pharmacies after the introduction of ulipristal acetate: a mystery shopping mixed-methods study.

PubMed

Collins, Jack Charles; Schneider, Carl Richard; Moles, Rebekah Jane

2018-05-09

To explore the supply of emergency contraception (EC) from Australian community pharmacies after the introduction of ulipristal acetate (UPA) and to explore pharmacists' knowledge, decision-making, attitudes and beliefs surrounding supplying EC. A mixed-methods approach of mystery shopping with structured interview was employed. From August to November 2017, 20 pharmacy students mystery-shopped 10 community pharmacies in metropolitan Sydney, Australia, requesting "the morning after pill." Each pharmacy was visited five times with varying scenarios. Structured interviews were conducted immediately postvisit. Visit data were analyzed descriptively and comparatively. Interviews were transcribed verbatim and categorically analyzed. Of 50 planned visits, 43 were analyzed. EC was supplied in 38 requests by pharmacists (54% male). Levonorgestrel (LNG) was more frequently supplied than UPA (74% vs. 26%). UPA was only supplied when intercourse occurred >72 h prior. Directions for use were provided in 35 supplies. No difference in questioning or counseling was found based on sex of requester. Female pharmacists provided more counseling points (MED=4 [IQR=4-5] vs. MED=3 [IQR=0-4]; p<.01). Two pharmacists asked all guideline questions, and no pharmacist provided all guideline counseling points. Interviews elicited supply guidelines, regulatory and clinical knowledge, financial considerations, privacy and stock availability as factors influencing EC supply. EC was supplied in accordance with local legislation in all instances, with the majority supplied within the licensed timeframe for each EC formulation. LNG was supplied more frequently than UPA. UPA was only supplied in the 72-120-h timeframe. Clinical and regulatory knowledge, availability and cost to consumer were identified as factors influencing supply. This study found that despite the introduction of ulipristal acetate to the Australian market, it is not frequently supplied. Interviews identified the need for continuing professional development regarding pharmacist clinical and regulatory knowledge. Future guideline development should consider utility and user needs to optimize the implementation of guidelines. Copyright © 2018. Published by Elsevier Inc.

Manufacturing of biodrugs: need for harmonization in regulatory standards.

PubMed

Sahoo, Niharika; Choudhury, Koel; Manchikanti, Padmavati

2009-01-01

Biodrugs (biologics) are much more complex than chemically synthesized drugs because of their structural heterogeneity and interactions within a given biologic system. The manufacturing process in the biodrug industry varies with each type of molecule and is far more elaborate and stringent due to the use of living organisms and complex substrates. Product purity and altered structural characteristics leading to potential immunogenicity have often been of concern when establishing quality and safety in the use of biodrugs. Regulatory compliance in manufacturing and commercialization of biodrugs involves quality control, quality assurance, and batch documentation. Many factors such as host cell development, cell bank establishment, cell culture, protein production, purification, analysis, formulation, storage, and handling are critical for ensuring the purity, activity, and safety of the finished product. Good Manufacturing Practice (GMP) for biodrugs has been developed in certain regions such as the EU, US, and Japan. Due to differences in manufacturing methods and systems, product-specific GMP guidelines are evolving. In general, there are variations in GMP guidelines between countries, which lead to difficulty for the manufacturers in conforming to different standards, thus entailing delays in the commercialization of biodrugs. There is a need to develop a unified regulatory guideline for biodrug manufacturing across various countries, which would be helpful in the marketing of products and trade. This review deals with the comparative framework and analysis of GMP regulation of biodrugs.

Federal Facilities (Executive Offices) Sector (NAICS 921110)

EPA Pesticide Factsheets

Find EPA regulatory information for federal facilities (NAICS 92), including information on base closures and transfers, hazardous waste, military munitions, perchorlate, environmentally preferable purchasing and comprehensive procurement guidelines

Food provision in early childhood education and care services: Exploring how staff determine nutritional adequacy.

PubMed

Cole, Amanda; Vidgen, Helen; Cleland, Phoebe

2017-02-01

The aim of this study was to explore the methods, processes and strategies used by early childhood education and care (ECEC) services when determining the nutritional adequacy of food provided to children in their care. Semi-structured interviews (n = 22) were conducted with directors, educators and cooks at long day care services (LDCS) (n = 12) regarding nutritional adequacy, the use of tools, guidelines and checklists, menu planning and identification and management of unhealthy foods. A qualitative thematic approach was used to identify anticipated and emergent themes. Case-by-case comparisons were then made, and tables and models were created to allow for comparative analysis. LDCS relied on personal knowledge, experience and 'common sense' when determining the nutritional adequacy of the food provided to children. LDCS demonstrated a lack of awareness and use of current regulatory requirements, nutrition guidelines and recommendations, although the services were confident in providing nutrition advice to parents/carers. LDCS staff use personal knowledge and experience over evidence-based nutrition guidelines and recommendations when determining if the food provided to children is nutritionally adequate. ECEC services are recognised as important settings for obesity prevention and the development of lifetime healthy eating habits. This study highlights the complexities and inconsistencies in providing food that is nutritious and appropriate to children in care while highlighting the need to improve the use and accessibility of nutrition guidelines. © 2016 Dietitians Association of Australia.

Chemicals of emerging concern in the Great Lakes Basin: an analysis of environmental exposures.

PubMed

Klecka, Gary; Persoon, Carolyn; Currie, Rebecca

2010-01-01

This review and statistical analysis was conducted to better understand the nature and significance of environmental exposures in the Great Lakes Basin and watershed to a variety of environmental contaminants. These contaminants of interest included current-use pesticides, pharmaceuticals, organic wastewater contaminants, alkylphenol ethoxylates, perfluorinated surfactants, flame retardants, and chlorinated paraffins. The available literature was critically reviewed and used to develop a database containing 19,611 residue values for 326 substances. In many papers, sampling locations were characterized as being downstream from municipal wastewater discharges, receiving waters for industrial facilities, areas susceptible to agricultural or urban contamination, or harbors and ports. To develop an initial assessment of their potential ecological significance, the contamination levels found were compared with currently available regulatory standards, guidelines, or criteria. This review was prepared for the IJC multi-board work group, and served as background material for an expert consultation, held in March, 2009, in which the significance of the contaminants found was discussed. Moreover, the consultation attempted to identify and assess opportunities for strengthening future actions that will protect the Great Lakes. Based on the findings and conclusions of the expert consultation, it is apparent that a wide variety of chemicals of emerging concern have been detected in environmental media (air, water, sediment, biota) from the Great Lakes Basin, although many are present at only trace levels. Although the presence of these contaminants raises concerns in the public and among the scientific community, the findings must be placed in context. Significant scientific interpretation is required to understand the extent to which these chemicals may pose a threat to the ecosystem and to human health. The ability to detect chemicals in environmental media greatly surpasses our ability to understand the implications of such findings. As advances in analytical technologies occur, it is probable that substances previously found to be non-detectable will be detected. However, their presence in environmental media should not be construed to mean that they are necessarily toxic or hazardous. Current-use pesticides are tightly regulated and extensive efforts have been made to analyze for their presence in surface waters from the Great Lakes Basin. The concentrations found in surface waters for many of the pesticides are below current regulatory criteria. However, the concentrations of certain pesticides exceeded current criteria in 6-32% of the samples analyzed. Detectable concentrations of pharmaceutical compounds were present in 34% of the surface water samples. Various prescription and non-prescription drugs were detected, most frequently at locations that were proximate to the point of discharge from wastewater treatment plants or agricultural operations. At present, there are no standards, guidelines, or criteria with which to compare these contaminant concentrations. Concentrations of alkylphenol ethoxylates and their metabolites have been well studied. All surface water nonylphenol concentrations were below US ambient water quality criteria. However, the concentrations reported for some locations exceeded Canadian guidelines for water or sediment. Only limited data were available for a wide variety of organic wastewater contaminants. Measured concentrations in Great Lakes waters were generally low. Where criteria exist for comparison, the concentrations found were generally below the associated regulatory standards. However, exceedences were noted for some classes of compounds, including phthalates and polycyclic aromatic hydrocarbons. The highest environmental concentrations were reported in biota for a number of persistent, bioaccumulative, and toxic compounds (e.g., polybrominated diphenyl ethers, perfluorinated surfactants). Various stewardship as well as government risk assessment and risk management programs have been implemented over the past years for many of these compounds. Because risk management strategies for some of these contaminants have been implemented only recently, their impact on environmental concentrations, to date, remains unclear. Current evidence suggests that the concentrations of some brominated flame retardants are trending downward, while the concentrations of others appear to be increasing. Regulatory criteria are not available for many of the chemicals of emerging concern that were detected in the Great Lakes Basin. When criteria do exist, it is important to recognize that they were developed based on the best available science at the time. As the science evolves, regulatory criteria must be reassessed in light of new findings (e.g., consideration of new endpoints and mechanisms of action). Further, there are significant scientific gaps in our ability to interpret environmental monitoring data, including the need for: (a) improving the understanding of the effects of mixtures, (b) information on use of, and the commercial life cycle of chemicals and products that contain them, (c) information on source contributions and exposure pathways, and (d) the need for thoughtful additional regulatory,environmental, and health criteria. Discharges from wastewater treatment plants were identified as an important source of contaminants to surface waters in the Great Lakes Basin. Combined sewer overflows and agricultural operations were also found to be important contributors to concentrations in surface waters. Concentrations of many of the chemicals were generally the highest in the vicinity of these sources, decline with increasing distance from sources, and were generally low or non-detectable in the open waters of the Great Lakes.

Clinical Research Environment in India: Challenges and Proposed Solutions

PubMed Central

Burt, Tal; Sharma, Pooja; Dhillon, Savita; Manchanda, Mukul; Mittal, Sanjay; Trehan, Naresh

2015-01-01

India has compelling need and keen aspirations for indigenous clinical research. Notwithstanding this need and previously reported growth the expected expansion of Indian clinical research has not materialized. We reviewed the scientific literature, lay press reports, and ClinicalTrials.gov data for information and commentary on projections, progress, and impediments associated with clinical trials in India. We also propose targeted solutions to identified challenges. The Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate) between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013. Phase-1 trials grew by (+) 43.5% CAGR from 2005–2013, phase-2 trials grew by (+) 19.8% CAGR from 2005–2009 and contracted by (-) 12.6% CAGR from 2009–2013, and phase-3 trials grew by (+) 13.0% CAGR from 2005–2010 and contracted by (-) 28.8% CAGR from 2010–2013. This was associated with a slowing of the regulatory approval process, increased media coverage and activist engagement, and accelerated development of regulatory guidelines and recuperative initiatives. We propose the following as potential targets for restorative interventions: Regulatory overhaul (leadership and enforcement of regulations, resolution of ambiguity in regulations, staffing, training, guidelines, and ethical principles [e.g., compensation]).Education and training of research professionals, clinicians, and regulators.Public awareness and empowerment. After a peak in 2009-2010, the clinical research sector in India appears to be experiencing a contraction. There are indications of challenges in regulatory enforcement of guidelines; training of clinical research professionals; and awareness, participation, partnership, and the general image amongst the non-professional media and public. Preventative and corrective principles and interventions are outlined with the goal of realizing the clinical research potential in India. PMID:25590017

Validation of cell-based fluorescence assays: practice guidelines from the ICSH and ICCS - part I - rationale and aims.

PubMed

Davis, Bruce H; Wood, Brent; Oldaker, Teri; Barnett, David

2013-01-01

Flow cytometry and other technologies of cell-based fluorescence assays are as a matter of good laboratory practice required to validate all assays, which when in clinical practice may pass through regulatory review processes using criteria often defined with a soluble analyte in plasma or serum samples in mind. Recently the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in the U.S. regarding their regulatory interest in laboratory developed tests (LDTs) or so-called "home brew" assays performed in clinical laboratories. The absence of well-defined guidelines for validation of cell-based assays using fluorescence detection has thus become a subject of concern for the International Council for Standardization of Haematology (ICSH) and International Clinical Cytometry Society (ICCS). Accordingly, a group of over 40 international experts in the areas of test development, test validation, and clinical practice of a variety of assay types using flow cytometry and/or morphologic image analysis were invited to develop a set of practical guidelines useful to in vitro diagnostic (IVD) innovators, clinical laboratories, regulatory scientists, and laboratory inspectors. The focus of the group was restricted to fluorescence reporter reagents, although some common principles are shared by immunohistochemistry or immunocytochemistry techniques and noted where appropriate. The work product of this two year effort is the content of this special issue of this journal, which is published as 5 separate articles, this being Validation of Cell-based Fluorescence Assays: Practice Guidelines from the ICSH and ICCS - Part I - Rationale and aims. © 2013 International Clinical Cytometry Society. © 2013 International Clinical Cytometry Society.

Performance of potential non-crop or wild species under OECD 208 testing guideline study conditions for terrestrial non-target plants.

PubMed

Pallett, Ken; Cole, Jon; Oberwalder, Christian; Porch, John

2007-02-01

The inclusion of 52 potential non-crop or wild species in new OECD guidelines for terrestrial non-target plant (TNTP) testing led to a ring test conducted by four laboratories experienced in regulatory testing. Species selected had shown potential to meet validity criteria of emergence for TNTP studies in a previous evaluation of the 52 species. OECD 208 guideline conditions were applied, with and without seed pretreatments recommended to enhance germination. These species were Abutilon theophrasti (L.) Medic., Avena fatua L., Fallopia convolvulus (L.) Adans., Galium aparine L., Ipomoea hederacea (L.) Jacq. and Veronica persica Poir. Only I. hederacea met the validity criterion of 70% emergence in all laboratories and showed a low variability in biomass. Of the other species, none led to 70% emergence in all four laboratories. The recommended pretreatments did not have a major impact on emergence. Biomass was also investigated with A. theophrasti, A. fatua, Centaurea cyanus L., I. hederacea and Rumex crispus L. Variability of biomass, a key parameter in TNTP regulatory studies, exceeded normal biomass variability of crop species used for TNTP studies. The addition of a thin layer of quartz sand to the soil surface resulted in improved emergence of C. cyanus, G. aparine and V. persica; however, such a procedure, while routine in screening studies to improve germination, is a deviation from the TNTP guidelines. These initial studies indicate that some species could meet the emergence criteria for TNTP testing. However, there is a need for further studies on seed source, seed quality and conditions for uniform emergence before their use in routine regulatory testing.

Pharmaceutical and Medicine Manufacturing Sector (NAICS 3254)

EPA Pesticide Factsheets

Find environmental regulatory and compliance information for the pharmaceutical manufacturing sector, including essential uses of CFCs, NESHAP for pharmaceutical production, effluent guidelines for wastewater and management of hazardous waste.

The emergence of diagnostic imaging technologies in breast cancer: discovery, regulatory approval, reimbursement, and adoption in clinical guidelines.

PubMed

Gold, Laura S; Klein, Gregory; Carr, Lauren; Kessler, Larry; Sullivan, Sean D

2012-01-25

In this article, we trace the chronology of developments in breast imaging technologies that are used for diagnosis and staging of breast cancer, including mammography, ultrasonography, magnetic resonance imaging, computed tomography, and positron emission tomography. We explore factors that affected clinical acceptance and utilization of these technologies from discovery to clinical use, including milestones in peer-reviewed publication, US Food and Drug Administration approval, reimbursement by payers, and adoption into clinical guidelines. The factors driving utilization of new imaging technologies are mainly driven by regulatory approval and reimbursement by payers rather than evidence that they provide benefits to patients. Comparative effectiveness research can serve as a useful tool to investigate whether these imaging modalities provide information that improves patient outcomes in real-world settings.

Regulatory perspective on remaining challenges for utilization of pharmacogenomics-guided drug developments.

PubMed

Otsubo, Yasuto; Ishiguro, Akihiro; Uyama, Yoshiaki

2013-01-01

Pharmacogenomics-guided drug development has been implemented in practice in the last decade, resulting in increased labeling of drugs with pharmacogenomic information. However, there are still many challenges remaining in utilizing this process. Here, we describe such remaining challenges from the regulatory perspective, specifically focusing on sample collection, biomarker qualification, ethnic factors, codevelopment of companion diagnostics and means to provide drugs for off-target patients. To improve the situation, it is important to strengthen international harmonization and collaboration among academia, industries and regulatory agencies, followed by the establishment of an international guideline on this topic. Communication with a regulatory agency from an early stage of drug development is also a key to success.

The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

PubMed

Molzon, J A; Giaquinto, A; Lindstrom, L; Tominaga, T; Ward, M; Doerr, P; Hunt, L; Rago, L

2011-04-01

The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.

Consensus Among International Ethical Guidelines for the Provision of Videoconferencing-Based Mental Health Treatments.

PubMed

Sansom-Daly, Ursula M; Wakefield, Claire E; McGill, Brittany C; Wilson, Helen L; Patterson, Pandora

2016-05-18

Online technologies may reduce barriers to evidence-based mental health care, yet they also create numerous ethical challenges. Recently, numerous professional organizations and expert groups have produced best-practice guidelines to assist mental health professionals in delivering online interventions in an ethically and clinically sound manner. However, there has been little critical examination of these international best-practice guidelines regarding appropriate electronic mental health (e-mental health) service delivery via technologies such as videoconferencing (including Skype), particularly for specific, vulnerable populations. Further, the extent to which concordance exists between these guidelines remains unclear. Synthesizing this literature to provide clear guidance to both mental health professionals and researchers is critical to ensure continued progress in the field of e-mental health. This study aims to review all currently available ethical and best-practice guidelines relating to videoconferencing-delivered mental health treatments in order to ascertain the recommendations for which international consensus could be found. Additionally, this review examines the extent to which each set of guidance addresses several key special populations, including children and young people, and populations living with illness. This systematic review examined guidelines using a two-armed search strategy, examining (1) professional organizations' published guidance; and (2) MEDLINE, PsycINFO, and EMBASE for the past ten years. In order to determine consensus for best-practice, a recommendation was considered "firm" if 50% or more of the reviewed guidelines endorsed it and "tentative" if recommended by fewer guidelines than these. The professional guidelines were also scored by two raters using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) criteria. In the study, 19 guidelines were included, yielding 11 specific "firm" and a further 123 "tentative-level" recommendations regarding the appropriateness of e-mental health, competence, legal and regulatory issues, confidentiality, consent, professional boundaries, and crisis management. International consensus yielded firm guidance across almost all areas except professional boundaries and some aspects of determining the appropriateness of e-mental health. Few guidelines specifically addressed special populations. Overall guideline quality varied; however, 42% (8/19) of the guidelines scored at least 5 out of 7. This synthesis of guidelines provides a foundation for clinicians and researchers utilizing e-mental health worldwide. The lack of specific guidance relating to special populations is an area warranting further attention in order to strengthen mental health professionals' and researchers' capacity to ethically and effectively tailor e-mental health interventions to these groups.

Thermal pasteurization of ready-to-eat foods and vegetables: Critical factors for process design and effects on quality.

PubMed

Peng, Jing; Tang, Juming; Barrett, Diane M; Sablani, Shyam S; Anderson, Nathan; Powers, Joseph R

2017-09-22

Increasing consumer desire for high quality ready-to-eat foods makes thermal pasteurization important to both food producers and researchers. To be in compliance with the Food Safety Modernization Act (FSMA), food companies seek regulatory and scientific guidelines to ensure that their products are safe. Clearly understanding the regulations for chilled or frozen foods is of fundamental importance to the design of thermal pasteurization processes for vegetables that meet food safety requirements. This article provides an overview of the current regulations and guidelines for pasteurization in the U.S. and in Europe for control of bacterial pathogens. Poorly understood viral pathogens, in terms of their survival in thermal treatments, are an increasing concern for both food safety regulators and scientists. New data on heat resistance of viruses in different foods are summarized. Food quality attributes are sensitive to thermal degradation. A review of thermal kinetics of inactivation of quality-related enzymes in vegetables and the effects of thermal pasteurization on vegetable quality is presented. The review also discusses shelf-life of thermally pasteurized vegetables.

Compliance of disease awareness campaigns in printed Dutch media with national and international regulatory guidelines.

PubMed

Leonardo Alves, Teresa; Martins de Freitas, Auramarina F; van Eijk, Martine E C; Mantel-Teeuwisse, Aukje K

2014-01-01

The European legislation prohibits prescription-only medicines' advertising but allows pharmaceutical companies to provide information to the public on health and diseases, provided there is no direct or indirect reference to a pharmaceutical product. Various forms of promotion have become increasingly common in Europe including "disease-oriented" campaigns. To explore examples of disease awareness campaigns by pharmaceutical companies in the Netherlands, by assessing their compliance with the World Health Organization (WHO) Ethical Criteria for medicinal drug promotion and the Dutch guidelines for provision of information by pharmaceutical companies. Materials referring to health/disease and treatments published in the most widely circulated newspapers and magazines were collected from March to May 2012. An evaluation tool was developed based on relevant underlying principles from the WHO ethical criteria and Dutch self-regulation guidelines. Collected disease awareness advertisements were used to pilot the evaluation tool and to explore the consistency of information provided with the WHO and Dutch criteria. Eighty materials met our inclusion criteria; 71 were published in newspapers and 9 in magazines. The large majority were news items but 21 were disease awareness advertisements, of which 5 were duplicates. Fifteen out of the 16 disease awareness campaigns were non-compliant with current guidelines mainly due to lack of balance (n = 12), absence of listed author and/or sponsor (n = 8), use of misleading or incomplete information (n = 5) and use of promotional information (n = 5). None mentioned a pharmaceutical product directly. Disease Awareness Campaigns are present in Dutch printed media. Although no brand names were mentioned, the lack of compliance of disease awareness campaigns with the current regulations is alarming. There were information deficiencies and evidence of information bias. A key concern is that the context in which the information is provided, mostly through indirect referral, is likely to support treatment with the sponsor's product.

Compliance of Disease Awareness Campaigns in Printed Dutch Media with National and International Regulatory Guidelines

PubMed Central

Leonardo Alves, Teresa; Martins de Freitas, Auramarina F.; van Eijk, Martine E. C.; Mantel-Teeuwisse, Aukje K.

2014-01-01

Background The European legislation prohibits prescription-only medicines' advertising but allows pharmaceutical companies to provide information to the public on health and diseases, provided there is no direct or indirect reference to a pharmaceutical product. Various forms of promotion have become increasingly common in Europe including “disease-oriented” campaigns. Objectives To explore examples of disease awareness campaigns by pharmaceutical companies in the Netherlands, by assessing their compliance with the World Health Organization (WHO) Ethical Criteria for medicinal drug promotion and the Dutch guidelines for provision of information by pharmaceutical companies. Methods Materials referring to health/disease and treatments published in the most widely circulated newspapers and magazines were collected from March to May 2012. An evaluation tool was developed based on relevant underlying principles from the WHO ethical criteria and Dutch self-regulation guidelines. Collected disease awareness advertisements were used to pilot the evaluation tool and to explore the consistency of information provided with the WHO and Dutch criteria. Findings Eighty materials met our inclusion criteria; 71 were published in newspapers and 9 in magazines. The large majority were news items but 21 were disease awareness advertisements, of which 5 were duplicates. Fifteen out of the 16 disease awareness campaigns were non-compliant with current guidelines mainly due to lack of balance (n = 12), absence of listed author and/or sponsor (n = 8), use of misleading or incomplete information (n = 5) and use of promotional information (n = 5). None mentioned a pharmaceutical product directly. Conclusion Disease Awareness Campaigns are present in Dutch printed media. Although no brand names were mentioned, the lack of compliance of disease awareness campaigns with the current regulations is alarming. There were information deficiencies and evidence of information bias. A key concern is that the context in which the information is provided, mostly through indirect referral, is likely to support treatment with the sponsor's product. PMID:25198776

Innovation under Regulatory Uncertainty: Evidence from Medical Technology

PubMed Central

Stern, Ariel Dora

2016-01-01

This paper explores how the regulatory approval process affects innovation incentives in medical technologies. Prior studies have found early mover regulatory advantages for drugs. I find the opposite for medical devices, where pioneer entrants spend 34 percent (7.2 months) longer than follow-on entrants in regulatory approval. Back-of-the- envelope calculations suggest that the cost of a delay of this length is upwards of 7 percent of the total cost of bringing a new high-risk device to market. Considering potential explanations, I find that approval times are largely unrelated to technological novelty, but are meaningfully reduced by the publication of objective regulatory guidelines. Finally, I consider how the regulatory process affects small firms’ market entry patterns and find that small firms are less likely to be pioneers in new device markets, a fact consistent with relatively higher costs of doing so for more financially constrained firms. PMID:28652646

Isolation of CD4+CD25+ regulatory T cells for clinical trials.

PubMed

Hoffmann, Petra; Boeld, Tina J; Eder, Ruediger; Albrecht, Julia; Doser, Kristina; Piseshka, Biserka; Dada, Ashraf; Niemand, Claudia; Assenmacher, Mario; Orsó, Evelyn; Andreesen, Reinhard; Holler, Ernst; Edinger, Matthias

2006-03-01

The adoptive transfer of donor CD4+CD25+ regulatory T cells has been shown to protect from lethal graft-versus-host disease after allogeneic bone marrow transplantation in murine disease models. Efficient isolation strategies that comply with good manufacturing practice (GMP) guidelines are prerequisites for the clinical application of human CD4+CD25+ regulatory T cells. Here we describe the isolation of CD4+CD25+ T cells with regulatory function from standard leukapheresis products by using a 2-step magnetic cell-separation protocol performed under GMP conditions. The generated cell products contained on average 49.5% CD4+CD25high T cells that phenotypically and functionally represented natural CD4+CD25+ regulatory T cells and showed a suppressive activity comparable to that of CD4+CD25+ regulatory T-cell preparations purified by non-GMP-approved fluorescence-activated cell sorting.

Review and comparison of quality standards, guidelines and regulations for laboratories.

PubMed

Datema, Tjeerd A M; Oskam, Linda; Klatser, Paul R

2012-01-01

The variety and number of laboratory quality standards, guidelines and regulations (hereafter: quality documents) makes it difficult to choose the most suitable one for establishing and maintaining a laboratory quality management system. There is a need to compare the characteristics, suitability and applicability of quality documents in view of the increasing efforts to introduce quality management in laboratories, especially in clinical diagnostic laboratories in low income and middle income countries. This may provide valuable insights for policy makers developing national laboratory policies, and for laboratory managers and quality officers in choosing the most appropriate quality document for upgrading their laboratories. We reviewed the history of quality document development and then selected a subset based on their current use. We analysed these documents following a framework for comparison of quality documents that was adapted from the Clinical Laboratory Standards Institute guideline GP26 Quality management system model for clinical laboratory services . Differences were identified between national and international, and non-clinical and clinical quality documents. The most salient findings were the absence of provisions on occurrence management and customer service in almost all non-clinical quality documents, a low number of safety requirements aimed at protecting laboratory personnel in international quality documents and no requirements regarding ethical behaviour in almost all quality documents. Each laboratory needs to investigate whether national regulatory standards are present. These are preferred as they most closely suit the needs of laboratories in the country. A laboratory should always use both a standard and a guideline: a standard sums up the requirements to a quality management system, a guideline describes how quality management can be integrated in the laboratory processes.

40 CFR 240.204-3 - Recommended procedures: Operations.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) SOLID WASTES GUIDELINES FOR THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended... acceptable levels. (b) In the event of an accidental spill, the local regulatory agency should be notified...

The Changing, Unchanging Politics of Gene Splicing

ERIC Educational Resources Information Center

Randal, Judith

1978-01-01

The House Interstate and Foreign Commerce Committee's regulatory legislation on recombinant DNA technology is discussed along with university reactions to it. Violations of federal guidelines and legal efforts are described. (LBH)

Plastics and Rubber Products Manufacturing (NAICS 326)

EPA Pesticide Factsheets

Find environmental regulatory and compliance information for plastics and rubber products manufacturing (which includes the manufacture of cellulose and other fibers) including information about NESHAPs and effluent guidelines for wastewater discharges

[A new update of the SIMLII Guidelines on carcinogens].

PubMed

Pira, Enrico; Giachino, Gian Mario; Discalzi, Gianluigi

2011-01-01

The second update of the Italian Society of Occupational Medicine and Industrial Hygiene (SIMLII) guidelines on Cancerogens and Mutagens, first published in 2003 and reviewed in 2007, is presented. The general setting of the guidelines remaines unmodified. In this new release some important developments on regulatory system, risk assessment, and health surveillance are discussed. The relevant evolution of the regulatory rules is illustrated in detail, with particular reference to the recent implementation in European Union and in Italy of the Regulation (EC) 1272/2008 on Classification, Labelling and Packaging of substances and mixtures. The recent tendencies of the European Scientific Committee on Occupational Exposure Limits in risk assessment, are presented. Some remarks on the use of new biomarkers in health surveillance, with reference to lung and bladder cancer, are discussed. The more recent results on the effectiveness of the use of LDTC scan on screening in asymptomatic persons at high risk for lung cancer, are presented. The use of this imaging technique in health surveillance of special group of workers (i.e., subjects with relevant past asbestos exposure and smokers) could be adopted.

Statutory Regulation of Traditional Medicine Practitioners and Practices: The Need for Distinct Policy Making Guidelines.

PubMed

Ijaz, Nadine; Boon, Heather

2018-04-01

The World Health Organization (WHO) has called for the increased statutory regulation of traditional and complementary medicine practitioners and practices, currently implemented in about half of nations surveyed. According to recent WHO data, however, the absence of policy guidelines in this area represents a significant barrier to implementation of such professional regulations. This commentary reviews several key challenges that distinguish the statutory regulation of traditional medicine practitioners and practices from biomedical professional regulation, providing a foundation for the development of policy making parameters in this area. Foremost in this regard are the ongoing impacts of the European colonial encounter, which reinforce biomedicine's disproportionate political dominance across the globe despite traditional medicine's ongoing widespread use (particularly in the global South). In this light, the authors discuss the conceptual and historical underpinnings of contemporary professional regulatory structures, the tensions between institutional and informal traditional medicine training pathways, and the policy challenges presented by the prospect of standardizing internally diverse indigenous healing approaches. Epistemic and evidentiary tensions, as well as the policy complexities surrounding the intersection of cultural and clinical considerations, present additional challenges to regulators. Conceptualizing professional regulation as an intellectual property claim under the law, the authors further consider what it means to protect traditional knowledge and prevent misappropriation in this context. Overall, the authors propose that innovative professional regulatory approaches are needed in this area to address safety, quality of care, and accessibility as key public interest concerns, while prioritizing the redress of historical inequities, protection of diverse indigenous knowledges, and delivery of care to underserved populations.

Statutory Regulation of Traditional Medicine Practitioners and Practices: The Need for Distinct Policy Making Guidelines

PubMed Central

Boon, Heather

2018-01-01

Abstract The World Health Organization (WHO) has called for the increased statutory regulation of traditional and complementary medicine practitioners and practices, currently implemented in about half of nations surveyed. According to recent WHO data, however, the absence of policy guidelines in this area represents a significant barrier to implementation of such professional regulations. This commentary reviews several key challenges that distinguish the statutory regulation of traditional medicine practitioners and practices from biomedical professional regulation, providing a foundation for the development of policy making parameters in this area. Foremost in this regard are the ongoing impacts of the European colonial encounter, which reinforce biomedicine's disproportionate political dominance across the globe despite traditional medicine's ongoing widespread use (particularly in the global South). In this light, the authors discuss the conceptual and historical underpinnings of contemporary professional regulatory structures, the tensions between institutional and informal traditional medicine training pathways, and the policy challenges presented by the prospect of standardizing internally diverse indigenous healing approaches. Epistemic and evidentiary tensions, as well as the policy complexities surrounding the intersection of cultural and clinical considerations, present additional challenges to regulators. Conceptualizing professional regulation as an intellectual property claim under the law, the authors further consider what it means to protect traditional knowledge and prevent misappropriation in this context. Overall, the authors propose that innovative professional regulatory approaches are needed in this area to address safety, quality of care, and accessibility as key public interest concerns, while prioritizing the redress of historical inequities, protection of diverse indigenous knowledges, and delivery of care to underserved populations. PMID:29359948

Towards a commercial process for the manufacture of genetically modified T cells for therapy

PubMed Central

Kaiser, A D; Assenmacher, M; Schröder, B; Meyer, M; Orentas, R; Bethke, U; Dropulic, B

2015-01-01

The recent successes of adoptive T-cell immunotherapy for the treatment of hematologic malignancies have highlighted the need for manufacturing processes that are robust and scalable for product commercialization. Here we review some of the more outstanding issues surrounding commercial scale manufacturing of personalized-adoptive T-cell medicinal products. These include closed system operations, improving process robustness and simplifying work flows, reducing labor intensity by implementing process automation, scalability and cost, as well as appropriate testing and tracking of products, all while maintaining strict adherence to Current Good Manufacturing Practices and regulatory guidelines. A decentralized manufacturing model is proposed, where in the future patients' cells could be processed at the point-of-care in the hospital. PMID:25613483

An unexplored ethical issue in clinical research: disclosure of individual findings in the Creando Posibilidades [Creating Possibilities] study.

PubMed

Stein, Karen Farchaus; Keller, Colleen; Fishstrom, Astrid

2013-06-01

Individual disclosure refers to the presumptive ethical responsibility of an investigator to communicate to a study participant information that was collected as a part of a research study protocol and is specific to the individual. Currently, there are no federal regulatory guidelines specifying the conditions and management of disclosure of health-related individual-specific information. In this report, the authors discuss the challenges associated with individual disclosure in the context of a longitudinal descriptive study. Arguments favoring disclosure and those challenging disclosure as a general ethical duty are presented. Finally, strategies for addressing individual disclosure are discussed using a research exemplar in which risk behaviors related to health outcomes were measured. Copyright © 2013 Wiley Periodicals, Inc.

A systematic review and appraisal of the quality of practice guidelines for the management of Neisseria gonorrhoeae infections.

PubMed

Dickson, Catherine; Arnason, Trevor; Friedman, Dara Spatz; Metz, Gila; Grimshaw, Jeremy M

2017-11-01

Clinical guidelines help ensure consistent care informed by current evidence. As shifts in antimicrobial resistance continue to influence first-line treatment, up-to-date guidelines are important for preventing treatment failure. A guideline's development process will influence its recommendations and users' trust. To assess the quality of current gonorrhoea guidelines' development processes. Multiple databases. Original and current English-language guidelines targeting health professionals and containing treatment recommendations for uncomplicated gonorrhoea in the general adult population. Two appraisers assessed the guidelines independently using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Scores were combined as per the AGREE II users' manual. We identified 10 guidelines meeting the inclusion criteria. The quality of the gonorrhoea treatment guidelines varied. Most scored poorly on Rigour of Development ; information on the evidence review process and methods for formulating recommendations was often missing. The WHO Guidelines for the Treatment of Neisseria gonorrhoeae and UK National Guideline for the Management of Gonorrhoea in Adults scored the highest on Rigour of Development . Methods to address conflicts of interest were often not described in the materials reviewed. Implementation of recommendations was often not addressed. By limiting our study to English-language guidelines, a small number of guidelines we identified were excluded. Our analysis was limited to either published or online materials that were readily available to users. We could not differentiate between items addressed in the development process but not documented from items that were not addressed. Gonorrhoea treatment guidelines may slow antimicrobial resistance. Many current guidelines are not in line with the current guideline development best practices; this might undermine the perceived trustworthiness of guidelines. By identifying current limitations, this study can help improve the quality of future guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Neonicotinoids in the Canadian aquatic environment: a literature review on current use products with a focus on fate, exposure, and biological effects.

PubMed

Anderson, J C; Dubetz, C; Palace, V P

2015-02-01

Developed to replace organophosphate and carbamate insecticides, neonicotinoids are structurally similar to nicotine. The three main neonicotinoid insecticides, imidacloprid, clothianidin, and thiamethoxam, are being re-evaluated by Health Canada's Pest Management Regulatory Agency (PMRA). An important aspect of the re-evaluation is the potential for effects in non-target organisms, including aquatic organisms. Leaching into surface waters is one of the major concerns surrounding extensive use of neonicotinoids, especially in close proximity to water bodies. The PMRA has classified IMI as 'persistent' with a 'high' leaching potential. Globally, neonicotinoids have been detected in a variety of water bodies, typically at concentrations in the low μg/L range. While IMI has been included in some monitoring exercises, there are currently very few published data for the presence of CLO and THM in Canadian water bodies. The majority of neonicotinoid toxicity studies have been conducted with IMI due to its longer presence on the market and high prevalence of use. Aquatic insects are particularly vulnerable to neonicotinoids and chronic toxicity has been observed at concentrations of IMI below 1 μg/L. Acute toxicity has been reported at concentrations below 20 μg/L for the most sensitive species, including Hyalella azteca, ostracods, and Chironomus riparius. Fish, algae, amphibians, and molluscs are relatively insensitive to IMI. However, the biological effects of THM and CLO have not been as well explored. The Canadian interim water quality guideline for IMI is 0.23 μg/L, but there is currently insufficient use, fate, and toxicological information available to establish guidelines for CLO and THM. Based on concentrations of neonicotinoids reported in surface waters in Canada and globally, there is potential for aquatic invertebrates to be negatively impacted by neonicotinoids. Therefore, it is necessary to address knowledge gaps to inform decisions around guidelines and registration status for neonicotinoid insecticides in Canada to protect our aquatic ecosystems. Copyright © 2014 Elsevier B.V. All rights reserved.

Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents).

PubMed

Calixto, J B

2000-02-01

This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

Regulatory Considerations for Physiological Closed-Loop Controlled Medical Devices Used for Automated Critical Care: Food and Drug Administration Workshop Discussion Topics.

PubMed

Parvinian, Bahram; Scully, Christopher; Wiyor, Hanniebey; Kumar, Allison; Weininger, Sandy

2018-06-01

Part of the mission of the Center for Devices and Radiological Health (CDRH) at the US Food and Drug Administration is to facilitate medical device innovation. Therefore, CDRH plays an important role in helping its stakeholders such as manufacturers, health care professionals, patients, patient advocates, academia, and other government agencies navigate the regulatory landscape for medical devices. This is particularly important for innovative physiological closed-loop controlled (PCLC) devices used in critical care environments, such as intensive care units, emergency settings, and battlefield environments. CDRH's current working definition of a PCLC medical device is a medical device that incorporates physiological sensor(s) for automatic manipulation of a physiological variable through actuation of therapy that is conventionally made by a clinician. These emerging devices enable automatic therapy delivery and may have the potential to revolutionize the standard of care by ensuring adequate and timely therapy delivery with improved performance in high workload and high-stress environments. For emergency response and military applications, automatic PCLC devices may play an important role in reducing cognitive overload, minimizing human error, and enhancing medical care during surge scenarios (ie, events that exceed the capability of the normal medical infrastructure). CDRH held an open public workshop on October 13 and 14, 2015 with the aim of fostering an open discussion on design, implementation, and evaluation considerations associated with PCLC devices used in critical care environments. CDRH is currently developing regulatory recommendations and guidelines that will facilitate innovation for PCLC devices. This article highlights the contents of the white paper that was central to the workshop and focuses on the ensuing discussions regarding the engineering, clinical, and human factors considerations.

Using FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) to isolate active regulatory DNA

PubMed Central

Simon, Jeremy M.; Giresi, Paul G.; Davis, Ian J.; Lieb, Jason D.

2013-01-01

Eviction or destabilization of nucleosomes from chromatin is a hallmark of functional regulatory elements of the eukaryotic genome. Historically identified by nuclease hypersensitivity, these regulatory elements are typically bound by transcription factors or other regulatory proteins. FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) is an alternative approach to identify these genomic regions and has proven successful in a multitude of eukaryotic cell and tissue types. Cells or dissociated tissues are crosslinked briefly with formaldehyde, lysed, and sonicated. Sheared chromatin is subjected to phenol-chloroform extraction and the isolated DNA, typically encompassing 1–3% of the human genome, is purified. We provide guidelines for quantitative analysis by PCR, microarrays, or next-generation sequencing. Regulatory elements enriched by FAIRE display high concordance with those identified by nuclease hypersensitivity or ChIP, and the entire procedure can be completed in three days. FAIRE exhibits low technical variability, which allows its use in large-scale studies of chromatin from normal or diseased tissues. PMID:22262007

Introduction to Immunotoxicity

EPA Science Inventory

Recognition that the immune system is vulnerable to adverse effects after exposure to xenobiotics led to the discipline of immunotoxicology and the subsequent addition of immunotoxicology testing to regulatory guidelines for toxicity. Immunotoxic effects can result in immunosuppr...

Oil and Gas Extraction Sector (NAICS 211)

EPA Pesticide Factsheets

Environmental regulatory information for oil and gas extraction sectors, including oil and natural gas drilling. Includes information about NESHAPs for RICE and stationary combustion engines, and effluent guidelines for synthetic-based drilling fluids

The emergence of diagnostic imaging technologies in breast cancer: discovery, regulatory approval, reimbursement, and adoption in clinical guidelines

PubMed Central

Klein, Gregory; Carr, Lauren; Kessler, Larry; Sullivan, Sean D.

2012-01-01

Abstract In this article, we trace the chronology of developments in breast imaging technologies that are used for diagnosis and staging of breast cancer, including mammography, ultrasonography, magnetic resonance imaging, computed tomography, and positron emission tomography. We explore factors that affected clinical acceptance and utilization of these technologies from discovery to clinical use, including milestones in peer-reviewed publication, US Food and Drug Administration approval, reimbursement by payers, and adoption into clinical guidelines. The factors driving utilization of new imaging technologies are mainly driven by regulatory approval and reimbursement by payers rather than evidence that they provide benefits to patients. Comparative effectiveness research can serve as a useful tool to investigate whether these imaging modalities provide information that improves patient outcomes in real-world settings. PMID:22275726

Fair Balance and Adequate Provision in Direct-to-Consumer Prescription Drug Online Banner Advertisements: A Content Analysis.

PubMed

Adams, Crystal

2016-02-18

The current direct-to-consumer advertising (DTCA) guidelines were developed with print, television, and radio media in mind, and there are no specific guidelines for online banner advertisements. This study evaluates how well Internet banner ads comply with existing Food and Drug Administration (FDA) guidelines for DTCA in other media. A content analysis was performed of 68 banner advertisements. A coding sheet was developed based on (1) FDA guidance documents for consumer-directed prescription drug advertisements and (2) previous DTCA content analyses. Specifically, the presence of a brief summary detailing the drug's risks and side effects or of a "major statement" identifying the drug's major risks, and the number and type of provisions made available to consumers for comprehensive information about the drug were coded. In addition, the criterion of "fair balance," the FDA's requirement that prescription drug ads balance information relating to the drug's risks with information relating to its benefits, was measured by numbering the benefit and risk facts identified in the ads and by examining the presentation of risk and benefit information. Every ad in the sample included a brief summary of risk information and at least one form of adequate provision as required by the FDA for broadcast ads that do not give audiences a brief summary of a drug's risks. No ads included a major statement. There were approximately 7.18 risk facts for every benefit fact. Most of the risks (98.85%, 1292/1307) were presented in the scroll portion of the ad, whereas most of the benefits (66.5%, 121/182) were presented in the main part of the ad. Out of 1307 risk facts, 1292 were qualitative and 15 were quantitative. Out of 182 benefit facts, 181 were qualitative and 1 was quantitative. The majority of ads showed neutral images during the disclosure of benefit and risk facts. Only 9% (6/68) of the ads displayed positive images and none displayed negative images when presenting risks facts. When benefit facts were being presented, 7% (5/68) showed only positive images. No ads showed negative images when the benefit facts were being presented. In the face of ambiguous regulatory guidelines for online banner promotion, drug companies appear to make an attempt to adapt to regulatory guidelines designed for traditional media. However, banner ads use various techniques of presentation to present the advertised drug in the best possible light. The FDA should formalize requirements that drug companies provide a brief summary and include multiple forms of adequate provision in banner ads.

The US and EU regulatory landscapes for locally acting generic/hybrid inhalation products intended for treatment of asthma and COPD.

PubMed

Fuglsang, Anders

2012-08-01

This is a review of the current regulatory requirements associated with development and submission of abridged dossiers for locally acting inhalation drugs intended for the treatment of asthma and chronic obstructive pulmonary disease. The current EU law does not provide for submission of such products as generics due to the definition of bioequivalence and bioavailability; instead they must be submitted as hybrids. A guideline from 2009 is available that suggests a stepwise approach toward approval. An applicant should first consider the degree of in vitro match with the reference product; provided that the match is extensive, approval may be granted. If the in vitro match cannot be proven, the next step is comparison of lung deposition and systemic exposure. If this match is proven, approval may be granted; otherwise, the final step is pharmacodynamic evaluation. In the United States, submission as a generic is possible, but only a single specific guidance document from 1989 is in force. It describes in vitro requirements for comparison of albuterol and metaproterenol pressurized metered dose inhalers. Applicants are encouraged to seek dialogue with regulators prior to and during development. Although parallel scientific advice procedures have been established between the US Food and Drug Administration and the European Medicines Agency, the two authorities give independent and individual advice.

Lubiprostone: pharmacokinetic, pharmacodynamic, safety and regulatory aspects in the treatment of constipation-predominant irritable bowel syndrome.

PubMed

Raschi, Emanuel; De Ponti, Fabrizio

2014-02-01

Lubiprostone acts locally (apical membrane of human intestinal epithelial cells) as a highly selective type-2 chloride channel activator. It was approved in the USA for chronic idiopathic constipation (January 2006) and in women aged ≥ 18 years suffering from irritable bowel syndrome with constipation (IBS-C) (April 2008). So far, the only other pro-secretory medication approved in IBS-C and currently available in USA and Europe (since August and November 2012, respectively) is linaclotide. This review outlines the regulatory history, pharmacokinetic, pharmacodynamic and safety data in the treatment of IBS-C with a European perspective. It is based on publicly available data, namely, published literature, drug labels and the FDA's spontaneous reporting system. Although interesting pharmacodynamic data suggest that lubiprostone may have additional mechanisms of action, its beneficial effects in IBS-C must be confirmed in the actual clinical scenario taking into account the new version of European Medicines Agency's guideline. This is especially important with regard to duration of studies (recommended to be at least 6 months) to adequately assess long-term sustained efficacy, withdrawal, rebound and safety. Further research is warranted in uncertain areas (i.e., males, pediatric and elderly patients). On the basis of current data, it is still too early to draw definite conclusions on the overall risk-benefit balance for IBS-C.

Drug-induced liver injury: Do we know everything?

PubMed Central

Alempijevic, Tamara; Zec, Simon; Milosavljevic, Tomica

2017-01-01

Interest in drug-induced liver injury (DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of LiverTox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain. PMID:28443154

Workgroup Report: Drinking-Water Nitrate and Health—Recent Findings and Research Needs

PubMed Central

Ward, Mary H.; deKok, Theo M.; Levallois, Patrick; Brender, Jean; Gulis, Gabriel; Nolan, Bernard T.; VanDerslice, James

2005-01-01

Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit. The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered. PMID:16263519

Workgroup report: Drinking-water nitrate and health - Recent findings and research needs

USGS Publications Warehouse

Ward, M.H.; deKok, T.M.; Levallois, P.; Brender, J.; Gulis, G.; Nolan, B.T.; VanDerslice, J.

2005-01-01

Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit. The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered.

Workgroup report: Drinking-water nitrate and health--recent findings and research needs.

PubMed

Ward, Mary H; deKok, Theo M; Levallois, Patrick; Brender, Jean; Gulis, Gabriel; Nolan, Bernard T; VanDerslice, James

2005-11-01

Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit. The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered.

Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability

PubMed Central

Treviño-Quintanilla, Luis Gerardo; Freyre-González, Julio Augusto; Martínez-Flores, Irma

2013-01-01

In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different σ/anti-σ controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these σ/anti-σ post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli. PMID:24396271

Regulatory considerations on new adjuvants and delivery systems.

PubMed

Sesardic, D

2006-04-12

New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

How well are national guidelines relating to the general sales of aspirin and paracetamol, adhered to by retail stores: a mystery shopper study

PubMed Central

Molloy, Phillip; Chambers, Ruth; Cork, Tania

2016-01-01

Objective To determine whether non-pharmaceutical retail outlets are aboding to the current Medicines and Healthcare products Regulatory Agency (MHRA) national guidelines for over-the-counter (OTC) sales of aspirin and paracetamol. Methods Stages 1 and 2 of the study deployed eight and four medical students, respectively, to undertake a mystery shopper style investigation. Stage 1: eight medical students attempted to buy ≥96 tablets/capsules aspirin or paracetamol in one transaction in 62 shops. Stage 2: four medical students attempted to purchase 32 paracetamol 500 mg along with a ‘flu remedy preparation also containing paracetamol, in 54 shops. Results Stage 1 data revealed that 58% and 57% retailers sold more than the MHRA guidelines recommended for paracetamol and aspirin, respectively. We observed that 23% and 28% retailers were willing to sell ≥96 tablets of paracetamol or aspirin with no questions asked. Stage 2 results showed that 57% retailers sold 32×500 mg paracetamol in conjunction with a paracetamol-containing ‘flu preparation; while 98% shops sold 16×paracetamol 500 mg along with a paracetamol-containing ‘flu remedy, with no questions asked of the shopper or advice given. Discussion MHRA national guidelines for OTC medicines sales appear to be poorly adhered to in non-pharmacy shops. Sales of aspirin and paracetamol OTC must be better regulated in the UK to ultimately reduce morbidity and mortality rates of deliberate and accidental overdoses. PMID:26781508

78 FR 26425 - Sentencing Guidelines for United States Courts

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-06

... tax system and the legal system as a whole. Therefore, to use them to reduce the tax loss would... undermine the public's confidence in the medical regulatory and distribution system. The Commission also...

Electric Power Generation, Transmission and Distribution (NAICS 2211)

EPA Pesticide Factsheets

Find EPA regulatory information for electrical utilities, including coal-fired power plants. Includes links to NESHAPs for RICE, stationary combustion engines, fossil fuel waste, cooling water, effluent guidelines. Find information on the MATS rule.

Sediment Toxicity Testing

EPA Science Inventory

Sediment toxicity testing has become a fundamental component of regulatory frameworks for assessing the risks posed by contaminated sediments and for development of chemical sediment quality guidelines. Over the past two decades, sediment toxicity testing methods have advanced co...

MO-A-BRC-00: TG167: Clinical Recommendations for Innovative Brachytherapy Devices and Applicators

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used to evaluate innovative radiotherapy devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining equivalence of the innovative device to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of an innovative brachytherapy device or application is a critical part in which physicists are actively involved. The physicist’s role, along with physician colleagues, in this process is highlighted for innovative products or applications and includes evaluation of 1)more » dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, 2) risks and benefits from regulatory and safety perspectives, and 3) resource assessment and preparedness. Further, calibration methods should be traceable to a primary standards dosimetry laboratory such as NIST in the U.S. or to other primary standards dosimetry laboratory located elsewhere. Clinical users should follow standards as approved by their country’s regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the ADCLs is encouraged before a source is introduced into widespread routine clinical use. The AAPM and GEC-ESTRO have developed guidelines for the safe and consistent application of brachytherapy using innovative brachytherapy devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. NRC, FDA, Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, European Commission for CE Marking, and institutional review boards and radiation safety committees. Learning Objectives: Understand the necessary dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use. Evaluate risks and benefits from regulatory and safety perspectives. Identify necessary resources and create a plan for clinical introduction of innovative brachytherapy device or applications. Consultant for Theragenics Corp.; R. Nath, Consultant to Theragenics Corp.« less

MO-A-BRC-02: TG167 Report - Detailed Description

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivard, M.

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used to evaluate innovative radiotherapy devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining equivalence of the innovative device to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of an innovative brachytherapy device or application is a critical part in which physicists are actively involved. The physicist’s role, along with physician colleagues, in this process is highlighted for innovative products or applications and includes evaluation of 1)more » dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, 2) risks and benefits from regulatory and safety perspectives, and 3) resource assessment and preparedness. Further, calibration methods should be traceable to a primary standards dosimetry laboratory such as NIST in the U.S. or to other primary standards dosimetry laboratory located elsewhere. Clinical users should follow standards as approved by their country’s regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the ADCLs is encouraged before a source is introduced into widespread routine clinical use. The AAPM and GEC-ESTRO have developed guidelines for the safe and consistent application of brachytherapy using innovative brachytherapy devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. NRC, FDA, Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, European Commission for CE Marking, and institutional review boards and radiation safety committees. Learning Objectives: Understand the necessary dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use. Evaluate risks and benefits from regulatory and safety perspectives. Identify necessary resources and create a plan for clinical introduction of innovative brachytherapy device or applications. Consultant for Theragenics Corp.; R. Nath, Consultant to Theragenics Corp.« less

MO-A-BRC-01: TG167 Report - Introduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nath, R.

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used to evaluate innovative radiotherapy devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining equivalence of the innovative device to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of an innovative brachytherapy device or application is a critical part in which physicists are actively involved. The physicist’s role, along with physician colleagues, in this process is highlighted for innovative products or applications and includes evaluation of 1)more » dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, 2) risks and benefits from regulatory and safety perspectives, and 3) resource assessment and preparedness. Further, calibration methods should be traceable to a primary standards dosimetry laboratory such as NIST in the U.S. or to other primary standards dosimetry laboratory located elsewhere. Clinical users should follow standards as approved by their country’s regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the ADCLs is encouraged before a source is introduced into widespread routine clinical use. The AAPM and GEC-ESTRO have developed guidelines for the safe and consistent application of brachytherapy using innovative brachytherapy devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. NRC, FDA, Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, European Commission for CE Marking, and institutional review boards and radiation safety committees. Learning Objectives: Understand the necessary dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use. Evaluate risks and benefits from regulatory and safety perspectives. Identify necessary resources and create a plan for clinical introduction of innovative brachytherapy device or applications. Consultant for Theragenics Corp.; R. Nath, Consultant to Theragenics Corp.« less

Regulatory issues with multiplicity in drug approval: Principles and controversies in a changing landscape.

PubMed

Benda, Norbert; Brandt, Andreas

2018-01-01

Recently, new draft guidelines on multiplicity issues in clinical trials have been issued by European Medicine Agency (EMA) and Food and Drug Administration (FDA), respectively. Multiplicity is an issue in clinical trials, if the probability of a false-positive decision is increased by insufficiently accounting for testing multiple hypotheses. We outline the regulatory principles related to multiplicity issues in confirmatory clinical trials intended to support a marketing authorization application in the EU, describe the reasons for an increasing complexity regarding multiple hypotheses testing and discuss the specific multiplicity issues emerging within the regulatory context and being relevant for drug approval.

AsMA Medical Guidelines for Air Travel: In-Flight Medical Care.

PubMed

Thibeault, Claude; Evans, Anthony D; Pettyjohn, Frank S; Alves, Paulo M

2015-06-01

Medical Guidelines for Airline Travel provide information that enables healthcare providers to properly advise patients who plan to travel by air. All airlines are required to provide first aid training for cabin crew, and the crew are responsible for managing any in-flight medical events. There are also regulatory requirements for the carriage of first aid and medical kits. AsMA has developed recommendations for first aid kits, emergency medical kits, and universal precaution kits.

History and future of genetically engineered food animal regulation: an open request.

PubMed

Wells, Kevin D

2016-06-01

Modern biotechnology resulted from of a series of incremental improvements in the understanding of DNA and the enzymes that nature evolved to manipulate it. As the potential impact of genetic engineering became apparent, scientists began the process of trying to identify the potential unintended consequences. Restrictions to recombinant DNA experimentation were at first self-imposed. Collaborative efforts between scientists and lawyers formalized an initial set of guidelines. These guidelines have been used to promulgate regulations around world. However, the initial guidelines were only intended as a starting point and were motivated by a specific set of concerns. As new data became available, the guidelines and regulations should have been adapted to the new knowledge. Instead, other social drivers drove the development of regulations. For most species and most applications, the framework that was established has slowly allowed some products to reach the market. However, genetically engineered livestock that are intended for food have been left in a regulatory state of limbo. To date, no genetically engineered food animal is available in the marketplace. A short history and a U.S.-based genetic engineer's perspective are presented. In addition, a request to regulatory agencies is presented for consideration as regulation continues to evolve. Regulators appear to have shown preference for the slow, random progression of evolution over the efficiency of intentional design.

Guidelines and methodological reviews concerning drug abuse liability assessment.

PubMed

Balster, Robert L; Bigelow, George E

2003-06-05

Regulatory control of drugs with abuse liability is an important component of drug control policy and is believed to help prevent nonmedical use. To be maximally effective, this requires a scientific assessment of abuse liability of drugs considered for regulatory control. These assessments have relied extensively on laboratory-based animal and human testing, but also utilize information from clinical trials, actual abuse and other sources. Here, we discuss recommendations and guidelines that have been proposed for abuse liability assessment and describe important review papers and conference proceedings that have addressed this matter, focusing primarily on drugs with medical usefulness. Historically, there is substantial consensus about how to approach abuse liability evaluation of drugs with actions similar to those of abused opiates, stimulants, depressants, and to a somewhat lesser extent, cannabinoids and hallucinogens, and much of what has been recommended for abuse potential assessment in the past remains valid and useful. On the other hand, novel CNS-active medications which cannot be readily classified with these traditional drugs of abuse are increasingly under development. In addition, advances in the science of abuse liability assessment need to be incorporated into future guidelines and recommendations on this subject. Developers of new medications need guidance on how to utilize scientific research to maximize therapeutic benefit while minimizing risk for abuse. Thus, another goal of this review has been to identify areas where critical thinking and new guideline development are needed.

Regulatory Guidance for Lightning Protection in Nuclear Power Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kisner, Roger A; Wilgen, John B; Ewing, Paul D

2006-01-01

Abstract - Oak Ridge National Laboratory (ORNL) was engaged by the U.S. Nuclear Regulatory Commission (NRC) Office of Nuclear Regulatory Research (RES) to develop the technical basis for regulatory guidance to address design and implementation practices for lightning protection systems in nuclear power plants (NPPs). Lightning protection is becoming increasingly important with the advent of digital and low-voltage analog systems in NPPs. These systems have the potential to be more vulnerable than older analog systems to the resulting power surges and electromagnetic interference (EMI) when lightning strikes facilities or power lines. This paper discusses the technical basis for guidance tomore » licensees and applicants covered in Regulatory Guide (RG) 1.204, Guidelines for Lightning Protection of Nuclear Power Plants, issued August 2005. RG 1.204 describes guidance for practices that are acceptable to the NRC staff for protecting nuclear power structures and systems from direct lightning strikes and the resulting secondary effects.« less

Regulatory guidance for lightning protection in nuclear power plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kisner, R. A.; Wilgen, J. B.; Ewing, P. D.

2006-07-01

Oak Ridge National Laboratory (ORNL) was engaged by the U.S. Nuclear Regulatory Commission (NRC) Office of Nuclear Regulatory Research (RES) to develop the technical basis for regulatory guidance to address design and implementation practices for lightning protection systems in nuclear power plants (NPPs). Lightning protection is becoming increasingly important with the advent of digital and low-voltage analog systems in NPPs. These systems have the potential to be more vulnerable than older analog systems to the resulting power surges and electromagnetic interference (EMI) when lightning strikes facilities or power lines. This paper discusses the technical basis for guidance to licensees andmore » applicants covered in Regulatory Guide (RG) 1.204, Guidelines for Lightning Protection of Nuclear Power Plants, issued August 2005. RG 1.204 describes guidance for practices that are acceptable to the NRC staff for protecting nuclear power structures and systems from direct lightning strikes and the resulting secondary effects. (authors)« less

Drug Development for Pediatric Populations: Regulatory Aspects

PubMed Central

Zisowsky, Jochen; Krause, Andreas; Dingemanse, Jasper

2010-01-01

Pediatric aspects are nowadays integrated early in the development process of a new drug. The stronger enforcement to obtain pediatric information by the regulatory agencies in recent years resulted in an increased number of trials in children. Specific guidelines and requirements from, in particular, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) form the regulatory framework. This review summarizes the regulatory requirements and strategies for pediatric drug development from an industry perspective. It covers pediatric study planning and conduct, considerations for first dose in children, appropriate sampling strategies, and different methods for data generation and analysis to generate knowledge about the pharmacokinetics (PK) and pharmacodynamics (PD) of a drug in children. The role of Modeling and Simulation (M&S) in pediatrics is highlighted—including the regulatory basis—and examples of the use of M&S are illustrated to support pediatric drug development. PMID:27721363

Regulatory Considerations in Toxicological Neuropathology

EPA Science Inventory

Pathological assessment of the nervous system is included in several US Environmental Protection Agency [US EPA or Agency] and Organization for Economic Cooperation and Development [OECD] testing guidelines for health effects of chemicals. A variety of considerations are importan...

Groundwater recharge with reclaimed municipal wastewater: health and regulatory considerations.

PubMed

Asano, Takashi; Cotruvo, Joseph A

2004-04-01

Groundwater recharge with reclaimed municipal wastewater presents a wide spectrum of technical and health challenges that must be carefully evaluated prior to undertaking a project. This review will provide a discussion of groundwater recharge and its management with special reference to health and regulatory aspects of groundwater recharge with reclaimed municipal wastewater. At present, some uncertainties with respect to health risk considerations have limited expanding use of reclaimed municipal wastewater for groundwater recharge, especially when a large portion of the groundwater contains reclaimed wastewater that may affect the domestic water supply. The proposed State of California criteria for groundwater recharge are discussed as an illustration of a cautious approach. In addition, a summary is provided of the methodology used in developing the World Health Organization's Guidelines for Drinking Water Quality to illustrate how numerical guideline values are generated for contaminants that may be applicable to groundwater recharge.

Guidelines for clinical supervision in health service psychology.

PubMed

2015-01-01

This document outlines guidelines for supervision of students in health service psychology education and training programs. The goal was to capture optimal performance expectations for psychologists who supervise. It is based on the premises that supervisors (a) strive to achieve competence in the provision of supervision and (b) employ a competency-based, meta-theoretical approach to the supervision process. The Guidelines on Supervision were developed as a resource to inform education and training regarding the implementation of competency-based supervision. The Guidelines on Supervision build on the robust literatures on competency-based education and clinical supervision. They are organized around seven domains: supervisor competence; diversity; relationships; professionalism; assessment/evaluation/feedback; problems of professional competence, and ethical, legal, and regulatory considerations. The Guidelines on Supervision represent the collective effort of a task force convened by the American Psychological Association (APA) Board of Educational Affairs (BEA). PsycINFO Database Record (c) 2015 APA, all rights reserved.

Risk disclosure and the recruitment of oocyte donors: are advertisers telling the full story?

PubMed

Alberta, Hillary B; Berry, Roberta M; Levine, Aaron D

2014-01-01

This study analyzes 435 oocyte donor recruitment advertisements to assess whether entities recruiting donors of oocytes to be used for in vitro fertilization (IVF) procedures include a disclosure of risks associated with the donation process in their advertisements. Such disclosure is required by the self-regulatory guidelines of the American Society for Reproductive Medicine (ASRM) and by law in California for advertisements placed in the state. We find very low rates of risk disclosure across entity types and regulatory regimes, although risk disclosure is more common in advertisements placed by entities subject to ASRM's self-regulatory guidelines. Advertisements placed in California are more likely to include risk disclosure, but disclosure rates are still quite low. California-based entities advertising outside the state are more likely to include risk disclosure than non-California entities, suggesting that California's law may have a modest "halo effect." Our results suggest that there is a significant ethical and policy problem with the status quo in light of the known and unknown risks of oocyte donation and the importance of risk disclosure to informed consent in the context of oocyte donation. © 2014 American Society of Law, Medicine & Ethics, Inc.

Regulations and guidelines should be strengthened urgently for re-evaluation on post-marketing medicines in China.

PubMed

Xie, Yan-Ming; Tian, Feng

2013-07-01

This paper reviewed the situation of regulations and guidelines on post-marketing medicines in the developed countries and in China. The developed countries have accumulated a lot of empirical principles and techniques on postmarketing surveillance (also named pharmacovigilance), therefore, their regulation systems are nearly perfect. In China, the regulations on post-marketing re-evaluation and relative technical guidelines do not cover the whole aspects, even lack in some important aspects, and long-term risk management mechanisms have not been established. So it is urgent to establish new regulations and improve the regulatory system in China based on the existing regulations and guidelines, by learning from the ideas of foreign advanced regulations, then fully integrating them with China's actual conditions, and cooperating with multidisciplinary researchers.

The Development of Human Factor Guidelines for Unmanned Aircraft System Control Stations

NASA Technical Reports Server (NTRS)

Hobbs, Alan

2014-01-01

Despite being referred to as unmanned some of the major challenges confronting unmanned aircraft systems (UAS) relate to human factors. NASA is conducting research to address the human factors relevant to UAS access to non-segregated airspace. This work covers the issues of pilot performance, interaction with ATC, and control station design. A major outcome of this research will be recommendations for human factors design guidelines for UAS control stations to support routine beyond-line-of-sight operations in the US national airspace system (NAS). To be effective, guidelines must be relevant to a wide range of systems, must not be overly prescriptive, and must not impose premature standardization on evolving technologies. In developing guidelines, we recognize that existing regulatory and guidance material may already provide adequate coverage of certain issues. In other cases suitable guidelines may be found in existing military or industry human factors standards. In cases where appropriate existing standards cannot be identified, original guidelines will be proposed.

The Feasibility of Establishing Operational Water Hyacinth-Based Systems at the Treatment Facilities of Existing Cities. [in Florida and Texas

NASA Technical Reports Server (NTRS)

1977-01-01

The wastewater treatment facilities of three communities in southern Florida and two in southern Texas areas having populations of 20,000 or fewer persons were surveyed to determine: (1) their performance characteristics and the nature of their customers; (2) facility upgrading requirements needed to meet current and future EPA and State standards; (3) their adaptability to water hyacinth utilization and harvested plant disposal; and (4) the level of community support. Guidelines for site selection were established and applied to five cities in Texas and four in Florida. An evaluation of the prospective sites reveals that the Florida locations are generally unsuitable for implementation of water hyacinth based systems because of regulatory philosophy. All five Texas sites have excellent potential.

Challenges in Oral Lipid-lowering Therapy: Position Document of the Spanish Society of Cardiology.

PubMed

Anguita Sánchez, Manuel; Castro Conde, Almudena; Cordero Fort, Alberto; García-Moll Marimón, Xavier; Gómez Doblas, Juan José; González-Juanatey, José R; Lidón Corbi, Rosa María; López-Sendón, José Luis; Mostaza Prieto, José; Rodríguez Padial, Luis

2016-11-01

Lipid-lowering therapy is one of the cornerstones of cardiovascular prevention and is one of the most effective strategies in the secondary prevention of ischemic heart disease. Nevertheless, the current treatment of lipid disorders, together with lifestyle changes, fails to achieve the targets recommended in clinical guidelines in a substantial proportion of patients. PCSK9 inhibitors have demonstrated safety and efficacy in the treatment of dyslipidemia. Due to their ability to reduce low-density lipoprotein cholesterol levels, these drugs have recently been approved for clinical use by Spanish regulatory agencies, with the aim of reducing cardiovascular risk in selected patient groups. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Hanford Environmental Information System (HEIS) Operator`s Manual. Volume 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreck, R.I.

1991-10-01

The Hanford Environmental Information System (HEIS) is a consolidated set of automated resources that effectively manage the data gathered during environmental monitoring and restoration of the Hanford Site. The HEIS includes an integrated database that provides consistent and current data to all users and promotes sharing of data by the entire user community. This manual describes the facilities available to the operational user who is responsible for data entry, processing, scheduling, reporting, and quality assurance. A companion manual, the HEIS User`s Manual, describes the facilities available-to the scientist, engineer, or manager who uses the system for environmental monitoring, assessment, andmore » restoration planning; and to the regulator who is responsible for reviewing Hanford Site operations against regulatory requirements and guidelines.« less

Mercury emission trend influenced by stringent air pollutants regulation for coal-fired power plants in Korea

NASA Astrophysics Data System (ADS)

Pudasainee, Deepak; Kim, Jeong-Hun; Seo, Yong-Chil

2009-12-01

Regulatory control of mercury emission from anthropogenic sources has become a global concern in the recent past. Coal-fired power plants are one of the largest sources of anthropogenic mercury emission into the atmosphere. This paper summarizes the current reducing trend of mercury emission as co-beneficial effect by more stringent regulation changes to control primary air pollutants with introducing test results from the commercial coal-fired facilities and suggesting a guideline for future regulatory development in Korea. On average, mercury emission concentrations ranged 16.3-2.7 μg Sm -3, 2.4-1.1 μg Sm -3, 3.1-0.7 μg Sm -3 from anthracite coal-fired power plants equipped with electrostatic precipitator (ESP), bituminous coal-fired power plants with ESP + flue gas desulphurization (FGD) and bituminous coal-fired power plants with selective catalytic reactor (SCR) + cold side (CS) - ESP + wet FGD, respectively. Among the existing air pollution control devices, the best configuration for mercury removal in coal-fired power plants was SCR + CS - ESP + wet FGD, which were installed due to the stringent regulation changes to control primary air pollutants emission such as SO 2, NOx and dust. It was estimated that uncontrolled and controlled mercury emission from coal-fired power plants as 10.3 ton yr -1 and 3.2 ton yr -1 respectively. After the installation of ESP, FGD and SCR system, following the enforcement of the stringent regulation, 7.1 ton yr -1 of mercury emission has been reduced (nearly 69%) from coal-fired power plants as a co-benefit control. Based on the overall study, a sample guideline including emission limits were suggested which will be applied to develop a countermeasure for controlling mercury emission from coal-fired power plants.

Application of natural resource valuation concepts for development of sustainable remediation plans for groundwater.

PubMed

Connor, John A; Paquette, Shawn; McHugh, Thomas; Gie, Elaine; Hemingway, Mark; Bianchi, Gino

2017-12-15

This paper explores the application of natural resource assessment and valuation procedures as a tool for developing groundwater remediation strategies that achieve the objectives for health and environmental protection, in balance with considerations of economic viability and conservation of natural resources. The natural resource assessment process, as applied under U.S. and international guidelines, entails characterization of groundwater contamination in terms of the pre-existing beneficial services of the impacted resource, the loss of these services caused by the contamination, and the measures and associated costs necessary to restore or replace the lost services. Under many regulatory programs, groundwater remediation objectives assume that the impacted groundwater may be used as a primary source of drinking water in the future, even if not presently in use. In combination with a regulatory preference for removal or treatment technologies, this assumed exposure, while protective of human health, can drive the remedy selection process toward remedies that may not be protective of the groundwater resource itself or of the other natural resources (energy, materials, chemicals, etc.) that may be consumed in the remediation effort. To achieve the same health and environmental protection goals under a sustainable remediation framework, natural resource assessment methods can be applied to restore the lost services and preserve the intact services of the groundwater so as to protect both current and future users of that resource. In this paper, we provide practical guidelines for use of natural resource assessment procedures in the remedy selection process and present a case study demonstrating the use of these protocols for development of sustainable remediation strategies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Performance testing of the environmental TLD system for the Three Mile Island Nuclear Station.

PubMed

Toke, L F; Carson, B H; Baker, G G; McBride, M H; Plato, P A; Miklos, J A

1984-05-01

Panasonic UD-801 thermoluminescent dosimeters ( TLDs ) containing two calcium sulfate phosphors were tested under Performance Specification 3.1 established by the American National Standard Institute ( ANSI75 ) and in the U.S. Nuclear Regulatory Commission's Regulatory Guide 4.13 ( NRC77 ). The specific qualifying tests included TLD uniformity, reproducibility, energy dependence and directional dependence. The overall measurement uncertainties and associated confidence levels are within the prescribed guidelines defined in the qualifying requirements for environmental TLDs .

Guidelines for use of fishes in research: revised and expanded

USGS Publications Warehouse

Jenkins, Jill A.; Bart, Henry L.; Bowker, James D.; Bowser, Paul R.; MacMillan, J. Randy; Nickum, John G.; Rachlin, Joseph W.; Rose, James D.; Sorensen, Peter W.; Warkentine, Barbara E.; Whitledge, Greg W.

2014-01-01

The Guidelines for the Use of Fishes in Research (2014; 2014 Guidelines), now available through the American fisheries Society (AFS) website and in print from the AFS bookstore, is a resource to aid researchers and regulatory authorities regarding responsible, scientifically valid research on fish and aquatic wildlife. The Guidelines for the Use of Fishes in Field Research (American Society of Ichthyologists and Herpetologists [ASIH] et al. 1987, 1988) emphasized field research and was followed by the 2004 Guidelines including laboratory research topics. Each version of the Guidelines has been jointly endorsed and/or published by the ASIH, the American Institute of Fishery Research Biologists (AIFRB), and AFS--each focusing on the scientific understanding, global conservation, and sustainability of aquatic animals, fisheries, and ecosystems. Changes with time necessitate revisions to make the Guidelines consistent with contemporary practices and scientific literature so to remain relevant as a technical resource. This document provides not only general principles relevant for field and laboratory research endeavors but includes specific requirements for researchers working within the United States and outside of the country. Within the scope of their expertise, the 2014 Uses of Fishers in Research (UFR) Committee members updated and revised sections, resulting in a 90-page 2014 Guidelines having undergone through peer review. As before, topical areas were addressed (see Table of Contents on page 416). Expanded coverage was provided on U.S. and international agencies and programs relevant to research with fishes. The Surgical Procedures and the Marking and Tagging section received special focus by a UFR Subcommittee. Feeds and Feeding and the Administration of Drugs, Biologics and Other Chemicals are just some of the newly added topics. The 2014 Guidelines is user-friendly by way of hyperlinks to external Internet sites, intradocument sections, and tables of acronyms with corresponding terms, low regulatory priority drugs, and Office of International des Epizooties notifiable disease agents. Again, the Institutional Animal Care and Use Committee (IACUC) role is explained, expectations for research are provided, and a brief checklist for IACUC readiness is included. Overall, the ,i>2014 Guidelines is the taxon-specific resource for our professional societies and is a principal document for standards on the care and use of fish and aquatic vertebrates in research.

77 FR 21592 - Guidelines for Preparing and Reviewing Licensing Applications for the Production of Radioisotopes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... Regulatory Commission. Jessie F. Quichocho, Chief, Research and Test Reactors Licensing Branch, Division of... information in comment submissions that you do not want to be publicly disclosed. The NRC posts all comment...

10 CFR 2.1001 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., magnetic, graphic matter, or other documentary material, regardless of form or characteristic. Documentary... documentary material shall be guided by the topical guidelines in the applicable NRC Regulatory Guide. DOE... Network means the combined system that makes documentary material available electronically to parties...

Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization.

PubMed

Fuchs, Anke; Gliwiński, Mateusz; Grageda, Nathali; Spiering, Rachel; Abbas, Abul K; Appel, Silke; Bacchetta, Rosa; Battaglia, Manuela; Berglund, David; Blazar, Bruce; Bluestone, Jeffrey A; Bornhäuser, Martin; Ten Brinke, Anja; Brusko, Todd M; Cools, Nathalie; Cuturi, Maria Cristina; Geissler, Edward; Giannoukakis, Nick; Gołab, Karolina; Hafler, David A; van Ham, S Marieke; Hester, Joanna; Hippen, Keli; Di Ianni, Mauro; Ilic, Natasa; Isaacs, John; Issa, Fadi; Iwaszkiewicz-Grześ, Dorota; Jaeckel, Elmar; Joosten, Irma; Klatzmann, David; Koenen, Hans; van Kooten, Cees; Korsgren, Olle; Kretschmer, Karsten; Levings, Megan; Marek-Trzonkowska, Natalia Maria; Martinez-Llordella, Marc; Miljkovic, Djordje; Mills, Kingston H G; Miranda, Joana P; Piccirillo, Ciriaco A; Putnam, Amy L; Ritter, Thomas; Roncarolo, Maria Grazia; Sakaguchi, Shimon; Sánchez-Ramón, Silvia; Sawitzki, Birgit; Sofronic-Milosavljevic, Ljiljana; Sykes, Megan; Tang, Qizhi; Vives-Pi, Marta; Waldmann, Herman; Witkowski, Piotr; Wood, Kathryn J; Gregori, Silvia; Hilkens, Catharien M U; Lombardi, Giovanna; Lord, Phillip; Martinez-Caceres, Eva M; Trzonkowski, Piotr

2017-01-01

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.

An Empirical Evaluation of the US Beer Institute’s Self-Regulation Code Governing the Content of Beer Advertising

PubMed Central

Xuan, Ziming; Damon, Donna; Noel, Jonathan

2013-01-01

Objectives. We evaluated advertising code violations using the US Beer Institute guidelines for responsible advertising. Methods. We applied the Delphi rating technique to all beer ads (n = 289) broadcast in national markets between 1999 and 2008 during the National Collegiate Athletic Association basketball tournament games. Fifteen public health professionals completed ratings using quantitative scales measuring the content of alcohol advertisements (e.g., perceived actor age, portrayal of excessive drinking) according to 1997 and 2006 versions of the Beer Institute Code. Results. Depending on the code version, exclusion criteria, and scoring method, expert raters found that between 35% and 74% of the ads had code violations. There were significant differences among producers in the frequency with which ads with violations were broadcast, but not in the proportions of unique ads with violations. Guidelines most likely to be violated included the association of beer drinking with social success and the use of content appealing to persons younger than 21 years. Conclusions. The alcohol industry’s current self-regulatory framework is ineffective at preventing content violations but could be improved by the use of new rating procedures designed to better detect content code violations. PMID:23947318

An empirical evaluation of the US Beer Institute's self-regulation code governing the content of beer advertising.

PubMed

Babor, Thomas F; Xuan, Ziming; Damon, Donna; Noel, Jonathan

2013-10-01

We evaluated advertising code violations using the US Beer Institute guidelines for responsible advertising. We applied the Delphi rating technique to all beer ads (n = 289) broadcast in national markets between 1999 and 2008 during the National Collegiate Athletic Association basketball tournament games. Fifteen public health professionals completed ratings using quantitative scales measuring the content of alcohol advertisements (e.g., perceived actor age, portrayal of excessive drinking) according to 1997 and 2006 versions of the Beer Institute Code. Depending on the code version, exclusion criteria, and scoring method, expert raters found that between 35% and 74% of the ads had code violations. There were significant differences among producers in the frequency with which ads with violations were broadcast, but not in the proportions of unique ads with violations. Guidelines most likely to be violated included the association of beer drinking with social success and the use of content appealing to persons younger than 21 years. The alcohol industry's current self-regulatory framework is ineffective at preventing content violations but could be improved by the use of new rating procedures designed to better detect content code violations.

[Recommendations on the use of belimumab in systemic lupus erythematosus. GEAS-SEMI Clinical Practice Guide].

PubMed

Ramos-Casals, M; Ruiz-Irastorza, G; Jiménez-Alonso, J; Khamashta, M A

2013-01-01

Biological therapies are based on the administration of various types of synthetic molecules related to the immune response. Their use has spread in recent years to the field of systemic autoimmune diseases, particularly to systemic lupus erythematosus (SLE). Until 2011, these diseases were not included in the therapeutic indications approved by international regulatory agencies. Therefore, the use of biological therapies was restricted to clinical trials and to compassionate use for cases refractory to standard treatments (off-label use), which require the approval of the Health Ministry. In 2011, belimumab, a human monoclonal antibody that specifically binds to the soluble form of the protein human B lymphocyte stimulator BlyS, was approved for use in patients with SLE. Because the clinical information on the use of this new drug in patients with SLE has only been obtained from the results of randomized trials, the Study Group of Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine (SEMI) has developed therapeutic guidelines. These guidelines are based on the current scientific evidence on the use of belimumab in SLE patients in the clinical practice. Copyright © 2012 Elsevier España, S.L. All rights reserved.

A Comparative Review of Marketing Authorization Decisions in Switzerland, the EU, and the USA.

PubMed

Dalla Torre Di Sanguinetto, Simon; Heinonen, Esa; Antonov, Janine; Bolte, Claus

2018-01-01

In this study we compared Swissmedic's (SMC's) regulatory marketing authorization decisions to those of the US Food and Drug Administration (FDA) and European drug regulatory authorities (EU). We investigated the overall similarity of the regulatory decisions, approval, and postmarketing withdrawal rates in the 3 jurisdictions. In case regulatory decisions diverged, we analyzed the reasons for rejection of marketing authorization applications (MAAs). The study comprises 255 new molecular entity (NME) MAAs assessed by SMC by the EU and FDA between 2005 through 2014. Study parameters included the regulatory decision, postmarketing withdrawal rates, and the official reasons for rejection. Regulatory decisions converged to a high degree among all 3 agencies (between 84% and 90%). SMC's average approval rate (84%) was slightly lower than those of the FDA (87%) and the EU (91%). Postmarketing withdrawal rates were generally low (4%-5%) but were 3 to 5 times higher when decisions among the drug regulatory authorities (DRAs) diverged. SMC's primary grounds for rejection were lack of efficacy (45%) and safety (40%). The 3 investigated DRAs adhere largely to the same scientific principles and regulatory guidelines; therefore, remaining disparities ought to be considered in a cultural, legal and public health priority context.

EPA Guidelines for States Regarding Online Asbestos Model Accreditation Plan (MAP) Annual Refresher Training

EPA Pesticide Factsheets

Memorandum dated July 9, 2007 from the Chief of the Fibers and Organics Branch, National Chemicals Program Division, Office of Prevention, Pesticides and Toxic Substances to EPA Regional Asbestos Coordinators and State Regulatory Stakeholders.

Implementation Guide for Minimum Retroreflectivity Requirements for Traffic Signs

DOT National Transportation Integrated Search

1998-04-01

Although the "Manual on Uniform Traffic Control Devices" (MUTCD) stipulates that all warning and regulatory signs be illuminated or reflectorized to show the same color and shape by day or night, there are no specific guidelines for required retroref...

Regulatory Scientific Advice on Non-Inferiority Drug Trials

PubMed Central

Knol, Mirjam J.; Klungel, Olaf H.; Gispen-De Wied, Christine C.; de Boer, Antonius; Hoes, Arno W.; Leufkens, Hubert G.; Mantel-Teeuwisse, Aukje K.

2013-01-01

The active-controlled trial with a non-inferiority design has gained popularity in recent years. However, non-inferiority trials present some methodological challenges, especially in determining the non-inferiority margin. Regulatory guidelines provide some general statements on how a non-inferiority trial should be conducted. Moreover, in a scientific advice procedure, regulators give companies the opportunity to discuss critical trial issues prior to the start of the trial. The aim of this study was to identify potential issues that may benefit from more explicit guidance by regulators. To achieve this, we collected and analyzed questions about non-inferiority trials posed by applicants for scientific advice in Europe in 2008 and 2009, as well as the responses given by the European Medicines Agency (EMA). In our analysis we included 156 final letters of advice from 2008 and 2009, addressed to 94 different applicants (manufacturers). Our analysis yielded two major findings: (1) applicants frequently asked questions ‘whether’ and ‘how’ to conduct a non-inferiority trial, 26% and 74%, respectively, and (2) the EMA regulators seem mainly concerned about the choice of the non-inferiority margin in non-inferiority trials (36% of total regulatory answers). In 40% of the answers, the EMA recommended using a stricter margin, and in 10% of the answers regarding non-inferiority margins, the EMA questioned the justification of the proposed non-inferiority margin. We conclude that there are still difficulties in selecting the appropriate methodology for non-inferiority trials. Straightforward and harmonized guidance regarding non-inferiority trials is required, for example on whether it is necessary to conduct such a trial and how the non-inferiority margin is determined. It is unlikely that regulatory guidelines can cover all therapeutic areas; therefore, in some cases regulatory scientific advice may be used as an opportunity for tailored advice. PMID:24040346

How well are national guidelines relating to the general sales of aspirin and paracetamol, adhered to by retail stores: a mystery shopper study.

PubMed

Molloy, Phillip; Chambers, Ruth; Cork, Tania

2016-01-18

To determine whether non-pharmaceutical retail outlets are aboding to the current Medicines and Healthcare products Regulatory Agency (MHRA) national guidelines for over-the-counter (OTC) sales of aspirin and paracetamol. Stages 1 and 2 of the study deployed eight and four medical students, respectively, to undertake a mystery shopper style investigation. Stage 1: eight medical students attempted to buy ≥ 96 tablets/capsules aspirin or paracetamol in one transaction in 62 shops. Stage 2: four medical students attempted to purchase 32 paracetamol 500 mg along with a 'flu remedy preparation also containing paracetamol, in 54 shops. Stage 1 data revealed that 58% and 57% retailers sold more than the MHRA guidelines recommended for paracetamol and aspirin, respectively. We observed that 23% and 28% retailers were willing to sell ≥ 96 tablets of paracetamol or aspirin with no questions asked. Stage 2 results showed that 57% retailers sold 32 × 500 mg paracetamol in conjunction with a paracetamol-containing 'flu preparation; while 98% shops sold 16 × paracetamol 500 mg along with a paracetamol-containing 'flu remedy, with no questions asked of the shopper or advice given. MHRA national guidelines for OTC medicines sales appear to be poorly adhered to in non-pharmacy shops. Sales of aspirin and paracetamol OTC must be better regulated in the UK to ultimately reduce morbidity and mortality rates of deliberate and accidental overdoses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder.

PubMed

Grunze, Heinz; Vieta, Eduard; Goodwin, Guy M; Bowden, Charles; Licht, Rasmus W; Azorin, Jean-Michel; Yatham, Lakshmi; Mosolov, Sergey; Möller, Hans-Jürgen; Kasper, Siegfried

2018-02-01

Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to supply a systematic overview of all scientific evidence pertaining to the acute and long-term treatment of bipolar mixed states in adults. Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A-F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode. Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention. The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands. Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2014-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use, in addition to 20 monographs and general texts for inclusion in The International Pharmacopoeia and 11 new International Chemical Reference Substances. The International Pharmacopoeia--updating mechanism for the section on radiopharmaceuticals; WHO good manufacturing practices for pharmaceutical products: main principles; Model quality assurance system for procurement agencies; Assessment tool based on the model quality assurance system for procurement agencies: aide-memoire for inspection; Guidelines on submission of documentation for prequalification of finished pharmaceutical products approved by stringent regulatory authorities; and Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product: quality part.

How to define responders in osteoarthritis

PubMed Central

Cooper, Cyrus; Adachi, Jonathan D.; Bardin, Thomas; Berenbaum, Francis; Flamion, Bruno; Jonsson, Helgi; Kanis, John A.; Pelousse, Franz; Lems, Willem F.; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Reiter, Susanne; Reginster, Jean-Yves; Rizzoli, René; Bruyère, Olivier

2013-01-01

Background Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain, functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of other joint structures. Scope Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis, review current regulatory guidelines for the conduct of clinical trials, and examine the concept of responder analyses for improving drug evaluation in osteoarthritis. Findings The ESCEO considers that the major challenges in DMOAD development are the absence of a precise definition of the disease, particularly in the early stages, and the lack of consensus on how to detect structural changes and link them to clinically meaningful endpoints. Responder criteria should help identify progression of disease and be clinically meaningful. The ideal criterion should be sensitive to change over time and should predict disease progression and outcomes such as joint replacement. Conclusion The ESCEO considers that, for knee osteoarthritis, clinical trial data indicate that radiographic joint space narrowing >0.5 mm over 2 or 3 years might be a reliable surrogate measure for total joint replacement. On-going research using techniques such as magnetic resonance imaging and biochemical markers may allow the identification of these patients earlier in the disease process. PMID:23557069

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition: guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestations on dogs and cats.

PubMed

Marchiondo, A A; Holdsworth, P A; Fourie, L J; Rugg, D; Hellmann, K; Snyder, D E; Dryden, M W

2013-05-01

These second edition guidelines, updated from the 2007 version (Marchiondo et al., 2007), are intended to assist the planning and conduct of laboratory and clinical studies to assess the efficacy of ectoparasiticides applied to dogs or cats for the purpose of treating, preventing and controlling flea and tick infestations. Major revisions to this second edition include guidelines on the assessment of systemic flea and tick products, an update of the geographical distribution of the common fleas and ticks species on dogs and cats, determination of flea and tick efficacy based on geometric versus arithmetic means with respect to geographic regulatory agencies, modification of tick categorization in the assessment of efficacy, expanded guidelines on repellency and anti-feeding effects, enhanced practical field study guidance, and considerations on the ranges of flea and ticks for infestations in laboratory studies. The term ectoparasiticide includes insecticidal and acaricidal compounds, as well as insect growth regulators. The range of biological activities from animal treatment that are considered include: repellency and anti-feeding effects, knockdown, speed of kill, immediate and persistent lethal effects, and interference with egg fertility and subsequent development of off-host life cycle stages. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping, interpretation of results and animal welfare. These guidelines are also intended to assist regulatory authorities involved in the approval and registration of new topical or systemic ectoparasiticides, and to facilitate the worldwide adoption of harmonized procedures.

Considerations on photochemical genotoxicity. II: report of the 2009 International Workshop on Genotoxicity Testing Working Group.

PubMed

Lynch, Anthony M; Guzzie, Peggy J; Bauer, Daniel; Gocke, Elmar; Itoh, Satoru; Jacobs, Abby; Krul, Cyrille A M; Schepky, Andreas; Tanaka, Noriho; Kasper, Peter

2011-08-16

A workshop to reappraise the previous IWGT recommendations for photogenotoxicity testing [E. Gocke, L. Muller, P.J. Guzzie, S. Brendler-Schwaab, S. Bulera, C.F. Chignell, L.M. Henderson, A. Jacobs, H. Murli, R.D. Snyder, N. Tanaka, Considerations on photochemical genotoxicity: report of the International Workshop on Genotoxicity Test Procedures working group, Environ. Mol. Mutagen., 35 (2000) 173-184] was recently held as part of the 5th International Workshop on Genotoxicity Testing (IWGT) meeting in Basel, Switzerland (August 17-19, 2009). An Expert Panel was convened from regulatory, academic and industrial scientists (with several members serving on the original panel) and chaired by Dr Peter Kasper (BfArM, Germany). The aim of the workshop was to review progress made in photo(geno)toxicity testing over the past decade; a period which saw the introduction of several regulatory photosafety guidances in particular in Europe and the USA. Based on current regulatory guidelines a substantial proportion of compounds trigger the requirements for photosafety testing. Moreover, there has been growing concern within industry about the performance of the in vitro photosafety tests in the "real world" of compound development. Therefore, the expert group reviewed the status of the current regulatory guidance's and the impact these have had on compound development in the context of the various triggers for photosafety testing. In addition, the performance of photogenotoxicity assays (old and new) was discussed, particularly in view of reports of pseudophotoclastogencity. The Expert Panel finished with an assessment of the positioning of photogenotoxicity testing within a photosafety testing strategy. The most significant conclusion made by the Expert Panel was that photogenotoxicity testing should no longer be recommended as part of the standard photosafety testing strategy. In addition, progress was made on the refinement of triggers for photosafety testing. For example, there was support for harmonisation of methods to determine the Molar Extinction Coefficient (MEC) and a consensus agreement that there should be no requirement for testing of compounds with a MEC<1000Lmol(-1)cm(-1). Copyright © 2011 Elsevier B.V. All rights reserved.

Air pollution management and control in Latin America and the Caribbean: implications for climate change.

PubMed

Riojas-Rodríguez, Horacio; da Silva, Agnes Soares; Texcalac-Sangrador, José Luis; Moreno-Banda, Grea Litai

2016-09-01

To assess the status of the legal framework for air quality control in all countries of Latin America and Caribbean (LAC); to determine the current distribution of air monitoring stations and mean levels of air pollutants in all capital and large cities (more than 100 000 inhabitants); and to discuss the implications for climate change and public policymaking. From January 2015-February 2016, searches were conducted of online databases for legislation, regulations, policies, and air pollution programs, as well as for the distribution of monitoring stations and the mean annual levels of air pollution in all LAC countries. Only 117 cities distributed among 17 of 33 LAC countries had official information on ground level air pollutants, covering approximately 146 million inhabitants. The annual mean of inhalable particles concentration in most of the cities were over the World Health Organization Air Quality Guidelines; notably, only Bolivia, Peru, and Guatemala have actually adopted the guidelines. Most of the cities did not have information on particulate matter of 2.5 microns or less, and only a few measured black carbon. The air quality regulatory framework should be updated to reflect current knowledge on health effects. Monitoring and control of ground level pollutants should be extended and strengthened to increase awareness and protect public health. Using the co-benefits of air pollution control for health and climate as a framework for policy and decision-making in LAC is recommended.

Food Web Bioaccumulation Model for Resident Killer Whales from the Northeastern Pacific Ocean as a Tool for the Derivation of PBDE-Sediment Quality Guidelines.

PubMed

Alava, Juan José; Ross, Peter S; Gobas, Frank A P C

2016-01-01

Resident killer whale populations in the NE Pacific Ocean are at risk due to the accumulation of pollutants, including polybrominated diphenyl ethers (PBDEs). To assess the impact of PBDEs in water and sediments in killer whale critical habitat, we developed a food web bioaccumulation model. The model was designed to estimate PBDE concentrations in killer whales based on PBDE concentrations in sediments and the water column throughout a lifetime of exposure. Calculated and observed PBDE concentrations exceeded the only toxicity reference value available for PBDEs in marine mammals (1500 μg/kg lipid) in southern resident killer whales but not in northern resident killer whales. Temporal trends (1993-2006) for PBDEs observed in southern resident killer whales showed a doubling time of ≈5 years. If current sediment quality guidelines available in Canada for polychlorinated biphenyls are applied to PBDEs, it can be expected that PBDE concentrations in killer whales will exceed available toxicity reference values by a large margin. Model calculations suggest that a PBDE concentration in sediments of approximately 1.0 μg/kg dw produces PBDE concentrations in resident killer whales that are below the current toxicity reference value for 95 % of the population, with this value serving as a precautionary benchmark for a management-based approach to reducing PBDE health risks to killer whales. The food web bioaccumulation model may be a useful risk management tool in support of regulatory protection for killer whales.

Differentiating low-molecular-weight heparins based on chemical, biological, and pharmacologic properties: implications for the development of generic versions of low-molecular-weight heparins.

PubMed

Jeske, Walter P; Walenga, Jeanine M; Hoppensteadt, Debra A; Vandenberg, Curtis; Brubaker, Aleah; Adiguzel, Cafer; Bakhos, Mamdouh; Fareed, Jawed

2008-02-01

Low-molecular-weight heparins (LMWHs) are polypharmacologic drugs used to treat thrombotic and cardiovascular disorders. These drugs are manufactured using different chemical and enzymatic methods, resulting in products with distinct chemical and pharmacologic profiles. Generic LMWHs have been introduced in Asia and South America, and several generic suppliers are seeking regulatory approval in the United States and the European Union. For simple small-molecule drugs, generic drugs have the same chemical structure, potency, and bioavailability as the innovator drug. Applying this definition to complex biological products such as the LMWHs has proved difficult. One major issue is defining appropriate criteria to demonstrate bioequivalence; pharmacopoeial specifications alone appear to be inadequate. Whereas available generic versions of LMWHs exhibit similar molecular and pharmacopoeial profiles, marked differences in their biological and pharmacologic behavior have been noted. Preliminary studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release after subcutaneous administration, as well as antiplatelet and profibrinolytic effects. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs with complex structures and activities and also underscore the importance of further pharmacologic studies involving animal models and human clinical trials. The U.S. Food and Drug Administration and the European Medicine Evaluation Agency are currently developing guidelines for the acceptance of biosimilar agents including LMWHs. Until such guidelines are complete, generic interchange may not be feasible.

2017 White Paper on recent issues in bioanalysis: aren't BMV guidance/guidelines 'Scientific'? (Part 1 - LCMS: small molecules, peptides and small molecule biomarkers).

PubMed

Welink, Jan; Yang, Eric; Hughes, Nicola; Rago, Brian; Woolf, Eric; Sydor, Jens; Coppola, Laura; Ackermann, Brad; Li, Wenkui; Alley, Stephen C; Arnold, Mark; Berger, Isabella; Briscoe, Chad; Buonarati, Michael; Bustard, Mark; Cancilla, Mark; Cho, Seongeun Julia; Duggan, Jeff; Fraier, Daniela; Garofolo, Fabio; Green, Rachel; Haidar, Sam; Hittle, Lucinda; Ishii-Watabe, Akiko; Islam, Rafiq; Jenkins, Rand; Jones, Barry; Kadavil, John; Kassim, Sean; Kavetska, Olga; Blaye, Olivier Le; Lee, Anita; Liu, Hanlan; Mehl, John; Lima Santos, Gustavo Mendes; Musuku, Adrien; Ramanathan, Ragu; Saito, Yoshiro; Savoie, Natasha; Summerfield, Scott; Surapaneni, Sekhar; Szapacs, Matthew; Tampal, Nilufer; Verhaeghe, Tom; Vinter, Stephen; Whale, Emma

2017-11-01

The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California from 3 April 2017 to 7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis, Biomarkers and Immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid LBA/LCMS and ligand-binding assay (LBA) approaches. This 2017 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for Small Molecules, Peptides and Small Molecule Biomarkers using LCMS. Part 2 (Biotherapeutics, Biomarkers and Immunogenicity Assays using Hybrid LBA/LCMS and Regulatory Agencies' Inputs) and Part 3 (LBA: Immunogenicity, Biomarkers and PK Assays) are published in volume 9 of Bioanalysis, issues 23 and 24 (2017), respectively.

2017 White Paper on recent issues in bioanalysis: a global perspective on immunogenicity guidelines & biomarker assay performance (Part 3 - LBA: immunogenicity, biomarkers and PK assays).

PubMed

Gupta, Shalini; Richards, Susan; Amaravadi, Lakshmi; Piccoli, Steven; Desilva, Binodh; Pillutla, Renuka; Stevenson, Lauren; Mehta, Devangi; Carrasco-Triguero, Montserrat; Neely, Robert; Partridge, Michael; Staack, Roland F; Zhao, Xuemei; Gorovits, Boris; Kolaitis, Gerry; Sumner, Giane; Stubenrauch, Kay-Gunnar; Zou, Linglong; Amur, Shashi; Beaver, Chris; Berger, Isabella; Berisha, Flora; Birnboeck, Herbert; Bower, Joe; Cho, Seongeun Julia; Cludts, Isabelle; Cocea, Laurent; Donato, Lorella Di; Fischer, Saloumeh; Fraser, Stephanie; Garofolo, Fabio; Haidar, Sam; Haulenbeek, Jonathan; Hottenstein, Charles; Hu, Jenny; Ishii-Watabe, Akiko; Islam, Rafiq; Jani, Darshana; Kadavil, John; Kamerud, John; Kramer, Daniel; Kurki, Pekka; MacMannis, Stephen; McNally, Jim; Mullan, Ashley; Papadimitriou, Apollon; Pedras-Vasconcelos, João; Ray, Soma; Safavi, Afshin; Saito, Yoshiro; Savoie, Natasha; Fjording, Marianne Scheel; Scheibner, Kara; Smeraglia, John; Song, An; Stouffer, Bruce; Tampal, Nilufer; der Strate, Barry van; Verch, Thorsten; Welink, Jan; Xu, Yuanxin; Yang, Tong-Yuan; Yengi, Lilian; Zeng, Jianing; Zhang, Yan; Zhang, Yanhua; Zoog, Stephen

2017-12-01

The 2017 11th Workshop on Recent Issues in Bioanalysis took place in Los Angeles/Universal City, California, on 3-7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule analysis involving LC-MS, hybrid ligand-binding assay (LBA)/LC-MS and LBA approaches. This 2017 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations for large-molecule bioanalysis, biomarkers and immunogenicity using LBA. Part 1 (LC-MS for small molecules, peptides and small molecule biomarkers) and Part 2 (hybrid LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) are published in volume 9 of Bioanalysis, issues 22 and 23 (2017), respectively.

Strategies to translate knowledge related to common musculoskeletal conditions into physiotherapy practice: a systematic review.

PubMed

Bérubé, Marie-Ève; Poitras, Stéphane; Bastien, Marc; Laliberté, Lydie-Anne; Lacharité, Anyck; Gross, Douglas P

2018-03-01

Many physiotherapists underuse evidence-based practice guidelines or recommendations when treating patients with musculoskeletal disorders, yet synthesis of knowledge translation interventions used within the field of physiotherapy fails to offer clear conclusions to guide the implementation of clinical practice guidelines. To evaluate the effectiveness of various knowledge translation interventions used to implement changes in the practice of current physiotherapists treating common musculoskeletal issues. A computerized literature search of MEDLINE, CINHAL and ProQuest of systematic reviews (from inception until May 2016) and primary research studies (from January 2010 until June 2016). Eligibility criteria specified articles evaluating interventions for translating knowledge into physiotherapy practice. Two reviewers independently screened the titles and abstracts, reviewed full-text articles, performed data extraction, and performed quality assessment. Of a total of 13014 articles located and titles and abstracts screened, 34 studies met the inclusion criteria, including three overlapping publications, resulting in 31 individual studies. Knowledge translation interventions appear to have resulted in a positive change in physiotherapist beliefs, attitudes, skills and guideline awareness. However, no consistent improvement in clinical practice, patient and economic outcomes were observed. The studies included had small sample sizes and low methodological quality. The heterogeneity of the studies was not conducive to pooling the data. The intensity and type of knowledge translation intervention seem to have an effect on practice change. More research targeting financial, organizational and regulatory knowledge translation interventions is needed. Copyright © 2017 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Smartphone Applications for the Clinical Oncologist in UK Practice.

PubMed

Rozati, Hamoun; Shah, Sonya Pratik; Shah, Neha

2015-06-01

A number of medical smartphone applications have been developed to assist clinical oncology specialists. Concerns have arisen that the information provided may not be under sufficient scrutiny. This study aims to analyse the current applications available for clinical oncologists in the UK. Applications aimed specifically at physician clinical oncologists were searched for on the major smartphone operating systems: Apple iOS; Google Android; Microsoft Windows OS; and Blackberry OS. All applications were installed and analysed. The applications were scrutinised to assess the following information: cost; whether the information included was referenced; when the information was last updated; and whether they made any reference to UK guidelines. A novel rating score based on these criteria was applied to each application. Fifty applications were identified: 24 for Apple's iOS; 23 for Google's Android; 2 for Blackberry OS; and 1 for Windows OS. The categories of applications available were: drug reference; journal reference; learning; clinical calculators; decision support; guidelines; and dictionaries. Journal reference and guideline applications scored highly on our rating system. Drug reference application costs were prohibitive. Learning tools were poorly referenced and not up-to-date. Smartphones provide easy access to information. There are numerous applications devoted to oncology physicians, many of which are free and contain referenced, up-to-date data. The cost and quality of drug reference and learning applications have significant scope for improvement. A regulatory body is needed to ensure the presence of peer-reviewed, validated applications to ensure their reliability.

Evolutionary toxicology: Meta-analysis of evolutionary events in response to chemical stressors.

PubMed

M Oziolor, Elias; De Schamphelaere, Karel; Matson, Cole W

2016-12-01

The regulatory decision-making process regarding chemical safety is most often informed by evidence based on ecotoxicity tests that consider growth, reproduction and survival as end-points, which can be quantitatively linked to short-term population outcomes. Changes in these end-points resulting from chemical exposure can cause alterations in micro-evolutionary forces (mutation, drift, selection and gene flow) that control the genetic composition of populations. With multi-generation exposures, anthropogenic contamination can lead to a population with an altered genetic composition, which may respond differently to future stressors. These evolutionary changes are rarely discussed in regulatory or risk assessment frameworks, but the growing body of literature that documents their existence suggests that these important population-level impacts should be considered. In this meta-analysis we have compared existing contamination levels of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) that have been documented to be associated with evolutionary changes in resident aquatic organisms to regulatory benchmarks for these contaminants. The original intent of this project was to perform a meta-analysis on evolutionary events associated with PCB and PAH contamination. However, this effort was hindered by a lack of consistency in congener selection for "total" PCB or PAH measurements. We expanded this manuscript to include a discussion of methods used to determine PCB and PAH total contamination in addition to comparing regulatory guidelines and contamination that has caused evolutionary effects. Micro-evolutionary responses often lead populations onto unique and unpredictable trajectories. Therefore, to better understand the risk of population-wide alterations occurring, we need to improve comparisons of chemical contamination between affected locations. In this manuscript we offer several possibilities to unify chemical comparisons for PCBs and PAHs that would improve comparability among evolutionary toxicology investigations, and with regulatory guidelines. In addition, we identify studies documenting evolutionary change in the presence of PCB and PAH contamination levels below applicable regulatory benchmarks.

Fair Balance and Adequate Provision in Direct-to-Consumer Prescription Drug Online Banner Advertisements: A Content Analysis

PubMed Central

2016-01-01

Background The current direct-to-consumer advertising (DTCA) guidelines were developed with print, television, and radio media in mind, and there are no specific guidelines for online banner advertisements. Objective This study evaluates how well Internet banner ads comply with existing Food and Drug Administration (FDA) guidelines for DTCA in other media. Methods A content analysis was performed of 68 banner advertisements. A coding sheet was developed based on (1) FDA guidance documents for consumer-directed prescription drug advertisements and (2) previous DTCA content analyses. Specifically, the presence of a brief summary detailing the drug’s risks and side effects or of a “major statement” identifying the drug’s major risks, and the number and type of provisions made available to consumers for comprehensive information about the drug were coded. In addition, the criterion of “fair balance,” the FDA’s requirement that prescription drug ads balance information relating to the drug’s risks with information relating to its benefits, was measured by numbering the benefit and risk facts identified in the ads and by examining the presentation of risk and benefit information. Results Every ad in the sample included a brief summary of risk information and at least one form of adequate provision as required by the FDA for broadcast ads that do not give audiences a brief summary of a drug’s risks. No ads included a major statement. There were approximately 7.18 risk facts for every benefit fact. Most of the risks (98.85%, 1292/1307) were presented in the scroll portion of the ad, whereas most of the benefits (66.5%, 121/182) were presented in the main part of the ad. Out of 1307 risk facts, 1292 were qualitative and 15 were quantitative. Out of 182 benefit facts, 181 were qualitative and 1 was quantitative. The majority of ads showed neutral images during the disclosure of benefit and risk facts. Only 9% (6/68) of the ads displayed positive images and none displayed negative images when presenting risks facts. When benefit facts were being presented, 7% (5/68) showed only positive images. No ads showed negative images when the benefit facts were being presented. Conclusions In the face of ambiguous regulatory guidelines for online banner promotion, drug companies appear to make an attempt to adapt to regulatory guidelines designed for traditional media. However, banner ads use various techniques of presentation to present the advertised drug in the best possible light. The FDA should formalize requirements that drug companies provide a brief summary and include multiple forms of adequate provision in banner ads. PMID:26892749

Assessment of Self-Regulatory Code Violations in Brazilian Television Beer Advertisements*

PubMed Central

Vendrame, Alan; Pinsky, Ilana; Souza E Silva, Rebeca; Babor, Thomas

2010-01-01

Objective: Research suggests that alcoholic beverage advertisements may have an adverse effect on teenagers and young adults, owing to their vulnerability to suggestive message content. This study was designed to evaluate perceived violations of the content guidelines of the Brazilian alcohol marketing self-regulation code, based on ratings of the five most popular beer advertisements broadcast on television in the summer of 2005–2006 and during the 2006 FIFA (Fédération Internationale de Football Association) World Cup games. Method: Five beer advertisements were selected from a previous study showing that they were perceived to be highly appealing to a sample of Brazilian teenagers. These advertisements were evaluated by a sample of Brazilian high school students using a rating procedure designed to measure the content of alcohol advertisements covered in industry self-regulation codes. Results: All five advertisements were found to violate multiple guidelines of the Brazilian code of marketing self-regulation. The advertisement with the greatest number of violations was Antarctica's “Male Repellent,” which was perceived to violate 11 of the 16 guidelines in the code. Two advertisements had nine violations, and one had eight. The guidelines most likely to be violated by these advertisements were Guideline 1, which is aimed at protecting children and teenagers, and Guideline 2, which prohibits content encouraging excessive and irresponsible alcoholic beverage consumption. Conclusions: The five beer advertisements rated as most appealing to Brazilian teenagers were perceived by a sample of the same population to have violated numerous principles of the Brazilian self-regulation code governing the marketing of alcoholic beverages. Because of these numerous perceived code violations, it now seems important for regulatory authorities to submit industry marketing content to more systematic evaluation by young people and public health experts and for researchers to focus more on the ways in which alcohol advertising influences early onset of drinking and excessive alcohol consumption. PMID:20409439

Assessment of self-regulatory code violations in Brazilian television beer advertisements.

PubMed

Vendrame, Alan; Pinsky, Ilana; e Silva, Rebeca Souza; Babor, Thomas

2010-05-01

Research suggests that alcoholic beverage advertisements may have an adverse effect on teenagers and young adults, owing to their vulnerability to suggestive message content. This study was designed to evaluate perceived violations of the content guidelines of the Brazilian alcohol marketing self-regulation code, based on ratings of the five most popular beer advertisements broadcast on television in the summer of 2005-2006 and during the 2006 FIFA (Federation Internationale de Football Association) World Cup games. Five beer advertisements were selected from a previous study showing that they were perceived to be highly appealing to a sample of Brazilian teenagers. These advertisements were evaluated by a sample of Brazilian high school students using a rating procedure designed to measure the content of alcohol advertisements covered in industry self-regulation codes. All five advertisements were found to violate multiple guidelines of the Brazilian code of marketing self-regulation. The advertisement with the greatest number of violations was Antarctica's "Male Repellent," which was perceived to violate 11 of the 16 guidelines in the code. Two advertisements had nine violations, and one had eight. The guidelines most likely to be violated by these advertisements were Guideline 1, which is aimed at protecting children and teenagers, and Guideline 2, which prohibits content encouraging excessive and irresponsible alcoholic beverage consumption. The five beer advertisements rated as most appealing to Brazilian teenagers were perceived by a sample of the same population to have violated numerous principles of the Brazilian self-regulation code governing the marketing of alcoholic beverages. Because of these numerous perceived code violations, it now seems important for regulatory authorities to submit industry marketing content to more systematic evaluation by young people and public health experts and for researchers to focus more on the ways in which alcohol advertising influences early onset of drinking and excessive alcohol consumption.

76 FR 37290 - Children's Online Privacy Protection Rule; Aristotle International, Inc.'s Application for Safe...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-27

...The Federal Trade Commission publishes a notice and request for public comment concerning proposed self-regulatory guidelines submitted by Aristotle International, Inc. (Aristotle) under the safe harbor provision of the Children's Online Privacy Protection Rule.

76 FR 16549 - ESBWR Design Certification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

... 73350; December 2, 2008). III. Regulatory and Policy Issues Human Factors Operational Programs The NRC... proposes to exclude the two Human Factors Engineering (HFE) operational program elements in Chapter 18 of... addresses existing NRC guidelines in NUREG- 0711, Revision 2, ``Human Factors Engineering Program Review...

An assessment of options for integrating taxicabs into an urban environment

DOT National Transportation Integrated Search

2001-03-01

Discussions surrounding the inclusion of taxicabs into the planning processes in urban areas have been ongoing since the oil crises of the 1970s. While there are some commonalties in the regulatory guidelines concerning taxicabs, most of the regulati...

Distinguishing allergens from non-allergenic homologues using Physical–Chemical Property (PCP) motifs

USDA-ARS?s Scientific Manuscript database

Motivation: Quantitative guidelines to distinguish allergenic proteins from related, but non-allergenic ones are urgently needed for regulatory agencies, biotech companies and physicians. Cataloguing the SDAP database has indicated that allergenic proteins populate a relatively small number of prote...

Regulatory guidelines for biosimilars in Malaysia.

PubMed

Abas, Arpah

2011-09-01

The biosimilars sector continues to attract huge interest and controversy. Biosimilars are new biopharmaceuticals that are "similar" but not identical to the innovator product. Characteristics of biopharmaceuticals are closely related to the manufacturing process, which implies that the products cannot be exactly duplicated. Minuscule differences in the product's structure and manufacturing process can result in different clinical outcome. This raises concerns over the safety, efficacy and even pharmacovigilance of biosimilars. Thus, biosimilars are unique - they are not a true chemical generic and are regulated via a distinct regulatory framework. This report discusses the features of Malaysian regulatory oversight of biosimilars and experience acquired in the evaluation of some products from various countries. Ensuring regulatory position adequately reflects scientific advancement, expertise/resources is key. The regulatory situation is an evolving process. Various guidance documents are being prepared with the aim of developing a uniform global framework towards assuring the dual goal of lower costs and patient safety while expediting the availability of important biosimilar products. Copyright © 2011. Published by Elsevier Ltd.

Thermal overload protection for electric motors on safety-related motor-operated valves: Generic Issue II. E. 6. 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothberg, O.

1988-06-01

NRC regulatory positions, as stated in Regulatory Guide 1.106, Revision 1, have been identified by the Office for Analysis and Evaluation of Operational Data (AEOD) as potential contributors to valve motor burnout. AEOD is particularly concerned about the allowed policy of bypassing thermal overload devices during normal or accident conditions. Regulatory Guide 1.106 favors compromising the function of thermal overload devices in favor of completing the safety-related action of valves. The purpose of this study was to determine if the guidance contained in Regulatory Guide 1.106 is appropriate and, if not, to recommend the necessary changes. This report describes thermalmore » overload devices commonly used to protect safety-related valve operator motors. The regulatory guidelines stated in Regulatory Guide 1.106 along with the limitations of thermal overload protection are discussed. Supplements and alternatives to thermal overload protection are also described. Findings and conclusions of several AEOD reports are discussed. Information obtained from the standard review plan, standard technical specifications, technical specifications from representative plants, and several papers are cited.« less

Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

PubMed

Bansal, Gulshan; Suthar, Nancy; Kaur, Jasmeen; Jain, Astha

2016-07-01

Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (-80 to 100 °C), humidity (0-100%) and duration (a few hours-36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Health care providers and direct-to-consumer access and advertising of genetic testing in the United States

PubMed Central

2011-01-01

Marketing pressures, regulatory policies, clinical guidelines, and consumer demand all affect health care providers' knowledge and use of health-related genetic tests that are sold and/or advertised to consumers. In addition, clinical guidelines, regulatory policies, and educational efforts are needed to promote the informed use of genetic tests that are sold and advertised to consumers and health care providers. A shift in culture regarding the regulation of genetic tests that are sold directly to consumers is suggested: by recent actions taken by the US Food and Drug Administration (FDA), including letters sent to direct-to-consumer (DTC) genetic testing companies stating that their tests meet the definition of medical devices; by public meetings held by the FDA to discuss laboratory developed tests; and by the convening of the Molecular and Clinical Genetics Panel to gather input on scientific issues concerning DTC genetic tests that make medical claims. This review provides a brief overview of DTC advertising and the regulation of pharmaceuticals and genetic tests in the United States. It highlights recent changes in the regulatory culture regarding genetic tests that are sold to consumers, and discusses the impact on health care providers of selling and advertising genetic tests directly to consumers. PMID:22204616

Health care providers and direct-to-consumer access and advertising of genetic testing in the United States.

PubMed

Myers, Melanie F

2011-12-28

Marketing pressures, regulatory policies, clinical guidelines, and consumer demand all affect health care providers' knowledge and use of health-related genetic tests that are sold and/or advertised to consumers. In addition, clinical guidelines, regulatory policies, and educational efforts are needed to promote the informed use of genetic tests that are sold and advertised to consumers and health care providers. A shift in culture regarding the regulation of genetic tests that are sold directly to consumers is suggested: by recent actions taken by the US Food and Drug Administration (FDA), including letters sent to direct-to-consumer (DTC) genetic testing companies stating that their tests meet the definition of medical devices; by public meetings held by the FDA to discuss laboratory developed tests; and by the convening of the Molecular and Clinical Genetics Panel to gather input on scientific issues concerning DTC genetic tests that make medical claims. This review provides a brief overview of DTC advertising and the regulation of pharmaceuticals and genetic tests in the United States. It highlights recent changes in the regulatory culture regarding genetic tests that are sold to consumers, and discusses the impact on health care providers of selling and advertising genetic tests directly to consumers.

“A question of balance”: addressing the public health impacts of multinational enterprises in the OECD Guidelines for Multinational Enterprises

PubMed Central

Yang, Joshua S.; McDaniel, Patricia A.; Malone, Ruth E.

2012-01-01

Background The global community is beginning to address non-communicable diseases, but how to increase the accountability of multinational enterprises (MNEs) for the health impacts of their products and practices remains unclear. We examine the Organization for Economic Cooperation and Development’s (OECD) efforts to do so through voluntary MNE guidelines. Methods We developed a historical case study of how the OECD Guidelines for Multinational Enterprises were developed and revised from 1973–2000 through an analysis of publicly available archived OECD and tobacco industry documents. Results The first edition of the Guidelines was a purely economic instrument. Outside pressures and a desire to ward off more stringent regulatory efforts resulted in the addition over time of guidelines related to the environment, consumer interests, sustainable development, and human rights. Conclusion Despite their voluntary nature, the Guidelines can play a role in efforts to help balance the interests of MNEs and public health by providing a starting point for efforts to create binding provisions addressing MNEs’ contributions to disease burden or disease reduction. PMID:23046298

Concept of biosimilar products in Jordan.

PubMed

Haddadin, Rania Dakhlallah

2011-09-01

After the expiration of patents on originator biological products, Jordanian local manufacturers and the agents of international pharmaceutical companies in Jordan started to submit registration dossiers for biosimilar products. The Jordan Food and Drug Administration (JFDA) is the national regulatory authority responsible for the registration of biosimilar products. Biosimilars are registered under the same regulations used for drugs until specific guidelines for registration of biological and biosimilar products are released. Those regulations are called Criteria of Registration of Drugs, Vaccines, Sera and Biological Products, the Renewal of its Registration and the Cancellation of Any of them which was published in the official gazette in 2004 under the Provisional Law Number 80 of the year 2001, Drug and Pharmacy Law and its amendments of the year 2003. Also, the JFDA follows the EMA guidelines on similar biological medicinal products for specific active biological substances for non-clinical and clinical studies requirements and the EMA guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues. A post marketing surveillance study is requested after a biosimilar product is authorized. The JFDA keeps pace with all advances in the regulatory issues related to biosimilars in order to be capable of authorizing biosimilar products with a safe, effective and good quality profile. Copyright © 2011. Published by Elsevier Ltd.

Nutritional Guidelines and Fermented Food Frameworks

PubMed Central

Bell, Victoria; Ferrão, Jorge; Fernandes, Tito

2017-01-01

This review examines different nutritional guidelines, some case studies, and provides insights and discrepancies, in the regulatory framework of Food Safety Management of some of the world’s economies. There are thousands of fermented foods and beverages, although the intention was not to review them but check their traditional and cultural value, and if they are still lacking to be classed as a category on different national food guides. For understanding the inconsistencies in claims of concerning fermented foods among various regulatory systems, each legal system should be considered unique. Fermented foods and beverages have long been a part of the human diet, and with further supplementation of probiotic microbes, in some cases, they offer nutritional and health attributes worthy of recommendation of regular consumption. Despite the impact of fermented foods and beverages on gastro-intestinal wellbeing and diseases, their many health benefits or recommended consumption has not been widely translated to global inclusion in world food guidelines. In general, the approach of the legal systems is broadly consistent and their structures may be presented under different formats. African traditional fermented products are briefly mentioned enhancing some recorded adverse effects. Knowing the general benefits of traditional and supplemented fermented foods, they should be a daily item on most national food guides. PMID:28783111

Awareness of radiographic guidelines for low back pain: a survey of Australian chiropractors.

PubMed

Jenkins, Hazel J

2016-01-01

Chiropractors have been shown to refer for lumbar radiography in clinical scenarios inconsistent with the current clinical guidelines for low back pain. It is unknown whether this is due to lack of adherence with known guidelines or a lack of awareness of relevant guidelines. Therefore, the aim of this study is to determine Australian chiropractors' awareness of, and reported adherence to, radiographic guidelines for low back pain. Demographic, chiropractic practice and radiographic usage characteristics will be investigated for association with poor guideline adherence. An online survey was distributed to Australian chiropractors from July to September, 2014. Survey questions assessed demographic, chiropractic practice and radiographic usage characteristics, awareness of radiographic guidelines for low back pain and the level of agreement with current guidelines. Results were analysed with descriptive statistics and logistic regression analysis. There were 480 surveys completed online. Only 49.6 % (95 % confidence interval (95 % CI): 44.9, 54.4) reported awareness of radiographic guidelines for low back pain. Chiropractors reported a likelihood of referring for radiographs for low back pain: in new patients (47.6 % (95 % CI: 42.9, 52.3)); to confirm biomechanical pathologies (69.0 % (95 % CI: 64.5, 73.1)); to perform biomechanical analysis (37.5 % (95 % CI: 33.1, 42.0)); or to screen for contraindications (39.4 % (95 % CI: 35.0, 44.0)). Chiropractors agreed that radiographs for low back pain could be useful for: acute low back pain (54.0 % (95 % CI: 49.2, 58.7)); screening for contraindications (55.8 % (95 % CI: 51.0, 60.5)); or to confirm diagnosis and direct treatment (61.3 % (95 % CI: 56.5, 65.9)). Poorer adherence to current guidelines was seen if the chiropractor referred to in-house radiographic facilities, practiced a technique other than diversified technique or was unaware or unsure of current radiographic guidelines for low back pain. Only 50 % of Australian chiropractors report awareness of current radiographic guidelines for low back pain. A poorer awareness of guidelines is associated with an increase in the reported likelihood of use, and the perceived usefulness of radiographs for low back pain, in clinical situations that fall outside of current guidelines. Therefore, education strategies may help to increase guideline knowledge and compliance.

Implementation of the SSHAC Guidelines for Level 3 and 4 PSHAs - Experience Gained from Actual Applications

USGS Publications Warehouse

Hanks, Thomas C.; Abrahamson, Norm A.; Boore, David M.; Coppersmith, Kevin J.; Knepprath, Nichole E.

2009-01-01

In April 1997, after four years of deliberations, the Senior Seismic Hazard Analysis Committee released its report 'Recommendations for Probabilistic Seismic Hazard Analysis: Guidance on Uncertainty and Use of Experts' through the U.S. Nuclear Regulatory Commission as NUREG/CR-6372, hereafter SSHAC (1997). Known informally ever since as the 'SSHAC Guidelines', SSHAC (1997) addresses why and how multiple expert opinions - and the intrinsic uncertainties that attend them - should be used in Probabilistic Seismic Hazard Analyses (PSHA) for critical facilities such as commercial nuclear power plants. Ten years later, in September 2007, the U.S. Geological Survey (USGS) entered into a 13-month agreement with the U.S. Nuclear Regulatory Commission (NRC) titled 'Practical Procedures for Implementation of the SSHAC Guidelines and for Updating PSHAs'. The NRC was interested in understanding and documenting lessons learned from recent PSHAs conducted at the higher SSHAC Levels (3 and 4) and in gaining input from the seismic community for updating PSHAs as new information became available. This study increased in importance in anticipation of new applications for nuclear power facilities at both existing and new sites. The intent of this project was not to replace the SSHAC Guidelines but to supplement them with the experience gained from putting the SSHAC Guidelines to work in practical applications. During the course of this project, we also learned that updating PSHAs for existing nuclear power facilities involves very different issues from the implementation of the SSHAC Guidelines for new facilities. As such, we report our findings and recommendations from this study in two separate documents, this being the first. The SSHAC Guidelines were written without regard to whether the PSHAs to which they would be applied were site-specific or regional in scope. Most of the experience gained to date from high-level SSHAC studies has been for site-specific cases, although three ongoing (as of this writing) studies are regional in scope. Updating existing PSHAs will depend more critically on the differences between site-specific and regional studies, and we will also address these differences in more detail in the companion report. Most of what we report here and in the second report on updating PSHAs emanates from three workshops held by the USGS at their Menlo Park facility: 'Lessons Learned from SSHAC Level 3 and 4 PSHAs' on January 30-31, 2008; 'Updates to Existing PSHAs' on May 6-7, 2008; and 'Draft Recommendations, SSHAC Implementation Guidance' on June 4-5, 2009. These workshops were attended by approximately 40 scientists and engineers familiar with hazard studies for nuclear facilities. This company included four of the authors of SSHAC (1997) and four other experts whose contributions to this document are mentioned in the Acknowledgments section; numerous scientists and engineers who in one role or another have participated in one or more high-level SSHAC PSHAs summarized later in this report; and representatives of the nuclear industry, the consulting world, the regulatory community, and academia with a keen interest and expertise in hazard analysis. This report is a community-based set of recommendations to NRC for improved practical procedures for implementation of the SSHAC Guidelines. In an early publication specifically addressing the SSHAC Guidelines, Hanks (1997) noted that the SSHAC Guidelines were likely to evolve for some time to come, and this remains true today. While the broad philosophical and theoretical dimensions of the SSHAC Guidelines will not change, much has been learned during the past decade from various applications of the SSHAC Guidelines to real PSHAs in terms of how they are implemented. We anticipate that, in their practical applications, the SSHAC Guidelines will continue to evolve as more experience is gained from future SSHAC applications. Indeed, to the extent that every PSHA has its

Guideline.gov: A Database of Clinical Specialty Guidelines.

PubMed

El-Khayat, Yamila M; Forbes, Carrie S; Coghill, Jeffrey G

2017-01-01

The National Guidelines Clearinghouse (NGC), also known as Guideline.gov, is a database of resources to assist health care providers with a central depository of guidelines for clinical specialty areas in medicine. The database is provided free of charge and is sponsored by the U.S. Department of Health and Human Services and the Agency for Healthcare Research and Quality. The guidelines for treatment are updated regularly, with new guidelines replacing older guidelines every five years. There are hundreds of current guidelines with more added each week. The purpose and goal of NGC is to provide physicians, nurses, and other health care providers, insurance companies, and others in the field of health care with a unified database of the most current, detailed, relevant, and objective clinical practice guidelines.

Regional forestry practices and forest management certification

Treesearch

Steverson O. Moffat; Frederick W. Cubbage; Matthew H. Pelkki

2001-01-01

Under a "mandated" management scenario, landowners in states with comprehensive forest practices laws meet more sustainable forestry standards and certification programs' guidelines than do owners in states with other regulatory approaches. This confers certification advantages to landowners in the Pacific Northwest where comprehensive forest laws...

75 FR 79799 - Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... the Americans With Disabilities Act of 1990 (ADA). Those regulations include the ADA Standards for... are consistent with the ADA Accessibility Guidelines (ADAAG) published by the U.S. Architectural and... ADA Standards, the Department is reviewing its title III regulations and expects to propose, in one or...

75 FR 21819 - Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... of the Americans With Disabilities Act of 1990 (ADA). Those regulations include the ADA Standards for... are consistent with the ADA Accessibility Guidelines (ADAAG) published by the U.S. Architectural and... ADA Standards, the Department is reviewing its title III regulations and expects to propose, in one or...

78 FR 64467 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... and Nutrition Service (FNS) annually for approval a Budget Projection Statement (FNS-366A), which... Officer for Agriculture, Office of Information and Regulatory Affairs, Office of Management and Budget... number. Food and Nutrition Service Title: Operating Guidelines, Forms and Waivers. OMB Control Number...

76 FR 1889 - Risk-Based Capital Guidelines: Market Risk

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

... regulatory measurement methodologies; and increase transparency through enhanced disclosures. The proposal... banks \\1\\ entitled International Convergence of Capital Measurement and Capital Standards (1988 Capital... the internal models approach (see http://www.bis.org/press/p970918a.htm ). \\5\\ 61 FR 47358 (September...

Internationalization of regulatory requirements.

PubMed

Juillet, Y

2003-02-01

The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

Aspartame, a bittersweet pill.

PubMed

Paolini, Moreno; Vivarelli, Fabio; Sapone, Andrea; Canistro, Donatella

2017-12-07

For the first time, the aspartame case shows how a corporation decided to ban an artificial ingredient in the wake of public opinion notwithstanding the regulatory assurance claims that it is safe. PepsiCo Inc. made an unprecedented decision most likely based on life-span carcinogenicity bioassay studies from the Cesare Maltoni Cancer Research Center of the Ramazzini Institute (CMCRC/RI), which provide consistent evidence of aspartame's carcinogenicity in rodents. Although CMCRC/RI experiments have been criticized for not complying with Organisation for Economic Co-operation and Development (OECD) guidelines, the newly launched aspartame-free soft drink may not be an isolated case. In the light of vinyl chloride-, formaldehyde- or benzene-associated carcinogenicity discovered for the first time by CMCRC/RI in the same way, it seems the guidelines need to be re-evaluated to avoid the credibility of international regulatory agencies being compromised by consumer opinion. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Regulatory requirements for genotoxicity assessment of plant protection product active ingredients, impurities, and metabolites.

PubMed

Booth, Ewan D; Rawlinson, Paul J; Maria Fagundes, Priscila; Leiner, Kevin A

2017-06-01

Active ingredients in plant protection products are subject to rigorous safety assessment during their development, including assessment of genotoxicity. Plant protection products are used for agriculture in multiple regions and for the registration of active ingredients it is necessary to satisfy the data requirements of these different regions. There are no overarching global agreements on which genotoxicity studies need to be conducted to satisfy the majority of regulatory authorities. The implementation of new OECD guidelines for the in vitro micronucleus, transgenic rodent somatic and germ cell gene mutation and in vivo comet assays, as well as the revision of a number of other OECD test guidelines has resulted in some changes to data requirements. This review describes the genotoxicity data requirements for chemical active ingredients as well as biologicals, microbials, ground water metabolites, metabolites, and impurities in a number of regions. Similarities and differences are highlighted. Environ. Mol. Mutagen. 58:325-344, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Implantation of an ergonomics administration system in a company: report of an occupational therapist specialist in ergonomics.

PubMed

Moraes, Berla; Andrade, Valéria Sousa

2012-01-01

This article aims to describe step-by-step the implementation of an ergonomics administration system in a company from March 2009 till March 2011 by an occupational therapist specialist in ergonomics based on the OSHAS 18001 guidelines and the Regulatory Norms 17 manual. The process began with the definition of five requisites with bases on the manual of application of the Regulatory Norms 17: survey; materials individual transportation and discharge; workplace furniture; workplace equipments; work environment and organization of the work to be managed with bases on the OSHAS 18001 guidelines. The following steps were established: sensitization of the company high administration, elaboration and institution of an ergonomics politics, development of ergonomics committees, ergonomics analysis of the work with recommendation of ergonomic improvements, implantation of improvements and evaluation or the results. This research experiment suggests the importance not only of a guiding axle but also of a professional qualification and participation of the company on the implementation of an ergonomics management system.

Current Status of Regulatory Science Education in Faculties of Pharmaceutical Science in Japan.

PubMed

Tohkin, Masahiro

2017-01-01

I introduce the current pharmaceutical education system in Japan, focusing on regulatory science. University schools or faculties of pharmaceutical science in Japan offer two courses: a six-year course for pharmacists and a four-year course for scientists and technicians. Students in the six-year pharmaceutical course receive training in hospitals and pharmacies during their fifth year, and those in the four-year life science course start research activities during their third year. The current model core curriculum for pharmaceutical education requires them to "explain the necessity and significance of regulatory science" as a specific behavior object. This means that pharmacists should understand the significance of "regulatory science", which will lead to the proper use of pharmaceuticals in clinical practice. Most regulatory science laboratories are in the university schools or faculties of pharmaceutical sciences; however, there are too few to conduct regulatory science education. There are many problems in regulatory science education, and I hope that those problems will be resolved not only by university-based regulatory science researchers but also by those from the pharmaceutical industry and regulatory authorities.

Cytotoxic Drug Dispersal, Cytotoxic Safety, and Cytotoxic Waste Management: Practices and Proposed India-specific Guidelines

PubMed Central

Capoor, Malini R; Bhowmik, Kumar Tapas

2017-01-01

This article deals with practices related to cytotoxic drug dispersal, cytotoxic safety, and cytotoxic waste management and attempts at India-specific guidelines for their dispersal and disposal. The articles related to cytotoxic drug dispersal, cytotoxic safety, and cytotoxic waste management were reviewed from PubMed and their applicability in Indian health-care facilities (HCFs) was also reviewed. All HCFs dealing with cytotoxic drugs should consider cytotoxic policy, patient safety and health-care worker safety, and environmental monitoring program as per the available international guidelines customized as per Indian conditions. Utmost care in handling cytotoxic waste is quintessential. The formation of India-specific cytotoxic guidelines requires the inputs from all stakeholders. Cytotoxic waste, cytotoxic safety, and cytotoxic waste management should be the subject of a national strategy with an infrastructure, cradle-to-grave legislation, competent regulatory authority, and trained personnel. PMID:28900329

Performance and data interpretation of the in vivo comet assay in pharmaceutical industry: EFPIA survey results.

PubMed

van der Leede, Bas-Jan; Doherty, Ann; Guérard, Melanie; Howe, Jonathan; O'Donovan, Mike; Plappert-Helbig, Ulla; Thybaud, Véronique

2014-12-01

In genotoxicity testing of pharmaceuticals the rodent alkaline comet assay is being increasingly used as a second in vivo assay in addition to the in vivo micronucleus assay to mitigate in vitro positive results as recommended by the ICH S2(R1) guideline. This paper summarizes a survey suggested by the Safety Working Party of European Medicines Agency (EMA), and conducted by the European Federation of Pharmaceutical Industries and Associations (EFPIA) to investigate the experience among European pharmaceutical companies by conducting the in vivo comet assay for regulatory purpose. A special focus was given on the typology of the obtained results and to identify potential difficulties encountered with the interpretation of study data. The participating companies reported a total of 147 studies (conducted in-house or outsourced) and shared the conclusion on the comet assay response for 136 studies. Most of the studies were negative (118/136). Only about 10% (14/136 studies) of the comet assays showed a positive response. None of the positive comet assay results were clearly associated with organ toxicity indicating that the positive responses are not due to cytotoxic effects of the compound in the tissue examined. The number of comet assays with an equivocal or inconclusive response was rare, respectively <1% (1/147 studies) and 2% (3/147 studies). In case additional information (e.g. repeat assay, organ toxicity, metabolism, tissue exposure) would have been available for evaluation, a final conclusion could most probably have been drawn for most or all of these studies. All (46) negative in vivo comet assays submitted alongside with a negative in vivo micronucleus assay were accepted by the regulatory authorities to mitigate a positive in vitro mammalian cell assay following the current ICH S2 guidance. The survey results demonstrate the robustness of the comet assay and the regulatory acceptance of the current ICH S2 guidance. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Antidepressants during pregnancy: Guideline adherence and current practice amongst Dutch gynaecologists and midwives.

PubMed

Molenaar, Nina M; Brouwer, Marlies E; Duvekot, Johannes J; Burger, Huibert; Knijff, Esther M; Hoogendijk, Witte J; Bockting, Claudi L H; de Wolf, G S; Lambregtse-van den Berg, Mijke P

2018-06-01

prescription rates of antidepressants during pregnancy range from 2-3% in The Netherlands to 6.2% in the USA. Inconclusive evidence about harms and benefits of antidepressants during pregnancy leads to variation in advice given by gynaecologists and midwives. The objective was to investigate familiarity with, and adherence to the Dutch multidisciplinary guideline on Selective Serotonin Reuptake Inhibitor (SSRI) use during pregnancy by gynaecologists and midwives in the Netherlands. an online survey was developed and send to Dutch gynaecologists and midwives. The survey consisted mainly of multiple-choice questions addressing guideline familiarity and current practice of the respondent. Also, caregiver characteristics associated with guideline adherence were investigated. a total of 178 gynaecologists and 139 midwives responded. Overall familiarity with the Dutch guideline was 92.7%. However, current practice and advice given to patients by caregivers differed substantially, both between gynaecologists and midwives as well as within both professions. Overall guideline adherence was 13.9%. Multivariable logistic regression showed that solely caregiver profession was associated with guideline adherence, with gynaecologists having a higher adherence rate (OR 2.10, 95%CI 1.02-4.33) than midwives. although reported familiarity with the guideline is high, adherence to the guideline is low, possibly resulting in advice to patients that is inconsistent with guidelines and unwanted variation in current practice. further implementation of the recommendations as given in the guideline should be stimulated. Additional research is needed to examine how gynaecologists and midwives can be facilitated to follow the recommendations of the clinical guideline on SSRI use during pregnancy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Online professional networks for physicians: risk management.

PubMed

Hyman, Jon L; Luks, Howard J; Sechrest, Randale

2012-05-01

The rapidly developing array of online physician-only communities represents a potential extraordinary advance in the availability of educational and informational resources to physicians. These online communities provide physicians with a new range of controls over the information they process, but use of this social media technology carries some risk. The purpose of this review was to help physicians manage the risks of online professional networking and discuss the potential benefits that may come with such networks. This article explores the risks and benefits of physicians engaging in online professional networking with peers and provides suggestions on risk management. Through an Internet search and literature review, we scrutinized available case law, federal regulatory code, and guidelines of conduct from professional organizations and consultants. We reviewed the OrthoMind.com site as a case example because it is currently the only online social network exclusively for orthopaedic surgeons. Existing case law suggests potential liability for orthopaedic surgeons who engage with patients on openly accessible social network platforms. Current society guidelines in both the United States and Britain provide sensible rules that may mitigate such risks. However, the overall lack of a strong body of legal opinions, government regulations as well as practical experience for most surgeons limit the suitability of such platforms. Closed platforms that are restricted to validated orthopaedic surgeons may limit these downside risks and hence allow surgeons to collaborate with one another both as clinicians and practice owners. Educating surgeons about the pros and cons of participating in these networking platforms is helping them more astutely manage risks and optimize benefits. This evolving online environment of professional interaction is one of few precedents, but the application of risk management strategies that physicians use in daily practice carries over into the online community. This participation should foster ongoing dialogue as new guidelines emerge. This will allow today's orthopaedic surgeon to feel more comfortable with online professional networks and better understand how to make an informed decision regarding their proper use.

Experiences with the in vivo and in vitro comet assay in regulatory testing.

PubMed

Frötschl, Roland

2015-01-01

The in vivo comet assay has recently been implemented into regulatory genotoxicity testing of pharmaceuticals with inclusion into the ICH S2R1 guidance. Regulatory genotoxicity testing aims to detect DNA alterations in form of gene mutations, larger scale chromosomal damage and recombination and aneuploidy. The ICH S2R1 guideline offers two options of standard batteries of tests for the detection of these endpoints. Both options start with an AMES assay and option 1 includes an in vitro mammalian cell assay and an in vivo micronucleus assay in rodent, whereas option 2 includes an in vivo micronucleus assay in bone marrow in rodent and a second in vivo assay in a second tissue with a second endpoint. The test recommended as second in vivo test is the comet assay in rat liver. The in vivo comet assay is considered as mature enough to ensure reliable detection of relevant in vivo genotoxicants in combination with the micronucleus test in bone marrow and the AMES assay. Although lots of research papers have been published using the in vitro comet assay, the in vitro version has not been implemented into official regulatory testing guidelines. A survey of the years 1999-2014 revealed 27 in vivo comet assays submitted to BfArM with market authorisation procedures, European and national advice procedures and clinical trial applications. In three procedures, in vitro comet assays had been submitted within the genetic toxicology packages. © The Author 2014. Published by Oxford University Press on behalf of the Mutagenesis Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Perspectives on Current Training Guidelines for Cardiac Imaging and Recommendations for the Future.

PubMed

Arrighi, James A; Kilic, Sena; Haines, Philip G

2018-04-23

To summarize current training guidelines for cardiac imaging and provide recommendations for future guidelines. The current structure of training in cardiac imaging is largely dictated by modality-specific guidelines. While there has been debate on how to define the advanced cardiac imager for over a decade, a uniform consensus has not emerged. We report the perspectives of three key stakeholders in this debate: a senior faculty member-former fellowship program director, a cardiology fellow, and an academic junior faculty imaging expert. The observations of these stakeholders suggest that there is no consensus on the definition of advanced cardiac imaging, leading to ambiguity in training guidelines. This may have negative impact on recruitment of fellows into cardiac imaging careers. Based on the current status of training in cardiac imaging, the authors suggest that the relevant professional groups reconvene to form a consensus in defining advanced cardiac imaging, in order to guide future revisions of training guidelines.

The OECD Fish Testing Framework Project

EPA Science Inventory

OECD Project 2.30 on a Fish Testing Framework was initiated in mid-2009, with the United States as the lead country. The objectives of the project are to review the regulatory needs and data requirements for fish testing and review the currency of existing OECD Test Guidelines. ...

77 FR 30030 - Monitoring the Effectiveness of Maintenance at Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0212] Monitoring the Effectiveness of Maintenance at... (RG) 1.160, ``Monitoring the Effectiveness of Maintenance at Nuclear Power Plants.'' This guide endorses Revision 4A to Nuclear Management and Resources Council (NUMARC) 93-01, ``Industry Guideline for...

77 FR 8002 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... Identifier No. 431 Americans With 3014-AA11 Disabilities Act (ADA) Accessibility Guidelines for... Actions Regulation Sequence No. Title Identifier No. 432 Americans With 3014-AA26 Disabilities Act (ADA... BARRIERS COMPLIANCE BOARD (ATBCB) Proposed Rule Stage 431. Americans With Disabilities Act (ADA...

Department of Justice Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... of the Americans With Disabilities Act of 1990 (ADA). Those regulations include the ADA Standards for... are consistent with the ADA Accessibility Guidelines (ADAAG) published by the U.S. Architectural and... ADA Standards, the Department is reviewing its title III regulations and expects to propose, in one or...

75 FR 73946 - Worker Safety and Health Program: Safety Conscious Work Environment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF ENERGY 10 CFR Part 851 Worker Safety and Health Program: Safety Conscious Work... Nuclear Regulatory Commission's ``Safety-Conscious Work Environment'' guidelines as a model. DOE published.... Second, not only would instituting a ``Safety-Conscious Work Environment'' by regulation be redundant...

40 CFR 256.22 - Recommendations for State regulatory powers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste... prohibit new open dumps and close or upgrade all existing open dumps. (a) Solid waste disposal standards... solid waste disposal facility. These procedures should include identification of future land use or the...

40 CFR 256.23 - Requirements for closing or upgrading open dumps.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid... classification of existing solid waste disposal facilities according to the criteria. This classification shall... solid waste disposal facility; (2) The availability of State regulatory and enforcement powers; and (3...

40 CFR 256.22 - Recommendations for State regulatory powers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste... prohibit new open dumps and close or upgrade all existing open dumps. (a) Solid waste disposal standards... solid waste disposal facility. These procedures should include identification of future land use or the...

40 CFR 256.21 - Requirements for State regulatory powers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste... be adequate to enforce solid waste disposal standards which are equivalent to or more stringent than the criteria for classification of solid waste disposal facilities (40 CFR part 257). Such authority...

40 CFR 256.21 - Requirements for State regulatory powers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste... be adequate to enforce solid waste disposal standards which are equivalent to or more stringent than the criteria for classification of solid waste disposal facilities (40 CFR part 257). Such authority...

40 CFR 256.23 - Requirements for closing or upgrading open dumps.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid... classification of existing solid waste disposal facilities according to the criteria. This classification shall... solid waste disposal facility; (2) The availability of State regulatory and enforcement powers; and (3...

Expansion: A Plan for Success.

ERIC Educational Resources Information Center

Callahan, A.P.

This report provides selling brokers' guidelines for the successful expansion of their operations outlining a basic method of preparing an expansion plan. Topic headings are: The Pitfalls of Expansion (The Language of Business, Timely Financial Reporting, Regulatory Agencies of Government, Preoccupation with the Facade of Business, A Business Is a…

Cable TV: The Re-regulation, Re-wiring, and Re-education of America.

ERIC Educational Resources Information Center

Nelson, Milo

1992-01-01

Discusses federal regulation of cable television. Topics addressed include Congressional legislation; Federal Communications Commission (FCC) guidelines; pricing; conflicts between broadcasters and the cable industry; the telephone industry's entrance into the cable market; and possible effects of regulatory changes on educational television. (LRW)

Summary of the British Transplantation Society Guidelines for Management of the Failing Kidney Transplant.

PubMed

Andrews, Peter A

2014-12-15

The British Transplantation Society "Guideline for Transplantation Management of the Failing Kidney Transplant" was published in May 2014. This is the first national guideline in this field. In line with previous guidelines published by the British Transplantation Society, the guideline has used the GRADE system to rate the strength of evidence and recommendations.This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for the management of the failing kidney graft in the United Kingdom and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at: http://www.bts.org.uk/MBR/Clinical/Guidelines/Current/Member/Clinical/Current_Guidelines.aspx.

Adherence to guidelines for cardiovascular screening in current high school preparticipation evaluation forms.

PubMed

Rausch, Christopher M; Phillips, George C

2009-10-01

We compared the content of the cardiac screening questions on US state high school athletic association preparticipation evaluation forms with current consensus recommendations. We reviewed the high school athletic association's approved, recommended, or required sports preparticipation form from each of the 50 US states and the District of Columbia, and compared the content of the personal and family history components with current recommendations for cardiac screening questions. We found that 85% of the preparticipation forms in current use contain all elements of the formerly recommended guidelines, but only 17% contain all elements of the new consensus guidelines. We conclude that although there appears to be some improvement in the content of the preparticipation forms in current use compared with previous studies, the vast majority of these forms are incomplete compared with current consensus guidelines.

Assessment of learning, memory and attention in developmental neurotoxicity regulatory studies: Introduction.

PubMed

Makris, Susan L; Vorhees, Charles V

2015-01-01

There are a variety of chemicals, including pharmaceuticals, that alter neurobehavior following developmental exposure and guidelines for the conduct of studies to detect such effects by statute in the United States and Europe. Guidelines for Developmental Neurotoxicity Testing (DNT) studies issued by the U.S. Environmental Protection Agency (EPA) under prevailing law and European Organization for Economic Cooperation and Development (OECD) recommendations to member countries provide that such studies include a series of neurobehavioral and neuropathological assessments. Among these are assessment of cognitive function, specifically learning and memory. After reviewing 69 DNT studies submitted to the EPA, tests of learning and memory were noted to have detected the lowest observed adverse effect level (LOAELs) less frequently than behavioral tests of locomotor activity and acoustic/auditory startle, but slightly more than for the developmental Functional Observational Battery (devFOB; which is less extensive than the full FOB), but the reasons for the lower LOAEL detection rate for learning and memory assessment could not be determined. A major concern identified in the review, however, was the adequacy of the methods employed in these studies rather than on the importance of learning and memory to the proper assessment of brain function. Accordingly, a symposium was conducted to consider how the guidelines for tests of learning and memory might be improved. Four laboratories with established histories investigating the effects of chemical exposures during development on learning, memory, and attention, were invited to review the topic and offer recommendations, both theoretical and practical, on approaches to improve the assessment of these vital CNS functions. Reviewers were asked to recommend methods that are grounded in functional importance to CNS integrity, well-validated, reliable, and amenable to the context of regulatory studies as well as to basic research on the underlying processes they measure. This Introduction sets the stage for the reviews by providing the background and regulatory context for improved tests for learning and memory in DNT and other regulatory studies, such as single- or multi-generational studies where similar methods are incorporated. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical decision guidelines for NHS cosmetic surgery: analysis of current limitations and recommendations for future development.

PubMed

Cook, S A; Rosser, R; Meah, S; James, M I; Salmon, P

2003-07-01

Because of increasing demand for publicly funded elective cosmetic surgery, clinical decision guidelines have been developed to select those patients who should receive it. The aims of this study were to identify: the main characteristics of such guidelines; whether and how they influence clinical decision making; and ways in which they should be improved. UK health authorities were asked for their current guidelines for elective cosmetic surgery and, in a single plastic surgery unit, we examined the impact of its guidelines by observing consultations and interviewing surgeons and managers. Of 115 authorities approached, 32 reported using guidelines and provided sufficient information for analysis. Guidelines mostly concerned arbitrary sets of cosmetic procedures and lacked reference to an evidence base. They allowed surgery for specified anatomical, functional or symptomatic reasons, but these indications varied between guidelines. Most guidelines also permitted surgery 'exceptionally' for psychological reasons. The guidelines that were studied in detail did not appreciably influence surgeons' decisions, which reflected criteria that were not cited in the guidelines, including cost of the procedure and whether patients sought restoration or improvement of their appearance. Decision guidelines in this area have several limitations. Future guidelines should: include all cosmetic procedures; be informed by a broad range of evidence; and, arguably, include several nonclinical criteria that currently inform surgeons' decision-making.

Regulatory system reform of occupational health and safety in China.

PubMed

Wu, Fenghong; Chi, Yan

2015-01-01

With the explosive economic growth and social development, China's regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined.

Regulatory system reform of occupational health and safety in China

PubMed Central

WU, Fenghong; CHI, Yan

2015-01-01

With the explosive economic growth and social development, China’s regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined. PMID:25843565

Ergonomics standards and guidelines for computer workstation design and the impact on users' health - a review.

PubMed

Woo, E H C; White, P; Lai, C W K

2016-03-01

This paper presents an overview of global ergonomics standards and guidelines for design of computer workstations, with particular focus on their inconsistency and associated health risk impact. Overall, considerable disagreements were found in the design specifications of computer workstations globally, particularly in relation to the results from previous ergonomics research and the outcomes from current ergonomics standards and guidelines. To cope with the rapid advancement in computer technology, this article provides justifications and suggestions for modifications in the current ergonomics standards and guidelines for the design of computer workstations. Practitioner Summary: A research gap exists in ergonomics standards and guidelines for computer workstations. We explore the validity and generalisability of ergonomics recommendations by comparing previous ergonomics research through to recommendations and outcomes from current ergonomics standards and guidelines.

Evolving PBPK applications in regulatory risk assessment: current situation and future goals

EPA Science Inventory

The presentation includes current applications of PBPK modeling in regulatory risk assessment and discussions on conflicts between assuring consistency with experimental data in current situation and the desire for animal-free model development.

Recurrent vulvovaginal candidiasis: A review of guideline recommendations.

PubMed

Matheson, Alexia; Mazza, Danielle

2017-04-01

Recurrent vulvovaginal candidiasis (VVC) is a difficult-to-manage condition that affects 5-8% of women of reproductive age. Current treatment regimes have high relapse rates, resulting in poor quality of life for the women affected. To compare the quality and content of current guidelines concerned with recurrent VVC and to develop a summary of recommendations to assist in the management of women with this condition. Relevant clinical guidelines were identified through a search of several databases (MEDLINE, SCOPUS and The Cochrane Library) and relevant websites. Five guidelines were identified. Each guideline was assessed for quality using the AGREE II instrument. Guideline recommendations were extracted, compared and contrasted. The identified guidelines were of mixed quality. This is not related to the level of evidence supporting them but is because of poor stakeholder involvement, applicability and lack of clarity concerning editorial independence. Current international guidelines for recurrent VVC are consistent in terms of their definition of the condition, diagnostic techniques and utilising induction and maintenance therapy as the treatment of choice. However, the regimen suggested by most guidelines (fluconazole weekly for six months) is not particularly effective; only 42.9% of patients are disease free after 12 months. An alternative regimen put forward by one of the guidelines cites a 77% cure rate after 12 months. Most guidelines lacked specific recommendations for the induction part of induction and maintenance treatment. The current most recommended treatment of recurrent VVC is sub-optimal. Studies performed on a larger scale are required to identify more effective treatments. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Space debris mitigation - engineering strategies

NASA Astrophysics Data System (ADS)

Taylor, E.; Hammond, M.

The problem of space debris pollution is acknowledged to be of growing concern by space agencies, leading to recent activities in the field of space debris mitigation. A review of the current (and near-future) mitigation guidelines, handbooks, standards and licensing procedures has identified a number of areas where further work is required. In order for space debris mitigation to be implemented in spacecraft manufacture and operation, the authors suggest that debris-related criteria need to become design parameters (following the same process as applied to reliability and radiation). To meet these parameters, spacecraft manufacturers and operators will need processes (supported by design tools and databases and implementation standards). A particular aspect of debris mitigation, as compared with conventional requirements (e.g. radiation and reliability) is the current and near-future national and international regulatory framework and associated liability aspects. A framework for these implementation standards is presented, in addition to results of in-house research and development on design tools and databases (including collision avoidance in GTO and SSTO and evaluation of failure criteria on composite and aluminium structures).

Analytical advances in pharmaceutical impurity profiling.

PubMed

Holm, René; Elder, David P

2016-05-25

Impurities will be present in all drug substances and drug products, i.e. nothing is 100% pure if one looks in enough depth. The current regulatory guidance on impurities accepts this, and for drug products with a dose of less than 2g/day identification of impurities is set at 0.1% levels and above (ICH Q3B(R2), 2006). For some impurities, this is a simple undertaking as generally available analytical techniques can address the prevailing analytical challenges; whereas, for others this may be much more challenging requiring more sophisticated analytical approaches. The present review provides an insight into current development of analytical techniques to investigate and quantify impurities in drug substances and drug products providing discussion of progress particular within the field of chromatography to ensure separation of and quantification of those related impurities. Further, a section is devoted to the identification of classical impurities, but in addition, inorganic (metal residues) and solid state impurities are also discussed. Risk control strategies for pharmaceutical impurities aligned with several of the ICH guidelines, are also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Legal and ethical issues in the international transaction of donor sperm and eggs.

PubMed

Heng, Boon Chin

2007-04-01

Pertinent ethical and legal issues in the international transaction of donor sperm and eggs are discussed. Firstly, there may be legislative and ethical "contradiction" by the local health authority in permitting import of donor gametes, due to varying policies on donor reimbursement in different countries. This is particularly significant in countries where the underlying principle of gamete donation is altruistic motivation, and where reimbursement is given only for direct "out-of-pocket" expenses i.e. traveling costs. Secondly, there is a lack of clear and coherent internationally-binding legislation and regulatory guidelines overseeing the exchange of donor gametes across international borders. In particular, provisions should be made for donor traceability if gametes are sourced from abroad. Thirdly, in the case of "frozen-egg donation" from abroad, patients must rightfully be informed that current cryopreservation technology is still sub-optimal, and all studies have consistently shown that the chances of conception are always lower with "frozen-eggs" compared to freshly-retrieved eggs. Finally, regulatory safeguards should be put in place to prevent fertility clinics and medical professionals from "re-selling" imported donor gametes at a profit to the patient, since it would be thoroughly unprofessional for them to earn a profit simply through the 'brokerage' of donated human material.

Development of medical writing in India: Past, present and future.

PubMed

Sharma, Suhasini

2017-01-01

Pharmaceutical medical writing has grown significantly in India in the last couple of decades. It includes preparing regulatory, safety, and publication documents as well as educational and communication material related to health and health-care products. Medical writing requires medical understanding, knowledge of drug development and the regulatory and safety domains, understanding of research methodologies, and awareness of relevant regulations and guidelines. It also requires the ability to analyze, interpret, and present biomedical scientific data in the required format and good writing skills. Medical writing is the fourth most commonly outsourced clinical development activity, and its global demand has steadily increased due to rising cost pressures on the pharmaceutical industry. India has the unique advantages of a large workforce of science graduates and medical professionals trained in English and lower costs, which make it a suitable destination for outsourcing medical writing services. However, the current share of India in global medical writing business is very small. This industry in India faces some real challenges, such as the lack of depth and breadth in domain expertise, inadequate technical writing skills, high attrition rates, and paucity of standardized training programs as well as quality assessment tools. Focusing our time, attention, and resources to address these challenges will help the Indian medical writing industry gain its rightful share in the global medical writing business.

Preparing clinical grade Ag-specific T cells for adoptive immunotherapy trials

PubMed Central

DiGiusto, DL; Cooper, LJN

2007-01-01

The production of clinical-grade T cells for adoptive immunotherapy has evolved from the ex vivo numerical expansion of tumor-infiltrating lymphocytes to sophisticated bioengineering processes often requiring cell selection, genetic modification and other extensive tissue culture manipulations, to produce desired cells with improved therapeutic potential. Advancements in understanding the biology of lymphocyte signaling, activation, homing and sustained in vivo proliferative potential have redefined the strategies used to produce T cells suitable for clinical investigation. When combined with new technical methods in cell processing and culturing, the therapeutic potential of T cells manufactured in academic centers has improved dramatically. Paralleling these technical achievements in cell manufacturing is the development of broadly applied regulatory standards that define the requirements for the clinical implementation of cell products with ever-increasing complexity. In concert with academic facilities operating in compliance with current good manufacturing practice, the prescribing physician can now infuse T cells with a highly selected or endowed phenotype that has been uniformly manufactured according to standard operating procedures and that meets federal guidelines for quality of investigational cell products. In this review we address salient issues related to the technical, immunologic, practical and regulatory aspects of manufacturing these advanced T-cell products for clinical use. PMID:17943498

An overview of the regulatory aspects of medical devices from the viewpoint of research and device manufacturing.

PubMed

Patrick, J

1993-01-01

To review the Food and Drug Administration's regulatory requirements for bringing a new or substantially changed medical device to market in the United States, noting the history and current requirements for the continuous spinal catheter. The relevant laws and guidelines for classifying, testing, and submitting a device to Food and Drug Administration approval are reviewed. The Food and Drug Administration categorizes medical devices into three classes, based on potential risk for illness or injury presented by a malfunction or failure. Class III devices are the most critical ones, and require a Premarket Approval that includes clinical trials before market introduction. Classes I and II usually require a 510(k), or premarket notification, which usually does not need any clinical data. Testing requirements include biocompatibility testing; physical, functional, and packaging testing; and sterility testing. The continuous spinal catheter (25-32 gauge) was marketed under a 510(k) claiming substantial equivalence to the Bizzarri-Giuffrida 24-gauge catheter, which was a pre-Amendment device. After incidences of cauda equina syndrome were reported with use of the continuous spinal technique, the Food and Drug Administration reclassified the small-gauge catheters as Class III devices, which require a Premarket Approval before being marketed.

Operating Procedures to Improve Efficiencies of In vitro Exposure Systems at the Air-Liquid Interface

EPA Science Inventory

The expanding use of in vitro exposure systems for toxicity assessments has created regulatory concerns. Many of these same concerns surround the proper conduct of in vivo inhalation toxicology studies that are addressed in guidelines and Good Laboratory Practice (GLPs) regulatio...

77 FR 49444 - Agency Information Collection Activities: Proposed Collection Renewal; Comment Request (3064-0152)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-16

...: Office of Information and Regulatory Affairs, Office of Management and Budget, New Executive Office... regarding identity theft with respect to their account holders and customers; (ii) regulations requiring... implementing the guidelines to identify possible risks to account holders or customers or to the safety and...

76 FR 38328 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-30

... regulations to evaluate their continued effectiveness in achieving the objectives for which they were adopted..., Mar. 10, 2011. The Commission also is engaged in a proposed rulemaking to adapt all applicable CFTC... Commission voluntarily adopt? Are there any principles or guidelines that are not appropriate for the...

77 FR 41206 - Guidelines for Preparing and Reviewing Licensing Applications for Instrumentation and Control...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-12

... Applications for Instrumentation and Control Upgrades for Non-Power Reactors AGENCY: Nuclear Regulatory... (NRC or the Commission) is requesting public comment on Chapter 7, Section 7.3, Reactor Control System...-Power Reactors: Format and Content,'' for instrumentation and control (I&C) upgrades and NUREG-1537...

12 CFR Appendix A to Part 570 - Interagency Guidelines Establishing Standards for Safety and Soundness

Code of Federal Regulations, 2010 CFR

2010-01-01

... risk assessment; 3. Timely and accurate financial, operational and regulatory reports; 4. Adequate... asset concentrations; and 6. Provide periodic asset reports with adequate information for management and... profile of the institution's assets and operations; 3. Assess the source, volatility, and sustainability...

12 CFR Appendix A to Part 30 - Interagency Guidelines Establishing Standards for Safety and Soundness

Code of Federal Regulations, 2010 CFR

2010-01-01

... risk assessment; 3. Timely and accurate financial, operational and regulatory reports; 4. Adequate... asset concentrations; and 6. Provide periodic asset reports with adequate information for management and... profile of the institution's assets and operations; 3. Assess the source, volatility, and sustainability...

49 CFR Appendix A to Part 355 - Guidelines for the Regulatory Review

Code of Federal Regulations, 2012 CFR

2012-10-01

... COMPATIBILITY OF STATE LAWS AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Pt. 355, App. A... drug and alcohol abuse; require a motor carrier to maintain a driver qualification file for each driver... Vehicles Prohibit possession, use, or driving under the influence of alcohol or other controlled substances...

49 CFR Appendix A to Part 355 - Guidelines for the Regulatory Review

Code of Federal Regulations, 2014 CFR

2014-10-01

... COMPATIBILITY OF STATE LAWS AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Pt. 355, App. A... drug and alcohol abuse; require a motor carrier to maintain a driver qualification file for each driver... Vehicles Prohibit possession, use, or driving under the influence of alcohol or other controlled substances...

49 CFR Appendix A to Part 355 - Guidelines for the Regulatory Review

Code of Federal Regulations, 2013 CFR

2013-10-01

... COMPATIBILITY OF STATE LAWS AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Pt. 355, App. A... drug and alcohol abuse; require a motor carrier to maintain a driver qualification file for each driver... Vehicles Prohibit possession, use, or driving under the influence of alcohol or other controlled substances...

49 CFR Appendix A to Part 355 - Guidelines for the Regulatory Review

Code of Federal Regulations, 2011 CFR

2011-10-01

... COMPATIBILITY OF STATE LAWS AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Pt. 355, App. A... drug and alcohol abuse; require a motor carrier to maintain a driver qualification file for each driver... Vehicles Prohibit possession, use, or driving under the influence of alcohol or other controlled substances...

A Guide to Disbursement, Refund, and Repayment.

ERIC Educational Resources Information Center

Guthrie, Marty; Rappaport, Renee

Guidelines are provided to assist in the interpretation of the regulatory requirements regarding disbursement of funds to students under Title IV student aid programs. Attention is also directed to the higher education community's self-regulation initiatives regarding refund and repayment, as well as the Department of Education's regulations in…

Post-chill antimicrobial treatments to control Salmonella, Listeria and Campylobacter contamination on chicken skin used in ground chicken

USDA-ARS?s Scientific Manuscript database

Ground poultry products are frequently contaminated with foodborne pathogens. With increased regulatory guidelines from USDA-FSIS, it is important to employ sufficient intervention strategies to control pathogen levels effectively. In this research, antimicrobials including 50 ppm chlorine and 1,2...

Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

EPA Science Inventory

Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

40 CFR 230.5 - General procedures to be followed.

Code of Federal Regulations, 2012 CFR

2012-07-01

... obtain an overview of the principal regulatory provisions of the Guidelines, review the restrictions on... consistent with the criteria and evaluations of § 230.11(f). (e) Evaluate the various physical and chemical..., related to their living communities or human uses (subparts D, E, and F). (g) Review Factual...

42 CFR 24.4 - Eligibility.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Eligibility. 24.4 Section 24.4 Public Health PUBLIC... agents that may affect the public health. The individual would normally have dealt with complex... regulatory guidelines for clinical research and been the recipient of invitations to speak at or to chair...

42 CFR 24.4 - Eligibility.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Eligibility. 24.4 Section 24.4 Public Health PUBLIC... agents that may affect the public health. The individual would normally have dealt with complex... regulatory guidelines for clinical research and been the recipient of invitations to speak at or to chair...

77 FR 63343 - Biweekly Notice: Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... PWR [Pressurized-Water Reactor] Steam Generator Tubes'' (Reference 32) and [Nuclear Energy Institute... maintains the required structural margins of the SG tubes for both normal and accident conditions. Nuclear Energy Institute 97-06, ``Steam Generator Program Guidelines'' (Reference 8), and NRC Regulatory Guide 1...

National Association Links, Alaska Oil and Gas Conservation Commission,

Science.gov Websites

Oil and Gas Conservation Commission Alaska Department of Administration, Alaska Oil and Gas Guidelines Regulatory Regulations Statutes Industry Guidance Bulletins Memorandums of Agreement Links Oil Field Terms (Schlumberger) Spot Price Information (DOE) West Coast Price - NS Oil (DOR) Calendar State

75 FR 79725 - Fall 2010 Semiannual Agenda of Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... to this order. By memorandum of July 23, 2010, the Office of Management and Budget issued guidelines... selected for periodic review under section 610 of the Regulatory Flexibility Act. In this edition of the... addition, beginning with the fall 2007 edition, the Internet became the basic means for disseminating the...

77 FR 7904 - Fall 2011 Semiannual Agenda of Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... to this order. By memorandum of June 30, 2011, the Office of Management and Budget issued guidelines... selected for periodic review under section 610 of the Regulatory Flexibility Act. In this edition of the... addition, beginning with the fall 2007 edition, the Internet became the basic means for disseminating the...

Regulatory cross-cutting topics for fuel cycle facilities.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denman, Matthew R.; Brown, Jason; Goldmann, Andrew Scott

This report overviews crosscutting regulatory topics for nuclear fuel cycle facilities for use in the Fuel Cycle Research & Development Nuclear Fuel Cycle Evaluation and Screening study. In particular, the regulatory infrastructure and analysis capability is assessed for the following topical areas: Fire Regulations (i.e., how applicable are current Nuclear Regulatory Commission (NRC) and/or International Atomic Energy Agency (IAEA) fire regulations to advance fuel cycle facilities) Consequence Assessment (i.e., how applicable are current radionuclide transportation tools to support risk-informed regulations and Level 2 and/or 3 PRA) While not addressed in detail, the following regulatory topic is also discussed: Integrated Security,more » Safeguard and Safety Requirement (i.e., how applicable are current Nuclear Regulatory Commission (NRC) regulations to future fuel cycle facilities which will likely be required to balance the sometimes conflicting Material Accountability, Security, and Safety requirements.)« less

Inflation of the type I error: investigations on regulatory recommendations for bioequivalence of highly variable drugs.

PubMed

Wonnemann, Meinolf; Frömke, Cornelia; Koch, Armin

2015-01-01

We investigated different evaluation strategies for bioequivalence trials with highly variable drugs on their resulting empirical type I error and empirical power. The classical 'unscaled' crossover design with average bioequivalence evaluation, the Add-on concept of the Japanese guideline, and the current 'scaling' approach of EMA were compared. Simulation studies were performed based on the assumption of a single dose drug administration while changing the underlying intra-individual variability. Inclusion of Add-on subjects following the Japanese concept led to slight increases of the empirical α-error (≈7.5%). For the approach of EMA we noted an unexpected tremendous increase of the rejection rate at a geometric mean ratio of 1.25. Moreover, we detected error rates slightly above the pre-set limit of 5% even at the proposed 'scaled' bioequivalence limits. With the classical 'unscaled' approach and the Japanese guideline concept the goal of reduced subject numbers in bioequivalence trials of HVDs cannot be achieved. On the other hand, widening the acceptance range comes at the price that quite a number of products will be accepted bioequivalent that had not been accepted in the past. A two-stage design with control of the global α therefore seems the better alternative.

Implementation Interventions Used in Nursing Homes and Hospitals: A Descriptive, Comparative Study between Austria, Germany, and The Netherlands.

PubMed

Breimaier, Helga E; Halfens, Ruud J G; Wilborn, Doris; Meesterberends, Esther; Haase Nielsen, Gunnar; Lohrmann, Christa

2013-01-01

Translating guidelines into nursing practice remains a considerable challenge. Until now, little attention has been paid to which interventions are used in practice to implement guidelines on changing clinical nursing practice. This cross-sectional study determined the current ranges and rates of implementation-related interventions in Austria, Germany, and The Netherlands and explored possible differences between these countries. An online questionnaire based on the conceptual framework of implementation interventions (professional, organizational, financial, and regulatory) from the Cochrane Effective Practice and Organization of Care (EPOC) data collection checklist was used to gather data from nursing homes and hospitals. Provision of written materials is the most frequently used professional implementation intervention (85%), whereas changes in the patient record system rank foremost among organisational interventions (78%). Financial incentives for nurses are rarely used. More interventions were used in Austria and Germany than in The Netherlands (20.3/20.2/17.3). Professional interventions are used more frequently in Germany and financial interventions more frequently in The Netherlands. Implementation efforts focus mainly on professional and organisational interventions. Nurse managers and other responsible personnel should direct their focus to a broader array of implementation interventions using the four different categories of EPOC's conceptual framework.

Effectiveness versus efficacy trials in COPD: how study design influences outcomes and applicability.

PubMed

Woodcock, Ashley; Boucot, Isabelle; Leather, David A; Crawford, Jodie; Collier, Susan; Bakerly, Nawar Diar; Hilton, Emma; Vestbo, Jørgen

2018-02-01

Guidelines for chronic obstructive pulmonary disease (COPD) management are based largely on results from double-blind randomised controlled trials (RCTs) of efficacy. These trials have high internal validity and test whether a drug is efficacious, but they are conducted in highly selected populations that may differ significantly from patients with COPD seen in routine practice.We compared the baseline characteristics, healthcare use and outcomes between the Salford Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale efficacy RCTs. We also calculated the proportion of SLS patients who would have been eligible for inclusion in an efficacy RCT by applying the inclusion criteria used in efficacy trials of combination treatments.SLS patients were older, included more females and more current smokers, had more comorbidities (including asthma), and had more often experienced exacerbations prior to inclusion. In the SLS, rates of moderate or severe exacerbations, incidence of overall serious adverse events (SAEs), and SAEs of pneumonia were more frequent. A maximum of 30% of patients enrolled in the SLS would have been eligible for a phase IIIa regulatory exacerbation study.Patients in large COPD efficacy RCTs have limited representativeness compared with an effectiveness trial. This should be considered when interpreting efficacy RCT outcomes and their inclusion into guidelines. Copyright ©ERS 2018.

78 FR 34431 - Effluent Limitations Guidelines and Standards for the Steam Electric Power Generating Point...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

...EPA is proposing a regulation that would strengthen the controls on discharges from certain steam electric power plants by revising technology-based effluent limitations guidelines and standards for the steam electric power generating point source category. Steam electric power plants alone contribute 50-60 percent of all toxic pollutants discharged to surface waters by all industrial categories currently regulated in the United States under the Clean Water Act. Furthermore, power plant discharges to surface waters are expected to increase as pollutants are increasingly captured by air pollution controls and transferred to wastewater discharges. This proposal, if implemented, would reduce the amount of toxic metals and other pollutants discharged to surface waters from power plants. EPA is considering several regulatory options in this rulemaking and has identified four preferred alternatives for regulation of discharges from existing sources. These four preferred alternatives differ with respect to the scope of requirements that would be applicable to existing discharges of pollutants found in two wastestreams generated at power plants. EPA estimates that the preferred options for this proposed rule would annually reduce pollutant discharges by 0.47 billion to 2.62 billion pounds, reduce water use by 50 billion to 103 billion gallons, cost $185 million to $954 million, and would be economically achievable.

Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

PubMed

Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

2014-11-01

Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Next generation and biosimilar monoclonal antibodies

PubMed Central

2011-01-01

The Next Generation and Biosimilar Monoclonal Antibodies: Essential Considerations Towards Regulatory Acceptance in Europe workshop, organized by the European Centre of Regulatory Affairs Freiburg (EUCRAF), was held February 3–4, 2011 in Freiburg, Germany. The workshop attracted over 100 attendees from 15 countries, including regulators from 11 agencies, who interacted over the course of two days. The speakers presented their authoritative views on monoclonal antibodies (mAbs) as attractive targets for development, the experience to date with the regulatory process for biosimilar medicinal products, the European Medicines Agency draft guideline on biosimilar mAbs, as well as key elements in the development of mAbs. Participants engaged in many lively discussions, and much speculation on the nature of the quality, non-clinical and clinical requirements for authorization of biosimilar mAbs. PMID:21487235

Contemporary Obstetric Triage.

PubMed

Sandy, Edward Allen; Kaminski, Robert; Simhan, Hygriv; Beigi, Richard

2016-03-01

The role of obstetric triage in the care of pregnant women has expanded significantly. Factors driving this change include the Emergency Medical Treatment and Active Labor Act, improved methods of testing for fetal well-being, increasing litigation risk, and changes in resident duty hour guidelines. The contemporary obstetric triage facility must have processes in place to provide a medical screening examination that complies with regulatory statues while considering both the facility's maternal level of care and available resources. This review examines the history of the development of obstetric triage, current considerations in a contemporary obstetric triage paradigm, and future areas for consideration. An example of a contemporary obstetric triage program at an academic medical center is presented. A successful contemporary obstetric triage paradigm is one that addresses the questions of "sick or not sick" and "labor or no labor," for every obstetric patient that presents for care. Failure to do so risks poor patient outcome, poor patient satisfaction, adverse litigation outcome, regulatory scrutiny, and exclusion from federal payment programs. Understanding the role of contemporary obstetric triage in the current health care environment is important for both providers and health care leadership. This study is for obstetricians and gynecologists as well as family physicians. After completing this activity, the learner should be better able to understand the scope of a medical screening examination within the context of contemporary obstetric triage; understand how a facility's level of maternal care influences clinical decision making in a contemporary obstetric triage setting; and understand the considerations necessary for the systematic evaluation of the 2 basic contemporary obstetric questions, "sick or not sick?" and "labor or no labor?"

Adherence to current guidelines for chronic obstructive pulmonary disease (COPD) among patients treated with combination of long-acting bronchodilators or inhaled corticosteroids.

PubMed

Asche, Carl Victor; Leader, Shelah; Plauschinat, Craig; Raparla, Swetha; Yan, Ming; Ye, Xiangyang; Young, Dave

2012-01-01

To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β(2)-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS). The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007. The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS. Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data. We examined the baseline characteristics of these patients along with their healthcare resource utilization. Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines. A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results. The adherent subgroup received COPD medications consistent with current GOLD guidelines. Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines. In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines. In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines. GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts. Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD. Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers.

Gamete and Embryo Donation and Surrogacy in Australia: The Social Context and Regulatory Framework

PubMed Central

Hammarberg, Karin; Johnson, Louise; Petrillo, Tracey

2011-01-01

The social and legal acceptability of third-party reproduction varies around the world. In Australia, gamete and embryo donation and surrogacy are permitted within the regulatory framework set out by federal and state governments. The aim of this paper is to describe the social context and regulatory framework for third-party reproduction in Australia. This is a review of current laws and regulations related to third-party reproduction in Australia. Although subtle between-state differences exist, third-party reproduction is by and large a socially acceptable and legally permissible way to form a family throughout Australia. The overarching principles that govern the practice of third-party reproduction are altruism; the right of donorconceived people to be informed of their biological origins; and the provision of comprehensive counselling about the social, psychological, physical, ethical, financial and legal implications of third-party reproduction to those considering donating or receiving gametes or embryos and entering surrogacy arrangements. These principles ensure that donors are not motivated by financial gain, donor offspring can identify and meet with the person or persons who donated gametes or embryos, and prospective donors and recipients are aware of and have carefully considered the potential consequences of third-party reproduction. Australian state laws and federal guidelines prohibit commercial and anonymous third-party reproduction; mandate counselling of all parties involved in gamete and embryo donation and surrogacy arrangements; and require clinics to keep records with identifying and non- identifying information about the donor/s to allow donor-conceived offspring to trace their biological origins. PMID:24851179

Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective.

PubMed

Salmikangas, Paula; Schuessler-Lenz, Martina; Ruiz, Sol; Celis, Patrick; Reischl, Ilona; Menezes-Ferreira, Margarida; Flory, Egbert; Renner, Matthias; Ferry, Nicolas

2015-01-01

With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk-based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs.

Design of clinical trials for therapeutic cancer vaccines development.

PubMed

Mackiewicz, Jacek; Mackiewicz, Andrzej

2009-12-25

Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

Gamete and embryo donation and surrogacy in australia: the social context and regulatory framework.

PubMed

Hammarberg, Karin; Johnson, Louise; Petrillo, Tracey

2011-01-01

The social and legal acceptability of third-party reproduction varies around the world. In Australia, gamete and embryo donation and surrogacy are permitted within the regulatory framework set out by federal and state governments. The aim of this paper is to describe the social context and regulatory framework for third-party reproduction in Australia. This is a review of current laws and regulations related to third-party reproduction in Australia. Although subtle between-state differences exist, third-party reproduction is by and large a socially acceptable and legally permissible way to form a family throughout Australia. The overarching principles that govern the practice of third-party reproduction are altruism; the right of donorconceived people to be informed of their biological origins; and the provision of comprehensive counselling about the social, psychological, physical, ethical, financial and legal implications of third-party reproduction to those considering donating or receiving gametes or embryos and entering surrogacy arrangements. These principles ensure that donors are not motivated by financial gain, donor offspring can identify and meet with the person or persons who donated gametes or embryos, and prospective donors and recipients are aware of and have carefully considered the potential consequences of third-party reproduction. Australian state laws and federal guidelines prohibit commercial and anonymous third-party reproduction; mandate counselling of all parties involved in gamete and embryo donation and surrogacy arrangements; and require clinics to keep records with identifying and non- identifying information about the donor/s to allow donor-conceived offspring to trace their biological origins.

[Collections of human biological resources for research purposes: from regulations to the need of a guide of good collection practices].

PubMed

Le Roux, N; de Montgolfier, S; di Donato, J-H; Boccon-Gibod, L; Teillac, P; Hervé, C; Berthon, P

2003-12-01

In France, collections of human biological resources are regulated by the "Bioethics Law", currently in revision. Hence, we analyse the regulatory and ethical issues of these practices in the context of scientific research. The ultimate aim of such collections is to improve biological and medical knowledge. We think that the French regulatory system is quite complicated and non-explicit for "collection holders". The multiplicity of legal texts concerning this activity has made their application difficult, especially in the absence of application decrees. The project amending the actual law has clarified the legal status of collections but it did not shed light on the status of human body detached parts. Furthermore, the text is still very far from the international bioethical recommendations, and does not reflect the actual collection's implementation. The establishment of a guideline of Good Collection Practices, based on clear principles, should help to simplify the situation, especially when it is imbedded in the regulation and linked to control procedures. It would allow a balance between collective interests and the protection of individuals, taking into account of the international highly competitive scientific and economical constraints. The major issue is to preserve and to perpetuate the existing and future collections because of their precious value as an important tool for biomedical knowledge. The efficiency of a regulation depends on its legibility and accessibility, two requirements that seem to determine the acceptance of the regulatory tool and its application allowing subsequently to reach fairness in proceedings.

Cell-Based Therapies for Joint Disease in Veterinary Medicine: What We Have Learned and What We Need to Know

PubMed Central

Bogers, Sophie Helen

2018-01-01

Biological cell-based therapies for the treatment of joint disease in veterinary patients include autologous-conditioned serum, platelet-rich plasma, and expanded or non-expanded mesenchymal stem cell products. This narrative review outlines the processing and known mechanism of action of these therapies and reviews current preclinical and clinical efficacy in joint disease in the context of the processing type and study design. The significance of variation for biological activity and consequently regulatory approval is also discussed. There is significant variation in study outcomes for canine and equine cell-based products derived from whole blood or stem cell sources such as adipose and bone marrow. Variation can be attributed to altering bio-composition due to factors including preparation technique and source. In addition, study design factors like selection of cases with early vs. late stage osteoarthritis (OA), or with intra-articular soft tissue injury, influence outcome variation. In this under-regulated field, variation raises concerns for product safety, consistency, and efficacy. Cell-based therapies used for OA meet the Food and Drug Administration’s (FDA’s) definition of a drug; however, researchers must consider their approach to veterinary cell-based research to meet future regulatory demands. This review explains the USA’s FDA guidelines as an example pathway for cell-based therapies to demonstrate safety, effectiveness, and manufacturing consistency. An understanding of the variation in production consistency, effectiveness, and regulatory concerns is essential for practitioners and researchers to determine what products are indicated for the treatment of joint disease and tactics to improve the quality of future research. PMID:29713634

[Current status of practice of providing dietary advice to pregnant women by members of the Japanese Midwives' Association. Knowledge and utilization of the "Dietary Guidelines for Pregnant and Lactating Women"].

PubMed

Takimoto, Hidemi; Yonezawa, Junko; Shimada, Marie; Kato, Noriko; Yokoyama, Tetsuji

2013-01-01

Midwives are actively involved in providing dietary advice to pregnant women. In order to describe the current status of prenatal dietary advice provided by midwives, we conducted a questionnaire survey inquiring about their knowledge and usage of the "Dietary Guidelines for Pregnant and Lactating Women" (Guidelines) issued by the Ministry of Health, Labour, and Welfare in 2006. In total, 2000 members of the Japanese Midwives' Association were randomly selected for administration of the questionnaire. The recovery rate was 42.1%, and 785 responses were eligible for analyses. The questionnaire collected information on the respondent's age, years of work experience, current involvement in delivery practice, number of deliveries per year in the current affiliation, provision of dietary advice to pregnant women, and knowledge and usage of the Guidelines. The proportion of respondents in their 20 s was low (1.8%). About half of the respondents were practicing delivery. Further, 66.1% (519 midwives) reported they had knowledge of the Guidelines. Among those who had knowledge of the Guidelines and were currently providing dietary advice (426 midwives), 88.0% were using the Guidelines. The most frequently used item in the Guidelines was "Diet for preventing anemia" (75.8%). The least used item was "Shoku-iku (diet and nutrition education) for pregnant and lactating women" (58.5%). Midwives who were practicing delivery showed a significantly lower usage of the Guidelines than those who were not (84.9% vs. 92.6%, P = 0.02). Among midwives practicing delivery, the most common reason for not using the Guidelines was "using original educational material produced by oneself or the facility." Providing dietary advice to pregnant women constituted a large fraction of midwives' duties as well as delivery practice. About 90% of the midwives, who had knowledge of the Guidelines and provided dietary advice, were using the Guidelines. In order to increase the usage of individual items of the Guidelines, ready-to-use brochures should be developed for midwives.

Draft secure medical database standard.

PubMed

Pangalos, George

2002-01-01

Medical database security is a particularly important issue for all Healthcare establishments. Medical information systems are intended to support a wide range of pertinent health issues today, for example: assure the quality of care, support effective management of the health services institutions, monitor and contain the cost of care, implement technology into care without violating social values, ensure the equity and availability of care, preserve humanity despite the proliferation of technology etc.. In this context, medical database security aims primarily to support: high availability, accuracy and consistency of the stored data, the medical professional secrecy and confidentiality, and the protection of the privacy of the patient. These properties, though of technical nature, basically require that the system is actually helpful for medical care and not harmful to patients. These later properties require in turn not only that fundamental ethical principles are not violated by employing database systems, but instead, are effectively enforced by technical means. This document reviews the existing and emerging work on the security of medical database systems. It presents in detail the related problems and requirements related to medical database security. It addresses the problems of medical database security policies, secure design methodologies and implementation techniques. It also describes the current legal framework and regulatory requirements for medical database security. The issue of medical database security guidelines is also examined in detailed. The current national and international efforts in the area are studied. It also gives an overview of the research work in the area. The document also presents in detail the most complete to our knowledge set of security guidelines for the development and operation of medical database systems.

Current issues in billing and coding in interventional pain medicine.

PubMed

Manchikanti, L

2000-10-01

Interventional pain management is a dynamic field with changes occurring on a daily basis, not only with technology but also with regulations that have a substantial financial impact on practices. Regulations are imposed not only by the federal government and other regulatory agencies, and also by a multitude of other payors, state governments and medical boards. Documentation of medical necessity with coding that correlates with multiple components of the patient's medical record, operative report, and billing statement is extremely important. Numerous changes which have occurred in the practice of interventional pain management in the new millennium continue to impact the financial viability of interventional pain practices along with patient access to these services. Thus, while complying with regulations of billing, coding and proper, effective, and ethical practice of pain management, it is also essential for physicians to understand financial aspects and the impact of various practice patterns. This article provides guidelines which are meant to provide practical considerations for billing and coding of interventional techniques in the management of chronic pain based on the current state of the art and science of interventional pain management. Hence, these guidelines do not constitute inflexible treatment, coding, billing or documentation recommendations. It is expected that a provider will establish a plan of care on a case-by-case basis taking into account an individual patient's medical condition, personal needs, and preferences, along with physician's experience and in a similar manner, billing and coding practices will be developed. Based on an individual patient's needs, treatment, billing and coding, different from what is outlined here is not only warranted but essential.

The OECD expert meeting on ecotoxicology and environmental fate--towards the development of improved OECD guidelines for the testing of nanomaterials.

PubMed

Kühnel, Dana; Nickel, Carmen

2014-02-15

On behalf of the OECD Working Party on Manufactured Nanomaterials (WPMN) an expert meeting on ecotoxicology and environmental fate of nanomaterials (NMs) took place in January 2013 in Berlin. At this meeting experts from science, industry and regulatory bodies discussed the applicability of OECD test guidelines (TGs) for chemicals to nanomaterials. The objective was to discuss the current state of the relevant science and provide recommendations to the OECD WPMN on (1) the need for updating current OECD TGs and the need for developing new ones specific to nanomaterials; and (2) guidance needed for the appropriate and valid testing of environmental fate and ecotoxicity endpoints for NMs. Experts at the workshop agreed that the majority of the OECD TG for chemicals were generally applicable for the testing of NM, with the exception of TG 105 (water solubility) and 106 (adsorption-desorption). Additionally, the workshop also highlighted considerations when conducting OECD chemical TG on nanomaterials (e.g., sample preparation, dispersion, analysis, dosimetry and characterisation). These considerations will lead to the future development of proposals for new TG and guidance documents (GDs) to ensure that OECD TG give meaningful, repeatable, and accurate results when used for nanomaterials. This report provides a short overview of topics discussed during the meeting and the main outcomes. A more detailed report of the workshop will become available through the OECD, however, due to the urgency of having OECD TG relevant for nanomaterials, this brief report is being shared with the scientific community through this communication. Copyright © 2013. Published by Elsevier B.V.

Guidelines for using electronic and social media: the regulatory perspective.

PubMed

Spector, Nancy; Kappel, Dawn M

2012-09-30

Social media can be a very effective way of communicating in nursing, but guidelines for appropriate use by healthcare providers are essential. This article briefly introduces the phenomenon of social media and introduces three actual scenarios where nurses unintentionally violated appropriate use of social media in healthcare. The scenarios are discussed related to social media, career, concerns, and nursing regulation. Incorporating these and other examples with data from board of nursing cases, the nature of complaints against nurses is explored as well as common myths and misunderstandings about using social media platforms. Guidelines for appropriate use by nurses and available resources to inform policy are highlighted. Next steps in social media in nursing should include development of organizational level policies and educational programs on the use of social media.

Impact of Current Versus Previous Cardiac Resynchronization Therapy Guidelines on the Proportion of Patients With Heart Failure Eligible for Therapy.

PubMed

Lyons, Kristin J; Ezekowitz, Justin A; Liang, Li; Heidenreich, Paul A; Yancy, Clyde W; DeVore, Adam D; Hernandez, Adrian F; Fonarow, Gregg C

2017-05-01

This study sought to ascertain the impact of heart failure (HF) guideline change on the number of patients eligible to undergo cardiac resynchronization therapy (CRT). The 2013 HF guideline of the American College of Cardiology Foundation and American Heart Association (ACCF/AHA) narrowed the recommendations for CRT. The impact of this guideline change on the number of eligible patients for CRT has not been described. Using data from Get With The Guidelines-Heart Failure between 2012 and 2015, this study evaluated the proportion of hospitalized patients with HF who were eligible for CRT on the basis of historical and current guideline recommendations. The authors identified 25,102 hospitalizations for HF that included patients with a left ventricular ejection fraction (LVEF) ≤35% from 283 hospitals. Patients with a medical, system-related, or patient-related reason for not undergoing CRT were excluded. Overall, 49.1% (n = 12,336) of patients with HF, an LVEF ≤35%, and no documented contraindication were eligible for CRT on the basis of historical guidelines, and 33.1% (n = 8,299) of patients were eligible for CRT on the basis of current guidelines, a 16.1% absolute reduction in eligibility (p < 0.0001). Patients eligible for CRT on the basis of current guidelines were more likely to have CRT with an implantable cardioverter-defibrillator or CRT with pacing only placed or prescribed at discharge (57.8% vs. 54.9%; p < 0.0001) compared with patients eligible for CRT on the basis of historical guidelines. In this population of patients with HF, an LVEF ≤35%, and no documented contraindication for CRT, the current ACCF/AHA HF guidelines reduce the proportion of patients eligible for CRT by approximately 15%. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The confusion in complying with good manufacturing practice requirements in Malaysia

NASA Astrophysics Data System (ADS)

Jali, Mohd Bakri; Ghani, Maaruf Abdul; Nor, Norazmir Md

2016-11-01

Food manufacturing operations need to fulfil regulatory requirements related to hygiene and good manufacturing practices (GMP) to successfully market their products as safe and quality products. GMP based on its ten elements used as guidelines to ensure control over biological, chemical and physical hazards. This study aims to investigate the confusion for design and facilities elements among food industries. Both qualitative and quantitative techniques are used as systematic tools. Design and facilities elements lay a firm foundation for good manufacturing practice to ensure food hygiene and should be used in conjunction with each specific code of hygiene practice and guidelines.

Regulatory incentives to ensure better medicines for older people: From ICH E7 to the EMA reflection paper on quality aspects.

PubMed

van Riet-Nales, Diana A; Hussain, Nasir; Sundberg, Katarina A E; Eggenschwyler, Doris; Ferris, Cristina; Robert, Jean-Louis; Cerreta, Francesca

2016-10-30

Ageing comes with an increased propensity in the alteration of human organ and body functions, which can e.g. result in multi-morbidity, frailty, polypharmacy, altered medication safety and/or efficacy, and problems with the practical use of medicines in a real world setting. Such problems may e.g. involve difficulties opening containers, swallowing large tablets, breaking tablets by hand, or correctly understanding the user instruction. This review aims to summarize the European regulatory activities towards better medicines for older people, with a main focus on formulation development and the overall drug product design. It addresses the ICH E7 guideline "Studies in support of special populations, geriatrics", the ICH Q8 guideline "Pharmaceutical development", the EMA good practice guide on "Risk minimisation and prevention of medication errors" and the forthcoming EMA CHMP QWP reflection paper on the "Quality aspects (pharmaceutical development) of medicines for older people". In addition, three key aspects to the practical use of medicines by older people are discussed in a wider context: multi-particulates including small tablets (also referred to as mini-tablets), ease of opening and storage conditions. Furthermore, attention is paid to work in progress e.g. incentives by the European national drug regulatory authorities, and patient centric drug product development. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Lung ultrasound for the diagnosis of community-acquired pneumonia in children.

PubMed

Stadler, Jacob A M; Andronikou, Savvas; Zar, Heather J

2017-10-01

Ultrasound (US) has been proposed as an alternative first-line imaging modality to diagnose community-acquired pneumonia in children. Lung US has the potential benefits over chest radiography of being radiation free, subject to fewer regulatory requirements, relatively lower cost and with immediate bedside availability of results. However, the uptake of lung US into clinical practice has been slow and it is not yet included in clinical guidelines for community-acquired pneumonia in children. The aim of this review is to give an overview of the equipment and techniques used to perform lung US in children with suspected pneumonia and the interpretation of relevant sonographic findings. We also summarise the current evidence of diagnostic accuracy and reliability of lung US compared to alternative imaging modalities in children and critically consider the strengths and limitations of lung US for use in children presenting with suspected community-acquired pneumonia.

Ethics of clinical trials in Nigeria.

PubMed

Okonta, Patrick I

2014-05-01

The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria.

Ethics of clinical trials in Nigeria

PubMed Central

Okonta, Patrick I.

2014-01-01

The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria. PMID:25013247

Developing therapeutic microRNAs for cancer

PubMed Central

Bader, AG; Brown, D; Stoudemire, J; Lammers, P

2014-01-01

Despite substantial progress in understanding the cancer-signaling network, effective therapies remain scarce due to insufficient disruption of oncogenic pathways, drug resistance and drug-induced toxicity. This complexity of cancer defines an urgent goal for researchers and clinicians to develop novel therapeutic strategies. The discovery of microRNAs (miRNAs) provides new hope for accomplishing this task. Supported by solid evidence for a critical role in cancer and bolstered by a unique mechanism of action, miRNAs are likely to yield a new class of targeted therapeutics. In contrast to current cancer medicines, miRNA-based therapies function by subtle repression of gene expression on a yet large number of oncogenic factors and are, therefore, anticipated to be highly efficacious. After the completion of target validation for several candidates, the development of therapeutic miRNAs is now moving to a new stage that involves pharmacological drug delivery, preclinical toxicology and regulatory guidelines. PMID:21633392

[Pharmaceutical product quality control and good manufacturing practices].

PubMed

Hiyama, Yukio

2010-01-01

This report describes the roles of Good Manufacturing Practices (GMP) in pharmaceutical product quality control. There are three keys to pharmaceutical product quality control. They are specifications, thorough product characterization during development, and adherence to GMP as the ICH Q6A guideline on specifications provides the most important principles in its background section. Impacts of the revised Pharmaceutical Affairs Law (rPAL) which became effective in 2005 on product quality control are discussed. Progress of ICH discussion for Pharmaceutical Development (Q8), Quality Risk Management (Q9) and Pharmaceutical Quality System (Q10) are reviewed. In order to reconstruct GMP guidelines and GMP inspection system in the regulatory agencies under the new paradigm by rPAL and the ICH, a series of Health Science studies were conducted. For GMP guidelines, product GMP guideline, technology transfer guideline, laboratory control guideline and change control system guideline were written. For the GMP inspection system, inspection check list, inspection memo and inspection scenario were proposed also by the Health Science study groups. Because pharmaceutical products and their raw materials are manufactured and distributed internationally, collaborations with other national authorities are highly desired. In order to enhance the international collaborations, consistent establishment of GMP inspection quality system throughout Japan will be essential.

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-ninth report.

PubMed

2015-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use. Revised procedure for the development of monographs and other texts for The International Pharmacopoeia; Revised updating mechanism for the section on radiopharmaceuticals in The International Pharmacopoeia; Revision of the supplementary guidelines on good manufacturing practices: validation, Appendix 7: non-sterile process validation; General guidance for inspectors on hold-time studies; 16 technical supplements to Model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products; Recommendations for quality requirements when plant-derived artemisinin is used as a starting material in the production of antimalarial active pharmaceutical ingredients; Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability: revision; Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products: revision; and Good review practices: guidelines for national and regional regulatory authorities.

A process to establish nutritional guidelines to address obesity: Lessons from Mexico.

PubMed

Charvel, Sofia; Cobo, Fernanda; Hernández-Ávila, Mauricio

2015-11-01

In 2010, the Mexican government implemented a multi-sector agreement to prevent obesity. In response, the Ministries of Health and Education launched a national school-based policy to increase physical activity, improve nutrition literacy, and regulate school food offerings through nutritional guidelines. We studied the Guidelines' negotiation and regulatory review process, including government collaboration and industry response. Within the government, conflicting positions were evident: the Ministries of Health and Education supported the Guidelines as an effective obesity-prevention strategy, while the Ministries of Economics and Agriculture viewed them as potentially damaging to the economy and job generation. The food and beverage industries opposed and delayed the process, arguing that regulation was costly, with negative impacts on jobs and revenues. The proposed Guidelines suffered revisions that lowered standards initially put forward. We documented the need to improve cross-agency cooperation to achieve effective policymaking. The 'siloed' government working style presented a barrier to efforts to resist industry's influence and strong lobbying. Our results are relevant to public health policymakers working in childhood obesity prevention.

75 FR 75485 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-03

... Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal... Guidelines for Federal Workplace Drug Testing Programs (Mandatory Guidelines). The Mandatory Guidelines were... Laboratories and Instrumented Initial Testing Facilities (IITF) must meet in order to conduct drug and specimen...

75 FR 62842 - Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-13

... Current List of Laboratories Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal... Guidelines for Federal Workplace Drug Testing Programs (Mandatory Guidelines). The Mandatory Guidelines were... and Instrumented Initial Testing Facilities (IITF) must meet in order to conduct drug and specimen...

Phase 1 environmental report for the Advanced Neutron Source at Oak Ridge National Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blasing, T.J.; Brown, R.A.; Cada, G.F.

1992-02-01

The US Department of Energy (DOE) has proposed the construction and operation of the Advanced Neutron Source (ANS), a 330-MW(f) reactor, at Oak Ridge National Laboratory (ORNL) to support neutron scattering and nuclear physics experiments. ANS would provide a steady-state source of neutrons that are thermalized to produce sources of hot, cold, and very coal neutrons. The use of these neutrons in ANS experiment facilities would be an essential component of national research efforts in basic materials science. Additionally, ANS capabilities would include production of transplutonium isotopes, irradiation of potential fusion and fission reactor materials, activation analysis, and production ofmore » medical and industrial isotopes such as {sup 252}Cf. Although ANS would not require licensing by the US Nuclear Regulatory Commission (NRC), DOE regards the design, construction, and operation of ANS as activities that would produce a licensable facility; that is, DOE is following the regulatory guidelines that NRC would apply if NRC were licensing the facility. Those guidelines include instructions for the preparation of an environmental report (ER), a compilation of available data and preliminary analyses regarding the environmental impacts of nuclear facility construction and operation. The ER, described and outlined in NRC Regulatory Guide 4.2, serves as a background document to facilitate the preparation of environmental impact statements (EISs). Using Regulatory Guide 4.2 as a model, this ANS ER provides analyses and information specific to the ANS site and area that can be adopted (and modified, if necessary) for the ANS EIS. The ER is being prepared in two phases. Phase 1 ER includes many of the data and analyses needed to prepare the EIS but does not include data or analyses of alternate sites or alternate technologies. Phase 2 ER will include the additional data and analyses stipulated by Regulatory Guide 4.2.« less

Patient Privacy in the Era of Big Data.

PubMed

Kayaalp, Mehmet

2018-01-20

Privacy was defined as a fundamental human right in the Universal Declaration of Human Rights at the 1948 United Nations General Assembly. However, there is still no consensus on what constitutes privacy. In this review, we look at the evolution of privacy as a concept from the era of Hippocrates to the era of social media and big data. To appreciate the modern measures of patient privacy protection and correctly interpret the current regulatory framework in the United States, we need to analyze and understand the concepts of individually identifiable information, individually identifiable health information, protected health information, and de-identification. The Privacy Rule of the Health Insurance Portability and Accountability Act defines the regulatory framework and casts a balance between protective measures and access to health information for secondary (scientific) use. The rule defines the conditions when health information is protected by law and how protected health information can be de-identified for secondary use. With the advents of artificial intelligence and computational linguistics, computational text de-identification algorithms produce de-identified results nearly as well as those produced by human experts, but much faster, more consistently and basically for free. Modern clinical text de-identification systems now pave the road to big data and enable scientists to access de-identified clinical information while firmly protecting patient privacy. However, clinical text de-identification is not a perfect process. In order to maximize the protection of patient privacy and to free clinical and scientific information from the confines of electronic healthcare systems, all stakeholders, including patients, health institutions and institutional review boards, scientists and the scientific communities, as well as regulatory and law enforcement agencies must collaborate closely. On the one hand, public health laws and privacy regulations define rules and responsibilities such as requesting and granting only the amount of health information that is necessary for the scientific study. On the other hand, developers of de-identification systems provide guidelines to use different modes of operations to maximize the effectiveness of their tools and the success of de-identification. Institutions with clinical repositories need to follow these rules and guidelines closely to successfully protect patient privacy. To open the gates of big data to scientific communities, healthcare institutions need to be supported in their de-identification and data sharing efforts by the public, scientific communities, and local, state, and federal legislators and government agencies.

Patient Privacy in the Era of Big Data

PubMed Central

Kayaalp, Mehmet

2018-01-01

Privacy was defined as a fundamental human right in the Universal Declaration of Human Rights at the 1948 United Nations General Assembly. However, there is still no consensus on what constitutes privacy. In this review, we look at the evolution of privacy as a concept from the era of Hippocrates to the era of social media and big data. To appreciate the modern measures of patient privacy protection and correctly interpret the current regulatory framework in the United States, we need to analyze and understand the concepts of individually identifiable information, individually identifiable health information, protected health information, and de-identification. The Privacy Rule of the Health Insurance Portability and Accountability Act defines the regulatory framework and casts a balance between protective measures and access to health information for secondary (scientific) use. The rule defines the conditions when health information is protected by law and how protected health information can be de-identified for secondary use. With the advents of artificial intelligence and computational linguistics, computational text de-identification algorithms produce de-identified results nearly as well as those produced by human experts, but much faster, more consistently and basically for free. Modern clinical text de-identification systems now pave the road to big data and enable scientists to access de-identified clinical information while firmly protecting patient privacy. However, clinical text de-identification is not a perfect process. In order to maximize the protection of patient privacy and to free clinical and scientific information from the confines of electronic healthcare systems, all stakeholders, including patients, health institutions and institutional review boards, scientists and the scientific communities, as well as regulatory and law enforcement agencies must collaborate closely. On the one hand, public health laws and privacy regulations define rules and responsibilities such as requesting and granting only the amount of health information that is necessary for the scientific study. On the other hand, developers of de-identification systems provide guidelines to use different modes of operations to maximize the effectiveness of their tools and the success of de-identification. Institutions with clinical repositories need to follow these rules and guidelines closely to successfully protect patient privacy. To open the gates of big data to scientific communities, healthcare institutions need to be supported in their de-identification and data sharing efforts by the public, scientific communities, and local, state, and federal legislators and government agencies. PMID:28903886

[On improvement of the mechanism for establishing and changing indicators of quality and food safety in the regulatory and legal acts of the Eurasian Economical Union].

PubMed

Arnautov, O V

2016-01-01

In accordance with the Treaty on the Eurasian Economic Union (EAEU) to ensure the sanitary and epidemiological welfare of the population within the Union, a coordinated policy in agreed policy in the sphere of application of sanitary measures is carried out. Sanitary measures are the obligatory requirements and procedures, including requirements for the final product, processing methods, production, transportation, storage and disposal, sampling procedures, methods of research (tests), risk assessment, the state registration, requirements for packaging directly aimed at ensuring the safety of products (goods) in order to protect human welfare, and they should be applied on the basis having a scientific explanation, and only to the extent that is necessary to protect human welfare. Sanitary measures applied within the Union should be based on international and regional standards, guidelines and (or) the recommendations, except when they based on appropriate scientific studies and explanations. In this case sanitary measures which could provide a higher level of sanitary protection are introduced. At present, the mechanism of the development, justification and approval of common sanitary and epidemiological requirements (ESR) and procedures of the Eurasian Economic Commission (the Commission) is not installed. The absence of a clear mechanism for the development, approval and implementation of the ESR to the products (goods) on the basis having a scientific explanation on the one hand could lead to the creation of unjustified barriers to foreign and mutual trade, on the other--to weaken the level of safety for human life and health of products (goods) placed on markets of the Union. In order to bring the regulatory legal acts of the Customs Union in accordance with the Treaty on the Eurasian Economic Union the Commission in cooperation with the competent authorities of the Member States in the field of sanitary and epidemiological welfare developed the project of Guidelines for development, approval, modification and application of common sanitary epidemiological and hygienic requirements and procedures (hereinafter--Guidelines) which is currently undergoing approval procedures. The project envisages that the Uniform sanitary requirements are established on the basis of scientific research, including the evaluation of the risk of harmful effects of the environment on the human factors, taking into consideration the analysis of international experience in order to harmonize common sanitary requirements with international standards, guidelines and (or) recommendations. Adoption of the draft Guidelines, as well as the application of common methodologies of risk assessment and the hygienic standardization in establishing and justifying safety performance of products (goods) in the Eurasian Economic Union allow quickly and transparently develop, validate, coordinate and approve the Uniform sanitary and epidemiological and hygienic requirements and procedures for sanitary inspection (control) of products (goods) and include them into technical regulations Union.

Advertising Content, Platform Characteristics and the Appeal of Beer Advertising on a Social Networking Site.

PubMed

Noel, Jonathan K; Babor, Thomas F; Grady, James J

2018-03-15

The current study was conducted to investigate how changes in the content of a social media ad, user engagement values associated with the ad and user-generated comments (UGCs) associated with the ad can influence the appeal (i.e. source appeal, informational appeal and emotional appeal) of a social media ad. Facebook beer ads that violated the guidelines of a relevant marketing code were rated as more emotionally appealing compared to Facebook beer ads that did not violated the guidelines. Increased emotional appeal in beer advertising increases the probability that the ad will be remembered and influence future drinking occasions. A 2 (ad regulatory compliance: compliant vs. non-compliant) × 2 (user engagement: low vs. high) × 2 (UGC congruence: pro- vs anti-alcohol) mixed factorial experiment was conducted with 120 young adults, 21-24 years old. Each participant viewed four Facebook beer ads that were previously evaluated for thematic content and regulatory compliance. Participants were randomized to view either high or low user engagement values and either pro- or anti-drinking user-generated comments. After each ad exposure, ad appeal was assessed. Statistical analysis was conducted using hierarchical linear modeling. Models were adjusted for demographics, Alcohol Use Disorders Identification Test (AUDIT) scores and Facebook involvement. Source appeal (P = 0.034) and informational appeal (P < 0.001) were significantly higher among ads that were compliant with existing advertising regulations. Emotional appeal was significantly higher among ads that were non-compliant (P = 0.004). The effect of user engagement and UGCs were non-significant (p's > 0.05). Additionally, AUDIT scores (p's < 0.01) and Facebook involvement scores (p's < 0.01) were positively associated with all forms of ad appeal. The appeal of Facebook beer ads may be primarily determined by ad content. Increased emotional appeal in advertising caused by non-compliant advertising may increase the probability that the ad will be remembered and influence future drinking occasions.

The integration of the risk management process with the lifecycle of medical device software.

PubMed

Pecoraro, F; Luzi, D

2014-01-01

The application of software in the Medical Device (MD) domain has become central to the improvement of diagnoses and treatments. The new European regulations that specifically address software as an important component of MD, require complex procedures to make software compliant with safety requirements, introducing thereby new challenges in the qualification and classification of MD software as well as in the performance of risk management activities. Under this perspective, the aim of this paper is to propose an integrated framework that combines the activities to be carried out by the manufacturer to develop safe software within the development lifecycle based on the regulatory requirements reported in US and European regulations as well as in the relevant standards and guidelines. A comparative analysis was carried out to identify the main issues related to the application of the current new regulations. In addition, standards and guidelines recently released to harmonise procedures for the validation of MD software have been used to define the risk management activities to be carried out by the manufacturer during the software development process. This paper highlights the main issues related to the qualification and classification of MD software, providing an analysis of the different regulations applied in Europe and the US. A model that integrates the risk management process within the software development lifecycle has been proposed too. It is based on regulatory requirements and considers software risk analysis as a central input to be managed by the manufacturer already at the initial stages of the software design, in order to prevent MD failures. Relevant changes in the process of MD development have been introduced with the recognition of software being an important component of MDs as stated in regulations and standards. This implies the performance of highly iterative processes that have to integrate the risk management in the framework of software development. It also makes it necessary to involve both medical and software engineering competences to safeguard patient and user safety.

Case studies on clinical evaluation of biosimilar monoclonal antibody: scientific considerations for regulatory approval.

PubMed

Kudrin, Alex; Knezevic, Ivana; Joung, Jeewon; Kang, Hye-Na

2015-01-01

The objective of this paper is to provide considerations based on comprehensive case studies important for regulatory evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs) with a special emphasis on clinical aspects. Scientific principles from WHO Guidelines on SBPs were used as a basis for the exercise. Working groups consisted of regulators, manufacturers and academia. The following topics were discussed by the working groups: clinical criteria for biosimilarity, extrapolation approach and the overall regulatory decision making process. In order to determine typical pitfalls in the design of a SBP clinical programme and evaluate the gap of knowledge, amongst different industry and regulatory stakeholders on the appraisal of the data arising from SBP clinical studies, we have presented two fictional but realistic clinical case studies. The first case consists of the fictional development programme for an infliximab SBP candidate. The second case describes clinical studies proposed for a fictional rituximab SBP candidate. In the first scenario a highly similar quality profile has been taken forward into clinical studies whereas there was an important residual difference in functional attributes for the rituximab SBP candidate. These case studies were presented at the WHO implementation workshop for the WHO guidelines on evaluation of similar biotherapeutic products held in Seoul, Republic of Korea, in May 2014. The goal was to illustrate the interpretation of the clinical data arising from studies with SBP candidates and elicit knowledge gaps in clinical assessment. This paper reflects the outcome of the exercise and discussions held in Seoul and offers an analysis of the case studies as a learning opportunity on clinical development and evaluation of SBPs. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Surgical Management of Osteoarthritis of the Knee: Evidence-based Guideline.

PubMed

McGrory, Brian J; Weber, Kristy L; Jevsevar, David S; Sevarino, Kaitlyn

2016-08-01

Surgical Management of Osteoarthritis of the Knee: Evidence-based Guideline is based on a systematic review of the current scientific and clinical research. The guideline contains 38 recommendations pertaining to the preoperative, perioperative, and postoperative care of patients with osteoarthritis (OA) of the knee who are considering surgical treatment. The purpose of this clinical practice guideline is to help improve surgical management of patients with OA of the knee based on current best evidence. In addition to guideline recommendations, the work group highlighted the need for better research on the surgical management of OA of the knee.

Self-Regulation of Beer Advertising: A Comparative Analysis of Perceived Violations by Adolescents and Experts.

PubMed

Vendrame, Alan; Silva, Rebeca; Xuan, Ziming; Sparks, Robert; Noel, Jonathan; Pinsky, Ilana

2015-09-01

We assessed the impact of the 2010 revisions to Brazil's self-regulatory alcohol marketing code using expert and adolescent raters. Five popular TV beer ads were selected. Ads were rated based on the 2010 Brazilian self-regulatory marketing code. The expert group (N = 31) represented health-related professions; the adolescent group (N = 110) were public high school students. At least 1 ad violated 11 of 17 guidelines included in the study. Ratings by experts and adolescents were similar. Both found violations in all sections of the self-regulatory code, but significant group differences were seen in applying the section that prohibits the promotion of excessive alcohol consumption, with experts identifying more violations than adolescents. Beer ads in the sample systematically violated the self-regulatory standards for alcohol advertising in Brazil according to both experts and youth. Public policies for more effective restrictions and prohibitions in alcohol ads should be considered. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Regulatory ecotoxicity testing of nanomaterials - proposed modifications of OECD test guidelines based on laboratory experience with silver and titanium dioxide nanoparticles.

PubMed

Hund-Rinke, Kerstin; Baun, Anders; Cupi, Denisa; Fernandes, Teresa F; Handy, Richard; Kinross, John H; Navas, José M; Peijnenburg, Willie; Schlich, Karsten; Shaw, Benjamin J; Scott-Fordsmand, Janeck J

2016-12-01

Regulatory ecotoxicity testing of chemicals is of societal importance and a large effort is undertaken at the OECD to ensure that OECD test guidelines (TGs) for nanomaterials (NMs) are available. Significant progress to support the adaptation of selected TGs to NMs was achieved in the context of the project MARINA ( http://www.marina-fp7.eu/ ) funded within the 7th European Framework Program. Eight OECD TGs were adapted based on the testing of at least one ion-releasing NM (Ag) and two inert NMs (TiO 2 ). With the materials applied, two main variants of NMs (ion releasing vs. inert NMs) were addressed. As the modifications of the test guidelines refer to general test topics (e.g. test duration or measuring principle), we assume that the described approaches and modifications will be suitable for the testing of further NMs with other chemical compositions. Firm proposals for modification of protocols with scientific justification(s) are presented for the following tests: growth inhibition using the green algae Raphidocelis subcapitata (formerly: Pseudokirchneriella subcapitata; TG 201), acute toxicity with the crustacean Daphnia magna (TG 202), development toxicity with the fish Danio rerio (TG 210), reproduction of the sediment-living worm Lumbriculus variegatus (TG 225), activity of soil microflora (TGs 216, 217), and reproduction of the invertebrates (Enchytraeus crypticus, Eisenia fetida, TGs 220, 222). Additionally, test descriptions for two further test systems (root elongation of plants in hydroponic culture; test on fish cells) are presented. Ecotoxicological data obtained with the modified test guidelines for TiO 2 NMs and Ag NM and detailed method descriptions are available.

Stability of Pigeon Body Weight under Free-Feeding Conditions

ERIC Educational Resources Information Center

Kangas, Brian D.; Branch, Marc N.

2006-01-01

Increases in regulatory oversight of animal research require verification of effects of standard practices. There are no formal guidelines for establishing free-feeding weights in adult pigeons. In the present study, pigeons were obtained from a commercial supplier, weighed upon arrival, and then held in quarantine for 7 days with free access to…

40 CFR Appendix W to Part 51 - Guideline on Air Quality Models

Code of Federal Regulations, 2011 CFR

2011-07-01

... sufficient spatial and temporal coverage are available. c. It would be advantageous to categorize the various... control strategies. These are referred to as refined models. c. The use of screening techniques followed... location of the source in question and its expected impacts. c. In all regulatory analyses, especially if...

Evaluation of Wetland Hydrology in Formerly Irrigated Areas

DTIC Science & Technology

2017-07-01

Laboratory 1987). The USACE requires defensible documentation identifying the presence or absence of wetland conditions when agricultural lands...irrigated agricultural areas (USACE 2008). In 2012, the USACE South Pacific Division (SPD) developed guidelines encouraging landowners to...geographic range; regulatory status; creation in agricultural landscapes; wildlife habitat; threatened and endangered species; water quality; hydrology

75 FR 3776 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-22

... participation programs and unlisted real estate investments trusts (collectively, ``Investment Programs''). In.... FINRA Rule 2310 requires that members participating in a public offering of an Investment Program meet... Investment Program, follow specific guidelines on suitability, and adhere to limits on non-cash compensation...

Understanding Federal regulations as guidelines for classical biological control programs

Treesearch

Michael E. Montgomery

2011-01-01

This chapter reviews the legislation and rules that provide the foundation for federal regulation of the introduction of natural enemies of insects as biological control agents. It also outlines the steps for complying with regulatory requirements, using biological control of Adelges tsugae Annand, the hemlock woolly adelgid (HWA), as an example. The...

12 CFR Appendix A to Part 364 - Interagency Guidelines Establishing Standards for Safety and Soundness

Code of Federal Regulations, 2010 CFR

2010-01-01

..., operational and regulatory reports; 4. Adequate procedures to safeguard and manage assets; and 5. Compliance... concentrations; and 6. Provide periodic asset reports with adequate information for management and the board of... and operations; 3. Assess the source, volatility, and sustainability of earnings, including the effect...

12 CFR Appendix D-1 to Part 208 - Interagency Guidelines Establishing Standards for Safety and Soundness

Code of Federal Regulations, 2010 CFR

2010-01-01

..., operational and regulatory reports; 4. Adequate procedures to safeguard and manage assets; and 5. Compliance... concentrations; and 6. Provide periodic asset reports with adequate information for management and the board of... and operations; 3. Assess the source, volatility, and sustainability of earnings, including the effect...

77 FR 27055 - National and Governmental Advisory Committees to the U.S. Representative to the Commission for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-08

... authorized under Articles 17 and 18 of the North American Agreement on Environmental Cooperation (NAAEC... strategic, scientific, technological, regulatory, and economic issues related to implementation and further... addressing the draft Guidelines for Submissions on Enforcement Matters under Articles 14 and 15 of the NAAEC...

50 CFR 679.31 - CDQ and PSQ reserves.

Code of Federal Regulations, 2010 CFR

2010-10-01

... point where the boundary of the IPHC regulatory area intersects land. (3) Crab CDQ reserves. Crab CDQ reserves for crab species governed by the Crab Rationalization Program are specified at § 680.40 (a)(1). For Norton Sound red king crab, 7.5 percent of the guideline harvest level specified by the State of...

50 CFR 679.31 - CDQ and PSQ reserves.

Code of Federal Regulations, 2011 CFR

2011-10-01

... point where the boundary of the IPHC regulatory area intersects land. (3) Crab CDQ reserves. Crab CDQ reserves for crab species governed by the Crab Rationalization Program are specified at § 680.40 (a)(1). For Norton Sound red king crab, 7.5 percent of the guideline harvest level specified by the State of...

76 FR 52355 - NUREG-1482, Revision 2, “Guidelines for Inservice Testing at Nuclear Power Plants, Draft Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-22

... Testing at Nuclear Power Plants, Draft Report for Comment'' AGENCY: Nuclear Regulatory Commission. ACTION... Testing at Nuclear Power Plants, Draft Report for Comment,'' and subtitled ``Inservice Testing of Pumps and Valves, and Inservice Examination and Testing of Dynamic Restraints (Snubbers) at Nuclear Power...

75 FR 22169 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-27

... election of directors. Under the Corporation's corporate governance guidelines previously adopted by the... resignation to the Nominating and Governance Committee of the Board (or another committee designated by the... resignation would not participate in the recommendation by the Nominating and Governance Committee or the...

Evaluating Crude Oil Chemical Dispersion Efficacy In A Flow-Through Wave Tank Under Regular Non-Breaking Wave And Breaking Wave Conditions

EPA Science Inventory

Testing dispersant effectiveness under conditions similar to that of the open environment is required for improvements in operational procedures and the formulation of regulatory guidelines. To this end, a novel wave tank facility was fabricated to study the dispersion of crude ...

Access to F.D.A. Information.

ERIC Educational Resources Information Center

Sinovic, Dianna

Prior to the enactment of the Freedom of Information Act (FOIA), little of the data collected by the Food and Drug Administration (FDA) was made public or could be obtained from the agency. Although the FDA files are now open, information is considered exempt from public disclosure when it involves regulatory procedures, program guidelines, work…

Listening to the Noise: Random Fluctuations Reveal Gene Network Parameters

NASA Astrophysics Data System (ADS)

Munsky, Brian; Trinh, Brooke; Khammash, Mustafa

2010-03-01

The cellular environment is abuzz with noise originating from the inherent random motion of reacting molecules in the living cell. In this noisy environment, clonal cell populations exhibit cell-to-cell variability that can manifest significant prototypical differences. Noise induced stochastic fluctuations in cellular constituents can be measured and their statistics quantified using flow cytometry, single molecule fluorescence in situ hybridization, time lapse fluorescence microscopy and other single cell and single molecule measurement techniques. We show that these random fluctuations carry within them valuable information about the underlying genetic network. Far from being a nuisance, the ever-present cellular noise acts as a rich source of excitation that, when processed through a gene network, carries its distinctive fingerprint that encodes a wealth of information about that network. We demonstrate that in some cases the analysis of these random fluctuations enables the full identification of network parameters, including those that may otherwise be difficult to measure. We use theoretical investigations to establish experimental guidelines for the identification of gene regulatory networks, and we apply these guideline to experimentally identify predictive models for different regulatory mechanisms in bacteria and yeast.

Guidelines for performing systematic reviews in the development of toxicity factors.

PubMed

Schaefer, Heather R; Myers, Jessica L

2017-12-01

The Texas Commission on Environmental Quality (TCEQ) developed guidance on conducting systematic reviews during the development of chemical-specific toxicity factors. Using elements from publicly available frameworks, the TCEQ systematic review process was developed in order to supplement the existing TCEQ Guidelines for developing toxicity factors (TCEQ Regulatory Guidance 442). The TCEQ systematic review process includes six steps: 1) Problem Formulation; 2) Systematic Literature Review and Study Selection; 3) Data Extraction; 4) Study Quality and Risk of Bias Assessment; 5) Evidence Integration and Endpoint Determination; and 6) Confidence Rating. This document provides guidance on conducting a systematic literature review and integrating evidence from different data streams when developing chemical-specific reference values (ReVs) and unit risk factors (URFs). However, this process can also be modified or expanded to address other questions that would benefit from systematic review practices. The systematic review and evidence integration framework can improve regulatory decision-making processes, increase transparency, minimize bias, improve consistency between different risk assessments, and further improve confidence in toxicity factor development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A practical guideline for identifying research intent with projects that collect private, identifiable health information.

PubMed

Amdur, Robert J; Speers, Marjorie A

2003-06-01

Radiation oncologists frequently engage in activities that involve the collection and analysis of data from medical records. Access to health information is an ethical issue because, if not done according to appropriate guidelines, it constitutes an invasion of privacy or breach in confidentiality. To protect patients for the social harm that may result from medical record review, our society has established laws and regulations that apply to projects that require medical record review. A major branch point in the guidelines for such projects is whether private information will be collected for research or nonresearch purposes. However, a problem with discussing privacy protection in terms of a research versus nonresearch model is that it is difficult to make this distinction for many kinds of projects. The purpose of this paper is to establish a practical guideline that can be used to decide if a project that involves analysis of private, identifiable medical information should be considered research from the regulatory standpoint.

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Fiftieth report.

PubMed

2016-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use. Good pharmacopoeial practices; FIP-WHO technical guidelines: points to consider in the provision by health-care professionals of children-specific preparations that are not available as authorized products; Guidance on good manufacturing practices for biological products; Guidance on good manufacturing practices: inspection report, including Appendix 1: Model inspection report; Guidance on good data and record management practices; Good trade and distribution practices for starting materials; Guidelines on the conduct of surveys of the quality of medicines; Collaborative procedure between the World Health Organization (WHO) prequalification team and national regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products and vaccines; Guidance for organizations performing in vivo bioequivalence studies; and World Health Organization (WHO) general guidance on variations to multisource pharmaceutical products.

Methodology for clinical trials involving patients with cancer who have febrile neutropenia: updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies.

PubMed

Feld, Ronald; Paesmans, Marianne; Freifeld, Alison G; Klastersky, Jean; Pizzo, Philip A; Rolston, Kenneth V I; Rubenstein, Edward; Talcott, James A; Walsh, Thomas J

2002-12-15

Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i.e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy.

Informed consent in human subject research: a comparison of current international and Nigerian guidelines.

PubMed

Fadare, Joseph O; Porteri, Corinna

2010-03-01

Informed consent is a basic requirement for the conduct of ethical research involving human subjects. Currently, the Helsinki Declaration of the World Medical Association and the International Ethical Guidelines for Biomedical Research of the Council for International Organizations of Medical Sciences (CIOMS) are widely accepted as international codes regulating human subject research and the informed consent sections of these documents are quite important. Debates on the applicability of these guidelines in different socio-cultural settings are ongoing and many workers have advocated the need for national or regional guidelines. Nigeria, a developing country, has recently adopted its national guideline regulating human subject research: the National Health Research Ethics Committee (NHREC) code. A content analysis of the three guidelines was done to see if the Nigerian guidelines confer any additional protection for research subjects. The concept of a Community Advisory Committee in the Nigerian guideline is a novel one that emphasizes research as a community burden and should promote a form of "research friendship" to foster the welfare of research participants. There is also the need for a regular update of the NHREC code so as to address some issues that were not considered in its current version.

Developmental Neurotoxicology: History and Outline of ...

EPA Pesticide Factsheets

The present work provides a brief review of basic concepts in developmental neurotoxicology, as well as current representative testing guidelines for evaluating developmental neurotoxicity (DNT) of xenobiotics. Historically, DNT was initially recognized as a “functional” teratogenicity: the main concern was that prenatal and/or early postnatal exposures to chemicals during critical periods of central nervous system (CNS) development would cause later functional abnormalities of the brain. Current internationally harmonized DNT study guidelines are thus intended to predict adverse effects of test compounds on the developing CNS by observing such postnatal parameters as motor activity, startle response, and learning and memory, as well as neropathological alterations. The reliability of current DNT study guidelines and sensitivity of testing methodologies recommended in these guidelines have been confirmed by retrospective evaluations of the many international and domestic collaborative validation studies in developed nations including Japan. Invited review with brief review of basic concepts in developmental neurotoxicology, as well as current representative testing guidelines for evaluating developmental neurotoxicity (DNT) of xenobiotics.

A Comparison of Current Guidelines of Five International Societies on Clostridium difficile Infection Management.

PubMed

Fehér, Csaba; Mensa, Josep

2016-09-01

Clostridium difficile infection (CDI) is increasingly recognized as an emerging healthcare problem of elevated importance. Prevention and treatment strategies are constantly evolving along with the apperance of new scientific evidence and novel treatment methods, which is well-reflected in the differences among consecutive international guidelines. In this article, we summarize and compare current guidelines of five international medical societies on CDI management, and discuss some of the controversial and currently unresolved aspects which should be addressed by future research.

Implementation of a commercial-grade dedication program - Benefits and lessons learned

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrington, M.; MacFarlane, I.

1991-01-01

The recent issuance of industry guidelines, the Nuclear Management and Resources Council procurement initiative, and a US Nuclear Regulatory Commission NRC generic letter on commercial-grade item dedication (CGD) has been viewed by many utility managers and executives as only adding to the existing burden of compliance with regulatory requirements. While the incorporation of these documents into existing CGD programs has created additional costs, the resulting enhanced dedication programs have also produced benefits beyond regulatory compliance, and some lessons have been learned. This paper discusses the benefits and the lessons learned during implementation of an enhanced CGD program at New Hampshiremore » Yankee's (NHY's) Seabrook nuclear plant. Based on NHY's experience, it is believed that the benefits described in this paper can be realized by other utilities implementing CGD programs.« less

Management of Naturally Occurring Radioactive Materials (NORM) in Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baweja, Anar S.; Tracy, Bliss L.

2008-08-07

In Canada, nuclear and radiological regulatory responsibilities are shared between the provinces/territories and the federal government. The Canadian Nuclear Safety Commission (CNSC) regulates nuclear fuel cycle materials and man-made radionuclides under the Nuclear Safety and Control Act (2000). The provinces and territories regulate NORM arising from industrial activities, not involving the nuclear fuel cycle materials. Present guideline--Canadian Guidelines for the Management of Naturally Occurring Radioactive Materials (NORM)--was published in 2000 in order to bring uniformity to the management of NORM-related procedures to provide adequate radiation protection for workers and the general public. The basic premise of these guidelines is thatmore » the NORM-related activities should not be posing any greater hazard than those activities regulated under the Nuclear Safety and Control Act; these concepts are described in this paper.« less

Adherence to current guidelines for chronic obstructive pulmonary disease (COPD) among patients treated with combination of long-acting bronchodilators or inhaled corticosteroids

PubMed Central

Asche, Carl Victor; Leader, Shelah; Plauschinat, Craig; Raparla, Swetha; Yan, Ming; Ye, Xiangyang; Young, Dave

2012-01-01

Background To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS). Methods The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007. The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS. Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data. We examined the baseline characteristics of these patients along with their healthcare resource utilization. Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines. Results A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results. The adherent subgroup received COPD medications consistent with current GOLD guidelines. Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines. In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines. In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines. GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts. Conclusion Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD. Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers. PMID:22500120

Direct-to-Consumer Broadcast Advertisements for Pharmaceuticals: Off-Label Promotion and Adherence to FDA Guidelines.

PubMed

Klara, Kristina; Kim, Jeanie; Ross, Joseph S

2018-05-01

Direct-to-consumer (DTC) advertisements for prescription drugs in the United States are regulated by the Food and Drug Administration (FDA). Off-label promotion, or the advertisement of a drug for an indication not approved by the FDA, is prohibited. Our objective was to examine the presence of off-label promotion in broadcast DTC ads and to assess their adherence to FDA guidelines mandating fair balance in presentation of risks and benefits and prohibiting misleading advertisement claims. All English-language broadcast DTC ads for prescription drugs that aired in the United States from January 2015 to July 2016 were obtained from AdPharm, an online collection of healthcare advertisements. Ad length was measured and adherence to FDA guidelines was assessed for several categories: key regulatory items, indicators of false or misleading ads, and indicators of fair balance in presentation of risks and benefits. Our sample included 97 unique DTC ads, representing 60 unique drugs and 67 unique drug-indication combinations. No ads described drug risks quantitatively, whereas drug efficacy was presented quantitatively in 25 (26%) ads. Thirteen (13%) ads, all for diabetes medications, suggested off-label uses for weight loss and blood pressure reduction. The most commonly advertised drugs were indicated for the treatment of inflammatory conditions (n = 12; 18%), diabetes or diabetic neuropathy (n = 11; 16%), bowel or bladder dysfunction (n = 6; 9%), and infections or allergic reaction (n = 6; 9%). More than three-quarters (n = 51; 76%) advertised drugs to treat chronic conditions. Few broadcast DTC ads were fully compliant with FDA guidelines. The overall quality of information provided in ads was low, and suggestions of off-label promotion were common for diabetes medications. The impact of current DTC ads and off-label marketing on patient and prescriber decisions merits further scrutiny.

Variability in delivered dose and respirable delivered dose from nebulizers: are current regulatory testing guidelines sufficient to produce meaningful information?

PubMed

Hatley, Ross Hm; Byrne, Sarah M

2017-01-01

To improve convenience to patients, there have been advances in the operation of nebulizers, resulting in fast treatment times and less drug lost to the environment. However, limited attention has been paid to the effects of these developments on the delivered dose (DD) and respirable delivered dose (RDD). Published pharmacopoeia and ISO testing guidelines for adult-use testing utilize a single breathing pattern, which may not be sufficient to enable effective comparisons between the devices. The DD of 5 mg of salbutamol sulfate into adult breathing patterns with inhalation:exhalation (I:E) ratios between 1:1 and 1:4 was determined. Droplet size was determined by laser diffraction and RDD calculated. Nine different nebulizer brands with different modes of operation (conventional, venturi, breath-enhanced, mesh, and breath-activated) were tested. Between the non-breath-activated nebulizers, a 2.5-fold difference in DD (~750-1,900 µg salbutamol) was found; with RDD, there was a more than fourfold difference (~210-980 µg). With increasing time spent on exhalation, there were progressive reductions in DD and RDD, with the RDD at an I:E ratio of 1:4 being as little as 40% of the dose with the 1:1 I:E ratio. The DD and RDD from the breath-activated mesh nebulizer were independent of the I:E ratio, and for the breath-activated jet nebulizer, there was less than 20% change in RDD between the I:E ratios of 1:1 and 1:4. Comparing nebulizers using the I:E ratio recommended in the guidelines does not predict relative performance between the devices at other ratios. There was significant variance in DD or RDD between different brands of non-breath-activated nebulizer. In future, consideration should be given to revision of the test protocols included in the guidelines, to reflect more accurately the potential therapeutic dose that is delivered to a realistic spectrum of breathing patterns.

75 FR 45685 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... list (see current List 7 titled Misrepresentation/Omissions, List 9 titled Negligence/Breach of... claims alleging misrepresentation/ omissions (see current List 8, Item 1), negligence/breach of fiduciary... claims alleging misrepresentation/ omission (see current List 8, Item 2), negligence/breach of fiduciary...

Regulatory considerations in application of encapsulated cell therapies.

PubMed

van Zanten, J; de Vos, Paul

2010-01-01

The encapsulation of tissue in semi-permeable membranes is a technology with high potential and in due time several new therapies based on this technology will be tested in clinical trials. Recent, new legislation requires that these investigational medicinal products used in clinical trials Phase I must be produced according to Good Manufacturing Practice (GMP). Consequently, the activities of GMP are expanding to the field of research and researchers might need to change developed protocols in order to meet GMP legislation. This chapters gives an overview of the overall guidelines covering GMP and more specific guidelines dealing with cell based therapies and gene therapy.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2011-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: procedure for adoption of International Chemical Reference Substances; WHO good practices for pharmaceutical microbiology laboratories; good manufacturing practices: main principles for pharmaceutical products; good manufacturing practices for blood establishments (jointly with the Expert Committee on Biological Standardization); guidelines on good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms; good manufacturing practices for sterile pharmaceutical products; guidelines on transfer of technology in pharmaceutical manufacturing; good pharmacy practice: standards for quality of pharmacy services (joint FIP/WHO); model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products (jointly with the Expert Committee on Biological Standardization); procedure for prequalification of pharmaceutical products; guide on submission of documentation for prequalification of innovator finished pharmaceutical products approved by stringent regulatory authorities; prequalification of quality control laboratories: procedure for assessing the acceptability, in principle, of quality control laboratories for use by United Nations agencies; guidelines for preparing a laboratory information file; guidelines for drafting a site master file; guidelines on submission of documentation for a multisource (generic) finished product: general format: preparation of product dossiers in common technical document format.

Clinical imaging guidelines part 4: challenges in identifying, engaging and collaborating with stakeholders.

PubMed

Bettmann, Michael A; Oikarinen, Helja; Rehani, Madan; Holmberg, Ola; del Rosario Perez, Maria; Naidoo, Anusha; Do, Kyung-Hyun; Dreyer, Keith; Ebdon-Jackson, Steve

2015-04-01

The effective development and use of clinical imaging guidelines requires an understanding of who the stakeholders are, what their interests in the process are, and what roles they should play. If the appropriate stakeholders are not engaged in the right roles, it is unlikely that clinical imaging guidelines will be successfully developed, relied on, and actually used. Some stakeholders are obvious: for the development of clinical imaging guidelines, both imagers and those who request examinations, such as general practitioners, internists, and medical specialists, must be involved. To gain acceptance, other relevant groups are stakeholders, including medical societies, other health care professionals, insurers, health IT experts and vendors, and patients. The role of stakeholders must be dictated by their specific interest. For some, involvement in the creation of guidelines is the right role. For others, such as regulators or insurers, reviews or invitations to comment are required, and for others, such as medical educators, it is probably sufficient to provide information and create awareness. Only through a careful consideration of who the stakeholders are and what are their interests are the successful development, acceptance, and use of clinical imaging guidelines likely to occur. Future efforts must focus on collaboration, particularly among groups that create clinical imaging guidelines and those that can support their use, and on regulatory roles and mandates. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Steam Generator tube integrity -- US Nuclear Regulatory Commission perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, E.L.; Sullivan, E.J.

1997-02-01

In the US, the current regulatory framework was developed in the 1970s when general wall thinning was the dominant degradation mechanism; and, as a result of changes in the forms of degradation being observed and improvements in inspection and tube repair technology, the regulatory framework needs to be updated. Operating experience indicates that the current U.S. requirements should be more stringent in some areas, while in other areas they are overly conservative. To date, this situation has been dealt with on a plant-specific basis in the US. However, the NRC staff is now developing a proposed steam generator rule asmore » a generic framework for ensuring that the steam generator tubes are capable of performing their intended safety functions. This paper discusses the current U.S. regulatory framework for assuring steam generator (SG) tube integrity, the need to update this regulatory framework, the objectives of the new proposed rule, the US Nuclear Regulatory Commission (NRC) regulatory guide (RG) that will accompany the rule, how risk considerations affect the development of the new rule, and some outstanding issues relating to the rule that the NRC is still dealing with.« less

When should acute exacerbations of COPD be treated with systemic corticosteroids and antibiotics in primary care: a systematic review of current COPD guidelines.

PubMed

Laue, Johanna; Reierth, Eirik; Melbye, Hasse

2015-02-19

Not all patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) benefit from treatment with systemic corticosteroids and antibiotics. The aim of the study was to identify criteria recommended in current COPD guidelines for treating acute exacerbations with systemic corticosteroids and antibiotics and to assess the underlying evidence. Current COPD guidelines were identified by a systematic literature search. The most recent guidelines as per country/organisation containing recommendations about treating acute exacerbations of COPD were included. Guideline development and criteria for treating acute exacerbations with systemic corticosteroids and antibiotics were appraised. Randomised controlled trials directly referred to in context with the recommendations were evaluated in terms of study design, setting, and study population. A total of 19 COPD guidelines were included. Systemic corticosteroids were often universally recommended to all patients with acute exacerbations. Criteria for treatment with antibiotics were mainly an increase in respiratory symptoms. Objective diagnostic tests or clinical examination were only rarely recommended. Only few criteria were directly linked to underlying evidence, and the trial patients represented a highly specific group of COPD patients. Current COPD guidelines are of little help in primary care to identify patients with acute exacerbations probably benefitting from treatment with systemic corticosteroids and antibiotics in primary care, and might contribute to overuse or inappropriate use of either treatment.

Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening.

PubMed

Smith, Robert A; Andrews, Kimberly S; Brooks, Durado; Fedewa, Stacey A; Manassaram-Baptiste, Deana; Saslow, Debbie; Brawley, Otis W; Wender, Richard C

2018-05-30

Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates from the National Health Interview Survey, and select issues related to cancer screening. In this 2018 update, we also summarize the new American Cancer Society colorectal cancer screening guideline and include a clarification in the language of the 2013 lung cancer screening guideline. CA Cancer J Clin 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

ENERGY STAR® Retail Products Platform (RPP): Conditions and Considerations in Evaluating Market Transformation Programs and Evaluation Guidance for RPP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Michael; Banwell, Peter

2018-01-09

The purpose of this guide is to provide a resource for state utility regulators, utilities, the evaluation community and regulatory stakeholders on methods to measure energy savings from the ENERGY STAR Retail Products Platform (link is external). The guidelines outlined in this document were developed by evaluation experts.

Termiticide testing in full swing USDA-FS's Mississippi site hit hard by hurricane katrina

Treesearch

Terry Wagner; Joe Mulrooney; Thomas Shelton

2006-01-01

The USDA-FS wrote and administered 44 termiticide testing agreements with industry; Hurricane Katrina hit hard the oldest U.S. Forest Service test sitel and the Termiticide Standards Committee of the Association of Structural PEst Control Regulatory Officials proposed a revision of the EPA's Product Performance Test Guideline, OPPTS 810.3600.

77 FR 71469 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-30

... Auction Process. \\4\\ See NYSE Arca Options Rule 6.37(b)(1). The big-ask [sic] guidelines specified in Rule... subject to a standard- width quote requirement puts the Exchange at a competitive disadvantage to other... Interested persons are invited to submit written data, views, and arguments concerning the foregoing...

In Brief: Carbon Sequestration Partnerships; Review of Peer Reviews

NASA Astrophysics Data System (ADS)

Showstack, Randy

The U.S. Department of Energy named seven regional partnerships on 16 August to study the best methods for the non-biological sequestration of carbon in different parts of the country.Peer review guidelines for science issued by the federal government which is related to regulatory topics could be tightened up under a 29 August White House proposal.

77 FR 31655 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-29

... controverted. In addition, the requestor/petitioner shall provide a brief explanation of the bases for the... against burst, as discussed in Regulatory Guide (RG) 1.121, ``Bases for Plugging Degraded PWR [Pressurized... Institute] 97-06, Revision 3, ``Steam Generator Program Guidelines'' (Reference 1) and RG 1.121, ``Bases for...

Review of invertebrate biological control agent regulation in Australia, New Zealand, Canada and the USA: recommendations for a harmonized European system

USDA-ARS?s Scientific Manuscript database

Europe lags far behind Australia, New Zealand, Canada and the USA in terms of implementing regulatory procedures for the import and release of invertebrate biological control agents (IBCAs). A number of standards, documents and guidelines have been produced over recent years in an attempt to harmon...

12 CFR Appendix B to Part 225 - Capital Adequacy Guidelines for Bank Holding Companies and State Member Banks: Leverage Measure

Code of Federal Regulations, 2012 CFR

2012-01-01

... analysis of applications acted upon by the Federal Reserve. The Board of Governors will review the... or State regulatory agencies for similar firms that are not affiliated with banking organizations, or... ratio falls will normally trigger the following supervisory responses, subject to qualitative analysis...

12 CFR Appendix B to Part 225 - Capital Adequacy Guidelines for Bank Holding Companies and State Member Banks: Leverage Measure

Code of Federal Regulations, 2011 CFR

2011-01-01

... analysis of applications acted upon by the Federal Reserve. The Board of Governors will review the... or State regulatory agencies for similar firms that are not affiliated with banking organizations, or... ratio falls will normally trigger the following supervisory responses, subject to qualitative analysis...

12 CFR Appendix B to Part 225 - Capital Adequacy Guidelines for Bank Holding Companies and State Member Banks: Leverage Measure

Code of Federal Regulations, 2013 CFR

2013-01-01

... analysis of applications acted upon by the Federal Reserve. The Board of Governors will review the... or State regulatory agencies for similar firms that are not affiliated with banking organizations, or... ratio falls will normally trigger the following supervisory responses, subject to qualitative analysis...

77 FR 16990 - Notification of Submission to the Secretary of Agriculture of Two Draft Regulatory Documents...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-23

... and Applicability; Clarification and Availability of Test Guideline''; and the second is entitled... Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4...) 305-5805. FOR FURTHER INFORMATION CONTACT: Rose Kyprianou, Field and External Affairs Division (7506P...

Opioid analgesic use in Australia and The Netherlands: a cross-country comparison.

PubMed

Wagemaakers, Francisca N; Hollingworth, Samantha A; Kreijkamp-Kaspers, Sanne; Tee, Ernest H L; Leendertse, Anne J; van Driel, Mieke L

2017-08-01

Background Increasing use of opioid analgesics (OA) has been reported worldwide. Objective To compare the use of OA in two countries in order to better understand these trends. Setting Outpatient settings in Australia and The Netherlands. Method We analysed publicly available government data on outpatient OA dispensing over 15 years (2000-2014). We compared dispensing trends for specific OA and explored medical (national clinical guidelines), contextual and policy-related factors to explain differences in use between the two countries. Main outcome measure OA prescribing in Australia and The Netherlands, absolute volume of use, preferred types of opioids and changes over time. Results The average annual increase in OA prescribing was 10% in Australia and 8% in The Netherlands between 2000 and 2014. In 2014, the total use of OA was 10.0 daily defined doses (DDD)/1000 population/day in Australia and 9.4 DDD/1000 population/day in The Netherlands. In Australia, the most commonly prescribed opioids were oxycodone and tramadol, compared to fentanyl and tramadol in The Netherlands. We found differences in prescribing guidelines, culture of prescribing and regulatory frameworks that could explain some of the observed differences. Conclusion OA prescribing has increased remarkably in both countries between 2000 and 2014 but the types of prescribed OA vary. Differences in national evidence-based guidelines influenced the types of OA used. Prescribing culture as well as regulatory policies and costs, may also contribute to the different patterns of OA use.

Comparative analysis of dietary guidelines in the Spanish-Speaking Caribbean.

PubMed

Fuster, Melissa

2016-03-01

Dietary guidelines are important education and policy tools to address local nutrition concerns. The current paper presents a comparative analysis of nutrition messages from three Spanish-speaking Caribbean countries (Cuba, Puerto Rico and Dominican Republic) to explore how these dietary guidelines address common public health nutrition concerns, contextualized in different changing food environments and food culture similarities. Qualitative, comparative analysis of current dietary guideline documents and key recommendations. Key recommendations were categorized into sixteen themes (two diet-based, ten food-based and four 'other'). Only the Cuban dietary guidelines included diet-based key recommendations. Of the ten food-based key recommendations, only four themes overlapped across the three dietary guidelines (the encouragement of fruits and vegetables, addressing protein sources and fat). Other overlaps were found between dietary guideline pairs, except between Cuba and Puerto Rico. Further analysis revealed differences in levels of specificity and acknowledgement of local dietary patterns and issues, as well as the need to revise the guidelines to account for current scientific advances. The present study underscored the importance of context in the framing of dietary advice and the influence of national socio-economic and political situations on nutrition policy and education efforts. The results contribute to inform efforts to improve nutrition communication in the region and among migrant communities.

Comparing the costs of three prostate cancer follow-up strategies: a cost minimisation analysis.

PubMed

Pearce, Alison M; Ryan, Fay; Drummond, Frances J; Thomas, Audrey Alforque; Timmons, Aileen; Sharp, Linda

2016-02-01

Prostate cancer follow-up is traditionally provided by clinicians in a hospital setting. Growing numbers of prostate cancer survivors mean that this model of care may not be economically sustainable, and a number of alternative approaches have been suggested. The aim of this study was to develop an economic model to compare the costs of three alternative strategies for prostate cancer follow-up in Ireland-the European Association of Urology (EAU) guidelines, the National Institute of Health Care Excellence (NICE) guidelines and current practice. A cost minimisation analysis was performed using a Markov model with three arms (EAU guidelines, NICE guidelines and current practice) comparing follow-up for men with prostate cancer treated with curative intent. The model took a health care payer's perspective over a 10-year time horizon. Current practice was the least cost efficient arm of the model, the NICE guidelines were most cost efficient (74 % of current practice costs) and the EAU guidelines intermediate (92 % of current practice costs). For the 2562 new cases of prostate cancer diagnosed in 2009, the Irish health care system could have saved €760,000 over a 10-year period if the NICE guidelines were adopted. This is the first study investigating costs of prostate cancer follow-up in the Irish setting. While economic models are designed as a simplification of complex real-world situations, these results suggest potential for significant savings within the Irish health care system associated with implementation of alternative models of prostate cancer follow-up care.