Sample records for acceptable regulatory limits

  1. 78 FR 28896 - Design Limits and Loading Combinations for Metal Primary Reactor Containment System Components

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0095] Design Limits and Loading Combinations for Metal... Regulatory Guide (RG) 1.57, ``Design Limits and Loading Combinations for Metal Primary Reactor Containment... the NRC staff considers acceptable for design limits and loading combinations for metal primary...

  2. 10 CFR 2.643 - Acceptance and docketing of application for limited work authorization.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... acceptable for processing, the Director of New Reactors or the Director of Nuclear Reactor Regulation will... 10 Energy 1 2013-01-01 2013-01-01 false Acceptance and docketing of application for limited work authorization. 2.643 Section 2.643 Energy NUCLEAR REGULATORY COMMISSION AGENCY RULES OF PRACTICE AND PROCEDURE...

  3. 10 CFR 2.643 - Acceptance and docketing of application for limited work authorization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Acceptance and docketing of application for limited work authorization. 2.643 Section 2.643 Energy NUCLEAR REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING... Construct Certain Utilization Facilities; and Advance Issuance of Limited Work Authorizations Phased...

  4. Legitimization of regulatory norms: Waterfowl hunter acceptance of changing duck bag limits

    USGS Publications Warehouse

    Schroeder, Susan A.; Fulton, David C.; Lawrence, Jeffrey S.; Cordts, Steven D.

    2014-01-01

    Few studies have examined response to regulatory change over time, or addressed hunter attitudes about changes in hunting bag limits. This article explores Minnesota waterfowl hunters’ attitudes about duck bag limits, examining attitudes about two state duck bag limits that were initially more restrictive than the maximum set by the U.S. Fish and Wildlife Service (USFWS), but then increased to match federal limits. Results are from four mail surveys that examined attitudes about bag limits over time. Following two bag limit increases, a greater proportion of hunters rated the new bag limit “too high” and a smaller proportion rated it “too low.” Several years following the first bag limit increase, the proportion of hunters who indicated that the limit was “too high” had declined, suggesting hunter acceptance of the new regulation. Results suggest that waterfowl bag limits may represent legal norms that influence hunter attitudes and gain legitimacy over time.

  5. The acceptance of in silico models for REACH: Requirements, barriers, and perspectives

    PubMed Central

    2011-01-01

    In silico models have prompted considerable interest and debate because of their potential value in predicting the properties of chemical substances for regulatory purposes. The European REACH legislation promotes innovation and encourages the use of alternative methods, but in practice the use of in silico models is still very limited. There are many stakeholders influencing the regulatory trajectory of quantitative structure-activity relationships (QSAR) models, including regulators, industry, model developers and consultants. Here we outline some of the issues and challenges involved in the acceptance of these methods for regulatory purposes. PMID:21982269

  6. 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.

  7. 17 CFR 240.13b2-2 - Representations and conduct in connection with the preparation of required reports and documents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... misleading” include, but are not limited to, actions taken at any time with respect to the professional... material violations of generally accepted accounting principles, generally accepted auditing standards, or other professional or regulatory standards); (ii) Not to perform audit, review or other procedures...

  8. 17 CFR 240.13b2-2 - Representations and conduct in connection with the preparation of required reports and documents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... misleading” include, but are not limited to, actions taken at any time with respect to the professional... material violations of generally accepted accounting principles, generally accepted auditing standards, or other professional or regulatory standards); (ii) Not to perform audit, review or other procedures...

  9. 17 CFR 240.13b2-2 - Representations and conduct in connection with the preparation of required reports and documents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... misleading” include, but are not limited to, actions taken at any time with respect to the professional... material violations of generally accepted accounting principles, generally accepted auditing standards, or other professional or regulatory standards); (ii) Not to perform audit, review or other procedures...

  10. 17 CFR 240.13b2-2 - Representations and conduct in connection with the preparation of required reports and documents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... misleading” include, but are not limited to, actions taken at any time with respect to the professional... material violations of generally accepted accounting principles, generally accepted auditing standards, or other professional or regulatory standards); (ii) Not to perform audit, review or other procedures...

  11. 17 CFR 240.13b2-2 - Representations and conduct in connection with the preparation of required reports and documents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... misleading” include, but are not limited to, actions taken at any time with respect to the professional... material violations of generally accepted accounting principles, generally accepted auditing standards, or other professional or regulatory standards); (ii) Not to perform audit, review or other procedures...

  12. 77 FR 76325 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-27

    ... Rule Change Relating to the Acceptance of Letters of Credit or Pass-Through Letters of Credit Deposits... accept Letters of Credit as permitted cover for certain clearing members for cleared energy futures. As part of the update to the Permitted Cover, ICE Clear Europe will consider new requests to use Letters...

  13. 10 CFR 2.643 - Acceptance and docketing of application for limited work authorization.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... § 2.101(a)(9) is incomplete and not acceptable for processing, the Director of New Reactors or the Director of Nuclear Reactor Regulation will inform the applicant of this determination and the respects in... authorization. 2.643 Section 2.643 Energy NUCLEAR REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING...

  14. Quality control for federal clean water act and safe drinking water act regulatory compliance.

    PubMed

    Askew, Ed

    2013-01-01

    QC sample results are required in order to have confidence in the results from analytical tests. Some of the AOAC water methods include specific QC procedures, frequencies, and acceptance criteria. These are considered to be the minimum controls needed to perform the method successfully. Some regulatory programs, such as those in 40 CFR Part 136.7, require additional QC or have alternative acceptance limits. Essential QC measures include method calibration, reagent standardization, assessment of each analyst's capabilities, analysis of blind check samples, determination of the method's sensitivity (method detection level or quantification limit), and daily evaluation of bias, precision, and the presence of laboratory contamination or other analytical interference. The details of these procedures, their performance frequency, and expected ranges of results are set out in this manuscript. The specific regulatory requirements of 40 CFR Part 136.7 for the Clean Water Act, the laboratory certification requirements of 40 CFR Part 141 for the Safe Drinking Water Act, and the ISO 17025 accreditation requirements under The NELAC Institute are listed.

  15. The limits of regulatory toxicology

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

    Carrington, Clark D.; Bolger, P. Michael, E-mail: mike.bolger@fda.hhs.go

    2010-03-01

    The Acceptable Daily Intake (ADI) has been used by regulatory and public health organizations (e.g., the U.S. Food and Drug and Administration, and the World Health Organization) for chemicals for more than 50 years. The ADI concept was also initially employed at the U.S. Environmental Protection Agency at its inception in 1971, although with the adoption of newer terminology, it later became known as the Reference Dose (RfD). It is clear from the literature that both were first devised as instruments of regulatory policy. In the intervening years, it has become common to use language that implies that these standardsmore » are statements of scientific fact. Similarly, some of the discretionary or default values that are used to derive regulatory standards are represented as scientific assumptions when in fact they also represent regulatory policy. This confusion impedes both the best use of the available science and informed public participation in policy making. In addition, the misconception of the ADI or the RfD as statements of scientific fact may impede the consideration of alternative means to reduce exposure to chemicals that may be harmful, including regulatory measures that do not involve prescribing a regulatory concentration limit.« less

  16. Regulatory perspectives on acceptability testing of dosage forms in children.

    PubMed

    Kozarewicz, Piotr

    2014-08-05

    Current knowledge about the age-appropriateness of different dosage forms is still fragmented or limited. Applicants are asked to demonstrate that the target age group(s) can manage the dosage form or propose an alternative strategy. However, questions remain about how far the applicant must go and what percentage of patients must find the strategy 'acceptable'. The aim of this overview is to provide an update on current thinking and understanding of the problem, and discuss issues relating to the acceptability testing. This overview should be considered as means to start a wider discussion which hopefully will result in a harmonised, globally acceptable approach for confirmation of the acceptability in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. A MODE-OF-ACTION-BASED QSAR APPROACH TO IMPROVE UNDERSTANDING OF DEVELOPMENTAL TOXICITY

    EPA Science Inventory

    QSAR models of developmental toxicity (devtox) have met with limited regulatory acceptance due to the use of ill-defined endpoints, lack of biological interpretability, and poor model performance. More generally, the lack of biological inference of many QSAR models is often due t...

  18. Prediction of adaptive self-regulatory responses to arthritis pain anxiety in exercising adults: does pain acceptance matter?

    PubMed

    Cary, Miranda Ashley; Gyurcsik, Nancy C; Brawley, Lawrence R

    2015-01-01

    Exercising for ≥ 150 min/week is a recommended strategy for self-managing arthritis. However, exercise nonadherence is a problem. Arthritis pain anxiety may interfere with regular exercise. According to the fear-avoidance model, individuals may confront their pain anxiety by using adaptive self-regulatory responses (eg, changing exercise type or duration). Furthermore, the anxiety-self-regulatory responses relationship may vary as a function of individuals' pain acceptance levels. To investigate pain acceptance as a moderator of the pain anxiety-adaptive self-regulatory responses relationship. The secondary objective was to examine whether groups of patients who differed in meeting exercise recommendations also differed in pain-related and self-regulatory responses. Adults (mean [± SD] age 49.75 ± 13.88 years) with medically diagnosed arthritis completed online measures of arthritis pain-related variables and self-regulatory responses at baseline, and exercise participation two weeks later. Individuals meeting (n=87) and not meeting (n=49) exercise recommendations were identified. Hierarchical multiple regression analysis revealed that pain acceptance moderated the anxiety-adaptive self-regulatory responses relationship. When pain anxiety was lower, greater pain acceptance was associated with less frequent use of adaptive responses. When anxiety was higher, adaptive responses were used regardless of pain acceptance level. MANOVA findings revealed that participants meeting the recommended exercise dose reported significantly lower pain and pain anxiety, and greater pain acceptance (P<0.05) than those not meeting the dose. Greater pain acceptance may help individuals to focus their efforts to adapt to their pain anxiety only when it is higher, leaving self-regulatory capacity to cope with additional challenges to exercise adherence (eg, busy schedule).

  19. Prediction of adaptive self-regulatory responses to arthritis pain anxiety in exercising adults: Does pain acceptance matter?

    PubMed Central

    Cary, Miranda A; Gyurcsik, Nancy C; Brawley, Lawrence R

    2015-01-01

    BACKGROUND: Exercising for ≥150 min/week is a recommended strategy for self-managing arthritis. However, exercise nonadherence is a problem. Arthritis pain anxiety may interfere with regular exercise. According to the fear-avoidance model, individuals may confront their pain anxiety by using adaptive self-regulatory responses (eg, changing exercise type or duration). Furthermore, the anxiety-self-regulatory responses relationship may vary as a function of individuals’ pain acceptance levels. OBJECTIVES: To investigate pain acceptance as a moderator of the pain anxiety-adaptive self-regulatory responses relationship. The secondary objective was to examine whether groups of patients who differed in meeting exercise recommendations also differed in pain-related and self-regulatory responses. METHODS: Adults (mean [± SD] age 49.75±13.88 years) with medically diagnosed arthritis completed online measures of arthritis pain-related variables and self-regulatory responses at baseline, and exercise participation two weeks later. Individuals meeting (n=87) and not meeting (n=49) exercise recommendations were identified. RESULTS: Hierarchical multiple regression analysis revealed that pain acceptance moderated the anxiety-adaptive self-regulatory responses relationship. When pain anxiety was lower, greater pain acceptance was associated with less frequent use of adaptive responses. When anxiety was higher, adaptive responses were used regardless of pain acceptance level. MANOVA findings revealed that participants meeting the recommended exercise dose reported significantly lower pain and pain anxiety, and greater pain acceptance (P<0.05) than those not meeting the dose. CONCLUSIONS: Greater pain acceptance may help individuals to focus their efforts to adapt to their pain anxiety only when it is higher, leaving self-regulatory capacity to cope with additional challenges to exercise adherence (eg, busy schedule). PMID:25621990

  20. Knowledge sharing to facilitate regulatory decision-making in regard to alternatives to animal testing: Report of an EPAA workshop.

    PubMed

    Ramirez, Tzutzuy; Beken, Sonja; Chlebus, Magda; Ellis, Graham; Griesinger, Claudius; De Jonghe, Sandra; Manou, Irene; Mehling, Annette; Reisinger, Kerstin; Rossi, Laura H; van Benthem, Jan; van der Laan, Jan Willem; Weissenhorn, Renate; Sauer, Ursula G

    2015-10-01

    The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a workshop Knowledge sharing to facilitate regulatory decision-making. Fifty invited participants from the European Commission, national and European agencies and bodies, different industry sectors (chemicals, cosmetics, fragrances, pharmaceuticals, vaccines), and animal protection organizations attended the workshop. Four case studies exemplarily revealed which procedures are in place to obtain regulatory acceptance of new test methods in different sectors. Breakout groups discussed the status quo identifying the following facilitators for regulatory acceptance of alternatives to animal testing: Networking and communication (including cross-sector collaboration, international cooperation and harmonization); involvement of regulatory agencies from the initial stages of test method development on; certainty on prerequisites for test method acceptance including the establishment of specific criteria for regulatory acceptance. Data sharing and intellectual property issues affect many aspects of test method development, validation and regulatory acceptance. In principle, all activities should address replacement, reduction and refinement methods (albeit animal testing is generally prohibited in the cosmetics sector). Provision of financial resources and education support all activities aiming at facilitating the acceptance and use of alternatives to animal testing. Overall, workshop participants recommended building confidence in new methodologies by applying and gaining experience with them. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. The risks of risk aversion in drug regulation.

    PubMed

    Eichler, Hans-Georg; Bloechl-Daum, Brigitte; Brasseur, Daniel; Breckenridge, Alasdair; Leufkens, Hubert; Raine, June; Salmonson, Tomas; Schneider, Christian K; Rasi, Guido

    2013-12-01

    Drugs are approved by regulatory agencies on the basis of their assessment of whether the available evidence indicates that the benefits of the drug outweigh its risks. In recent years, regulatory agencies have been criticized both for being overly tolerant of risks or being excessively risk-averse, which reflects the challenge in determining an appropriate balance between benefit and risk with the limited data that is typically available before drug approval. The negative consequences of regulatory tolerance in allowing drugs onto the market that turn out to be unsafe are obvious, but the potential for adverse effects on public health owing to the absence of new drugs because of regulatory risk-aversion is less apparent. Here, we discuss the consequences of regulatory risk-aversion for public health and suggest what might be done to best align acceptance of risk and uncertainty by regulators with the interests of public health.

  2. Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: expert opinions on the state of affairs and the way forward.

    PubMed

    Schiffelers, Marie-Jeanne W A; Blaauboer, Bas J; Bakker, Wieger E; Beken, Sonja; Hendriksen, Coenraad F M; Koëter, Herman B W M; Krul, Cyrille

    2014-06-01

    Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being accepted for regulatory risk management purposes. This paper describes the barriers and drivers and options to optimize this acceptance process as identified by two expert panels, one on pharmaceuticals and one on chemicals. To untangle the complex acceptance process, the multilevel perspective on technology transitions is applied. This perspective defines influences at the micro-, meso- and macro level which need alignment to induce regulatory acceptance of a 3R model. This paper displays that there are many similar mechanisms within both sectors that prevent 3R models from becoming accepted for regulatory risk assessment and management. Shared barriers include the uncertainty about the value of the new 3R models (micro level), the lack of harmonization of regulatory requirements and acceptance criteria (meso level) and the high levels of risk aversion (macro level). In optimizing the process commitment, communication, cooperation and coordination are identified as critical drivers. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. 10 CFR 2.603 - Acceptance and docketing of application for early review of site suitability issues in a...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING PROCEEDINGS AND ISSUANCE OF ORDERS Additional... Issuance of Limited Work Authorizations Early Partial Decisions on Site Suitability-Construction Permit § 2... processing, the Director of the Office of New Reactors or the Director of the Office of Nuclear Reactor...

  4. 10 CFR 2.621 - Acceptance and docketing of application for early review of site suitability issues in a combined...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING PROCEEDINGS AND ISSUANCE OF ORDERS Additional... Issuance of Limited Work Authorizations Early Partial Decisions on Site Suitability-Combined License Under... Director of the Office of New Reactors or the Director of the Office of Nuclear Reactor Regulation, as...

  5. Wireless smart meters and public acceptance: the environment, limited choices, and precautionary politics.

    PubMed

    Hess, David J; Coley, Jonathan S

    2014-08-01

    Wireless smart meters (WSMs) promise numerous environmental benefits, but they have been installed without full consideration of public acceptance issues. Although societal-implications research and regulatory policy have focused on privacy, security, and accuracy issues, our research indicates that health concerns have played an important role in the public policy debates that have emerged in California. Regulatory bodies do not recognize non-thermal health effects for non-ionizing electromagnetic radiation, but both homeowners and counter-experts have contested the official assurances that WSMs pose no health risks. Similarities and differences with the existing social science literature on mobile phone masts are discussed, as are the broader political implications of framing an alternative policy based on an opt-out choice. The research suggests conditions under which health-oriented precautionary politics can be particularly effective, namely, if there is a mandatory technology, a network of counter-experts, and a broader context of democratic contestation.

  6. 78 FR 38411 - Vogtle Electric Generating Plant, Unit 4; Inspections, Tests, Analyses, and Acceptance Criteria

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    ... Plant, Unit 4; Inspections, Tests, Analyses, and Acceptance Criteria AGENCY: Nuclear Regulatory Commission. ACTION: Determination of inspections, tests, analyses, and acceptance criteria completion. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) staff has determined that the inspections, tests...

  7. 76 FR 23845 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-28

    ... draft guide in the agency's ``Regulatory Guide'' series. This series was developed to describe and make... approach that the staff of the NRC considers acceptable for use in developing an appropriate surveillance... steel. The recommendations described in this draft regulatory guide are an approach acceptable to the...

  8. Failure of the public health testing program for ballast water treatment systems.

    PubMed

    Cohen, Andrew N; Dobbs, Fred C

    2015-02-15

    Since 2004, an international testing program has certified 53 shipboard treatment systems as meeting ballast water discharge standards, including limits on certain microbes to prevent the spread of human pathogens. We determined how frequently certification tests failed a minimum requirement for a meaningful evaluation, that the concentration of microbes in the untreated (control) discharge must exceed the regulatory limit for treated discharges. In 95% of cases where the result was accepted as evidence that the treatment system reduced microbes to below the regulatory limit, the discharge met the limit even without treatment. This shows that the certification program for ballast water treatment systems is dysfunctional in protecting human health. In nearly all cases, the treatment systems would have equally well "passed" these tests even if they had never been turned on. Protocols must require minimum concentrations of targeted microbes in test waters, reflecting the upper range of concentrations in waters where ships operate. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. 77 FR 20452 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... of Acceptance, Waiver and Consent No. EAF0401000001 (MML Distributors, LLC) (Oct. 2005); NASD Letter of Acceptance, Waiver and Consent No. EAF0401240001 (AFSG Securities Corp.) (Oct. 2005); FINRA Letter...

  10. 12 CFR 363.1 - Scope and definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... accepted accounting principles for the insured depository institution or its holding company and financial statements prepared for regulatory reporting purposes. For recognition and measurement purposes, financial statements prepared for regulatory reporting purposes shall conform to generally accepted accounting...

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

    Metzler, D.; Gibb, J.P.; Glover, W.A.

    Compliance with the mandate of the Uranium Mill Tailings Radiation Control Act (UMTRCA) at Uranium Mill Tailings Remedial Action (UMTRA) Project sites requires implementation of a groundwater remedial action plan that meets the requirements of Subpart B of the US Environmental Protection Agency`s proposed groundwater protection standards (40 CFR 192). The UMTRA Groundwater Project will ensure that unacceptable current risk or potential risk to the public health, safety and the environment resulting from the groundwater contamination attributable to the UMTRA sites, is mitigated in a timely and cost-efficient manner. For each UMTRA processing site and vicinity property where contamination exists,more » a groundwater remedial action plan must be developed that identifies hazardous constituents and establishes acceptable concentration limits for the hazardous constituents as either (a) alternate concentration limits (ACL), (b) maximum concentration limits (MCLs), (c) supplemental standards, or (d) background groundwater quality levels. Project optimization is a strategy that will aggressively work within the current regulatory framework using all available options to meet regulatory requirements. This strategy is outlined within.« less

  12. The Effect of Soil Properties on Metal Bioavailability: Field Scale Validation to Support Regulatory Acceptance

    DTIC Science & Technology

    2013-06-01

    Bioavailability, metals, soil, bioaccessibility, ecological risk, arsenic, cadmium , chromium, lead 16. SECURITY CLASSIFICATION OF:U 17. LIMITATION...located in Sacramento, CA. Soils from a former wastewater treatment lagoon are contaminated with high concentrations of lead , chromium, and cadmium ...in soil. Soil and Sediment Contamination, 2003. 12(1): p. 1-21. 23. Pierzynski, G.M. and A.P. Schwab, Bioavailability of Zinc, Cadmium , and Lead

  13. Setting limits for acceptable change in sediment particle size composition following marine aggregate dredging.

    PubMed

    Cooper, Keith M

    2012-08-01

    In the UK, Government policy requires marine aggregate extraction companies to leave the seabed in a similar physical condition after the cessation of dredging. This measure is intended to promote recovery, and the return of a similar faunal community to that which existed before dredging. Whilst the policy is sensible, and in line with the principles of sustainable development, the use of the word 'similar' is open to interpretation. There is, therefore, a need to set quantifiable limits for acceptable change in sediment composition. Using a case study site, it is shown how such limits could be defined by the range of sediment particle size composition naturally found in association with the faunal assemblages in the wider region. Whilst the approach offers a number of advantages over the present system, further testing would be required before it could be recommended for use in the regulatory context. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  14. Tracking of time-varying genomic regulatory networks with a LASSO-Kalman smoother

    PubMed Central

    2014-01-01

    It is widely accepted that cellular requirements and environmental conditions dictate the architecture of genetic regulatory networks. Nonetheless, the status quo in regulatory network modeling and analysis assumes an invariant network topology over time. In this paper, we refocus on a dynamic perspective of genetic networks, one that can uncover substantial topological changes in network structure during biological processes such as developmental growth. We propose a novel outlook on the inference of time-varying genetic networks, from a limited number of noisy observations, by formulating the network estimation as a target tracking problem. We overcome the limited number of observations (small n large p problem) by performing tracking in a compressed domain. Assuming linear dynamics, we derive the LASSO-Kalman smoother, which recursively computes the minimum mean-square sparse estimate of the network connectivity at each time point. The LASSO operator, motivated by the sparsity of the genetic regulatory networks, allows simultaneous signal recovery and compression, thereby reducing the amount of required observations. The smoothing improves the estimation by incorporating all observations. We track the time-varying networks during the life cycle of the Drosophila melanogaster. The recovered networks show that few genes are permanent, whereas most are transient, acting only during specific developmental phases of the organism. PMID:24517200

  15. 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

  16. 78 FR 53484 - Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 4

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-29

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 052-00026; NRC-2008-0252] Inspections, Tests, Analyses... Commission. ACTION: Determination of inspections, tests, analyses, and acceptance criteria (ITAAC) completion. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) staff has determined that the inspections, tests...

  17. 78 FR 65007 - Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 3

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-30

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 052-00026; NRC-2008-0252] Inspections, Tests, Analyses... Commission. ACTION: Determination of inspections, tests, analyses, and acceptance criteria completion. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) staff has determined that the inspections, tests...

  18. 78 FR 53483 - Inspections, Tests, Analyses, and Acceptance Criteria; Vogtle Electric Generating Plant, Unit 3

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-29

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 052-00025; NRC-2008-0252] Inspections, Tests, Analyses... Commission. ACTION: Determination of inspections, tests, analyses, and acceptance criteria (ITAAC) completion. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) staff has determined that the inspections, tests...

  19. Good modeling practice guidelines for applying multimedia models in chemical assessments.

    PubMed

    Buser, Andreas M; MacLeod, Matthew; Scheringer, Martin; Mackay, Don; Bonnell, Mark; Russell, Mark H; DePinto, Joseph V; Hungerbühler, Konrad

    2012-10-01

    Multimedia mass balance models of chemical fate in the environment have been used for over 3 decades in a regulatory context to assist decision making. As these models become more comprehensive, reliable, and accepted, there is a need to recognize and adopt principles of Good Modeling Practice (GMP) to ensure that multimedia models are applied with transparency and adherence to accepted scientific principles. We propose and discuss 6 principles of GMP for applying existing multimedia models in a decision-making context, namely 1) specification of the goals of the model assessment, 2) specification of the model used, 3) specification of the input data, 4) specification of the output data, 5) conduct of a sensitivity and possibly also uncertainty analysis, and finally 6) specification of the limitations and limits of applicability of the analysis. These principles are justified and discussed with a view to enhancing the transparency and quality of model-based assessments. Copyright © 2012 SETAC.

  20. A cross-cultural study of perceived benefit versus risk as mediators in the trust-acceptance relationship.

    PubMed

    Bronfman, Nicolás C; Vázquez, Esperanza López

    2011-12-01

    Several recent studies have identified the significant role social trust in regulatory organizations plays in the public acceptance of various technologies and activities. In a cross-cultural investigation, the current work explores empirically the relationship between social trust in management authorities and the degree of public acceptability of hazards for individuals residing in either developed or emerging Latin American economies using confirmatory rather than exploratory techniques. Undergraduates in Mexico, Brazil, and Chile and the United States and Spain assessed trust in regulatory authorities, public acceptance, personal knowledge, and the risks and benefits for 23 activities and technological hazards. Four findings were encountered. (i) In Latin American nations trust in regulatory entities was strongly and significantly (directly as well as indirectly) linked with the public's acceptance of any activity or technology. In developed countries trust and acceptability are essentially linked indirectly (through perceived risk and perceived benefit). (ii) Lack of knowledge strengthened the magnitude and statistical significance of the trust-acceptability relationship in both developed and developing countries. (iii) For high levels of claimed knowledge, the impact on the trust-acceptability relationship varied depending upon the origin of the sample. (iv) Confirmatory analysis revealed the relative importance of perceived benefit over perceived risk in meditating the trust-acceptability causal chain. © 2011 Society for Risk Analysis.

  1. Issues and approaches for ensuring effective communication on acceptable daily exposure (ADE) values applied to pharmaceutical cleaning.

    PubMed

    Olson, Michael J; Faria, Ellen C; Hayes, Eileen P; Jolly, Robert A; Barle, Ester Lovsin; Molnar, Lance R; Naumann, Bruce D; Pecquet, Alison M; Shipp, Bryan K; Sussman, Robert G; Weideman, Patricia A

    2016-08-01

    This manuscript centers on communication with key stakeholders of the concepts and program goals involved in the application of health-based pharmaceutical cleaning limits. Implementation of health-based cleaning limits, as distinct from other standards such as 1/1000th of the lowest clinical dose, is a concept recently introduced into regulatory domains. While there is a great deal of technical detail in the written framework underpinning the use of Acceptable Daily Exposures (ADEs) in cleaning (for example ISPE, 2010; Sargent et al., 2013), little is available to explain how to practically create a program which meets regulatory needs while also fulfilling good manufacturing practice (GMP) and other expectations. The lack of a harmonized approach for program implementation and communication across stakeholders can ultimately foster inappropriate application of these concepts. Thus, this period in time (2014-2017) could be considered transitional with respect to influencing best practice related to establishing health-based cleaning limits. Suggestions offered in this manuscript are intended to encourage full and accurate communication regarding both scientific and administrative elements of health-based ADE values used in pharmaceutical cleaning practice. This is a large and complex effort that requires: 1) clearly explaining key terms and definitions, 2) identification of stakeholders, 3) assessment of stakeholders' subject matter knowledge, 4) formulation of key messages fit to stakeholder needs, 5) identification of effective and timely means for communication, and 6) allocation of time, energy, and motivation for initiating and carrying through with communications. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Measuring transplant center performance: The goals are not controversial but the methods and consequences can be.

    PubMed

    Jay, Colleen; Schold, Jesse D

    2017-03-01

    Risks of regulatory scrutiny has generated widespread concern about increasingly risk averse transplant center behaviors regarding both donor and candidate acceptance patterns. To address potential unintended consequences threatening access to care, we discuss recent changes in regulatory metrics and potential improvements in quality oversight of transplant centers. Despite many recent changes to one-year patient and graft survival regulatory criteria, the capacity to accurately identify true underperforming centers and avoiding false positive flagging remains an area of great concern. Numerous studies have demonstrated restrictions in transplant volume and access following transplant center flagging. Current regulatory criteria are limited in their capacity to accurately identify poorly performing centers and potentially encourage risk-averse behavior by transplant centers. Efforts to address these concerns should focus on (1) improving risk-adjustment models with better data which captures the acuity of candidate and donor risk, (2) reconsidering primary outcomes measured to assess comprehensive transplant center performance, (3) improving education to address rational or perceived disincentives, and (4) using data more effectively to share best practices.

  3. Consumer acceptance of irradiated chicken and produce in the U.S.A.

    NASA Astrophysics Data System (ADS)

    Cottee, Jim; Kunstadt, Peter; Fraser, Frank

    1995-02-01

    There is a demonstrated dichotomy between perceived consumer acceptance of irradiated foods, and the consumers' choice of food in grocery stores. Indeed the perception has been that most consumers were against irradiated foods and that massive educational campaigns would be needed to change their minds. Meanwhile, some initial sales of irradiated foods have been unexpectedly brisk when supported by limited, point-of-sale information. There is strong agreement between recent studies, with respect to consumers willing to buy irradiated foods once the benefits are explained. A large segment of approximately 50% of all respondents indicate that they would buy irradiated foods. Consumers have also shown that they put a great deal of trust in their grocers and in regulatory bodies.

  4. 75 FR 80854 - Toshiba Corporation; Acceptance for Docketing of an Application for Renewal of the U.S. Advanced...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-23

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 52-044; NRC-2010-0361] Toshiba Corporation; Acceptance for Docketing of an Application for Renewal of the U.S. Advanced Boiling Water Reactor Design Certification On November 2, 2010, Toshiba Corporation (Toshiba) submitted an application to the U.S. Nuclear Regulatory Commission (NRC) for a design...

  5. Task 2 - Limits for High-Frequency Conducted Susceptibility Testing - CS114 (NRC-HQ-60-14-D-0015)

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

    Wood, Richard Thomas; Ewing, Paul D.; Moses, Rebecca J.

    2015-09-01

    A principal focus of Task 2 under this project was for ORNL to evaluate the basis for susceptibility testing against high-frequency conducted interference and to establish recommendations to resolve concerns about the severity of test limits for the conducted susceptibility (CS) test, CS114, from MIL-STD-461. The primary concern about the test limit has been characterized by the EPRI EMI Working Group in the following terms: Demonstrating compliance with the CS114 test limits recommended in TR-102323 has proven to be problematic, even for components that have been tested to commercial standards and demonstrated proper operation in industrial applications [6]. Specifically, EPRImore » notes that the CS114 limits approved in regulatory documents are significantly higher than those invoked by the US military and similar commercial standards in the frequency range below 200 kHz. For this task, ORNL evaluated the original approach to establishing the test limit, EPRI technical findings from a review of the limit, and the regulatory basis through which the currently approved limits were accepted. Based on this analysis, strategies have been developed regarding changes to the CS114 limit that can resolve the technical concerns raised by the industry. Guided by the principles that reasonable assurance of safety must not be compromised but excessive conservatism should be reduced, recommendations on a suitable basis for a revised limit have been developed and can be incorporated into the planned Revision 2 of RG 1.180.« less

  6. Pain acceptance, psychological functioning, and self-regulatory fatigue in temporomandibular disorder.

    PubMed

    Eisenlohr-Moul, Tory A; Burris, Jessica L; Evans, Daniel R

    2013-12-01

    A growing body of evidence suggests that chronic pain patients suffer from chronic self-regulatory fatigue: difficulty controlling thoughts, emotions, and behavior. Pain acceptance, which involves responding to pain and related experiences without attempts to control or avoid them (pain willingness), and pursuit of valued life activities regardless of pain (activity engagement) has been associated with various favorable outcomes in chronic pain patients, including better psychological functioning. The study presented here tested the hypotheses that pain acceptance is associated with less psychological distress, higher psychological well-being, and reduced self-regulatory fatigue in temporomandibular disorder (TMD) patients, particularly for those with longer pain duration. Cross-sectional data were provided by 135 TMD patients during an initial evaluation at a university-based tertiary orofacial pain clinic. Results of hierarchical linear regression models indicated that, controlling for pain severity, pain willingness is associated with less psychological distress and lower self-regulatory fatigue, and activity engagement is associated with greater psychological well-being. Furthermore, the effect of pain willingness on psychological distress was moderated by pain duration such that pain willingness was more strongly associated with less psychological distress in patients with longer pain duration; this moderating effect was fully mediated by self-regulatory fatigue. These findings suggest pain willingness may buffer against self-regulatory fatigue in those with longer pain duration, and such conservation of self-regulatory resources may protect against psychological symptoms.

  7. Surrogate outcomes: experiences at the Common Drug Review

    PubMed Central

    2013-01-01

    Background Surrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada’s Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns. Methods Final recommendations were identified from CDR inception (September 2003) to December 31, 2010. Recommendations were classified by type of outcome (surrogate, final, other) and acceptability of surrogates (determined by the presence/absence of statements of concern regarding surrogates). Descriptive and statistical analyses examined factors related to surrogate use and acceptability. For thirteen surrogate-based submissions, recommendations from international HTA and regulatory agencies were reviewed for statements about surrogate acceptability. Results Of 156 final recommendations, 68 (44%) involved surrogates. The overall ‘do not list’ (DNL) rate was 48%; the DNL rate for surrogates was 41% (p = 0.175). The DNL rate was 64% for non-accepted surrogates (n = 28) versus 25% for accepted surrogates (odds ratio 5.4, p = 0.002). Clinical uncertainty, use of economic evidence over price alone, and a premium price were significantly associated with non-accepted surrogates. Surrogates were used most commonly for HIV, diabetes, rare diseases, cardiovascular disease and cancer. For the subset of drugs studied, other HTA agencies did not express concerns for most recommendations, while regulatory agencies frequently stated surrogate acceptance. Conclusions The majority of surrogates were accepted at the CDR. Non-accepted surrogates were significantly associated with clinical uncertainty and a DNL recommendation. There was inconsistency of surrogate acceptability across several international agencies. Stakeholders should consider collaboratively establishing guidelines on the use, validation, and acceptability of surrogates. PMID:24341379

  8. Underclad cracking of pressure vessel steels for light-water reactors

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

    Lopez, H.F.

    1987-06-01

    Although fracture mechanics analyses have shown that underclad cracks have no detrimental effect on the integrity of thick walled pressure vessels (40 year service), in order to avoid unexpected failures the US Nuclear Regulatory Commission has issued Regulatory Guide 1.43 which sets limits on the extent of fissures permitted and describes acceptable means of controlling the weld cladding processes. Cavitation and intergranular fissuring in SA508-2 and 22NiMoCr37 steels can occur in the presence or absence of intergranular particles. The observations of intergranular fissuring and cavitation in those HAZ free from overlapping effects are attributed to grain boundary segregation. Other probablemore » void nucleation sites are the grain boundary-lath interface intersections which facilitate the formation of grain boundary discontinuities.« less

  9. Air pollution control residues from waste incineration: current UK situation and assessment of alternative technologies.

    PubMed

    Rani, D Amutha; Boccaccini, A R; Deegan, D; Cheeseman, C R

    2008-11-01

    Current disposal options for APC residues in the UK and alternative treatment technologies developed world-wide have been reviewed. APC residues are currently landfilled in the UK where they undergo in situ solidification, although the future acceptability of this option is uncertain because the EU waste acceptance criteria (WAC) introduce strict limits on leaching that are difficult to achieve. Other APC residue treatment processes have been developed which are reported to reduce leaching to below relevant regulatory limits. The Ferrox process, the VKI process, the WES-PHix process, stabilisation/solidification using cementitious binders and a range of thermal treatment processes are reviewed. Thermal treatment technologies convert APC residues combined with other wastes into inert glass or glass-ceramics that encapsulate heavy metals. The waste management industry will inevitably use the cheapest available option for treating APC residues and strict interpretation and enforcement of waste legislation is required if new, potentially more sustainable technologies are to become commercially viable.

  10. 17 CFR 1.52 - Self-regulatory organization adoption and surveillance of minimum financial requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Self-regulatory organization... Miscellaneous § 1.52 Self-regulatory organization adoption and surveillance of minimum financial requirements... accounting and auditing firm that is acceptable to the Commission; and (2) Self-regulatory organization means...

  11. 77 FR 51880 - Requirements for Maintenance of Inspections, Tests, Analyses, and Acceptance Criteria

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-28

    ... Maintenance of Inspections, Tests, Analyses, and Acceptance Criteria AGENCY: Nuclear Regulatory Commission... construction activities through inspections, tests, analyses, and acceptance criteria (ITAAC) under a combined... inspections, tests, or analyses were performed as required, or that acceptance criteria are met, and to notify...

  12. AERMOD performance evaluation for three coal-fired electrical generating units in Southwest Indiana.

    PubMed

    Frost, Kali D

    2014-03-01

    An evaluation of the steady-state dispersion model AERMOD was conducted to determine its accuracy at predicting hourly ground-level concentrations of sulfur dioxide (SO2) by comparing model-predicted concentrations to a full year of monitored SO2 data. The two study sites are comprised of three coal-fired electrical generating units (EGUs) located in southwest Indiana. The sites are characterized by tall, buoyant stacks,flat terrain, multiple SO2 monitors, and relatively isolated locations. AERMOD v12060 and AERMOD v12345 with BETA options were evaluated at each study site. For the six monitor-receptor pairs evaluated, AERMOD showed generally good agreement with monitor values for the hourly 99th percentile SO2 design value, with design value ratios that ranged from 0.92 to 1.99. AERMOD was within acceptable performance limits for the Robust Highest Concentration (RHC) statistic (RHC ratios ranged from 0.54 to 1.71) at all six monitors. Analysis of the top 5% of hourly concentrations at the six monitor-receptor sites, paired in time and space, indicated poor model performance in the upper concentration range. The amount of hourly model predicted data that was within a factor of 2 of observations at these higher concentrations ranged from 14 to 43% over the six sites. Analysis of subsets of data showed consistent overprediction during low wind speed and unstable meteorological conditions, and underprediction during stable, low wind conditions. Hourly paired comparisons represent a stringent measure of model performance; however given the potential for application of hourly model predictions to the SO2 NAAQS design value, this may be appropriate. At these two sites, AERMOD v12345 BETA options do not improve model performance. A regulatory evaluation of AERMOD utilizing quantile-quantile (Q-Q) plots, the RHC statistic, and 99th percentile design value concentrations indicates that model performance is acceptable according to widely accepted regulatory performance limits. However, a scientific evaluation examining hourly paired monitor and model values at concentrations of interest indicates overprediction and underprediction bias that is outside of acceptable model performance measures. Overprediction of 1-hr SO2 concentrations by AERMOD presents major ramifications for state and local permitting authorities when establishing emission limits.

  13. Regulatory withdrawal of medicines marketed with uncertain benefits: the bevacizumab case study.

    PubMed

    Vitry, Agnes; Nguyen, Tuan; Entwistle, Vikky; Roughead, Elizabeth

    2015-01-01

    Withdrawal of conditional regulatory approval or subsidization of new medicines when subsequent evidence does not confirm early trial results may not be well understood or accepted by the public. We present a case study of the US Food and Drug Administration (FDA)'s decision to withdraw the indication of bevacizumab for the treatment of advanced breast cancer and include an analysis of the reactions of stakeholders with a view to identifying opportunities for improving risk management for new medicines with conditional approval or funding. We drew on a range of information sources, including FDA documents, medical journals and media reports, to describe the evidentiary basis of the FDA decisions. We analysed the reactions and perspectives of the stakeholders. In 2008 bevacizumab was granted conditional approval for treatment of advanced breast cancer by the FDA pending submission of supplementary satisfactory evidence. In 2011 the FDA decision to withdraw the indication was met with a hostile reaction from many clinicians and cancer survivors. There were different interpretations of the therapeutic value of bevacizumab with strong beliefs among cancer survivors that the medicine was effective and potential harm was manageable. High expectations of the public may have been encouraged by overly positive media reports and limited understanding by the public of the complexity of the scientific evaluation of new medicines and of the regulatory processes. Improving understanding and acceptance of approval or coverage schemes conditional to evidence development may require the development of risk management plans by regulatory and funding institutions. They may include a range of strategies such as requirements for formal patient acknowledgment of the conditional availability of the medicine, 'black-triangle' equivalent labels that identify full approval is based on pending evidence, and ongoing communication with the media, public and health professionals.

  14. Global Acceptance of Biosimilars: Importance of Regulatory Consistency, Education, and Trust.

    PubMed

    Cazap, Eduardo; Jacobs, Ira; McBride, Ali; Popovian, Robert; Sikora, Karol

    2018-05-16

    Globally, biosimilars are expected to have a key role in improving patient access to biological therapies and addressing concerns regarding the escalating cost of health care. Indeed, in Europe, increased use of biologics and reduced drug prices have been observed after the introduction of biosimilars. Recently, several monoclonal antibody biosimilars of anticancer therapies have been approved, and numerous others are in various stages of clinical development. Biosimilars are authorized via a regulatory pathway separate from that used for generic drugs; they are also regulated separately from novel biologics. Biosimilar approval pathways in many major regulatory regions worldwide are, to a broad degree, scientifically aligned. However, owing to regional differences in health care priorities, policies, and resources, some important regulatory inconsistencies are evident. Acceptance of biosimilars by health care systems, health care professionals, and patients will be a key factor in the uptake of these therapies, and such regulatory variations could contribute to confusion and diminished confidence regarding the quality, efficacy, and reliability of these agents. Furthermore, the need for manufacturers to account for regulatory inconsistencies introduces inefficiencies and delays into biosimilar development programs. These issues should be addressed if biosimilars are to attain their maximal global potential. This review summarizes the evolution of the global biosimilar landscape and provides examples of inconsistencies between regulatory requirements in different regions. In addition, we review ongoing efforts to improve regulatory alignment and highlight the importance of education as a crucial factor in generating trust in, and acceptance of, biosimilars on a worldwide scale. Biosimilars of monoclonal antibody anticancer therapies are beginning to emerge, and more are likely to become available for clinical use in the near future. The extent to which biosimilars can contribute to cancer care will depend on their level of acceptance by health care systems, health care professionals, and patients. A better understanding of the regulatory basis for the approval of biosimilars may enhance confidence and trust in these agents. In order to have informed discussions about treatment choices with their patients, oncologists should familiarize themselves with the biosimilar paradigm. © AlphaMed Press 2018.

  15. Using science soundly: The Yucca Mountain standard

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

    Fri, R.W.

    1995-09-01

    Using sound science to shape government regulation is one of the most hotly argued topics in the ongoing debate about regulatory reform. Even though no one advaocates using unsound science, the belief that even the best science will sweep away regulatory controversy is equally foolish. As chair of a National Research Council (NRC) committee that studied the scientific basis for regulating high-level nuclear waste disposal, the author learned that science alone could resolve few of the key regulatory questions. Developing a standard that specifies a socially acceptable limit on the human health effects of nuclear waste releases involves many decisions.more » As the NRC committee learned in evaluating the scientific basis for the Yucca Mountain standard, a scientifically best decision rarely exists. More often, science can only offer a useful framework and starting point for policy debates. And sometimes, science`s most helpful contribution is to admit that it has nothing to say. The Yucca mountain study clearly illustrates that excessive faith in the power of science is more likely to produce messy frustration than crisp decisions. A better goal for regulatory reform is the sound use of science to clarify and contain the inevitable policy controversy.« less

  16. Liminality and the Limits of Law in Health Research Regulation: What are we Missing in the Spaces in-Between?

    PubMed Central

    2017-01-01

    Abstract This article fundamentally challenges the way in which law currently regulates human health research. It invokes the anthropological concept of liminality—the quality of in-between-ness—to suggest deeper ways of understanding ongoing challenges in delivering acceptable and effective regulation of research involving human participants. In stark contrast to the structural regulatory spaces constructed by law, the metaphor of the liminal space is explored to explain what is lost through our failure to see health research regulation as an inherently human experiential process, involving potentially profound transformative events for participants and researchers alike. The implications for the future of health research regulation are then examined. In particular, the analysis calls into question key features of the current regulatory paradigm, and demands that we reconsider our own demands of law in this context. The argument is made that health research is a liminal process and that we fail to treat it as such. This requires a rethink of corollary regulation also in processual terms. Ultimately, the charge is to undertake a radical reimagining of regulatory space to accommodate and promote liminal regulatory spaces. PMID:27940525

  17. Liminality and the Limits of Law in Health Research Regulation: What are we Missing in the Spaces in-Between?

    PubMed

    Laurie, Graeme

    2017-02-01

    This article fundamentally challenges the way in which law currently regulates human health research. It invokes the anthropological concept of liminality-the quality of in-between-ness-to suggest deeper ways of understanding ongoing challenges in delivering acceptable and effective regulation of research involving human participants. In stark contrast to the structural regulatory spaces constructed by law, the metaphor of the liminal space is explored to explain what is lost through our failure to see health research regulation as an inherently human experiential process, involving potentially profound transformative events for participants and researchers alike. The implications for the future of health research regulation are then examined. In particular, the analysis calls into question key features of the current regulatory paradigm, and demands that we reconsider our own demands of law in this context. The argument is made that health research is a liminal process and that we fail to treat it as such. This requires a rethink of corollary regulation also in processual terms. Ultimately, the charge is to undertake a radical reimagining of regulatory space to accommodate and promote liminal regulatory spaces. © The Author 2016. Published by Oxford University Press.

  18. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods.

    PubMed

    Dozier, Samantha; Brown, Jeffrey; Currie, Alistair

    2011-11-29

    In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.

  19. 75 FR 45171 - Notice of Issuance of Regulatory Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-02

    ... Engineering, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555...-3040. This guide describes some engineering practices and methods generally considered by the NRC to be... they reflect the latest general engineering approaches that are acceptable to the NRC staff. If future...

  20. Satiated with belongingness? Effects of acceptance, rejection, and task framing on self-regulatory performance.

    PubMed

    DeWall, C Nathan; Baumeister, Roy F; Vohs, Kathleen D

    2008-12-01

    Seven experiments showed that the effects of social acceptance and social exclusion on self-regulatory performance depend on the prospect of future acceptance. Excluded participants showed decrements in self-regulation, but these decrements were eliminated if the self-regulation task was ostensibly a diagnostic indicator of the ability to get along with others. No such improvement was found when the task was presented as diagnostic of good health. Accepted participants, in contrast, performed relatively poorly when the task was framed as a diagnostic indicator of interpersonally attractive traits. Furthermore, poor performance among accepted participants was not due to self-handicapping or overconfidence. Offering accepted participants a cash incentive for self-regulating eliminated the self-regulation deficits. These findings provide evidence that the need to belong fits standard motivational patterns: Thwarting the drive intensifies it, whereas satiating it leads to temporary reduction in drive. Accepted people are normally good at self-regulation but are unwilling to exert the effort to self-regulate if self-regulation means gaining the social acceptance they have already obtained.

  1. Satiated with Belongingness? Effects of Acceptance, Rejection, and Task Framing on Self-Regulatory Performance

    PubMed Central

    DeWall, C. Nathan; Baumeister, Roy F.; Vohs, Kathleen D.

    2008-01-01

    Seven experiments showed that the effects of social acceptance and social exclusion on self-regulatory performance depend on the prospect of future acceptance. Excluded participants showed decrements in self-regulation, but these decrements were eliminated if the self-regulation task was ostensibly a diagnostic indicator of the ability to get along with others. No such improvement was found when the task was presented as diagnostic of good health. Accepted participants, in contrast, performed relatively poorly when the task was framed as a diagnostic indicator of interpersonally attractive traits. Furthermore, poor performance among accepted participants was not due to self-handicapping or overconfidence. Offering accepted participants a cash incentive for self-regulating eliminated the self-regulation deficits. These findings provide evidence that the need to belong fits standard motivational patterns: thwarting the drive intensifies it, whereas satiating it leads to temporary reduction in drive. Accepted people are normally good at self-regulation but are unwilling to exert the effort to self-regulate if self-regulation means gaining the social acceptance they have already obtained. PMID:19025289

  2. A future scenario of the global regulatory landscape regarding genome-edited crops

    PubMed Central

    Araki, Motoko

    2017-01-01

    ABSTRACT The global agricultural landscape regarding the commercial cultivation of genetically modified (GM) crops is mosaic. Meanwhile, a new plant breeding technique, genome editing is expected to make genetic engineering-mediated crop breeding more socially acceptable because it can be used to develop crop varieties without introducing transgenes, which have hampered the regulatory review and public acceptance of GM crops. The present study revealed that product- and process-based concepts have been implemented to regulate GM crops in 30 countries. Moreover, this study analyzed the regulatory responses to genome-edited crops in the USA, Argentina, Sweden and New Zealand. The findings suggested that countries will likely be divided in their policies on genome-edited crops: Some will deregulate transgene-free crops, while others will regulate all types of crops that have been modified by genome editing. These implications are discussed from the viewpoint of public acceptance. PMID:27960622

  3. 13 CFR 120.463 - Regulatory accounting-What are SBA's regulatory accounting requirements for SBA Supervised Lenders?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... basis in accordance with Generally Accepted Accounting Principles (GAAP) as promulgated by the Financial Accounting Standards Board (FASB), supplemented by Regulatory Accounting Principles (RAP) as identified by... set forth in FASB Statement of Financial Accounting Standards No. 15, Accounting by Debtors and...

  4. International guidelines for bioequivalence of systemically available orally administered generic drug products: a survey of similarities and differences.

    PubMed

    Davit, Barbara; Braddy, April C; Conner, Dale P; Yu, Lawrence X

    2013-10-01

    The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Association, Japan, Mexico, Singapore, South Korea, Switzerland, the USA, and the World Health Organization. We began with a comparison of how the various jurisdictions and organizations define a generic product and its corresponding reference product. We then compared the following bioequivalence approaches: recommended bioequivalence study designs, method of pharmacokinetic calculations and bioequivalence acceptance limits, recommendations for modifying bioequivalence study designs and limits for highly variable drugs and narrow therapeutic index drugs, provisions for waiving bioequivalence study requirements (granting biowaivers), and implementation of the Biopharmaceutics Classification System. We observed that, overall, there are more similarities than differences in bioequivalence approaches among the regulatory authorities surveyed.

  5. 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.

  6. Use of physiologically relevant biopharmaceutics tools within the pharmaceutical industry and in regulatory sciences: Where are we now and what are the gaps?

    PubMed

    Flanagan, Talia; Van Peer, Achiel; Lindahl, Anders

    2016-08-25

    Regulatory interactions are an important part of the drug development and licensing process. A survey on the use of biopharmaceutical tools for regulatory purposes has been carried out within the industry community of the EU project OrBiTo within Innovative Medicines Initiative (IMI). The aim was to capture current practice and experience in using in vitro and in silico biopharmaceutics tools at various stages of development, what barriers exist or are perceived, and to understand the current gaps in regulatory biopharmaceutics. The survey indicated that biorelevant dissolution testing and physiologically based modelling and simulation are widely applied throughout development to address a number of biopharmaceutics issues. However, data from these in vitro and in silico predictive biopharmaceutics tools are submitted to regulatory authorities far less often than they are used for internal risk assessment and decision making. This may prevent regulators from becoming familiar with these tools and how they are applied in industry, and limits the opportunities for biopharmaceutics scientists working in industry to understand the acceptability of these tools in the regulatory environment. It is anticipated that the advanced biopharmaceutics tools and understanding delivered in the next years by OrBiTo and other initiatives in the area of predictive tools will also be of value in the regulatory setting, and provide a basis for more informed and confident biopharmaceutics risk assessment and regulatory decision making. To enable the regulatory potential of predictive biopharmaceutics tools to be realized, further scientific dialogue is needed between industry, regulators and scientists in academia, and more examples need to be published to demonstrate the applicability of these tools. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Gaining Regulator Acceptance of Natural Attenuation as a Remediation Tool

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

    Hughes, M.B.

    Monitored natural attenuation (MNA) makes use of biological degradation, chemical reactions with natural materials, and other processes to clean up contaminated soils and groundwater. In the past, the regulatory community has been slow to accept natural attenuation due to a misperception that natural attenuation is a ''do nothing'' approach. Recently however, regulators have been more open to considering MNA as part of an overall clean-up plan that includes active treatment technologies to remove or contain the source of contamination at a site. MNA is currently being implemented at the Savannah River Site for remediation of selected contaminants. The South Carolinamore » Department of Health and Environmental Control, who has regulatory authority over these actions, has accepted this process. Significant overall cost savings are forecast. Additionally, there will be less disruption to the ecosystem, compared with engineered technologies. This paper describes the monitored natural attenuation concept as well as the process of constructive engagement with the regulators to achieve acceptance. Application to DOE, DOD, and commercial sites, as well as acceptability to other regulatory bodies, will be discussed with an emphasis on strategies to prevent false starts in the negotiation process and inventing options that result in mutual gains for all parties.« less

  8. Agro-economic impact of cattle cloning.

    PubMed

    Faber, D C; Ferre, L B; Metzger, J; Robl, J M; Kasinathan, P

    2004-01-01

    The purpose of this paper is to review the economic and social implications of cloned cattle, their products, and their offspring as related to production agriculture. Cloning technology in cattle has several applications outside of traditional production agriculture. These applications can include bio-medical applications, such as the production of pharmaceuticals in the blood or milk of transgenic cattle. Cloning may also be useful in the production of research models. These models may or may not include genetic modifications. Uses in agriculture include many applications of the technology. These include making genetic copies of elite seed stock and prize winning show cattle. Other purposes may range from "insurance" to making copies of cattle that have sentimental value, similar to cloning of pets. Increased selection opportunities available with cloning may provide for improvement in genetic gain. The ultimate goal of cloning has often been envisioned as a system for producing quantity and uniformity of the perfect dairy cow. However, only if heritability were 100%, would clone mates have complete uniformity. Changes in the environment may have significant impact on the productivity and longevity of the resulting clones. Changes in consumer preferences and economic input costs may all change the definition of the perfect cow. The cost of producing such animals via cloning must be economically feasible to meet the intended applications. Present inefficiencies limit cloning opportunities to highly valued animals. Improvements are necessary to move the applications toward commercial application. Cloning has additional obstacles to conquer. Social and regulatory acceptance of cloning is paramount to its utilization in production agriculture. Regulatory acceptance will need to address the animal, its products, and its offspring. In summary, cloning is another tool in the animal biotechnology toolbox, which includes artificial insemination, sexing of semen, embryo sexing and in vitro fertilization. While it will not replace any of the above mentioned, its degree of utilization will depend on both improvement in efficiency as well as social and regulatory acceptance.

  9. 77 FR 33253 - Regulatory Guide 8.24, Revision 2, Health Physics Surveys During Enriched Uranium-235 Processing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-05

    ... NUCLEAR REGULATORY COMMISSION [NRC-2010-0115] Regulatory Guide 8.24, Revision 2, Health Physics..., ``Health Physics Surveys During Enriched Uranium-235 Processing and Fuel Fabrication'' was issued with a... specifically with the following aspects of an acceptable occupational health physics program that are closely...

  10. 78 FR 37848 - ASME Code Cases Not Approved for Use

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-1233, ``ASME Code Cases not Approved for Use.'' This regulatory guide lists the American Society of Mechanical Engineers (ASME) Code Cases that the NRC has determined not to be acceptable for use on a generic basis.

  11. Regulatory ozone modeling: status, directions, and research needs.

    PubMed Central

    Georgopoulos, P G

    1995-01-01

    The Clean Air Act Amendments (CAAA) of 1990 have established selected comprehensive, three-dimensional, Photochemical Air Quality Simulation Models (PAQSMs) as the required regulatory tools for analyzing the urban and regional problem of high ambient ozone levels across the United States. These models are currently applied to study and establish strategies for meeting the National Ambient Air Quality Standard (NAAQS) for ozone in nonattainment areas; State Implementation Plans (SIPs) resulting from these efforts must be submitted to the U.S. Environmental Protection Agency (U.S. EPA) in November 1994. The following presentation provides an overview and discussion of the regulatory ozone modeling process and its implications. First, the PAQSM-based ozone attainment demonstration process is summarized in the framework of the 1994 SIPs. Then, following a brief overview of the representation of physical and chemical processes in PAQSMs, the essential attributes of standard modeling systems currently in regulatory use are presented in a nonmathematical, self-contained format, intended to provide a basic understanding of both model capabilities and limitations. The types of air quality, emission, and meteorological data needed for applying and evaluating PAQSMs are discussed, as well as the sources, availability, and limitations of existing databases. The issue of evaluating a model's performance in order to accept it as a tool for policy making is discussed, and various methodologies for implementing this objective are summarized. Selected interim results from diagnostic analyses, which are performed as a component of the regulatory ozone modeling process for the Philadelphia-New Jersey region, are also presented to provide some specific examples related to the general issues discussed in this work. Finally, research needs related to a) the evaluation and refinement of regulatory ozone modeling, b) the characterization of uncertainty in photochemical modeling, and c) the improvement of the model-based ozone-attainment demonstration process are presented to identify future directions in this area. Images Figure 7. Figure 7. Figure 7. Figure 8. Figure 9. PMID:7614934

  12. Systems identification and the adaptive management of waterfowl in the United States

    USGS Publications Warehouse

    Williams, B.K.; Nichols, J.D.

    2001-01-01

    Waterfowl management in the United States is one of the more visible conservation success stories in the United States. It is authorized and supported by appropriate legislative authorities, based on large-scale monitoring programs, and widely accepted by the public. The process is one of only a limited number of large-scale examples of effective collaboration between research and management, integrating scientific information with management in a coherent framework for regulatory decision-making. However, harvest management continues to face some serious technical problems, many of which focus on sequential identification of the resource system in a context of optimal decision-making. The objective of this paper is to provide a theoretical foundation of adaptive harvest management, the approach currently in use in the United States for regulatory decision-making. We lay out the legal and institutional framework for adaptive harvest management and provide a formal description of regulatory decision-making in terms of adaptive optimization. We discuss some technical and institutional challenges in applying adaptive harvest management and focus specifically on methods of estimating resource states for linear resource systems.

  13. Revisiting phage therapy: new applications for old resources.

    PubMed

    Nobrega, Franklin L; Costa, Ana Rita; Kluskens, Leon D; Azeredo, Joana

    2015-04-01

    The success of phage therapy is dependent on the development of strategies able to overcome the limitations of bacteriophages as therapeutic agents, the creation of an adequate regulatory framework, the implementation of safety protocols, and acceptance by the general public. Many approaches have been proposed to circumvent phages' intrinsic limitations but none have proved to be completely satisfactory. In this review we present the major hurdles of phage therapy and the solutions proposed to circumvent them. A thorough discussion of the advantages and drawbacks of these solutions is provided and special attention is given to the genetic modification of phages as an achievable strategy to shape bacteriophages to exhibit desirable biological properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The regulatory function of self-esteem: testing the epistemic and acceptance signaling systems.

    PubMed

    Stinson, Danu Anthony; Logel, Christine; Holmes, John G; Wood, Joanne V; Forest, Amanda L; Gaucher, Danielle; Fitzsimons, Grainné M; Kath, Jennifer

    2010-12-01

    The authors draw on sociometer theory (e.g., Leary, 2004) and self-verification theory (e.g., Swann, 1997) to propose an expanded model of the regulatory function of self-esteem. The model suggests that people not only possess an acceptance signaling system that indicates whether relational value is high or low but also possess an epistemic signaling system that indicates whether social feedback is consistent or inconsistent with chronic perceived relational value (i.e., global self-esteem). One correlational study and 5 experiments, with diverse operationalizations of social feedback, demonstrated that the epistemic signaling system responds to self-esteem consistent or inconsistent relational-value feedback with increases or deceases in epistemic certainty. Moreover, Studies 3-6 demonstrated that the acceptance and epistemic signaling systems respond uniquely to social feedback. Finally, Studies 5 and 6 provide evidence that the epistemic signaling system is part of a broader self-regulatory system: Self-esteem inconsistent feedback caused cognitive efforts to decrease the discrepancy between self-views and feedback and caused depleted self-regulatory capacity on a subsequent self-control task. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  15. 78 FR 11903 - Acceptability of Corrective Action Programs for Fuel Cycle Facilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-20

    ... Cycle Facilities AGENCY: Nuclear Regulatory Commission. ACTION: Draft NUREG; request for public comment... ``Acceptability of Corrective Action Programs for Fuel Cycle Facilities.'' The draft NUREG provides guidance to... a fuel cycle facility is acceptable. DATES: Comments may be submitted by April 22, 2013. Comments...

  16. Steps towards the international regulatory acceptance of non-animal methodology in safety assessment.

    PubMed

    Sewell, Fiona; Doe, John; Gellatly, Nichola; Ragan, Ian; Burden, Natalie

    2017-10-01

    The current animal-based paradigm for safety assessment must change. In September 2016, the UK National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs) brought together scientists from regulatory authorities, academia and industry to review progress in bringing new methodology into regulatory use, and to identify ways to expedite progress. Progress has been slow. Science is advancing to make this possible but changes are necessary. The new paradigm should allow new methodology to be adopted once it is developed rather than being based on a fixed set of studies. Regulatory authorities can help by developing Performance-Based Standards. The most pressing need is in repeat dose toxicology, although setting standards will be more complex than in areas such as sensitization. Performance standards should be aimed directly at human safety, not at reproducing the results of animal studies. Regulatory authorities can also aid progress towards the acceptance of non-animal based methodology by promoting "safe-haven" trials where traditional and new methodology data can be submitted in parallel to build up experience in the new methods. Industry can play its part in the acceptance of new methodology, by contributing to the setting of performance standards and by actively contributing to "safe-haven" trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. USING CFD TO ANALYZE NUCLEAR SYSTEMS BEHAVIOR: DEFINING THE VALIDATION REQUIREMENTS

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

    Richard Schultz

    2012-09-01

    A recommended protocol to formulate numeric tool specifications and validation needs in concert with practices accepted by regulatory agencies for advanced reactors is described. The protocol is based on the plant type and perceived transient and accident envelopes that translates to boundary conditions for a process that gives the: (a) key phenomena and figures-of-merit which must be analyzed to ensure that the advanced plant can be licensed, (b) specification of the numeric tool capabilities necessary to perform the required analyses—including bounding calculational uncertainties, and (c) specification of the validation matrices and experiments--including the desired validation data. The result of applyingmore » the process enables a complete program to be defined, including costs, for creating and benchmarking transient and accident analysis methods for advanced reactors. By following a process that is in concert with regulatory agency licensing requirements from the start to finish, based on historical acceptance of past licensing submittals, the methods derived and validated have a high probability of regulatory agency acceptance.« less

  18. ReNE: A Cytoscape Plugin for Regulatory Network Enhancement

    PubMed Central

    Politano, Gianfranco; Benso, Alfredo; Savino, Alessandro; Di Carlo, Stefano

    2014-01-01

    One of the biggest challenges in the study of biological regulatory mechanisms is the integration, americanmodeling, and analysis of the complex interactions which take place in biological networks. Despite post transcriptional regulatory elements (i.e., miRNAs) are widely investigated in current research, their usage and visualization in biological networks is very limited. Regulatory networks are commonly limited to gene entities. To integrate networks with post transcriptional regulatory data, researchers are therefore forced to manually resort to specific third party databases. In this context, we introduce ReNE, a Cytoscape 3.x plugin designed to automatically enrich a standard gene-based regulatory network with more detailed transcriptional, post transcriptional, and translational data, resulting in an enhanced network that more precisely models the actual biological regulatory mechanisms. ReNE can automatically import a network layout from the Reactome or KEGG repositories, or work with custom pathways described using a standard OWL/XML data format that the Cytoscape import procedure accepts. Moreover, ReNE allows researchers to merge multiple pathways coming from different sources. The merged network structure is normalized to guarantee a consistent and uniform description of the network nodes and edges and to enrich all integrated data with additional annotations retrieved from genome-wide databases like NCBI, thus producing a pathway fully manageable through the Cytoscape environment. The normalized network is then analyzed to include missing transcription factors, miRNAs, and proteins. The resulting enhanced network is still a fully functional Cytoscape network where each regulatory element (transcription factor, miRNA, gene, protein) and regulatory mechanism (up-regulation/down-regulation) is clearly visually identifiable, thus enabling a better visual understanding of its role and the effect in the network behavior. The enhanced network produced by ReNE is exportable in multiple formats for further analysis via third party applications. ReNE can be freely installed from the Cytoscape App Store (http://apps.cytoscape.org/apps/rene) and the full source code is freely available for download through a SVN repository accessible at http://www.sysbio.polito.it/tools_svn/BioInformatics/Rene/releases/. ReNE enhances a network by only integrating data from public repositories, without any inference or prediction. The reliability of the introduced interactions only depends on the reliability of the source data, which is out of control of ReNe developers. PMID:25541727

  19. Stereoselective synthesis from a process research perspective.

    PubMed

    Hillier, Michael C; Reider, Paul J

    2002-03-01

    The process chemists' primary responsibility is to develop efficient and reproducible syntheses of pharmaceutically active compounds. This task is complicated when dealing with chiral molecules that often must be made as single isomers according to regulatory guidelines. The presence of any isomeric impurity in the final product, even in small amounts, is usually not acceptable. This requirement necessitates an exquisite understanding of the methods employed in the construction of chiral drugs. However, the chemistry available for this purpose is sometimes limited and often requires a significant amount of effort and creativity to be made both functional and consistent.

  20. 10 CFR 26.111 - Checking the acceptability of the urine specimen.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Checking the acceptability of the urine specimen. 26.111 Section 26.111 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.111 Checking the acceptability of the urine specimen. (a) Immediately after the donor...

  1. 10 CFR 26.111 - Checking the acceptability of the urine specimen.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Checking the acceptability of the urine specimen. 26.111 Section 26.111 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.111 Checking the acceptability of the urine specimen. (a) Immediately after the donor...

  2. 78 FR 73897 - SHINE Medical Technologies, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-09

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 50-608; NRC-2013-0053] SHINE Medical Technologies, Inc. AGENCY: Nuclear Regulatory Commission. ACTION: License application; docketing. SUMMARY: The U.S. Nuclear... construction permit, submitted by SHINE Medical Technologies, Inc. (SHINE) is acceptable for docketing...

  3. Community pharmacies as sites of adult vaccination: A systematic review.

    PubMed

    Burson, Randall C; Buttenheim, Alison M; Armstrong, Allison; Feemster, Kristen A

    2016-12-01

    Vaccine-preventable deaths among adults remain a major public health concern, despite continued efforts to increase vaccination rates in this population. Alternative approaches to immunization delivery may help address under-vaccination among adults. This systematic review assesses the feasibility, acceptability, and effectiveness of community pharmacies as sites for adult vaccination. We searched 5 electronic databases (PubMed, EMBASE, Scopus, Cochrane, LILACS) for studies published prior to June 2016 and identified 47 relevant articles. We found that pharmacy-based immunization services (PBIS) have been facilitated by state regulatory changes and training programs that allow pharmacists to directly provide vaccinations. These services are widely accepted by both patients and pharmacy staff, and are capable of improving access and increasing vaccination rates. However, political and organizational barriers limit the feasibility and effectiveness of vaccine delivery in pharmacies. These studies provide evidence to inform policy and organizational efforts that promote the efficacy and sustainability of PBIS.

  4. Community pharmacies as sites of adult vaccination: A systematic review

    PubMed Central

    Burson, Randall C.; Buttenheim, Alison M.; Armstrong, Allison; Feemster, Kristen A.

    2016-01-01

    ABSTRACT Vaccine-preventable deaths among adults remain a major public health concern, despite continued efforts to increase vaccination rates in this population. Alternative approaches to immunization delivery may help address under-vaccination among adults. This systematic review assesses the feasibility, acceptability, and effectiveness of community pharmacies as sites for adult vaccination. We searched 5 electronic databases (PubMed, EMBASE, Scopus, Cochrane, LILACS) for studies published prior to June 2016 and identified 47 relevant articles. We found that pharmacy-based immunization services (PBIS) have been facilitated by state regulatory changes and training programs that allow pharmacists to directly provide vaccinations. These services are widely accepted by both patients and pharmacy staff, and are capable of improving access and increasing vaccination rates. However, political and organizational barriers limit the feasibility and effectiveness of vaccine delivery in pharmacies. These studies provide evidence to inform policy and organizational efforts that promote the efficacy and sustainability of PBIS. PMID:27715409

  5. Micro-CT imaging: Developing criteria for examining fetal skeletons in regulatory developmental toxicology studies - A workshop report.

    PubMed

    Solomon, Howard M; Makris, Susan L; Alsaid, Hasan; Bermudez, Oscar; Beyer, Bruce K; Chen, Antong; Chen, Connie L; Chen, Zhou; Chmielewski, Gary; DeLise, Anthony M; de Schaepdrijver, Luc; Dogdas, Belma; French, Julian; Harrouk, Wafa; Helfgott, Jonathan; Henkelman, R Mark; Hesterman, Jacob; Hew, Kok-Wah; Hoberman, Alan; Lo, Cecilia W; McDougal, Andrew; Minck, Daniel R; Scott, Lelia; Stewart, Jane; Sutherland, Vicki; Tatiparthi, Arun K; Winkelmann, Christopher T; Wise, L David; Wood, Sandra L; Ying, Xiaoyou

    2016-06-01

    During the past two decades the use and refinements of imaging modalities have markedly increased making it possible to image embryos and fetuses used in pivotal nonclinical studies submitted to regulatory agencies. Implementing these technologies into the Good Laboratory Practice environment requires rigorous testing, validation, and documentation to ensure the reproducibility of data. A workshop on current practices and regulatory requirements was held with the goal of defining minimal criteria for the proper implementation of these technologies and subsequent submission to regulatory agencies. Micro-computed tomography (micro-CT) is especially well suited for high-throughput evaluations, and is gaining popularity to evaluate fetal skeletons to assess the potential developmental toxicity of test agents. This workshop was convened to help scientists in the developmental toxicology field understand and apply micro-CT technology to nonclinical toxicology studies and facilitate the regulatory acceptance of imaging data. Presentations and workshop discussions covered: (1) principles of micro-CT fetal imaging; (2) concordance of findings with conventional skeletal evaluations; and (3) regulatory requirements for validating the system. Establishing these requirements for micro-CT examination can provide a path forward for laboratories considering implementing this technology and provide regulatory agencies with a basis to consider the acceptability of data generated via this technology. Published by Elsevier Inc.

  6. LIMS user acceptance testing.

    PubMed

    Klein, Corbett S

    2003-01-01

    Laboratory Information Management Systems (LIMS) play a key role in the pharmaceutical industry. Thorough and accurate validation of such systems is critical and is a regulatory requirement. LIMS user acceptance testing is one aspect of this testing and enables the user to make a decision to accept or reject implementation of the system. This paper discusses key elements in facilitating the development and execution of a LIMS User Acceptance Test Plan (UATP).

  7. 10 CFR 26.91 - Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use. 26.91 Section 26.91 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.91 Acceptable devices for conducting initial...

  8. 10 CFR 26.91 - Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use. 26.91 Section 26.91 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.91 Acceptable devices for conducting initial...

  9. 10 CFR 26.91 - Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use. 26.91 Section 26.91 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.91 Acceptable devices for conducting initial...

  10. 10 CFR 26.91 - Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use. 26.91 Section 26.91 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.91 Acceptable devices for conducting initial...

  11. 10 CFR 26.91 - Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Acceptable devices for conducting initial and confirmatory tests for alcohol and methods of use. 26.91 Section 26.91 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.91 Acceptable devices for conducting initial...

  12. Basic regulatory principles of Escherichia coli's electron transport chain for varying oxygen conditions.

    PubMed

    Henkel, Sebastian G; Ter Beek, Alexander; Steinsiek, Sonja; Stagge, Stefan; Bettenbrock, Katja; de Mattos, M Joost Teixeira; Sauter, Thomas; Sawodny, Oliver; Ederer, Michael

    2014-01-01

    For adaptation between anaerobic, micro-aerobic and aerobic conditions Escherichia coli's metabolism and in particular its electron transport chain (ETC) is highly regulated. Although it is known that the global transcriptional regulators FNR and ArcA are involved in oxygen response it is unclear how they interplay in the regulation of ETC enzymes under micro-aerobic chemostat conditions. Also, there are diverse results which and how quinones (oxidised/reduced, ubiquinone/other quinones) are controlling the ArcBA two-component system. In the following a mathematical model of the E. coli ETC linked to basic modules for substrate uptake, fermentation product excretion and biomass formation is introduced. The kinetic modelling focusses on regulatory principles of the ETC for varying oxygen conditions in glucose-limited continuous cultures. The model is based on the balance of electron donation (glucose) and acceptance (oxygen or other acceptors). Also, it is able to account for different chemostat conditions due to changed substrate concentrations and dilution rates. The parameter identification process is divided into an estimation and a validation step based on previously published and new experimental data. The model shows that experimentally observed, qualitatively different behaviour of the ubiquinone redox state and the ArcA activity profile in the micro-aerobic range for different experimental conditions can emerge from a single network structure. The network structure features a strong feed-forward effect from the FNR regulatory system to the ArcBA regulatory system via a common control of the dehydrogenases of the ETC. The model supports the hypothesis that ubiquinone but not ubiquinol plays a key role in determining the activity of ArcBA in a glucose-limited chemostat at micro-aerobic conditions.

  13. 78 FR 663 - Decommissioning Planning During Operations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-04

    ...] Decommissioning Planning During Operations AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide..., ``Decommissioning Planning During Operations.'' The guide describes a method that the NRC staff considers acceptable for use by holders of licenses in complying with the NRC's Decommissioning Planning Rule (DPR) (76 FR...

  14. The regulatory acceptance of alternatives in the European Union.

    PubMed

    Warbrick, E Vicky; Evans, Peter F

    2004-06-01

    Recently, progress has been made toward the regulatory acceptance of replacements in the European Union (EU), particularly with the introduction of in vitro methods for the prediction of skin corrosivity, dermal penetration, phototoxicity and embryotoxicity. In vitro genotoxicity tests are well established, and testing for this endpoint can be completed without animals, provided that clear negative outcomes are obtained. Tiered approaches including in vitro tests can also be used to address skin and eye irritation endpoints. Reductions and/or refinements in animal use are being achieved following the replacement of the oral LD50 test with alternative methods and the adoption of reduced test packages for materials, such as closed-system intermediates and certain polymers. Furthermore, the use of a "read-across" approach has reduced animal testing. Substantial gains in refinement will also be made with the recent acceptance of the local lymph node assay for skin sensitisation and the development of an acute inhalation toxicity method that avoids lethality as the endpoint. For the future, under the proposed EU Registration, Evaluation and Authorisation of Chemicals (REACH) scheme, it is envisaged that, where suitable in vitro methods exist, these should be used to support registration of substances produced at up to ten tonnes per annum. This proposal can only accelerate the further development, validation and regulatory acceptance of such alternative methods.

  15. Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused?

    PubMed

    Kemp, Robert; Prasad, Vinay

    2017-07-21

    Surrogate outcomes are not intrinsically beneficial to patients, but are designed to be easier and faster to measure than clinically meaningful outcomes. The use of surrogates as an endpoint in clinical trials and basis for regulatory approval is common, and frequently exceeds the guidance given by regulatory bodies. In this article, we demonstrate that the use of surrogates in oncology is widespread and increasing. At the same time, the strength of association between the surrogates used and clinically meaningful outcomes is often unknown or weak. Attempts to validate surrogates are rarely undertaken. When this is done, validation relies on only a fraction of available data, and often concludes that the surrogate is poor. Post-marketing studies, designed to ensure drugs have meaningful benefits, are often not performed. Alternatively, if a drug fails to improve quality of life or overall survival, market authorization is rarely revoked. We suggest this reliance on surrogates, and the imprecision surrounding their acceptable use, means that numerous drugs are now approved based on small yet statistically significant increases in surrogates of questionable reliability. In turn, this means the benefits of many approved drugs are uncertain. This is an unacceptable situation for patients and professionals, as prior experience has shown that such uncertainty can be associated with significant harm. The use of surrogate outcomes should be limited to situations where a surrogate has demonstrated robust ability to predict meaningful benefits, or where cases are dire, rare or with few treatment options. In both cases, surrogates must be used only when continuing studies examining hard endpoints have been fully recruited.

  16. The Expected Net Present Value of Developing Weight Management Drugs in the Context of Drug Safety Litigation.

    PubMed

    Chawla, Anita; Carls, Ginger; Deng, Edmund; Tuttle, Edward

    2015-07-01

    Following withdrawals, failures, and significant litigation settlements, drug product launches in the anti-obesity category slowed despite a large and growing unmet need. Litigation concerns, a more risk-averse regulatory policy, and the difficulty of developing a product with a compelling risk-benefit profile in this category may have limited innovators' expected return on investment and restricted investment in this therapeutic area. The objective of the study was to estimate perceived manufacturer risk associated with product safety litigation and increased development costs vs. revenue expectations on anticipated return on investment and to determine which scenarios might change a manufacturer's investment decision. Expected net present value of a weight-management drug entering pre-clinical trials was calculated for a range of scenarios representing evolving expectations of development costs, revenue, and litigation risk over the past 25 years. These three factors were based on published estimates, historical data, and analogs from other therapeutic areas. The main driver in expected net present value calculations is expected revenue, particularly if one assumes that litigation risk and demand are positively correlated. Changes in development costs associated with increased regulatory concern with potential safety issues for the past 25 years likely did not impact investment decisions. Regulatory policy and litigation risk both played a role in anti-obesity drug development; however, product revenue-reflecting efficacy at acceptable levels of safety-was by far the most important factor. To date, relatively modest sales associated with recent product introductions suggest that developing a product that is sufficiently efficacious with an acceptable level of safety continues to be the primary challenge in this market.

  17. 77 FR 72997 - Low-Level Waste Disposal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-07

    ...-2011-0012] RIN 3150-AI92 Low-Level Waste Disposal AGENCY: Nuclear Regulatory Commission. ACTION... Regulatory Commission (NRC) is proposing to amend its regulations that govern low-level radioactive waste... development of criteria for waste acceptance based on the results of these analyses. These amendments will...

  18. Expert views on societal responses to different applications of nanotechnology: a comparative analysis of experts in countries with different economic and regulatory environments

    NASA Astrophysics Data System (ADS)

    Gupta, Nidhi; Fischer, Arnout R. H.; George, Saji; Frewer, Lynn J.

    2013-08-01

    The introduction of different applications of nanotechnology will be informed by expert views regarding which (types of) application will be most societally acceptable. Previous research in Northern Europe has indicated that experts believe that various factors will be influential, predominant among these being public perceptions of benefit, need and consumer concern about contact with nanomaterials. These factors are thought by experts to differentiate societal acceptance and rejection of nanotechnology applications. This research utilises a larger sample of experts ( N = 67) drawn from Northern America, Europe, Australasia, India and Singapore to examine differences in expert opinion regarding societal acceptance of different applications of nanotechnology within different technological environments, consumer cultures and regulatory regimes. Perceived risk and consumer concerns regarding contact with nano-particles are thought by all experts to drive rejection, and perceived benefits to influence acceptance, independent of country. Encapsulation and delivery of nutrients in food was thought to be the most likely to raise societal concerns, while targeted drug delivery was thought most likely to be accepted. Lack of differentiation between countries suggests that expert views regarding social acceptance may be homogenous, independent of local contextual factors.

  19. Decontamination issues for chemical and biological warfare agents: how clean is clean enough?

    PubMed

    Raber, E; Jin, A; Noonan, K; McGuire, R; Kirvel, R D

    2001-06-01

    The objective of this assessment is to determine what level of cleanup will be required to meet regulatory and stakeholder needs in the case of a chemical and/or biological incident at a civilian facility. A literature review for selected, potential chemical and biological warfare agents shows that dose information is often lacking or controversial. Environmental regulatory limits or other industrial health guidelines that could be used to help establish cleanup concentration levels for such agents are generally unavailable or not applicable for a public setting. Although dose information, cleanup criteria, and decontamination protocols all present challenges to effective planning, several decontamination approaches are available. Such approaches should be combined with risk-informed decision making to establish reasonable cleanup goals for protecting health, property, and resources. Key issues during a risk assessment are to determine exactly what constitutes a safety hazard and whether decontamination is necessary or not for a particular scenario. An important conclusion is that cleanup criteria are site dependent and stakeholder specific. The results of a modeling exercise for two outdoor scenarios are presented to reinforce this conclusion. Public perception of risk to health, public acceptance of recommendations based on scientific criteria, political support, time constraints, and economic concerns must all be addressed in the context of a specific scenario to yield effective and acceptable decontamination.

  20. Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview.

    PubMed

    Woolacott, Nerys; Corbett, Mark; Jones-Diette, Julie; Hodgson, Robert

    2017-10-01

    Regulatory authorities are approving innovative therapies with limited evidence. Although this level of data is sufficient for the regulator to establish an acceptable risk-benefit balance, it is problematic for downstream health technology assessment, where assessment of cost-effectiveness requires reliable estimates of effectiveness relative to existing clinical practice. Some key issues associated with a limited evidence base include using data, from nonrandomized studies, from small single-arm trials, or from single-center trials; and using surrogate end points. We examined these methodological challenges through a pragmatic review of the available literature. Methods to adjust nonrandomized studies for confounding are imperfect. The relative treatment effect generated from single-arm trials is uncertain and may be optimistic. Single-center trial results may not be generalizable. Surrogate end points, on average, overestimate treatment effects. Current methods for analyzing such data are limited, and effectiveness claims based on these suboptimal forms of evidence are likely to be subject to significant uncertainty. Assessments of cost-effectiveness, based on the modeling of such data, are likely to be subject to considerable uncertainty. This uncertainty must not be underestimated by decision makers: methods for its quantification are required and schemes to protect payers from the cost of uncertainty should be implemented. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. Implementation of the 3Rs (refinement, reduction, and replacement): validation and regulatory acceptance considerations for alternative toxicological test methods.

    PubMed

    Schechtman, Leonard M

    2002-01-01

    Toxicological testing in the current regulatory environment is steeped in a history of using animals to answer questions about the safety of products to which humans are exposed. That history forms the basis for the testing strategies that have evolved to satisfy the needs of the regulatory bodies that render decisions that affect, for the most part, virtually all phases of premarket product development and evaluation and, to a lesser extent, postmarketing surveillance. Only relatively recently have the levels of awareness of, and responsiveness to, animal welfare issues reached current proportions. That paradigm shift, although sluggish, has nevertheless been progressive. New and alternative toxicological methods for hazard evaluation and risk assessment have now been adopted and are being viewed as a means to address those issues in a manner that considers humane treatment of animals yet maintains scientific credibility and preserves the goal of ensuring human safety. To facilitate this transition, regulatory agencies and regulated industry must work together toward improved approaches. They will need assurance that the methods will be reliable and the results comparable with, or better than, those derived from the current classical methods. That confidence will be a function of the scientific validation and resultant acceptance of any given method. In the United States, to fulfill this need, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and its operational center, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), have been constituted as prescribed in federal law. Under this mandate, ICCVAM has developed a process and established criteria for the scientific validation and regulatory acceptance of new and alternative methods. The role of ICCVAM in the validation and acceptance process and the criteria instituted toward that end are described. Also discussed are the participation of the US Food and Drug Administration (FDA) in the ICCVAM process and that agency's approach to the application and implementation of ICCVAM-recommended methods.

  3. 29 CFR 1926.29 - Acceptable certifications.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Acceptable certifications. (a) Pressure vessels. Current and valid certification by an insurance company or... by an insurance company or regulatory authority attesting to the safe installation, inspection, and... types of pressure vessels and similar equipment are contained in subparts F and O of this part. ...

  4. 75 FR 77675 - AREVA NP, Inc.; Confirmatory Order (Effective Immediately)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-13

    ..., appropriate notification of regulatory authorities, safety culture and safety conscious work environment...., outside the global AREVA organization), safety culture assessment in accordance with an accepted nuclear....e., outside the global AREVA organization), safety culture assessment in accordance with an accepted...

  5. 78 FR 64030 - Monitoring Criteria and Methods To Calculate Occupational Radiation Doses

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0234] Monitoring Criteria and Methods To Calculate... regulatory guide (DG), DG-8031, ``Monitoring Criteria and Methods to Calculate Occupational Radiation Doses.'' This guide describes methods that the NRC staff considers acceptable for licensees to use to determine...

  6. Approaches for Increasing Acceptance of Physiologically Based Pharmacokinetic Models in Public Health Risk Assessment

    EPA Science Inventory

    Physiologically based pharmacokinetic (PBPK) models have great potential for application in regulatory and non-regulatory public health risk assessment. The development and application of PBPK models in chemical toxicology has grown steadily since their emergence in the 1980s. Ho...

  7. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Nebraska. Preliminary background report

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

    Feurer, D A; Weaver, C L; Gallagher, K C

    1980-01-01

    The state agency with principal authority to regulate electric public utilities is the Power Review Board (Board). However, the Board in fact, exercised little regulatory authority over heat and power utilities because all electrical power in Nebraska is currently supplied by public authorities and is not subject to regulation by the Board. Gas and water utilities are also subject to general supervision by municipalities. The Board is compised of five members - an attorney, an engineer, one accountant, two lay - persons appointed by the governor and confirmed by the legislature. All members are appointed to overlapping four-year terms, andmore » none may serve more than two consecutive terms. Decisions by the Board require the approval of a majority of its members. The Public Service Commission of Nebraska is a constitutionally created body. Its powers and duties include the regulation of rates, service, and general control of common carriers as the legislature may provide by law. Other state agencies also possess limited regulatory jurisdiction which may be relevant to an energy facility. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.« less

  8. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... applications. 50.8 Section 50.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT APPLICATIONS FOR PERMITS TO SITE INTERSTATE ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be...

  9. 75 FR 61530 - Issuance of Regulatory Guides

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Materials Code Case Acceptability, ASME Section III,'' and RG 1.147, Rev. 16, ``Inservice Inspection Code Case Acceptability, ASME Section XI, Division 1.'' FOR FURTHER INFORMATION CONTACT: Wallace E. Norris... specific problems or postulated accidents, and data the staff needs in its review of applications for...

  10. State and Local Perspective on Implementation of the Centers for Disease Control and Prevention Dog Confinement Agreement.

    PubMed

    Zaganjor, I; Sinclair, J R; Coleman, M S

    2015-12-01

    The Centers for Disease Control and Prevention (CDC) works in conjunction with state, territorial, local and tribal agencies (STLTAs) to prevent the transmission of infectious agents. Issuance of confinement agreements using CDC Form 75.37 'Notice to Owners and Importers of Dogs' to importers of dogs that are not vaccinated or incompletely vaccinated against rabies is part of the agency's regulatory programme to prevent the entry of dogs infected with rabies. Although this is a regulatory programme that depends heavily on partnerships between CDC and STLTAs, CDC had never formally evaluated the acceptability of the confinement agreement process with these partners. Thus, a short survey of nine STLTAs was conducted to evaluate whether these partners have enough personnel and resources to implement the regulation and their general opinions of the confinement agreement process. The results illustrate that CDC partners are dissatisfied to some extent with the process, and there are multiple issues limiting their success in enforcing the regulation. © 2015 Blackwell Verlag GmbH.

  11. 77 FR 1119 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-09

    ... in 1984 by agreement of the Financial Accounting Foundation (``FAF'') and ten national associations... standards of accounting and financial reporting for U.S. state and local governments.\\3\\ The GASB is... and publication of the generally accepted accounting principles (``GAAP'') for state and local...

  12. 75 FR 36717 - Washington State University; Notice of Acceptance for Docketing and Opportunity for Hearing on...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... University (the licensee, WSU) to operate the Washington State University Modified TRIGA Nuclear Radiation... NUCLEAR REGULATORY COMMISSION [Docket No. 50-27; Facility Operating License No. R-76; NRC-2010... Safeguards Information and Sensitive Unclassified Non-Safeguards Information AGENCY: Nuclear Regulatory...

  13. 12 CFR 1263.11 - Financial condition requirement for depository institutions and CDFI credit unions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... following documents: (1) Regulatory financial reports. The regulatory financial reports filed by the... standards by a certified public accounting firm which submits a report on the applicant; (ii) The most... accepted auditing standards by a certified public accounting firm which submits a report on the...

  14. 12 CFR 1263.11 - Financial condition requirement for depository institutions and CDFI credit unions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... following documents: (1) Regulatory financial reports. The regulatory financial reports filed by the... standards by a certified public accounting firm which submits a report on the applicant; (ii) The most... accepted auditing standards by a certified public accounting firm which submits a report on the...

  15. 12 CFR 1263.11 - Financial condition requirement for depository institutions and CDFI credit unions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... following documents: (1) Regulatory financial reports. The regulatory financial reports filed by the... standards by a certified public accounting firm which submits a report on the applicant; (ii) The most... accepted auditing standards by a certified public accounting firm which submits a report on the...

  16. 12 CFR 1263.11 - Financial condition requirement for depository institutions and CDFI credit unions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... following documents: (1) Regulatory financial reports. The regulatory financial reports filed by the... standards by a certified public accounting firm which submits a report on the applicant; (ii) The most... accepted auditing standards by a certified public accounting firm which submits a report on the...

  17. 10 CFR 51.108 - Public hearings on Commission findings that inspections, tests, analyses, and acceptance criteria...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CFR 52.103(b), the Commission will not admit any contentions on environmental issues, the adequacy of... NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National Environmental Policy Act-Regulations Implementing Section 102(2...

  18. 77 FR 8938 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... contained sufficient clarity for certain definitions, such as ``commodities,'' ``corporate debt,'' ``US... internal definitions of business lines and to comply with generally accepted accounting principles (``GAAP... and equitable principles of trade,'' and, ``in general, to protect investors and the public interest...

  19. 76 FR 8724 - First Light Hydro Generating Company; Notice of Application Accepted for Filing, Soliciting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2485-059] First Light Hydro..., Federal Energy Regulatory Commission, 888 First Street, NE., Washington, DC 20426. Commenters can submit... photovoltaic solar array will provide power to Northfield Mountain Visitor's Center. The solar array would be...

  20. 76 FR 7183 - Verdant Power, LLC; Notice of Application Accepted for Filing, Soliciting Motions To Intervene...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-09

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12611-005] Verdant Power.... Name of Project: Roosevelt Island Tidal Energy (RITE) Project f. Location: The proposed project would..., mail an original and seven copies to: Kimberly D. Bose, Secretary, Federal Energy Regulatory Commission...

  1. 77 FR 36014 - Initial Test Program of Emergency Core Cooling Systems for Boiling-Water Reactors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0134] Initial Test Program of Emergency Core Cooling... for public comment draft regulatory guide (DG), DG-1277, ``Initial Test Program of Emergency Core... acceptable to implement with regard to initial testing features of emergency core cooling systems (ECCSs) for...

  2. MULTI-MEDIA MICROBIOLOGICAL RISK ASSESSMENT METHODOLOGY FOR MUNICIPAL WASTEWATER SLUDGES

    EPA Science Inventory

    In order to reduce the risk of municipal sludge to acceptable levels, the U.S. EPA has undertaken a regulatory program based on risk assessment and risk management. The key to such a program is the development of a methodology which allows the regulatory agency to quantify the re...

  3. 75 FR 16202 - Notice of Issuance of Regulatory Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ..., Revision 2, ``An Acceptable Model and Related Statistical Methods for the Analysis of Fuel Densification.... Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing a revision to an existing guide in the... nuclear power reactors. To meet these objectives, the guide describes statistical methods related to...

  4. 75 FR 68657 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-08

    ... LLC To Increase the Maximum Order Size Accepted by Floor Broker Systems From 25,000,000 Shares to 99... order size accepted by Floor broker systems from 25,000,000 shares to 99,000,000 shares. The text of the... systems shall accept a maximum order size of 99,000,000, an increase from the current 25,000,000 share...

  5. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods

    PubMed Central

    Dozier, Samantha; Brown, Jeffrey; Currie, Alistair

    2011-01-01

    Simple Summary Many vaccines are tested for quality in experiments that require the use of large numbers of animals in procedures that often cause significant pain and distress. Newer technologies have fostered the development of vaccine quality control tests that reduce or eliminate the use of animals, but the availability of these newer methods has not guaranteed their acceptance by regulators or use by manufacturers. We discuss a strategic approach that has been used to assess and ultimately increase the use of non-animal vaccine quality tests in the U.S. and U.K. Abstract In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches. PMID:26486625

  6. 78 FR 73566 - Standard Format and Content for a License Application for an Independent Spent Fuel Storage...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-3042, ``Standard Format and Content for a License Application for an Independent Spent Fuel Storage Installation or a Monitored Retrievable Storage Facility.'' This draft regulatory guide is proposed revision 2 of Regulatory Guide 3.50, which provides a format that the NRC considers acceptable for submitting the information for license applications to store spent nuclear fuel, high-level radioactive waste, and/or reactor-related Greater than Class C waste.

  7. Factors Influencing Acceptability and Perceived Impacts of a Mandatory ePortfolio Implemented by an Occupational Therapy Regulatory Organization.

    PubMed

    Vachon, Brigitte; Foucault, Marie-Lyse; Giguère, Charles-Édouard; Rochette, Annie; Thomas, Aliki; Morel, Martine

    2018-01-01

    The use of ePortfolios has been implemented in several regulatory organizations to encourage clinicians' engagement in continuing professional development (CPD). However, their use has achieved mixed success, and multiple personal and contextual factors can influence their impacts on practice change. The aim of this study was to identify which factors influence the acceptability and perceived impacts of an ePortfolio implemented by an occupational therapy regulatory organization in one Canadian province. A cross-sectional online survey design was used. The survey was sent to registered occupational therapists in Quebec. Multiple regression analyses were conducted to identify factors influencing acceptability and outcomes: ease of use, satisfaction, impact on implementation of the CPD plan, and competence improvement. The survey was fully completed by 546 participants. Factors significantly influencing the ePortfolio acceptability and perceived impacts were attitude toward and familiarity with the portfolio, confidence in reflective skills, engagement in the CPD plan, and desire for feedback. Time spent completing the ePortfolio and the fact of completing it in teams were negatively associated with the outcomes. Shaping more favorable user attitudes, helping users recognize and experience the tool's benefits for their practice, and fostering confidence in their reflective skills are important factors that can be addressed to improve ePortfolio acceptability and outcomes. Contextual factors, such as time spent completing the ePortfolio and completing it in teams, seem to reflect greater difficulty with using the tool. Study findings can contribute to improving ePortfolio implementation in the CPD context.

  8. 75 FR 36710 - The Texas Engineering Experiment Station/Texas A&M University System; Notice of Acceptance for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... for the Nuclear Science Center Reactor and Order Imposing Procedures for Access To Safeguards Information and Sensitive Unclassified Non- Safeguards Information AGENCY: Nuclear Regulatory Commission. ACTION: Notice of acceptance for docketing. FOR FURTHER INFORMATION CONTACT: Christian Cowdrey, Project...

  9. 10 CFR 32.110 - Acceptance sampling procedures under certain specific licenses.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Acceptance sampling procedures under certain specific licenses. 32.110 Section 32.110 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL Quality Control Sampling Procedures § 32...

  10. 10 CFR 32.110 - Acceptance sampling procedures under certain specific licenses.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Acceptance sampling procedures under certain specific licenses. 32.110 Section 32.110 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL Quality Control Sampling Procedures § 32...

  11. 75 FR 8320 - Coastal Hydropower LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13618-000] Coastal Hydropower LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications February 18, 2010. On November 5, 2009, Coastal Hydropower...

  12. 78 FR 45983 - Acceptability of Corrective Action Programs for Fuel Cycle Facilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-30

    ... Programs for Fuel Cycle Facilities AGENCY: Nuclear Regulatory Commission. ACTION: Draft NUREG; withdrawal... withdrawing draft NUREG-2154, ``Acceptability of Corrective Action Programs for Fuel Cycle Facilities,'' based... determine whether a submittal for a Corrective Action Program (CAP), voluntarily submitted by fuel cycle...

  13. 75 FR 74697 - Central Oregon Irrigation District; Notice of Competing Preliminary Permit Application Accepted...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-01

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13858-000] Central Oregon Irrigation District; Notice of Competing Preliminary Permit Application Accepted for Filing and Soliciting Comments and Interventions November 22, 2010. On October 6, 2010, Central Oregon Irrigation District filed...

  14. Thermoluminescent dosimeters (TLD) quality assurance network in the Czech Republic.

    PubMed

    Kroutilķková, Daniela; Novotný, Josef; Judas, Libor

    2003-02-01

    The Czech thermoluminescent dosimeters (TLD) quality assurance network was established in 1997. Its aim is to pursue a regular independent quality audit in Czech radiotherapy centres and to support state supervision. The audit is realised via mailed TL dosimetry. The TLD system consists of encapsulated LiF:Mg,Ti powder (type MT-N) read with Harshaw manual reader model 4000. Basic mode of the TLD audit covers measurements under reference conditions, specifically beam calibration checks for all clinically used photon and electron beams. Advanced mode consists of measurements under both reference and non-reference conditions using a solid multipurpose phantom ('Leuven phantom') for photon beams. The radiotherapy centres are instructed to deliver to the TLD on central beam axis absorbed dose of 2 Gy calculated with their treatment planning system for a particular treatment set-up. The TLD measured doses are compared with the calculated ones. Deviations of +/-3% are considered acceptable for both basic and advanced mode of the audit. There are 34 radiotherapy centres in the Czech Republic. They undergo the basic mode of the TLD audit regularly every 2 years. If a centre shows a deviation outside the acceptance level, it is audited more often. Presently, most of the checked beams comply with the acceptance level. The advanced TLD audit has been implemented as a pilot study for the present. The results were mostly within the acceptance limit for the measurements on-axis, whereas for off-axis points they fell beyond the limit more frequently, especially for set-ups with inhomogeneities, oblique incidence and wedges. The results prove the importance of the national TLD quality assurance network. It has contributed to the improvement of clinical dosimetry in the Czech Republic. In addition, it helps the regulatory authority to monitor effectively and regularly radiotherapy centres.

  15. A Web-based Tool to Aid the Identification of Chemicals Potentially Posing a Health Risk through Percutaneous Exposure.

    PubMed

    Gorman Ng, Melanie; Milon, Antoine; Vernez, David; Lavoué, Jérôme

    2016-04-01

    Occupational hygiene practitioners typically assess the risk posed by occupational exposure by comparing exposure measurements to regulatory occupational exposure limits (OELs). In most jurisdictions, OELs are only available for exposure by the inhalation pathway. Skin notations are used to indicate substances for which dermal exposure may lead to health effects. However, these notations are either present or absent and provide no indication of acceptable levels of exposure. Furthermore, the methodology and framework for assigning skin notation differ widely across jurisdictions resulting in inconsistencies in the substances that carry notations. The UPERCUT tool was developed in response to these limitations. It helps occupational health stakeholders to assess the hazard associated with dermal exposure to chemicals. UPERCUT integrates dermal quantitative structure-activity relationships (QSARs) and toxicological data to provide users with a skin hazard index called the dermal hazard ratio (DHR) for the substance and scenario of interest. The DHR is the ratio between the estimated 'received' dose and the 'acceptable' dose. The 'received' dose is estimated using physico-chemical data and information on the exposure scenario provided by the user (body parts exposure and exposure duration), and the 'acceptable' dose is estimated using inhalation OELs and toxicological data. The uncertainty surrounding the DHR is estimated with Monte Carlo simulation. Additional information on the selected substances includes intrinsic skin permeation potential of the substance and the existence of skin notations. UPERCUT is the only available tool that estimates the absorbed dose and compares this to an acceptable dose. In the absence of dermal OELs it provides a systematic and simple approach for screening dermal exposure scenarios for 1686 substances. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  16. Public Acceptance of Plant Biotechnology and GM Crops

    PubMed Central

    Lucht, Jan M.

    2015-01-01

    A wide gap exists between the rapid acceptance of genetically modified (GM) crops for cultivation by farmers in many countries and in the global markets for food and feed, and the often-limited acceptance by consumers. This review contrasts the advances of practical applications of agricultural biotechnology with the divergent paths—also affecting the development of virus resistant transgenic crops—of political and regulatory frameworks for GM crops and food in different parts of the world. These have also shaped the different opinions of consumers. Important factors influencing consumer’s attitudes are the perception of risks and benefits, knowledge and trust, and personal values. Recent political and societal developments show a hardening of the negative environment for agricultural biotechnology in Europe, a growing discussion—including calls for labeling of GM food—in the USA, and a careful development in China towards a possible authorization of GM rice that takes the societal discussions into account. New breeding techniques address some consumers’ concerns with transgenic crops, but it is not clear yet how consumers’ attitudes towards them will develop. Discussions about agriculture would be more productive, if they would focus less on technologies, but on common aims and underlying values. PMID:26264020

  17. Public Acceptance of Plant Biotechnology and GM Crops.

    PubMed

    Lucht, Jan M

    2015-07-30

    A wide gap exists between the rapid acceptance of genetically modified (GM) crops for cultivation by farmers in many countries and in the global markets for food and feed, and the often-limited acceptance by consumers. This review contrasts the advances of practical applications of agricultural biotechnology with the divergent paths-also affecting the development of virus resistant transgenic crops-of political and regulatory frameworks for GM crops and food in different parts of the world. These have also shaped the different opinions of consumers. Important factors influencing consumer's attitudes are the perception of risks and benefits, knowledge and trust, and personal values. Recent political and societal developments show a hardening of the negative environment for agricultural biotechnology in Europe, a growing discussion-including calls for labeling of GM food-in the USA, and a careful development in China towards a possible authorization of GM rice that takes the societal discussions into account. New breeding techniques address some consumers' concerns with transgenic crops, but it is not clear yet how consumers' attitudes towards them will develop. Discussions about agriculture would be more productive, if they would focus less on technologies, but on common aims and underlying values.

  18. Validation in Support of Internationally Harmonised OECD Test Guidelines for Assessing the Safety of Chemicals.

    PubMed

    Gourmelon, Anne; Delrue, Nathalie

    Ten years elapsed since the OECD published the Guidance document on the validation and international regulatory acceptance of test methods for hazard assessment. Much experience has been gained since then in validation centres, in countries and at the OECD on a variety of test methods that were subjected to validation studies. This chapter reviews validation principles and highlights common features that appear to be important for further regulatory acceptance across studies. Existing OECD-agreed validation principles will most likely generally remain relevant and applicable to address challenges associated with the validation of future test methods. Some adaptations may be needed to take into account the level of technique introduced in test systems, but demonstration of relevance and reliability will continue to play a central role as pre-requisite for the regulatory acceptance. Demonstration of relevance will become more challenging for test methods that form part of a set of predictive tools and methods, and that do not stand alone. OECD is keen on ensuring that while these concepts evolve, countries can continue to rely on valid methods and harmonised approaches for an efficient testing and assessment of chemicals.

  19. Time to Reject the Linear-No Threshold Hypothesis and Accept Thresholds and Hormesis: A Petition to the U.S. Nuclear Regulatory Commission.

    PubMed

    Marcus, Carol S

    2015-07-01

    On February 9, 2015, I submitted a petition to the U.S. Nuclear Regulatory Commission (NRC) to reject the linear-no threshold (LNT) hypothesis and ALARA as the bases for radiation safety regulation in the United States, using instead threshold and hormesis evidence. In this article, I will briefly review the history of LNT and its use by regulators, the lack of evidence supporting LNT, and the large body of evidence supporting thresholds and hormesis. Physician acceptance of cancer risk from low dose radiation based upon federal regulatory claims is unfortunate and needs to be reevaluated. This is dangerous to patients and impedes good medical care. A link to my petition is available: http://radiationeffects.org/wp-content/uploads/2015/03/Hormesis-Petition-to-NRC-02-09-15.pdf, and support by individual physicians once the public comment period begins would be extremely important.

  20. Nuclear regulation: an evaluative study. [Monograph

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

    Wood, W.C.

    This paper gives an overview of nuclear regulation, followed by an account of the legislative rationale and the economic rationale for safety regulation of nuclear technology. It goes on to review the structure and safety programs of the Nuclear Regulatory Commission (NRC) and to show how many of the NRC's problems are unlike those facing other regulatory agencies. In assessing the results of nuclear regulation, it examines whether regulation has produced an acceptable level of safety and the nature of the evidence on acceptability. It concludes that the existing level of safety achievement is not cost-effective, and identifies some sourcesmore » of regulatory failure as a failure to make hard decisions on risk, diffuse responsibility for safety, and economic dissincentives to cost-effective safety. Recommendations for reforming NRC are to separate technical issues from social ones and to correct the incentives for safety. 153 references, 6 figures, 4 tables.« less

  1. 75 FR 53962 - Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13823-000] Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting... Currents Energy Services, LLC filed an application for a preliminary permit, pursuant to section 4(f) of...

  2. 10 CFR 26.111 - Checking the acceptability of the urine specimen.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Checking the acceptability of the urine specimen. 26.111 Section 26.111 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for..., the collector shall measure the temperature of the specimen. The temperature-measuring device used...

  3. 10 CFR 26.111 - Checking the acceptability of the urine specimen.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Checking the acceptability of the urine specimen. 26.111 Section 26.111 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for..., the collector shall measure the temperature of the specimen. The temperature-measuring device used...

  4. 75 FR 61479 - Kendall Head Tidal Energy Project; Notice of Preliminary Permit Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13801-000] Kendall Head Tidal Energy Project; Notice of Preliminary Permit Application Accepted for Filing and Soliciting... Federal Power Act, proposing to study the feasibility of the Kendall Head Tidal Energy Project, located in...

  5. 75 FR 47586 - New York Tidal Energy Company; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ...) 50 to 150 Tidal In Stream Energy Conversion (TISEC) devices consisting of, (2) rotating propeller... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13730-000] New York Tidal Energy Company; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments...

  6. 10 CFR 26.111 - Checking the acceptability of the urine specimen.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Checking the acceptability of the urine specimen. 26.111 Section 26.111 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for..., the collector shall measure the temperature of the specimen. The temperature-measuring device used...

  7. 75 FR 7469 - Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ...-Stream Energy Conversion Devices (TISEC devices) to transmit the electricity from the turbines to the... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13605-000] Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting...

  8. 75 FR 26208 - Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12731-004] Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting... April 7, 2010, Natural Currents Energy Services, LLC, filed an application for a preliminary permit...

  9. 75 FR 78235 - Dodge Mill Realty, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13890-000] Dodge Mill Realty, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications December 8, 2010. On December 3, 2010, Dodge Mill Realty...

  10. 76 FR 25322 - Oklahoma Rose Water LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13854-000] Oklahoma Rose Water LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On September 30, 2010, Oklahoma Rose Water LLC filed an...

  11. 76 FR 25321 - Wild Flower Water LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13842-000] Wild Flower Water LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On September 23, 2010, Wild Flower Water LLC filed an...

  12. 75 FR 2128 - Basin Farm Renewable, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-14

    ... the feasibility of the Basin Farm Renewable Energy Project, to be located on Saxtons River, in... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13640-000] Basin Farm Renewable, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments...

  13. 75 FR 2127 - Basin Farm Renewable, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-14

    ... the feasibility of the Basin Farm Renewable Energy Project Project, to be located on Saxtons River, in... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13643-000] Basin Farm Renewable, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments...

  14. 76 FR 6459 - Mahoning Hydropower, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-04

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13954-000] Mahoning Hydropower, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments... Hydropower, LLC filed an application for a preliminary permit, pursuant to section 4(f) of the Federal Power...

  15. 75 FR 34725 - Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13795-000] Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications; Mahoning Hydropower, LLC June 10, 2010. On May 25, 2010, Mahoning Hydropower, LLC filed an...

  16. 76 FR 1613 - Mahoning Hydropower, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-11

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13877-000] Mahoning Hydropower, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications January 4, 2011. On November 4, 2010, Mahoning Hydro, LLC...

  17. 76 FR 7838 - Mahoning Hydropower, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-11

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13953-000] Mahoning Hydropower, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments... Hydropower, LLC filed an application for a preliminary permit, pursuant to section 4(f) of the Federal Power...

  18. 76 FR 45252 - Reliable Storage 1 LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-28

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14125-000] Reliable Storage 1 LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On March 25, 2011, Reliable Storage 1 LLC, filed an...

  19. 76 FR 45251 - Reliable Storage 1 LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-28

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14121-000] Reliable Storage 1 LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On March 25, 2011, Reliable Storage 1 LLC, filed an...

  20. 76 FR 45252 - Reliable Storage 1 LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-28

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14122-000] Reliable Storage 1 LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On March 25, 2011, Reliable Storage 1 LLC, filed an...

  1. 76 FR 45251 - Reliable Storage 1 LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-28

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14124-000] Reliable Storage 1 LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On March 25, 2011, Reliable Storage 1 LLC, filed an...

  2. 75 FR 65312 - Vortex Hydro Energy, LLC; Notice of Competing Preliminary Permit Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13831-000] Vortex Hydro Energy, LLC; Notice of Competing Preliminary Permit Application Accepted for Filing and Soliciting Comments and Interventions October 15, 2010. On August 9, 2010, Vortex Hydro Energy, LLC filed an...

  3. 78 FR 2989 - PayneBridge, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13346-002] PayneBridge, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On November 1, 2012, PayneBridge, LLC filed an application for a...

  4. Alkali activated solidification/stabilisation of air pollution control residues and co-fired pulverised fuel ash.

    PubMed

    Shirley, Robin; Black, Leon

    2011-10-30

    This paper examines the potential treatment by solidification/stabilisation (S/S) of air pollution control (APC) residues using only waste materials otherwise bound for disposal, namely a pulverised fuel ash (PFA) from a co-fired power station and a waste caustic solution. The use of waste materials to stabilise hazardous wastes in order to meet waste acceptance criteria (WAC) would offer an economical and efficient method for reducing the environmental impact of the hazardous waste. The potential is examined against leach limits for chlorides, sulphates and total dissolved solids, and compressive strength performance described in the WAC for stable non-reactive (SNR) hazardous waste landfill cells in England and Wales. The work demonstrates some potential for the treatment, including suitable compressive strengths to meet regulatory limits. Monolithic leach results showed good encapsulation compared to previous work using a more traditional cement binder. However, consistent with previous work, SNR WAC for chlorides was not met, suggesting the need for a washing stage. The potential problems of using a non-EN450 PFA for S/S applications were also highlighted, as well as experimental results which demonstrate the effect of ionic interactions on the mobility of phases during regulatory leach testing. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. 76 FR 71960 - KC Hydo LLC of New Hampshire; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-21

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14244-000] KC Hydo LLC of... electrical generating equipment with total hydraulic capacity of 160 cubic feet per second (cfs) and total... D. Bose, Secretary, Federal Energy Regulatory Commission, 888 First Street, NE., Washington, DC...

  6. 76 FR 72202 - The City of East Providence; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14306-000] The City of East... powerhouse; (4) a new or refurbished vertical Francis turbine/generator with total hydraulic capacity of 100...: Kimberly D. Bose, Secretary, Federal Energy Regulatory Commission, 888 First Street NE., Washington, DC...

  7. 78 FR 62348 - Erie Boulevard Hydropower, L.P.; Notice of Application Accepted for Filing and Soliciting Motions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-18

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 7320-042] Erie Boulevard...: Secretary, Federal Energy Regulatory Commission, 888 First Street NE., Washington, DC 20426. The first page... of: (1) A 201-foot-long, 32- foot-high maximum height concrete gravity-type dam having a spillway...

  8. 76 FR 63917 - Ocean Renewable Power Company, LLC; Notice of Application Accepted for Filing, Soliciting Motions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-14

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12711-005] Ocean Renewable... Company, LLC. e. Name of Project: Cobscook Bay Tidal Energy Project. f. Location: The proposed project..., mail an original and seven copies to: Kimberly D. Bose, Secretary, Federal Energy Regulatory Commission...

  9. Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

    USGS Publications Warehouse

    McCarty, L.S.; Landrum, P.F.; Luoma, S.N.; Meador, J.P.; Merten, A.A.; Shephard, B.K.; van Wezelzz, A.P.

    2011-01-01

    The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residueeffect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions. ??:2010 SETAC.

  10. 10 CFR 40.60 - Reporting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... to avoid exposures to radiation or radioactive materials that could exceed regulatory limits or... releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The equipment is required to be...

  11. 10 CFR 40.60 - Reporting requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... to avoid exposures to radiation or radioactive materials that could exceed regulatory limits or... releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The equipment is required to be...

  12. 10 CFR 40.60 - Reporting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... to avoid exposures to radiation or radioactive materials that could exceed regulatory limits or... releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The equipment is required to be...

  13. [Regulatory policies and public opinion: the case of smoking].

    PubMed

    Saltó, Esteve; Joan R, Villalbí; Valverde, Araceli; Baranda, Lucía; Plasencia, Antoni

    2006-01-01

    Collecting and disseminating information about the public opinion on a regulatory process gives visibility to the silent social support and facilitates the process, which often confronts resistance from interest groups. This paper presents a survey about a proposed legislation on tobacco in its final stages and its results, and some considerations on the use of this sort of information in change processes. Cross sectional descriptive study. In December 2005 a brief telephone survey was made to a population sample of 18 and more years of age (N=830) in Catalonia (Spain). The questionnaire explored opinions on the proposed regulations under discussion. We present the degree of support and the rating of nine regulatory measures, stratified by the respondents use of tobacco. Daily smokers are 26.3% of the surveyed population. Awareness and general support for tobacco regulation are very high. Aspects with wider support include bans on sales to minors (97.3%), smoking in enclosed public places (92.8%) and workplaces (89%), and publicity (90.8%). The aspect with less social support is banning smoking in bars and cafes (80.2%). The population supports widely tobacco regulation. This reinforces the process and weakens the arguments of those against it. Although smokers are less supportive, most of them accept the regulations, except for limitations in bars and cafes.

  14. 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.

  15. 77 FR 71023 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-28

    ... Acceptance Cut-Off Time Cannot Be Past 4:30 p.m. November 21, 2012. Pursuant to Section 19(b)(1) of the... that the order acceptance cut-off time cannot be past 4:30 p.m. The text of the proposed rule change is... order acceptance cut-off time cannot be past 4:30 p.m. (or 30 minutes after the scheduled close in the...

  16. 77 FR 73106 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-07

    ... Amending Rule 123C(9)(a)(1)(ii)--Equities To Delete the Requirement That the Order Acceptance Cut-Off Time... order acceptance cut-off time cannot be past 4:30 p.m. The text of the proposed rule change is available... acceptance cut-off time cannot be past 4:30 p.m. (or 30 minutes after the scheduled close in the case of an...

  17. Canadian regulatory perspectives on genome engineered crops

    PubMed Central

    Smyth, Stuart J.

    2017-01-01

    ABSTRACT New breeding techniques in plant agriculture exploded upon the scene about two years ago, in 2014. While these innovative plant breeding techniques, soon to be led by CRISPR/Cas9, initially appear to hold tremendous promise for plant breeding, if not a revolution for the industry, the question of how the products of these technologies will be regulated is rapidly becoming a key aspect of the technology's future potential. Regulation of innovative technologies and products has always lagged that of the science, but in the past decade, regulatory systems in many jurisdictions have become gridlocked as they try to regulate genetically modified (GM) crops. This regulatory incapability to efficiently assess and approve innovative new agricultural products is particularly important for new plant breeding techniques as if these techniques are classified as genetically modified breeding techniques, then their acceptance and future will diminish considerably as they will be rejected by the European Union. Conversely, if the techniques are accepted as conventional plant breeding, then the future is blindingly bright. This article examines the international debate about the regulation of new plant breeding techniques and then assesses how the Canadian regulatory system has approached the regulation of these technologies through two more public product approvals, GM apples and GM potatoes, then discusses other crop variety approval and those in the regulatory pipeline. PMID:27858499

  18. Rationales for regulatory activity

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

    Perhac, R.M.

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  19. Teratology studies in the minipig.

    PubMed

    McAnulty, Peter A

    2013-01-01

    The minipig is a suitable species for regulatory teratology testing and may be regarded as an alternative to the rabbit, dog, and primate. The first successful regulatory teratology studies in the minipig were performed in the 1990s. It became clear that minipigs have several benefits over the other non-rodents, as they are purpose-bred for laboratory use, they are sexually mature at approximately 5 months of age, and they produce multiple offspring. The minipig has subsequently gained regulatory acceptance in the teratology testing of new drugs.

  20. 75 FR 47586 - New York Tidal Energy Company; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12665-004] New York Tidal Energy Company; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications July 30, 2010. On May 12, 2010, New York Tidal Energy...

  1. 75 FR 7467 - Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ... of 300 kW; (3) one or more clusters of Tidal In-Stream Energy Conversion Devices (TISEC devices) to... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13606-000] Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting...

  2. 76 FR 9340 - Mill Town Power Project; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13995-000] Mill Town Power Project; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On January 4, 2011, Mill Town Power Project filed an application for a...

  3. 76 FR 74783 - American River Power II, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-01

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14325-000] American River Power II, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions to Intervene, and Competing Applications On November 10, 2011, American River Power II, LLC (AMP...

  4. 76 FR 35201 - Jersey Central Power and Light; PSEG Fossil LLC; Notice of Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2309-019] Jersey Central Power and Light; PSEG Fossil LLC; Notice of Application Accepted for Filing, Soliciting Motions To...: Jersey Central Power and Light and PSEG Fossil LLC. e. Name of Project: Yards Creek Pumped Storage...

  5. 75 FR 18190 - New Jersey Water Supply Authority; Notice of Preliminary Permit Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... Contact: Edward Buss, P.E., New Jersey Water Supply Authority, 1851 State Hwy. 31, Clinton, NJ 08800, (908... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13399-000] New Jersey Water Supply Authority; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments...

  6. 76 FR 34071 - Lock Hydro Friends Fund I; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14107-000] Lock Hydro Friends Fund I; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On March 4, 2011, Lock Hydro Friends Fund I, filed an...

  7. 76 FR 18755 - Lock Hydro Friends Fund LII; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13810-000] Lock Hydro Friends Fund LII; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On July 12, 2010, Lock Hydro Friends Fund LII, filed an...

  8. 75 FR 27769 - Lock+ Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-18

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13711-000] Lock+ Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications May 11, 2010. On April 13, 2010 Lock+ Hydro Friends Fund...

  9. 76 FR 18755 - Lock Hydro Friends Fund LI; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13818-000] Lock Hydro Friends Fund LI; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On July 16, 2010, Lock Hydro Friends Fund LI, filed an...

  10. 75 FR 27770 - Lock+ Hydro Friends Fund VIII; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-18

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13710-000] Lock+ Hydro Friends Fund VIII; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications May 11, 2010. On April 13, 2010 Lock+ Hydro Friends Fund...

  11. 77 FR 14516 - Lock+ Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14339-000] Lock+ Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On December 22, 2011, Lock+ Hydro Friends Fund VII filed...

  12. 76 FR 54765 - Lock+ Hydro Friends Fund IV; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-02

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14253-000] Lock+ Hydro Friends Fund IV; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On August 10, 2011, the Lock+ Hydro Friends Fund IV filed...

  13. 76 FR 66710 - Erie Boulevard Hydropower, L.P.; Notice of Application Accepted for Filing, Soliciting Comments...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-27

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 5984-063] Erie Boulevard Hydropower, L.P.; Notice of Application Accepted for Filing, Soliciting Comments, Motions To Intervene, and....: 5984-063. c. Date Filed: May 10, 2011. d. Applicant: Erie Boulevard Hydropower, L.P. (dba Brookfield...

  14. 77 FR 10503 - Fall River Community Hydro Project; Notice of Preliminary Permit Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14216-000] Fall River Community Hydro Project; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On June 27, 2011, Fall River Valley Community Service District, California, filed an...

  15. 78 FR 59919 - Pershing County Water Conservation District; Notice of Application Accepted for Filing With the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14327-000] Pershing County Water Conservation District; Notice of Application Accepted for Filing With the Commission, Intent to Waive Scoping, Soliciting Motions to Intervene and Protests, Ready For Environmental Analysis, and Soliciting Comments, Terms and Conditions,...

  16. 76 FR 34975 - U.S. Farmers, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14102-000] U.S. Farmers, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On February 22, 2011, U.S. Farmers, LLC filed an application for a...

  17. 18 CFR Appendix A to Part 2 - Guidance for Determining the Acceptable Construction Area for Replacements

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Guidance for Determining the Acceptable Construction Area for Replacements A Appendix A to Part 2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES GENERAL POLICY...

  18. 18 CFR Appendix A to Part 2 - Guidance for Determining the Acceptable Construction Area for Replacements

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Guidance for Determining the Acceptable Construction Area for Replacements A Appendix A to Part 2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES GENERAL POLICY...

  19. 18 CFR Appendix A to Part 2 - Guidance for Determining the Acceptable Construction Area for Replacements

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Guidance for Determining the Acceptable Construction Area for Replacements A Appendix A to Part 2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES GENERAL POLICY...

  20. Acceptance Factors Influencing Adoption of National Institute of Standards and Technology Information Security Standards: A Quantitative Study

    ERIC Educational Resources Information Center

    Kiriakou, Charles M.

    2012-01-01

    Adoption of a comprehensive information security governance model and security controls is the best option organizations may have to protect their information assets and comply with regulatory requirements. Understanding acceptance factors of the National Institute of Standards and Technology (NIST) Risk Management Framework (RMF) comprehensive…

  1. 75 FR 38799 - Reedsport OPT Wave Park, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13666-000] Reedsport OPT Wave Park, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications June 24, 2010. Reedsport OPT Wave Park, LLC filed on...

  2. 77 FR 7143 - Green Wave Mendocino Wave Park; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14291-000] Green Wave Mendocino Wave Park; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments... (FPA), proposing to study the feasibility of the Green Wave Mendocino Wave Park (Mendocino Wave Project...

  3. 76 FR 71961 - KC Hydro LLC of New Hampshire; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-21

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14246-000] KC Hydro LLC of... equipment with total hydraulic capacity of 246 cubic feet per second (cfs) and total installed generating...-file, mail an original and seven copies to: Kimberly D. Bose, Secretary, Federal Energy Regulatory...

  4. 77 FR 2103 - Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-13

    ... Institutional Brokers utilize an acceptable, integrated order management system. Proposed Rule 5(a) provides a... purposes of the Act. The Exchange believes that its provision of an order management system for certain of... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66118; File No. SR-CHX-2011-33] Self-Regulatory...

  5. A harmonization effort for acceptable daily exposure application to pharmaceutical manufacturing - Operational considerations.

    PubMed

    Hayes, Eileen P; Jolly, Robert A; Faria, Ellen C; Barle, Ester Lovsin; Bercu, Joel P; Molnar, Lance R; Naumann, Bruce D; Olson, Michael J; Pecquet, Alison M; Sandhu, Reena; Shipp, Bryan K; Sussman, Robert G; Weideman, Patricia A

    2016-08-01

    A European Union (EU) regulatory guideline came into effect for all new pharmaceutical products on June 1st, 2015, and for all existing pharmaceutical products on December 1st, 2015. This guideline centers around the use of the Acceptable Daily Exposure (ADE) [synonymous with the Permitted Daily Exposure (PDE)] and operational considerations associated with implementation are outlined here. The EU guidance states that all active pharmaceutical ingredients (API) require an ADE; however, other substances such as starting materials, process intermediates, and cleaning agents may benefit from an ADE. Problems in setting ADEs for these additional substances typically relate to toxicological data limitations precluding the ability to establish a formal ADE. Established methodologies such as occupational exposure limits or bands (OELs or OEBs) and the threshold of toxicological concern (TTC) can be used or adjusted for use as interim ADEs when only limited data are available and until a more formal ADE can be established. Once formal ADEs are derived, it is important that the documents are routinely updated and that these updates are communicated to appropriate stakeholders. Another key operational consideration related to data-poor substances includes the use of maximum daily dose (MDD) in setting cross-contamination limits. The MDD is an important part of the maximum allowable/safe concentration (MAC/MSC) calculation and there are important considerations for its use and definition. Finally, other considerations discussed include operational aspects of setting ADEs for pediatrics, considerations for large molecules, and risk management in shared facilities. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Nonclinical dose formulation analysis method validation and sample analysis.

    PubMed

    Whitmire, Monica Lee; Bryan, Peter; Henry, Teresa R; Holbrook, John; Lehmann, Paul; Mollitor, Thomas; Ohorodnik, Susan; Reed, David; Wietgrefe, Holly D

    2010-12-01

    Nonclinical dose formulation analysis methods are used to confirm test article concentration and homogeneity in formulations and determine formulation stability in support of regulated nonclinical studies. There is currently no regulatory guidance for nonclinical dose formulation analysis method validation or sample analysis. Regulatory guidance for the validation of analytical procedures has been developed for drug product/formulation testing; however, verification of the formulation concentrations falls under the framework of GLP regulations (not GMP). The only current related regulatory guidance is the bioanalytical guidance for method validation. The fundamental parameters for bioanalysis and formulation analysis validations that overlap include: recovery, accuracy, precision, specificity, selectivity, carryover, sensitivity, and stability. Divergence in bioanalytical and drug product validations typically center around the acceptance criteria used. As the dose formulation samples are not true "unknowns", the concept of quality control samples that cover the entire range of the standard curve serving as the indication for the confidence in the data generated from the "unknown" study samples may not always be necessary. Also, the standard bioanalytical acceptance criteria may not be directly applicable, especially when the determined concentration does not match the target concentration. This paper attempts to reconcile the different practices being performed in the community and to provide recommendations of best practices and proposed acceptance criteria for nonclinical dose formulation method validation and sample analysis.

  7. Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal--Part I.

    PubMed

    Hubert, Ph; Nguyen-Huu, J-J; Boulanger, B; Chapuzet, E; Chiap, P; Cohen, N; Compagnon, P-A; Dewé, W; Feinberg, M; Lallier, M; Laurentie, M; Mercier, N; Muzard, G; Nivet, C; Valat, L

    2004-11-15

    This paper is the first part of a summary report of a new commission of the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP). The main objective of this commission was the harmonization of approaches for the validation of quantitative analytical procedures. Indeed, the principle of the validation of theses procedures is today widely spread in all the domains of activities where measurements are made. Nevertheless, this simple question of acceptability or not of an analytical procedure for a given application, remains incompletely determined in several cases despite the various regulations relating to the good practices (GLP, GMP, ...) and other documents of normative character (ISO, ICH, FDA, ...). There are many official documents describing the criteria of validation to be tested, but they do not propose any experimental protocol and limit themselves most often to the general concepts. For those reasons, two previous SFSTP commissions elaborated validation guides to concretely help the industrial scientists in charge of drug development to apply those regulatory recommendations. If these two first guides widely contributed to the use and progress of analytical validations, they present, nevertheless, weaknesses regarding the conclusions of the performed statistical tests and the decisions to be made with respect to the acceptance limits defined by the use of an analytical procedure. The present paper proposes to review even the bases of the analytical validation for developing harmonized approach, by distinguishing notably the diagnosis rules and the decision rules. This latter rule is based on the use of the accuracy profile, uses the notion of total error and allows to simplify the approach of the validation of an analytical procedure while checking the associated risk to its usage. Thanks to this novel validation approach, it is possible to unambiguously demonstrate the fitness for purpose of a new method as stated in all regulatory documents.

  8. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    PubMed

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

  9. 78 FR 29795 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc ; Notice of Filing of Proposed Rule Change for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-21

    ... To Permit BX Options To Accept Inbound Options Orders From NASDAQ OMX PHLX LLC and NASDAQ Options... to permit the BX Options System to accept inbound options orders routed by Nasdaq Options Services LLC (``NOS'') from NASDAQ OMX PHLX LLC (``Phlx'') and The NASDAQ Stock Market LLC's NASDAQ Options...

  10. 77 FR 21551 - New York City Department of Environmental Protection; Notice of Application Accepted for filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-10

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13287-004] New York City Department of Environmental Protection; Notice of Application Accepted for filing And Soliciting Motions To Intervene and Protests Take notice that the following hydroelectric application has been filed with the Commission and is available for public...

  11. 78 FR 34360 - Public Utility District No. 2 of Grant County, Washington; Notice of Application Accepted for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-07

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2114-209] Public Utility District No. 2 of Grant County, Washington; Notice of Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Protests Take notice that the following hydroelectric application has been filed with the Commission and is...

  12. 77 FR 101 - Rumford Falls Hydro, LLC; Notice of Application Accepted for Filing, Soliciting Comments, Motions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-03

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2333-078] Rumford Falls Hydro, LLC; Notice of Application Accepted for Filing, Soliciting Comments, Motions To Intervene, and Protests Take notice that the following hydroelectric application has been filed with the Commission and is available for public inspection: a. Types...

  13. 78 FR 78355 - San Diego County Water Authority; Notice of Preliminary Permit Application Accepted For Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12747-002] San Diego County Water Authority; Notice of Preliminary Permit Application Accepted For Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On July 1, 2013, the San Diego County Water Authority filed an application for a preliminary...

  14. 78 FR 41398 - City of Berlin, Berlin Water Works; Notice of Preliminary Permit Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-10

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14529-000] City of Berlin, Berlin Water Works; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On June 19, 2013, the City of Berlin, Berlin Water Works, filed an application for a...

  15. 77 FR 63302 - San Gabriel Valley Water Company dba, Fontana Water Company; Notice of Application Accepted for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14428-000] San Gabriel Valley Water Company dba, Fontana Water Company; Notice of Application Accepted for Filing and Soliciting Comments, Motions To Intervene, Protests, Recommendations, and Terms and Conditions October 10, 2012. Take notice that the following hydroelectric...

  16. 78 FR 19698 - Lucid Energy, Inc., The City of Portland Water Bureau; Notice of Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-02

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14498-000] Lucid Energy, Inc., The City of Portland Water Bureau; Notice of Application Accepted for Filing and Soliciting Comments, Motions To Intervene, Protests, Recommendations, and Terms and Conditions Take notice that the following hydroelectric application has been...

  17. 78 FR 75553 - Cedar Rapids Water Board; Notice of Application Accepted for Filing, Soliciting Comments, Motions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 4344-011] Cedar Rapids Water Board; Notice of Application Accepted for Filing, Soliciting Comments, Motions To Intervene, and Protests Take notice that the following hydroelectric application has been filed with the Commission and is available for public inspection: a. Type o...

  18. 78 FR 39046 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-28

    ... Permit BX Options To Accept Inbound Options Orders From NASDAQ OMX PHLX LLC and NASDAQ Options Market... permanent approval of the Exchange's pilot program that permits the BX Options System to accept inbound orders routed by Nasdaq Options Services LLC (``NOS'') from the NASDAQ OMX PHLX LLC (``PHLX'') and The...

  19. 18 CFR Appendix A to Part 2 - Guidance for Determining the Acceptable Construction Area for Auxiliary and Replacement Facilities

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Guidance for Determining the Acceptable Construction Area for Auxiliary and Replacement Facilities A Appendix A to Part 2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL...

  20. 77 FR 61042 - Self-Regulatory Organizations; ICE Clear Credit LLC; Notice of Filing and Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-05

    ... requires, among other things, that ICC accept or reject trades submitted for clearance that are executed... other things, that ICC accept or reject trades submitted for clearance that are not executed... the Commission's Internet comment form ( http://www.sec.gov/rules/sro.shtml ); or Send an email to...

  1. 76 FR 51962 - Oregon Department of Fish and Wildlife; Notice of Application Accepted for Filing and Soliciting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14235-000] Oregon Department of Fish and Wildlife; Notice of Application Accepted for Filing and Soliciting Comments, Motions To Intervene, Protests, Recommendations, and Terms and Conditions Take notice that the following hydroelectric application has been filed with the...

  2. 78 FR 38739 - Standard Format and Content for Post-Shutdown Decommissioning Activities Report

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-27

    ...The U.S. Nuclear Regulatory Commission (NRC) is issuing Revision 1 of Regulatory Guide (RG) 1.185, ``Standard Format and Content for Post-shutdown Decommissioning Activities Report.'' This guide describes a method that the NRC staff considers acceptable for use in complying with the Commission's requirements regarding the submission of a post-shutdown decommissioning activities report (PSDAR).

  3. 77 FR 75198 - Standard Format and Content for Post-Shutdown Decommissioning Activities Report

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-1272, ``Standard Format and Content for Post-shutdown Decommissioning Activities Report.'' This guide describes a method that the NRC staff considers acceptable for use in complying with the Commission's requirements regarding the submission of a post-shutdown decommissioning activities report (PSDAR).

  4. 78 FR 79055 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 71158; File No. SR-NASDAQ-2013-158] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to Acceptable Trade Range December 20, 2013. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act''),\\1...

  5. A Review of Information for Managing Aging in Nuclear Power Plants

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

    WC Morgan; JV Livingston

    1995-09-01

    Age related degradation effects in safety related systems of nuclear power plants should be managed to prevent safety margins from eroding below the acceptable limits provided in plant design bases. The Nuclear Plant Aging Research (NPAR) Pro- gram, conducted under the auspices of the U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, and other related aging management programs are developing technical information on managing aging. The aging management process central to these efforts consists of three key elements: 1) selecting structures, systems, and components (SSCs) in which aging should be controlled; 2) understanding the mechanisms and rates ofmore » degradation in these SSCs; and 3) managing degradation through effective inspection, surveillance, condition monitoring, trending, record keeping, mainten- ance, refurbishment, replacement, and adjustments in the operating environment and service conditions. This document concisely reviews and integrates information developed under the NPAR Program and other aging management studies and other available information related to understanding and managing age-related degradation effects and provides specific refer- ences to more comprehensive information on the same subjects.« less

  6. Implementation of Good Laboratory Practices (GLP) in basic scientific research: Translating the concept beyond regulatory compliance.

    PubMed

    Jena, G B; Chavan, Sapana

    2017-10-01

    The principles of Good Laboratory Practices (GLPs) are mainly intended for the laboratories performing studies for regulatory compliances. However, today GLP can be applied to broad disciplines of science to cater to the needs of the experimental objectives, generation of quality data and assay reproducibility. Considering its significance, it can now be applied in academics; industries as well as government set ups throughout the world. GLP is the best way to promote the reliability, reproducibility of the test data and hence facilitates the international acceptability. Now it is high time to translate and implement the concept of GLP beyond regulatory studies. Thus, it can pave the way for better understanding of scientific problems and help to maintain a good human and environmental health. Through this review, we have made an attempt to explore the uses of GLP principles in different fields of science and its acceptability as well as looking for its future perspectives. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Willingness-To-Accept Pharmaceutical Retail Inconvenience: Evidence from a Contingent Choice Experiment

    PubMed Central

    Finlay, Keith; Stoecker, Charles; Cunningham, Scott

    2015-01-01

    Objectives Restrictions on retail purchases of pseudoephedrine are one regulatory approach to reduce the social costs of methamphetamine production and use, but may impose costs on legitimate users of nasal decongestants. This is the first study to evaluate the costs of restricting access to medications on consumer welfare. Our objective was to measure the inconvenience cost consumers place on restrictions for cold medication purchases including identification requirements, purchase limits, over-the-counter availability, prescription requirements, and the active ingredient. Methods We conducted a contingent choice experiment with Amazon Mechanical Turk workers that presented participants with randomized, hypothetical product prices and combinations of restrictions that reflect the range of public policies. We used a conditional logit model to calculate willingness-to-accept each restriction. Results Respondents’ willingness-to-accept prescription requirements was $14.17 ($9.76–$18.58) and behind-the-counter restrictions was $9.68 ($7.03–$12.33) per box of pseudoephedrine product. Participants were willing to pay $4.09 ($1.66–$6.52) per box to purchase pseudoephedrine-based products over phenylephrine-based products. Conclusions Restricting access to medicines as a means of reducing the social costs of non-medical use can imply large inconvenience costs for legitimate consumers. These results are relevant to discussions of retail access restrictions on other medications. PMID:26024444

  8. Willingness-to-accept pharmaceutical retail inconvenience: evidence from a contingent choice experiment.

    PubMed

    Finlay, Keith; Stoecker, Charles; Cunningham, Scott

    2015-01-01

    Restrictions on retail purchases of pseudoephedrine are one regulatory approach to reduce the social costs of methamphetamine production and use, but may impose costs on legitimate users of nasal decongestants. This is the first study to evaluate the costs of restricting access to medications on consumer welfare. Our objective was to measure the inconvenience cost consumers place on restrictions for cold medication purchases including identification requirements, purchase limits, over-the-counter availability, prescription requirements, and the active ingredient. We conducted a contingent choice experiment with Amazon Mechanical Turk workers that presented participants with randomized, hypothetical product prices and combinations of restrictions that reflect the range of public policies. We used a conditional logit model to calculate willingness-to-accept each restriction. Respondents' willingness-to-accept prescription requirements was $14.17 ($9.76-$18.58) and behind-the-counter restrictions was $9.68 ($7.03-$12.33) per box of pseudoephedrine product. Participants were willing to pay $4.09 ($1.66-$6.52) per box to purchase pseudoephedrine-based products over phenylephrine-based products. Restricting access to medicines as a means of reducing the social costs of non-medical use can imply large inconvenience costs for legitimate consumers. These results are relevant to discussions of retail access restrictions on other medications.

  9. Hunter perceptions and acceptance of alternative deer management regulations

    USGS Publications Warehouse

    Cornicelli, L.; Fulton, D.C.; Grund, M.D.; Fieberg, J.

    2011-01-01

    Wildlife managers are often confronted with a policy paradox where a majority of the public supports an outcome, but there is no agreement on specific management strategies to achieve this outcome. Previous research has also reported a link between regulatory acceptance, hunter satisfaction, and hunter participation rates. Thus, human dimensions research aimed at understanding hunter motivations and behavior is needed for effective management. In 2005, we surveyed Minnesota (USA) deer hunters (n = 6,000; 59% response) to evaluate attitudes regarding alternative deer (Odocoileus virginianus) harvest regulations. We also conducted a series of forced choice experiments in which respondents were asked to select an option from a list of representative regulations that might be adopted to achieve a particular deer management goal. Specifically, we modeled 5 deer population scenarios ranging from low populations with high buck-harvest rates to populations 50% over goal density. Our results indicate that hunters preferred different regulations depending on the population scenario, but generally preferred antler-point restrictions and disliked limiting buck licenses through a lottery. We also found consistency among scenarios, in that a small percentage of respondents indicated they would not hunt if regulations were changed. The results from this study should help wildlife managers design deer harvest regulations that are both acceptable to hunters and achieve management objectives. ?? 2011 The Wildlife Society.

  10. Anxiety sensitivity and affect regulatory strategies: individual and interactive risk factors for anxiety-related symptoms.

    PubMed

    Kashdan, Todd B; Zvolensky, Michael J; McLeish, Alison C

    2008-01-01

    Studies have shown that anxiety sensitivity (AS) is a risk factor in the development of pathological anxiety. Recent theoretical models emphasize the additional importance of how people handle their anxious experiences. The present study examined whether high AS and being fixated on the control and regulation of unwanted anxious feelings or being unable to properly modulate affect as needed lead to particularly problematic outcomes. We examined the interactive influence of AS and affect regulatory strategies on the frequency and intensity of anxiety symptoms. Questionnaires were completed by 248 young adults in the community. Results showed a general pattern with anxiety symptoms being the most severe when high AS was paired with affect regulatory difficulties. Of participants high in AS, anxious arousal and worry were heightened in the presence of less acceptance of emotional distress; anxious arousal, worry, and agoraphobic cognitions were heightened when fewer resources were available to properly modulate affect; and agoraphobic cognitions were heightened in the presence of high emotion expressiveness. As evidence of construct specificity, an alternative model with anhedonic depressive symptoms as a main effect and interaction effect (with regulatory strategies) failed to predict anxiety symptoms. However, anxiety sensitivity and less acceptance of emotional distress were associated with greater anhedonia. Results are discussed in the context of how and when affect regulatory behavior shifts individuals from normative anxiety to pathology.

  11. Unique Regulatory Approach for Licensing the Port Hope Remediation Project in Canada - 13315

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

    Kostova, M.; Howard, D.; Elder, P.

    2013-07-01

    The Port Hope remediation project is a part of a larger initiative of the Canadian Federal Government the Port Hope Area Initiative (PHAI) which is based upon a community proposal. The Government of Canada, through Natural Resources Canada (NRCan) is investing $1.28 billion over 10 years to clean up historic low-level radioactive waste in the Port Hope Area and to provide long-term safe management of the low-level radioactive wastes in the Port Hope Area. These wastes arose from the activities of a former Federal Crown Corporation (Eldorado Nuclear) and its private sector predecessors. In Canada, historic waste are defined asmore » low-level radioactive waste that was managed in a manner no longer considered acceptable, but for which the original producer cannot reasonably be held responsible or no longer exists and for which the Federal Government has accepted responsibility. In Canada, under the current regulatory framework, the environmental remediation is not considered as a distinct phase of the nuclear cycle. The regulatory approach for dealing with existing sites contaminated with radioactive residues is defined on the basis of risk and application of existing regulations. A unique regulatory approach was taken by the Canadian Nuclear Safety Commission (CNSC) to address the various licensing issues and to set out the requirements for licensing of the Port Hope Project within the current regulatory framework. (authors)« less

  12. 18 CFR 5.22 - Notice of acceptance and ready for environmental analysis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Notice of acceptance and ready for environmental analysis. 5.22 Section 5.22 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT INTEGRATED LICENSE APPLICATION PROCESS § 5.22 Notice o...

  13. 78 FR 37217 - Ted P. Sorenson; Notice of Preliminary Permit Application Accepted for Filing and Soliciting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14519-000] Ted P. Sorenson; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On May 1, 2013, Ted P. Sorenson filed an application for a preliminary permit, pursuant to section 4(f) of the...

  14. The application of probabilistic fracture analysis to residual life evaluation of embrittled reactor vessels

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

    Dickson, T.L.; Simonen, F.A.

    1992-05-01

    Probabilistic fracture mechanics analysis is a major element of comprehensive probabilistic methodology on which current NRC regulatory requirements for pressurized water reactor vessel integrity evaluation are based. Computer codes such as OCA-P and VISA-II perform probabilistic fracture analyses to estimate the increase in vessel failure probability that occurs as the vessel material accumulates radiation damage over the operating life of the vessel. The results of such analyses, when compared with limits of acceptable failure probabilities, provide an estimation of the residual life of a vessel. Such codes can be applied to evaluate the potential benefits of plant-specific mitigating actions designedmore » to reduce the probability of failure of a reactor vessel. 10 refs.« less

  15. The application of probabilistic fracture analysis to residual life evaluation of embrittled reactor vessels

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

    Dickson, T.L.; Simonen, F.A.

    1992-01-01

    Probabilistic fracture mechanics analysis is a major element of comprehensive probabilistic methodology on which current NRC regulatory requirements for pressurized water reactor vessel integrity evaluation are based. Computer codes such as OCA-P and VISA-II perform probabilistic fracture analyses to estimate the increase in vessel failure probability that occurs as the vessel material accumulates radiation damage over the operating life of the vessel. The results of such analyses, when compared with limits of acceptable failure probabilities, provide an estimation of the residual life of a vessel. Such codes can be applied to evaluate the potential benefits of plant-specific mitigating actions designedmore » to reduce the probability of failure of a reactor vessel. 10 refs.« less

  16. Self-organization, entropy and allostery.

    PubMed

    Kornev, Alexandr P

    2018-06-19

    Allostery is a fundamental regulatory mechanism in biology. Although generally accepted that it is a dynamics-driven process, the exact molecular mechanism of allosteric signal transmission is hotly debated. We argue that allostery is as a part of a bigger picture that also includes fractal-like properties of protein interior, hierarchical protein folding and entropy-driven molecular recognition. Although so far all these phenomena were studied separately, they stem from the same common root: self-organization of polypeptide chains and, thus, has to be studied collectively. This merge will allow the cross-referencing of a broad spectrum of multi-disciplinary data facilitating progress in all these fields. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  17. 76 FR 53511 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing of Proposed Rule Change Amending...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-26

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65184; File No. SR-NYSEAmex-2011-63] Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing of Proposed Rule Change Amending NYSE Amex Equities Rule 17(c)(2)(B) To Make Permanent the Pilot Program that Permits the Exchange To Accept Inbound Orders Routed by Archipelago Securities LLC in...

  18. Looking to the future of organ-on-chip and toxicity assessment: a regulator's opinion.

    PubMed

    Jones, David R

    2016-12-01

    David R Jones talks to Francesca Lake, Managing Editor: David R Jones is an Expert Pharmaco-Toxicologist within the Licensing Division of the Medicines and Healthcare products Regulatory Agency. We met him at the Organ-on-a-chip Europe 2016 conference in Cambridge (UK), where he presented 'A UK Regulatory View on the Acceptability of Organ on a Chip Data'.

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

    Roussel, G.

    Leak-Before-Break (LBB) technology has not been applied in the first design of the seven Pressurized Water Reactors the Belgian utility is currently operating. The design basis of these plants required to consider the dynamic effects associated with the ruptures to be postulated in the high energy piping. The application of the LBB technology to the existing plants has been recently approved by the Belgian Safety Authorities but with a limitation to the primary coolant loop. LBB analysis has been initiated for the Doel 3 and Tihange 2 plants to allow the withdrawal of some of the reactor coolant pump snubbersmore » at both plants and not reinstall some of the restraints after steam generator replacement at Doel 3. LBB analysis was also found beneficial to demonstrate the acceptability of the primary components and piping to the new conditions resulting from power uprating and stretch-out operation. LBB analysis has been subsequently performed on the primary coolant loop of the Tihange I plant and is currently being performed for the Doel 4 plant. Application of the LBB to the primary coolant loop is based in Belgium on the U.S. Nuclear Regulatory Commission requirements. However the Belgian Safety Authorities required some additional analyses and put some restrictions on the benefits of the LBB analysis to maintain the global safety of the plant at a sufficient level. This paper develops the main steps of the safety evaluation performed by the Belgian Safety Authorities for accepting the application of the LBB technology to existing plants and summarizes the requirements asked for in addition to the U.S. Nuclear Regulatory Commission rules.« less

  20. An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

    PubMed Central

    Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

    2016-01-01

    As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

  1. Occurrence and risk assessment of potentially toxic elements and typical organic pollutants in contaminated rural soils.

    PubMed

    Xu, Yongfeng; Dai, Shixiang; Meng, Ke; Wang, Yuting; Ren, Wenjie; Zhao, Ling; Christie, Peter; Teng, Ying

    2018-07-15

    The residual levels and risk assessment of several potentially toxic elements (PTEs), phthalate esters (PAEs) and polycyclic aromatic hydrocarbons (PAHs) in rural soils near different types of pollution sources in Tianjin, China, were studied. The soils were found to be polluted to different extents with PTEs, PAEs and PAHs from different pollution sources. The soil concentrations of chromium (Cr), nickel (Ni), di-n-butyl phthalate (DnBP), acenaphthylene (Any) and acenaphthene (Ane) were higher than their corresponding regulatory reference limits. The health risk assessment model used to calculate human exposure indicates that both non-carcinogenic and carcinogenic risks from selected pollutants were generally acceptable or close to acceptable. Different types of pollution sources and soil physicochemical properties substantially affected the soil residual concentrations of and risks from these pollutants. PTEs in soils collected from agricultural lands around industrial and residential areas and organic pollutants (PAEs and PAHs) in soils collected from agricultural areas around livestock breeding were higher than those from other types of pollution sources and merit long-term monitoring. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms

    PubMed Central

    Lopez, Felipe L; Ernest, Terry B; Tuleu, Catherine; Gul, Mine Orlu

    2015-01-01

    Introduction: Most conventional drug delivery systems are not acceptable for pediatric patients as they differ in their developmental status and dosing requirements from other subsets of the population. Technology platforms are required to aid the development of age-appropriate medicines to maximize patient acceptability while maintaining safety, efficacy, accessibility and affordability. Areas covered: The current approaches and novel developments in the field of age-appropriate drug delivery for pediatric patients are critically discussed including patient-centric formulations, administration devices and packaging systems. Expert opinion: Despite the incentives provided by recent regulatory modifications and the efforts of formulation scientists, there is still a need for implementation of pharmaceutical technologies that enable the manufacture of licensed age-appropriate formulations. Harmonization of endeavors from regulators, industry and academia by sharing learning associated with data obtained from pediatric investigation plans, product development pathways and scientific projects would be the way forward to speed up bench-to-market age appropriate formulation development. A collaborative approach will benefit not only pediatrics, but other patient populations such as geriatrics would also benefit from an accelerated patient-centric approach to drug delivery. PMID:26165848

  3. Expert opinions on the acceptance of alternative methods in food safety evaluations: Formulating recommendations to increase acceptance of non-animal methods for kinetics.

    PubMed

    Punt, Ans; Bouwmeester, Hans; Schiffelers, Marie-Jeanne W A; Peijnenburg, Ad A C M

    2018-02-01

    Inclusion of alternative methods that replace, reduce, or refine (3R) animal testing within regulatory safety evaluations of chemicals generally faces many hurdles. The goal of the current work is to i) collect responses from key stakeholders involved in food safety evaluations on what they consider the most relevant factors that influence the acceptance and use of 3R methods and to ii) use these responses to formulate activities needed to increase the acceptance and use of 3R methods, particularly for kinetics. The stakeholders were contacted by e-mail for their opinions, asking the respondents to write down three barriers and/or drivers and scoring these by distributing 5 points over the three factors. The main barriers that obtained the highest aggregated scores were i) uncertain predictability 3R methods/lack of validation, ii) insufficient guidance regulators/industry and iii) insufficient harmonization of legislation. The major driver identified was the possibility of 3R methods to provide more mechanistic information. Based on the results, recommendations are given to enhance the acceptance and application of 3R toxicokinetic methods in food safety evaluations. These include steering of regulatory data requirements as well as creating (funding) opportunities for development and validation of alternative methods for kinetics and development of guidances. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Regulatory Fit and Equal Opportunity/Diversity: Implications for DEOMI

    DTIC Science & Technology

    2013-01-01

    than demographic diversity ( Ivancevich & Gilbert, 2000); the goal of equality is to create and manage a heterogeneous mix of abilities, skills, ideas...accepted. Recruiting of minorities and women are not seen as violations of EO laws (Kravitz, 2008; Newman & Lyon , 2009; Pyburn, et al., 2008). Similarly...209-213. REGULATORY FIT AND EQUAL OPPORTUNITY/DIVERSITY 23 Ivancevich , J. M. & Gilbert, J. A. (2000). Diversity management: Time for a new approach

  5. Looking to the future of organ-on-chip and toxicity assessment: a regulator's opinion

    PubMed Central

    Jones, David R

    2016-01-01

    David R Jones talks to Francesca Lake, Managing Editor: David R Jones is an Expert Pharmaco-Toxicologist within the Licensing Division of the Medicines and Healthcare products Regulatory Agency. We met him at the Organ-on-a-chip Europe 2016 conference in Cambridge (UK), where he presented ‘A UK Regulatory View on the Acceptability of Organ on a Chip Data’. PMID:28116135

  6. 75 FR 68656 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-08

    ... Shares to 99,000,000 Shares November 2, 2010. Pursuant to Section 19(b)(1) \\1\\ of the Securities Exchange... size accepted by Floor broker systems from 25,000,000 shares to 99,000,000 shares. The text of the... systems shall accept a maximum order size of 99,000,000, an increase from the current 25,000,000 share...

  7. Vibration safety limits for magnetic resonance elastography.

    PubMed

    Ehman, E C; Rossman, P J; Kruse, S A; Sahakian, A V; Glaser, K J

    2008-02-21

    Magnetic resonance elastography (MRE) has been demonstrated to have potential as a clinical tool for assessing the stiffness of tissue in vivo. An essential step in MRE is the generation of acoustic mechanical waves within a tissue via a coupled mechanical driver. Motivated by an increasing volume of human imaging trials using MRE, the objectives of this study were to audit the vibration amplitude of exposure for our IRB-approved human MRE studies, to compare these values to a conservative regulatory standard for vibrational exposure and to evaluate the applicability and implications of this standard for MRE. MRE displacement data were examined from 29 MRE exams, including the liver, brain, kidney, breast and skeletal muscle. Vibrational acceleration limits from a European Union directive limiting occupational exposure to whole-body and extremity vibrations (EU 2002/44/EC) were adjusted for time and frequency of exposure, converted to maximum displacement values and compared to the measured in vivo displacements. The results indicate that the vibrational amplitudes used in MRE studies are below the EU whole-body vibration limit, and the EU guidelines represent a useful standard that could be readily accepted by Institutional Review Boards to define standards for vibrational exposures for MRE studies in humans.

  8. Vibration safety limits for magnetic resonance elastography

    PubMed Central

    Ehman, E C; Rossman, P J; Kruse, S A; Sahakian, A V; Glaser, K J

    2010-01-01

    Magnetic resonance elastography (MRE) has been demonstrated to have potential as a clinical tool for assessing the stiffness of tissue in vivo. An essential step in MRE is the generation of acoustic mechanical waves within tissue via a coupled mechanical driver. Motivated by an increasing volume of human imaging trials using MRE, the objectives of this study were to audit the vibration amplitude of exposure for our IRB-approved human MRE studies, to compare these values to a conservative regulatory standard for vibrational exposure, and to evaluate the applicability and implications of this standard for MRE. MRE displacement data were examined from 29 MRE exams, including the liver, brain, kidney, breast, and skeletal muscle. Vibrational acceleration limits from a European Union directive limiting occupational exposure to whole-body and extremity vibrations (EU 2002/44/EC) were adjusted for time and frequency of exposure, converted to maximum displacement values, and compared to the measured in vivo displacements. The results indicate that the vibrational amplitudes used in MRE studies are below the EU whole-body vibration limit and the EU guidelines represent a useful standard that could be readily accepted by Institutional Review Boards to define standards for vibrational exposures for MRE studies in humans. PMID:18263949

  9. The Regulatory Framework for Privacy and Security

    NASA Astrophysics Data System (ADS)

    Hiller, Janine S.

    The internet enables the easy collection of massive amounts of personally identifiable information. Unregulated data collection causes distrust and conflicts with widely accepted principles of privacy. The regulatory framework in the United States for ensuring privacy and security in the online environment consists of federal, state, and self-regulatory elements. New laws have been passed to address technological and internet practices that conflict with privacy protecting policies. The United States and the European Union approaches to privacy differ significantly, and the global internet environment will likely cause regulators to face the challenge of balancing privacy interests with data collection for many years to come.

  10. Design of a sampling plan to detect ochratoxin A in green coffee.

    PubMed

    Vargas, E A; Whitaker, T B; Dos Santos, E A; Slate, A B; Lima, F B; Franca, R C A

    2006-01-01

    The establishment of maximum limits for ochratoxin A (OTA) in coffee by importing countries requires that coffee-producing countries develop scientifically based sampling plans to assess OTA contents in lots of green coffee before coffee enters the market thus reducing consumer exposure to OTA, minimizing the number of lots rejected, and reducing financial loss for producing countries. A study was carried out to design an official sampling plan to determine OTA in green coffee produced in Brazil. Twenty-five lots of green coffee (type 7 - approximately 160 defects) were sampled according to an experimental protocol where 16 test samples were taken from each lot (total of 16 kg) resulting in a total of 800 OTA analyses. The total, sampling, sample preparation, and analytical variances were 10.75 (CV = 65.6%), 7.80 (CV = 55.8%), 2.84 (CV = 33.7%), and 0.11 (CV = 6.6%), respectively, assuming a regulatory limit of 5 microg kg(-1) OTA and using a 1 kg sample, Romer RAS mill, 25 g sub-samples, and high performance liquid chromatography. The observed OTA distribution among the 16 OTA sample results was compared to several theoretical distributions. The 2 parameter-log normal distribution was selected to model OTA test results for green coffee as it gave the best fit across all 25 lot distributions. Specific computer software was developed using the variance and distribution information to predict the probability of accepting or rejecting coffee lots at specific OTA concentrations. The acceptation probability was used to compute an operating characteristic (OC) curve specific to a sampling plan design. The OC curve was used to predict the rejection of good lots (sellers' or exporters' risk) and the acceptance of bad lots (buyers' or importers' risk).

  11. Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice.

    PubMed

    McCarty, Lynn S; Borgert, Christopher J; Mihaich, Ellen M

    2012-07-01

    There is an ongoing discussion on the provenance of toxicity testing data regarding how best to ensure its validity and credibility. A central argument is whether journal peer-review procedures are superior to Good Laboratory Practice (GLP) standards employed for compliance with regulatory mandates. We sought to evaluate the rationale for regulatory decision making based on peer-review procedures versus GLP standards. We examined pertinent published literature regarding how scientific data quality and validity are evaluated for peer review, GLP compliance, and development of regulations. Some contend that peer review is a coherent, consistent evaluative procedure providing quality control for experimental data generation, analysis, and reporting sufficient to reliably establish relative merit, whereas GLP is seen as merely a tracking process designed to thwart investigator corruption. This view is not supported by published analyses pointing to subjectivity and variability in peer-review processes. Although GLP is not designed to establish relative merit, it is an internationally accepted quality assurance, quality control method for documenting experimental conduct and data. Neither process is completely sufficient for establishing relative scientific soundness. However, changes occurring both in peer-review processes and in regulatory guidance resulting in clearer, more transparent communication of scientific information point to an emerging convergence in ensuring information quality. The solution to determining relative merit lies in developing a well-documented, generally accepted weight-of-evidence scheme to evaluate both peer-reviewed and GLP information used in regulatory decision making where both merit and specific relevance inform the process.

  12. 12 CFR 562.2 - Regulatory reports.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

  13. 76 FR 40755 - Impact of Reduced Dose Limits on NRC Licensed Activities; Solicitation of Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... NUCLEAR REGULATORY COMMISSION [NRC-2009-0279] Impact of Reduced Dose Limits on NRC Licensed Activities; Solicitation of Public Comment AGENCY: Nuclear Regulatory Commission. ACTION: Solicitation of public comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or Commission) is seeking public...

  14. International regulatory requirements for skin sensitization testing.

    PubMed

    Daniel, Amber B; Strickland, Judy; Allen, David; Casati, Silvia; Zuang, Valérie; Barroso, João; Whelan, Maurice; Régimbald-Krnel, M J; Kojima, Hajime; Nishikawa, Akiyoshi; Park, Hye-Kyung; Lee, Jong Kwon; Kim, Tae Sung; Delgado, Isabella; Rios, Ludmila; Yang, Ying; Wang, Gangli; Kleinstreuer, Nicole

    2018-06-01

    Skin sensitization test data are required or considered by chemical regulation authorities around the world. These data are used to develop product hazard labeling for the protection of consumers or workers and to assess risks from exposure to skin-sensitizing chemicals. To identify opportunities for regulatory uses of non-animal replacements for skin sensitization tests, the needs and uses for skin sensitization test data must first be clarified. Thus, we reviewed skin sensitization testing requirements for seven countries or regions that are represented in the International Cooperation on Alternative Test Methods (ICATM). We noted the type of skin sensitization data required for each chemical sector and whether these data were used in a hazard classification, potency classification, or risk assessment context; the preferred tests; and whether alternative non-animal tests were acceptable. An understanding of national and regional regulatory requirements for skin sensitization testing will inform the development of ICATM's international strategy for the acceptance and implementation of non-animal alternatives to assess the health hazards and risks associated with potential skin sensitizers. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Heavy metals (lead, cadmium, methylmercury, arsenic) in commonly imported rice grains (Oryza sativa) sold in Saudi Arabia and their potential health risk.

    PubMed

    Al-Saleh, Iman; Abduljabbar, Mai

    2017-10-01

    The levels of heavy metals (lead, cadmium, methylmercury and arsenic) were determined in 37 brands of imported rice commonly consumed in Saudi Arabia after soaking and rinsing with water, and their potential health risks to residents were estimated by three indices: hazard quotient (HQ), hazard index (HI) and cancer risk (CR). The mean levels of lead, cadmium, methylmercury and total arsenic in soaked (rinsed) rice grains were 0.034 (0.057), 0.015 (0.027), 0.004 (0.007) and 0.202 (0.183) μg/g dry weight, respectively. Soaking or rinsing rice grains with water decreased lead and cadmium levels in all brands to safe levels. All brands had total arsenic above the acceptable regulatory limits, irrespective of soaking or rinsing, and eight soaked and 12 rinsed brands contained methylmercury. The levels of all heavy metals except cadmium were above the acceptable regulatory limits when the rice was neither rinsed nor soaked. Weekly intakes of lead, cadmium, methylmercury and total arsenic from soaked (rinsed) grains were 0.638 (1.068), 0.279 (0.503), 0.271 (0.309) and 3.769 (3.407) μg/kg body weight (bw). The weekly intakes of lead and methylmercury from the consumption of one rinsed and two soaked rice brands respectively, exceeded the Provisional Tolerance Weekly Intake set by the Food and Agriculture Organization and the World Health Organization. The weekly intake of total arsenic for all brands was above the lowest benchmark dose lower confidence limit (BMDL 01 ) level of 0.3μg/kg bw/d for an increased cancer risk set by European Food Safety Authority. Either soaking or rinsing grains before consumption can minimize the non-carcinogenic health risks to residents from cadmium and lead (HQ<1). Our local consumers, though, may experience health consequences from rice contaminated mainly with arsenic (HQ>1 all brands) and to a lesser extent with methylmercury (HQ>1 in 4 brands), even when soaked or rinsed with water before consumption. The combined non-carcinogenic effect of all metals expressed as HI was >1, including soaked or rinsed rice, with total arsenic the major contributor followed by methylmercury. CR for total arsenic, whether consuming soaked, rinsed, un-soaked or unrinsed grains, exceeded the acceptable level of 10 -4 . Long-term consumption of rice contaminated with heavy metals, particularly arsenic, can pose potential health risks to the local population, especially vulnerable groups (pregnant women, children, elderly and patients). More attention should thus be given to contaminated rice and preventive measures should be taken. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Contagious equine metritis: artificial reproduction changes the epidemiologic paradigm.

    PubMed

    Schulman, Martin Lance; May, Catherine Edith; Keys, Bronwyn; Guthrie, Alan John

    2013-11-29

    Recent CEM outbreak reports reflect a novel epidemiologic manifestation with a markedly different risk association for transmission via artificial reproduction and subsequent to inadvertent importation of unapparent carrier stallions. Artificial breeding has an increased association with horizontal or fomite-associated transmission. Reported risk factors include inadequate biosecurity protocols at centralised breeding facilities associated with stallion management and methods of semen collection, processing and transport. Detection of carriers is based on traditional bacteriology from genital swabs and despite limitations inherent to Taylorella equigenitalis is currently the gold standard applied in all international trade and movement protocols. These limitations are reported to be overcome by PCR assays improving diagnostic sensitivity and specificity, practicality, turn-around times, through-put and cost efficacy. Molecular methods have increased understanding of the Taylorelleae, facilitate epidemiologic surveillance and outbreak control strategies. Validation and international regulatory acceptance of a robust PCR-based assay and the undefined risks in association with cryopreserved semen and embryos are future areas warranting further investigation. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Normative Databases for Imaging Instrumentation.

    PubMed

    Realini, Tony; Zangwill, Linda M; Flanagan, John G; Garway-Heath, David; Patella, Vincent M; Johnson, Chris A; Artes, Paul H; Gaddie, Ian B; Fingeret, Murray

    2015-08-01

    To describe the process by which imaging devices undergo reference database development and regulatory clearance. The limitations and potential improvements of reference (normative) data sets for ophthalmic imaging devices will be discussed. A symposium was held in July 2013 in which a series of speakers discussed issues related to the development of reference databases for imaging devices. Automated imaging has become widely accepted and used in glaucoma management. The ability of such instruments to discriminate healthy from glaucomatous optic nerves, and to detect glaucomatous progression over time is limited by the quality of reference databases associated with the available commercial devices. In the absence of standardized rules governing the development of reference databases, each manufacturer's database differs in size, eligibility criteria, and ethnic make-up, among other key features. The process for development of imaging reference databases may be improved by standardizing eligibility requirements and data collection protocols. Such standardization may also improve the degree to which results may be compared between commercial instruments.

  18. Normative Databases for Imaging Instrumentation

    PubMed Central

    Realini, Tony; Zangwill, Linda; Flanagan, John; Garway-Heath, David; Patella, Vincent Michael; Johnson, Chris; Artes, Paul; Ben Gaddie, I.; Fingeret, Murray

    2015-01-01

    Purpose To describe the process by which imaging devices undergo reference database development and regulatory clearance. The limitations and potential improvements of reference (normative) data sets for ophthalmic imaging devices will be discussed. Methods A symposium was held in July 2013 in which a series of speakers discussed issues related to the development of reference databases for imaging devices. Results Automated imaging has become widely accepted and used in glaucoma management. The ability of such instruments to discriminate healthy from glaucomatous optic nerves, and to detect glaucomatous progression over time is limited by the quality of reference databases associated with the available commercial devices. In the absence of standardized rules governing the development of reference databases, each manufacturer’s database differs in size, eligibility criteria, and ethnic make-up, among other key features. Conclusions The process for development of imaging reference databases may be improved by standardizing eligibility requirements and data collection protocols. Such standardization may also improve the degree to which results may be compared between commercial instruments. PMID:25265003

  19. The relationship of state Medicaid coverage to Medicaid acceptance among substance abuse providers in the United States.

    PubMed

    Andrews, Christina M

    2014-10-01

    The Affordable Care Act will dramatically increase the number of Americans with Medicaid coverage for substance abuse treatment (SAT). Currently, few SAT providers accept Medicaid, and consequently, there is concern that newly-eligible Medicaid enrollees will have difficulty finding SAT providers willing to serve them. However, little is known about why few SAT providers accept Medicaid. In response, this study examines how features of state Medicaid coverage for SAT, including benefits, eligibility, and oversight, are associated with Medicaid acceptance among SAT providers. Medicaid acceptance was positively associated with the number of SAT services covered, and the number of optional categorical expansions implemented by the state. Requirements for physician involvement were associated with lower odds of acceptance. The results suggest that more generous Medicaid coverage may encourage SAT providers to accept Medicaid, but regulatory policies may inhibit their ability to do so.

  20. Report for Batch Leach Analyses on Sediments at 100-HR-3 Operable Unit, Boreholes C7620, C7621, C7622, C7623, C7626, C7627, C7628, C7629, C7630, and C7866. Revision 1.

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

    Lindberg, Michael J.

    2012-04-25

    This is a revision to a previously released report. This revision contains additional analytical results for the sample with HEIS number B2H4X7. Between November 4, 2010 and October 26, 2011 sediment samples were received from 100-HR-3 Operable Unit for geochemical studies. The analyses for this project were performed at the 331 building located in the 300 Area of the Hanford Site. The analyses were performed according to Pacific Northwest National Laboratory (PNNL) approved procedures and/or nationally recognized test procedures. The data sets include the sample identification numbers, analytical results, estimated quantification limits (EQL), and quality control data. The preparatory andmore » analytical quality control requirements, calibration requirements, acceptance criteria, and failure actions are defined in the on-line QA plan 'Conducting Analytical Work in Support of Regulatory Programs' (CAW). This QA plan implements the Hanford Analytical Services Quality Assurance Requirements Documents (HASQARD) for PNNL. Samples were received with a chain of custody (COC) and were analyzed according to the sample identification numbers supplied by the client. All Samples were refrigerated upon receipt until prepared for analysis. All samples were received with custody seals intact unless noted in the Case Narrative. Holding time is defined as the time from sample preparation to the time of analyses. The prescribed holding times were met for all analytes unless noted in the Case Narrative. All reported analytical results meet the requirements of the CAW or client specified SOW unless noted in the case narrative. Due to the requirements of the statement of work and sampling events in the field, the 28 day and the 48 hr requirements cannot be met. The statement of work requires samples to be selected at the completion of the borehole. It is not always possible to complete a borehole and have the samples shipped to the laboratory within the hold time requirements. Duplicate RPD for Uranium 238 (38.9%) was above the acceptance limit (35) in 1E05003-DUP1 for ICPMS-Tc-U-WE The sample result is less than 10 times the detection limits. Duplicate recoveries are not applicable to this analyte. Duplicate RPD for Silver 107 (68.2%) was above the acceptance limit (35) in 2C06004-DUP1 for ICPMS-RCRA-AE The sample result is less than 10 times the detection limits. Duplicate recoveries are not applicable to this analyte. Matrix Spike Recovery for Chromium, Hexavalent (48.8%) was outside acceptance limits (75-125) in 1E23001-MS1 for Hexavalent Chromium/Soil. Potential Matrix interference. Sample results associated with this batch are below the EQL. There should be no impact to the data as reported. Matrix Spike Recovery for Chromium, Hexavalent (50.2%) was outside acceptance limits (75-125) in 2B22010-MS1 for Hexavalent Chromium/Soil. Potential Matrix interference. Sample results associated with this batch are below the EQL. There should be no impact to the data as reported.« less

  1. 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...

  2. 78 FR 63517 - Control of Ferrite Content in Stainless Steel Weld Metal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ...The U.S. Nuclear Regulatory Commission (NRC) is issuing a revision to Regulatory Guide (RG) 1.31, ``Control of Ferrite Content in Stainless Steel Weld Metal.'' This guide (Revision 4) describes a method that the NRC staff considers acceptable for controlling ferrite content in stainless steel weld metal. It updates the guide to remove references to outdated standards and to remove an appendix that has been incorporated into relevant specifications.

  3. Local tolerance testing under REACH: Accepted non-animal methods are not on equal footing with animal tests.

    PubMed

    Sauer, Ursula G; Hill, Erin H; Curren, Rodger D; Raabe, Hans A; Kolle, Susanne N; Teubner, Wera; Mehling, Annette; Landsiedel, Robert

    2016-07-01

    In general, no single non-animal method can cover the complexity of any given animal test. Therefore, fixed sets of in vitro (and in chemico) methods have been combined into testing strategies for skin and eye irritation and skin sensitisation testing, with pre-defined prediction models for substance classification. Many of these methods have been adopted as OECD test guidelines. Various testing strategies have been successfully validated in extensive in-house and inter-laboratory studies, but they have not yet received formal acceptance for substance classification. Therefore, under the European REACH Regulation, data from testing strategies can, in general, only be used in so-called weight-of-evidence approaches. While animal testing data generated under the specific REACH information requirements are per se sufficient, the sufficiency of weight-of-evidence approaches can be questioned under the REACH system, and further animal testing can be required. This constitutes an imbalance between the regulatory acceptance of data from approved non-animal methods and animal tests that is not justified on scientific grounds. To ensure that testing strategies for local tolerance testing truly serve to replace animal testing for the REACH registration 2018 deadline (when the majority of existing chemicals have to be registered), clarity on their regulatory acceptance as complete replacements is urgently required. 2016 FRAME.

  4. 78 FR 59401 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-26

    ...\\ directs the Commission to approve a proposed rule change of a self-regulatory organization if it finds... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70464; File No. SR-ICEEU-2013-11] Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change Related To Enhanced...

  5. Inadequate environmental monitoring around offshore oil and gas platforms on the Grand Bank of Eastern Canada: are risks to marine birds known?

    PubMed

    Burke, C M; Montevecchi, W A; Wiese, F K

    2012-08-15

    Petroleum exploration and production on the Grand Bank of eastern Canada overlaps with productive marine habitat that supports over 40 million marine birds annually. Environmental assessments for oil and gas projects in the region predict insignificant adverse effects on marine birds from oil spills, incineration in platform flares and collisions. Limited baseline data on seasonal occupancies and a failure to quantify the nature and extent of marine bird attraction to platforms and related mortality undermines these assessments. We conducted 22 surveys to offshore platforms on the Grand Bank during 1999-2003 to measure avian associations with platforms and to determine the level of monitoring needed to assess the risks to marine birds. We document seasonal shifts in marine bird occurrences and higher densities of auks (fall) and shearwaters (summer) around platforms relative to surrounding areas. The limited temporal and spatial coverage of our surveys is more robust than existing industry monitoring efforts, yet it is still inadequate to quantify the scale of marine bird associations with platforms or their associated mortality risks. Systematic observations by independent biologists on vessels and platforms are needed to generate reliable assessments of risks to marine birds. Instead, the regulatory body for offshore oil and gas in eastern Canada (Canada - Newfoundland and Labrador Offshore Petroleum Board; C-NLOPB) supports industry self-reporting as the accepted form of environmental monitoring. Conflicting responsibilities of oil and gas regulatory agencies for both energy development and environmental monitoring are major barriers to transparency, unbiased scientific inquiry and adequate environmental protection. Similar conflicts with the oil and gas regulatory body in the United States, the former Minerals and Management Service (MMS) were identified by the U.S. President as a major contributor to the Deepwater Horizon disaster in the Gulf of Mexico. The MMS has since been restructured into the Bureau of Ocean Energy Management, (BOEM) with separate departments responsible for drilling leases and the regulation of drilling activities. Similar restructuring of the oil and gas regulatory bodies in Canada is needed for better public information, scientific investigation and environmental protection in the offshore. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Proposed Activities to Address Regulatory Gaps and Challenges for Licensing Advanced Reactors Using Seismic Isolation

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

    Coleman, Justin Leigh; Kammerer, Annie M.; Whittaker, Andrew S.

    Over the last decade, particularly since implementation of the certified design regulatory approaches outlined in 10 CFR 52, “Licenses, Certifications, and Approvals for Nuclear Power Plants,” interest has been increasing in the use of seismic isolation (SI) technology to support seismic safety in nuclear facilities. In 2009, the United States (U.S.) Nuclear Regulatory Commission (NRC) initiated research activities to develop new guidance targeted at isolated facilities because SI is being considered for nuclear power plants in the U.S. One product of that research, which was developed around a risk-informed regulatory approach, is a draft NRC NUREG series (NUREG/CR) report thatmore » investigates and discusses considerations for use of SI in otherwise traditionally founded large light water reactors (LWRs). A coordinated effort led to new provisions for SI of LWRs in the American Society of Civil Engineers standard ASCE/SEI 4-16, “Seismic Analysis of Safety Related Nuclear Structures.” The risk-informed design philosophy that underpinned development of the technical basis for these documents led to a set of proposed performance objectives and acceptance criteria intended to serve as the foundation for future NRC guidance on the use of SI and related technology. Although the guidance provided in the draft SI NUREG/CR report and ASCE/SEI 4 16 provides a sound basis for further development of nuclear power plant designs incorporating SI, these initial documents were focused on surface-founded or near-surface-founded LWRs and were, necessarily, limited in scope. For example, there is limited information in both the draft NUREG/CR report and ASCE/SEI 4-16 related to nonlinear analysis of soil-structure systems for deeply-embedded reactors, the isolation of components, and the use of vertical isolation systems. Also not included in the draft SI NUREG/CR report are special considerations for licensing of isolated facilities using the certified design approach in 10 CFR 52 and a detailed discussion of seismic probabilistic risk assessments for isolated facilities.« less

  7. Adaptive trials for tuberculosis: early reflections on theory and practice.

    PubMed

    Montgomery, C M

    2016-08-01

    Adaptive designs (ADs) have been proposed for anti-tuberculosis treatment trials. This call for innovation occurs against the backdrop of fundamental changes in the acceptable evidence base in anti-tuberculosis treatment. To contextualise ADs for tuberculosis (TB) and explore early responses from those working in the field. In this qualitative study investigating processes of theoretical and practical change in randomised controlled trials, 24 interviews were conducted with professionals involved in AD trials, half of whom worked in the TB field. Clinical trialists working on AD trials in TB are positive about the efficiency these designs offer, but remain cautious about their suitability. In addition to technical concerns, informants discussed the challenges of implementing AD in developing countries, including limited regulatory capacity to evaluate proposals, investments needed in infrastructure and site capacity, and challenges regarding informed consent. Respondents identified funding, interdisciplinary communication and regulatory and policy responses as additional concerns potentially affecting the success of AD for TB. Empirical research is needed into patient experiences of AD, including informed consent. Further consideration of the contexts of innovation in trial design is needed. These are fundamental to the successful translation of theory into practice.

  8. Advancing technician practice: Deliberations of a regulatory board.

    PubMed

    Adams, Alex J

    2018-01-01

    In 2016, the Idaho State Board of Pharmacy (U.S.) undertook a major rulemaking initiative to advance pharmacy practice by broadening the ability of pharmacists to delegate tasks to pharmacy technicians. The new rules of the Board thus moved the locus of control in technician scope of practice from law to pharmacist delegation. Pharmacist delegation is individualistic and takes into account the individual technician's capabilities, the pharmacist's comfort level, facility policies, and the risk mitigation strategies present at the facility, among other factors. State law limits, by contrast, are rigid and can mean that pharmacists are unable to delegate tasks that are or could otherwise be within the abilities of their technicians. The expanded technician duties are in two domains: 1) medication dispensing support (e.g., tech-check-tech, accepting verbal prescriptions, transferring prescriptions, and performing remote data entry); and 2) technical support for pharmacist clinical services (e.g., administering immunizations). This commentary reviews the evidence behind these expanded duties, as well as the key regulatory decision points for each task. The Board's rules and approach may prove useful to other states and even other governing bodies outside the U.S. as they consider similar issues. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Immunization in pregnancy clinical research in low- and middle-income countries - Study design, regulatory and safety considerations.

    PubMed

    Kochhar, Sonali; Bonhoeffer, Jan; Jones, Christine E; Muñoz, Flor M; Honrado, Angel; Bauwens, Jorgen; Sobanjo-Ter Meulen, Ajoke; Hirschfeld, Steven

    2017-12-04

    Immunization of pregnant women is a promising public health strategy to reduce morbidity and mortality among both the mothers and their infants. Establishing safety and efficacy of vaccines generally uses a hybrid design between a conventional interventional study and an observational study that requires enrolling thousands of study participants to detect an unknown number of uncommon events. Historically, enrollment of pregnant women in clinical research studies encountered many barriers based on risk aversion, lack of knowledge, and regulatory ambiguity. Conducting research enrolling pregnant women in low- and middle-income countries can have additional factors to address such as limited availability of baseline epidemiologic data on disease burden and maternal and neonatal outcomes during and after pregnancy; challenges in recruiting and retaining pregnant women in research studies, variability in applying and interpreting assessment methods, and variability in locally acceptable and available infrastructure. Some measures to address these challenges include adjustment of study design, tailoring recruitment, consent process, retention strategies, operational and logistical processes, and the use of definitions and data collection methods that will align with efforts globally. Copyright © 2017. Published by Elsevier Ltd.

  10. Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

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

    Wilson, Vickie S., E-mail: wilson.vickie@epa.gov; Keshava, Nagalakshmi; Hester, Susan

    2013-09-15

    The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanismmore » or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment.« less

  11. AP1000{sup R} licensing and deployment in the United States

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

    Jordan, R. P.; Russ, P. A.; Filiak, P. P.

    2012-07-01

    In recent years, both domestic and foreign utilities have turned to the standardized Westinghouse AP1000 plant design in satisfying their near - and long-term - sustainable energy needs. As direct support to these actions, licensing the AP1000 design has played a significant role by providing one of the fundamental bases in clearing regulatory hurdles leading to the start of new plant construction. Within the U.S. alone, Westinghouse AP1000 licensing activities have reached unprecedented milestones with the approvals of both AP1000 Design Certification and Southern Company's combined construction permit and operating license (COL) application directly supporting the construction of two newmore » nuclear plants in Georgia. Further COL application approvals are immediately pending for an additional two AP1000 plants in South Carolina. And, across the U.S. nuclear industry spectrum, there are 10 other COL applications under regulatory review representing some 16 new plants at 10 sites. In total, these actions represent the first wave of new plant licensing under the regulatory approval process since 1978. Fundamental to the Nuclear Regulatory Commission's AP1000 Design Certification is the formal recognition of the AP1000 passive safety design through regulatory acceptance rulemaking. Through recognition and deployment of the AP1000 Design Certification, the utility licensee / operator of this reactor design are now offered an opportunity to use a simplified 'one-step' combined license process, thereby managing substantial back-end construction schedule risk from regulatory and intervention delays. Application of this regulatory philosophy represents both acceptance and encouragement of standardized reactor designs like the AP1000. With the recent AP1000 Design Certification and utility COL acceptances, the fundamental licensing processes of this philosophy have successfully proven the attainment of significant milestones with the next stage licensing actions directed towards deployment. AP1000 Design Certification and COL deployment, and management of the plant construction in accordance with the conditions within these approvals, remain as significant site and corporate responsibilities. These licensing-construction integrated activities must now focus on identifying and resolving 'as-built' departures from the standardized design as assessed against the certified AP1000 technical and licensing basis. Within this paper, significant aspects of the AP1000 U.S. licensing will be discussed, including identifying systems and processes used in ensuring compliance while deploying the standardized design. Critical licensing steps, licensing deployment actions as plant construction progresses and defining the road forward to a successful completion of licensing actions will be addressed. (authors)« less

  12. 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

  13. 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

  14. Multicriteria mapping of stakeholder preferences in regulating nanotechnology

    NASA Astrophysics Data System (ADS)

    Hansen, Steffen Foss

    2010-08-01

    In order to facilitate stakeholder discussions on how to regulate nanotechnology, the opensource program multicriteria mapping (MCM) was used to structure 26 interviews with stakeholders in the USA. MCM offers a systematic part quantitative, part qualitative approach to clarify why some regulatory options (bans, moratoriums, voluntary measures, etc.) were deemed to be acceptable/unacceptable by various stakeholders and which criteria stakeholders used to evaluate the different regulatory options. Adopting an incremental approach and implementing a new regulatory framework was evaluated as the best options whereas a complete ban and no additional regulation of nanotechnology were found to be the least favorable. Criteria applied differed substantially among stakeholders and included social, ethical, regulatory, environmental, and health issues. Opinions on future regulation seem far less polarized than expected and it seems that stakeholders would welcome a combination of voluntary measures, an incremental approach and forming of a new regulatory framework.

  15. Use of QSARs in international decision-making frameworks to predict ecologic effects and environmental fate of chemical substances.

    PubMed Central

    Cronin, Mark T D; Walker, John D; Jaworska, Joanna S; Comber, Michael H I; Watts, Christopher D; Worth, Andrew P

    2003-01-01

    This article is a review of the use, by regulatory agencies and authorities, of quantitative structure-activity relationships (QSARs) to predict ecologic effects and environmental fate of chemicals. For many years, the U.S. Environmental Protection Agency has been the most prominent regulatory agency using QSARs to predict the ecologic effects and environmental fate of chemicals. However, as increasing numbers of standard QSAR methods are developed and validated to predict ecologic effects and environmental fate of chemicals, it is anticipated that more regulatory agencies and authorities will find them to be acceptable alternatives to chemical testing. PMID:12896861

  16. Department of Defense Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... Register is mandated for the regulatory flexibility agendas required by the Regulatory Flexibility Act (5 U... the Agency's regulatory flexibility agenda, in accordance with the Regulatory Flexibility Act, because... Flexibility Act. Printing of these entries is limited to fields that contain information required by the...

  17. 77 FR 60478 - Control of Ferrite Content in Stainless Steel Weld Metal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ...The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing for public comment draft regulatory guide (DG), DG-1279, ``Control of Ferrite Content in Stainless Steel Weld Metal.'' This guide describes a method that the NRC staff considers acceptable for controlling ferrite content in stainless steel weld metal. Revision 4 updates the guide to remove references to outdated standards and to remove an appendix that has been incorporated into relevant specifications.

  18. Regulatory Fit and Equal Opportunity/Diversity: Implications for the Defense Equal Opportunity Management Institute (DEOMI)

    DTIC Science & Technology

    2013-01-01

    than demographic diversity ( Ivancevich & Gilbert, 2000); the goal of equality is to create and manage a heterogeneous mix of abilities, skills, ideas...accepted. Recruiting of minorities and women are not seen as violations of EO laws (Kravitz, 2008; Newman & Lyon , 2009; Pyburn, et al., 2008). Similarly...209-213. REGULATORY FIT AND EQUAL OPPORTUNITY/DIVERSITY 23 Ivancevich , J. M. & Gilbert, J. A. (2000). Diversity management: Time for a new approach

  19. 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.

  20. A Pharmacovigilance Signaling System Based on FDA Regulatory Action and Post-Marketing Adverse Event Reports.

    PubMed

    Hoffman, Keith B; Dimbil, Mo; Tatonetti, Nicholas P; Kyle, Robert F

    2016-06-01

    Many serious drug adverse events (AEs) only manifest well after regulatory approval. Therefore, the development of signaling methods to use with post-approval AE databases appears vital to comprehensively assess real-world drug safety. However, with millions of potential drug-AE pairs to analyze, the issue of focus is daunting. Our objective was to develop a signaling platform that focuses on AEs with historically demonstrated regulatory interest and to analyze such AEs with a disproportional reporting method that offers broad signal detection and acceptable false-positive rates. We analyzed over 1500 US FDA regulatory actions (safety communications and drug label changes) from 2008 to 2015 to construct a list of eligible signal AEs. The FDA Adverse Event Reporting System (FAERS) was used to evaluate disproportional reporting rates, constrained by minimum case counts and confidence interval limits, of these selected AEs for 109 training drugs. This step led to 45 AEs that appeared to have a low likelihood of being added to a label by FDA, so they were removed from the signal eligible list. We measured disproportional reporting for the final group of eligible AEs on a test group of 29 drugs that were not used in either the eligible list construction or the training steps. In a group of 29 test drugs, our model reduced the number of potential drug-AE signals from 41,834 to 97 and predicted 73 % of individual drug label changes. The model also predicted at least one AE-drug pair label change in 66 % of all the label changes for the test drugs. By concentrating on AE types with already demonstrated interest to FDA, we constructed a signaling system that provided focus regarding drug-AE pairs and suitable accuracy with regard to the issuance of FDA labeling changes. We suggest that focus on historical regulatory actions may increase the utility of pharmacovigilance signaling systems.

  1. Gynecologic Oncology Group quality assurance audits: analysis and initiatives for improvement.

    PubMed

    Blessing, John A; Bialy, Sally A; Whitney, Charles W; Stonebraker, Bette L; Stehman, Frederick B

    2010-08-01

    The Gynecologic Oncology Group (GOG) is a multi-institution, multi-discipline Cooperative Group funded by the National Cancer Institute (NCI) to conduct clinical trials which investigate the treatment, prevention, control, quality of survivorship, and translational science of gynecologic malignancies. In 1982, the NCI initiated a program of on-site quality assurance audits of participating institutions. Each is required to be audited at least once every 3 years. In GOG, the audit mandate is the responsibility of the GOG Quality Assurance Audit Committee and it is centralized in the Statistical and Data Center (SDC). Each component (Regulatory, Investigational Drug Pharmacy, Patient Case Review) is classified as Acceptable, Acceptable, follow-up required, or Unacceptable. To determine frequently occurring deviations and develop focused innovative solutions to address them. A database was created to examine the deviations noted at the most recent audit conducted at 57 GOG parent institutions during 2004-2007. Cumulatively, this involved 687 patients and 306 protocols. The results documented commendable performance: Regulatory (39 Acceptable, 17 Acceptable, follow-up, 1 Unacceptable); Pharmacy (41 Acceptable, 3 Acceptable, follow-up, 1 Unacceptable, 12 N/A): Patient Case Review (31 Acceptable, 22 Acceptable, follow-up, 4 Unacceptable). The nature of major and lesser deviations was analyzed to create and enhance initiatives for improvement of the quality of clinical research. As a result, Group-wide proactive initiatives were undertaken, audit training sessions have emphasized recurring issues, and GOG Data Management Subcommittee agendas have provided targeted instruction and training. The analysis was based upon parent institutions only; affiliate institutions and Community Clinical Oncology Program participants were not included, although it is assumed their areas of difficulty are similar. The coordination of the GOG Quality Assurance Audit program in the SDC has improved data quality by enhancing our ability to identify frequently occurring deviations and develop innovative solutions to avoid or minimize their occurrence in the future.

  2. 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

  3. 76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

  4. What a Difference a Year Makes.

    ERIC Educational Resources Information Center

    Birt, Carina

    1998-01-01

    Addresses the growth of signatures in document management. Describes the three basic types of electronic signature technology: image signatures, digital signatures, and digitized biometric signatures. Discusses legal and regulatory acceptability and bringing signatures into document management. (AEF)

  5. 17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

  6. 17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

  7. 17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

  8. 17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

  9. 17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

  10. Justifiability and Animal Research in Health: Can Democratisation Help Resolve Difficulties?

    PubMed

    Khoo, Shaun Yon-Seng

    2018-02-14

    Current animal research ethics frameworks emphasise consequentialist ethics through cost-benefit or harm-benefit analysis. However, these ethical frameworks along with institutional animal ethics approval processes cannot satisfactorily decide when a given potential benefit is outweighed by costs to animals. The consequentialist calculus should, theoretically, provide for situations where research into a disease or disorder is no longer ethical, but this is difficult to determine objectively. Public support for animal research is also falling as demand for healthcare is rising. Democratisation of animal research could help resolve these tensions through facilitating ethical health consumerism or giving the public greater input into deciding the diseases and disorders where animal research is justified. Labelling drugs to disclose animal use and providing a plain-language summary of the role of animals may help promote public understanding and would respect the ethical beliefs of objectors to animal research. National animal ethics committees could weigh the competing ethical, scientific, and public interests to provide a transparent mandate for animal research to occur when it is justifiable and acceptable. Democratic processes can impose ethical limits and provide mandates for acceptable research while facilitating a regulatory and scientific transition towards medical advances that require fewer animals.

  11. Chemistry Testing on Plasma Versus Serum Samples in Dialysis Patients: Clinical and Quality Improvement Implications.

    PubMed

    Carey, Roger Neill; Jani, Chinu; Johnson, Curtis; Pearce, Jim; Hui-Ng, Patricia; Lacson, Eduardo

    2016-09-07

    Plasma samples collected in tubes containing separator gels have replaced serum samples for most chemistry tests in many hospital and commercial laboratories. Use of plasma samples for blood tests in the dialysis population eliminates delays in sample processing while waiting for clotting to complete, laboratory technical issues associated with fibrin formation, repeat sample collection, and patient care issues caused by delay of results because of incompletely clotted specimens. Additionally, a larger volume of plasma is produced than serum for the same amount of blood collected. Plasma samples are also acceptable for most chemical tests involved in the care of patients with ESRD. This information becomes very important when United States regulatory requirements for ESRD inadvertently limit the type of sample that can be used for government reporting, quality assessment, and value-based payment initiatives. In this narrative, we summarize the renal community experience and how the subsequent resolution of the acceptability of phosphorus levels measured from serum and plasma samples may have significant implications in the country's continued development of a value-based Medicare ESRD Quality Incentive Program. Copyright © 2016 by the American Society of Nephrology.

  12. Status of nuclear Class 1 component requalification: Final report

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

    Cooper, W.E.

    1986-12-01

    Qualification relates to assurance of acceptability of the component with respect to structural integrity, operability and functional capability. Requalification is required if existing qualification is lost because of: expiration of the qualified service life (life extension); reactivation of a cancelled or suspended plant; failure to conform with certain requirements of the Technical Specifications, or revision to the applicable Regulatory requirements. The alternatives to requalification are replacement or removal from service. The choice between requalification, replacement and removal from service is governed by economics. The purpose of requalification standards is to ensure the acceptability of the requalification process. A previous EPRImore » Report prepared by Teledyne Engineering Services (TES) (NP-1921) developed a rationale for, and a draft of, a generic requalification standard for Class 1 Pressure Boundary Components presently considered by the Boiler and Pressure Vessel Code published by The American Society of Mechanical Engineers (ASME/BPVC). International Energy Associates Limited (IEA) prepared another report for EPRI shortly thereafter (NP-2418), which reviewed the economic and technologies factors of nuclear plant life extension, and concluded that NP-1921 makes a strong case that the nuclear industry will benefit from the development of the proposed standard.« less

  13. 78 FR 25129 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Withdrawal of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-29

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Withdrawal of Proposed Rule Change Regarding Central Counterparty Resolution and Recovery Procedures April 22, 2013. On March 7, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission (``Commission...

  14. 77 FR 43620 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-25

    ... self-regulatory organization consents, the Commission shall either approve the proposed rule change...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to the Handling of Stop and Stop Limit...

  15. 75 FR 21773 - Improving Government Regulations; Unified Agenda of Federal Regulatory and Deregulatory Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... Register is mandated for the regulatory flexibility agendas required by the Regulatory Flexibility Act (5 U... the Agency's regulatory flexibility agenda, in accordance with the Regulatory Flexibility Act, because... Flexibility Act. Printing of these entries is limited to fields that contain information required by the...

  16. Developing acceptance limits for measured bearing wear of the Space Shuttle Main Engine high pressure oxidizer turbopump

    NASA Technical Reports Server (NTRS)

    Genge, Gary G.

    1991-01-01

    The probabilistic design approach currently receiving attention for structural failure modes has been adapted for obtaining measured bearing wear limits in the Space Shuttle Main Engine high-pressure oxidizer turbopump. With the development of the shaft microtravel measurements to determine bearing health, an acceptance limit was neeed that protects against all known faiure modes yet is not overly conservative. This acceptance criteria limit has been successfully determined using probabilistic descriptions of preflight hardware geometry, empirical bearing wear data, mission requirements, and measurement tool precision as an input for a Monte Carlo simulation. The result of the simulation is a frequency distribution of failures as a function of preflight acceptance limits. When the distribution is converted into a reliability curve, a conscious risk management decision is made concerning the acceptance limit.

  17. Governing nanobiotechnology: lessons from agricultural biotechnology regulation

    NASA Astrophysics Data System (ADS)

    Johnson, Robbin S.

    2011-04-01

    This article uses lessons from biotechnology to help inform the design of oversight for nanobiotechnology. Those lessons suggest the following: first, oversight needs to be broadly defined, encompassing not just regulatory findings around safety and efficacy, but also public understanding and acceptance of the technology and its products. Second, the intensity of scrutiny and review should reflect not just risks but also perceptions of risk. Finally, a global marketplace argues for uniform standards or commercially practical solutions to differences in standards. One way of designing oversight to achieve these purposes is to think about it in three phases—precaution, prudence, and promotion. Precaution comes early in the technology or product's development and reflects real and perceived uncertainties. Prudence governs when risks and hazards have been identified, containment approaches established, and benefits broadly defined. Transparency and public participation rise to the fore. The promotional phase moves toward shaping public understanding and acceptance and involves marketing issues rather than safety ones. This flexible, three-phase approach to oversight would have avoided some of the early regulatory problems with agricultural biotechnology. It also would have led to a more risk-adjusted pathway to regulatory approval. Furthermore, it would avoid some of the arbitrary, disruptive marketing issues that have arisen.

  18. Potential Impact of Risk and Loss Aversion on the Process of Accepting Kidneys for Transplantation.

    PubMed

    Heilman, Raymond L; Green, Ellen P; Reddy, Kunam S; Moss, Adyr; Kaplan, Bruce

    2017-07-01

    Behavioral economic theory suggests that people make decisions based on maximizing perceived value; however, this may be influenced more by the risk of loss rather than of potential gain. Additionally, individuals may seek certainty over uncertainty. These are termed loss aversion and risk aversion, respectively. Loss aversion is particularly sensitive to how the decision is "framed." Thus, labeling a kidney as high Kidney Donor Profile Index results in higher discard rates because this creates a nonlinearity in perceived risk. There is also evidence that the perceived loss due to regulatory sanction results in increased organ discard rates. This may be due to the overuse of terminology that stresses regulatory sanctions and thus perpetuates fear of loss through a form of nudging. Our goal is to point out how these concepts of behavioral economics may negatively influence the decision process to accept these suboptimal organs. We hope to make the community more aware of these powerful psychological influences and thus potentially increase the utilization of these suboptimal organs. Further, we would urge regulatory bodies to avoid utilizing strategies that frame outcomes in terms of loss due to flagging and build models that are less prone to uncertain expected versus observed outcomes.

  19. Unlocking the potential of small unmanned aircraft systems (sUAS) for Earth observation

    NASA Astrophysics Data System (ADS)

    Hugenholtz, C.; Riddell, K.; Barchyn, T. E.

    2012-12-01

    Small unmanned aircraft systems (sUAS, < 25 kg) are emerging as a viable alternative to conventional remote sensing platforms for Earth observation (EO). sUAS technology affords greater control, lower cost, and flexibility for scientists, and provides new opportunities to match the scale of sUAS data to the scale of the geophysical phenomenon under investigation. Although a mechanism is in place to make sUAS available to researchers and other non-military users through the US Federal Aviation Administration's Modernization and Reform Act of 2012 (FAAMRA), there are many regulatory hurdles before they are fully accepted and integrated into the National Airspace System. In this talk we will provide a brief overview of the regulatory landscape for sUAS, both in the USA and in Canada, where sUAS regulations are more flexible. We critically outline potential advantages and disadvantages of sUAS for EO applications under current and potential regulations. We find advantages: relatively low cost, potentially high temporal resolution, rapidly improving technology, and operational flexibility. We also find disadvantages: limited temporal and spatial extent, limited accuracy assessment and methodological development, and an immature regulatory landscape. From a case study we show an example of the accuracy of a photogrammetrically-derived digital terrain map (DTM) from sUAS imagery. We also compare the sUAS DTM to a LiDAR DTM. Our results suggest that sUAS-acquired imagery may provide a low-cost, rapid, and flexible alternative to airborne LiDAR. Overall, we are encouraged about the potential of sUAS for geophysical measurements; however, understanding and compliance with regulations is paramount to ensure that research is conducted legally and responsibly. Because UAS are new outside of military operations, we hope researchers will proceed carefully to ensure this great scientific opportunity remains a long term tool.

  20. Rail vehicle qualification test compendium.

    DOT National Transportation Integrated Search

    2015-02-01

    Qualification and acceptance testing and analysis for new passenger rail vehicles for transit systems has been specified by the transit/commuter agency for which the cars will be supplied to and/or by government agencies. Regulatory testing defined b...

  1. 76 FR 41438 - International Traffic in Arms Regulations: International Import Certificate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ... authoritative basis for the Department to do so. DATES: The Department of State will accept comments on this... year, there is no statutory, regulatory, or other authoritative basis for the Department of State to...

  2. 77 FR 26066 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ...-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change to Provide for a T+1 Settlement of the Initial Payment Related to the CDS Contracts Cleared by ICE Clear Europe Limited April 26, 2012. I. Introduction On March 6, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the...

  3. Hydroponic phytoremediation of heavy metals and radionuclides

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

    Hartong, J.; Szpak, J.; Hamric, T.

    1998-07-01

    It is estimated that the Departments of Defense, Energy, and Agriculture will spend up to 300 billion federal dollars on environmental remediation during the next century. Current remediation processes can be expensive, non-aesthetic, and non-versatile. Therefore, the need exists for more innovative and cost effective solutions. Phytoremediation, the use of vegetation for the remediation of contaminated sediments, soils, and ground water, is an emerging technology for treating several categories of persistent, toxic contaminants. Although effective, phytoremediation is still in a developmental stage, and therefore is not a widely accepted technology by regulatory agencies and public groups. Research is currently beingmore » conducted to validate the processes effectiveness as well as increase regulatory and community acceptance. This research will focus on the ability of plants to treat an aquifer contaminated with heavy metals and radionuclides. Specifically, the effectiveness of hydroponically grown dwarf sunflowers and mustard seed will be investigated.« less

  4. Regulatory T cells in the control of host-microorganism interactions (*).

    PubMed

    Belkaid, Yasmine; Tarbell, Kristin

    2009-01-01

    Each microenvironment requires a specific set of regulatory elements that are finely and constantly tuned to maintain local homeostasis. Various populations of regulatory T cells contribute to the maintenance of this equilibrium and establishment of controlled immune responses. In particular, regulatory T cells limit the magnitude of effector responses, which may result in failure to adequately control infection. However, regulatory T cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses against pathogenic microbes as well as commensals. In this review, we describe various situations in which the balance between regulatory T cells and effector immune functions influence the outcome of host-microorganism coexistence and discuss current hypotheses and points of polemic associated with the origin, target, and antigen specificity of both endogenous and induced regulatory T cells during these interactions.

  5. Regulatory challenges associated with conducting multicountry clinical trials in resource-limited settings.

    PubMed

    Ndebele, Paul; Blanchard-Horan, Christina; Shahkolahi, Akbar; Sanne, Ian

    2014-01-01

    International public health and infectious diseases research has expanded to become a global enterprise transcending national and continental borders in organized networks addressing high-impact diseases. In conducting multicountry clinical trials, sponsors and investigators have to ensure that they meet regulatory requirements in all countries in which the clinical trials will be conducted. Some of these requirements include review and approval by national drug regulatory authorities and recognized research ethics committees. A limiting factor to the efficient conduct of multicountry clinical trials is the regulatory environment in each collaborating country, with significant differences determined by various factors including the laws and the procedures used in each country. The long regulatory processes in resource-limited countries may hinder the efficient implementation of multisite clinical trials, delaying research important to the health of populations in these countries and costing millions of dollars a year.

  6. United States direct broadcast satellite system development

    NASA Astrophysics Data System (ADS)

    Dement, D. K.

    1984-03-01

    As the technology appears increasingly likely to meet the needs and as DBS regulatory activity becomes fixed, investment decisions will be made. With only modest technical risk for even the high-powered satellites, with little doubt that mass-produced earth terminals' gain-over-temperature of 10 dB or more can be attained for an acceptable price, and with the advent of acceptably priced individual descramblers for pay television, interest in DBS continues to grow. Present concerns center on market acceptance, competition, and programming availability. The variety of operational approaches revealed in FCC permit applications is seen as showing a willingness to risk, innovate, and move forward as quickly as possible.

  7. 76 FR 76153 - Allco Renewable Energy Limited v. Massachusetts Electric Company d/b/a National Grid; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL12-12-000] Allco Renewable Energy Limited v. Massachusetts Electric Company d/b/a National Grid; Notice of Complaint Take notice... Public Utilities Regulatory Policies Act (PURPA), Allco Renewable Energy Limited filed a formal complaint...

  8. 78 FR 51248 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change Related to... August 14, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange... been prepared primarily by ICE Clear Europe. The Commission is publishing this notice to solicit...

  9. 78 FR 19057 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing Proposed Rule Changes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing Proposed Rule Changes Regarding Central..., 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission... prepared primarily by ICE Clear Europe. The Commission is publishing this notice to solicit comments on the...

  10. 78 FR 7844 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Withdrawal of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Withdrawal of Proposed Rule Change To Clear Western European Sovereign CDS Contracts January 29, 2013. On October 15, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission (``Commission''), pursuant to...

  11. 78 FR 54718 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-05

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed... given that on August 20, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities..., which Items have been prepared primarily by ICE Clear Europe. ICE Clear Europe filed the proposal...

  12. 78 FR 28680 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-15

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend Delivery Procedures To Reflect the Clearing Relationship for ICE Futures Europe... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 24, 2013, ICE Clear Europe Limited...

  13. 78 FR 333 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-03

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed...''),\\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 19, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission (``Commission'') the...

  14. Animals and the 3Rs in toxicology research and testing: The way forward.

    PubMed

    Stokes, W S

    2015-12-01

    Despite efforts to eliminate the use of animals in testing and the availability of many accepted alternative methods, animals are still widely used for toxicological research and testing. While research using in vitro and computational models has dramatically increased in recent years, such efforts have not yet measurably impacted animal use for regulatory testing and are not likely to do so for many years or even decades. Until regulatory authorities have accepted test methods that can totally replace animals and these are fully implemented, large numbers of animals will continue to be used and many will continue to experience significant pain and distress. In order to positively impact the welfare of these animals, accepted alternatives must be implemented, and efforts must be directed at eliminating pain and distress and reducing animal numbers. Animal pain and distress can be reduced by earlier predictive humane endpoints, pain-relieving medications, and supportive clinical care, while sequential testing and routine use of integrated testing and decision strategies can reduce animal numbers. Applying advances in science and technology to the development of scientifically sound alternative testing models and strategies can improve animal welfare and further reduce and replace animal use. © The Author(s) 2015.

  15. 77 FR 22825 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Filing and Order...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-17

    ... Proposed Rule Change Regarding Acceptance of Additional Interest Rate Swaps and Related Interbank Rates for... organization offering interest rate swap (``IRS'') clearing services. More specifically, the proposed rule... Dollar (``AUD'') [[Page 22826

  16. IN SILICO MODELLING OF HAZARDOUS ENDPOINTS: CURRENT PROBLEMS AND PROSPECTIVES

    EPA Science Inventory

    The primary hurdles for Quantitative Structure-Activity Relationships (QSARs) to overcome their acceptance for regulatory purposes will be discussed. They include (a) the development of more mechanistic representations of chemical structure, (b) the classification of toxicity pa...

  17. Conception et validation d'un modele d'analyse et de suivi pour une politique energetique durable et acceptable de l'energie eolienne: Une etude comparative France-Quebec

    NASA Astrophysics Data System (ADS)

    Feurtey, Evariste

    In this research, we built a conceptual model of a sustainable and acceptable wind power policy that we tried to validate through the case study of France and Quebec in the wind energy sector. Our qualitative and comparative approach helps us to illustrate the interaction of institutional variables studied, including the national context of emergence, the balance of power between pressure groups, the supranational and exogenous influences, level of political commitment, policy and regulatory instruments, social acceptance and energy policy mechanisms. The research confirms that the neo-corporatism is present in France as in Quebec. With the unfavorable energy context (low cost of electricity tariff, lack of electricity demand, and an already low zero carbon electric mix), it is an important factor explaining : 1) the 20 years delay accumulated by France and Quebec in the development of wind projects or industrial sector; 2) the 10% limited penetration scale given to wind energy. We also demonstrate that the political commitment to develop wind energy fluctuates with the government majority, the energy context or the influence of pressure groups. This manifests itself in a lack of continuity of policies and tariff instruments used. In both national case studies, the results also show that balanced policies and regulations ensure sustainable development of wind energy only if they allow a sufficient market size. The search results also illustrates that the conceptual division made between acceptance of wind sector, acceptance of ownership, local acceptance is very instructive. Social controversies, though multifactorial, are connected to both a critique of the development model too industrial and private, territorial dilemmas (closed environment), energy context (electric surplus in Quebec), or related to strategic planning system and centralized decision. An important issue for a more acceptable wind policy in the future will come to a greater plurality of ownership, variety of wind projects scale, diversity of financial support mechanisms. This transformation to a more territorial policy that require renewables also calls for decentralization and ecological modernization of institutions. Sustainable and acceptable energy policy requires obtaining a stabilized consensus on the long-term energy mix, which should be done by a comprehensive energy and public debate upstream the development of energy policy. Keywords: energy policy, social acceptance, wind energy, environmental assessment, components, interactions.

  18. Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications.

    PubMed

    Paini, Alicia; Leonard, Jeremy A; Kliment, Tomas; Tan, Yu-Mei; Worth, Andrew

    2017-11-01

    Physiologically based kinetic (PBK) models are used widely throughout a number of working sectors, including academia and industry, to provide insight into the dosimetry related to observed adverse health effects in humans and other species. Use of these models has increased over the last several decades, especially in conjunction with emerging alternative methods to animal testing, such as in vitro studies and data-driven in silico quantitative-structure-activity-relationship (QSAR) predictions. Experimental information derived from these new approach methods can be used as input for model parameters and allows for increased confidence in models for chemicals that did not have in vivo data for model calibration. Despite significant advancements in good modelling practice (GMP) for model development and evaluation, there remains some reluctance among regulatory agencies to use such models during the risk assessment process. Here, the results of a survey disseminated to the modelling community are presented in order to inform the frequency of use and applications of PBK models in science and regulatory submission. Additionally, the survey was designed to identify a network of investigators involved in PBK modelling and knowledgeable of GMP so that they might be contacted in the future for peer review of PBK models, especially in regards to vetting the models to such a degree as to gain a greater acceptance for regulatory purposes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. A simple approach for a spatial terrestrial exposure assessment of the insecticide fenoxycarb, based on a high-resolution landscape analysis.

    PubMed

    Thomas, Kai; Resseler, Herbert; Spatz, Robert; Hendley, Paul; Sweeney, Paul; Urban, Martin; Kubiak, Roland

    2016-11-01

    The objective was to refine the standard regulatory exposure scenario used in plant protection product authorisations by developing a more realistic landscape-related GIS-based exposure assessment for terrestrial non-target arthropods. We quantified the proportion of adjacent off-target area in agricultural landscapes potentially exposed to insecticide drift from applications of the active substance fenoxycarb. High-resolution imagery, landscape classification and subsequent stepwise analysis of a whole landscape using drift and interception functions were applied to selected areas in representative fruit-producing regions in Germany. Even under worst-case assumptions regarding treated area, use rate and drift, less than 12% of the non-agricultural habitat area would potentially be exposed to fenoxycarb drift above regulatory acceptable concentrations. Additionally, if the filtering effect of tall vegetation were taken into account, this number would decrease to 6.6%. Further refinements to landscape elements and application conditions indicate that less than 5% of the habitat area might be exposed above regulatory acceptable concentrations, meaning that 95% of the non-agricultural habitat area will be unimpacted (i.e. no unacceptable effects) and can serve as refuge for recolonisation. Approaches and tools are proposed for standardisable and transparent refinements in regulatory risk assessments on the landscape level. © 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  20. Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies.

    PubMed

    Lin, Ja-An; He, Pei

    2015-06-01

    Recently, new clinical trial designs involving biomarkers have been studied and proposed in cancer clinical research, in the hope of incorporating the rapid growing basic research into clinical practices. Journal articles related to various biomarkers and their role in cancer clinical trial, articles and books about statistical issues in trial design, and regulatory website, documents, and guidance for submission of targeted cancer therapies. The drug development process involves four phases. The confirmatory Phase III is essential in regulatory approval of a special treatment. Regulatory agency has restrictions on confirmatory trials 'using adaptive designs'. No rule of thumb to pick the most appropriate design for biomarker-related trials. Statistical issues to solve in new designs. Regulatory acceptance of the 'newly proposed trial designs'. Biomarker-related trial designs that can resolve the statistical issues and satisfy the regulatory requirement. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Multicriteria mapping of stakeholder preferences in regulating nanotechnology.

    PubMed

    Hansen, Steffen Foss

    2010-08-01

    In order to facilitate stakeholder discussions on how to regulate nanotechnology, the opensource program multicriteria mapping (MCM) was used to structure 26 interviews with stakeholders in the USA. MCM offers a systematic part quantitative, part qualitative approach to clarify why some regulatory options (bans, moratoriums, voluntary measures, etc.) were deemed to be acceptable/unacceptable by various stakeholders and which criteria stakeholders used to evaluate the different regulatory options. Adopting an incremental approach and implementing a new regulatory framework was evaluated as the best options whereas a complete ban and no additional regulation of nanotechnology were found to be the least favorable. Criteria applied differed substantially among stakeholders and included social, ethical, regulatory, environmental, and health issues. Opinions on future regulation seem far less polarized than expected and it seems that stakeholders would welcome a combination of voluntary measures, an incremental approach and forming of a new regulatory framework. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11051-010-0006-3) contains supplementary material, which is available to authorized users.

  2. 77 FR 37458 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-21

    ...; facilitate the display of customer limit orders under FINRA Rule 6460 (Display of Customer Limit Orders); \\4... the Commission to evaluate the impact of the proposed pilot on the over-the-counter (``OTC'') equity... tiers, facilitate the display of customer limit orders under FINRA Rule 6460,\\15\\ and expand the Rule's...

  3. 78 FR 64255 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-28

    ... Amending Commentary .07 to Rule 904 To Extend the Pilot Program That Eliminated the Position Limits for... that eliminated the position limits for options on SPDR S&P 500 ETF (``SPY'') (``SPY Pilot Program...- regulatory organizations (``SROs'') have adopted similar rules eliminating position limits on SPY and market...

  4. 77 FR 7652 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Proposed Rule Change To Revise...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Proposed Rule Change To Revise Rules and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January 24, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission (``Commission'') the proposed...

  5. 77 FR 11607 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting Accelerated Approval... \\2\\ notice is hereby given that on February 7, 2012, ICE Clear Europe Limited (``ICE Clear Europe... in Items I, II and III below, which Items have been prepared primarily by ICE Clear Europe. The...

  6. 78 FR 15775 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-12

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting Accelerated Approval...\\ notice is hereby given that on February 28, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed... Items I and II below, which Items have been prepared primarily by ICE Clear Europe. The Commission is...

  7. 78 FR 58576 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Clear Contracts Traded on ICE Endex September 18, 2013. Pursuant to Section 19(b)(1) of... that on September 18, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities...

  8. 77 FR 62289 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-12

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting Accelerated Approval... thereunder,\\2\\ notice is hereby given that on September 25, 2012, ICE Clear Europe Limited (``ICE Clear... described in Items I and II below, which items have been prepared primarily by ICE Clear Europe. The...

  9. 77 FR 76315 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-27

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Delivery Procedures To Reflect the Clearing Relationship for ICE Futures U.S. Inc... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 19, 2012, ICE Clear Europe Limited...

  10. Determination and evaluation of acceptable force limits in single-digit tasks.

    PubMed

    Nussbaum, Maury A; Johnson, Hope

    2002-01-01

    Acceptable limits derived from psychophysical methodologies have been proposed, measured, and employed in a range of applications. There is little existing work, however, on such limits for single-digit exertions and relatively limited evidence on several fundamental issues related to data collection and processing of a sequence of self-regulated exertion levels. An experimental study was conducted using 14 male and 10 female participants (age range 18-31 years) from whom maximal voluntary exertions and maximal acceptable limits (MALs) were obtained using the index finger and thumb. Moderate to high levels of consistency were found for both measures between sessions separated by one day. Single MAL values, determined from a time series of exertions, were equivalent across three divergent processing methods and between values obtained from 5- and 25-min samples. A critical interpretation of these and earlier results supports continued use of acceptable limits but also suggests that they should be used with some caution and not equated with safe limits. This research can be applied toward future development of exertion limits based on perceived acceptability.

  11. 77 FR 70515 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-26

    ... Effectiveness of Proposed Rule Change To Establish a Limited Waiver of the TRACE Professional Real-Time Data... limited waiver of the Professional Real-Time Data Display Fee of $60 to access Real-Time Trade Reporting...

  12. 10 CFR 30.50 - Reporting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... prevents immediate protective actions necessary to avoid exposures to radiation or radioactive materials... license condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

  13. 10 CFR 70.50 - Reporting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... event that prevents immediate protective actions necessary to avoid exposures to radiation or... licensee condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

  14. 10 CFR 70.50 - Reporting requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... event that prevents immediate protective actions necessary to avoid exposures to radiation or... licensee condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

  15. 10 CFR 30.50 - Reporting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... prevents immediate protective actions necessary to avoid exposures to radiation or radioactive materials... license condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

  16. 10 CFR 70.50 - Reporting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... event that prevents immediate protective actions necessary to avoid exposures to radiation or... licensee condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

  17. 10 CFR 30.50 - Reporting requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... prevents immediate protective actions necessary to avoid exposures to radiation or radioactive materials... license condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

  18. Parameters for Pesticide QSAR and PBPK/PD Models to inform Human Risk Assessments

    EPA Science Inventory

    Physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling has emerged as an important computational approach supporting quantitative risk assessment of agrochemicals. However, before complete regulatory acceptance of this tool, an assessment of assets and liabi...

  19. Monitored natural attenuation forum: MNA of metals and radionuclides

    EPA Science Inventory

    While the natural attenuation of many organic compounds is established and accepted by the regulated and regulatory communities, there is some debate whether monitored natural attenuation (MNA) of metals and radionuclides is a reasonable remedial alternative to consider. Do you...

  20. 76 FR 5215 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-28

    ... Compliance with Packaging Requirements for Shipment and Receipt of Radioactive Material,'' is temporarily... Code of Federal Regulations, Part 71, ``Packaging and Transportation of Radioactive Material'' (10 CFR... Compliance with Packaging Requirements for Shipments of Radioactive Materials,'' as an acceptable process for...

  1. 78 FR 60364 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... accepted. Finally, the Exchange believes that it is subject to significant competitive forces, as described... they deem fee levels at a particular venue to be excessive. In such an environment, the Exchange must...

  2. USEPA SITE PROGRAM APPROACH TO TECHNOLOGY TRANSFER AND REGULATORY ACCEPTANCE

    EPA Science Inventory

    The SITE Program was created to meet the increased demand for innovative technologies for hazardous waste treatment. To accomplish this mission, the program seeks to advance the development, implementation and commercialization of innovative technologies for hazardous waste chara...

  3. 75 FR 7934 - Airworthiness Directives; McCauley Propeller Systems 1A103/TCM Series Propellers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-23

    ... with cracks that do not meet acceptable limits, and rework of propellers with cracks that meet..., replacement of propellers with cracks that do not meet acceptable limits, and rework of propellers with cracks... propeller hub, removal from service of propellers with cracks that do not meet acceptable limits, and rework...

  4. The regulatory network analysis of long noncoding RNAs in human colorectal cancer.

    PubMed

    Zhang, Yuwei; Tao, Yang; Li, Yang; Zhao, Jinshun; Zhang, Lina; Zhang, Xiaohong; Dong, Changzheng; Xie, Yangyang; Dai, Xiaoyu; Zhang, Xinjun; Liao, Qi

    2018-05-01

    Colorectal cancer (CRC) is among one of the most prevalent and lethiferous diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to function as a key regulatory factor in human cancer, but the potential regulatory mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated several expression profiles to obtain 55 differentially expressed (DE) lncRNAs. We first detected lncRNA interactions with transcription factors, microRNAs, mRNAs, and RNA-binding proteins to construct a regulatory network and then create functional enrichment analyses for them using bioinformatics approaches. We found the upregulated genes in the regulatory network are enriched in cell cycle and DNA damage response, while the downregulated genes are enriched in cell differentiation, cellular response, and cell signaling. We then employed module-based methods to mine several intriguing modules from the overall network, which helps to classify the functions of genes more specifically. Next, we confirmed the validity of our network by comparisons with a randomized network using computational method. Finally, we attempted to annotate lncRNA functions based on the regulatory network, which indicated its potential application. Our study of the lncRNA regulatory network provided significant clues to unveil lncRNAs potential regulatory mechanisms in CRC and laid a foundation for further experimental investigation.

  5. 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.

  6. International Harmonization and Cooperation in the Validation of Alternative Methods.

    PubMed

    Barroso, João; Ahn, Il Young; Caldeira, Cristiane; Carmichael, Paul L; Casey, Warren; Coecke, Sandra; Curren, Rodger; Desprez, Bertrand; Eskes, Chantra; Griesinger, Claudius; Guo, Jiabin; Hill, Erin; Roi, Annett Janusch; Kojima, Hajime; Li, Jin; Lim, Chae Hyung; Moura, Wlamir; Nishikawa, Akiyoshi; Park, HyeKyung; Peng, Shuangqing; Presgrave, Octavio; Singer, Tim; Sohn, Soo Jung; Westmoreland, Carl; Whelan, Maurice; Yang, Xingfen; Yang, Ying; Zuang, Valérie

    The development and validation of scientific alternatives to animal testing is important not only from an ethical perspective (implementation of 3Rs), but also to improve safety assessment decision making with the use of mechanistic information of higher relevance to humans. To be effective in these efforts, it is however imperative that validation centres, industry, regulatory bodies, academia and other interested parties ensure a strong international cooperation, cross-sector collaboration and intense communication in the design, execution, and peer review of validation studies. Such an approach is critical to achieve harmonized and more transparent approaches to method validation, peer-review and recommendation, which will ultimately expedite the international acceptance of valid alternative methods or strategies by regulatory authorities and their implementation and use by stakeholders. It also allows achieving greater efficiency and effectiveness by avoiding duplication of effort and leveraging limited resources. In view of achieving these goals, the International Cooperation on Alternative Test Methods (ICATM) was established in 2009 by validation centres from Europe, USA, Canada and Japan. ICATM was later joined by Korea in 2011 and currently also counts with Brazil and China as observers. This chapter describes the existing differences across world regions and major efforts carried out for achieving consistent international cooperation and harmonization in the validation and adoption of alternative approaches to animal testing.

  7. Development of a novel regulatory pharmacovigilance prioritisation system: an evaluation of its performance at the UK Medicines and Healthcare products Regulatory Agency.

    PubMed

    Seabroke, Suzie; Wise, Lesley; Waller, Patrick

    2013-10-01

    The prioritisation of drug safety issues for further evaluation or regulatory action is critical to ensure that acceptable timelines and appropriate resource allocation are defined to meet public health and regulatory obligations. Our objective was to develop, pilot and implement a novel tool for prioritising pharmacovigilance issues within the Medicines and Healthcare products Regulatory Agency (MHRA). An initial system was developed empirically and then piloted over a 10-month period in the pharmacovigilance signal management meeting at the MHRA that discusses potential pharmacovigilance issues, and determines, through consensus, their priority and a timescale for action. The priority assigned by the tool was compared with the priority decided by collective judgement at the meeting. Once an acceptable level of concordance between the tool and the meeting had been achieved, the finalised tool was implemented into routine use at the MHRA, with an evaluation of its performance conducted after the first year. The Regulatory Pharmacovigilance Prioritisation System (RPPS) tool prioritises pharmacovigilance issues according to the following four broad categories, each with four inputs: strength of evidence, public health implications, agency regulatory obligations and public perceptions. A weighted scoring system links the inputs to a pre-defined number of points where if a threshold is reached then the points are awarded. The overall priority is determined by the sum of all points obtained from each of the inputs. The pilot study included a total of 73 pharmacovigilance issues during the 10-month study period, with an overall exact agreement between the RPPS priority and the collective judgement of the meeting of 60.3 %. Where exact agreement was not obtained, the RPPS generally prioritised the issues slightly higher than the meeting. Over the first year following implementation, the RPPS achieved an overall exact agreement of 82.2 %. Following the pilot study and implementation at the UK MHRA, the RPPS has provided a systematic approach to drug safety issue prioritisation that should help to reduce the subjectivity of reliance on individual judgement.

  8. [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.

  9. Regulating transgenic crops sensibly: lessons from plant breeding, biotechnology and genomics.

    PubMed

    Bradford, Kent J; Van Deynze, Allen; Gutterson, Neal; Parrott, Wayne; Strauss, Steven H

    2005-04-01

    The costs of meeting regulatory requirements and market restrictions guided by regulatory criteria are substantial impediments to the commercialization of transgenic crops. Although a cautious approach may have been prudent initially, we argue that some regulatory requirements can now be modified to reduce costs and uncertainty without compromising safety. Long-accepted plant breeding methods for incorporating new diversity into crop varieties, experience from two decades of research on and commercialization of transgenic crops, and expanding knowledge of plant genome structure and dynamics all indicate that if a gene or trait is safe, the genetic engineering process itself presents little potential for unexpected consequences that would not be identified or eliminated in the variety development process before commercialization. We propose that as in conventional breeding, regulatory emphasis should be on phenotypic rather than genomic characteristics once a gene or trait has been shown to be safe.

  10. A Regulatory Framework for Nanotechnology

    DTIC Science & Technology

    informed by a map of the regulatory landscape of nanotechnology and a review of the regulatory frameworks for the aviation and biotechnology industries...aviation and biotechnology and maps the regulatory landscape in the United States by examining stakeholders, regulatory entities, and applicable legislation...state of nanotechnology if the limitations of technical expertise are addressed. This expertise can be provided by advisory committees of technical

  11. 75 FR 27606 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-17

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to the Trade Reporting Facility Limited Liability Company...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 27, 2010, the Financial Industry...

  12. 21 CFR 312.86 - Focused FDA regulatory research.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

  13. 21 CFR 312.86 - Focused FDA regulatory research.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

  14. 21 CFR 312.86 - Focused FDA regulatory research.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

  15. 21 CFR 312.86 - Focused FDA regulatory research.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

  16. 21 CFR 312.86 - Focused FDA regulatory research.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

  17. 76 FR 65544 - Standard Format and Content of License Applications for Mixed Oxide Fuel Fabrication Facilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-21

    ...The U.S. Nuclear Regulatory Commission (NRC or Commission) is issuing a revision to regulatory guide (RG) 3.39, ``Standard Format and Content of License Applications for Mixed Oxide Fuel Fabrication Facilities.'' This guide endorses the standard format and content for license applications and integrated safety analysis (ISA) summaries described in the current version of NUREG-1718, ``Standard Review Plan for the Review of an Application for a Mixed Oxide (MOX) Fuel Fabrication Facility,'' as a method that the NRC staff finds acceptable for meeting the regulatory requirements of Title 10 of the Code of Federal Regulations (10 CFR) part 70, ``Domestic Licensing of Special Nuclear Material'' for mixed oxide fuel fabrication facilities.

  18. Health Risks and Adverse Reactions to Functional Foods.

    PubMed

    Ameratunga, Rohan; Crooks, Christine; Simmons, Greg; Woon, See-Tarn

    2016-01-01

    Functional foods have become increasingly popular with consumers anxious to mitigate the effects of an unhealthy lifestyle or aging. In spite of attractive health claims, these products do not have legal or regulatory status in most countries and are regulated through their health claims. Regulation of functional foods by health claims does not address health risks and adverse effects of these products. In this essay regulatory aspects of functional foods are reviewed along with adverse effects published in the peer-reviewed literature. We detail why the lack of an internationally accepted definition of functional foods places consumers at risk of adverse outcomes. Our review will assist regulatory agencies, manufacturers and consumer groups to assess the benefits and reduce the risks associated with these products.

  19. What exactly is an exact copy? And why it matters when trying to ban human reproductive cloning in Australia.

    PubMed

    Gogarty, B

    2003-04-01

    This paper examines the current Australian regulatory response to human reproductive cloning. The central consideration is the capacity of the current regulatory regime to effectively deter human cloning efforts. A legislative prohibition on human cloning must be both effective and clear enough to allow researchers to know what practices are acceptable. This paper asks whether the current Australian regime evinces these qualities and suggests that Australia should follow the example set in the UK by the enactment of the Human Reproductive Cloning Act 2001.

  20. 78 FR 73911 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-09

    ... 3120 To Extend the Pilot Program That Eliminated the Position Limits for Options on SPDR S&P 500 ETF... extend the pilot program that eliminated the position limits for options on SPDR S&P 500 ETF (``SPY...- regulatory organizations (``SROs'') have adopted similar rules eliminating position limits on SPY and market...

  1. 78 FR 35335 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Amendment No. 2 to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-12

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Amendment No. 2 to Proposed Rule...\\ notice is hereby given that on June 4, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with... proposed rule changes to implement a clearing relationship in which ICE Clear Europe will clear contracts...

  2. 77 FR 75466 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Designation of a Longer Period...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-20

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Designation of a Longer Period for Commission... October 15, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange...-day time period. \\5\\ 15 U.S.C. 78s(b)(2). The proposed rule change would permit ICE Clear Europe to...

  3. 77 FR 16105 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change To Provide for a T+1 Settlement of the Initial Payment Related to the CDS Contracts Cleared by ICE Clear Europe...\\ and Rule 19b-4 thereunder \\2\\ notice is hereby given that on March 6, 2012, ICE Clear Europe Limited...

  4. 77 FR 27254 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-09

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66911; File No. SR-ICEEU-2012-05] Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change To Amend the ICE Clear Europe Limited CDS Procedures, Finance Procedures, and Rules With Respect to the Calculation and Payment of Interest on Mark-To-Market Margin on...

  5. 75 FR 61366 - Montana Regulatory Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Mining Reclamation and Enforcement, Interior. ACTION: Proposed rule; public comment period and opportunity for public hearing on proposed amendment. SUMMARY: We are announcing receipt of a proposed... that we will follow for the public hearing, if one is requested. DATES: We will accept written comments...

  6. 77 FR 54490 - Alabama Regulatory Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... Mining Reclamation and Enforcement, Interior. ACTION: Proposed rule; public comment period and opportunity for public hearing on proposed amendment. SUMMARY: We, the Office of Surface Mining Reclamation... will follow for the public hearing, if one is requested. DATES: We will accept written comments on this...

  7. 75 FR 29785 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... Guide, DG-1248, ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License..., ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License Examinations, and... or acceptance of a nuclear power plant simulation facility for use in operator and senior operator...

  8. 78 FR 13004 - Wyoming Regulatory Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... Mining Reclamation and Enforcement, Interior. ACTION: Proposed rule; public comment period and opportunity for public hearing on proposed amendment. SUMMARY: We are announcing receipt of a proposed... will follow for the public hearing, if one is requested. DATES: We will accept written comments on this...

  9. 75 FR 15701 - City of Keene, NH; Notice of Application Accepted for Filing and Soliciting Comments, Motions To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-30

    ..., NH 03431; (603) 357-9804; JMacLean@ci.keene.nh.us . i. FERC Contact: Kelly Houff, (202) 502-6393... Hydropower Administration and Compliance, Office of Energy Projects, Federal Energy Regulatory Commission, at...

  10. 77 FR 24196 - Alaska Village Electric Cooperative; Notice of Preliminary Permit Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-23

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No., 13272-003] Alaska Village... access road would extend from powerhouse to the existing community drinking water tank access road. The... Harbor. The transmission line [[Page 24197

  11. BMDExpress Data Viewer: A Visualization Tool to Analyze BMDExpress Datasets(SoTC)

    EPA Science Inventory

    Background: Benchmark Dose (BMD) modelling is a mathematical approach used to determine where a dose-response change begins to take place relative to controls following chemical exposure. BMDs are being increasingly applied in regulatory toxicology to estimate acceptable exposure...

  12. Quantifying uncertainty in read-across assessment – an algorithmic approach - (SOT)

    EPA Science Inventory

    Read-across is a popular data gap filling technique within category and analogue approaches for regulatory purposes. Acceptance of read-across remains an ongoing challenge with several efforts underway for identifying and addressing uncertainties. Here we demonstrate an algorithm...

  13. BMDExpress Data Viewer: A Visualization Tool to Analyze BMDExpress Datasets (STC symposium)

    EPA Science Inventory

    Background: Benchmark Dose (BMD) modelling is a mathematical approach used to determine where a dose-response change begins to take place relative to controls following chemical exposure. BMDs are being increasingly applied in regulatory toxicology to estimate acceptable exposure...

  14. 78 FR 39342 - SHINE Medical Technologies, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 50-608; NRC-2013-0053] SHINE Medical Technologies, Inc... Technologies, Inc., is acceptable for docketing. ADDRESSES: Please refer to Docket ID NRC-2013-0053 when...: [email protected] . SUPPLEMENTARY INFORMATION: On March 26, 2013, SHINE Medical Technologies (SHINE...

  15. 7 CFR 42.143 - Operating Characteristic (OC) curves for on-line sampling and inspection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...=Number of sample units in a subgroup. T=Subgroup tolerance.L=Acceptance limit.S=Starting value. EC02SE91... ng=Number of sample units in a subgroup. T=Subgroup tolerance. L=Acceptance limit. S=Starting value... of sample units in a subgroup. T=Subgroup tolerance. L=Acceptance limit. S=Starting value. EC02SE91...

  16. A Survey of Social-Regulatory Practices in Selected Michigan Community Colleges.

    ERIC Educational Resources Information Center

    Hollander, Martin Elliot

    This study surveyed social-regulatory practices of selected community colleges in Michigan to find out: origin and extent of written social-regulatory policies and the provisions for change; types of rules of conduct; and communication and enforcement of social-regulatory practices and rules. The study was limited to commuter-type publicly…

  17. Initial interlaboratory validation of an analytical method for the determination of lead in canned tuna to be used for monitoring and regulatory purposes.

    PubMed

    Santiago, E C; Bello, F B B

    2003-06-01

    The Association of Official Analytical Chemists (AOAC) Standard Method 972.23 (dry ashing and flame atomic absorption spectrophotometry (FAAS)), applied to the analysis of lead in tuna, was validated in three selected local laboratories to determine the acceptability of the method to both the Codex Alimentarius Commission (Codex) and the European Union (EU) Commission for monitoring lead in canned tuna. Initial validation showed that the standard AOAC method as performed in the three participating laboratories cannot satisfy the Codex/EU proposed criteria for the method detection limit for monitoring lead in fish at the present regulation level of 0.5 mg x kg(-1). Modification of the standard method by chelation/concentration of the digest solution before FAAS analysis showed that the modified method has the potential to meet Codex/EU criteria on sensitivity, accuracy and precision at the specified regulation level.

  18. Decay heat uncertainty quantification of MYRRHA

    NASA Astrophysics Data System (ADS)

    Fiorito, Luca; Buss, Oliver; Hoefer, Axel; Stankovskiy, Alexey; Eynde, Gert Van den

    2017-09-01

    MYRRHA is a lead-bismuth cooled MOX-fueled accelerator driven system (ADS) currently in the design phase at SCK·CEN in Belgium. The correct evaluation of the decay heat and of its uncertainty level is very important for the safety demonstration of the reactor. In the first part of this work we assessed the decay heat released by the MYRRHA core using the ALEPH-2 burnup code. The second part of the study focused on the nuclear data uncertainty and covariance propagation to the MYRRHA decay heat. Radioactive decay data, independent fission yield and cross section uncertainties/covariances were propagated using two nuclear data sampling codes, namely NUDUNA and SANDY. According to the results, 238U cross sections and fission yield data are the largest contributors to the MYRRHA decay heat uncertainty. The calculated uncertainty values are deemed acceptable from the safety point of view as they are well within the available regulatory limits.

  19. Newer antipsychotics and upcoming molecules for schizophrenia.

    PubMed

    George, Melvin; Amrutheshwar, Radhika; Rajkumar, Ravi Philip; Kattimani, Shivanand; Dkhar, Steven Aibor

    2013-08-01

    The management of schizophrenia has seen significant strides over the last few decades, due to the increasing availability of a number of antipsychotics. Yet, the diminished efficacy in relation to the negative and cognitive symptoms of schizophrenia, and the disturbing adverse reactions associated with the current antipsychotics, reflect the need for better molecules targeting unexplored pathways. To review the salient features of the recently approved antipsychotics; namely, iloperidone, asenapine, lurasidone and blonanserin. We discuss the advantages, limitations and place in modern pharmacotherapy of each of these drugs. In addition, we briefly highlight the new targets that are being explored. Promising strategies include modulation of the glutamatergic and GABAergic pathways, as well as cholinergic systems. Although regulatory bodies have approved only a handful of antipsychotics in recent years, the wide spectrum of targets that are being explored could eventually bring out antipsychotics with improved efficacy and acceptability, as well as the potential to revolutionize psychiatric practice.

  20. Aircraft ground damage and the use of predictive models to estimate costs

    NASA Astrophysics Data System (ADS)

    Kromphardt, Benjamin D.

    Aircraft are frequently involved in ground damage incidents, and repair costs are often accepted as part of doing business. The Flight Safety Foundation (FSF) estimates ground damage to cost operators $5-10 billion annually. Incident reports, documents from manufacturers or regulatory agencies, and other resources were examined to better understand the problem of ground damage in aviation. Major contributing factors were explained, and two versions of a computer-based model were developed to project costs and show what is possible. One objective was to determine if the models could match the FSF's estimate. Another objective was to better understand cost savings that could be realized by efforts to further mitigate the occurrence of ground incidents. Model effectiveness was limited by access to official data, and assumptions were used if data was not available. However, the models were determined to sufficiently estimate the costs of ground incidents.

  1. Possible implications of large scale radiation processing of food

    NASA Astrophysics Data System (ADS)

    Zagórski, Z. P.

    Large scale irradiation has been discussed in terms of the participation of processing cost in the final value of the improved product. Another factor has been taken into account and that is the saturation of the market with the new product. In the case of succesful projects the participation of irradiation cost is low, and the demand for the better product is covered. A limited availability of sources makes the modest saturation of the market difficult with all food subjected to correct radiation treatment. The implementation of the preservation of food needs a decided selection of these kinds of food which comply to all conditions i.e. of acceptance by regulatory bodies, real improvement of quality and economy. The last condition prefers the possibility of use of electron beams of low energy. The best fullfilment of conditions for succesful processing is observed in the group of dry food, in expensive spices in particular.

  2. Switching between nitrogen and glucose limitation: Unraveling transcriptional dynamics in Escherichia coli.

    PubMed

    Löffler, Michael; Simen, Joana Danica; Müller, Jan; Jäger, Günter; Laghrami, Salaheddine; Schäferhoff, Karin; Freund, Andreas; Takors, Ralf

    2017-09-20

    Transcriptional control under nitrogen and carbon-limitation conditions have been well analyzed for Escherichia coli. However, the transcriptional dynamics that underlie the shift in regulatory programs from nitrogen to carbon limitation is not well studied. In the present study, cells were cultivated at steady state under nitrogen (ammonia)-limited conditions then shifted to carbon (glucose) limitation to monitor changes in transcriptional dynamics. Nitrogen limitation was found to be dominated by sigma 54 (RpoN) and sigma 38 (RpoS), whereas the "housekeeping" sigma factor 70 (RpoD) and sigma 38 regulate cellular status under glucose limitation. During the transition, nitrogen-mediated control was rapidly redeemed and mRNAs that encode active uptake systems, such as ptsG and manXYZ, were quickly amplified. Next, genes encoding facilitators such as lamB were overexpressed, followed by high affinity uptake systems such as mglABC and non-specific porins such as ompF. These regulatory programs are complex and require well-equilibrated and superior control. At the metabolome level, 2-oxoglutarate is the likely component that links carbon- and nitrogen-mediated regulation by interacting with major regulatory elements. In the case of dual glucose and ammonia limitation, sigma 24 (RpoE) appears to play a key role in orchestrating these complex regulatory networks. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 14 CFR 189.3 - Kinds of messages accepted or relayed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... essential to the safety or regulatory of aircraft operation; (ii) Essential to efficient functioning of... refers, containing information required for weight and balance computation and remarks essential to the... aircraft operating agencies or their representatives that directly bear on the efficient and economic...

  4. 18 CFR 351.1 - Financial statements released by carriers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Commission, based on generally accepted accounting principles for which there is authoritative support... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Financial statements... REGULATORY COMMISSION, DEPARTMENT OF ENERGY ACCOUNTS UNDER THE INTERSTATE COMMERCE ACT FINANCIAL STATEMENTS...

  5. 75 FR 13599 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ... Guide, DG-8040, ``Health Physics Surveys During Enriched Uranium-235 Processing and Fuel Fabrication... it deal specifically with the following aspects of an acceptable occupational health physics program that are closely related to surveys: (1) The number and qualification of the health physics staff, (2...

  6. 75 FR 48663 - Combined Notice of Filings #1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 1 August 4.... Applicants: Westar Energy, Inc. Description: Westar Energy, Inc submits amended filing to provide clarity to... Energy LLC. Description: REP Energy LLC submits the amended Petition for Acceptance of Initial Rate...

  7. 75 FR 58444 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... Guide, DG-1244, ``Availability of Electric Power Sources.'' FOR FURTHER INFORMATION CONTACT: Satish..., ``Availability of Electric Power Sources'' temporarily identified by its task number, DG- 1244, which should be... Commission (NRC) considers acceptable when the available electric power sources are less than the number of...

  8. 18 CFR 367.8 - Extraordinary items.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Extraordinary items. 367.8 Section 367.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... are considered generally accepted accounting principles. These items are related to the effects of...

  9. 76 FR 66089 - Access Authorization Program for Nuclear Power Plants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... NUCLEAR REGULATORY COMMISSION [NRC-2011-0245] Access Authorization Program for Nuclear Power... Program for Nuclear Power Plants.'' This guide describes a method that NRC staff considers acceptable to... Regulations (10 CFR), section 73.56, ``Personnel Access Authorization Requirements for Nuclear Power Plants...

  10. 10 CFR 950.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., tests, analyses and acceptance criteria established under the combined license; (2) The conduct of pre... facility the reactor design for which is approved after December 31, 1993, by the Nuclear Regulatory Commission (and such design or a substantially similar design of comparable capacity was not approved on or...

  11. 10 CFR 950.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., tests, analyses and acceptance criteria established under the combined license; (2) The conduct of pre... facility the reactor design for which is approved after December 31, 1993, by the Nuclear Regulatory Commission (and such design or a substantially similar design of comparable capacity was not approved on or...

  12. 10 CFR 950.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., tests, analyses and acceptance criteria established under the combined license; (2) The conduct of pre... facility the reactor design for which is approved after December 31, 1993, by the Nuclear Regulatory Commission (and such design or a substantially similar design of comparable capacity was not approved on or...

  13. 10 CFR 950.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., tests, analyses and acceptance criteria established under the combined license; (2) The conduct of pre... facility the reactor design for which is approved after December 31, 1993, by the Nuclear Regulatory Commission (and such design or a substantially similar design of comparable capacity was not approved on or...

  14. 10 CFR 950.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., tests, analyses and acceptance criteria established under the combined license; (2) The conduct of pre... facility the reactor design for which is approved after December 31, 1993, by the Nuclear Regulatory Commission (and such design or a substantially similar design of comparable capacity was not approved on or...

  15. SOURCE CONTROL BY HYDROLOGICAL ISOLATION: APPLICATION OF THE ANKENY MOAT

    EPA Science Inventory

    Treatment of NAPLs as source areas for plumes of contamination in ground water has proven problematic under certain regulatory programs. Under the EPA risk management paradigm, hydrological isolation of a fuel spill is a valid and acceptable alternative to treatment. A system o...

  16. 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...

  17. 78 FR 58530 - Puget Sound Energy, Inc.;

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2150-111] Puget Sound Energy, Inc.; Notice of Application Accepted for Filing, Soliciting Comments, Motions to Intervene, and... No.: 2150-111 c. Date Filed: August 27, 2013 d. Applicant: Puget Sound Energy, Inc. e. Name of...

  18. Generalized Read-Across (GenRA) prediction using chemical and biological information (BOSC)

    EPA Science Inventory

    Read-across is a popular data gap filling technique within category and analogue approaches for regulatory purposes. Acceptance of read-across remains a challenge with several efforts underway for identifying and addressing uncertainties. To date, these approaches have been quali...

  19. 46 CFR 298.42 - Reporting requirements-financial statements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... independent certified public accountants licensed to practice by the regulatory authority of a State or other political subdivision of the United States or, licensed public accountants licensed to practice by the... statements be in accordance with generally accepted accounting principles, by accountants as described in...

  20. 46 CFR 298.42 - Reporting requirements-financial statements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... independent certified public accountants licensed to practice by the regulatory authority of a State or other political subdivision of the United States or, licensed public accountants licensed to practice by the... statements be in accordance with generally accepted accounting principles, by accountants as described in...

  1. 46 CFR 298.42 - Reporting requirements-financial statements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... independent certified public accountants licensed to practice by the regulatory authority of a State or other political subdivision of the United States or, licensed public accountants licensed to practice by the... statements be in accordance with generally accepted accounting principles, by accountants as described in...

  2. 46 CFR 298.42 - Reporting requirements-financial statements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... independent certified public accountants licensed to practice by the regulatory authority of a State or other political subdivision of the United States or, licensed public accountants licensed to practice by the... statements be in accordance with generally accepted accounting principles, by accountants as described in...

  3. Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues

    PubMed Central

    Kant, Cavit D.; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Yamada, Yohei; Connolly, Sarah E; Marino, Jose; Tocco, Georges; Benichou, Gilles

    2014-01-01

    In this study, we show that aly/aly mice, which are devoid of lymph nodes and Peyer’s patches, rejected acutely fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts were also rejected acutely by splenectomized aly/aly mice (aly/aly-spl−) devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8+ T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected in aly/aly-spl− mice. Actually, aly/aly-spl− mice having spontaneously accepted a heart allotransplant displayed donor-specific tolerance also accepted skin grafts from the same but not a third-party donor via a mechanism involving CD4+ regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs. PMID:25535285

  4. Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance.

    PubMed

    Headen, Devon M; Woodward, Kyle B; Coronel, María M; Shrestha, Pradeep; Weaver, Jessica D; Zhao, Hong; Tan, Min; Hunckler, Michael D; Bowen, William S; Johnson, Christopher T; Shea, Lonnie; Yolcu, Esma S; García, Andrés J; Shirwan, Haval

    2018-06-04

    Islet transplantation is a promising therapy for type 1 diabetes. However, chronic immunosuppression to control rejection of allogeneic islets induces morbidities and impairs islet function. T effector cells are responsible for islet allograft rejection and express Fas death receptors following activation, becoming sensitive to Fas-mediated apoptosis. Here, we report that localized immunomodulation using microgels presenting an apoptotic form of the Fas ligand with streptavidin (SA-FasL) results in prolonged survival of allogeneic islet grafts in diabetic mice. A short course of rapamycin treatment boosted the immunomodulatory efficacy of SA-FasL microgels, resulting in acceptance and function of allografts over 200 days. Survivors generated normal systemic responses to donor antigens, implying immune privilege of the graft, and had increased CD4 + CD25 + FoxP3 + T regulatory cells in the graft and draining lymph nodes. Deletion of T regulatory cells resulted in acute rejection of established islet allografts. This localized immunomodulatory biomaterial-enabled approach may provide an alternative to chronic immunosuppression for clinical islet transplantation.

  5. The Detrimental Effects of Adolescents' Chronic Loneliness on Motivation and Emotion Regulation in Social Situations.

    PubMed

    Vanhalst, Janne; Luyckx, Koen; Van Petegem, Stijn; Soenens, Bart

    2018-01-01

    In adolescence, when establishing and maintaining satisfying social relationships is a key developmental task, chronic loneliness is related to a host of negative outcomes. This study aimed at examining motivational and regulatory factors related to chronic loneliness. Specifically, this study investigated chronically lonely adolescents' responses to hypothetical vignettes of social inclusion and exclusion, thereby focusing on (a) adolescents' willingness and motivation to approach social inclusion and (b) emotion regulation strategies to deal with social exclusion. A total of 730 adolescents (Mage = 15.43 years, 72% female) participated in this four-wave study with annual loneliness assessments and hypothetical vignettes of social inclusion and exclusion at the final wave. After each social inclusion vignette, participants rated their willingness to accept the invitation for social inclusion and five types of motivation to approach the situation. After each social exclusion vignette, participants rated nine cognitive emotion regulation strategies. Compared to individuals following other trajectories, chronically lonely adolescents were less likely to accept invitations for social inclusion and the quality of their motivation for accepting such invitations was lower. Further, they were more likely to employ maladaptive emotion regulation strategies. In sum, this study adds significantly to understanding the motivational and regulatory processes that differentiate chronically lonely adolescents from adolescents following other trajectories.

  6. Genome editing of crops: A renewed opportunity for food security.

    PubMed

    Georges, Fawzy; Ray, Heather

    2017-01-02

    Genome editing of crop plants is a rapidly advancing technology whereby targeted mutations can be introduced into a plant genome in a highly specific manner and with great precision. For the most part, the technology does not incorporate transgenic modifications and is far superior to conventional chemical mutagenesis. In this study we bring into focus some of the underlying differences between the 3 existing technologies: classical plant breeding, genetic modification and genome editing. We discuss some of the main achievements from each area and highlight their common characteristics and individual limitations, while emphasizing the unique capabilities of genome editing. We subsequently examine the possible regulatory mechanisms which governments may be inclined to use in assessing the status of genome edited products. If assessed on the basis of their phenotype rather than the process by which they are obtained, these products will be categorized as equivalent to those produced by classical mutagenesis. This would mean that genome edited products will not be subject to the restrictions imposed on genetically modified products, except in some cases where the mutation involves a large sequence insertion into the genome. We conclude by examining the potential of societal acceptance of genome editing technology, reinforced by a scientific perspective on promoting such acceptance.

  7. Genome editing of crops: A renewed opportunity for food security

    PubMed Central

    Georges, Fawzy

    2017-01-01

    ABSTRACT Genome editing of crop plants is a rapidly advancing technology whereby targeted mutations can be introduced into a plant genome in a highly specific manner and with great precision. For the most part, the technology does not incorporate transgenic modifications and is far superior to conventional chemical mutagenesis. In this study we bring into focus some of the underlying differences between the 3 existing technologies: classical plant breeding, genetic modification and genome editing. We discuss some of the main achievements from each area and highlight their common characteristics and individual limitations, while emphasizing the unique capabilities of genome editing. We subsequently examine the possible regulatory mechanisms which governments may be inclined to use in assessing the status of genome edited products. If assessed on the basis of their phenotype rather than the process by which they are obtained, these products will be categorized as equivalent to those produced by classical mutagenesis. This would mean that genome edited products will not be subject to the restrictions imposed on genetically modified products, except in some cases where the mutation involves a large sequence insertion into the genome. We conclude by examining the potential of societal acceptance of genome editing technology, reinforced by a scientific perspective on promoting such acceptance. PMID:28075688

  8. Management of fear of radiation exposure in carers of outpatients treated with iodine-131.

    PubMed

    Calais, Phillipe J; Page, Andrew C; Turner, J Harvey

    2012-07-01

    To characterise potential fear of radiation exposure in a normal population of individuals who have volunteered to care for a radioactive family member or friend after outpatient radioimmunotherapy (RIT) treatment for cancer, and obtain their knowing and willing acceptance of the risk. Over 750 carers of 300 patients confined to their homes for 1 week following outpatient iodine-131 rituximab RIT of lymphoma were interviewed by a nuclear medicine physicist according to a multi-visit integrated protocol designed to minimise radiation exposure, define risk and gain informed consent. Median radiation exposure of carers was 0.49 mSv (range 0.01-3.7 mSv) which is below the Western Australian regulatory limit of 5 mSv for consenting adult carers of radioactive patients. After signing a declaration of consent, only 2 carers of 750 abrogated their responsibility and none of those who carried out their duties expressed residual concerns at the end of the exit interview with respect to their radiation exposure. Fear of radiation exposure in a normal population may be characterised as a normal emotional response. In the special case of carers of radioactive patients, this fear may be successfully managed by rational, authoritative and empathic explanation to define the risk and gain willing acceptance within the context of domiciliary patient care.

  9. 10 CFR 51.35 - Requirement to publish finding of no significant impact; limitation on Commission action.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Requirement to publish finding of no significant impact; limitation on Commission action. 51.35 Section 51.35 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National...

  10. 10 CFR 72.75 - Reporting requirements for specific events and conditions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... regulatory limits, to prevent exposures to radiation or radioactive materials that could exceed regulatory limits, or to mitigate the consequences of an accident; and (ii) No redundant equipment was available and... waste involved in the event; and (v) Any personnel radiation exposure data. (f) Follow-up notification...

  11. 10 CFR 72.75 - Reporting requirements for specific events and conditions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... regulatory limits, to prevent exposures to radiation or radioactive materials that could exceed regulatory limits, or to mitigate the consequences of an accident; and (ii) No redundant equipment was available and... waste involved in the event; and (v) Any personnel radiation exposure data. (f) Follow-up notification...

  12. 10 CFR 72.75 - Reporting requirements for specific events and conditions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... regulatory limits, to prevent exposures to radiation or radioactive materials that could exceed regulatory limits, or to mitigate the consequences of an accident; and (ii) No redundant equipment was available and... waste involved in the event; and (v) Any personnel radiation exposure data. (f) Follow-up notification...

  13. 10 CFR 72.75 - Reporting requirements for specific events and conditions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... regulatory limits, to prevent exposures to radiation or radioactive materials that could exceed regulatory limits, or to mitigate the consequences of an accident; and (ii) No redundant equipment was available and... waste involved in the event; and (v) Any personnel radiation exposure data. (f) Follow-up notification...

  14. Headquarters summary reports

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The status is summarized of the NASA sponsored involvement in high speed civil transport research and technology, including major cooperative efforts. That involvement is currently focussed on the High Speed Research Program. The program goals are an acceptable level of ozone depletion or sonic boom, the definition of which is a regulatory and political process. The HSRP goal is to provide technical bases for acceptability criteria. Community noise is currently regulated, and it seems clear that HSCT aircraft will have to comply with at least the spirit of the current subsonic constraint, FAR 36, Stage 3.

  15. Reference dose (RfD): description and use in health risk assessments

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

    Barnes, D.G.; Dourson, M.

    1988-12-01

    For many years the concept of the acceptable daily intake has served the toxicological and regulatory fields quite well. However, as approaches to assessing the health significance of exposures to noncarcinogenic substances receive greater scrutiny, some difficulties with this traditional approach have become more apparent. Consequently, the concept of the reference dose is introduced in order to avoid use of prejudicial terms (e.g., safety and acceptable), to promote greater consistency in the assessment of noncarcinogenic chemicals, and to maintain the functional separation between risk assessment and risk management.

  16. Regulatory immune cells and functions in autoimmunity and transplantation immunology.

    PubMed

    Papp, Gabor; Boros, Peter; Nakken, Britt; Szodoray, Peter; Zeher, Margit

    2017-05-01

    In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Pharmacogenetics and pharmacogenomics in drug development and regulatory decision making: report of the first FDA-PWG-PhRMA-DruSafe Workshop.

    PubMed

    Lesko, Lawrence J; Salerno, Ronald A; Spear, Brian B; Anderson, Donald C; Anderson, Timothy; Brazell, Celia; Collins, Jerry; Dorner, Andrew; Essayan, David; Gomez-Mancilla, Baltazar; Hackett, Joseph; Huang, Shiew-Mei; Ide, Susan; Killinger, Joanne; Leighton, John; Mansfield, Elizabeth; Meyer, Robert; Ryan, Stephen G; Schmith, Virginia; Shaw, Peter; Sistare, Frank; Watson, Mark; Worobec, Alexandra

    2003-04-01

    The use of pharmacogenetics and pharmacogenomics in the drug development process, and in the assessment of such data submitted to regulatory agencies by industry, has generated significant enthusiasm as well as important reservations within the scientific and medical communities. This situation has arisen because of the increasing number of exploratory and confirmatory investigations into variations in RNA expression patterns and DNA sequences being conducted in the preclinical and clinical phases of drug development, and the uncertainty surrounding the acceptance of these data by regulatory agencies. This report summarizes the outcome of a workshop cosponsored by the Food and Drug Administration (FDA), the Pharmacogenetics Working Group (PWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the PhRMA Preclinical Safety Committee (DruSafe). The specific aim of the workshop was to identify key issues associated with the application of pharmacogenetics and pharmacogenomics, including the feasibility of a regulatory "safe harbor" for exploratory genome-based data, and to provide a forum for industry-regulatory agency dialogue on these important issues.

  18. Regulatory Aspects of Sabin Type 2 Withdrawal From Trivalent Oral Poliovirus Vaccine: Process and Lessons Learned.

    PubMed

    Decina, Daniela; Fournier-Caruana, Jacqueline; Takane, Marina; Ostad Ali Dehaghi, Razieh; Sutter, Roland

    2017-07-01

    Withdrawal of type 2 oral poliovirus vaccine (OPV) in OPV-using countries required regulatory approval for use of inactivated poliovirus vaccine and bivalent OPV in routine immunization. Worldwide, a variety of mechanisms were used by member states, with some differences in approach observed between inactivated poliovirus vaccine and bivalent OPV. These included acceptance for use of World Health Organization (WHO) prequalified vaccines, registration and licensure pathways, participation in WHO-convened joint reviews of licensing dossiers, as well as pragmatic application of alternatively available mechanisms, when appropriate. Simple but effective tools were used to monitor progress and to record, authenticate, and share information. Essential to achievement of regulatory targets was ongoing communication with key stakeholders, including switch-country national regulatory authorities, vaccine manufacturers, partner organizations, and relevant units within WHO. Understanding of the regulatory environment gained through the OPV switch can be helpful in supporting further stages of the polio end game and other time-sensitive vaccine introduction programs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  19. 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

  20. 76 FR 18467 - Pennsylvania Regulatory Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-04

    ... Surface Mining Reclamation and Enforcement (OSM), Interior. ACTION: Proposed rule; reopening of the public comment period. SUMMARY: We are reopening the public comment period related to an amendment to the... procedures that we will follow for the public hearing, if one is requested. DATES: We will accept written...

  1. 75 FR 49929 - Music Mountain Hydro, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13760-000] Music Mountain..., Motions To Intervene, and Competing Applications August 9, 2010. On May 18, 2010, Music Mountain Hydro..., proposing to study the feasibility of the Music [[Page 49930

  2. 77 FR 41457 - Aging Management Associated With Wall Thinning Due to Erosion Mechanisms

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0170] Aging Management Associated With Wall Thinning Due... management program (AMP) in NUREG-1801, Revision 2, ``Generic Aging Lessons Learned (GALL) Report,'' and the NRC staff's aging management review procedure and acceptance criteria contained in NUREG-1800...

  3. CHALLENGES IN SLUDGE STABILIZATION: REGULATORY COMPLIANCE IN THE DESIGN AND OPERATION OF FACILITIES

    EPA Science Inventory

    Successful sewage sludge management involving the beneficial use of biosolids is predicated on acceptable quality of the product. Sludge quality can be defined in many ways. One of the most critical qualities affecting product marketability is sludge stability. While the terms &q...

  4. Neural indicators of emotion regulation via acceptance vs reappraisal in remitted major depressive disorder

    PubMed Central

    Keng, Shian-Ling; Ji, Jie Lisa; Moore, Tyler; Minkel, Jared; Dichter, Gabriel S.

    2015-01-01

    Mood disorders are characterized by impaired emotion regulation abilities, reflected in alterations in frontolimbic brain functioning during regulation. However, little is known about differences in brain function when comparing regulatory strategies. Reappraisal and emotional acceptance are effective in downregulating negative affect, and are components of effective depression psychotherapies. Investigating neural mechanisms of reappraisal vs emotional acceptance in remitted major depressive disorder (rMDD) may yield novel mechanistic insights into depression risk and prevention. Thirty-seven individuals (18 rMDD, 19 controls) were assessed during a functional magnetic resonance imaging task requiring reappraisal, emotional acceptance or no explicit regulation while viewing sad images. Lower negative affect was reported following reappraisal than acceptance, and was lower following acceptance than no explicit regulation. In controls, the acceptance > reappraisal contrast revealed greater activation in left insular cortex and right prefrontal gyrus, and less activation in several other prefrontal regions. Compared with controls, the rMDD group had greater paracingulate and right midfrontal gyrus (BA 8) activation during reappraisal relative to acceptance. Compared with reappraisal, acceptance is associated with activation in regions linked to somatic and emotion awareness, although this activation is associated with less reduction in negative affect. Additionally, a history of MDD moderated these effects. PMID:25617820

  5. Development and Single-Laboratory Validation of a Liquid Chromatography Tandem Mass Spectrometry Method for Quantitation of Tetrodotoxin in Mussels and Oysters.

    PubMed

    Turner, Andrew D; Boundy, Michael J; Rapkova, Monika Dhanji

    2017-09-01

    In recent years, evidence has grown for the presence of tetrodotoxin (TTX) in bivalve mollusks, leading to the potential for consumers of contaminated products to be affected by Tetrodotoxin Shellfish Poisoning (TSP). A single-laboratory validation was conducted for the hydrophilic interaction LC (HILIC) tandem MS (MS/MS) analysis of TTX in common mussels and Pacific oysters-the bivalve species that have been found to contain TTXs in the United Kingdom in recent years. The method consists of a single-step dispersive extraction in 1% acetic acid, followed by a carbon SPE cleanup step before dilution and instrumental analysis. The full method was developed as a rapid tool for the quantitation of TTX, as well as for the associated analogs 4-epi-TTX; 5,6,11-trideoxy TTX; 11-nor TTX-6-ol; 5-deoxy TTX; and 4,9-anhydro TTX. The method can also be run as the acquisition of TTX together with paralytic shellfish toxins. Results demonstrated acceptable method performance characteristics for specificity, linearity, recovery, ruggedness, repeatability, matrix variability, and within-laboratory reproducibility for the analysis of TTX. The LOD and LOQ were fit-for-purpose in comparison to the current action limit for TTX enforced in The Netherlands. In addition, aspects of method performance (LOD, LOQ, and within-laboratory reproducibility) were found to be satisfactory for three other TTX analogs (11-nor TTX-6-ol, 5-deoxy TTX, and 4,9-anhydro TTX). The method was found to be practical and suitable for use in regulatory testing, providing rapid turnaround of sample analysis. Plans currently underway on a full collaborative study to validate a HILIC-MS/MS method for paralytic shellfish poisoning toxins will be extended to include TTX in order to generate international acceptance, ultimately for use as an alternative official control testing method should regulatory controls be adopted.

  6. What exactly is an exact copy? And why it matters when trying to ban human reproductive cloning in Australia

    PubMed Central

    Gogarty, B

    2003-01-01

    This paper examines the current Australian regulatory response to human reproductive cloning. The central consideration is the capacity of the current regulatory regime to effectively deter human cloning efforts. A legislative prohibition on human cloning must be both effective and clear enough to allow researchers to know what practices are acceptable. This paper asks whether the current Australian regime evinces these qualities and suggests that Australia should follow the example set in the UK by the enactment of the Human Reproductive Cloning Act 2001. PMID:12672887

  7. 76 FR 71007 - Shetek Wind Inc., Jeffers South, LLC and Allco Renewable Energy Limited, Midwest Independent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL11-53-000] Shetek Wind Inc., Jeffers South, LLC and Allco Renewable Energy Limited, Midwest Independent Transmission System Operator... an original and 14 copies of the protest or intervention to the Federal Energy Regulatory Commission...

  8. 21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  9. 21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  10. 76 FR 12101 - Jordan Hydroelectric Limited Partnership; Notice of Environmental Assessment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-04

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [ Project No. 12737-002] Jordan Hydroelectric Limited Partnership; Notice of Environmental Assessment In accordance with the National Environmental Policy Act of 1969 and the Federal Energy Regulatory Commission's regulations, 18 CFR part 380 (Order No. 486, 52 FR 447897), the Office of...

  11. 78 FR 73912 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-09

    ... Rule Change To Extend the Pilot Program That Eliminated the Position and Exercise Limits for Options on... amend its rules to extend the pilot program that eliminated position and exercise limits for physically..., because not all self- regulatory organizations (``SROs'') have adopted similar rules eliminating position...

  12. 21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  13. 21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  14. 21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  15. 21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  16. 21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  17. 21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  18. Why are investors not interested in my radiotracer? The industrial and regulatory constraints in the development of radiopharmaceuticals.

    PubMed

    Zimmermann, Richard G

    2013-02-01

    Four criteria are essential in the acceptance by investors of new radiopharmaceuticals: the existence of a market and a medical need, the quality of the science and technology behind the new molecule, the feasibility and compliance with regulations and the limited competitive landscape. Potential investors need to get more convincing market evidence, largely beyond the nice preclinical data generated to the point of first discussion. A properly protected compound not jeopardized by earlier published results is a must. A guarantee of an easy and secured source of the ligand is obvious. A safe access to the radionuclide in volumes corresponding to the targeted market is rarely taken into account, but of utmost importance. The evaluation of new drugs by investors will include the evaluation of the real market size for the targeted indication and the position of the drug in the healthcare environment at the time to market. This includes the potential competition with other radiopharmaceuticals, but also with conventional drugs or competitive modalities also at time to market. Both criteria are usually not easily accessible to researchers whose acquaintance remains limited to the scientific and technical part. Starting from this set of information, a first business plan can be deduced based on a best estimate for price per dose and a rough evaluation about the chance and level of reimbursement. In the following most of the events are covered that could jeopardize the development of the drug, focusing on the industrial, economic and regulatory aspects, comprehending the detailed analysis of the currently best available radionuclides. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Intrinsic limits to gene regulation by global crosstalk

    NASA Astrophysics Data System (ADS)

    Friedlander, Tamar; Prizak, Roshan; Guet, Calin; Barton, Nicholas H.; Tkacik, Gasper

    Gene activity is mediated by the specificity of binding interactions between special proteins, called transcription factors, and short regulatory sequences on the DNA, where different protein species preferentially bind different DNA targets. Limited interaction specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to spurious interactions or remains erroneously inactive. Since each protein can potentially interact with numerous DNA targets, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyze the effects of global crosstalk on gene regulation, using statistical mechanics. We find that crosstalk in regulatory interactions puts fundamental limits on the reliability of gene regulation that are not easily mitigated by tuning proteins concentrations or by complex regulatory schemes proposed in the literature. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant agreement Nr. 291734 (T.F.) and ERC Grant Nr. 250152 (N.B.).

  20. The Benefits and Limitations of Hydraulic Modeling for Ordinary High Water Mark Delineation

    DTIC Science & Technology

    2016-02-01

    ER D C/ CR RE L TR -1 6- 1 Wetland Regulatory Assistance Program (WRAP) The Benefits and Limitations of Hydraulic Modeling for Ordinary...client/default. Wetland Regulatory Assistance Program (WRAP) ERDC/CRREL TR-16-1 February 2016 The Benefits and Limitations of Hydraulic Modeling...Approved for public release; distribution is unlimited. Prepared for Headquarters, U.S. Army Corps of Engineers Washington, DC 20314-1000 Under Wetlands

  1. 77 FR 54491 - Utah Regulatory Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... Reclamation and Enforcement, Interior. ACTION: Proposed rule; public comment period and opportunity for public... on the amendment, and the procedures that we will follow for the public hearing, if one is requested... requested, we will hold a public hearing on the amendment on October 1, 2012. We will accept requests to...

  2. 77 FR 58194 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ....S. Generally Accepted Accounting Principles. Canadian clearing members that use Form 1 report the... Organizations; The Options Clearing Corporation; Notice of Filing of Proposed Rule Change Relating to Financial... technical ``housekeeping'' changes to OCC's By-Laws and Rules relating to financial reporting by Canadian...

  3. 78 FR 934 - Duke Energy Carolinas, LLC; Notice of Application Accepted For Filing, Soliciting Comments...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    .... Description of Request: As required by article 408 of the license, Duke Energy Carolinas, LLC requests... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2698-059] Duke Energy.... Date Filed: June 29, 2012. d. Applicant: Duke Energy Carolinas, LLC. [[Page 935

  4. 78 FR 21921 - Duke Energy Carolinas, LLC; Notice of Application Accepted for Filing and Soliciting Comments...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2603-024] Duke Energy...: Duke Energy Carolinas, LLC. e. Name of Project: Franklin Hydroelectric Project. f. Location: The... Contact: Dennis Whitaker, Duke Energy--Lake Services, 526 S. Church St., Charlotte, NC, 28202, (704) 382...

  5. 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...

  6. Systematically evaluating read-across prediction and performance using a local validity approach characterized by chemical structure and bioactivity information

    EPA Science Inventory

    Read-across is a popular data gap filling technique within category and analogue approaches for regulatory purposes. Acceptance of read-across remains an ongoing challenge with several efforts underway for identifying and addressing uncertainties. Here we demonstrate an algorithm...

  7. Distribution System Residuals – Is “Detectable” Still Acceptable for Chloramines?

    EPA Science Inventory

    Recently, Roberson (2014) noted that one of the distribution system issues currently on the regulatory radar is, “Should disinfectant residual requirements be a specific number as opposed to the current detectable residual?” As our title suggests, we seek to assess what it means...

  8. TECHNICAL CHALLENGES INVOLVED IN IMPLEMENTATION OF VOC REACTIVITY-BASED CONTROL OF OZONE

    EPA Science Inventory

    The control of VOC emissions based on their individual contribution to ozone formation has been the subject of intensive discussion and research in the past five years, and has gained a large degree of acceptance in the air pollution regulatory community for certain industrial op...

  9. 75 FR 27768 - Current Connection, LLC; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-18

    ..., Motions To Intervene, and Competing Applications May 11, 2010. On March 30, 2010, Current Connection, LLC.... Applicant Contact: Timothy D. Smith, CEO, Current Connection, LLC, 1300 Rankin Drive, Troy, MI 48083; phone... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13694-000] Current...

  10. 76 FR 52656 - Rhode Island Department of Environmental Management; Notice of Preliminary Permit Application...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14211-000] Rhode Island Department of Environmental Management; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On June 10, 2011, the Rhode Island Department of Environmental Management...

  11. 76 FR 26282 - Buckeye Power, Inc.; Notice of Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-06

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL11-36-000] Buckeye Power...) (2010), Buckeye Power, Inc. (Buckeye) filed a petition for acceptance or approval of its monthly revenue requirement for its contribution to the supply of Reactive Power and Voltage Control from Generation Sources...

  12. 18 CFR 157.8 - Acceptance for filing or rejection of applications.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., the Director of the Office of Energy Projects or the Director of the Office of Energy Market... Projects or the Director of the Office of Energy Market Regulation may also reject an application after it... ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR...

  13. 18 CFR 157.8 - Acceptance for filing or rejection of applications.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., the Director of the Office of Energy Projects or the Director of the Office of Energy Market... Projects or the Director of the Office of Energy Market Regulation may also reject an application after it... ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR...

  14. 18 CFR 157.8 - Acceptance for filing or rejection of applications.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., the Director of the Office of Energy Projects or the Director of the Office of Energy Market... Projects or the Director of the Office of Energy Market Regulation may also reject an application after it... ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR...

  15. 18 CFR 157.8 - Acceptance for filing or rejection of applications.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., the Director of the Office of Energy Projects or the Director of the Office of Energy Market... Projects or the Director of the Office of Energy Market Regulation may also reject an application after it... ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR...

  16. 78 FR 25135 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-29

    ... burden, to (1) Office of Information and Regulatory Affairs, Office of Management and Budget, Attention.... Upon completion, the information will be used by the Tribe and ITG to develop training needs... transactions for businesses who accept this form of payment. The IRS is launching pilots aimed at determining...

  17. Evaluation of the ToxRTool's ability to rate the reliability of toxicological data for human health hazard assessments

    EPA Science Inventory

    Regulatory agencies often utilize results from peer reviewed publications for hazard assessments.A problem in doing so is the lack of well-accepted tools to objectively, efficiently and systematically assess the quality of published toxicological studies. Herein, we evaluated the...

  18. 77 FR 73056 - Initial Test Programs for Water-Cooled Nuclear Power Plants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-07

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0293] Initial Test Programs for Water-Cooled Nuclear Power... (DG), DG-1259, ``Initial Test Programs for Water-Cooled Nuclear Power Plants.'' This guide describes the general scope and depth that the staff of the NRC considers acceptable for Initial Test Programs...

  19. 78 FR 21000 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-08

    ... adequate accounting system, internal accounting controls, and procedures for safeguarding customer and firm... an adequate accounting system, internal accounting controls, and procedures for safeguarding customer... ability to provide to the Exchange in an acceptable form a complete set of equity system reports...

  20. 76 FR 9339 - Village of Swanton, VT; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14085-000] Village of... To Intervene, and Competing Applications On February 4, 2011, the Village of Swanton, Vermont... be located on the Missisquoi River in the Village of Swanton, Franklin County, Vermont. The sole...

  1. USEPA SITE PROGRAM APPROACH TO TECHNOLOGY TRANSFER AND REGULATORY ACCEPTANCE

    EPA Science Inventory

    The USEPA's SITE program was created to meet the demand for innovative technologies for hazardous waste treatment. The primary mission of the SITe Program is to expedite the cleanup of sites on the NPL. These sites often have multiple contaminants in soil and groundwater, and few...

  2. Proceedings of GLOBAL 2013: International Nuclear Fuel Cycle Conference - Nuclear Energy at a Crossroads

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

    NONE

    2013-07-01

    The Global conference is a forum for the discussion of the scientific, technical, social and regulatory aspects of the nuclear fuel cycle. Relevant topics include global utilization of nuclear energy, current fuel cycle technologies, advanced reactors, advanced fuel cycles, nuclear nonproliferation and public acceptance.

  3. 76 FR 35213 - AJT Mining Properties, Inc.; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14115-000] AJT Mining..., Motions To Intervene, and Competing Applications On March 21, 2011, AJT Mining Properties, Inc., filed an...,000 megawatt-hours. Applicant Contact: Mr. Scott Willis, AJT Mining Properties, Inc., 5601 Tonsgard...

  4. 77 FR 39693 - Natural Currents Energy Services, LLC; Notice of Preliminary Permit Application Accepted for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14395-000] Natural Currents... Comments, Motions To Intervene, and Competing Applications On April 24, 2012, Natural Currents Energy... the feasibility of the Fisher's Island Tidal Energy Project, which would be located on the Long Island...

  5. 76 FR 71968 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-21

    ... thereby be included in regulatory capital. Although the accounting for capital contributions is not... contributions in their FR Y-9C report in accordance with generally accepted accounting principles (GAAP). In.... The accounting for capital contributions in the form of notes receivable is set forth in ASC Subtopic...

  6. 78 FR 10615 - Westfield Water Resources Department; Notice of Application Accepted for Filing and Soliciting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-14

    ... Water Resources Department. e. Name of Project: Sackett Filtration Plant Hydroelectric Project. f.... 791a-825r h. Applicant Contact: Mr. Charles Darling, Water Systems Engineer, Westfield Water Resources... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14483-000] Westfield Water...

  7. 78 FR 22537 - Green Mountain Power Corporation; Notice of Application Accepted for Filing, Soliciting Comments...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-16

    .... b. Project No.: 2558-033. c. Date Filed: March 29, 2013. d. Applicant: Green Mountain Power... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2558-033] Green Mountain... Contact: Mr. Mike Scarzello, Green Mountain Power Corporation, 77 Grove Street, Rutland, VT 05701-3400...

  8. 76 FR 13928 - Amendment to the International Traffic in Arms Regulations: Replacement Parts/Components and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-15

    ... International Traffic in Arms Regulations: Replacement Parts/Components and Incorporated Articles AGENCY... incorporated articles. DATES: The Department of State will accept comments on this proposed rule until April 14... Controls Policy, Attn: Regulatory Changes--Replacement Parts/Components and Incorporated Articles, Bureau...

  9. 77 FR 25163 - Stoughton Water Power Company; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... hydropower turbines and generators having a total combined generating capacity of 192 kilowatts; (4) an... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14335-000] Stoughton Water..., Motions To Intervene, and Competing Applications On December 7, 2011, the Stoughton Water Power Company...

  10. 77 FR 14775 - Stoughton Water Power Company; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ... hydropower turbines and generators having a total combined generating capacity of 192 kilowatts; (4) an... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14335-000] Stoughton Water..., Motions To Intervene, and Competing Applications On December 7, 2011, the Stoughton Water Power Company...

  11. 39 CFR 3050.13 - Additional documentation required in the Postal Service's section 3652 report.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Service's section 3652 report. 3050.13 Section 3050.13 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL PERIODIC REPORTING § 3050.13 Additional documentation required in the Postal Service's section... recent Annual Compliance Determination was issued and the reasons that those changes were accepted. ...

  12. 75 FR 36378 - JD Products, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-25

    ... to study the feasibility of the proposed San Onofre OWEG Electricity Farm Project (project). The proposed project would utilize 11,443 Ocean Wave Electricity Generation (OWEG) units, an experimental... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13679-000] JD Products, LLC...

  13. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.

    PubMed

    Herzog, Thomas J; Armstrong, Deborah K; Brady, Mark F; Coleman, Robert L; Einstein, Mark H; Monk, Bradley J; Mannel, Robert S; Thigpen, J Tate; Umpierre, Sharee A; Villella, Jeannine A; Alvarez, Ronald D

    2014-01-01

    To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken. Copyright © 2013. Published by Elsevier Inc.

  14. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

    PubMed Central

    Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

    2015-01-01

    Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken. PMID:24239753

  15. Regulating smokeless tobacco and processed areca nut in South-East Asia region: The journey so far and the road ahead.

    PubMed

    Kaur, Jagdish; Thamarangsi, Thaksaphon; Rinkoo, Arvind Vashishta

    2017-09-01

    South-East Asia Region (SEAR) has more smokeless tobacco users as compared to smokers. The growing prevalence and cultural acceptance of consumption of flavored areca nut and related products, for example, supari and pan masala in many countries are confounding the scenario. The prevalence of a variety of tobacco products makes regulation a challenge which gets more complicated in view of weak enforcement of regulatory policies aggressive marketing of such products by the tobacco industry. Some countries have attempted to regulate smokeless tobacco and related products by enforcing bans. However, limited evidence base along with lack of technical and regulatory capacities have restricted the SEAR countries to effectively implement product regulation in respect of smokeless tobacco and related products. This paper lays out specific priorities for research and need to enhance regulatory capacity for smokeless tobacco and processed areca nut in the SEAR countries. A systematic and comprehensive search was conducted to identify all original published literature related to regulating smokeless tobacco and processed areca nut. Studies reporting on the same were obtained through searches in relevant academic databases. Relevant World Health Organization (WHO) documents and reports on tobacco products regulation were consulted. Generating the right evidence along with the need to build the capacity of the countries to test the smokeless tobacco and processed areca nut products by establishing testing facilities and providing practical guidelines is of paramount importance. The countries of the SEAR need to prioritize the implementation of Articles 9 and 10 of the WHO Framework Convention on Tobacco Control to strengthen the regulation of smokeless tobacco and processed areca nut products.

  16. Act on the Registration and Evaluation of Chemicals (K-REACH) and replacement, reduction or refinement best practices

    PubMed Central

    2016-01-01

    Objectives Korea’s Act on the Registration and Evaluation of Chemicals (K-REACH) was enacted for the protection of human health and the environment in 2015. Considering that about 2000 new substances are introduced annually across the globe, the extent of animal testing requirement could be overwhelming unless regulators and companies work proactively to institute and enforce global best practices to replace, reduce or refine animal use. In this review, the way to reduce the animal use for K-REACH is discussed. Methods Background of the enforcement of the K-REACH and its details was reviewed along with the papers and regulatory documents regarding the limitation of animal experiments and its alternatives in order to discuss the regulatory adoption of alternative tests. Results Depending on the tonnage of the chemical used, the data required ranges from acute and other short-term studies for a single exposure route to testing via multiple exposure routes and costly, longer-term studies such as a full two-generation reproducibility toxicity. The European Registration, Evaluation, Authorization and Restriction of Chemicals regulation provides for mandatory sharing of vertebrate test data to avoid unnecessary duplication of animal use and test costs, and obligation to revise data requirements and test guidelines “as soon as possible” after relevant, validated replacement, reduction or refinement (3R) methods become available. Furthermore, the Organization for Economic Cooperation and Development actively accepts alternative animal tests and 3R to chemical toxicity tests. Conclusions Alternative tests which are more ethical and efficient than animal experiments should be widely used to assess the toxicity of chemicals for K-REACH registration. The relevant regulatory agencies will have to make efforts to actively adopt and uptake new alternative tests and 3R to K-REACH. PMID:28118702

  17. Protocol proposal for, and evaluation of, consistency in nicotine delivery from the liquid to the aerosol of electronic cigarettes atomizers: regulatory implications.

    PubMed

    Farsalinos, Konstantinos E; Yannovits, Nikoletta; Sarri, Theoni; Voudris, Vassilis; Poulas, Konstantinos

    2016-06-01

    To propose a protocol and evaluate the consistency in nicotine delivery to the aerosol of different types of electronic cigarette (EC) atomizers, as required by regulatory authorities. Three cartomizer and four tank-type atomizer products were tested (three samples per product). The aerosol from three 20-puff sessions from each sample was collected using a smoke machine. Three cartridges from a nicotine inhaler and three tobacco cigarettes were also tested. Analytical laboratory in Greece. Aerosol nicotine levels were measured. Relative standard deviation (RSD, i.e. coefficient of variation) was calculated separately for each cartomizer and replacement atomizer head sample (intrasample RSD) and between different samples (intersample RSD). The percentage difference from the mean, which is used to assess the quality of medicinal nebulizers, was also calculated. The aerosol nicotine levels were 1.01-10.61 mg/20 puffs for ECs, 0.12-0.18 mg/20 puffs for the nicotine inhaler and 1.76-2.20 mg/cigarette for the tobacco cigarettes. The intrasample RSDs were 3.7-12.5% for ECs and 14.3% for the nicotine inhaler and 11.1% for the tobacco cigarettes. The intersample RSDs were higher in cartomizers (range: 6.9-37.8%) compared with tank systems (range: 6.4-9.3%). All tank-type atomizers and one cartomizer were within 75-125% of the mean, as dictated for medicinal nebulizers. Electronic cigarettes that use tank-type atomizers appear to deliver nicotine in more consistent quantities (within the acceptable limits for medicinal nebulizers and similar to the nicotine inhaler) than electronic cigarettes that use cartomizers. The protocol for testing nicotine delivery consistency described in this paper could be used effectively for regulatory purposes. © 2016 Society for the Study of Addiction.

  18. Review of various approaches for assessing public health risks in regulatory decision making: choosing the right approach for the problem.

    PubMed

    Dearfield, Kerry L; Hoelzer, Karin; Kause, Janell R

    2014-08-01

    Stakeholders in the public health risk analysis community can possess differing opinions about what is meant by "conduct a risk assessment." In reality, there is no one-size-fits-all risk assessment that can address all public health issues, problems, and regulatory needs. Although several international and national organizations (e.g., Codex Alimentarius Commission, Office International des Epizooties, Food and Agricultural Organization, World Health Organization, National Research Council, and European Food Safety Authority) have addressed this issue, confusion remains. The type and complexity of a risk assessment must reflect the risk management needs to appropriately inform a regulatory or nonregulatory decision, i.e., a risk assessment is ideally "fit for purpose" and directly applicable to risk management issues of concern. Frequently however, there is a lack of understanding by those not completely familiar with risk assessment regarding the specific utility of different approaches for assessing public health risks. This unfamiliarity can unduly hamper the acceptance of risk assessment results by risk managers and may reduce the usefulness of such results for guiding public health policies, practices, and operations. Differences in interpretation of risk assessment terminology further complicate effective communication among risk assessors, risk managers, and stakeholders. This article provides an overview of the types of risk assessments commonly conducted, with examples primarily from the food and agricultural sectors, and a discussion of the utility and limitations of these specific approaches for assessing public health risks. Clarification of the risk management issues and corresponding risk assessment design needs during the formative stages of the risk analysis process is a key step for ensuring that the most appropriate assessment of risk is developed and used to guide risk management decisions.

  19. Is there a need for a universal benefit-risk assessment framework for medicines? Regulatory and industry perspectives.

    PubMed

    Leong, James; McAuslane, Neil; Walker, Stuart; Salek, Sam

    2013-09-01

    To explore the current status and need for a universal benefit-risk framework for medicines in regulatory agencies and pharmaceutical companies. A questionnaire was developed and sent to 14 mature regulatory agencies and 24 major companies. The data were analysed using descriptive statistics, for a minority of questions preceded by manual grouping of the responses. Overall response rate was 82%, and study participants included key decision makers from agencies and companies. None used a fully quantitative system, most companies preferring a qualitative method. The major reasons for this group not using semi-quantitative or quantitative systems were lack of a universal and scientifically validated framework. The main advantages of a benefit-risk framework were that it provided a systematic standardised approach to decision-making and that it acted as a tool to enhance quality of communication. It was also reported that a framework should be of value to both agencies and companies throughout the life cycle of a product. They believed that it is possible to develop an overarching benefit-risk framework that should involve relevant stakeholders in the development, validation and application of a universal framework. The entire cohort indicated common barriers to implementing a framework were resource limitations, a lack of knowledge and a scientifically validated and acceptable framework. Stakeholders prefer a semi-quantitative, overarching framework that incorporates a toolbox of different methodologies. A coordinating committee of relevant stakeholders should be formed to guide its development and implementation. Through engaging the stakeholders, these outcomes confirm sentiments and need for developing a universal benefit-risk assessment framework. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Arizona. Preliminary background report

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

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.

    1980-01-01

    This report is one of a series of preliminary reports describing the laws and regulatory programs of the United States and each of the 50 states affecting the siting and operation of energy generating facilities likely to be used in Integrated Community Energy Systems (ICES). Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES. This report describes laws and regulatory programs in Arizona. The Arizona state constitution establishes themore » Arizona Corporation Commission to regulate public service corporations. Within the area of its jurisdiction, the Commission has exclusive power and may not be interfered with by the legislature except in one narrow instance as described in the case Corporation Commission v. Pacific Greyhound Lines.« less

  1. The Arabidopsis halophytic relative Thellungiella halophila tolerates nitrogen-limiting conditions by maintaining growth, nitrogen uptake, and assimilation.

    PubMed

    Kant, Surya; Bi, Yong-Mei; Weretilnyk, Elizabeth; Barak, Simon; Rothstein, Steven J

    2008-07-01

    A comprehensive knowledge of mechanisms regulating nitrogen (N) use efficiency is required to reduce excessive input of N fertilizers while maintaining acceptable crop yields under limited N supply. Studying plant species that are naturally adapted to low N conditions could facilitate the identification of novel regulatory genes conferring better N use efficiency. Here, we show that Thellungiella halophila, a halophytic relative of Arabidopsis (Arabidopsis thaliana), grows better than Arabidopsis under moderate (1 mm nitrate) and severe (0.4 mm nitrate) N-limiting conditions. Thellungiella exhibited a lower carbon to N ratio than Arabidopsis under N limitation, which was due to Thellungiella plants possessing higher N content, total amino acids, total soluble protein, and lower starch content compared with Arabidopsis. Furthermore, Thellungiella had higher amounts of several metabolites, such as soluble sugars and organic acids, under N-sufficient conditions (4 mm nitrate). Nitrate reductase activity and NR2 gene expression in Thellungiella displayed less of a reduction in response to N limitation than in Arabidopsis. Thellungiella shoot GS1 expression was more induced by low N than in Arabidopsis, while in roots, Thellungiella GS2 expression was maintained under N limitation but was decreased in Arabidopsis. Up-regulation of NRT2.1 and NRT3.1 expression was higher and repression of NRT1.1 was lower in Thellungiella roots under N-limiting conditions compared with Arabidopsis. Differential transporter gene expression was correlated with higher nitrate influx in Thellungiella at low (15)NO(3)(-) supply. Taken together, our results suggest that Thellungiella is tolerant to N-limited conditions and could act as a model system to unravel the mechanisms for low N tolerance.

  2. The Arabidopsis Halophytic Relative Thellungiella halophila Tolerates Nitrogen-Limiting Conditions by Maintaining Growth, Nitrogen Uptake, and Assimilation1[W][OA

    PubMed Central

    Kant, Surya; Bi, Yong-Mei; Weretilnyk, Elizabeth; Barak, Simon; Rothstein, Steven J.

    2008-01-01

    A comprehensive knowledge of mechanisms regulating nitrogen (N) use efficiency is required to reduce excessive input of N fertilizers while maintaining acceptable crop yields under limited N supply. Studying plant species that are naturally adapted to low N conditions could facilitate the identification of novel regulatory genes conferring better N use efficiency. Here, we show that Thellungiella halophila, a halophytic relative of Arabidopsis (Arabidopsis thaliana), grows better than Arabidopsis under moderate (1 mm nitrate) and severe (0.4 mm nitrate) N-limiting conditions. Thellungiella exhibited a lower carbon to N ratio than Arabidopsis under N limitation, which was due to Thellungiella plants possessing higher N content, total amino acids, total soluble protein, and lower starch content compared with Arabidopsis. Furthermore, Thellungiella had higher amounts of several metabolites, such as soluble sugars and organic acids, under N-sufficient conditions (4 mm nitrate). Nitrate reductase activity and NR2 gene expression in Thellungiella displayed less of a reduction in response to N limitation than in Arabidopsis. Thellungiella shoot GS1 expression was more induced by low N than in Arabidopsis, while in roots, Thellungiella GS2 expression was maintained under N limitation but was decreased in Arabidopsis. Up-regulation of NRT2.1 and NRT3.1 expression was higher and repression of NRT1.1 was lower in Thellungiella roots under N-limiting conditions compared with Arabidopsis. Differential transporter gene expression was correlated with higher nitrate influx in Thellungiella at low 15NO3− supply. Taken together, our results suggest that Thellungiella is tolerant to N-limited conditions and could act as a model system to unravel the mechanisms for low N tolerance. PMID:18467466

  3. Building Synergy between Regulatory and HTA Agencies beyond Processes and Procedures-Can We Effectively Align the Evidentiary Requirements? A Survey of Stakeholder Perceptions.

    PubMed

    Wang, Ting; McAuslane, Neil; Liberti, Lawrence; Leufkens, Hubert; Hövels, Anke

    2018-06-01

    To evaluate the current practice of companies and agencies to assess the changes made in aligning regulatory and health technology assessment (HTA) stakeholders; to identify areas of commonality of evidentiary requirements that could occur; and to identify strategic issues and trends of regulatory and HTA synergy. Two separate questionnaires were developed to assess stakeholders' perceptions on regulatory and HTA alignment, one for pharmaceutical companies and the other for regulatory and HTA agencies. The responses were analyzed using descriptive statistics. Seven regulatory and 8 HTA agencies from Australia, Canada, and Europe and 19 international companies developing innovative medicine responded to the survey. This study provided a snapshot of the current regulatory and HTA landscape. Changes made over the past 5 years were reflected in three main areas: there is an increasing interaction between regulatory and HTA agencies; current conditional regulatory approvals are not always linked with flexible HTA approaches; and companies are more supportive of joint scientific advice. Four types of evidentiary requirements were identified as building blocks for better alignment: acceptable primary end points, inclusion of an active comparator, use of patient-reported outcomes, and choice and use of surrogate end point. The study showed that the gap between regulatory and HTA requirements has narrowed over the past 5 years. All respondents supported synergy between regulatory and HTA stakeholders, and the study provided several recommendations on how to further improve evidentiary alignment including the provision of joint scientific advice, which was rated as a key strategy by both agencies and companies. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  4. Intrinsic limits to gene regulation by global crosstalk

    PubMed Central

    Friedlander, Tamar; Prizak, Roshan; Guet, Călin C.; Barton, Nicholas H.; Tkačik, Gašper

    2016-01-01

    Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. PMID:27489144

  5. 78 FR 9083 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ... FINRA to determine whether Rule 11892 is necessary once the Plan is operational and, if so, whether... in Connection With the Limit Up-Limit Down Plan February 1, 2013. Pursuant to Section 19(b)(1) of the... also proposes to adopt new supplementary material in connection with the upcoming operation of the Plan...

  6. 77 FR 27825 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting Accelerated Approval...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on May 5, 2012, ICE Clear Europe... such as the FSA, CFTC, SEC, Banque de France, Bundesbank, Bundesanstalt f[uuml]r...

  7. 78 FR 13922 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-01

    ... the Regulation NMS Plan to Address Extraordinary Market Volatility. The text of the proposed rule... text of these statements may be examined at the places specified in Item IV below. FINRA has prepared... thereunder.\\6\\ The Limit Up-Limit Down mechanism is intended to address the type of sudden price movements...

  8. 21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a food additive, may be established to define a level of contamination at which a food may be... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  9. 21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a food additive, may be established to define a level of contamination at which a food may be... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

  10. 78 FR 15790 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-12

    ... Security ``(ABS'') (except ABS traded To Be Announced (``TBA'')), in the limited instances when members... Factor in the limited instances when the member effects a transaction in an ABS (except a TBA transaction...-conforming Factor'').\\13\\ As a result of the proposed rule change, when an ABS transaction (except for a TBA...

  11. Attempting to be active: Self-efficacy and barrier limitation differentiate activity levels of working mothers.

    PubMed

    Gierc, Madelaine; Locke, Sean; Jung, Mary; Brawley, Lawrence

    2016-07-01

    Working mothers are less physically active than working women without children and mothers who do not work. The purpose of this study was to examine concurrent self-regulatory efficacy and barriers to physical activity in a sample of working mothers. Women completed a mixed-methods survey which included measures of physical activity, concurrent self-regulatory efficacy, and barriers. Sufficiently active women experienced significantly greater concurrent self-regulatory efficacy and significantly less barrier limitation and frequency. No significant group differences were found for age, domestic duties performed, and children's extracurricular activities. Thematic analysis of barriers revealed six themes of common and unique factors, including limited time and family activities. © The Author(s) 2014.

  12. Impacts of Extraction Methods in the Rapid Determination of Atrazine Residues in Foods using Supercritical Fluid Chromatography and Enzyme-Linked Immunosorbent Assay: Microwave Solvent vs. Supercritical Fluid Extractions

    PubMed Central

    El-Saeid, Mohamed H.; Kanu, Ijeoma; Anyanwu, Ebere C.; Saleh, Mahmoud A.

    2005-01-01

    It is an accepted fact that many food products that we eat today have the possibility of being contaminated by various chemicals used from planting to processing. These chemicals have been shown to cause illnesses for which some concerned government agencies have instituted regulatory mechanisms to minimize the risks and the effects on humans. It is for these concerns that reliable and accurate rapid determination techniques are needed to effect proper regulatory standards for the protection of people's nutritional health. This paper, therefore, reports the comparative evaluation of the extraction methods in the determination of atrazine (commonly used in agricultural as a herbicide) residues in foods using supercritical fluid chromatography (SFC) and enzyme-linked immunosorbent assay (ELISA) techniques. Supercritical fluid extraction (SFE) and microwave solvent extraction (MSE) methods were used to test samples of frozen vegetables, fruit juice, and jam from local food markets in Houston. Results showed a high recovery percentage of atrazine residues using supercritical fluid coupled with ELISA and SFC than with MSE. Comparatively, however, atrazine was detected 90.9 and 54.5% using SFC and ELISA techniques, respectively. ELISA technique was, however, less time consuming, lower in cost, and more sensitive with low detection limit of atrazine residues than SFC technique. PMID:15674445

  13. Bridging the gap between regulatory acceptance and industry use of non-animal methods.

    PubMed

    Clippinger, Amy J; Hill, Erin; Curren, Rodger; Bishop, Patricia

    2016-01-01

    Collaboration between industry and regulators resulted in the development of a decision tree approach using in vitro or ex vivo assays to replace animal tests when determining the eye irritation potential of antimicrobial cleaning products (AMCPs) under the United States Environmental Protection Agency (EPA) Office of Pesticide Programs' hazard classification and labeling system. A policy document issued by the EPA in 2013 and updated in 2015 describes the alternate testing framework that industry could apply to new registrations of AMCPs and, on a case-by-case basis, to conventional pesticide products. Despite the collaborative effort, the availability of relevant non-animal methods, and the EPA's change in policy, only a limited number of AMCPs have been registered using the framework. Companies continue to conduct animal tests when registering AMCPs due to various challenges surrounding adoption of the new testing framework; however, recent discussions between industry, regulators, and other interested parties have identified ways these challenges may be overcome. In this article we explore how use of the alternate framework could be expanded through efforts such as increasing international harmonization, more proactively publicizing the framework, and enhancing the training of regulatory reviewers. Not only can these strategies help to increase use of the EPA alternate eye irritation framework, they can also be applied to facilitate the uptake of other alternative approaches to animal testing in the future.

  14. Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance.

    PubMed

    Bhat, Virunya S; Meek, M E Bette; Valcke, Mathieu; English, Caroline; Boobis, Alan; Brown, Richard

    2017-10-01

    The application of chemical-specific toxicokinetic or toxicodynamic data to address interspecies differences and human variability in the quantification of hazard has potential to reduce uncertainty and better characterize variability compared with the use of traditional default or categorically-based uncertainty factors. The present review summarizes the state-of-the-science since the introduction of the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) guidance on chemical-specific adjustment factors (CSAF) in 2005 and the availability of recent applicable guidance including the WHO/IPCS guidance on physiologically-based pharmacokinetic (PBPK) modeling in 2010 as well as the U.S. EPA guidance on data-derived extrapolation factors in 2014. A summary of lessons learned from an analysis of more than 100 case studies from global regulators or published literature illustrates the utility and evolution of CSAF in regulatory decisions. Challenges in CSAF development related to the adequacy of, or confidence in, the supporting data, including verification or validation of PBPK models. The analysis also identified issues related to adequacy of CSAF documentation, such as inconsistent terminology and often limited and/or inconsistent reporting, of both supporting data and/or risk assessment context. Based on this analysis, recommendations for standardized terminology, documentation and relevant interdisciplinary research and engagement are included to facilitate the continuing evolution of CSAF development and guidance.

  15. Incorporating patient-preference evidence into regulatory decision making.

    PubMed

    Ho, Martin P; Gonzalez, Juan Marcos; Lerner, Herbert P; Neuland, Carolyn Y; Whang, Joyce M; McMurry-Heath, Michelle; Hauber, A Brett; Irony, Telba

    2015-10-01

    Patients have a unique role in deciding what treatments should be available for them and regulatory agencies should take their preferences into account when making treatment approval decisions. This is the first study designed to obtain quantitative patient-preference evidence to inform regulatory approval decisions by the Food and Drug Administration Center for Devices and Radiological Health. Five-hundred and forty United States adults with body mass index (BMI) ≥ 30 kg/m(2) evaluated tradeoffs among effectiveness, safety, and other attributes of weight-loss devices in a scientific survey. Discrete-choice experiments were used to quantify the importance of safety, effectiveness, and other attributes of weight-loss devices to obese respondents. A tool based on these measures is being used to inform benefit-risk assessments for premarket approval of medical devices. Respondent choices yielded preference scores indicating their relative value for attributes of weight-loss devices in this study. We developed a tool to estimate the minimum weight loss acceptable by a patient to receive a device with a given risk profile and the maximum mortality risk tolerable in exchange for a given weight loss. For example, to accept a device with 0.01 % mortality risk, a risk tolerant patient will require about 10 % total body weight loss lasting 5 years. Patient preference evidence was used make regulatory decision making more patient-centered. In addition, we captured the heterogeneity of patient preferences allowing market approval of effective devices for risk tolerant patients. CDRH is using the study tool to define minimum clinical effectiveness to evaluate new weight-loss devices. The methods presented can be applied to a wide variety of medical products. This study supports the ongoing development of a guidance document on incorporating patient preferences into medical-device premarket approval decisions.

  16. Virtual online consultations: advantages and limitations (VOCAL) study.

    PubMed

    Greenhalgh, Trisha; Vijayaraghavan, Shanti; Wherton, Joe; Shaw, Sara; Byrne, Emma; Campbell-Richards, Desirée; Bhattacharya, Satya; Hanson, Philippa; Ramoutar, Seendy; Gutteridge, Charles; Hodkinson, Isabel; Collard, Anna; Morris, Joanne

    2016-01-29

    Remote video consultations between clinician and patient are technically possible and increasingly acceptable. They are being introduced in some settings alongside (and occasionally replacing) face-to-face or telephone consultations. To explore the advantages and limitations of video consultations, we will conduct in-depth qualitative studies of real consultations (microlevel) embedded in an organisational case study (mesolevel), taking account of national context (macrolevel). The study is based in 2 contrasting clinical settings (diabetes and cancer) in a National Health Service (NHS) acute trust in London, UK. Main data sources are: microlevel--audio, video and screen capture to produce rich multimodal data on 45 remote consultations; mesolevel--interviews, ethnographic observations and analysis of documents within the trust; macrolevel--key informant interviews of national-level stakeholders and document analysis. Data will be analysed and synthesised using a sociotechnical framework developed from structuration theory. City Road and Hampstead NHS Research Ethics Committee, 9 December 2014, reference 14/LO/1883. We plan outputs for 5 main audiences: (1) academics: research publications and conference presentations; (2) service providers: standard operating procedures, provisional operational guidance and key safety issues; (3) professional bodies and defence societies: summary of relevant findings to inform guidance to members; (4) policymakers: summary of key findings; (5) patients and carers: 'what to expect in your virtual consultation'. The research literature on video consultations is sparse. Such consultations offer potential advantages to patients (who are spared the cost and inconvenience of travel) and the healthcare system (eg, they may be more cost-effective), but fears have been expressed that they may be clinically risky and/or less acceptable to patients or staff, and they bring significant technical, logistical and regulatory challenges. We anticipate that this study will contribute to a balanced assessment of when, how and in what circumstances this model might be introduced. 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/

  17. 77 FR 21866 - Safety Zone; Sunken Vessel, Puget Sound, Everett, WA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... significant regulatory action due to being limited in size and duration. Small Entities Under the Regulatory... impact on a substantial number of small entities. The term ``small entities'' comprises small businesses... duration. Assistance for Small Entities Under section 213(a) of the Small Business Regulatory Enforcement...

  18. 77 FR 7930 - Improving Government Regulations; Unified Agenda of Federal Regulatory and Deregulatory Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ... the Regulatory Flexibility Act (5 U.S.C. 602), the Department of Defense's printed agenda entries... section 610 of the Regulatory Flexibility Act. Printing of these entries is limited to fields that contain...D Intelligence Interrogations, Detainee Debriefings, and Tactical Questioning. This rule only...

  19. Full-Scale Cask Testing and Public Acceptance of Spent Nuclear Fuel Shipments - 12254

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

    Dilger, Fred; Halstead, Robert J.; Ballard, James D.

    Full-scale physical testing of spent fuel shipping casks has been proposed by the National Academy of Sciences (NAS) 2006 report on spent nuclear fuel transportation, and by the Presidential Blue Ribbon Commission (BRC) on America's Nuclear Future 2011 draft report. The U.S. Nuclear Regulatory Commission (NRC) in 2005 proposed full-scale testing of a rail cask, and considered 'regulatory limits' testing of both rail and truck casks (SRM SECY-05-0051). The recent U.S. Department of Energy (DOE) cancellation of the Yucca Mountain project, NRC evaluation of extended spent fuel storage (possibly beyond 60-120 years) before transportation, nuclear industry adoption of very largemore » dual-purpose canisters for spent fuel storage and transport, and the deliberations of the BRC, will fundamentally change assumptions about the future spent fuel transportation system, and reopen the debate over shipping cask performance in severe accidents and acts of sabotage. This paper examines possible approaches to full-scale testing for enhancing public confidence in risk analyses, perception of risk, and acceptance of spent fuel shipments. The paper reviews the literature on public perception of spent nuclear fuel and nuclear waste transportation risks. We review and summarize opinion surveys sponsored by the State of Nevada over the past two decades, which show consistent patterns of concern among Nevada residents about health and safety impacts, and socioeconomic impacts such as reduced property values along likely transportation routes. We also review and summarize the large body of public opinion survey research on transportation concerns at regional and national levels. The paper reviews three past cask testing programs, the way in which these cask testing program results were portrayed in films and videos, and examines public and official responses to these three programs: the 1970's impact and fire testing of spent fuel truck casks at Sandia National Laboratories, the 1980's regulatory and demonstration testing of MAGNOX fuel flasks in the United Kingdom (the CEGB 'Operation Smash Hit' tests), and the 1980's regulatory drop and fire tests conducted on the TRUPACT II containers used for transuranic waste shipments to the Waste Isolation Pilot Plant in New Mexico. The primary focus of the paper is a detailed evaluation of the cask testing programs proposed by the NRC in its decision implementing staff recommendations based on the Package Performance Study, and by the State of Nevada recommendations based on previous work by Audin, Resnikoff, Dilger, Halstead, and Greiner. The NRC approach is based on demonstration impact testing (locomotive strike) of a large rail cask, either the TAD cask proposed by DOE for spent fuel shipments to Yucca Mountain, or a similar currently licensed dual-purpose cask. The NRC program might also be expanded to include fire testing of a legal-weight truck cask. The Nevada approach calls for a minimum of two tests: regulatory testing (impact, fire, puncture, immersion) of a rail cask, and extra-regulatory fire testing of a legal-weight truck cask, based on the cask performance modeling work by Greiner. The paper concludes with a discussion of key procedural elements - test costs and funding sources, development of testing protocols, selection of testing facilities, and test peer review - and various methods of communicating the test results to a broad range of stakeholder audiences. (authors)« less

  20. Assessment of the benefits and impacts in the U.S. Nuclear Power Industry of hypothesized lower occupational dose limits

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

    Andersen, R.L.; Schmitt, J.F.

    1995-03-01

    The International Commission on Radiological Protection and the National Council on Radiation Protection and Measurements have issued recommendations that would limit occupational exposure of individuals to doses lower than regulatory limits contained in the Nuclear Regulatory Commission`s 10 CFR Part 20, {open_quotes}Standards for Protection Against Radiation{close_quotes}. Because of this situation, there is interest in the potential benefits and impacts that would be associated with movement of the NRC regulatory limits toward the advisory bodies recommendations. The records of occupational worker doses in the U.S. commercial nuclear power industry show that the vast majority of these workers have doses that aremore » significantly below the regulatory limit of 50 mSv (5 rem) per year. Some workers doses do approach the limits, however. This is most common in the case of specially skilled workers, especially those with skills utilized in support of plant outage work. Any consideration of the potential benefits and impacts of hypothesized lower dose limits must address these workers as an important input to the overall assessment. There are also, of course, many other areas in which the benefits and impacts must be evaluated. To prepare to provide valid, constructive input on this matter, the U.S. nuclear power industry is undertaking an assessment, facilitated by the Nuclear Energy Institute (NEI), of the potential benefits and impacts at its facilities associated with hypothesized lower occupational dose limits. Some preliminary results available to date from this assessment are provided.« less

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