Sample records for accelerated approval products

  1. Accelerated approval of oncology products: the food and drug administration experience.

    PubMed

    Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard

    2011-04-20

    We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

  2. Examination of the relationship between oncology drug labeling revision frequency and FDA product categorization.

    PubMed

    Berlin, Robert J

    2009-09-01

    I examined the relationship between the Food and Drug Administration's (FDA's) use of special regulatory designations and the frequency with which labels of oncology drugs are revised to explore how the FDA's designation of products relates to product development and refinement. One hundred oncology drugs, designated by the FDA as accelerated approval, priority review, orphan drug, or traditional review, were identified from publicly available information. Drug information for each product was evaluated to assess the rate at which manufacturers revised product labeling. Rates were compared between specially categorized products and traditional review products (e.g., orphan vs nonorphan drugs) to produce revision rate ratios for each special category. Labeling for accelerated approval and priority review products are revised significantly more frequently than are labels for traditional products. Accelerated approval products are approved based on surrogate endpoints; this approval process anticipates subsequent labeling refinement. Priority review products, however, are approved through a process that is ostensibly as rigorous as traditional review. Their higher than expected label revision rate may suggest deficiencies in the FDA's current priority review evaluation processes.

  3. Accelerated approval of oncology products: a decade of experience.

    PubMed

    Dagher, Ramzi; Johnson, John; Williams, Grant; Keegan, Patricia; Pazdur, Richard

    2004-10-20

    We review the regulatory history of the accelerated approval process and summarize the U.S. Food and Drug Administration experience with accelerated approvals in oncology. The accelerated approval regulations, promulgated in 1992, allow approval of drugs for serious or life-threatening diseases on the basis of a surrogate endpoint that is reasonably likely to predict clinical benefit, such as survival or symptom benefit, pending completion of studies designed to confirm clinical benefit, referred to as phase 4 commitments, which are required to be conducted with due diligence. From 1992 to 2004, 22 applications involving anticancer drugs or biologics were approved. Of these 22 applications, accelerated approval was granted to 15 on the basis of findings from studies without an active comparator (i.e., single-arm studies or studies comparing two dose levels) and to the remaining seven on the basis of one or more randomized studies. Of the 22 approved applications, six (i.e., applications for dexrazoxane, irinotecan, capecitabine, docetaxel, imatinib mesylate, and oxaliplatin) have had one or more indications converted to regular approval. This review reports information that was presented at an Oncologic Drugs Advisory Committee meeting held in March 2003; it also presents a discussion of accelerated approval study designs, the study populations evaluated in the accelerated approval and confirmatory settings, and the integration of accelerated approval into a comprehensive drug development plan.

  4. Review of oncology and hematology drug product approvals at the US Food and Drug Administration between July 2005 and December 2007.

    PubMed

    Sridhara, Rajeshwari; Johnson, John R; Justice, Robert; Keegan, Patricia; Chakravarty, Aloka; Pazdur, Richard

    2010-02-24

    The Office of Oncology Drug Products (OODP) in the Center for Drug Evaluation and Research at the US Food and Drug Administration began reviewing marketing applications for oncological and hematologic indications in July 2005. We conducted an overview of products that were reviewed by the OODP for marketing approval and the regulatory actions taken during July 2005 to December 2007. We identified all applications that were reviewed by the OODP from July 1, 2005, through December 31, 2007, and reviewed the actions that OODP took. We also sought the basis for the actions taken, including the clinical trial design, endpoints used, patient accrual in the trial(s) supporting approval, and the type of regulatory approval. During the study period, the OODP reviewed marketing applications for 60 new indications and took regulatory action on 58 indications. Regulatory action was based on a risk-benefit evaluation of the data submitted with each application. Products that demonstrated efficacy and had an acceptable risk-benefit ratio were granted either regular or accelerated marketing approval for use in the specific indication that was studied. Regular approval was based on endpoints that demonstrated that the drug provided clinical benefit as evidenced by a longer or better life or a favorable effect on an established surrogate for a longer or better life. Accelerated approval was based on a less well-established surrogate endpoint that was reasonably likely to predict a longer or better life. Of the 53 new indications that were approved during the study period, 39 received regular approval, nine received accelerated approval, and five were converted from accelerated to regular approval. Five applications were not approved, and two applications were withdrawn before any regulatory action was taken. Eighteen of the 53 indications that were approved were for new molecular entities. During the study period, regulatory action was taken on 58 of the 60 marketing applications. Fifty-three applications were approved. A variety of clinical trial endpoints were used in the approval trials.

  5. Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014).

    PubMed

    Gnanasakthy, Ari; DeMuro, Carla; Clark, Marci; Haydysch, Emily; Ma, Esprit; Bonthapally, Vijayveer

    2016-06-01

    To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging. © 2016 by American Society of Clinical Oncology.

  6. [Development of guidance for the approval process of brand-new medical products and regenerative medicine products].

    PubMed

    Niimi, Shingo

    2015-01-01

    Ministry of Health, Labour and Weltare has been conducting development of guidance for the approval process of brand-new medical products/development of guidance for medical devices in collaboration with Ministry of Economy, Trade and Industry as part of measures to promote practical use of brand-new medical products since 2005. The objective of this project is to expedite the processes from developmental process of medical devices to approval review and to introduce the medical devices to medical front quickly.. Ministry of Health, Labour and Welfare side has been making guidance for the guide in approval process of brand-new medical products and regeneration medicine products to aim at acceleration and facilitation of development and approval process of innovative medical products. Twenty-two of the guidance have been issued as director of the evaluation and licensing division. The evaluation index about safety and efficacy required for medical devices and regenerative medicine products in progress were put together in these guidance and useful for medical devices developer to understand the point at the approved review. Therefore, I think that the evaluation index could also contribute to the efficient product development. The guidance about implantable artificial heart is issued as the representative example which was useful in the approved review.

  7. FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum‐Containing Chemotherapy

    PubMed Central

    Suzman, Daniel; Maher, V. Ellen; Zhang, Lijun; Tang, Shenghui; Ricks, Tiffany; Palmby, Todd; Fu, Wentao; Liu, Qi; Goldberg, Kirsten B.; Kim, Geoffrey; Pazdur, Richard

    2017-01-01

    Abstract Until recently in the United States, no products were approved for second‐line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum‐containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum‐containing chemotherapy. Atezolizumab is a programmed death‐ligand 1 (PD‐L1) blocking antibody and represents the first approved product directed against PD‐L1. This accelerated approval was based on results of a single‐arm trial in 310 patients with locally advanced or metastatic urothelial carcinoma who had disease progression after prior platinum‐containing chemotherapy. Patients received atezolizumab 1,200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Key efficacy measures were objective response rate (ORR), as assessed by Independent Review per RECIST 1.1, and duration of response (DoR). With a median follow‐up of 14.4 months, confirmed ORR was 14.8% (95% CI: 11.1, 19.3) in all treated patients. Median DoR was not reached and response durations ranged from 2.1+ to 13.8+ months. Of the 46 responders, 37 patients had an ongoing response for ≥ 6 months. The most common adverse reactions (≥20%) were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. Infection and immune‐related adverse events also occurred, including pneumonitis, hepatitis, colitis, endocrine disorders, and rashes. Overall, the benefit‐risk assessment was favorable to support accelerated approval. The observed clinical benefits need to be verified in confirmatory trial(s). Implications for Practice. This accelerated approval of atezolizumab for second‐line use in advanced urothelial carcinoma provides patients with an effective, novel treatment option for the management of their disease. This represents the first immunotherapy approved in this disease setting. PMID:28424325

  8. FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum-Containing Chemotherapy.

    PubMed

    Ning, Yang-Min; Suzman, Daniel; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Ricks, Tiffany; Palmby, Todd; Fu, Wentao; Liu, Qi; Goldberg, Kirsten B; Kim, Geoffrey; Pazdur, Richard

    2017-06-01

    Until recently in the United States, no products were approved for second-line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Atezolizumab is a programmed death-ligand 1 (PD-L1) blocking antibody and represents the first approved product directed against PD-L1. This accelerated approval was based on results of a single-arm trial in 310 patients with locally advanced or metastatic urothelial carcinoma who had disease progression after prior platinum-containing chemotherapy. Patients received atezolizumab 1,200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Key efficacy measures were objective response rate (ORR), as assessed by Independent Review per RECIST 1.1, and duration of response (DoR). With a median follow-up of 14.4 months, confirmed ORR was 14.8% (95% CI: 11.1, 19.3) in all treated patients. Median DoR was not reached and response durations ranged from 2.1+ to 13.8+ months. Of the 46 responders, 37 patients had an ongoing response for ≥ 6 months. The most common adverse reactions (≥20%) were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. Infection and immune-related adverse events also occurred, including pneumonitis, hepatitis, colitis, endocrine disorders, and rashes. Overall, the benefit-risk assessment was favorable to support accelerated approval. The observed clinical benefits need to be verified in confirmatory trial(s). This accelerated approval of atezolizumab for second-line use in advanced urothelial carcinoma provides patients with an effective, novel treatment option for the management of their disease. This represents the first immunotherapy approved in this disease setting. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  9. Timing and Characteristics of Cumulative Evidence Available on Novel Therapeutic Agents Receiving Food and Drug Administration Accelerated Approval.

    PubMed

    Naci, Huseyin; Wouters, Olivier J; Gupta, Radhika; Ioannidis, John P A

    2017-06-01

    Policy Points: Randomized trials-the gold standard of evaluating effectiveness-constitute a small minority of existing evidence on agents given accelerated approval. One-third of randomized trials are in therapeutic areas outside of FDA approval and less than half evaluate the therapeutic benefits of these agents but use them instead as common backbone treatments. Agents receiving accelerated approval are often tested concurrently in several therapeutic areas. For most agents, no substantial time lag is apparent between the average start dates of randomized trials evaluating their effectiveness and those using them as part of background therapies. There appears to be a tendency for therapeutic agents receiving accelerated approval to quickly become an integral component of standard treatment, despite potential shortcomings in their evidence base. Therapeutic agents treating serious conditions are eligible for Food and Drug Administration (FDA) accelerated approval. The clinical evidence accrued on agents receiving accelerated approval has not been systematically evaluated. Our objective was to assess the timing and characteristics of available studies. We first identified clinical studies of novel therapeutic agents receiving accelerated approval. We then (1) categorized those studies as randomized or nonrandomized, (2) explored whether they evaluated the FDA-approved indications, and (3) documented the available treatment comparisons. We also meta-analyzed the difference in start times between randomized studies that (1) did or did not evaluate approved indications and (2) were or were not designed to evaluate the agent's effectiveness. In total, 37 novel therapeutic agents received accelerated approval between 2000 and 2013. Our search of ClinicalTrials.gov identified 7,757 studies, which included 1,258,315 participants. Only one-third of identified studies were randomized controlled trials. Of 1,631 randomized trials with advanced recruitment status, 906 were conducted in therapeutic areas for which agents received initial accelerated approval, 202 were in supplemental indications, and 523 were outside approved indications. Only 411 out of 906 (45.4%) trials were designed to test the effectiveness of agents that received accelerated approval ("evaluation" trials); others used these agents as common background treatment in both arms ("background" trials). There was no detectable lag between average start times of trials conducted within and outside initially approved indications. Evaluation trials started on average 1.52 years (95% CI: 0.87 to 2.17) earlier than background trials. Cumulative evidence on agents with accelerated approvals has major limitations. Most clinical studies including these agents are small and nonrandomized, and about a third are conducted in unapproved areas, typically concurrently with those conducted in approved areas. Most randomized trials including these therapeutic agents are not designed to directly evaluate their clinical benefits but to incorporate them as standard treatment. © 2017 Milbank Memorial Fund.

  10. Priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals?

    PubMed

    Alqahtani, Saad; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Eguale, Tewodros

    2015-07-01

    The US Food and Drug Administration (FDA) priority review process applies to a drug that is considered a significant improvement over the available alternatives. The European Medicines Agency (EMA) accelerated approval applies to a product that is of major public health interest. This study assessed differences in the characteristics of priority review new molecular entities and new therapeutic biologic products approved by the FDA and the EMA. This study includes regulatory information on drug applications, approvals, indications, and orphan designations of all priority review drugs approved by the FDA and the EMA in the period 1999-2011. Descriptive statistics, t-tests, and chi-squared and Wilcoxon tests were performed. Overall, 100 FDA priority review new molecular entities and new therapeutic biologics were approved by both agencies; 87.0% of the products were first approved by the FDA. The average FDA review time (9.2 ± 8.4 months) was significantly lower than the EMA average review time (14.6 ± 4.0 months) (p < 0.0001). The FDA and the EMA granted orphan designation to 43.0% and 33.0%, respectively, of the applications. There were differences in the administration route (1.0% of all products), dosage (8.0%), strength (23%), posology (51.0%), indications (30.0%), restrictions of use (52.0%), limitations of use (19.0%), and outcomes limitations (28.0%) approved by both regulatory agencies. Significant differences exist in the characteristics of the priority review drugs approved by the FDA and the EMA. Harmonization of the US and European regulatory frameworks may facilitate timely approval of pharmaceutical products. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Trial endpoints for drug approval in oncology: Chemoprevention.

    PubMed

    Beitz, J

    2001-04-01

    As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

  12. Sterile products: advances and challenges in formulation, manufacturing and regulatory aspects--a regulatory review perspective.

    PubMed

    Hussong, David

    2010-09-01

    For several decades, the FDA has undertaken many initiatives to improve the quality and safety of sterile drug products. In recent years, efforts have also been undertaken to accelerate the rate for application approval by adding earlier involvement of microbiology reviewers in drug development. Product and manufacturing process development, as well as safe use and product design, are among the elements of enhanced technical involvement. An overview of the product quality microbiology aspects for sterile drugs is provided.

  13. Effects of a Commercial Drink on Acceleration Tolerance and Cognitive Performance

    DTIC Science & Technology

    2009-11-01

    funded by a $120,000 grant from Coca - Cola Company, Atlanta GA. The authors wish to thank Mr. Mac Baker, Capt Julia McGregor, Mr. Tom Beltran, and Mr...recommendation or endorsement of the Coca Cola Company or the product tested. v Approved for public release; distribution unlimited; Approved by 311 th...drink (Full Throttle®, made by the Coca - Cola Company, at volumes equating to a caffeine dose of 5 mg caffeine per kg of body weight), an uncaffeinated

  14. Available Tools to Facilitate Early Patient Access to Medicines in the EU and the USA: Analysis of Conditional Approvals and the Implications for Personalized Medicine.

    PubMed

    Leyens, Lada; Richer, Étienne; Melien, Øyvind; Ballensiefen, Wolfgang; Brand, Angela

    2015-01-01

    Scientific knowledge and our understanding of the human body and diseases have limited any possible treatment tailoring to each patient. The technological advances enabling the integration of various data sets (e.g. '-omics', microbiome, epigenetics and environmental exposure) have facilitated a greater understanding of the human body, the molecular basis of disease and all the factors influencing disease onset, progression and response to treatment, thereby ushering in the era of personalized medicine. We evaluate the regulatory approaches available to facilitate early patient access to efficacious and safe compounds in the EU and the USA in order to make more informed recommendations in the future as to the gaps in regulations for early patient access. An in-depth analysis of conditional approvals (EU) and accelerated approvals (USA) is performed based on the publicly available information (European public assessment reports and a summary review of products approved under both programmes). The types of product, indications, time to approval and type of evidence submitted were analysed. Between 2007 and early 2015, 17 products were conditionally approved in the EU and 25 in the USA, most of them in the area of oncology and based on evidence from phase II clinical trial data. Early approval of promising products based on data from early phases of development is already possible in the EU and the USA. Some of the improvements could entail implementing a rolling assessment of evidence in Europe and extending the scope of early dialogues. © 2015 S. Karger AG, Basel.

  15. 78 FR 38349 - Draft Guidance for Industry on Expedited Programs for Serious Conditions-Drugs and Biologics...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    ... approval, and priority review designation. DATES: Although you can comment on any guidance at any time (see... designation, (3) accelerated approval, and (4) priority review designation. The draft guidance describes... (the FD&C Act) (Enhancement of Accelerated Approval Access to New Medical Treatments) within 1 year of...

  16. Characteristics of Preapproval and Postapproval Studies for Drugs Granted Accelerated Approval by the US Food and Drug Administration

    PubMed Central

    Smalley, Katelyn R.; Kesselheim, Aaron S.

    2017-01-01

    Importance Drugs treating serious or life-threatening conditions can receive US Food and Drug Administration (FDA) accelerated approval based on showing an effect in surrogate measures that are only reasonably likely to predict clinical benefit. Confirmatory trials are then required to determine whether these effects translate to clinical improvements. Objective To characterize preapproval and confirmatory clinical trials of drugs granted accelerated approval. Design and Setting Publicly available FDA documents were reviewed to identify the preapproval trials leading to accelerated approval between 2009 and 2013. Information on the status and findings of required confirmatory studies was extracted from the FDA’s database of postmarketing requirements and commitments, ClinicalTrials.gov, and matched peer-reviewed publications. Follow-up ended on April 7, 2017. Exposures Granting of accelerated approval. Main Outcomes and Measures Characteristics of preapproval and confirmatory studies were compared in terms of study design features (randomization, blinding, comparator, primary end point). Subsequent regulatory decisions and estimated time between accelerated approval and fulfillment of regulatory requirements were summarized. Results The FDA granted accelerated approval to 22 drugs for 24 indications (19 for indications involving cancer treatment) between 2009 and 2013. A total of 30 preapproval studies supported the 24 indications. The median number of participants enrolled in the preapproval studies was 132 (interquartile range, 89-224). Eight studies (27%) included fewer than 100 participants and 20 (67%) included fewer than 200. At a minimum 3 years of follow-up, 19 of 38 (50%) required confirmatory studies were completed, including 18 published reports. Twenty-five of the 38 (66%) examined clinical efficacy, 7 (18%) evaluated longer follow-up, and 6 (16%) focused on safety The proportion of studies with randomized designs did not differ before and after accelerated approval (12/30 [40%] vs 10/18 [56%]; difference, 16%; 95% CI, −15% to 46%; P = .31). Postapproval requirements were completed and demonstrated efficacy in 10 of 24 indications (42%) on the basis of trials that evaluated surrogate measures. Among the 14 of 24 indications (58%) that had not yet completed all requirements, at least 1 of the confirmatory studies failed to demonstrate clinical benefit in 2 (8%), were terminated in 2 (8%), and were delayed by more than 1 year in 3 (13%). Studies were progressing according to target timelines for the remaining 7 indications (29%). Clinical benefit had not yet been confirmed for 8 indications that had been initially approved 5 or more years prior. Conclusions and Relevance Among 22 drugs with 24 indications granted accelerated approval by the FDA in 2009-2013, efficacy was often confirmed in postapproval trials a minimum of 3 years after approval, although confirmatory trials and preapproval trials had similar design elements, including reliance on surrogate measures as outcomes. PMID:28810023

  17. Low-Torque Seal Development

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Borowski, Richard

    2009-01-01

    The EcoTurn Class K production prototypes have passed all AAR qualification tests and received conditional approval. The accelerated life test on the second set of seals is in progress. Due to the performance of the first set, no problems are expected.The seal has demonstrated superior performance over the HDL seal in the test lab with virtually zero torque and excellent contamination exclusion and grease retention.

  18. Using Kokkos for Performant Cross-Platform Acceleration of Liquid Rocket Simulations

    DTIC Science & Technology

    2017-05-08

    NUMBER (Include area code) 08 May 2017 Briefing Charts 05 April 2017 - 08 May 2017 Using Kokkos for Performant Cross-Platform Acceleration of Liquid ...ERC Incorporated RQRC AFRL-West Using Kokkos for Performant Cross-Platform Acceleration of Liquid Rocket Simulations 2DISTRIBUTION A: Approved for... Liquid Rocket Combustion Simulation SPACE simulation of rotating detonation engine (courtesy of Dr. Christopher Lietz) 3DISTRIBUTION A: Approved

  19. Desperately seeking cancer drugs: explaining the emergence and outcomes of accelerated pharmaceutical regulation.

    PubMed

    Davis, Courtney; Abraham, John

    2011-07-01

    Government regulators have increasingly accelerated new cancer drugs on to the market by granting them approval based on less clinical data supporting drug efficacy than permitted under standard regulations. With more lenient regulatory standards, pharmaceutical companies have keenly sought to develop cancer drugs. Focusing on the US, this article examines how the emergence and implementation of such accelerated approvals should be understood, particularly in relation to corporate bias and disease-politics theories. Drawing on longitudinal and case study data analysis, it is argued that the emergence of accelerated approval regulations for cancer drugs should be regarded primarily as part of a deregulatory regime driven by the interests of the pharmaceutical industry in partnership with all major aspects of the state, rather than as a response to patient activism in the aftermath of AIDS. Furthermore, even in cases when some patients successfully demand accelerated marketing approval of cancer drugs, such approval by regulators, while in manufacturers' interests, may not be in the interests of patients' health because the political culture of the regulatory agency is reluctant to uphold its own techno-regulatory standards of public-health protection when that would challenge the agenda-setting influence of manufacturers, including industry collaborations with patients and the medical profession. © 2011 The Authors. Sociology of Health & Illness © 2011 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  20. 78 FR 21996 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69341; File No. SR-NASDAQ-2013-048] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval of a Proposed Rule... in a Limit State or Straddle State, and unlike normal circumstances, may not be a true reflection of...

  1. 77 FR 27529 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Granting Accelerated Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-10

    ... Organizations; ICE Clear Credit LLC; Order Granting Accelerated Approval of Proposed Rule Change to Membership Qualifications May 4, 2012. I. Introduction On April 3, 2012, ICE Clear Credit LLC (``ICC'') filed with the... limitations provided for in ICC Rule 203(b)) require such Clearing Participant to prepay and maintain with ICE...

  2. 75 FR 21688 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval of Proposed Rule... 20, 2010. I. Introduction On March 11, 2010, The NASDAQ Stock Market LLC (``Nasdaq'' or ``Exchange.... Strike prices for ETF options are permitted in $1 or greater intervals where the strike price is $200 or...

  3. 78 FR 21982 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Granting Accelerated Approval of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69343; File No. SR-BX-2013-026] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Granting Accelerated Approval of a Proposed Rule Change To Adopt... not be a true reflection of the value of the series being quoted. In response to these concerns, the...

  4. 78 FR 22001 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Accelerated Approval of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69344; File No. SR-Phlx-2013-29] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Accelerated Approval of a Proposed Rule Change... not be a true reflection of the value of the series being quoted. In response to these concerns, the...

  5. 76 FR 27332 - Proposal To Withdraw Approval for the Breast Cancer Indication for Bevacizumab; Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ...] Proposal To Withdraw Approval for the Breast Cancer Indication for Bevacizumab; Hearing AGENCY: Food and...) proposal to withdraw approval of the breast cancer indication for bevacizumab (Avastin). Genentech is the... accelerated approval of the metastatic [[Page 27333

  6. The potential investment impact of improved access to accelerated approval on the development of treatments for low prevalence rare diseases

    PubMed Central

    2011-01-01

    Background Over 95% of rare diseases lack treatments despite many successful treatment studies in animal models. To improve access to treatments, the Accelerated Approval (AA) regulations were implemented allowing the use of surrogate endpoints to achieve drug approval and accelerate development of life-saving therapies. Many rare diseases have not utilized AA due to the difficulty in gaining acceptance of novel surrogate endpoints in untreated rare diseases. Methods To assess the potential impact of improved AA accessibility, we devised clinical development programs using proposed clinical or surrogate endpoints for fifteen rare disease treatments. Results We demonstrate that better AA access could reduce development costs by approximately 60%, increase investment value, and foster development of three times as many rare disease drugs for the same investment. Conclusion Our research brings attention to the need for well-defined and practical qualification criteria for the use of surrogate endpoints to allow more access to the AA approval pathway in clinical trials for rare diseases. PMID:21733145

  7. Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

    NASA Astrophysics Data System (ADS)

    Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

    2016-10-01

    Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

  8. 42 CFR 412.116 - Method of payment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as hospital bills are... made on an interim basis. (f) Accelerated payments—(1) General rule. Upon request, an accelerated... intermediary beyond its normal billing cycle. (2) Approval of payment. A hospital's request for an accelerated...

  9. 42 CFR 412.116 - Method of payment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as hospital bills are... made on an interim basis. (f) Accelerated payments—(1) General rule. Upon request, an accelerated... intermediary beyond its normal billing cycle. (2) Approval of payment. A hospital's request for an accelerated...

  10. 42 CFR 412.116 - Method of payment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as hospital bills are... made on an interim basis. (f) Accelerated payments—(1) General rule. Upon request, an accelerated... intermediary beyond its normal billing cycle. (2) Approval of payment. A hospital's request for an accelerated...

  11. 42 CFR 412.116 - Method of payment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as hospital bills are... made on an interim basis. (f) Accelerated payments—(1) General rule. Upon request, an accelerated... intermediary beyond its normal billing cycle. (2) Approval of payment. A hospital's request for an accelerated...

  12. Price competition in the Chinese pharmaceutical market.

    PubMed

    Wang, Y Richard

    2006-06-01

    We study price competition between high-quality global products and low-quality local products in a developing country, i.e., China, Nearly all previous studies on pharmaceutical price competition focused on developed countries with bioequivalent generics. In China, local generic products are not bioequivalent and are deemed of lower quality, while global products in the same class are considered similar in quality and better substitutes. We hypothesize that local generic competition drives down local product price but not global product price. In addition, we hypothesize that therapeutic competition among similar global products lowers global product price. Our empirical results support both hypotheses. Number of local generic competitors has a significantly negative effect on local product price but no effect on global product price, while number of global therapeutic competitors has a significantly negative effect on global product price. Policy changes that encourage bioequivalent local products and accelerate global product approvals will enhance price competition in China.

  13. 42 CFR 412.632 - Method of payment under the inpatient rehabilitation facility prospective payment system.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as inpatient rehabilitation...) Accelerated payments—(1) General rule. Upon request, an accelerated payment may be made to an inpatient.... (2) Approval of payment. An inpatient rehabilitation facility's request for an accelerated payment...

  14. 42 CFR 412.632 - Method of payment under the inpatient rehabilitation facility prospective payment system.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as inpatient rehabilitation...) Accelerated payments—(1) General rule. Upon request, an accelerated payment may be made to an inpatient.... (2) Approval of payment. An inpatient rehabilitation facility's request for an accelerated payment...

  15. 42 CFR 412.632 - Method of payment under the inpatient rehabilitation facility prospective payment system.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as inpatient rehabilitation...) Accelerated payments—(1) General rule. Upon request, an accelerated payment may be made to an inpatient.... (2) Approval of payment. An inpatient rehabilitation facility's request for an accelerated payment...

  16. 42 CFR 412.632 - Method of payment under the inpatient rehabilitation facility prospective payment system.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as inpatient rehabilitation...) Accelerated payments—(1) General rule. Upon request, an accelerated payment may be made to an inpatient.... (2) Approval of payment. An inpatient rehabilitation facility's request for an accelerated payment...

  17. A drug's life: the pathway to drug approval.

    PubMed

    Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

    2013-10-01

    In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

  18. Accelerating the domestication of forest trees in a changing world.

    PubMed

    Harfouche, Antoine; Meilan, Richard; Kirst, Matias; Morgante, Michele; Boerjan, Wout; Sabatti, Maurizio; Scarascia Mugnozza, Giuseppe

    2012-02-01

    In light of impending water and arable land shortages, population growth and climate change, it is more important than ever to examine how forest tree domestication can be accelerated to sustainably meet future demands for wood, biomass, paper, fuel and biomaterials. Because of long breeding cycles, tree domestication cannot be rapidly achieved through traditional genetic improvement methods alone. Integrating modern genetic and genomic techniques with conventional breeding will expedite tree domestication. Breeders will only embrace these technologies if they are cost-effective and readily accessible, and forest landowners will only adopt end-products that meet with regulatory approval and public acceptance. All parties involved must work together to achieve these objectives for the benefit of society. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Shielding calculations for industrial 5/7.5MeV electron accelerators using the MCNP Monte Carlo Code

    NASA Astrophysics Data System (ADS)

    Peri, Eyal; Orion, Itzhak

    2017-09-01

    High energy X-rays from accelerators are used to irradiate food ingredients to prevent growth and development of unwanted biological organisms in food, and by that extend the shelf life of the products. The production of X-rays is done by accelerating 5 MeV electrons and bombarding them into a heavy target (high Z). Since 2004, the FDA has approved using 7.5 MeV energy, providing higher production rates with lower treatments costs. In this study we calculated all the essential data needed for a straightforward concrete shielding design of typical food accelerator rooms. The following evaluation is done using the MCNP Monte Carlo code system: (1) Angular dependence (0-180°) of photon dose rate for 5 MeV and 7.5 MeV electron beams bombarding iron, aluminum, gold, tantalum, and tungsten targets. (2) Angular dependence (0-180°) spectral distribution simulations of bremsstrahlung for gold, tantalum, and tungsten bombarded by 5 MeV and 7.5 MeV electron beams. (3) Concrete attenuation calculations in several photon emission angles for the 5 MeV and 7.5 MeV electron beams bombarding a tantalum target. Based on the simulation, we calculated the expected increase in dose rate for facilities intending to increase the energy from 5 MeV to 7.5 MeV, and the concrete width needed to be added in order to keep the existing dose rate unchanged.

  20. Postmarket Safety Outcomes for New Molecular Entity (NME) Drugs Approved by the Food and Drug Administration Between 2002 and 2014.

    PubMed

    Pinnow, Ellen; Amr, Sania; Bentzen, Søren M; Brajovic, Sonja; Hungerford, Laura; St George, Diane Marie; Dal Pan, Gerald

    2017-12-20

    We ascertained a comprehensive list of postmarket safety outcomes, defined as a safety-related market withdrawal or an update to a safety-related section of product label for 278 new molecular entity drugs (NMEs) with a follow-up period of up to 13 years. At least one safety-related update was added to 195 (70.1%) labels of the drugs studied. Updates occurred as early as 160 days after approval and throughout the follow-up period. The period between the second and eighth postapproval year was the most active, with a slight attenuation thereafter. The times to the first safety outcome were significantly shorter for NMEs approved with a fast-track designation (P = 0.02) or under an accelerated approval using a surrogate endpoint (P = 0.03). Our findings underscore the importance of a robust safety surveillance system throughout a drug's lifecycle and for practitioners and patients to remain updated on drug safety profiles. © 2017, The American Society for Clinical Pharmacology and Therapeutics.

  1. Do the EMA accelerated assessment procedure and the FDA priority review ensure a therapeutic added value? 2006-2015: a cohort study.

    PubMed

    Boucaud-Maitre, Denis; Altman, Jean-Jacques

    2016-10-01

    The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have both implemented procedures in order to shorten review time for marketing authorizations with potential therapeutic added value, called priority review and accelerated assessment procedure, respectively. The aim of this study is to compare the new molecular entities (NME) assessed in shorter review time by both agencies and to investigate whether granting a shorter review time status subsequently predicts its therapeutic value attributed by a health technology assessment agency, the French Haute Autorité de Santé (HAS). All NME approved by the EMA and the FDA with a therapeutic added value between 2007 and June 30, 2015 were extracted. We assessed the sensibility, the positive predictive value, and the EMA review time. One hundred seventy-eight NME were approved by the FDA and the EMA and a therapeutic value was available for 160 NME. Eighty-eight (55.0 %) NME were on FDA priority review, 24 (15.0 %) on EMA accelerated procedure and 43 (26.9 %) were considered of high clinical added value. The sensibility was 86.0 % for the FDA and 30.2 % for the EMA. The positive predictive value was, respectively, 42.0 and 54.2 %. Twenty-five NME on FDA priority review and of high therapeutic added value were not on EMA accelerated assessment procedure, leading to a supplementary mean EMA review time of 146 days. The EMA was restrictive to grant a shorten review time status for products with therapeutic interest during the study period.

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

    PubMed

    Uchida, Eriko; Igarashi, Yuka; Sato, Yoji

    2014-01-01

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

  3. Overcoming obstacles to repurposing for neurodegenerative disease

    PubMed Central

    Shineman, Diana W; Alam, John; Anderson, Margaret; Black, Sandra E; Carman, Aaron J; Cummings, Jeffrey L; Dacks, Penny A; Dudley, Joel T; Frail, Donald E; Green, Allan; Lane, Rachel F; Lappin, Debra; Simuni, Tanya; Stefanacci, Richard G; Sherer, Todd; Fillit, Howard M

    2014-01-01

    Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments to patients but is also fraught with significant commercial, regulatory, and reimbursement challenges. The Alzheimer’s Drug Discovery Foundation (ADDF) and the Michael J. Fox Foundation for Parkinson’s Research (MJFF) convened an advisory panel in October 2013 to understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegenerative diseases. Here, we present opportunities on how philanthropy, industry, and government can begin to address these challenges, promote policy changes, and develop targeted funding strategies to accelerate the potential of FDA-approved repurposed drugs. PMID:25356422

  4. Committee approves bill to boost NIH funding.

    PubMed

    2015-08-01

    A U.S. House of Representatives committee approved the 21st Century Cures Act. If passed by Congress, the bill would boost funding for the NIH and FDA and introduce new strategies for accelerating the approval of drugs and devices. ©2015 American Association for Cancer Research.

  5. Treatment of foods with high-energy X rays

    NASA Astrophysics Data System (ADS)

    Cleland, M. R.; Meissner, J.; Herer, A. S.; Beers, E. W.

    2001-07-01

    The treatment of foods with ionizing energy in the form of gamma rays, accelerated electrons, and X rays can produce beneficial effects, such as inhibiting the sprouting in potatoes, onions, and garlic, controlling insects in fruits, vegetables, and grains, inhibiting the growth of fungi, pasteurizing fresh meat, poultry, and seafood, and sterilizing spices and food additives. After many years of research, these processes have been approved by regulatory authorities in many countries and commercial applications have been increasing. High-energy X rays are especially useful for treating large packages of food. The most attractive features are product penetration, absorbed dose uniformity, high utilization efficiency and short processing time. The ability to energize the X-ray source only when needed enhances the safety and convenience of this technique. The availability of high-energy, high-power electron accelerators, which can be used as X-ray generators, makes it feasible to process large quantities of food economically. Several industrial accelerator facilities already have X-ray conversion equipment and several more will soon be built with product conveying systems designed to take advantage of the unique characteristics of high-energy X rays. These concepts will be reviewed briefly in this paper.

  6. Roadmap for the international, accelerator-based neutrino programme

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

    Cao, J.; de Gouvêa, A.; Duchesneau, D.

    In line with its terms of reference the ICFA Neutrino Panel has developed a roadmap for the international, accelerator-based neutrino programme. A "roadmap discussion document" was presented in May 2016 taking into account the peer-group-consultation described in the Panel's initial report. The "roadmap discussion document" was used to solicit feedback from the neutrino community---and more broadly, the particle- and astroparticle-physics communities---and the various stakeholders in the programme. The roadmap, the conclusions and recommendations presented in this document take into account the comments received following the publication of the roadmap discussion document. With its roadmap the Panel documents the approved objectivesmore » and milestones of the experiments that are presently in operation or under construction. Approval, construction and exploitation milestones are presented for experiments that are being considered for approval. The timetable proposed by the proponents is presented for experiments that are not yet being considered formally for approval. Based on this information, the evolution of the precision with which the critical parameters governinger the neutrino are known has been evaluated. Branch or decision points have been identified based on the anticipated evolution in precision. The branch or decision points have in turn been used to identify desirable timelines for the neutrino-nucleus cross section and hadro-production measurements that are required to maximise the integrated scientific output of the programme. The branch points have also been used to identify the timeline for the R&D required to take the programme beyond the horizon of the next generation of experiments. The theory and phenomenology programme, including nuclear theory, required to ensure that maximum benefit is derived from the experimental programme is also discussed.« less

  7. The application of the Accelerated Stability Assessment Program (ASAP) to quality by design (QbD) for drug product stability.

    PubMed

    Waterman, Kenneth Craig

    2011-09-01

    An isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a fixed degradant level, is shown to compensate for the complex, non-single order kinetics of solid drug products. A humidity-corrected Arrhenius equation provides reliable estimates for temperature and relative humidity effects on degradation rates. A statistical protocol is employed to determine best fits for chemical stability data, which in turn allows for accurate estimations of shelf life (with appropriate confidence intervals) at any storage condition including inside packaging (based on the moisture vapor transmission rate of the packaging and moisture sorption isotherms of the internal components). These methodologies provide both faster results and far better predictions of chemical stability limited shelf life (expiry) than previously possible. Precise shelf-life estimations are generally determined using a 2-week, product-specific protocol. Once the model for a product is developed, it can play a critical role in providing the product understanding necessary for a quality by design (QbD) filing for product approval and enable rational control strategies to assure product stability. Moreover, this Accelerated Stability Assessment Program (ASAP) enables the coupling of product attributes (e.g., moisture content, packaging options) to allow for flexibility in how control strategies are implemented to provide a balance of cost, speed, and other factors while maintaining adequate stability.

  8. Results of Accelerated Life Testing of LCLS-II Cavity Tuner Motor

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

    Huque, Naeem; Daly, Edward; Pischalnikov, Yuriy

    An Accelerated Life Test (ALT) of the Phytron stepper motor used in the LCLS-II cavity tuner has been conducted at JLab. Since the motor will reside inside the cryomodule, any failure would lead to a very costly and arduous repair. As such, the motor was tested for the equivalent of 30 lifetimes before being approved for use in the production cryomodules. The 9-cell LCLS-II cavity is simulated by disc springs with an equivalent spring constant. Plots of the motor position vs. tuner position ' measured via an installed linear variable differential transformer (LVDT) ' are used to measure motor motion.more » The titanium spindle was inspected for loss of lubrication. The motor passed the ALT, and is set to be installed in the LCLS-II cryomodules.« less

  9. RESULTS OF ACCELERATED LIFE TESTING OF LCLS-II CAVITY TUNER MOTOR

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

    Huque, Naeem; Daly, Edward F.; Pischalnikov, Yuriy

    An Accelerated Life Test (ALT) of the Phytron stepper motor used in the LCLS-II cavity tuner has been conducted at JLab. Since the motor will reside inside the cryomodule, any failure would lead to a very costly and arduous repair. As such, the motor was tested for the equivalent of 30 lifetimes before being approved for use in the production cryomodules. The 9-cell LCLS-II cavity is simulated by disc springs with an equivalent spring constant. Plots of the motor position vs. tuner position ' measured via an installed linear variable differential transformer (LVDT) ' are used to measure motor motion.more » The titanium spindle was inspected for loss of lubrication. The motor passed the ALT, and is set to be installed in the LCLS-II cryomodules.« less

  10. 77 FR 24724 - Sanofi-aventis, U.S., LLC; Withdrawal of Approval of a New Drug Application for OFORTA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... withdrawing approval of a new drug application (NDA) for OFORTA (fludarabine phosphate) Tablets held by sanofi... (fludarabine phosphate) Tablets on December 18, 2008, under the Agency's accelerated approval regulations, 21..., 2011, FDA requested that sanofi-aventis voluntarily withdraw OFORTA (fludarabine phosphate) Tablets...

  11. Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

    PubMed Central

    Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

    2016-01-01

    Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes. PMID:27767027

  12. FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia.

    PubMed

    de Claro, R Angelo; McGinn, Karen M; Verdun, Nicole; Lee, Shwu-Luan; Chiu, Haw-Jyh; Saber, Haleh; Brower, Margaret E; Chang, C J George; Pfuma, Elimika; Habtemariam, Bahru; Bullock, Julie; Wang, Yun; Nie, Lei; Chen, Xiao-Hong; Lu, Donghao Robert; Al-Hakim, Ali; Kane, Robert C; Kaminskas, Edvardas; Justice, Robert; Farrell, Ann T; Pazdur, Richard

    2015-08-15

    On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea. ©2015 American Association for Cancer Research.

  13. Clinical evaluation of the Novacor totally implantable ventricular assist system. Current status.

    PubMed

    Daniel, M A; Lee, J; LaForge, D H; Chen, H; Billich, J; Miller, P J; Ramasamy, N; Strauss, L R; Jassawalla, J S; Portner, P M

    1991-01-01

    The totally implantable Novacor left ventricular assist system (LVAS) is currently approaching clinical evaluation. In vivo testing and production are underway with National Institutes of Health (NIH) support. Activity over the past year has focused on manufacturing engineering, preproduction quality assurance, and in vivo experiment completion. Subsequent to successful completion of the NIH-sponsored, 2-year preclinical device readiness test (DRT), a number of refinements were identified and approved by the NIH technical/data review board. Most of these were necessitated by obsolescence or unavailability of electronic components and the decision to use only high reliability military (MIL) qualified electronic components and processes. A few additional refinements were identified to increase design margins, all of which were qualified by accelerated testing. The development of production processes, automated test programs, and MIL compliant environmental stress screening procedures was completed. Production of LVAS subsystems, including core electronic components (hybrids, application-specific integrated circuits, and surface mount boards), was initiated. Animal studies are underway. The clinical trial, at Presbyterian-University Hospital of Pittsburgh and St. Louis University Medical Center, awaits completion of in vivo experiments, protocol development, and Food and Drug Administration approval.

  14. 76 FR 70795 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice and Order Granting Accelerated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ...-Regulatory Organizations; New York Stock Exchange LLC; Notice and Order Granting Accelerated Approval to..., New York Stock Exchange LLC (``NYSE'' or ``Exchange'') filed with the Securities and Exchange... 70796

  15. Phytosanitary irradiation of fresh tropical commodities in Hawaii: Generic treatments, commercial adoption, and current issues

    NASA Astrophysics Data System (ADS)

    Follett, Peter A.; Weinert, Eric D.

    2012-08-01

    Hawaii is a pioneer in the use of phytosanitary irradiation. The commercial X-ray irradiation facility, Hawaii Pride LLC, has been shipping papaya and other tropical fruits and vegetables to the United States mainland using irradiation for 11 years. Irradiation is an approved treatment to control quarantine pests in 17 fruits and 7 vegetables for export from Hawaii to the US mainland. Hawaiian purple sweet potato is the highest volume product with annual exports of more than 12 million lbs (5500 t). The advent of generic radiation treatments for tephritid fruit flies (150 Gy) and other insects (400 Gy) will accelerate commodity export approvals and facilitate worldwide adoption. Lowering doses for specific pests and commodities can lower treatment costs and increase capacity owing to shorter treatment times, and will minimize any quality problems. Current impediments to wider adoption include the 1 kGy limit for fresh horticultural products, the labeling requirement, and non-acceptance of phytosanitary irradiation in Japan, the European Union, and elsewhere. Irradiation has potential as a treatment for unregulated imports to prevent new pest incursions.

  16. Radiation Safety System for SPIDER Neutral Beam Accelerator

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

    Sandri, S.; Poggi, C.; Coniglio, A.

    2011-12-13

    SPIDER (Source for Production of Ion of Deuterium Extracted from RF Plasma only) and MITICA (Megavolt ITER Injector Concept Advanced) are the ITER neutral beam injector (NBI) testing facilities of the PRIMA (Padova Research Injector Megavolt Accelerated) Center. Both injectors accelerate negative deuterium ions with a maximum energy of 1 MeV for MITICA and 100 keV for SPIDER with a maximum beam current of 40 A for both experiments. The SPIDER facility is classified in Italy as a particle accelerator. At present, the design of the radiation safety system for the facility has been completed and the relevant reports havemore » been presented to the Italian regulatory authorities. Before SPIDER can operate, approval must be obtained from the Italian Regulatory Authority Board (IRAB) following a detailed licensing process. In the present work, the main project information and criteria for the SPIDER injector source are reported together with the analysis of hypothetical accidental situations and safety issues considerations. Neutron and photon nuclear analysis is presented, along with special shielding solutions designed to meet Italian regulatory dose limits. The contribution of activated corrosion products (ACP) to external exposure of workers has also been assessed. Nuclear analysis indicates that the photon contribution to worker external exposure is negligible, and the neutron dose can be considered by far the main radiation protection issue. Our results confirm that the injector has no important radiological impact on the population living around the facility.« less

  17. 42 CFR 412.632 - Method of payment under the inpatient rehabilitation facility prospective payment system.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and for costs of an approved education program and other costs paid outside the prospective payment... must be approved by the intermediary and us. (3) Amount of payment. The amount of the accelerated...

  18. Advances in the vaccination of the elderly against influenza: role of a high-dose vaccine.

    PubMed

    Sullivan, Seth J; Jacobson, Robert; Poland, Gregory A

    2010-10-01

    On 23 December 2009, the US FDA approved Fluzone® High Dose, a high-dose formulation of the trivalent inactivated influenza vaccine, for prevention of influenza in people 65 years of age and older. As it was approved via an accelerated process designed to allow expeditious availability of safe and effective products with promise to treat or prevent serious or life-threatening diseases, the manufacturer is required to conduct further studies to demonstrate effectiveness. Although these studies are underway, a recently completed randomized, controlled trial demonstrated that this vaccine, containing four-times more hemagglutinin than standard-dose inactivated influenza vaccines, can produce an enhanced immunologic response in subjects of 65 years of age and older, while maintaining a favorable safety profile. This article introduces the vaccine, presents currently available safety and immunogenicity data, discusses current recommendations for use, and proposes what we can expect in the coming years.

  19. Japan-Specific Key Regulatory Aspects for Development of New Biopharmaceutical Drug Products.

    PubMed

    Desai, Kashappa Goud; Obayashi, Hirokazu; Colandene, James D; Nesta, Douglas P

    2018-03-28

    Japan represents the third largest pharmaceutical market in the world. Developing a new biopharmaceutical drug product for the Japanese market is a top business priority for global pharmaceutical companies while aligning with ethical drivers to treat more patients in need. Understanding Japan-specific key regulatory requirements is essential to achieve successful approvals. Understanding the full context of Japan-specific regulatory requirements/expectations is challenging to global pharmaceutical companies due to differences in language and culture. This article summarizes key Japan-specific regulatory aspects/requirements/expectations applicable to new drug development, approval, and postapproval phases. Formulation excipients should meet Japan compendial requirements with respect to the type of excipient, excipient grade, and excipient concentration. Preclinical safety assessments needed to support clinical phases I, II, and III development are summarized. Japanese regulatory authorities have taken appropriate steps to consider foreign clinical data, thereby enabling accelerated drug development and approval in Japan. Other important topics summarized in this article include: Japan new drug application-specific bracketing strategies for critical and noncritical aspects of the manufacturing process, regulatory requirements related to stability studies, release specifications and testing methods, standard processes involved in pre and postapproval inspections, management of postapproval changes, and Japan regulatory authority's consultation services available to global pharmaceutical companies. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Osimertinib: First Global Approval.

    PubMed

    Greig, Sarah L

    2016-02-01

    Osimertinib (Tagrisso(™), AZD9291) is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that is being developed by AstraZeneca for the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib has been designed to target the EGFR T790M mutation that is often present in NSCLC patients with acquired EGFR TKI resistance, while sparing wild-type EGFR. In November 2015, the tablet formulation of osimertinib was granted accelerated approval in the USA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC (as detected by an FDA-approved test) who have progressed on or after EGFR TKI therapy. Osimertinib has also been granted accelerated assessment status for this indication in the EU, and is in phase III development for first- and second-line and adjuvant treatment of advanced EGFR mutation-positive NSCLC in several countries. Phase I trials in patients with advanced solid tumours are also being conducted. This article summarizes the milestones in the development of osimertinib leading to this first approval for NSCLC.

  1. High Frequency, High Gradient Dielectric Wakefield Acceleration Experiments at SLAC and BNL

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

    Rosenzweig, James; /UCLA; Travish, Gil

    Given the recent success of >GV/m dielectric wakefield accelerator (DWA) breakdown experiments at SLAC, and follow-on coherent Cerenkov radiation production at the UCLA Neptune, a UCLA-USC-SLAC collaboration is now implementing a new set of experiments that explore various DWA scenarios. These experiments are motivated by the opportunities presented by the approval of FACET facility at SLAC, as well as unique pulse-train wakefield drivers at BNL. The SLAC experiments permit further exploration of the multi-GeV/m envelope in DWAs, and will entail investigations of novel materials (e.g. CVD diamond) and geometries (Bragg cylindrical structures, slab-symmetric DWAs), and have an over-riding goal ofmore » demonstrating >GeV acceleration in {approx}33 cm DWA tubes. In the nearer term before FACET's commissioning, we are planning measurements at the BNL ATF, in which we drive {approx}50-200 MV/m fields with single pulses or pulse trains. These experiments are of high relevance to enhancing linear collider DWA designs, as they will demonstrate potential for efficient operation with pulse trains.« less

  2. Accelerating regenerative medicine: the Japanese experiment in ethics and regulation.

    PubMed

    Lysaght, Tamra

    2017-09-01

    In 2014, the Japanese National Diet introduced new laws aimed at promoting the clinical translation of stem cells and regenerative medicine. The basic action of these laws is to allow the early introduction of regenerative medicine products into the Japanese market through an accelerated approval process, while providing patients with access to certain types of stem cell and cell-based therapies in the context of private clinical practice. While this framework appears to offer enormous opportunities for the translation of stem cell science, it raises ethical challenges that have not yet been fully explored. This paper critically analyzes this framework with respect to the prioritization of safety over clinical benefit, distributive justice and public trust in science and medicine. It is argued that the framework unfairly burdens patients and strained healthcare systems without any clear benefits, and may undermine the credibility of the regenerative medicine field as it emerges.

  3. 77 FR 3828 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... Organizations; The Options Clearing Corporation; Order Granting Approval of Accelerated Delivery of Supplement to the Options Disclosure Document Reflecting Certain Changes to Disclosure Regarding Relative Performance Options January 19, 2012. On August 15, 2011, The Options Clearing Corporation (``OCC'') submitted...

  4. Neuromuscular Control of Rapid Linear Accelerations in Fish

    DTIC Science & Technology

    2016-06-22

    2014 30-Apr-2015 Approved for Public Release; Distribution Unlimited Final Report: Neuromuscular Control of Rapid Linear Accelerations in Fish The...it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. Tufts University Research... Control of Rapid Linear Accelerations in Fish Report Title In this project, we measured muscle activity, body movements, and flow patterns during linear

  5. 30 CFR 7.8 - Post-approval product audit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Post-approval product audit. 7.8 Section 7.8... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY General § 7.8 Post-approval product audit...-holder may observe any tests conducted during this audit. (c) An approved product shall be subject to...

  6. 75 FR 30451 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-01

    ... May 14, 2010. The ODD currently contains general disclosures on the characteristics and risks of...-linked securities. Accordingly, the ODD disclosure only covers the characteristics and risks of options...; Order Granting Approval of Accelerated Delivery of Supplement to the Options Disclosure Document...

  7. Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010

    PubMed Central

    Downing, Nicholas S.; Shah, Nilay D.; Aminawung, Jenerius A.; Pease, Alison M.; Zeitoun, Jean-David; Krumholz, Harlan M.

    2017-01-01

    Importance Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. Objectives To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Design and Setting Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Exposures Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time. Main Outcomes and Measures A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. Results From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near–regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Conclusions and Relevance Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near–regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle. PMID:28492899

  8. Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010.

    PubMed

    Downing, Nicholas S; Shah, Nilay D; Aminawung, Jenerius A; Pease, Alison M; Zeitoun, Jean-David; Krumholz, Harlan M; Ross, Joseph S

    2017-05-09

    Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near-regulatory deadline approval, and regulatory review time. A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near-regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near-regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.

  9. FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum‐Containing Chemotherapy

    PubMed Central

    Blumenthal, Gideon M.; Yuan, Weishi; He, Kun; Sridhara, Rajeshwari; Subramaniam, Sriram; Zhao, Hong; Liu, Chao; Yu, Jingyu; Goldberg, Kirsten B.; McKee, Amy E.; Keegan, Patricia; Pazdur, Richard

    2017-01-01

    Abstract On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum‐containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi‐cohort trial (KEYNOTE‐012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum‐containing chemotherapy. Patients received either intravenous pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks. ORR was determined by independent review according to Response Evaluation Criteria in Solid Tumors 1.1. ORR was 16% (95% confidence interval 11, 22) with a complete response rate of 5%. DoR ranged from 2.4+ months to 27.7+ months. Twenty‐three of 28 responding patients (82%) had response durations of ≥6 months. Safety was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab. Frequent (≥2%) serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune‐mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit‐risk profile of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE‐040, is ongoing. Implications for Practice. This accelerated approval expands the U.S. Food and Drug Administration‐approved indications for pembrolizumab, providing health care providers with new information regarding pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum‐containing chemotherapy. Pembrolizumab is the first drug to receive approval for treatment of patients with HNSCC since cetuximab was approved for this indication in 2006. PMID:28533473

  10. 75 FR 38187 - Proposed Collection; Comment Request for Regulation Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... the Accelerated Cost Recovery System (Sec. 1.168(i)-1). DATES: Written comments should be received on... . SUPPLEMENTARY INFORMATION: Title: General Asset Accounts under the Accelerated Cost Recovery System. OMB Number... approved collection. Affected Public: Business or other for-profit organizations and Farms. Estimated...

  11. 77 FR 65917 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Accelerated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-31

    ... Organizations; The Options Clearing Corporation; Order Granting Accelerated Approval of Proposed Rule Change To Accommodate Equity Options That Have a Unit of Trading of 10 Shares October 25, 2012. I. Introduction On September 12, 2012, the Options Clearing Corporation (``OCC'') filed with the Securities and Exchange...

  12. 76 FR 19100 - Maria Carmen Palazzo: Debarment Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-06

    ... development or approval, including the process for development or approval, of any drug product or otherwise... development or approval, including the process for development or approval, of any drug product or otherwise... approval, including the process for development or approval, of any drug product and otherwise relating to...

  13. Industry and Government Perspective in Influenza Control

    PubMed Central

    Slater, Eve E.

    2004-01-01

    We have had recent reminders of the threats posed by naturally occurring and bioengineered pandemic respiratory infections. It is estimated that if a pandemic infection were to arise anywhere in the world, such an infection would become widespread within 3 months and would have its maximum effect within 6 months. At present, the fastest that a vaccine effective against a new combination of antigens can be developed, purified, and produced is 9–12 months, not counting time for mass production. The current rate at which the production of influenza vaccines can be accelerated is limited by the fact that production is carried out in eggs. Therefore, there is urgent need for cell-based vaccine technologies. These are under way in several centers, yet attainment of a safe product remains several years away. Furthermore, there is need for public and private investment in manufacturing surge capacity and/or dedicated National Institutes of Health facilities to enable accelerated production. We must support efforts to shorten development time by developing and approving subunit antigens and immunogens that anticipate the most virulent viral mutations. Surveillance sites and their electronic interconnections must be expanded. Another component still lacking is funding for laboratories with high throughput screening and strong informatics capabilities to enable the fingerprinting and cataloguing of all known specimens of influenza and other pathogenic organisms for rapid identification of emerging or bioengineered pathogens. In all these efforts, we look to the federal government and to the biomedical research community in both public and private sectors. PMID:15061626

  14. A fresh perspective on comparing the FDA and the CHMP/EMA: approval of antineoplastic tyrosine kinase inhibitors

    PubMed Central

    Shah, Rashmi R; Roberts, Samantha A; Shah, Devron R

    2013-01-01

    We compared and determined the reasons for any differences in the review and approval times of tyrosine kinase inhibitors (TKIs) by the US Food and Drug Administration (FDA) and the European EMA/CHMP. Applications for these novel cancer drugs were submitted to them within a mean of 31.2 days of each other, providing a fair basis for comparison. The FDA had granted priority review to 12 TKIs but the EMA/CHMP did not grant the equivalent accelerated assessment to any. The FDA granted accelerated approvals to six (38%) and CHMP granted (the equivalent) conditional approvals to four (29%) of these agents. On average, the review and approval times were 205.3 days in the US compared with 409.6 days in the European Union (EU). The active review times, however, were comparable (225.4 days in the EU and 205.3 days in the US). Since oncology drug development lasts about 7 years, the 20 days difference in review times between the two agencies is inconsequential. Clock stops during review and the time required to issue an approval had added the extra 184.2 days to review time in the EU. We suggest possible solutions to expedite the EU review and approval processes. However, post-marketing emergence of adverse efficacy and safety data on gefitinib and lapatinib, respectively, indicate potential risks of expedited approvals. We challenge the widely prevalent myth that early approval translates into early access or beneficial impact on public health. Both the agencies collaborate closely but conduct independent assessments and make decisions based on distinct legislation, procedures, precedents and societal expectations. PMID:23362829

  15. 14 CFR 193.17 - How must design and production approval holders handle information they receive from the FAA...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false How must design and production approval... REGULATIONS PROTECTION OF VOLUNTARILY SUBMITTED INFORMATION § 193.17 How must design and production approval... under § 193.9(a)(2) to the holders of design approvals of production approvals issued by the FAA, the...

  16. FDA and NIST collaboration on standards development activities supporting innovation and translation of regenerative medicine products.

    PubMed

    Arcidiacono, Judith A; Bauer, Steven R; Kaplan, David S; Allocca, Clare M; Sarkar, Sumona; Lin-Gibson, Sheng

    2018-06-01

    The development of standards for the field of regenerative medicine has been noted as a high priority by several road-mapping activities. Additionally, the U.S. Congress recognizes the importance of standards in the 21st Century Cure Act. Standards will help to accelerate and streamline cell and gene therapy product development, ensure the quality and consistency of processes and products, and facilitate their regulatory approval. Although there is general agreement for the need of additional standards for regenerative medicine products, a shared understanding of standards is required for real progress toward the development of standards to advance regenerative medicine. Here, we describe the roles of standards in regenerative medicine as well as the process for standards development and the interactions of different entities in the standards development process. Highlighted are recent coordinated efforts between the U.S. Food and Drug Administration and the National Institute of Standards and Technology to facilitate standards development and foster science that underpins standards development. Published by Elsevier Inc.

  17. 77 FR 22374 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... I. Gross, Director, Edward Pekarek, Assistant Director, and Genavieve Shingle, Student Intern... finds good cause, pursuant to Section 19(b)(2) of the Act \\11\\ for approving the proposed rule change... that good cause exists to approve the proposal, as modified by Amendment No. 1, on an accelerated basis...

  18. 30 CFR 15.10 - Post-approval product audit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Post-approval product audit. 15.10 Section 15... General Provisions § 15.10 Post-approval product audit. (a) Approved explosives and sheathed explosive... observe any tests conducted during this audit. (c) An approved explosive or sheathed explosive unit shall...

  19. Antioxidant therapies for wound healing: a clinical guide to currently commercially available products.

    PubMed

    Fitzmaurice, S D; Sivamani, R K; Isseroff, R R

    2011-01-01

    Many facets of wound healing under redox control require a delicate balance between oxidative stress and antioxidants. While the normal physiology of wound healing depends on low levels of reactive oxygen species and oxidative stress, an overexposure to oxidative stress leads to impaired wound healing. Antioxidants are postulated to help control wound oxidative stress and thereby accelerate wound healing. Many antioxidants are available over the counter or by prescription, but only one, Medihoney®, has been specifically FDA approved for wound healing. Here we review the existing evidence for the use of antioxidants for wound healing, with a review of the pertinent animal and clinical studies. Natural products and naturally derived antioxidants are becoming more popular, and we specifically review the evidence for the use of naturally derived antioxidants in wound healing. Antioxidant therapy for wound healing is promising, but only few animal studies and even fewer clinical studies are available. Because only few products have undergone FDA approval, the consumer is advised to scrutinize them for purity and contaminants prior to use, and this may require direct contact with the companies that sell them. As a field of science, the use of antioxidants for wound healing is in its infancy, and future studies will better elucidate the role of antioxidants in wound healing. Copyright © 2011 S. Karger AG, Basel.

  20. Gore offers to help drug companies pursue research.

    PubMed

    1996-03-08

    A meeting convened between Vice President Al Gore and executives of leading pharmaceutical companies to determine means of accelerating efforts to develop vaccines, therapeutics, and microbicides for people with HIV. Gore explained that the administration will work with pharmaceutical companies to determine the long-term effectiveness of drugs approved by the Food and Drug Administration (FDA), work with international groups to increase investment in vaccine development, help develop new microbicides for women with HIV, and identify promising areas of AIDS research. According to advocates, the Clinton Administration has made great strides in improving and accelerating the FDA's drug approval process. The next goal of the pharmaceutical research agenda should be to include consumer advocates in the decision-making process.

  1. The United States Particle Accelerator School: Educating the Next Generation of Accelerator Scientists and Engineers

    NASA Astrophysics Data System (ADS)

    Barletta, William A.

    2009-03-01

    Only a handful of universities in the US offer any formal training in accelerator science. The United States Particle Accelerator School (USPAS) is National Graduate Educational Program that has developed a highly successful educational paradigm that, over the past twenty-years, has granted more university credit in accelerator/beam science and technology than any university in the world. Sessions are held twice annually, hosted by major US research universities that approve course credit, certify the USPAS faculty, and grant course credit. The USPAS paradigm is readily extensible to other rapidly developing, cross-disciplinary research areas such as high energy density physics.

  2. 6 CFR 25.9 - Procedures for certification of approved products for Homeland Security.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Procedures for certification of approved products for Homeland Security. (a) Application Procedure. An applicant seeking a Certification of anti-terrorism Technology as an Approved Product for Homeland Security... application for renewal must be made using the “Application for Certification of an Approved Product for...

  3. Biomarkers for immunotherapy in bladder cancer: a moving target.

    PubMed

    Aggen, David H; Drake, Charles G

    2017-11-21

    Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U.S. Food and Drug Administration (FDA). The PD-1 antibody nivolumab also demonstrated an overall survival benefit, in this case in comparison to historical controls. Similarly, antibodies targeting PD-L1 including atezolizumab, durvalumab, and avelumab have now received accelerated approval from the FDA as second line treatments for mUC, with durable response lasting more than 1 year in some patients. Some of these agents are approved in the first line setting as well - based on single-arm phase II studies atezolizumab and pembrolizumab received accelerated approval for first-line treatment of cisplatin ineligible patients. Despite these multiple approvals, the development of clinically useful biomarkers to determine the optimal treatment for patients remains somewhat elusive. In this review, we examine key clinical trial results with anti-PD1/PD-L1 antibodies and discuss progress towards developing novel biomarkers beyond PD-L1 expression.

  4. Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study.

    PubMed

    Kesselheim, Aaron S; Wang, Bo; Franklin, Jessica M; Darrow, Jonathan J

    2015-09-23

    To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Cohort study. FDA approved novel therapeutics between 1987 and 2014. Publicly available sources provided each drug's year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA's four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review. Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not. The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P<0.001), and a 2.4% increase in the proportion of drugs associated with at least one such program (odds ratio 1.024, 95% confidence interval 1.006 to 1.043, P=0.009). Driving this trend was an increase in the proportion of approved, non-first in class drugs associated with at least one program for drugs (P=0.03 for interaction). In the past two decades, drugs newly approved by the FDA have been associated with an increasing number of expedited development or review programs. Though expedited programs should be strictly limited to drugs providing noticeable clinical advances, this trend is being driven by drugs that are not first in class and thus potentially less innovative. © Kesselheim et al 2015.

  5. 14 CFR 21.325 - Export airworthiness approvals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Export airworthiness approvals. 21.325... AIRCRAFT CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS Export Airworthiness Approvals § 21.325 Export airworthiness approvals. (a) Kinds of approvals. (1) Export airworthiness approval of Class I products is issued...

  6. Versatile graphene biosensors for enhancing human cell therapy.

    PubMed

    Vlăsceanu, George M; Amărandi, Roxana-Maria; Ioniță, Mariana; Tite, Teddy; Iovu, Horia; Pilan, Luisa; Burns, Jorge S

    2018-05-01

    Technological advances in engineering and cell biology stimulate novel approaches for medical treatment, in particular cell-based therapy. The first cell-based gene therapy against cancer was recently approved by the US Food and Drug Administration. Progress in cancer diagnosis includes a blood test detecting five cancer types. Numerous stem cell phase I/II clinical trials showing safety and efficacy will soon pursue qualifying criteria for advanced therapy medicinal products (ATMP), aspiring to join the first stem-cell therapy approved by the European Medicines Agency. Cell based therapy requires extensive preclinical characterisation of biomarkers indicating mechanisms of action crucial to the desired therapeutic effect. Quantitative analyses monitoring critical functions for the manufacture of optimal cell and tissue-based clinical products include successful potency assays for implementation. The challenge to achieve high quality measurement is increasingly met by progress in biosensor design. We adopt a cell therapy perspective to highlight recent examples of graphene-enhanced biointerfaces for measurement of biomarkers relevant to cancer treatment, diagnosis and tissue regeneration. Graphene based biosensor design problems can thwart their use for health care transformative point of care testing and real-time applications. We discuss concerns to be addressed and emerging solutions for establishing clinical grade biosensors to accelerate human cell therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Accelerating drug development and approval.

    PubMed

    Cole, Patrick

    2010-01-01

    Regulatory agencies are the gateway between the pharma/biotech industry and patients and can serve as stimulators of new drug development. This article highlights several means of doing so implemented thus far, many with already impressive histories, such as orphan drug legislation, and others of a more experimental nature, such as the FDA's priority review voucher program. These initiatives represent different approaches to finding treatments for rare and widespread but neglected diseases, as well as speeding the development process for pharmaceutical and biological agents more generally. Commercial incentives, streamlined regulatory processing, exploratory trial designs, research assistance and cash infusions are all means of promoting drug development being explored in the United States, Europe and beyond. In some cases, such as fast track designation and priority review vouchers, regulatory agencies have turned their own processes into incentives, offering advantageous alternative routes to product approval, like a faster lane on the highway for vehicles carrying multiple passengers. In 2009, regulatory agencies and the governments they represent also had to confront two tremendous challenges: the global recession and the H1N1 influenza virus pandemic. These tests have been met with increased funding in the former case and coordinated efforts to develop, approve and stockpile H1N1 vaccines in the latter.

  8. Configuration Manual Polarized Proton Collider at RHIC

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

    Alekseev, I.; Allgower, C.; Bai, M.

    2006-01-01

    In this report we present our design to accelerate and store polarized protons in RHIC, with the level of polarization, luminosity, and control of systematic errors required by the approved RHIC spin physics program. We provide an overview of the physics to be studied using RHIC with polarized proton beams, and a brief description of the accelerator systems required for the project.

  9. TrackPlot Enhancements: Support for Multiple Animal Tracks and Gyros

    DTIC Science & Technology

    2015-09-30

    visualization and kinematic analysis of marine animal movements derived from archival tag data. Tags are supported that have sensors for pressure, acceleration...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. TrackPlot Enhancements: Support for Multiple Animal ...in combination with accelerometer and magnetometer data. 2) the extraction and frequency analysis of accelerations and rotation in animal

  10. Early Patient Access to Medicines: Health Technology Assessment Bodies Need to Catch Up with New Marketing Authorization Methods.

    PubMed

    Leyens, Lada; Brand, Angela

    National and international medicines agencies have developed innovative methods to expedite promising new medicines to the market and facilitate early patient access. Some of these approval pathways are the conditional approval and the adaptive pathways by the European Medicines Agency (EMA); the Promising Innovative Medicine (PIM) designation and the Early Access to Medicines Scheme (EAMS) by the Medicines and Healthcare Products Regulatory Agency (MHRA), as well as the Fast Track, Breakthrough or Accelerated Approval methods by the Food and Drug Administration (FDA). However, at least in Europe, these methods cannot achieve the goal of improving timely access for patients to new medicines on their own; the reimbursement process also has to become adaptive and flexible. In the past 2 years, the effective access (national patient access) to newly approved oncology drugs ranged from 1 to 30 months, with an extremely high variability between European countries. The goal of early patient access in Europe can only be achieved if the national health technology assessment bodies, such as NICE (ENG), HAS (FR), G-BA (DE) or AIFA (IT), provide harmonized, transparent, flexible, conditional and adaptive methods that adopt the level of evidence accepted by the medicines agencies. The efforts from medicines agencies are welcome but will be in vain if health technology assessments do not follow with similar initiatives, and the European 'postcode' lottery will continue. © 2016 S. Karger AG, Basel.

  11. Landscape of Innovation for Cardiovascular Pharmaceuticals: From Basic Science to New Molecular Entities.

    PubMed

    Beierlein, Jennifer M; McNamee, Laura M; Walsh, Michael J; Kaitin, Kenneth I; DiMasi, Joseph A; Ledley, Fred D

    2017-07-01

    This study examines the complete timelines of translational science for new cardiovascular therapeutics from the initiation of basic research leading to identification of new drug targets through clinical development and US Food and Drug Administration (FDA) approval of new molecular entities (NMEs) based on this research. This work extends previous studies by examining the association between the growth of research on drug targets and approval of NMEs associated with these targets. Drawing on research on innovation in other technology sectors, where technological maturity is an important determinant in the success or failure of new product development, an analytical model was used to characterize the growth of research related to the known targets for all 168 approved cardiovascular therapeutics. Categorizing and mapping the technological maturity of cardiovascular therapeutics reveal that (1) there has been a distinct transition from phenotypic to targeted methods for drug discovery, (2) the durations of clinical and regulatory processes were significantly influenced by changes in FDA practice, and (3) the longest phase of the translational process was the time required for technology to advance from initiation of research to a statistically defined established point of technology maturation (mean, 30.8 years). This work reveals a normative association between metrics of research maturation and approval of new cardiovascular therapeutics and suggests strategies for advancing translational science by accelerating basic and applied research and improving the synchrony between the maturation of this research and drug development initiatives. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  12. Quasi-Drugs Developed in Japan for the Prevention or Treatment of Hyperpigmentary Disorders

    PubMed Central

    Ando, Hideya; Matsui, Mary S.; Ichihashi, Masamitsu

    2010-01-01

    Excess production of melanin or its abnormal distribution, or both, can cause irregular hyperpigmentation of the skin, leading to melasma and age spots. To date, various quasi-drugs that prevent or improve hyperpigmentary disorders have been developed and officially approved by the Ministry of Health, Labor and Welfare of Japan. Many of these inhibit the activity of tyrosinase, an enzyme required for melanin synthesis, for example, by competitive or non-competitive inhibition of its catalytic activity, by inhibiting its maturation, or by accelerating its degradation. In this review, we categorize the quasi-drugs developed in Japan to prevent or treat hyperpigmentary disorders, or both, and discuss perspectives for future development. PMID:20640168

  13. 27 CFR 17.133 - Food product formulas.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Food product formulas. 17... PRODUCTS Formulas and Samples Approval of Formulas § 17.133 Food product formulas. Formulas for nonbeverage food products on TTB Form 5154.1 may be approved if they are unfit for beverage purposes. Approval does...

  14. 27 CFR 17.133 - Food product formulas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Food product formulas. 17... PRODUCTS Formulas and Samples Approval of Formulas § 17.133 Food product formulas. Formulas for nonbeverage food products on TTB Form 5154.1 may be approved if they are unfit for beverage purposes. Approval does...

  15. 27 CFR 17.133 - Food product formulas.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Food product formulas. 17... PRODUCTS Formulas and Samples Approval of Formulas § 17.133 Food product formulas. Formulas for nonbeverage food products on TTB Form 5154.1 may be approved if they are unfit for beverage purposes. Approval does...

  16. 27 CFR 17.133 - Food product formulas.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Food product formulas. 17... PRODUCTS Formulas and Samples Approval of Formulas § 17.133 Food product formulas. Formulas for nonbeverage food products on TTB Form 5154.1 may be approved if they are unfit for beverage purposes. Approval does...

  17. 27 CFR 17.133 - Food product formulas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Food product formulas. 17... PRODUCTS Formulas and Samples Approval of Formulas § 17.133 Food product formulas. Formulas for nonbeverage food products on TTB Form 5154.1 may be approved if they are unfit for beverage purposes. Approval does...

  18. An Integrating Dosimeter for Pulsed Radiation,

    DTIC Science & Technology

    1983-12-01

    obtained using 10 MeV electrons from a linear accelerator and placing the TLDs in an aluminum package equivalent to the thickness of the pin diode * --. and...Radiation Dosimetry System overcomes this problem by electronic - ally integrating the output of a pin diode. The integrator section of the system...for publication. APPROVED: BOBBY L. BUCHANAN, Chief Radiation Hardened Electronics Technology Branch V-. Solid State Sciences Division APPROVED

  19. Bivalent rLP2086 (Trumenba®): Development of a well-characterized vaccine through commercialization.

    PubMed

    Sunasara, Khurram; Cundy, John; Srinivasan, Sriram; Evans, Brad; Sun, Weiqiang; Cook, Scott; Bortell, Eric; Farley, John; Griffin, Daniel; Bailey Piatchek, Michele; Arch-Douglas, Katherine

    2018-05-24

    The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation. Bivalent rLP2086 contains two rLP2086 antigens and is licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B in individuals 10-25years of age in the United States. This paper discusses the development of the manufacturing process of the two antigens for the purpose of making it amenable to any manufacturing facility. For the journey to commercialization, the operating model used to manage this highly accelerated program led to a framework that ensured "right the first time" execution, robust process characterization, and proactive process monitoring. This framework enabled quick problem identification and proactive resolutions, resulting in a robust control strategy for the commercial process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 30 CFR 14.10 - Post-approval product audit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Post-approval product audit. 14.10 Section 14... General Provisions § 14.10 Post-approval product audit. (a) Approved conveyor belts will be subject to... applicant and other persons agreed upon by MSHA and the applicant may be present during audit tests and...

  1. 30 CFR 14.10 - Post-approval product audit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Post-approval product audit. 14.10 Section 14... General Provisions § 14.10 Post-approval product audit. (a) Approved conveyor belts will be subject to... applicant and other persons agreed upon by MSHA and the applicant may be present during audit tests and...

  2. 30 CFR 14.10 - Post-approval product audit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Post-approval product audit. 14.10 Section 14... General Provisions § 14.10 Post-approval product audit. (a) Approved conveyor belts will be subject to... applicant and other persons agreed upon by MSHA and the applicant may be present during audit tests and...

  3. 46 CFR 160.023-4 - Approval and production tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Approval and production tests. 160.023-4 Section 160.023-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand Combination Flare and Smoke Distress Signals § 160.023-4 Approval and production tests...

  4. 46 CFR 160.022-4 - Approval and production tests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Approval and production tests. 160.022-4 Section 160.022-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Floating Orange Smoke Distress Signals (5 Minutes) § 160.022-4 Approval and production test...

  5. 46 CFR 160.023-4 - Approval and production tests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Approval and production tests. 160.023-4 Section 160.023-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand Combination Flare and Smoke Distress Signals § 160.023-4 Approval and production tests...

  6. 46 CFR 160.028-4 - Approval and production tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Approval and production tests. 160.028-4 Section 160.028-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Signal Pistols for Red Flare Distress Signals § 160.028-4 Approval and production tests. (a...

  7. 77 FR 56646 - Wayne E. Spencer: Debarment Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ..., including the process for development or approval, of a drug product under the FD&C Act. Dr. Spencer was..., including the process for development or approval, of a drug product under the FD&C Act. On March 7, 2012... to the development or approval, including the process for development or approval, of a drug product...

  8. 78 FR 29780 - Fees for Testing, Evaluation, and Approval of Mining Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-21

    ... Approval of Mining Products AGENCY: Mine Safety and Health Administration, Labor. ACTION: Notice. SUMMARY..., and approval of mining products; it allows MSHA to collect fees up to $2,499,000 for the testing, evaluation, and approval of certain mining equipment. MSHA is continuing to collect these fees for 2013 as...

  9. Biosimilars: it's not as simple as cost alone.

    PubMed

    Roger, S D; Goldsmith, D

    2008-10-01

    Biosimilars or follow-on biologics (FoB) are biopharmaceuticals that, unlike small molecule generic products, are copies of larger, much more complex proteins. As such, data generated from one biopharmaceutical cannot be extrapolated to another. Unlike small molecule generics, FoB require a full developmental programme, albeit smaller than for an originator product. This has been recognized by European regulatory authorities and it is becoming clear that accelerated processes for FoB marketing approval are not feasible. To determine the balance between costs surrounding FoB (including relatively extensive developmental programmes and subsequent price to the market) and the necessity to ensure efficacy and safety. It is important that FoB are sufficiently tested to ensure patient safety is not compromised. Conducting such a development programme followed by sound pharmacovigilance is very challenging and costly. Cost-savings associated with FoB may be limited.

  10. 9 CFR 592.300 - Approval of official identification.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Approval of official identification. 592.300 Section 592.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.300 Approval of official...

  11. 9 CFR 592.300 - Approval of official identification.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Approval of official identification. 592.300 Section 592.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.300 Approval of official...

  12. 9 CFR 592.300 - Approval of official identification.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Approval of official identification. 592.300 Section 592.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.300 Approval of official...

  13. 9 CFR 592.300 - Approval of official identification.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Approval of official identification. 592.300 Section 592.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.300 Approval of official...

  14. Approval Summary: Letrozole (Femara® Tablets) for Adjuvant and Extended Adjuvant Postmenopausal Breast Cancer Treatment: Conversion of Accelerated to Full Approval

    PubMed Central

    Johnson, John R.; Justice, Robert; Pazdur, Richard

    2011-01-01

    On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor–positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76–1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen. PMID:22089970

  15. Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval.

    PubMed

    Cohen, Martin H; Johnson, John R; Justice, Robert; Pazdur, Richard

    2011-01-01

    On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor-positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76-1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen.

  16. 77 FR 3829 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Order Granting Accelerated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66192; File No. SR-NYSEArca-2012-02] Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Order Granting Accelerated Approval of a Proposed Rule Amendments to NYSE Arca Rule 9.4 and NYSE Equities Inc. Rules 5.3(d) and 9.4 Relating to Discretionary Proxy Voting on Executive...

  17. An Audit of Selected Private School Programs: Accelerated Christian Education, Alpha Omega, Mennonite Schools, Seventh-Day Adventist Schools, and A BEKA Instructional Resources.

    ERIC Educational Resources Information Center

    Alberta Dept. of Education, Edmonton.

    This report, commissioned by the Minister of Education of Alberta, reviews the programs of study and instructional materials used in four groups of approved private schools: schools using the Accelerated Christian Education curriculum; schools using the Alpha Omega program; Mennonite parochial schools; and Seventh Day Adventist schools. The review…

  18. Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective.

    PubMed

    Abelin, Atika; Colegate, Tony; Gardner, Stephen; Hehme, Norbert; Palache, Abraham

    2011-02-01

    As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness. The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade. During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply. Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure. Enhancing international regulatory co-operation and mutual recognition of approvals could accelerate vaccine supply, while maintaining safety standards. Strengthening communications with the public and healthcare workers using new approaches and new channels could help improve vaccine uptake. Finally, increasing seasonal vaccine coverage will be particularly important to extend and sustain pandemic vaccine production capacity. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Working with the U.S. Food and Drug Administration to obtain approval of products under the Animal Rule.

    PubMed

    Park, Glen D; Mitchel, Jules T

    2016-06-01

    While the development of medical products and approval by the U.S. Food and Drug Administration (FDA) is well known, the development of countermeasures against exposure to toxic levels of radiation, chemicals, and infectious agents requires special consideration, and there has been, to date, little experience in working with the FDA to obtain approval of these products. The FDA has published a regulation entitled "Approval of Biological Products when Human Efficacy Studies are not Ethical or Feasible." This regulation, known simply as the "Animal Rule," was designed to permit approval or licensing of drugs and biologics when efficacy studies in humans are not ethical or feasible. To date, 12 products have been approved under the Animal Rule. It is highly recommended that sponsors of products that are to be developed under the Animal Rule meet with the FDA and other government entities early in the development process to ensure that the efficacy and safety studies that are planned will meet the FDA's requirements for approval of the product. © 2016 New York Academy of Sciences.

  20. 14 CFR 29.1459 - Flight data recorders.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) The vertical acceleration sensor is rigidly attached, and located longitudinally within the approved...) Have a reflective tape affixed to its external surface to facilitate its location under water; and (3...

  1. 14 CFR 27.1459 - Flight data recorders.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) The vertical acceleration sensor is rigidly attached, and located longitudinally within the approved...) Have a reflective tape affixed to its external surface to facilitate its location under water; and (3...

  2. DARHT: INTEGRATION OF AUTHORIZATION BASIS REQUIREMENTS AND WORKER SAFETY

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

    D. A. MC CLURE; C. A. NELSON; R. L. BOUDRIE

    2001-04-01

    This document describes the results of consensus agreements reached by the DARHT Safety Planning Team during the development of the update of the DARHT Safety Analysis Document (SAD). The SAD is one of the Authorization Basis (AB) Documents required by the Department prior to granting approval to operate the DARHT Facility. The DARHT Safety Planning Team is lead by Mr. Joel A. Baca of the Department of Energy Albuquerque Operations Office (DOE/AL). Team membership is drawn from the Department of Energy Albuquerque Operations Office, the Department of Energy Los Alamos Area Office (DOE/LAAO), and several divisions of the Los Alamosmore » National Laboratory. Revision 1 of the DARHT SAD had been written as part of the process for gaining approval to operate the Phase 1 (First Axis) Accelerator. Early in the planning stage for the required update of the SAD for the approval to operate both Phase 1 and Phase 2 (First Axis and Second Axis) DARHT Accelerator, it was discovered that a conflict existed between the Laboratory approach to describing the management of facility and worker safety.« less

  3. 14 CFR 25.1459 - Flight data recorders.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... acceleration sensor is rigidly attached, and located longitudinally either within the approved center of... reflective tape affixed to its external surface to facilitate its location under water; and (3) Have an...

  4. 77 FR 26706 - Food Ingredients and Sources of Radiation Listed and Approved for Use in the Production of Meat...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... Listed and Approved for Use in the Production of Meat and Poultry Products AGENCY: Food Safety and... the regulations prohibit for use in meat or poultry products. Under this proposal, new uses of these substances in meat or poultry products would continue to be approved by the Food and Drug Administration (FDA...

  5. Analysis of Drug Development Paradigms for Immune Checkpoint Inhibitors.

    PubMed

    Jardim, Denis L; de Melo Gagliato, Débora; Giles, Francis J; Kurzrock, Razelle

    2018-04-15

    Immune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough therapy designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months [avelumab had the shortest timeline (52.33 months)]. Response rates during early phase I trials (median = 16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early-phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified. Clin Cancer Res; 24(8); 1785-94. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Are government-approved products containing new psychoactive substances perceived to be safer and more socially acceptable than alcohol, tobacco and illegal drugs? Findings from a survey of police arrestees in New Zealand.

    PubMed

    Rychert, Marta; Wilkins, Chris; Parker, Karl; Witten, Karen

    2018-03-01

    In July 2013, New Zealand passed the Psychoactive Substances Act (PSA), which established a legal regulated market for government-approved products containing new psychoactive substances (NPS). One of the aims of the PSA was to separate the market for approved NPS products from unapproved products and illegal drugs. The aim of this study was to explore perceived health risks and social acceptability of government-approved NPS compared to unapproved NPS and other drugs. About 834 police arrestees were surveyed about the health risks and social acceptability of regularly using nine drug types, including approved and unapproved synthetic cannabinoids (SC) and 'party pills' (PP) under the interim PSA regime. Statistical analyses included fitted analysis of variance and logistic ordinal regression models. Approved SC were considered riskier to health than (natural) cannabis, alcohol, approved and unapproved PP, tobacco and ecstasy, but safer than unapproved SC and methamphetamine. Younger participants (16-29 years) were more likely than older participants (30+ years) to give approved SC a high health-risk score. Approved SC were considered less socially acceptable than alcohol, tobacco and cannabis, but more socially acceptable than methamphetamine, unapproved SC and unapproved PP. Frequent SC users were more likely to rate the social acceptability of approved legal SC higher than other drug users. Approved PP received more positive health and social acceptability scores than approved SC. The PSA was partially successful at separating approved NPS from other drugs. High health-risk and low social acceptability scores for approved SC may reflect the absence of product testing during the interim PSA market. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  7. The Tropical Disease Priority Review Voucher: A Game-Changer for Tropical Disease Products.

    PubMed

    Berman, Jonathan; Radhakrishna, Tanya

    2017-01-11

    The Neglected Tropical Disease Voucher Program is a Congressionally-mandated program intended to promote approval of products for tropical diseases because it provides spectacular financial compensation consequent to FDA approval of a priority product. Three drug approvals-artemether/lumifantrine for malaria, bedaquiline for multidrug resistant tuberculosis, miltefosine for leishmaniasis-have received Tropical Disease Vouchers to date. We give our view of the type of products that might qualify for a Tropical Disease Voucher, financial considerations in venturing capital to support product development, clinical ramifications of a successful product approval, and an overall evaluation of the Program. © The American Society of Tropical Medicine and Hygiene.

  8. Characteristics of rare disease marketing applications associated with FDA product approvals 2006-2010.

    PubMed

    Pariser, Anne R; Slack, Daniel J; Bauer, Larry J; Warner, Catherine A; Tracy, LaRee A

    2012-08-01

    New drug and biologic product marketing applications submitted to FDA's Center for Drug Evaluation and Research (CDER) between 2006 and 2010 were analyzed to identify rare disease application characteristics associated with higher approval rates. The results show that approval rates were similar for rare and common disease applications. Larger company size, prior regulatory experience and priority review designation were associated with higher approval rates. The study findings show that rare disease product development is feasible, and increased interactions between product developers and FDA in early investigational phases can facilitate product development. Published by Elsevier Ltd.

  9. Comparison of the new Japanese legislation for expedited approval of regenerative medicine products with the existing systems in the USA and European Union

    PubMed Central

    Jokura, Yoji; Yano, Kazuo

    2017-01-01

    Abstract Legislation for expedited‐approval pathways and programmes for drugs, biologics or medical devices has been enacted for rapid commercialization of innovative products in the United States of America (USA) and the European Union (EU). However, less innovative products are increasingly benefitting from these expedited‐approval pathways, and obligations to collect and report post‐marketing data on approved products are being bypassed frequently. The Japanese government recently enacted legislation for a new conditional and time‐limited approval pathway dedicated to regenerative medicine products. The current study examines this new legislation and compares it with existing US and EU regulatory frameworks, with a particular focus on how it addresses the limitations of existing systems. Regulations, guidance documents and approval information were gathered from the websites of the respective authorities in the USA, the EU and Japan, and the systems were categorized through qualitative analysis. The pathways and programmes from each region were categorized into four groups, based on the requirement of pre‐ or post‐marketing clinical data. Expedited‐approval pathways in the USA and the EU provide similar qualification criteria, such as severity of target disease; however, such criteria are not specified for the new pathway in Japan. Only the Japanese pathway stipulates a time limitation on exceptional approval, requiring post‐marketing study for conditional and time‐limited products. Continuous improvement is necessary to solve previously addressed issues within the expedited‐approval pathways and programmes and to ensure that innovative medical products are rigourously screened, but also readily available to patients in need. The time limitation of conditional approval could be a potential solution to some of these problems. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd. PMID:28211195

  10. 30 CFR 14.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS General Provisions § 14.2... manufactures or controls the production of a conveyor belt and applies to MSHA for approval of conveyor belt... conveyor belt as approved. Extension of approval. A document issued by MSHA, which states that a change to...

  11. 77 FR 2308 - Approval of Altol Petroleum Product Service, as a Commercial Gauger

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-17

    ... DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Approval of Altol Petroleum... Security. ACTION: Notice of approval of Altol Petroleum Product Service, as a commercial gauger. SUMMARY: Notice is hereby given that, pursuant to 19 CFR 151.13, Altol Petroleum Product Service, Calle Gregorio...

  12. Fibrin sealants: surgical hemostat, sealant and adhesive.

    PubMed

    Mandell, Samuel P; Gibran, Nicole S

    2014-06-01

    Fibrin sealants (FS) have been approved for use in the United States since 1998. Since approval, they have been used in a wide variety of clinical settings and new products continue to be introduced. This review covers the literature supporting the USA FDA-approved indications for FS products produced by Baxter Corp. Literature review of PubMed, the Cochrane Library, FDA approval documents and product websites yielded information contained in this article. Mechanism of action, efficacy and safety of these products are covered. FS are generally safe, popular and are used for a wide variety of off-label indications. Their use appears to be expanding rapidly. For many uses, including approved ones, large well-controlled trials are still needed. Additionally, cost-effectiveness data for these products would be a great benefit in guiding their future use.

  13. Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

    PubMed

    Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

    2010-07-01

    The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.

  14. Amprenavir, new protease inhibitor, approved.

    PubMed

    James, J S

    1999-05-07

    A new protease inhibitor, amprenavir (Agenerase), has received FDA marketing approval. The approval was based on two 24-week controlled trials and safety data in more than 1,400 patients under FDA accelerated-approval rules. Amprenavir is approved for patients 4 years of age and older. The drug is taken twice daily, with or without food. Side effects include gastrointestinal disturbances, rashes, and oral paresthesia. Severe or life-threatening rashes have occurred in 1 percent of all patients. Pregnant women should not use the drug unless necessary. The drug was developed by Vertex Pharmaceuticals Inc. and is being marketed by Glaxo Wellcome. Some studies suggest that amprenavir is less likely than other protease inhibitors to be associated with lipid metabolism problems. It may have a resistance profile different from that of other protease inhibitors, and therefore may cause different cross resistance problems. Amprenavir appears to be synergistic with abacavir (Ziagen) in laboratory tests.

  15. Scientific and Regulatory Considerations for Generic Complex Drug Products Containing Nanomaterials.

    PubMed

    Zheng, Nan; Sun, Dajun D; Zou, Peng; Jiang, Wenlei

    2017-05-01

    In the past few decades, the development of medicine at the nanoscale has been applied to oral and parenteral dosage forms in a wide range of therapeutic areas to enhance drug delivery and reduce toxicity. An obvious response to these benefits is reflected in higher market shares of complex drug products containing nanomaterials than that of conventional formulations containing the same active ingredient. The surging market interest has encouraged the pharmaceutical industry to develop cost-effective generic versions of complex drug products based on nanotechnology when the associated patent and exclusivity on the reference products have expired. Due to their complex nature, nanotechnology-based drugs present unique challenges in determining equivalence standards between generic and innovator products. This manuscript attempts to provide the scientific rationales and regulatory considerations of key equivalence standards (e.g., in vivo studies and in vitro physicochemical characterization) for oral drugs containing nanomaterials, iron-carbohydrate complexes, liposomes, protein-bound drugs, nanotube-forming drugs, and nano emulsions. It also presents active research studies in bridging regulatory and scientific gaps for establishing equivalence of complex products containing nanomaterials. We hope that open communication among industry, academia, and regulatory agencies will accelerate the development and approval processes of generic complex products based on nanotechnology.

  16. Era of faster FDA drug approval has also seen increased black-box warnings and market withdrawals.

    PubMed

    Frank, Cassie; Himmelstein, David U; Woolhandler, Steffie; Bor, David H; Wolfe, Sidney M; Heymann, Orlaith; Zallman, Leah; Lasser, Karen E

    2014-08-01

    After approval, many prescription medications that patients rely on subsequently receive new black-box warnings or are withdrawn from the market because of safety concerns. We examined whether the frequency of these safety problems has increased since 1992, when the Prescription Drug User Fee Act, legislation designed to accelerate the drug approval process at the Food and Drug Administration, was passed. We found that drugs approved after the act's passage were more likely to receive a new black-box warning or be withdrawn than drugs approved before its passage (26.7 per 100.0 drugs versus 21.2 per 100.0 drugs at up to sixteen years of follow-up). We could not establish causality, however. Our findings suggest the need for reforms to reduce patients' exposure to unsafe drugs, such as a statement or symbol in the labeling, medication guides for patients, and marketing materials indicating that a drug was approved only recently. Project HOPE—The People-to-People Health Foundation, Inc.

  17. 75 FR 4124 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Accelerated Approval of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ... sub-adviser. The Bank of New York Mellon Corporation is the administrator, Fund accountant, transfer..., portfolio holdings and policies, distributions and taxes, availability of information, trading rules and...

  18. 75 FR 9472 - Self-Regulatory Organizations; Notice of Filing and Order Granting Accelerated Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    .... (``NASD''), and NYSE Regulation, Inc. (``NYSER'') consolidated their member firm regulation operations...) (Reduction of Elimination of Loans and Advances), 328 (Sale-And-Leasebacks, Factoring, Financing and Similar...

  19. Storage and transport of reconstituted omacetaxine mepesuccinate: Considerations for home administration.

    PubMed

    Parikh, Alpa; van de Rijn, Jennifer; Melville, Chris; Sarkari, Marazban; Peltier, Sylvie; McKean, Robert

    2018-04-01

    Purpose Omacetaxine mepesuccinate ("omacetaxine") is approved by the US Food and Drug Administration for the treatment of adult patients with chronic- or accelerated-phase chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. In May 2014, the US Food and Drug Administration approved revisions to the packaging information that included directions for home administration of reconstituted omacetaxine by patients or caregivers using syringes filled at a healthcare facility. We developed recommendations for the transport, storage, and spill-clean procedure of reconstituted omacetaxine for home and clinic administration. Methods We conducted chemical stability and microbial growth studies of reconstituted omacetaxine solution stored in vials and syringes at room temperature or refrigerated for various durations. Several shipping configurations were tested in simulated transport conditions to evaluate their ability to contain solution leakage and maintain product quality during distribution. In addition, we evaluated cleaning products and procedures for their effectiveness in removing residual omacetaxine from household surfaces after mock spills. Results Reconstituted omacetaxine showed limited degradation when refrigerated for 14 days in vials and syringes, and no microbial growth was observed for 12 days after intentional inoculation. In shipping studies, the configurations maintained prepared syringes within the recommended storage temperature range throughout transport and could contain leaks if spills occurred. In the event of an accidental spill in a home environment, effective cleaning can be achieved using household cleaning products and defined procedures. Conclusion These data provide important information regarding the safe transportation and administration of reconstituted omacetaxine in the home and clinic.

  20. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  1. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  2. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  3. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  4. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  5. 9 CFR 327.6 - Products for importation; program inspection, time and place; application for approval of...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... inspection, time and place; application for approval of facilities as official import inspection... § 327.6 Products for importation; program inspection, time and place; application for approval of..., wholesome, and otherwise not adulterated at the time the products are offered for importation into the...

  6. 9 CFR 327.6 - Products for importation; program inspection, time and place; application for approval of...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... inspection, time and place; application for approval of facilities as official import inspection... § 327.6 Products for importation; program inspection, time and place; application for approval of..., wholesome, and otherwise not adulterated at the time the products are offered for importation into the...

  7. 9 CFR 327.6 - Products for importation; program inspection, time and place; application for approval of...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... inspection, time and place; application for approval of facilities as official import inspection... § 327.6 Products for importation; program inspection, time and place; application for approval of..., wholesome, and otherwise not adulterated at the time the products are offered for importation into the...

  8. 9 CFR 327.6 - Products for importation; program inspection, time and place; application for approval of...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... inspection, time and place; application for approval of facilities as official import inspection... § 327.6 Products for importation; program inspection, time and place; application for approval of..., wholesome, and otherwise not adulterated at the time the products are offered for importation into the...

  9. 46 CFR 159.007-9 - Production inspections and tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Production inspections and tests. 159.007-9 Section 159.007-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of Approved Equipment and Materials §...

  10. 46 CFR 159.007-5 - Production inspections and tests: Application for acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Production inspections and tests: Application for acceptance. 159.007-5 Section 159.007-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of Approved...

  11. 46 CFR 159.007-5 - Production inspections and tests: Application for acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Production inspections and tests: Application for acceptance. 159.007-5 Section 159.007-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of Approved...

  12. 46 CFR 159.007-9 - Production inspections and tests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Production inspections and tests. 159.007-9 Section 159.007-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of Approved Equipment and Materials §...

  13. 46 CFR 159.007-13 - Production inspections and tests: Records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Production inspections and tests: Records. 159.007-13 Section 159.007-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of Approved Equipment and...

  14. 46 CFR 159.007-13 - Production inspections and tests: Records.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Production inspections and tests: Records. 159.007-13 Section 159.007-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of Approved Equipment and...

  15. 46 CFR 159.007-11 - Production inspections and tests: Yearly report.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Production inspections and tests: Yearly report. 159.007-11 Section 159.007-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of Approved Equipment an...

  16. 75 FR 82074 - Fee Adjustment for Testing, Evaluation, and Approval of Mining Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ..., and Approval of Mining Products AGENCY: Mine Safety and Health Administration (MSHA), Labor. ACTION..., evaluating, and approving mining products as provided by 30 CFR part 5. MSHA charges applicants a fee to... materials manufactured for use in the mining industry. The new fee schedule, effective January 1, 2011, is...

  17. 46 CFR 159.007-11 - Production inspections and tests: Yearly report.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Production inspections and tests: Yearly report. 159.007-11 Section 159.007-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of Approved Equipment an...

  18. Unintended Effects of Orphan Product Designation for Rare Neurological Diseases

    PubMed Central

    Murphy, Sinéad M; Puwanant, Araya; Griggs, Robert C.

    2012-01-01

    Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits and, perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs; both for newly developed drugs and even for drugs which were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington’s disease, adrenocorticotropic hormone for infantile spasms and enzyme replacement therapy with alglucosidase alpha for Pompe’s disease we highlight these paradoxical effects. PMID:23109143

  19. Savannah River Site Footprint Reduction Results under the American Recovery and Reinvestment Act - 13302

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

    Flora, Mary; Adams, Angelia; Pope, Robert

    2013-07-01

    The Savannah River Site (SRS) is an 802 square-kilometer United States Department of Energy (US DOE) nuclear facility located along the Savannah River near Aiken, South Carolina, managed and operated by Savannah River Nuclear Solutions. Construction of SRS began in the early 1950's to enhance the nation's nuclear weapons capability. Nuclear weapons material production began in the early 1950's, eventually utilizing five production reactors constructed to support the national defense mission. Past operations have resulted in releases of hazardous constituents and substances to soil and groundwater, resulting in 515 waste sites with contamination exceeding regulatory thresholds. More than 1,000 facilitiesmore » were constructed onsite with approximately 300 of them considered radiological, nuclear or industrial in nature. In 2003, SRS entered into a Memorandum of Agreement with its regulators to accelerate the cleanup using an Area Completion strategy. The strategy was designed to focus cleanup efforts on the 14 large industrial areas of the site to realize efficiencies of scale in the characterization, assessment, and remediation activities. This strategy focuses on addressing the contaminated surface units and the vadose zone and addressing groundwater plumes subsequently. This approach streamlines characterization and remediation efforts as well as the required regulatory documentation, while enhancing the ability to make large-scale cleanup decisions. In February 2009, Congress approved the American Reinvestment and Recovery Act (ARRA) to create jobs and promote economic recovery. At SRS, ARRA funding was established in part to accelerate the completion of environmental remediation and facility deactivation and decommissioning (D and D). By late 2012, SRS achieved 85 percent footprint reduction utilizing ARRA funding by accelerating and coupling waste unit remediation with D and D of remnant facilities. Facility D and D activities were sequenced and permitted with waste unit remediation activities to streamline regulatory approval and execution. Achieving footprint reduction fulfills the Government's responsibility to address legacy contamination; allows earlier completion of legally enforceable compliance agreement milestones; and enables future potential reuse of DOE resources, including land and infrastructure for other missions. Over the last 3.5 years significant achievements were met that contributed to footprint reduction, including the closure of 41 waste units (including 20 miles of radiologically contaminated stream) and decommissioning of 30 facilities (including the precedent setting in situ closure of two former production reactors, the first in the DOE Complex). Other notable achievements included the removal of over 39,750 cubic meters of debris and 68,810 cubic meters of contaminated soils, including 9175 cubic meters of lead-contaminated soil from a former site small arms testing range and treatment of 1,262 cubic meters of tritium-laden soils and concrete using a thermal treatment system. (authors)« less

  20. Greater Yellowstone regional traveler and weather information system evaluation plan

    DOT National Transportation Integrated Search

    2002-04-19

    The ITS Integration Program is being conducted to accelerate the integration and interoperability of intelligent transportation systems in metropolitan and rural areas. Projects approved for funding have been assessed as supporting the improvements o...

  1. Comparison of the new Japanese legislation for expedited approval of regenerative medicine products with the existing systems in the USA and European Union.

    PubMed

    Jokura, Yoji; Yano, Kazuo; Yamato, Masayuki

    2018-02-01

    Legislation for expedited-approval pathways and programmes for drugs, biologics or medical devices has been enacted for rapid commercialization of innovative products in the United States of America (USA) and the European Union (EU). However, less innovative products are increasingly benefitting from these expedited-approval pathways, and obligations to collect and report post-marketing data on approved products are being bypassed frequently. The Japanese government recently enacted legislation for a new conditional and time-limited approval pathway dedicated to regenerative medicine products. The current study examines this new legislation and compares it with existing US and EU regulatory frameworks, with a particular focus on how it addresses the limitations of existing systems. Regulations, guidance documents and approval information were gathered from the websites of the respective authorities in the USA, the EU and Japan, and the systems were categorized through qualitative analysis. The pathways and programmes from each region were categorized into four groups, based on the requirement of pre- or post-marketing clinical data. Expedited-approval pathways in the USA and the EU provide similar qualification criteria, such as severity of target disease; however, such criteria are not specified for the new pathway in Japan. Only the Japanese pathway stipulates a time limitation on exceptional approval, requiring post-marketing study for conditional and time-limited products. Continuous improvement is necessary to solve previously addressed issues within the expedited-approval pathways and programmes and to ensure that innovative medical products are rigourously screened, but also readily available to patients in need. The time limitation of conditional approval could be a potential solution to some of these problems. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd.

  2. The therapeutic monoclonal antibody market

    PubMed Central

    Ecker, Dawn M; Jones, Susan Dana; Levine, Howard L

    2015-01-01

    Since the commercialization of the first therapeutic monoclonal antibody product in 1986, this class of biopharmaceutical products has grown significantly so that, as of November 10, 2014, forty-seven monoclonal antibody products have been approved in the US or Europe for the treatment of a variety of diseases, and many of these products have also been approved for other global markets. At the current approval rate of ∼ four new products per year, ∼70 monoclonal antibody products will be on the market by 2020, and combined world-wide sales will be nearly $125 billion. PMID:25529996

  3. A Sweet Spot for Molecular Diagnostics: Coupling Isothermal Amplification and Strand Exchange Circuits to Glucometers

    NASA Astrophysics Data System (ADS)

    Du, Yan; Hughes, Randall A.; Bhadra, Sanchita; Jiang, Yu Sherry; Ellington, Andrew D.; Li, Bingling

    2015-06-01

    Strand exchange nucleic acid circuitry can be used to transduce isothermal nucleic acid amplification products into signals that can be readable on an off-the-shelf glucometer. Loop-mediated isothermal amplification (LAMP) is limited by the accumulation of non-specific products, but nucleic acid circuitry can be used to probe and distinguish specific amplicons. By combining this high temperature isothermal amplification method with a thermostable invertase, we can directly transduce Middle-East respiratory syndrome coronavirus and Zaire Ebolavirus templates into glucose signals, with a sensitivity as low as 20-100 copies/μl, equating to atto-molar (or low zepto-mole). Virus from cell lysates and synthetic templates could be readily amplified and detected even in sputum or saliva. An OR gate that coordinately triggered on viral amplicons further guaranteed fail-safe virus detection. The method describes has potential for accelerating point-of-care applications, in that biological samples could be applied to a transducer that would then directly interface with an off-the-shelf, approved medical device.

  4. 30 CFR 6.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... MSHA. Equivalent non-MSHA product safety standards. A non-MSHA product safety standard, or group of... PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.2... manufactures or controls the assembly of a product and applies to MSHA for approval of that product. Approval...

  5. 30 CFR 6.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... MSHA. Equivalent non-MSHA product safety standards. A non-MSHA product safety standard, or group of... PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.2... manufactures or controls the assembly of a product and applies to MSHA for approval of that product. Approval...

  6. 30 CFR 6.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MSHA. Equivalent non-MSHA product safety standards. A non-MSHA product safety standard, or group of... PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.2... manufactures or controls the assembly of a product and applies to MSHA for approval of that product. Approval...

  7. 30 CFR 6.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MSHA. Equivalent non-MSHA product safety standards. A non-MSHA product safety standard, or group of... PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.2... manufactures or controls the assembly of a product and applies to MSHA for approval of that product. Approval...

  8. 30 CFR 6.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MSHA. Equivalent non-MSHA product safety standards. A non-MSHA product safety standard, or group of... PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.2... manufactures or controls the assembly of a product and applies to MSHA for approval of that product. Approval...

  9. 7 CFR 70.50 - Approval of official identification and wording on labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF POULTRY PRODUCTS AND RABBIT PRODUCTS Grading of Poultry Products and Rabbit Products Identifying and Marking Products § 70.50 Approval of official identification... CFR part 381. Poultry Products Inspection Regulations. Labeling requirements for ready-to-cook rabbits...

  10. Therapeutic nucleic acids: current clinical status

    PubMed Central

    Sridharan, Kannan

    2016-01-01

    Abstract Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are simple linear polymers that have been the subject of considerable research in the last two decades and have now moved into the realm of being stand‐alone therapeutic agents. Much of this has stemmed from the appreciation that they carry out myriad functions that go beyond mere storage of genetic information and protein synthesis. Therapy with nucleic acids either uses unmodified DNA or RNA or closely related compounds. From both a development and regulatory perspective, they fall somewhere between small molecules and biologics. Several of these compounds are in clinical development and many have received regulatory approval for human use. This review addresses therapeutic uses of DNA based on antisense oligonucleotides, DNA aptamers and gene therapy; and therapeutic uses of RNA including micro RNAs, short interfering RNAs, ribozymes, RNA decoys and circular RNAs. With their specificity, functional diversity and limited toxicity, therapeutic nucleic acids hold enormous promise. However, challenges that need to be addressed include targeted delivery, mass production at low cost, sustaining efficacy and minimizing off‐target toxicity. Technological developments will hold the key to this and help accelerate drug approvals in the years to come. PMID:27111518

  11. 75 FR 9468 - Self-Regulatory Organizations; Notice of Filing and Order Granting Accelerated Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    ... member firm regulation operations into a combined organization, FINRA. Pursuant to Rule 17d-2 under the... Loans and Advances), 328 (Sale-And-Leasebacks, Factoring, Financing and Similar Arrangements), 416.20...

  12. Evaluating the Effectiveness of Various Blast Loading Descriptors as Occupant Injury Predictors for Underbody Blast Events

    DTIC Science & Technology

    2014-01-09

    of Hybrid III ATD LSDYNA model with FTSS v7.1.6 finite element dummy 6 Unclassified: Distribution Statement A. Approved for public release...descriptors as occupant injury predictors for underbody blast events Recording injury metrics Response from the dummy especially pelvic acceleration and...Ciip(H&ad CG,2) "’"’ "-......--------, I Max : 122.669 @59.81 7!; Time, ms Pelvic Z acceleration, g I I Clip: -4.75737 Ts:97.4138 Te: 104.414

  13. Oil spill treatment products approval: the UK approach and potential application to the Gulf region.

    PubMed

    Kirby, Mark F; Law, Robin J

    2008-07-01

    The environmental threat from oil spills remains significant across the globe and particularly in regions of high oil production and transport such as the Gulf. The ultimate damage caused can be limited by mitigation actions that responders deploy. The responsible and appropriate use of oil spill treatment products (e.g. dispersants, sorbents etc.) can offer response options that can result in substantial net environmental benefit. However, the approval and choice of what products to use needs careful consideration. The United Kingdom has had in place a statutory approval scheme for oil spill treatment products for 30 years. It is based on measures of efficiency and environmental acceptability. Two toxicity tests form an integral part of the assessment, the Sea test and the Rocky Shore test, and work on the premise that approved products will not make the situation significantly worse when added to spilled oil. This paper outlines the UK approach and how its rationale might be applied to the approval of products specific for the Gulf region. Issues such as species choice, higher temperatures and salinity and regional environmental conditions are considered.

  14. Consumer and health literacy: The need to better design tobacco-cessation product packaging, labels, and inserts.

    PubMed

    Weiss, Stephanie M; Smith-Simone, Stephanie Y

    2010-03-01

    Tobacco-cessation product packaging and instruction materials may not be appropriate for some smokers and may contribute to the underuse and misuse of evidence-based treatments. The dual goals of this project are to analyze literacy levels of Food and Drug Administration (FDA)-approved and non-approved tobacco-cessation product packaging, directions, and claims, and to identify and categorize claims found on product packaging. The Campaign for Tobacco Free Kids (CTFK) maintains the Quitting and Reducing Tobacco Use Inventory of Products (QuiTIP) database, which catalogs products marketed and sold to consumers to reduce or quit use of tobacco products. It also includes all medications approved by the FDA for tobacco cessation as well as a sample of non-approved products such as homeopathic, herbal, nutritional, or dietary supplements commonly marketed as either cessation aids or alternative tobacco/nicotine products. This paper assesses the reading levels required to understand product packaging, labeling, and instructions using the Simple Measure of Gobbledygook (SMOG) and identifies claims on the product package labels using standard qualitative methods. Key findings show that the average reading levels needed to understand instructions for both FDA-approved and non-approved cessation products are above the reading levels recommended to ensure maximum comprehension. Improving the packaging and directions of evidence-based tobacco-cessation products so that they are preferably at or below a fifth-grade reading level, along with using consumer-based design principles to develop packaging, may help smokers take advantage of and correctly use products that will greatly increase their chances of successful quitting. 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  15. FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

    PubMed

    Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

    2015-11-01

    On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

  16. 46 CFR 160.023-4 - Approval and production tests.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 6 2012-10-01 2012-10-01 false Approval and production tests. 160.023-4 Section 160.023-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand Combination Flare and Smoke Distress...

  17. 46 CFR 160.023-4 - Approval and production tests.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 6 2013-10-01 2013-10-01 false Approval and production tests. 160.023-4 Section 160.023-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand Combination Flare and Smoke Distress...

  18. 46 CFR 160.023-4 - Approval and production tests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 6 2014-10-01 2014-10-01 false Approval and production tests. 160.023-4 Section 160.023-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand Combination Flare and Smoke Distress...

  19. 78 FR 31885 - Patent Term Extension

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-28

    ... patents for drug products, medical devices, food additives, or color additives are potentially eligible... using the approved product, or a method of manufacturing the approved product. 35 U.S.C. 156(d) also...

  20. 30 CFR 14.7 - Approval marking and distribution records.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS General Provisions § 14.7 Approval marking and distribution records. (a) An approved conveyor belt must be marketed only under the name specified in the approval. (b) Approved conveyor belt must be legibly and...

  1. 9 CFR 592.300 - Approval of official identification.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Approval of official identification. 592.300 Section 592.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products...

  2. 12 CFR 563b.500. - What management stock benefit plans may I implement?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... endorse or approve the plan in any way. You may not make any written or oral representations to the... 20 percent per year. (11) Your plan permits accelerated vesting only for disability or death, or if...

  3. The Tropical Disease Priority Review Voucher: A Game-Changer for Tropical Disease Products

    PubMed Central

    Berman, Jonathan; Radhakrishna, Tanya

    2017-01-01

    The Neglected Tropical Disease Voucher Program is a Congressionally-mandated program intended to promote approval of products for tropical diseases because it provides spectacular financial compensation consequent to FDA approval of a priority product. Three drug approvals–artemether/lumifantrine for malaria, bedaquiline for multidrug resistant tuberculosis, miltefosine for leishmaniasis–have received Tropical Disease Vouchers to date. We give our view of the type of products that might qualify for a Tropical Disease Voucher, financial considerations in venturing capital to support product development, clinical ramifications of a successful product approval, and an overall evaluation of the Program. PMID:27573627

  4. CuAAC click chemistry accelerates the discovery of novel chemical scaffolds as promising protein tyrosine phosphatases inhibitors.

    PubMed

    He, X-P; Xie, J; Tang, Y; Li, J; Chen, G-R

    2012-01-01

    Protein tyrosine phosphatases (PTPs) are crucial regulators for numerous biological processes in nature. The dysfunction and overexpression of many PTP members have been demonstrated to cause fatal human diseases such as cancers, diabetes, obesity, neurodegenerative diseases and autoimmune disorders. In the past decade, considerable efforts have been devoted to the production of PTPs inhibitors by both academia and the pharmaceutical industry. However, there are only limited drug candidates in clinical trials and no commercial drugs have been approved, implying that further efficient discovery of novel chemical entities competent for inhibition of the specific PTP target in vivo remains yet a challenge. In light of the click-chemistry paradigm which advocates the utilization of concise and selective carbon-heteroatom ligation reactions for the modular construction of useful compound libraries, the Cu(I)-catalyzed azidealkyne 1,3-dipolar cycloaddition reaction (CuAAC) has fueled enormous energy into the modern drug discovery. Recently, this ingenious chemical ligation tool has also revealed efficacious and expeditious in establishing large combinatorial libraries for the acquisition of novel PTPs inhibitors with promising pharmacological profiles. We thus offer here a comprehensive review highlighting the development of PTPs inhibitors accelerated by the CuAAC click chemistry.

  5. Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA's Office of Pharmaceutical Quality.

    PubMed

    Fisher, Adam C; Lee, Sau L; Harris, Daniel P; Buhse, Lucinda; Kozlowski, Steven; Yu, Lawrence; Kopcha, Michael; Woodcock, Janet

    2016-12-30

    Failures surrounding pharmaceutical quality, particularly with respect to product manufacturing issues and facility remediation, account for the majority of drug shortages and product recalls in the United States. Major scientific advancements pressure established regulatory paradigms, especially in the areas of biosimilars, precision medicine, combination products, emerging manufacturing technologies, and the use of real-world data. Pharmaceutical manufacturing is increasingly globalized, prompting the need for more efficient surveillance systems for monitoring product quality. Furthermore, increasing scrutiny and accelerated approval pathways provide a driving force to be even more efficient with limited regulatory resources. To address these regulatory challenges, the Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA) harbors a rigorous science and research program in core areas that support drug quality review, inspection, surveillance, standards, and policy development. Science and research is the foundation of risk-based quality assessment of new drugs, generic drugs, over-the-counter drugs, and biotechnology products including biosimilars. This is an overview of the science and research activities in OPQ that support the mission of ensuring that safe, effective, and high-quality drugs are available to the American public. Published by Elsevier B.V.

  6. 46 CFR 160.036-4 - Approval and production tests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Approval and production tests. 160.036-4 Section 160.036-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare...

  7. 46 CFR 160.036-4 - Approval and production tests.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 6 2013-10-01 2013-10-01 false Approval and production tests. 160.036-4 Section 160.036-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare...

  8. 46 CFR 160.036-4 - Approval and production tests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 6 2014-10-01 2014-10-01 false Approval and production tests. 160.036-4 Section 160.036-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare...

  9. 46 CFR 160.036-4 - Approval and production tests.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 6 2012-10-01 2012-10-01 false Approval and production tests. 160.036-4 Section 160.036-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare...

  10. 46 CFR 160.036-4 - Approval and production tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Approval and production tests. 160.036-4 Section 160.036-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare...

  11. 9 CFR 590.680 - Approval of labeling for egg products processed in exempted egg products processing plants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Approval of labeling for egg products processed in exempted egg products processing plants. 590.680 Section 590.680 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF...

  12. 9 CFR 590.680 - Approval of labeling for egg products processed in exempted egg products processing plants.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Approval of labeling for egg products processed in exempted egg products processing plants. 590.680 Section 590.680 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF...

  13. 9 CFR 590.435 - Wholesomeness and approval of materials.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Entry of Material into Official Egg Products Plants § 590.435 Wholesomeness and approval of materials. (a) Substances and ingredients used in the manufacture or preparation of any egg product capable...

  14. 9 CFR 590.640 - Application for exemption; approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.640 Application for exemption; approval. Any person desiring to process egg..., a Supervisory Egg Products Inspector will make a survey and inspection of the premises and plant to...

  15. 9 CFR 590.640 - Application for exemption; approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.640 Application for exemption; approval. Any person desiring to process egg..., a Supervisory Egg Products Inspector will make a survey and inspection of the premises and plant to...

  16. 78 FR 57406 - Approval of Altol Petroleum Product Service, as a Commercial Gauger

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ..., has been approved to gauge petroleum, petroleum products, organic chemicals and vegetable oils for... products, organic chemicals and vegetable oils for customs purposes, in accordance with the provisions of...

  17. Control of Parts Shipped Prior to Type Certificate Issuance

    DOT National Transportation Integrated Search

    1992-10-14

    This advisory circular provides information and guidance concerning the control of parts proposed to be shipped by manufacturers with an approved production inspection system (APIS) or production certificate (PC) (production approval : holders) in ad...

  18. 30 CFR 18.99 - Notice of approval or disapproval; letters of approval and approval plates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... approval or disapproval of the machine. (a) If the qualified electrical representative recommends field..., DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.99 Notice of approval or...

  19. 30 CFR 18.99 - Notice of approval or disapproval; letters of approval and approval plates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... approval or disapproval of the machine. (a) If the qualified electrical representative recommends field..., DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.99 Notice of approval or...

  20. 78 FR 65293 - Collection of Information; Proposed Extension of Approval; Comment Request-Publicly Available...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... Extension of Approval; Comment Request--Publicly Available Consumer Product Safety Information Database... Publicly Available Consumer Product Safety Information Database. The Commission will consider all comments... intention to seek extension of approval of a collection of information for a database on the safety of...

  1. New Opioid Analgesic Approvals and Outpatient Utilization of Opioid Analgesics in the United States, 1997 through 2015.

    PubMed

    Chai, Grace; Xu, Jing; Osterhout, James; Liberatore, Mark A; Miller, Kathleen L; Wolff, Carolyn; Cruz, Marisa; Lurie, Peter; Dal Pan, Gerald

    2018-05-01

    The opioid epidemic, driven in part by increased prescribing, is a public health emergency. This study examines dispensed prescription patterns and approvals of new opioid analgesic products to investigate whether the introduction of these new drugs increases prescribing. Prescribing patterns based on dispensed prescription claims from the U.S. retail setting were assessed with new brand and generic opioid analgesic products approved in the United States from 1997 through 2015. From 1997 through 2015, the U.S. Food and Drug Administration (Silver Spring, Maryland) approved 263 opioid analgesic products, including 33 brand products. Dispensed prescriptions initially increased 80% from 145 million prescriptions in 1997 to a peak of 260 million prescriptions in 2012 before decreasing by 12% to 228 million prescriptions in 2015. Morphine milligram equivalents dispensed per prescription increased from 486 in 1997 to a peak of 950 in 2010, before decreasing to 905 in 2015. In 2015, generic products accounted for 96% (218/228 million prescriptions) of all opioid analgesic prescriptions dispensed. The remaining prescriptions were dispensed for brand products, of which nearly half were dispensed for one brand product (OxyContin, Purdue, USA). There has been a dramatic increase in prescriptions dispensed for opioid analgesics since 1997 and an increasing number of opioid analgesic approvals; however, the number of prescriptions dispensed has declined since 2012 despite an increasing number of approvals. Examination of dispensed prescriptions shows a shifting and complex market where multiple factors likely influence prescribing; the approval of new products alone may not be sufficient to be a primary driver of increased prescribing. An online visual overview is available for this article at http://links.lww.com/ALN/B705.

  2. Certification Archives

    EPA Pesticide Factsheets

    The requirements of this product certification system are applicable to EPA-approved accreditation bodies (approved accreditation bodies), licensed certifying bodies, and the manufacturers that are obtaining product certification.

  3. 75 FR 20561 - Patent Term Extension

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-20

    ... drug products, medical devices, food additives, and color additives are eligible for extension. The... approved product, or a method of manufacturing the approved product. In addition, the application for... of manufacturing a product shall be extended if the term of the patent has not expired before an...

  4. 18 CFR 35.35 - Transmission infrastructure investment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... base; (iii) Recovery of prudently incurred pre-commercial operations costs; (iv) Hypothetical capital structure; (v) Accelerated depreciation used for rate recovery; (vi) Recovery of 100 percent of prudently... of the public utility; (vii) Deferred cost recovery; and (viii) Any other incentives approved by the...

  5. 18 CFR 35.35 - Transmission infrastructure investment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... base; (iii) Recovery of prudently incurred pre-commercial operations costs; (iv) Hypothetical capital structure; (v) Accelerated depreciation used for rate recovery; (vi) Recovery of 100 percent of prudently... of the public utility; (vii) Deferred cost recovery; and (viii) Any other incentives approved by the...

  6. 18 CFR 35.35 - Transmission infrastructure investment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... base; (iii) Recovery of prudently incurred pre-commercial operations costs; (iv) Hypothetical capital structure; (v) Accelerated depreciation used for rate recovery; (vi) Recovery of 100 percent of prudently... of the public utility; (vii) Deferred cost recovery; and (viii) Any other incentives approved by the...

  7. Regulatory Challenges for Cartilage Repair Technologies.

    PubMed

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

  8. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  9. Pharma Success in Product Development—Does Biotechnology Change the Paradigm in Product Development and Attrition.

    PubMed

    Evens, Ronald P

    2016-01-01

    The biotechnology segment of the overall biopharma industry has existed for only about 40–45 years, as a driver of new product development. This driving force was initiated with the FDA approval of recombinant human insulin in 1982, originating from the Genentech company. The pharma industry in the early years of 1970s and 1980s engaged with biotechnology companies only to a small extent with their in-licensing of a few recombinant molecules, led by Roche, Eli Lilly, and Johnson and Johnson. However, subsequently and dramatically over the last 25 years, biotechnology has become a primary driver of product and technology innovation and has become a cornerstone in new product development by all biopharma companies. This review demonstrates these evolutionary changes regarding approved products, product pipelines, novelty of the products, FDA approval rates, product sales, financial R&D investments in biotechnology, partnerships, mergers and acquisitions, and patent issues. We now have about 300 biotechnology products approved in USA covering 16 medical disciplines and about 250 indications, with the engagement of 25 pharma companies, along with their biotechnology company innovators and partners. The biotechnology pipeline involves over 1000 molecules in clinical trials, including over 300 molecules associated with the top 10 pharma companies. Product approval rates by the FDA for biotechnology products are over double the rate for drugs. Yes, the R&D paradigm has changed with biotechnology now as one of the major focuses for new product development with novel molecules by the whole biopharma industry.

  10. 30 CFR 7.49 - Approval marking.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Battery Assemblies § 7.49 Approval marking. Each approved battery assembly shall be identified by a legible and permanent approval plate inscribed with the assigned MSHA approval number and securely attached to the battery box. ...

  11. 30 CFR 7.49 - Approval marking.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Battery Assemblies § 7.49 Approval marking. Each approved battery assembly shall be identified by a legible and permanent approval plate inscribed with the assigned MSHA approval number and securely attached to the battery box. ...

  12. 30 CFR 7.49 - Approval marking.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Battery Assemblies § 7.49 Approval marking. Each approved battery assembly shall be identified by a legible and permanent approval plate inscribed with the assigned MSHA approval number and securely attached to the battery box. ...

  13. 78 FR 7442 - Accreditation and Approval of Chemical and Petrochemical Inspections, LP, as a Commercial Gauger...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    ... approved to gauge and accredited to test petroleum and petroleum products, organic chemicals and vegetable... approved to gauge and accredited to test petroleum and petroleum products, organic chemicals and vegetable... Chemical and Petrochemical Inspections, LP, as a Commercial Gauger and Laboratory AGENCY: U.S. Customs and...

  14. 78 FR 66758 - Accreditation and Approval of AMSPEC Services, LLC, as a Commercial Gauger

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ... approved to gauge petroleum and petroleum products, organic chemicals and vegetable oils for customs... INFORMATION: Notice is hereby given pursuant to 19 CFR 151.13, AmSpec Services, LLC, Chemical Division, 11725 Port Road, Seabrook, TX 77586, has been approved to gauge petroleum and petroleum products, organic...

  15. 9 CFR 147.48 - Approval of conference recommendations by the Department.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Approval of conference recommendations by the Department. 147.48 Section 147.48 Animals and Animal Products ANIMAL AND PLANT HEALTH... Department for incorporation into the provisions of the NPIP. The Department reserves the right to approve or...

  16. 9 CFR 147.48 - Approval of conference recommendations by the Department.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Approval of conference recommendations by the Department. 147.48 Section 147.48 Animals and Animal Products ANIMAL AND PLANT HEALTH... Department for incorporation into the provisions of the NPIP. The Department reserves the right to approve or...

  17. 9 CFR 147.48 - Approval of conference recommendations by the Department.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Approval of conference recommendations by the Department. 147.48 Section 147.48 Animals and Animal Products ANIMAL AND PLANT HEALTH... Department for incorporation into the provisions of the NPIP. The Department reserves the right to approve or...

  18. 9 CFR 147.48 - Approval of conference recommendations by the Department.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Approval of conference recommendations by the Department. 147.48 Section 147.48 Animals and Animal Products ANIMAL AND PLANT HEALTH... Department for incorporation into the provisions of the NPIP. The Department reserves the right to approve or...

  19. 78 FR 40090 - Notice of Request for Revision of a Currently Approved Information Collection (Interstate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-03

    ... Request for Revision of a Currently Approved Information Collection (Interstate Shipment of Meat and...: Interstate Shipment of Meat and Poultry Products. Type of Request: Revision of an approved information... Federal Meat Inspection Act (FMIA) (21 U.S.C. 601, et seq.) and the Poultry Products Inspection Act (PPIA...

  20. 75 FR 65565 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-26

    ... 558 [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications; Aklomide; Levamisole Hydrochloride; Nitromide and Sulfanitran AGENCY...) is amending the animal drug regulations by removing those portions that reflect approval of eight new...

  1. 27 CFR 24.26 - Authority to approve.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Authority to approve. 24.26 Section 24.26 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU...)) (Approved by the Office of Management and Budget under control number 1512-0292) [T.D. ATF-299, 55 FR 24989...

  2. 27 CFR 24.26 - Authority to approve.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Authority to approve. 24.26 Section 24.26 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU...)) (Approved by the Office of Management and Budget under control number 1512-0292) [T.D. ATF-299, 55 FR 24989...

  3. 46 CFR 160.040-5 - Approval and production tests.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Rocket Type (and Equipment) § 160.040-5 Approval and production tests. (a) Approval tests. An independent... lot of rockets which fails the inspections and tests must not be represented as meeting this subpart... rockets at least once each year. The inspection must determine that the appliances and rockets are being...

  4. 46 CFR 160.040-5 - Approval and production tests.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Rocket Type (and Equipment) § 160.040-5 Approval and production tests. (a) Approval tests. An independent... lot of rockets which fails the inspections and tests must not be represented as meeting this subpart... rockets at least once each year. The inspection must determine that the appliances and rockets are being...

  5. 46 CFR 160.040-5 - Approval and production tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Rocket Type (and Equipment) § 160.040-5 Approval and production tests. (a) Approval tests. An independent... lot of rockets which fails the inspections and tests must not be represented as meeting this subpart... rockets at least once each year. The inspection must determine that the appliances and rockets are being...

  6. 46 CFR 160.040-5 - Approval and production tests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Rocket Type (and Equipment) § 160.040-5 Approval and production tests. (a) Approval tests. An independent... lot of rockets which fails the inspections and tests must not be represented as meeting this subpart... rockets at least once each year. The inspection must determine that the appliances and rockets are being...

  7. 46 CFR 160.040-5 - Approval and production tests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Rocket Type (and Equipment) § 160.040-5 Approval and production tests. (a) Approval tests. An independent... lot of rockets which fails the inspections and tests must not be represented as meeting this subpart... rockets at least once each year. The inspection must determine that the appliances and rockets are being...

  8. 75 FR 62615 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Order Granting Accelerated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... Silver Trust \\8\\ and ETFS Gold Trust.\\9\\ The Commission also has previously approved listing on the Exchange of shares of the Sprott Physical Gold Trust, streetTRACKS Gold Trust, and iShares COMEX Gold Trust...

  9. 40 CFR 153.155 - Seed treatment products.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... products. (a) Pesticide products intended for use in treating seeds must contain an EPA-approved dye to... established under the Federal Food, Drug and Cosmetic Act for residues of the pesticide. (b) The following... the user to add an EPA-approved dye with the pesticide during the seed treatment process. (2) Products...

  10. 40 CFR 153.155 - Seed treatment products.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... products. (a) Pesticide products intended for use in treating seeds must contain an EPA-approved dye to... established under the Federal Food, Drug and Cosmetic Act for residues of the pesticide. (b) The following... the user to add an EPA-approved dye with the pesticide during the seed treatment process. (2) Products...

  11. 40 CFR 153.155 - Seed treatment products.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... products. (a) Pesticide products intended for use in treating seeds must contain an EPA-approved dye to... established under the Federal Food, Drug and Cosmetic Act for residues of the pesticide. (b) The following... the user to add an EPA-approved dye with the pesticide during the seed treatment process. (2) Products...

  12. 45 CFR 1201.5 - Testimony and production of documents prohibited unless approved by appropriate Corporation...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Testimony and production of documents prohibited... Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE PRODUCTION OR... and production of documents prohibited unless approved by appropriate Corporation officials. (a...

  13. 22 CFR 172.4 - Testimony and production of documents prohibited unless approved by appropriate Department...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Testimony and production of documents... DEPARTMENT OF STATE ACCESS TO INFORMATION SERVICE OF PROCESS; PRODUCTION OR DISCLOSURE OF OFFICIAL... § 172.4 Testimony and production of documents prohibited unless approved by appropriate Department...

  14. 7 CFR 70.34 - Application for grading service in official plants; approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF POULTRY PRODUCTS AND RABBIT PRODUCTS Grading of Poultry Products and Rabbit Products Application for Grading Service § 70.34 Application for grading service in... plant survey for poultry or rabbit grading has been completed and approved in accordance with the...

  15. 7 CFR 70.34 - Application for grading service in official plants; approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF POULTRY PRODUCTS AND RABBIT PRODUCTS Grading of Poultry Products and Rabbit Products Application for Grading Service § 70.34 Application for grading service in... plant survey for poultry or rabbit grading has been completed and approved in accordance with the...

  16. 9 CFR 381.132 - Labeling approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Labeling approval. 381.132 Section 381.132 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POULTRY PRODUCTS INSPECTION...

  17. 9 CFR 381.133 - Generically approved labeling.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Generically approved labeling. 381.133 Section 381.133 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POULTRY PRODUCT...

  18. 9 CFR 592.330 - Unauthorized use or disposition of approved labels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Unauthorized use or disposition of approved labels. 592.330 Section 592.330 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and...

  19. 9 CFR 592.140 - Application for inspection in official plants; approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Application for inspection in official plants; approval. 592.140 Section 592.140 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Application for...

  20. 30 CFR 6.1 - Purpose and effective date.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY... based on non-MSHA product safety standards once MSHA has determined that the non-MSHA standards are equivalent to MSHA's applicable product approval requirements or can be modified to provide at least the same...

  1. 30 CFR 6.1 - Purpose and effective date.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY... based on non-MSHA product safety standards once MSHA has determined that the non-MSHA standards are equivalent to MSHA's applicable product approval requirements or can be modified to provide at least the same...

  2. 30 CFR 6.1 - Purpose and effective date.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY... based on non-MSHA product safety standards once MSHA has determined that the non-MSHA standards are equivalent to MSHA's applicable product approval requirements or can be modified to provide at least the same...

  3. 30 CFR 6.1 - Purpose and effective date.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING AND EVALUATION BY INDEPENDENT LABORATORIES AND NON-MSHA PRODUCT SAFETY... based on non-MSHA product safety standards once MSHA has determined that the non-MSHA standards are equivalent to MSHA's applicable product approval requirements or can be modified to provide at least the same...

  4. A Statistical Perspective on Highly Accelerated Testing

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

    Thomas, Edward V.

    Highly accelerated life testing has been heavily promoted at Sandia (and elsewhere) as a means to rapidly identify product weaknesses caused by flaws in the product's design or manufacturing process. During product development, a small number of units are forced to fail at high stress. The failed units are then examined to determine the root causes of failure. The identification of the root causes of product failures exposed by highly accelerated life testing can instigate changes to the product's design and/or manufacturing process that result in a product with increased reliability. It is widely viewed that this qualitative use ofmore » highly accelerated life testing (often associated with the acronym HALT) can be useful. However, highly accelerated life testing has also been proposed as a quantitative means for "demonstrating" the reliability of a product where unreliability is associated with loss of margin via an identified and dominating failure mechanism. It is assumed that the dominant failure mechanism can be accelerated by changing the level of a stress factor that is assumed to be related to the dominant failure mode. In extreme cases, a minimal number of units (often from a pre-production lot) are subjected to a single highly accelerated stress relative to normal use. If no (or, sufficiently few) units fail at this high stress level, some might claim that a certain level of reliability has been demonstrated (relative to normal use conditions). Underlying this claim are assumptions regarding the level of knowledge associated with the relationship between the stress level and the probability of failure. The primary purpose of this document is to discuss (from a statistical perspective) the efficacy of using accelerated life testing protocols (and, in particular, "highly accelerated" protocols) to make quantitative inferences concerning the performance of a product (e.g., reliability) when in fact there is lack-of-knowledge and uncertainty concerning the assumed relationship between the stress level and performance. In addition, this document contains recommendations for conducting more informative accelerated tests.« less

  5. Similar pharmacokinetics and pharmacodynamics of rapid-acting insulin lispro products SAR342434 and US- and EU-approved Humalog in subjects with type 1 diabetes.

    PubMed

    Kapitza, Christoph; Nowotny, Irene; Lehmann, Anne; Bergmann, Karin; Rotthaeuser, Baerbel; Nosek, Leszek; Becker, Reinhard H A

    2017-05-01

    To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 3 rapid-acting insulin lispro products: SAR342434 solution, United States (US)-approved Humalog and European Union (EU)-approved Humalog. In a single-centre, randomized, double-blind, 3-treatment, 3-period, 6-sequence, crossover, euglycaemic clamp study (NCT02273258), adult male subjects with type 1 diabetes were randomized to receive 0.3 U/kg of SAR342434 solution, US-approved and EU-approved Humalog under fasted conditions. PK and PD (glucose infusion rate [GIR]) were assessed up to 12 hours. Of the 30 subjects randomized, 28 completed all 3 treatment periods. Mean concentration and GIR vs time profiles were similar for all 3 products. Exposure (INS-C max , INS-AUC last and INS-AUC) and activity (GIR max and GIR-AUC 0-12h ) of SAR342434, US-approved and EU-approved Humalog were similar in all comparisons (point estimates of treatment ratios, 0.95-1.03 for PK parameters and 1.00-1.07 for PD parameters), with 90% confidence intervals for the ratios of geometric least squares means within the pre-specified bioequivalence limit (0.80-1.25) and no significant differences in time-related parameters. Within-subject variability of exposure and activity was low across the 3 clamps, indicating high day-to-day reproducibility in clamp performance, irrespective of the individual product. Adverse events were similar for all 3 products. No safety concerns were noted in vital signs or in laboratory and electrocardiogram data. The results of this study demonstrate similarity in insulin lispro exposure profiles and PD activity of SAR342434 solution to both US- and EU-approved Humalog, and between both US- and EU-approved Humalog, supporting the use of SAR342434 solution for injection as a follow-on product. © 2016 John Wiley & Sons Ltd.

  6. Spatial Relationships of Auroral Particle Acceleration Relative to High Latitude Plasma Boundaries

    NASA Technical Reports Server (NTRS)

    Ghielmetti, Arthur G.

    1997-01-01

    This final report describes the activities under NASA contract to Lockheed Missiles and Space Company. It covers the period from 10-1-94 to 12-31-97. The objective of this investigation is to identify and characterize the spatial relationships of auroral particle acceleration features relative to the characteristic transition features in the surrounding polar ionospheric plasmas. Due to the reduced funding level approved for this contract, the original scope of the proposed work was readjusted with the focus placed on examining spatial relationships with respect to particle structures.

  7. 9 CFR 592.330 - Unauthorized use or disposition of approved labels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Unauthorized use or disposition of approved labels. 592.330 Section 592.330 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.330 Unauthorized use...

  8. 9 CFR 592.330 - Unauthorized use or disposition of approved labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Unauthorized use or disposition of approved labels. 592.330 Section 592.330 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.330 Unauthorized use...

  9. 9 CFR 592.330 - Unauthorized use or disposition of approved labels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Unauthorized use or disposition of approved labels. 592.330 Section 592.330 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.330 Unauthorized use...

  10. 9 CFR 592.330 - Unauthorized use or disposition of approved labels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Unauthorized use or disposition of approved labels. 592.330 Section 592.330 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Identifying and Marking Products § 592.330 Unauthorized use...

  11. Regulatory Challenges for Cartilage Repair Technologies

    PubMed Central

    Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)–approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product’s attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible. PMID:26069647

  12. mAbs

    PubMed Central

    2009-01-01

    The twenty two monoclonal antibodies (mAbs) currently marketed in the U.S. have captured almost half of the top-20 U.S. therapeutic biotechnology sales for 2007. Eight of these products have annual sales each of more than $1 B, were developed in the relatively short average period of six years, qualified for FDA programs designed to accelerate drug approval, and their cost has been reimbursed liberally by payers. With growth of the product class driven primarily by advancements in protein engineering and the low probability of generic threats, mAbs are now the largest class of biological therapies under development. The high cost of these drugs and the lack of generic competition conflict with a financially stressed health system, setting reimbursement by payers as the major limiting factor to growth. Advances in mAb engineering are likely to result in more effective mAb drugs and an expansion of the therapeutic indications covered by the class. The parallel development of biomarkers for identifying the patient subpopulations most likely to respond to treatment may lead to a more cost-effective use of these drugs. To achieve the success of the current top-tier mAbs, companies developing new mAb products must adapt to a significantly more challenging commercial environment. PMID:20061824

  13. 78 FR 66757 - Accreditation and Approval of Amspec Services, LLC, as a Commercial Gauger and Laboratory

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ... Services, LLC, has been approved to gauge and accredited to test petroleum and petroleum products, organic chemicals and vegetable oils for customs purposes for the next three years as of February 20, 2013. DATES... 07036, has been approved to gauge and accredited to test petroleum and petroleum products, organic...

  14. 78 FR 6828 - Accreditation and Approval of Saybolt LP, as a Commercial Gauger and Laboratory

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ... been approved to gauge and accredited to test petroleum and petroleum products, organic chemicals and... 90810, has been approved to gauge and accredited to test petroleum and petroleum products, organic chemicals and vegetable oils for customs purposes, in accordance with the provisions of 19 CFR 151.12 and 19...

  15. 40 CFR 60.17 - Incorporations by reference.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... in Petroleum Products (General Bomb Method), IBR approved for §§ 60.106(j)(2), 60.335(b)(10)(i), and... Petroleum Products (General Bomb Method), IBR approved for § 60.4415(a)(1)(i). (10) ASTM D240-76, 92, Standard Test Method for Heat of Combustion of Liquid Hydrocarbon Fuels by Bomb Calorimeter, IBR approved...

  16. 30 CFR 18.93 - Application for field approval; filing procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Application for field approval; filing... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.93 Application for field approval; filing...

  17. 30 CFR 18.93 - Application for field approval; filing procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Application for field approval; filing... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.93 Application for field approval; filing...

  18. [Comparison and review on specifications of fermented Cordyceps sinensis products].

    PubMed

    Yang, Ping; Zhao, Xiao-Xia; Zhang, Yong-Wen

    2018-02-01

    There are five kinds of fermented Cordyceps crude drug and their preparations that have been approved as medicine on the market. Since the initial strains of the crude drug were all isolated from natural Cordyceps sinensis， they have similar names， chemical components and even clinical applications. However， because of the different strain species and fermentation processes， there was significant difference in quality. As a result， they should be clearly distinguished in clinical use. Most of the products were researched and developed during the 1980s and 1990s， so there was difference in quality standards for different products， and their quality control levels of some products were not perfect. At present， some of the products are approved as Chinese medicine， others are approved as chemical drugs， with a confusion in products name， management and clinical application. In this paper， the approval numbers， quality standards and clinical applications， and current problems of these products were summarized and compared; some suggestions were put forward， such as standardizing the product name， unifying the management of approval number category， and increasing the specific quality control attributes， in order to provide reference for standard implementation， quality control and drug regulation for fermented Cordyceps crude drugs and their preparations. Copyright© by the Chinese Pharmaceutical Association.

  19. Corona-Solar Wind Coupling Review

    DTIC Science & Technology

    1987-06-01

    been reviewed and is approved for publication" E. G. Mullen E. G. Mullen Contract Manager Chief, Space Particles Environment Branch FOR THR COIN 1a...modeled, partly because the acceleration mechanism is still under study. Conclusions This review has been a survey of the current state of knowlede of

  20. Piezoelectric Non-linear Nanomechanical Temperature and Acceleration Intensive Clocks (PENNTAC)

    DTIC Science & Technology

    2014-05-01

    ways to mitigate the resonator flicker noise will be identified. 8 Approved for public release; distribution unlimited. Figure 8: (Top...2 3.0 Mitigation of Anchor Losses and Interfacial Dissipation in AlN Contour-Mode Resonators...6 3.2 1/f Resonator Flicker Noise

  1. Renewal: New Aspects of Acceleration and Transport of Solar Energetic Particles (SEPs) from the Sun to the Earth

    DTIC Science & Technology

    2014-10-31

    Hole .......................................................4 2. SOHO EIT Image with Coronal Holes and FPA Vector...Diagram of CME Deflection by a Coronal Hole Figure 2: SOHO EIT Image with Coronal Holes and FPA Vector Approved for public release; distribution

  2. 12 CFR 1253.4 - New product approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... § 1253.4 New product approval. (a) Public notice. If the Director determines that the new activity is a new product, FHFA shall publish a public notice soliciting comments on the proposed product for a 30...) The Director will consider all public comments received by the closing date of the comment period. (3...

  3. 78 FR 38053 - Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

    ...] Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug Application 21-610... (oxymorphone hydrochloride (HCl)) Extended-Release Tablet products approved under new drug application (NDA) 21... refer to these drug products, and it will allow FDA to continue to approve ANDAs for oxymorphone HCl...

  4. 30 CFR 19.11 - How approvals are granted.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.11 How approvals are granted. (a) All approvals are... engineers judge that the lamp has met the requirements of the part and MSHA's records concerning the lamp...

  5. 30 CFR 19.11 - How approvals are granted.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.11 How approvals are granted. (a) All approvals are... engineers judge that the lamp has met the requirements of the part and MSHA's records concerning the lamp...

  6. 30 CFR 19.11 - How approvals are granted.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.11 How approvals are granted. (a) All approvals are... engineers judge that the lamp has met the requirements of the part and MSHA's records concerning the lamp...

  7. 30 CFR 19.11 - How approvals are granted.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.11 How approvals are granted. (a) All approvals are... engineers judge that the lamp has met the requirements of the part and MSHA's records concerning the lamp...

  8. 30 CFR 19.11 - How approvals are granted.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.11 How approvals are granted. (a) All approvals are... engineers judge that the lamp has met the requirements of the part and MSHA's records concerning the lamp...

  9. 30 CFR 19.12 - Wording, purpose, and use of approval plate.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.12 Wording, purpose, and use of approval... Administration and be inscribed as follows: “Permissible Electric Cap Lamp. Approval No. ____ issued to the...

  10. Off-label use of medical products in radiation therapy: Summary of the Report of AAPM Task Group No. 121

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

    Thomadsen, Bruce R.; Thompson, Heaton H. II; Jani, Shirish K.

    Medical products (devices, drugs, or biologics) contain information in their labeling regarding the manner in which the manufacturer has determined that the products can be used in a safe and effective manner. The Food and Drug Administration (FDA) approves medical products for use for these specific indications which are part of the medical product's labeling. When medical products are used in a manner not specified in the labeling, it is commonly referred to as off-label use. The practice of medicine allows for this off-label use to treat individual patients, but the ethical and legal implications for such unapproved use canmore » be confusing. Although the responsibility and, ultimately, the liability for off-label use often rests with the prescribing physician, medical physicists and others are also responsible for the safe and proper use of the medical products. When these products are used for purposes other than which they were approved, it is important for medical physicists to understand their responsibilities. In the United States, medical products can only be marketed if officially cleared, approved, or licensed by the FDA; they can be used if they are not subject to or specifically exempt from FDA regulations, or if they are being used in research with the appropriate regulatory safeguards. Medical devices are either cleared or approved by FDA's Center for Devices and Radiological Health. Drugs are approved by FDA's Center for Drug Evaluation and Research, and biological products such as vaccines or blood are licensed under a biologics license agreement by FDA's Center for Biologics Evaluation and Research. For the purpose of this report, the process by which the FDA eventually clears, approves, or licenses such products for marketing in the United States will be referred to as approval. This report summarizes the various ways medical products, primarily medical devices, can legally be brought to market in the United States, and includes a discussion of the approval process, along with manufacturers' responsibilities, labeling, marketing and promotion, and off-label use. This is an educational and descriptive report and does not contain prescriptive recommendations. This report addresses the role of the medical physicist in clinical situations involving off-label use. Case studies in radiation therapy are presented. Any mention of commercial products is for identification only; it does not imply recommendations or endorsements of any of the authors or the AAPM. The full report, containing extensive background on off-label use with several appendices, is available on the AAPM website (http://www.aapm.org/pubs/reports/).« less

  11. 9 CFR 590.411 - Requirement of formulas and approval of labels for use in official egg products plants.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... products than for bulk packaged egg products not for sale or distribution to household consumers, label... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Requirement of formulas and approval of labels for use in official egg products plants. 590.411 Section 590.411 Animals and Animal...

  12. 9 CFR 590.411 - Requirement of formulas and approval of labels for use in official egg products plants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... products than for bulk packaged egg products not for sale or distribution to household consumers, label... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Requirement of formulas and approval of labels for use in official egg products plants. 590.411 Section 590.411 Animals and Animal...

  13. 12 CFR 1253.8 - Availability of new product to an Enterprise after it has been approved for the other Enterprise.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Availability of new product to an Enterprise... HOUSING FINANCE AGENCY ENTERPRISES PRIOR APPROVAL FOR ENTERPRISE PRODUCTS § 1253.8 Availability of new... a new product for one Enterprise or the new product is otherwise available to that Enterprise under...

  14. Need for certification of household water treatment products: examples from Haiti.

    PubMed

    Murray, Anna; Pierre-Louis, Jocelyne; Joseph, Flaurine; Sylvain, Ginelove; Patrick, Molly; Lantagne, Daniele

    2015-04-01

    To evaluate four household water treatment (HWT) products currently seeking approval for distribution in Haiti, through the application of a recently-developed national HWT product certification process. Four chemical treatment products were evaluated against the certification process validation stage by verifying international product certifications confirming treatment efficacy and reviewing laboratory efficacy data against WHO HWT microbiological performance targets; and against the approval stage by confirming product composition, evaluating treated water chemical content against national and international drinking water quality guidelines and reviewing packaging for dosing ability and usage directions in Creole. None of the four evaluated products fulfilled validation or approval stage requirements. None was certified by an international agency as efficacious for drinking water treatment, and none had data demonstrating its ability to meet WHO HWT performance targets. All product sample compositions differed from labelled composition by >20%, and no packaging included complete usage directions in Creole. Product manufacturers provided information that was inapplicable, did not demonstrate product efficacy, and was insufficient to ensure safe product use. Capacity building is needed with country regulatory agencies to objectively evaluate HWT products. Products should be internationally assessed against WHO performance targets and also locally approved, considering language, culture and usability, to ensure effective HWT. © 2014 John Wiley & Sons Ltd.

  15. Need for certification of household water treatment products: examples from Haiti

    PubMed Central

    Murray, Anna; Pierre-Louis, Jocelyne; Joseph, Flaurine; Sylvain, Ginelove; Patrick, Molly; Lantagne, Daniele

    2015-01-01

    OBJECTIVE To evaluate four household water treatment (HWT) products currently seeking approval for distribution in Haiti, through the application of a recently-developed national HWT product certification process. METHODS Four chemical treatment products were evaluated against the certification process validation stage by verifying international product certifications confirming treatment efficacy and reviewing laboratory efficacy data against WHO HWT microbiological performance targets; and against the approval stage by confirming product composition, evaluating treated water chemical content against national and international drinking water quality guidelines and reviewing packaging for dosing ability and usage directions in Creole. RESULTS None of the four evaluated products fulfilled validation or approval stage requirements. None was certified by an international agency as efficacious for drinking water treatment, and none had data demonstrating its ability to meet WHO HWT performance targets. All product sample compositions differed from labelled composition by >20%, and no packaging included complete usage directions in Creole. CONCLUSIONS Product manufacturers provided information that was inapplicable, did not demonstrate product efficacy, and was insufficient to ensure safe product use. Capacity building is needed with country regulatory agencies to objectively evaluate HWT products. Products should be internationally assessed against WHO performance targets and also locally approved, considering language, culture and usability, to ensure effective HWT. PMID:25441711

  16. 30 CFR 28.20 - Certificates of approval; scope of approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Certificates of approval; scope of approval. 28.20 Section 28.20 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS FUSES FOR USE WITH DIRECT CURRENT IN PROVIDING SHORT-CIRCUIT...

  17. 30 CFR 22.9 - How approvals are granted.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false How approvals are granted. 22.9 Section 22.9 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.9 How approvals are granted. All approvals are...

  18. 9 CFR 147.52 - Approved tests.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Approved tests. 147.52 Section 147.52... Approved Tests § 147.52 Approved tests. (a) The procedures for the bacteriological examination of poultry and poultry environments described in this part are approved tests for use in the NPIP. In addition...

  19. 9 CFR 147.52 - Approved tests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Approved tests. 147.52 Section 147.52... Approved Tests § 147.52 Approved tests. (a) The procedures for the bacteriological examination of poultry and poultry environments described in this part are approved tests for use in the NPIP. In addition...

  20. 30 CFR 18.4 - Electrical equipment for which approval is issued.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES General Provisions § 18.4 Electrical equipment for which approval is issued. An approval will be issued... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical equipment for which approval is...

  1. 76 FR 58462 - Information Collection; Qualified Products List for Water Enhancers (Gels) for Wildland Firefighting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... DEPARTMENT OF AGRICULTURE Forest Service Information Collection; Qualified Products List for Water... approved information collection, Qualified Products List for Water Enhancers (Gels) for Wildland... Water Enhancers (Gels) for Wildland Firefighting. OMB Number: 0596-0182. Expiration Date of Approval...

  2. 48 CFR 4.1302 - Acquisition of approved products and services for personal identity verification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... products and services for personal identity verification. 4.1302 Section 4.1302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Personal Identity Verification 4.1302 Acquisition of approved products and services for personal identity verification. (a) In...

  3. 76 FR 15953 - Agency Information Collection Activities; Announcement of Office of Management and Budget...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... CONSUMER PRODUCT SAFETY COMMISSION Agency Information Collection Activities; Announcement of Office of Management and Budget Approval; Publicly Available Consumer Product Safety Information Database... Product Safety Information Database has been approved by the Office of Management and Budget (OMB) under...

  4. 48 CFR 4.1302 - Acquisition of approved products and services for personal identity verification.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... products and services for personal identity verification. 4.1302 Section 4.1302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Personal Identity Verification 4.1302 Acquisition of approved products and services for personal identity verification. (a) In...

  5. 48 CFR 4.1302 - Acquisition of approved products and services for personal identity verification.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... products and services for personal identity verification. 4.1302 Section 4.1302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Personal Identity Verification 4.1302 Acquisition of approved products and services for personal identity verification. (a) In...

  6. 48 CFR 4.1302 - Acquisition of approved products and services for personal identity verification.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... products and services for personal identity verification. 4.1302 Section 4.1302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Personal Identity Verification 4.1302 Acquisition of approved products and services for personal identity verification. (a) In...

  7. 48 CFR 4.1302 - Acquisition of approved products and services for personal identity verification.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... products and services for personal identity verification. 4.1302 Section 4.1302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Personal Identity Verification 4.1302 Acquisition of approved products and services for personal identity verification. (a) In...

  8. 30 CFR 7.311 - Approval checklist.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.311 Approval checklist. Each motor assembly bearing an MSHA approval marking shall be accompanied by a list of items necessary for maintenance of the motor assembly as approved. ...

  9. Challenges of the Health Research System in a Medical Research Institute in Iran: A Qualitative Content Analysis

    PubMed Central

    Bahadori, Mohammadkarim; Momeni, Khalil; Ravangard, Ramin; Yaghoubi, Maryam; Alimohammadzadeh, Khalil; Teymourzadeh, Ehsan; Tavana, Ali Mehrabi

    2015-01-01

    Background and Aim: Medical research institute is the main basis for knowledge production through conducting research, and paying attention to the research is one of the most important things in the scientific communities. At present, there is a large gap between knowledge production in Iran compared to that in other countries. This study aimed to identify the challenge of research system in a research institute of medical sciences in Iran. Matherials and Methods: This was a descriptive and qualitative study conducted in the first 6 months of 2013. A qualitative content analysis was conducted on 16 heads of research centers in a research institute of medical sciences. The required data were gathered using semi-structured interviews. The collected data were analyzed using MAXQDA 10.0 software. Results: Six themes identified as challenges of research system. The themes included barriers related to the design and development, and approval of research projects, the implementation of research projects, the administrative and managerial issues in the field of research, the personal problems, publishing articles, and guidelines and recommendations. Conclusion: Based on the results of the present study, the following suggestions can be offered: pushing the research towards solving the problems of society, employing the strong executive and scientific reseach directors in the field of research, providing training courses for researchers on how to write proposals, implementing administrative reforms in the Deputy of Research and Technology, accelerating the approval of the projects through automating the administrative and peer-reviewing processes. PMID:25560335

  10. 7 CFR 58.343 - Storage of finished product in coolers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (CONTINUED) GRADING AND INSPECTION, GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading... ready for distribution or shipment. The products shall not be placed directly on floors or exposed to...

  11. 77 FR 63800 - Proposed Extension of Approval of Information Collection; Comment Request-Safety Standard for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... CONSUMER PRODUCT SAFETY COMMISSION Proposed Extension of Approval of Information Collection; Comment Request--Safety Standard for Walk-Behind Power Lawn Mowers AGENCY: Consumer Product Safety.... Chapter 35), the Consumer Product Safety Commission (CPSC) requested comments on a proposed extension of...

  12. 9 CFR 355.34 - Labels, approval of, by Administrator.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Labels, approval of, by Administrator. 355.34 Section 355.34 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION...

  13. 75 FR 29787 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting Accelerated Approval of Proposed Rule Change To Permit $1 Strikes for Options on Trust Issued Receipts May 20, 2010. I. Introduction On April 13, 2010, the Chicago Board Options Exchange, Incorporated (``CBOE'' or ``Exchange...

  14. 14 CFR 29.549 - Fuselage and rotor pylon structures.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... flight conditions, must be considered. (c) Each engine mount and adjacent fuselage structure must be designed to withstand the loads occurring under accelerated flight and landing conditions, including engine torque. (d) [Reserved] (e) If approval for the use of 21/2-minute OEI power is requested, each engine...

  15. 14 CFR 29.549 - Fuselage and rotor pylon structures.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... flight conditions, must be considered. (c) Each engine mount and adjacent fuselage structure must be designed to withstand the loads occurring under accelerated flight and landing conditions, including engine torque. (d) [Reserved] (e) If approval for the use of 21/2-minute OEI power is requested, each engine...

  16. 14 CFR 29.549 - Fuselage and rotor pylon structures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... flight conditions, must be considered. (c) Each engine mount and adjacent fuselage structure must be designed to withstand the loads occurring under accelerated flight and landing conditions, including engine torque. (d) [Reserved] (e) If approval for the use of 21/2-minute OEI power is requested, each engine...

  17. 14 CFR 29.549 - Fuselage and rotor pylon structures.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... flight conditions, must be considered. (c) Each engine mount and adjacent fuselage structure must be designed to withstand the loads occurring under accelerated flight and landing conditions, including engine torque. (d) [Reserved] (e) If approval for the use of 21/2-minute OEI power is requested, each engine...

  18. 14 CFR 29.549 - Fuselage and rotor pylon structures.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... flight conditions, must be considered. (c) Each engine mount and adjacent fuselage structure must be designed to withstand the loads occurring under accelerated flight and landing conditions, including engine torque. (d) [Reserved] (e) If approval for the use of 21/2-minute OEI power is requested, each engine...

  19. 78 FR 16752 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; International...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-18

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69124; File Nos. SR-CBOE-2013-016; SR-ISE-2013... Securities Exchange, LLC; Order Granting Accelerated Approval of Proposed Rule Changes To Permit the Minimum... Security March 12, 2013. I. Introduction On January 31, 2013, Chicago Board Options Exchange, Incorporated...

  20. Evaluating and Selecting Sport Management Undergraduate Programs.

    ERIC Educational Resources Information Center

    Cuneen, Jacquelyn; Sidwell, M. Joy

    1998-01-01

    States that the accelerated growth of sport management undergraduate programs that began in the 1980s has continued into the current decade. There are currently 180 sport management major programs in American colleges and universities. Describes the sports management approval process and suggests useful strategies to evaluate sport management…

  1. 77 FR 21880 - Federal Housing Administration (FHA): Multifamily Accelerated Processing-Enhancing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... applications for FHA multifamily mortgage insurance, which generally involve the refinance, purchase, new... to date through direct instructions to FHA-approved lenders under a MAP Guide. Given its experience... mortgage insurance programs. Based on HUD's experience to date with MAP, this proposed rule strives not...

  2. 9 CFR 592.140 - Application for inspection in official plants; approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Application for inspection in official plants; approval. 592.140 Section 592.140 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Application for Service § 592.140 Application for...

  3. 9 CFR 592.140 - Application for inspection in official plants; approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Application for inspection in official plants; approval. 592.140 Section 592.140 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Application for Service § 592.140 Application for...

  4. 9 CFR 592.140 - Application for inspection in official plants; approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Application for inspection in official plants; approval. 592.140 Section 592.140 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Application for Service § 592.140 Application for...

  5. 9 CFR 592.140 - Application for inspection in official plants; approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Application for inspection in official plants; approval. 592.140 Section 592.140 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Application for Service § 592.140 Application for...

  6. 78 FR 66759 - Approval of American Cargo Assurance, as a Commercial Gauger

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ... gauge petroleum, petroleum products, organic chemicals and vegetable oils for customs purposes for the... 70663, has been approved to gauge petroleum, petroleum products, organic chemicals and vegetable oils...

  7. Drug Discovery Prospect from Untapped Species: Indications from Approved Natural Product Drugs

    PubMed Central

    Qin, Chu; Tao, Lin; Liu, Xin; Shi, Zhe; Zhang, Cun Long; Tan, Chun Yan; Chen, Yu Zong; Jiang, Yu Yang

    2012-01-01

    Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery. PMID:22808057

  8. 30 CFR 22.10 - Approval plate.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.10 Approval plate. (a) Attachment to be made by manufacturers. (1) Manufacturers shall attach, stamp, or mold an approval plate on each permissible methane... follows: Permissible Methane Detector (or Permissible Methane Indicating Detector) Approval No. ___ issued...

  9. 42 CFR 447.502 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... NDA and a covered outpatient drug approved under a product license approval (PLA), establishment... covered outpatient drug approved under a biological license application, PLA, ELA, or ADA. States means...

  10. 30 CFR 22.9 - How approvals are granted.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.9 How approvals are granted. All approvals are granted by official letter from MSHA. A detector will be approved under this part only when the testing..., including drawings from the manufacturer that show the detector as it is to be commercially made. No verbal...

  11. 30 CFR 22.9 - How approvals are granted.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.9 How approvals are granted. All approvals are granted by official letter from MSHA. A detector will be approved under this part only when the testing..., including drawings from the manufacturer that show the detector as it is to be commercially made. No verbal...

  12. 30 CFR 22.9 - How approvals are granted.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.9 How approvals are granted. All approvals are granted by official letter from MSHA. A detector will be approved under this part only when the testing..., including drawings from the manufacturer that show the detector as it is to be commercially made. No verbal...

  13. 30 CFR 22.9 - How approvals are granted.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.9 How approvals are granted. All approvals are granted by official letter from MSHA. A detector will be approved under this part only when the testing..., including drawings from the manufacturer that show the detector as it is to be commercially made. No verbal...

  14. Bioactive natural products in cancer prevention and therapy: Progress and promise.

    PubMed

    Bishayee, Anupam; Sethi, Gautam

    2016-10-01

    Natural products represent a rich source for the discovery and development of cancer preventive and anticancer drugs. Nearly, 80% of all drugs approved by the United States Food and Drug Administration during the last three decades for cancer therapy are either natural products per se or are based thereon, or mimicked natural products in one form or another. With the advent and refinement of new technologies, such as genetic techniques for production of secondary plant metabolites, combinatorial synthesis and high-throughput screening, it is expected that novel compounds from natural sources, including medicinal plants, would be identified and developed as safe and effective chemopreventive and anticancer drugs. Numerous bioactive natural compounds have been shown to be useful in prevention and therapy of cancer by targeting various signaling molecules and pathways. Extensive literature underscores the anticancer and chemopreventive activity of a plethora of naturally occurring agents, including phytochemicals. Several of these molecules have been tested in clinical trials and some of them have shown promise in combination therapy when administered along with standard chemotherapeutic agents. Thus, accelerated chemopreventive and chemotherapeutic drug development from natural sources is of great importance. In this special theme issue, contributions from eminent scientists and scholars around the world presented critical analysis of the current progress and promise of natural bioactive constituents in cancer prevention and therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 78 FR 68997 - Approval and Promulgation of Implementation Plans; Florida; Approval of Revision to the State...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-18

    ... Production.'' EPA has determined that this provision was erroneously incorporated into the SIP. Therefore....) entitled ``Synthetic Organic Fiber Production'' was inadvertently incorporated into the Florida SIP on June... synthetic organic fiber production facilities in northwest Florida. The rule was only concerned with...

  16. 77 FR 63800 - Proposed Extension of Approval of Information Collection; Comment Request-Safety Standard for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... CONSUMER PRODUCT SAFETY COMMISSION Proposed Extension of Approval of Information Collection; Comment Request--Safety Standard for Automatic Residential Garage Door Operators AGENCY: Consumer Product... 1995 (44 U.S.C. Chapter 35), the Consumer Product Safety Commission (CPSC) requested comments on a...

  17. 10 CFR 431.303 - Materials incorporated by reference.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Transmission Properties by Means of the Heat Flow Meter Apparatus, approved May 1, 2004, IBR approved for § 431... insulation products for buildings—Factory made products of extruded polystyrene foam (XPS)—Specification..., (“DIN EN 13165”), Thermal insulation products for buildings—Factory made rigid polyurethane foam (PUR...

  18. 78 FR 26618 - Collection of Information; Proposed Extension of Approval; Comment Request-Follow-Up Activities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-07

    ... CONSUMER PRODUCT SAFETY COMMISSION [Docket No. CPSC-2009-0102] Collection of Information; Proposed Extension of Approval; Comment Request--Follow-Up Activities for Product-Related Injuries AGENCY: Consumer Product Safety Commission. ACTION: Notice. SUMMARY: As required by the Paperwork Reduction Act of 1995...

  19. 77 FR 5696 - Exceptions or Alternatives to Labeling Requirements for Products Held by the Strategic National...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-06

    ... products in the SNS that are approved, licensed, or cleared for marketing.\\2\\ Labels on investigational... the implementation of this rule, when investigational products were ultimately approved for marketing... that any statements concerning preemption can be justified under legal principles governing preemption...

  20. 78 FR 56225 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; NESHAP...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-12

    ... Submitted to OMB for Review and Approval; Comment Request; NESHAP for Plywood and Composite Products... Protection Agency has submitted an information collection request (ICR), ``NESHAP for Plywood and Composite... Composite Products covers both new and existing plywood and composite wood products (PCWP) facilities...

  1. 75 FR 47303 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-05

    ... Approval; Comment Request; NESHAP for Plywood and Composite Products (Renewal) AGENCY: Environmental... . Title: NESHAP for Plywood and Composite Products (Renewal). ICR Numbers: EPA ICR Number 1984.04, OMB... National Emission Standards for Hazardous Air Pollutants (NESHAP) for Plywood and Composite Products were...

  2. 77 FR 27591 - Labeling and Effectiveness Testing; Sunscreen Drug Products for Over-the-Counter Human Use; Delay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... products containing specified active ingredients and marketed without approved applications. It also amends... certain OTC sunscreen products containing specified active ingredients and marketed without approved... risk of skin cancer and early skin aging caused by the sun. If the timeline for implementation...

  3. 76 FR 75809 - Prior Label Approval System: Generic Label Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... tracking and reporting systems; and (4) design and implement a survey of the effects of the limited generic... and poultry product inspection programs designed to assure consumers that meat and poultry products... mandatory features are designed to ensure that meat and poultry products are accurately and truthfully...

  4. 9 CFR 112.5 - Review and approval of labeling.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Review and approval of labeling. 112.5 Section 112.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING...

  5. 9 CFR 112.5 - Review and approval of labeling.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Review and approval of labeling. 112.5 Section 112.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING...

  6. 9 CFR 112.5 - Review and approval of labeling.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Review and approval of labeling. 112.5 Section 112.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING...

  7. 9 CFR 112.5 - Review and approval of labeling.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Review and approval of labeling. 112.5 Section 112.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING...

  8. 9 CFR 112.5 - Review and approval of labeling.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Review and approval of labeling. 112.5 Section 112.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING...

  9. 77 FR 60686 - Proposed Extension of Approval of Information Collection; Comment Request-Safety Standard for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-04

    ... CONSUMER PRODUCT SAFETY COMMISSION [Docket No. CPSC-2013-0001] Proposed Extension of Approval of... AGENCY: Consumer Product Safety Commission. ACTION: Notice. SUMMARY: As required by the Paperwork Reduction Act (44 U.S.C. chapter 35), the Consumer Product Safety Commission (CPSC or Commission) requests...

  10. Overview of Accelerator Applications in Energy

    NASA Astrophysics Data System (ADS)

    Garnett, Robert W.; Sheffield, Richard L.

    An overview of the application of accelerators and accelerator technology in energy is presented. Applications span a broad range of cost, size, and complexity and include large-scale systems requiring high-power or high-energy accelerators to drive subcritical reactors for energy production or waste transmutation, as well as small-scale industrial systems used to improve oil and gas exploration and production. The enabling accelerator technologies will also be reviewed and future directions discussed.

  11. 12 CFR Appendix to Part 1253 - Prior Approval for Enterprise Products-Instructions and Notice of New Activity Form

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Approval for Enterprise Products—Instructions and Notice of New Activity Form ER02JY09.000 ER02JY09.001... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Prior Approval for Enterprise Products-Instructions and Notice of New Activity Form Appendix to Part 1253 Banks and Banking FEDERAL HOUSING FINANCE...

  12. 78 FR 52557 - Approval of SGS North America, Inc., as a Commercial Gauger

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... petroleum, petroleum products, organic chemicals and vegetable oils for customs purposes for the next three... 77541, has been approved to gauge petroleum, petroleum products, organic chemicals and vegetable oils...

  13. 78 FR 6129 - Approval of Petrospect, Inc., as a Commercial Gauger

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-29

    ..., petroleum products, organic chemicals and vegetable oils for customs purposes for the next three years as of..., Honolulu, HI 96817, has been approved to gauge petroleum, petroleum products, organic chemicals and...

  14. 12 CFR 1253.6 - Certifying and nullifying an approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... this paragraph, an Enterprise's authority to offer a new product or engage in a new activity by reason... PRODUCTS § 1253.6 Certifying and nullifying an approval. (a) An Enterprise shall certify, through an...

  15. A decade of marketing approval of gene and cell-based therapies in the United States, European Union and Japan: An evaluation of regulatory decision-making.

    PubMed

    Coppens, D G M; de Wilde, S; Guchelaar, H J; De Bruin, M L; Leufkens, H G M; Meij, P; Hoekman, J

    2018-05-02

    There is a widely held expectation of clinical advance with the development of gene and cell-based therapies (GCTs). Yet, establishing benefits and risks is highly uncertain. We examine differences in decision-making for GCT approval between jurisdictions by comparing regulatory assessment procedures in the United States (US), European Union (EU) and Japan. A cohort of 18 assessment procedures was analyzed by comparing product characteristics, evidentiary and non-evidentiary factors considered for approval and post-marketing risk management. Product characteristics are very heterogeneous and only three products are marketed in multiple jurisdictions. Almost half of all approved GCTs received an orphan designation. Overall, confirmatory evidence or indications of clinical benefit were evident in US and EU applications, whereas in Japan approval was solely granted based on non-confirmatory evidence. Due to scientific uncertainties and safety risks, substantial post-marketing risk management activities were requested in the EU and Japan. EU and Japanese authorities often took unmet medical needs into consideration in decision-making for approval. These observations underline the effects of implemented legislation in these two jurisdictions that facilitate an adaptive approach to licensing. In the US, the recent assessments of two chimeric antigen receptor-T cell (CAR-T) products are suggestive of a trend toward a more permissive approach for GCT approval under recent reforms, in contrast to a more binary decision-making approach for previous approvals. It indicates that all three regulatory agencies are currently willing to take risks by approving GCTs with scientific uncertainties and safety risks, urging them to pay accurate attention to post-marketing risk management. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  16. Developing regulatory strategy for microbicides.

    PubMed

    Nardi, Ronald; Arterburn, Linda; Carlton, Lisa

    2014-01-01

    Ever since the discovery that a virus was responsible for AIDS, prevention of HIV infection has been a drug/vaccine development target in therapeutic research. Microbicide products are a viable, globally applicable option; however, to date, no product has been approved anywhere in the world. Development of such a product will need to account for the changing disease landscape and will need to leverage available regulatory pathways to gain approvals in the developed world and emerging markets. In countries where the regulatory pathway is not clear which is the case in several emerging markets, sponsors will need to employ a flexible approach to gather and meet local regulatory requirements and ultimately gain product approvals.

  17. 30 CFR 14.9 - Disclosure of information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS General... applicant or approval holder of requests for disclosure of information concerning its conveyor belts, and...

  18. 40 CFR 152.114 - Approval of registration under FIFRA sec. 3(c)(7)-Products that contain a new active ingredient.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sec. 3(c)(7)-Products that contain a new active ingredient. 152.114 Section 152.114 Protection of...)(7)—Products that contain a new active ingredient. An application for registration of a pesticide containing an active ingredient not in any currently registered product may be conditionally approved for a...

  19. 40 CFR 152.114 - Approval of registration under FIFRA sec. 3(c)(7)-Products that contain a new active ingredient.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sec. 3(c)(7)-Products that contain a new active ingredient. 152.114 Section 152.114 Protection of...)(7)—Products that contain a new active ingredient. An application for registration of a pesticide containing an active ingredient not in any currently registered product may be conditionally approved for a...

  20. Freshwater ecosystems could become the biggest losers of the Paris Agreement.

    PubMed

    Hermoso, Virgilio

    2017-09-01

    Securing access to energy for a growing population under the international commitment of reduction of greenhouse emissions requires increasing the contribution of renewable sources to the global share. Hydropower energy, which accounts for >80% of green energy, is experiencing a boom fostered by international investment mainly in developing countries. This boom could be further accelerated by the recent climate agreement reached in Paris. Despite its flexibility, hydropower production entails social, economic and ecological risks that need to be carefully considered before investing in the development of potentially thousands of planned hydropower projects worldwide. This is especially relevant given the weak or nonexistent legislation that regulates hydropower project approval and construction in many countries. I highlight the need for adequate policy to provide the Paris Agreement with new financial and planning mechanisms to avoid further and irreversible damage to freshwater ecosystem services and biodiversity. © 2017 John Wiley & Sons Ltd.

  1. On Quantizing Ride Comfort and Allowable Accelerations

    DTIC Science & Technology

    1976-07-01

    UnImited and approved for Public release. ,.Io. 7 D5Xt4WX.AX..JL.1.X.1LJ -’a~ft IF I.,, I. ’W No 1 -0.U /cM Report) MAR 3 19M0 III. SUPPLEMENTARY NOTES...vehicle’s habitability for a given tive. This is for three main reasons: acceleration-time history. These indices are: Mankind is very variable, and even an...though the limits may not be entirely "correct" in an absolute sense,.e ~utIY* review the l~steryof an analogousawL I Hey~ f .,B 7 -tisom e To better

  2. An Analysis of the Potential Use of Red Horse Capabilities and Training Activities to Perform or Accelerate Air Force Environmental Cleanups

    DTIC Science & Technology

    1992-09-01

    capable of remediating sites contaminated with VOCs. Technologies which are innovative , emerging or not applicable are all considered to be...AD-A261 422 AFIT/GEE/CE%’/92S-’ AN" ANALYSIS OF T1’E, P’OTEN-TIAL USE OF RED HORSE CAPABILITIES AND TRAINING ACTIVITIES TO PEPFORM OR ACCELERATE AIR...Approved for public release; distribution unlimited 93 2 2-5 1󈧤 A.FIT/GEE/CEV/92S-7 AIN A.N.AýLYSIS OF THE POTENTIAL USE OF RED HORSE CAPABILITIES

  3. Recent drug approvals from the US FDA and EMEA: what the future holds.

    PubMed

    Pevarello, Paolo

    2009-04-01

    The decreased productivity of the pharmaceutical industry in terms of new medical entities approved by the US FDA and the European Medicines Agency (EMEA) on a yearly basis has long been debated. This review will analyze overall new drug applications (NDAs) approved by both the FDA and EMEA in 2007, with the aim of finding trends (also looking at the past) that can be used to predict what the future may be. After a general introduction to the regulatory terminology, NDA approvals in 2007 are divided into categories (new applications of old medicines, metabolites, enantiomers and prodrugs, biological products, natural products and small organic molecule new molecular entities) and discussed. General aspects of the NDA approvals, such as historical trends, the length of the drug-discovery process, geography, differences among therapeutic areas, and the relative role of biotech and pharma industries are also outlined. From this analysis, a perspective is gained on some aspects that will probably influence future drug approvals. The conclusion is that 2007 may represent an inflexion point, in terms of quality if not quantity of new approvals, and that the future may be brighter than previously forecast.

  4. Adaptation through Collaboration: Developing Novel Platforms to Advance the Delivery of Advanced Therapies to Patients

    PubMed Central

    Papadaki, Magdalini

    2017-01-01

    For the nascent field of advanced therapies, collaboration will be a game-changer, turning scientific progress that was once unimaginable into transformative medical practice. Despite promise for lifelong management and even cure of disease, skepticism remains about the feasibility of their delivery to patients, fueling investment risks. With the potential for long-term effectiveness in need of frequent reassessment, current approaches to predict real-life drug performance bear little relevance, necessitating novel and iterative schemes to monitoring the benefit–risk profiles throughout the life span of advanced therapies. This work explains that reinventing an adoption route for Advanced Therapy Medicinal Products is as much about the scientific and clinical components, as it is about the organizational structures, requiring an unprecedented level of interactions between stakeholders not traditionally connected; from developers and regulators, to payers, patients, and funders. By reflecting on the successes and lessons learned from the growing space of global precompetitive consortia and public–private partnerships, as well as a number of emerging accelerated development pathways, this work aims to inform the foundations for a future roadmap that can smooth the path to approval, reimbursement, and access, while delivering value to all stakeholders. Echoing the growing demands to bring these transformative products to patients, it provides critical insights to enhance our capacity in three fundamental domains: deploying the operational flexibilities offered by the growing space of collaborations, utilizing emerging flexible and accelerated pathways to tackle challenges in quantifying long-term effectiveness, and building the necessary digital and clinical infrastructure for knowledge development. PMID:28611985

  5. Simulation prediction and experiment setup of vacuum laser acceleration at Brookhaven National Lab-Accelerator Test Facility

    NASA Astrophysics Data System (ADS)

    Shao, L.; Cline, D.; Ding, X.; Ho, Y. K.; Kong, Q.; Xu, J. J.; Pogorelsky, I.; Yakimenko, V.; Kusche, K.

    2013-02-01

    This paper presents the pre-experiment plan and prediction of the first stage of vacuum laser acceleration (VLA) collaborating by UCLA, Fudan University and ATF-BNL. This first stage experiment is a proof-of-principle to support our previously posted novel VLA theory. Simulations show that based on ATF's current experimental conditions the electron beam with initial energy of 15 MeV can get net energy gain from an intense CO2 laser beam. The difference in electron beam energy spread is observable by the ATF beam line diagnostics system. Further, this energy spread expansion effect increases along with an increase in laser intensity. The proposal has been approved by the ATF committee and the experiment will be our next project.

  6. The European Medicines Agency's approval of new medicines for type 2 diabetes.

    PubMed

    Blind, Eberhard; Janssen, Heidi; Dunder, Kristina; de Graeff, Pieter A

    2018-05-08

    Since 2005, more than 40 new medicines for the treatment of type 2 diabetes have been introduced on the market. These consist of 15 new active substances establishing three new classes of non-insulin products, and several new or modified insulin products and combinations. The approval of these products in Europe is regulated via the centralized procedure at the European Medicines Agency. Demonstration of benefit with regard to improved glucose control remains the principal outcome required from confirmatory studies to demonstrate efficacy. For the majority of these new medicines approved since 2005, cardiovascular outcome trials have now been completed, and have invariably supported the cardiovascular safety of these products. In some of these trials additional important benefits have been observed, for instance, a reduction in major adverse cardiovascular events and improvement of renal outcome. The existing regulatory framework and the continuous adaption of regulatory requirements to emerging developments will continue to guide the approval of new products in the future. © 2018 John Wiley & Sons Ltd.

  7. Cheminformatic comparison of approved drugs from natural product versus synthetic origins.

    PubMed

    Stratton, Christopher F; Newman, David J; Tan, Derek S

    2015-11-01

    Despite the recent decline of natural product discovery programs in the pharmaceutical industry, approximately half of all new drug approvals still trace their structural origins to a natural product. Herein, we use principal component analysis to compare the structural and physicochemical features of drugs from natural product-based versus completely synthetic origins that were approved between 1981 and 2010. Drugs based on natural product structures display greater chemical diversity and occupy larger regions of chemical space than drugs from completely synthetic origins. Notably, synthetic drugs based on natural product pharmacophores also exhibit lower hydrophobicity and greater stereochemical content than drugs from completely synthetic origins. These results illustrate that structural features found in natural products can be successfully incorporated into synthetic drugs, thereby increasing the chemical diversity available for small-molecule drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 77 FR 2308 - Approval of Altol Petroleum Product Service, as a Commercial Gauger

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-17

    ...: Notice is hereby given that, pursuant to 19 CFR 151.13, Altol Petroleum Product Service, Parque Industrial Sabanetas, Edificio M- 1380-01-02, Ponce, PR 00731, has been approved to gauge petroleum...

  9. 78 FR 29376 - Accreditation and Approval of Quality Custom Inspections & Laboratories, LLC, as a Commercial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-20

    ..., has been approved to gauge and accredited to test petroleum and petroleum products, organic chemicals... petroleum and petroleum products, organic chemicals and vegetable oils for customs purposes, in accordance...

  10. 78 FR 57408 - Accreditation and Approval of Saybolt, LP, as a Commercial Gauger and Laboratory

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ..., has been approved to gauge and accredited to test petroleum and petroleum products, organic chemicals... accredited to test petroleum and petroleum products, organic chemicals and vegetable oils for customs...

  11. 78 FR 57407 - Approval of Altol Petroleum Product Service, as a Commercial Gauger

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... approved to gauge petroleum, petroleum products, organic chemicals and vegetable oils for customs purposes..., organic chemicals and vegetable oils for customs purposes, in accordance with the provisions of 19 CFR 151...

  12. 78 FR 39001 - Accreditation and Approval of Saybolt, LP, as a Commercial Gauger and Laboratory

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-28

    ..., has been approved to gauge and accredited to test petroleum and petroleum products, organic chemicals... gauge and accredited to test petroleum and petroleum products, organic chemicals and vegetable oils for...

  13. 78 FR 59949 - Accreditation and Approval of Inspectorate America Corporation, as a Commercial Gauger and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... test petroleum and petroleum products, organic chemicals and vegetable oils for customs purposes for... approved to gauge and accredited to test petroleum and petroleum products, organic chemicals and vegetable...

  14. 78 FR 69102 - Accreditation and Approval of Inspectorate America Corporation, as a Commercial Gauger and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-18

    ... test petroleum and petroleum products, organic chemicals and vegetable oils for customs purposes for... approved to gauge and accredited to test petroleum and petroleum products, organic chemicals and vegetable...

  15. 78 FR 52556 - Accreditation and Approval of Saybolt, LP, as a Commercial Gauger and Laboratory

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ..., has been approved to gauge and accredited to test petroleum and petroleum products, organic chemicals... accredited to test petroleum and petroleum products, organic chemicals and vegetable oils for customs...

  16. SMART empirical approaches for predicting field performance of PV modules from results of reliability tests

    NASA Astrophysics Data System (ADS)

    Hardikar, Kedar Y.; Liu, Bill J. J.; Bheemreddy, Venkata

    2016-09-01

    Gaining an understanding of degradation mechanisms and their characterization are critical in developing relevant accelerated tests to ensure PV module performance warranty over a typical lifetime of 25 years. As newer technologies are adapted for PV, including new PV cell technologies, new packaging materials, and newer product designs, the availability of field data over extended periods of time for product performance assessment cannot be expected within the typical timeframe for business decisions. In this work, to enable product design decisions and product performance assessment for PV modules utilizing newer technologies, Simulation and Mechanism based Accelerated Reliability Testing (SMART) methodology and empirical approaches to predict field performance from accelerated test results are presented. The method is demonstrated for field life assessment of flexible PV modules based on degradation mechanisms observed in two accelerated tests, namely, Damp Heat and Thermal Cycling. The method is based on design of accelerated testing scheme with the intent to develop relevant acceleration factor models. The acceleration factor model is validated by extensive reliability testing under different conditions going beyond the established certification standards. Once the acceleration factor model is validated for the test matrix a modeling scheme is developed to predict field performance from results of accelerated testing for particular failure modes of interest. Further refinement of the model can continue as more field data becomes available. While the demonstration of the method in this work is for thin film flexible PV modules, the framework and methodology can be adapted to other PV products.

  17. Apparatus for nuclear transmutation and power production using an intense accelerator-generated thermal neutron flux

    DOEpatents

    Bowman, C.D.

    1992-11-03

    Apparatus for nuclear transmutation and power production using an intense accelerator-generated thermal neutron flux. High thermal neutron fluxes generated from the action of a high power proton accelerator on a spallation target allows the efficient burn-up of higher actinide nuclear waste by a two-step process. Additionally, rapid burn-up of fission product waste for nuclides having small thermal neutron cross sections, and the practicality of small material inventories while achieving significant throughput derive from employment of such high fluxes. Several nuclear technology problems are addressed including 1. nuclear energy production without a waste stream requiring storage on a geological timescale, 2. the burn-up of defense and commercial nuclear waste, and 3. the production of defense nuclear material. The apparatus includes an accelerator, a target for neutron production surrounded by a blanket region for transmutation, a turbine for electric power production, and a chemical processing facility. In all applications, the accelerator power may be generated internally from fission and the waste produced thereby is transmuted internally so that waste management might not be required beyond the human lifespan.

  18. Apparatus for nuclear transmutation and power production using an intense accelerator-generated thermal neutron flux

    DOEpatents

    Bowman, Charles D.

    1992-01-01

    Apparatus for nuclear transmutation and power production using an intense accelerator-generated thermal neutron flux. High thermal neutron fluxes generated from the action of a high power proton accelerator on a spallation target allows the efficient burn-up of higher actinide nuclear waste by a two-step process. Additionally, rapid burn-up of fission product waste for nuclides having small thermal neutron cross sections, and the practicality of small material inventories while achieving significant throughput derive from employment of such high fluxes. Several nuclear technology problems are addressed including 1. nuclear energy production without a waste stream requiring storage on a geological timescale, 2. the burn-up of defense and commercial nuclear waste, and 3. the production of defense nuclear material. The apparatus includes an accelerator, a target for neutron production surrounded by a blanket region for transmutation, a turbine for electric power production, and a chemical processing facility. In all applications, the accelerator power may be generated internally from fission and the waste produced thereby is transmuted internally so that waste management might not be required beyond the human lifespan.

  19. Avelumab: First Global Approval.

    PubMed

    Kim, Esther S

    2017-05-01

    Avelumab (Bavencio ® ) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.

  20. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Biologics; products subject to license control... to license control. (a) If a drug has an approved license under section 351 of the Public Health.... (b) To obtain marketing approval for radioactive biological products for human use, as defined in...

  1. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Biologics; products subject to license control... to license control. (a) If a drug has an approved license under section 351 of the Public Health.... (b) To obtain marketing approval for radioactive biological products for human use, as defined in...

  2. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Biologics; products subject to license control... to license control. (a) If a drug has an approved license under section 351 of the Public Health.... (b) To obtain marketing approval for radioactive biological products for human use, as defined in...

  3. 46 CFR 159.007-3 - Production inspections and tests: Independent laboratory's procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Production inspections and tests: Independent laboratory's procedures. 159.007-3 Section 159.007-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of...

  4. 46 CFR 159.007-3 - Production inspections and tests: Independent laboratory's procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Production inspections and tests: Independent laboratory's procedures. 159.007-3 Section 159.007-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection and Tests of...

  5. 78 FR 77660 - Proposed Extension of Approval of Information Collection; Comment Request-Safety Standards for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... CONSUMER PRODUCT SAFETY COMMISSION [Docket No. CPSC-2010-0075] Proposed Extension of Approval of... Cribs AGENCY: Consumer Product Safety Commission. ACTION: Notice. SUMMARY: As required by the Paperwork Reduction Act of 1995 (44 U.S.C. chapter 35), the Consumer Product Safety Commission (CPSC or Commission...

  6. 6 CFR 5.44 - Testimony and production of documents prohibited unless approved by appropriate Department...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Testimony and production of documents prohibited... in Litigation § 5.44 Testimony and production of documents prohibited unless approved by appropriate... or request, including in connection with any litigation, provide oral or written testimony by...

  7. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Biologics; products subject to license control... to license control. (a) If a drug has an approved license under section 351 of the Public Health.... (b) To obtain marketing approval for radioactive biological products for human use, as defined in...

  8. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Biologics; products subject to license control... to license control. (a) If a drug has an approved license under section 351 of the Public Health.... (b) To obtain marketing approval for radioactive biological products for human use, as defined in...

  9. 9 CFR 381.137 - Evidence of labeling and devices approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Evidence of labeling and devices approval. 381.137 Section 381.137 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION...

  10. An analysis of FDA-approved drugs: natural products and their derivatives.

    PubMed

    Patridge, Eric; Gareiss, Peter; Kinch, Michael S; Hoyer, Denton

    2016-02-01

    Natural products contribute greatly to the history and landscape of new molecular entities (NMEs). An assessment of all FDA-approved NMEs reveals that natural products and their derivatives represent over one-third of all NMEs. Nearly one-half of these are derived from mammals, one-quarter from microbes and one-quarter from plants. Since the 1930s, the total fraction of natural products has diminished, whereas semisynthetic and synthetic natural product derivatives have increased. Over time, this fraction has also become enriched with microbial natural products, which represent a significant portion of approved antibiotics, including more than two-thirds of all antibacterial NMEs. In recent years, the declining focus on natural products has impacted the pipeline of NMEs from specific classes, and this trend is likely to continue without specific investment in the pursuit of natural products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  12. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  13. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  14. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  15. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  16. Rheological and molecular weight comparisons of approved hyaluronic acid products - preliminary standards for establishing class III medical device equivalence.

    PubMed

    Braithwaite, Gavin J C; Daley, Michael J; Toledo-Velasquez, David

    2016-01-01

    Hyaluronic acid of various molecular weights has been in use for the treatment of osteoarthritis knee pain for decades. Worldwide, these products are regulated as either as drugs or devices and in some countries as both. In the US, this class of products is regulated as Class III medical devices, which places specific regulatory requirements on developers of these materials under a Pre-Market Approval process, typically requiring data from prospective randomized controlled clinical studies. In 1984 pharmaceutical manufacturers became able to file an Abbreviated New Drug Application for approval of a generic drug, thus establishing standards for demonstrating equivalence to an existing chemical entity. Recently, the first biosimilar, or 'generic biologic', was approved. Biosimilars are biological products that are approved by the FDA because they are 'highly similar' to a reference product, and have been shown to have no clinically meaningful differences from the reference product. For devices, Class II medical devices have a pathway for declaring equivalence to an existing product by filing a 510 k application for FDA clearance. However, until recently no equivalent regulatory pathway was available to Class III devices. In this paper, we consider the critical mechanical performance parameters for intra-articular hyaluronic products to demonstrate indistinguishable characteristics. Analogous to the aforementioned pathways that allow for a demonstration of equivalence, we examine these parameters for an existing, marketed device and compare molecular weight and rheological properties of multiple batches of a similar product. We propose that this establishes a scientific rationale for establishing Class III medical device equivalence.

  17. 30 CFR 20.13 - Approval plate.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approval plate. 20.13 Section 20.13 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.13 Approval plate. The...

  18. 30 CFR 7.309 - Approval marking.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.309 Approval marking. Each approved motor assembly shall be identified by a legible and permanent approval plate inscribed.... The plate shall be securely attached to the motor assembly in a manner that does not impair any...

  19. 30 CFR 18.11 - Approval plate.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approval plate. 18.11 Section 18.11 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES General Provisions § 18.11 Approval...

  20. 76 FR 70790 - Self-Regulatory Organizations; NYSE Amex LLC; Notice and Order Granting Accelerated Approval to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ... accounting fraud allegations that have arisen with respect to Reverse Merger companies. In its filing, the... information about the Reverse Merger transaction, including audited financial statements, with the Commission... containing audited financial statements for a full fiscal year commencing on a date after the date of filing...

  1. 76 FR 77034 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    ... Accelerated Approval of Proposed Rule Change To Amend FINRA Rule 4512 (Customer Account Information) December... the Proposed Rule Change FINRA proposes to amend FINRA Rule 4512 (Customer Account Information) to... requires firms to maintain certain information relating to customer accounts, and it is based on existing...

  2. 75 FR 17457 - Self-Regulatory Organizations; NYSE Amex LLC; Order Granting Accelerated Approval of the Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... protection. The proposal requires ATP holders to indicate whether Customer orders are ``Professional Customer'' orders.\\5\\ To comply with this requirement, ATP holders would be required to review their customers... represented as Professional Customer orders for the next calendar quarter. ATP Holders would be required to...

  3. ESPC Common Model Architecture

    DTIC Science & Technology

    2014-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. ESPC Common Model Architecture Earth System Modeling...Operational Prediction Capability (NUOPC) was established between NOAA and Navy to develop common software architecture for easy and efficient...development under a common model architecture and other software-related standards in this project. OBJECTIVES NUOPC proposes to accelerate

  4. 75 FR 21689 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Granting Accelerated Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... To Establish Strike Price Intervals and Trading Hours for Options on Index-Linked Securities April 20... establish strike-price intervals for options on Index-Linked Securities and to establish trading hours for... exchange-traded notes (``ETN'')), Phlx has proposed to establish strike price intervals and trading hours...

  5. 75 FR 42471 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Accelerated Approval of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ... Commission (``Commission''), pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act'') \\1... addition includes other Depositary Receipts (``DRs''), which include Global Depositary Receipts (``GDRs''), Euro Depositary Receipts (``Euro DRs'') and New York Shares (``NYSs'').\\6\\ \\4\\ The Trust is registered...

  6. 14 CFR Appendix - Special Federal Aviation Regulation No. 23

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and CAS, in flight and during the accelerate takeoff ground run. The ground run calibration must be... approved ranges of altitude and weight. The ground run calibration will be determined assuming an engine... of the engine compressor from the turbine or from loss of the turbine blades are considered to be...

  7. 14 CFR Appendix - Special Federal Aviation Regulation No. 23

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and CAS, in flight and during the accelerate takeoff ground run. The ground run calibration must be... approved ranges of altitude and weight. The ground run calibration will be determined assuming an engine... of the engine compressor from the turbine or from loss of the turbine blades are considered to be...

  8. 14 CFR Appendix - Special Federal Aviation Regulation No. 23

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... and CAS, in flight and during the accelerate takeoff ground run. The ground run calibration must be... approved ranges of altitude and weight. The ground run calibration will be determined assuming an engine... of the engine compressor from the turbine or from loss of the turbine blades are considered to be...

  9. 14 CFR Appendix - Special Federal Aviation Regulation No. 23

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... and CAS, in flight and during the accelerate takeoff ground run. The ground run calibration must be... approved ranges of altitude and weight. The ground run calibration will be determined assuming an engine... of the engine compressor from the turbine or from loss of the turbine blades are considered to be...

  10. 14 CFR Appendix - Special Federal Aviation Regulation No. 23

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and CAS, in flight and during the accelerate takeoff ground run. The ground run calibration must be... approved ranges of altitude and weight. The ground run calibration will be determined assuming an engine... of the engine compressor from the turbine or from loss of the turbine blades are considered to be...

  11. 76 FR 77036 - Self-Regulatory Organizations; Chicago Mercantile Exchange, Inc.; Notice of Filing and Order...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    ... Organizations; Chicago Mercantile Exchange, Inc.; Notice of Filing and Order Granting Accelerated Approval of...,\\2\\ notice is hereby given that on November 25, 2011, the Chicago Mercantile Exchange Inc. (``CME... currency derivatives for over-the counter (``OTC'') cash settlement; and (2) eleven new FX non-deliverable...

  12. 78 FR 42815 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-17

    ... the Securities Committee with respect to determinations of corporate issuers to accelerate or defer... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69977; File No. SR-OCC-2013-05] Self-Regulatory..., Rather Than an Adjustment Panel of the Securities Committee, Will Determine Adjustments to the Terms of...

  13. 75 FR 20028 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Accelerated Approval of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... a ``neutral'' investment strategy intended to track the changes in the price of the Benchmark... regarding the Units, USBO, the investment objective, policies, investment strategies, accountability levels... at the same time. \\6\\ 17 CFR 240.10A-3. The net assets of USBO will consist primarily of investments...

  14. 78 FR 21675 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving, on an Accelerated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... by significant amounts in a very short time period before suddenly reversing to prices consistent... circuit breaker pilot program, which was implemented through a series of rule filings by the equity exchanges and by FINRA.\\6\\ The single-stock circuit breaker was designed to reduce extraordinary market...

  15. 7 CFR 58.705 - Meaning of words.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Supplemental Specifications for Plants Manufacturing, Processing and Packaging Pasteurized Process Cheese and Related Products...

  16. 7 CFR 58.705 - Meaning of words.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Supplemental Specifications for Plants Manufacturing, Processing and Packaging Pasteurized Process Cheese and Related Products...

  17. 7 CFR 58.705 - Meaning of words.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Supplemental Specifications for Plants Manufacturing, Processing and Packaging Pasteurized Process Cheese and Related Products...

  18. 7 CFR 58.705 - Meaning of words.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Supplemental Specifications for Plants Manufacturing, Processing and Packaging Pasteurized Process Cheese and Related Products...

  19. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  20. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  1. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  2. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  3. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  4. 30 CFR 19.5 - General requirements for approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., AND APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.5 General requirements for approval. Electric cap lamps shall be complete units. They shall be durable in construction, practical in operation, and...

  5. 30 CFR 18.81 - Field modification of approved (permissible) equipment; application for approval of modification...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES... and Certification Center, 765 Technology Drive, Triadelphia, WV 26059. (b) Proposed modifications...

  6. 30 CFR 7.51 - Approval checklist.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Battery Assemblies § 7.51 Approval checklist. Each battery assembly bearing an MSHA approval plate shall be accompanied by a description of what is necessary to maintain the battery assembly as approved. [53 FR 23500, June 22, 1988, as amended at 60 FR 33723...

  7. 30 CFR 19.6 - Specific requirements for approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Specific requirements for approval. 19.6 Section 19.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.6 Specific requirements for approval. (a...

  8. 7 CFR 58.124 - Denial or suspension of plant approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Denial or suspension of plant approval. 58.124 Section... (CONTINUED) GRADING AND INSPECTION, GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading...

  9. 30 CFR 18.91 - Electric equipment for which field approvals will be issued.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment for which field approvals... OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.91 Electric equipment...

  10. 30 CFR 18.91 - Electric equipment for which field approvals will be issued.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electric equipment for which field approvals... OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.91 Electric equipment...

  11. 30 CFR 7.51 - Approval checklist.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Battery Assemblies § 7.51 Approval checklist. Each battery assembly bearing an MSHA approval plate shall be accompanied by a description of what is necessary to maintain the battery assembly as approved. [53 FR 23500, June 22, 1988, as amended at 60 FR 33723...

  12. 30 CFR 7.51 - Approval checklist.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Battery Assemblies § 7.51 Approval checklist. Each battery assembly bearing an MSHA approval plate shall be accompanied by a description of what is necessary to maintain the battery assembly as approved. [53 FR 23500, June 22, 1988, as amended at 60 FR 33723...

  13. [Interchangeability of biological drugs: considerations about the approval of biogeneric formulations in Chile].

    PubMed

    Saavedra S, Iván; Quiñones S, Luis

    2006-12-01

    Once drug patents expire, the health authorities can approve the registry of similar products. They must request to the manufacturer, the bibliographic background of the original product and the analytical results that certify drug quality. An inspection of the premises of the manufacturer is also required. The main goal of this approval is to decrease cost, considering that the original product is usually more expensive. This is a current situation due to the imminent expiration of the patents of many biopharmaceutical products. Therefore, in Chile, the Public Health (ISP) and the Ministry of Health should consider that for this kind of products, until now, there are no interchangeable generic drugs, and that the similar drugs that are offered have a different chemical composition, since they have been manufactured through different processes. In the case of biological drugs (e.g. erythropoietir, somatotropin, heparin) the quality and homogeneity depend from the manufacture process. Its complete composition can not be absolutely elucidated; therefore small impurities or conformational variants can elicit an altered immune response or unexpected adverse reactions. This indicates that the approval of a biogeneric drug requires in addition to pharmacokinetic studies, preclinical and clinical analytical studies such as physicochemical assays, biological and immunological test. This issues have been established by WHO and have been incorporated for the main drug registry entities all over the world (FDA, EMEA, ANVISA) to approve biogeneric products.

  14. Watson will see you now: a supercomputer to help clinicians make informed treatment decisions.

    PubMed

    Doyle-Lindrud, Susan

    2015-02-01

    IBM has collaborated with several cancer care providers to develop and train the IBM supercomputer Watson to help clinicians make informed treatment decisions. When a patient is seen in clinic, the oncologist can input all of the clinical information into the computer system. Watson will then review all of the data and recommend treatment options based on the latest evidence and guidelines. Once the oncologist makes the treatment decision, this information can be sent directly to the insurance company for approval. Watson has the ability to standardize care and accelerate the approval process, a benefit to the healthcare provider and the patient.

  15. 46 CFR 159.007-7 - Application for acceptance for production inspections and tests: Coast Guard action.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Application for acceptance for production inspections and tests: Coast Guard action. 159.007-7 Section 159.007-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection...

  16. 46 CFR 159.007-7 - Application for acceptance for production inspections and tests: Coast Guard action.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Application for acceptance for production inspections and tests: Coast Guard action. 159.007-7 Section 159.007-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF EQUIPMENT AND MATERIALS Production Inspection...

  17. 76 FR 45769 - Notice of Request for Extension of Approval of an Information Collection; Pork and Poultry...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-01

    ...] Notice of Request for Extension of Approval of an Information Collection; Pork and Poultry Products From... regulations for pork and poultry products from Mexico transiting the United States. DATES: We will consider... information on pork and poultry products from Mexico transiting the United States, contact Dr. Lynette...

  18. 9 CFR 381.138 - Unauthorized use or disposition of approved labeling or devices.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Unauthorized use or disposition of approved labeling or devices. 381.138 Section 381.138 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION...

  19. FDA's Flexibility in Subpart H Approvals: Assessing Quantum of Effectiveness Evidence.

    PubMed

    Sasinowski, Frank J; Varond, Alexander J

    2016-08-01

    This article examines the strength of scientific and clinical evidence for FDA's nineteen non-AIDS, non-cancer Subpart H approval determinations over the Accelerated Approval program's twenty-four year existence. The authors researched the bases for FDA's determinations when an unvalidated surrogate or intermediate clinical endpoint is "reasonably likely to predict clinical benefit." The four key factors set forth in FDA's "Guidance for Industry, Expedited Programs for Serious Conditions - Drugs and Biologics" were applied to past Subpart H approvals. For the nineteen precedents, the authors found wide variances between the quantum and quality of evidence on each of the four factors, indicating that a lack of evidence on any single factor was not disqualifying in and of itself. The results of this study, therefore, show that FDA exercises extraordinarily more regulatory flexibility than either FDA's foundational statutes or even FDA' s most recent 2014 Expedited Programs Guidance explicitly express. Given recent legislative exhortations and the increasing promise of personalized medicine and translational sciences, the authors conclude that Subpart H should be further explored and utilized. The authors provide a detailed analysis of the orecedents established in the nineteen approvals.

  20. Tanning accelerators: prevalence, predictors of use, and adverse effects.

    PubMed

    Herrmann, Jennifer L; Cunningham, Rachel; Cantor, Alan; Elewski, Boni E; Elmets, Craig A

    2015-01-01

    Tanning accelerators are topical products used by indoor tanners to augment and hasten the tanning process. These products contain tyrosine, psoralens, and/or other chemicals. We sought to better define the population using accelerators, identify predictors of their use, and describe any related adverse effects. This cross-sectional study surveyed 200 indoor tanners about their tanning practices and accelerator use. Primary analysis compared accelerator users with nonusers with respect to questionnaire variables. Descriptive statistics and χ(2) contingency tables were applied to identify statistically significant variables. Of respondents, 53% used accelerators; 97% were female and 3% were male with a median age of 22 years (range: 19-67). Users were more likely to spray tan, tan frequently, and be addicted to tanning. Acne and rashes were more common in accelerator users. Adverse reactions to accelerators prevented their further use 31% of the time. A limited adult population was evaluated; exact accelerator ingredients were not examined. Tanning accelerator users are high-risk indoor tanners who tan more frequently and who are more likely addicted to tanning. Acne and rashes are more common with these products and act as only mild deterrents to continued use. Additional research should investigate accelerators' longer-term health effects. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Trends in global approvals of biotech crops (1992–2014)

    PubMed Central

    Aldemita, Rhodora R; Reaño, Ian Mari E; Solis, Renando O; Hautea, Randy A

    2015-01-01

    ABSTRACT With the increasing number of genetically modified (GM) events, traits, and crops that are developed to benefit the global population, approval of these technologies for food, feed, cultivation and import in each country may vary depending on needs, demand and trade interest. ISAAA established a GMO Approval Database to document global approvals of biotech crops. GM event name, crops, traits, developer, year of approval for cultivation, food/feed, import, and relevant dossiers were sourced from credible government regulatory websites and biosafety clearinghouses. This paper investigates the trends in GM approvals for food, feed and cultivation based on the number of approving countries, GM crops, events, and traits in the last 23 y (1992–2014), rationale for approval, factors influencing approvals, and their implications in GM crop adoption. Results show that in 2014, there was an accumulative increase in the number of countries granting approvals at 29 (79% developing countries) for commercial cultivation and 31 (70% developing countries) for food and 19 (80% developing developing) for feed; 2012 had the highest number of approving countries and cultivation approvals; 2011 had the highest number of country approvals for feed, and 2014 for food approvals. Herbicide tolerance trait had the highest events approved, followed by insect tolerance traits. Approvals for food product quality increased in the second decade. Maize had the highest number of events approved (single and stacked traits), and stacked traits product gradually increased which is already 30% of the total trait approvals. These results may indicate understanding and acceptance of countries to enhance regulatory capability to be able to benefit from GM crop commercialization. Hence, the paper provided information on the trends on the growth of the GM crop industry in the last 23 y which may be vital in predicting future GM crops and traits. PMID:26039675

  2. Trends in global approvals of biotech crops (1992-2014).

    PubMed

    Aldemita, Rhodora R; Reaño, Ian Mari E; Solis, Renando O; Hautea, Randy A

    2015-01-01

    With the increasing number of genetically modified (GM) events, traits, and crops that are developed to benefit the global population, approval of these technologies for food, feed, cultivation and import in each country may vary depending on needs, demand and trade interest. ISAAA established a GMO Approval Database to document global approvals of biotech crops. GM event name, crops, traits, developer, year of approval for cultivation, food/feed, import, and relevant dossiers were sourced from credible government regulatory websites and biosafety clearinghouses. This paper investigates the trends in GM approvals for food, feed and cultivation based on the number of approving countries, GM crops, events, and traits in the last 23 y (1992-2014), rationale for approval, factors influencing approvals, and their implications in GM crop adoption. Results show that in 2014, there was an accumulative increase in the number of countries granting approvals at 29 (79% developing countries) for commercial cultivation and 31 (70% developing countries) for food and 19 (80% developing developing) for feed; 2012 had the highest number of approving countries and cultivation approvals; 2011 had the highest number of country approvals for feed, and 2014 for food approvals. Herbicide tolerance trait had the highest events approved, followed by insect tolerance traits. Approvals for food product quality increased in the second decade. Maize had the highest number of events approved (single and stacked traits), and stacked traits product gradually increased which is already 30% of the total trait approvals. These results may indicate understanding and acceptance of countries to enhance regulatory capability to be able to benefit from GM crop commercialization. Hence, the paper provided information on the trends on the growth of the GM crop industry in the last 23 y which may be vital in predicting future GM crops and traits.

  3. 7 CFR 52.2 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... this part, setting forth in addition to appropriate descriptive information relative to a processed... plant facilities, sanitation, and methods of operation have been surveyed and approved for specific... have been surveyed and approved for specific product(s) by the Administrator as suitable and adequate...

  4. 7 CFR 52.2 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... this part, setting forth in addition to appropriate descriptive information relative to a processed... plant facilities, sanitation, and methods of operation have been surveyed and approved for specific... have been surveyed and approved for specific product(s) by the Administrator as suitable and adequate...

  5. 7 CFR 52.2 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... this part, setting forth in addition to appropriate descriptive information relative to a processed... plant facilities, sanitation, and methods of operation have been surveyed and approved for specific... have been surveyed and approved for specific product(s) by the Administrator as suitable and adequate...

  6. 7 CFR 52.2 - Terms defined.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... this part, setting forth in addition to appropriate descriptive information relative to a processed... plant facilities, sanitation, and methods of operation have been surveyed and approved for specific... have been surveyed and approved for specific product(s) by the Administrator as suitable and adequate...

  7. 7 CFR 52.2 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... this part, setting forth in addition to appropriate descriptive information relative to a processed... plant facilities, sanitation, and methods of operation have been surveyed and approved for specific... have been surveyed and approved for specific product(s) by the Administrator as suitable and adequate...

  8. Pneumococcal conjugate vaccine use in adults - Addressing an unmet medical need for non-bacteremic pneumococcal pneumonia.

    PubMed

    Sings, Heather L

    2017-09-25

    Streptococcus pneumoniae is a frequent cause of community acquired pneumonia (CAP), with the largest burden of disease attributed to non-bacteremic pneumonia. Due to the high persistent burden of disease, pneumococcal pneumonia, particularly non-bacteremic pneumococcal pneumonia, continues to be a major public health concern. There are currently two pneumococcal vaccines approved for use in adults in the United States (US) and other countries worldwide: a 23-valent pneumococcal simple polysaccharide vaccine (PPV23), and a 13-valent pneumococcal conjugate vaccine (PCV13). The capsular polysaccharides included in PPV23 induce antibodies primarily by a T-cell independent mechanism, thus the immune response is short lived and lacks the ability to elicit an anamnestic response. PCV13, on the other hand, has the bacterial polysaccharides covalently conjugated to an immunogenic carrier protein resulting in the formation of memory B lymphocytes, thus proving long-acting immunologic memory and an anamnestic response. Despite 30years of use, the question of PPV23 vaccine efficacy, particularly with respect to efficacy for non-bacteremic pneumonia, has been extensively debated and investigated; whereas PCV13 efficacy against vaccine-type pneumococcal CAP, both bacteremic and non-bacteremic, was confirmed in a large randomized controlled trial in older adults. PCV13 was approved under the US Food and Drug Administration's accelerated pathway, which allows for earlier approval of products that provide meaningful benefit over existing treatments - in this case, protection of adults from non-bacteremic pneumococcal pneumonia. Its use is now increasingly recommended globally. This article summarizes the history and use of PPV23 and PCV13 in adults and how vaccination of adults with PCV13 addresses an unmet medical need. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. mAbs: a business perspective.

    PubMed

    Scolnik, Pablo A

    2009-01-01

    The twenty two monoclonal antibodies (mAbs) currently marketed in the U.S. have captured almost half of the top-20 U.S. therapeutic biotechnology sales for 2007. Eight of these products have annual sales each of more than $1 B, were developed in the relatively short average period of six years, qualified for FDA programs designed to accelerate drug approval, and their cost has been reimbursed liberally by payers. With growth of the product class driven primarily by advancements in protein engineering and the low probability of generic threats, mAbs are now the largest class of biological therapies under development. The high cost of these drugs and the lack of generic competition conflict with a financially stressed health system, setting reimbursement by payers as the major limiting factor to growth. Advances in mAb engineering are likely to result in more effective mAb drugs and an expansion of the therapeutic indications covered by the class. The parallel development of biomarkers for identifying the patient subpopulations most likely to respond to treatment may lead to a more cost-effective use of these drugs. To achieve the success of the current top-tier mAbs, companies developing new mAb products must adapt to a significantly more challenging commercial environment.

  10. The use of the United States FDA programs as a strategy to advance the development of drug products for neglected tropical diseases.

    PubMed

    Sachs-Barrable, Kristina; Conway, Jocelyn; Gershkovich, Pavel; Ibrahim, Fady; Wasan, Kishor M

    2014-11-01

    Neglected tropical diseases (NTDs) are infections which are endemic in poor populations in lower- and middle-income countries (LMIC). Approximately one billion people have now or are at risk of getting an NTD and yet less than 5% of research dollars are focused on providing treatments and prevention of these highly debilitating and deadly conditions. The United States Food and Drug Administration (FDA) Orphan Drug Designation program (ODDP) provides orphan status to drugs and biologics, defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200 000 people in the United States, or that affect more than 200 000 persons but are not expected to recover the costs of developing and marketing a treatment drug. These regulations have led to the translation of rare disease knowledge into innovative rare disease therapies. The FDA Guidance for Industry on developing drugs for the treatment and prevention of NTDs describes the following regulatory strategies: Orphan Product Designation, Fast Track Designation, Priority Review Designation, Accelerated Approval and Tropical Disease Priority Review Voucher. This paper will discuss how these regulations and especially the ODDP can improve the clinical development and accessibility of drug products for NTDs.

  11. ILU industrial electron accelerators for medical-product sterilization and food treatment

    NASA Astrophysics Data System (ADS)

    Bezuglov, V. V.; Bryazgin, A. A.; Vlasov, A. Yu.; Voronin, L. A.; Panfilov, A. D.; Radchenko, V. M.; Tkachenko, V. O.; Shtarklev, E. A.

    2016-12-01

    Pulse linear electron accelerators of the ILU type have been developed and produced by the Institute of Nuclear Physics, Siberian Branch, Russian Academy of Sciences, for more than 30 years. Their distinctive features are simplicity of design, convenience in operation, and reliability during long work under conditions of industrial production. ILU accelerators have a range of energy of 0.7-10 MeV at a power of accelerated beam of up to 100 kW and they are optimally suitable for use as universal sterilizing complexes. The scientific novelty of these accelerators consists of their capability to work both in the electron-treatment mode of production and in the bremsstrahlung generation mode, which has high penetrating power.

  12. BG 12: BG 00012, BG 12/Oral Fumarate, FAG-201, second-generation fumarate derivative--Fumapharm/Biogen Idec.

    PubMed

    2005-01-01

    Fumapharm AG has developed a second-generation fumarate (fumaric acid) derivative, BG 12 [BG 00012, FAG-201, BG 12/Oral Fumarate], for the oral treatment of psoriasis. Biogen Idec is currently evaluating the product in clinical trials as an oral treatment for multiple sclerosis (phase II) and psoriasis (phase III) trials.BG 12 has an immunomodulatory mechanism of action. It seems that this product has been developed to reduce the adverse effects associated with a first-generation product containing fumaric acid esters (mixed dimethylfumarate and monoethylfumarate salts), Fumaderm. Fumaderm was approved in Germany in August 1994 and is currently the leading oral systemic therapy for moderate-to-severe psoriasis in Germany. One of the problems associated with Fumaderm capsules has been its gastrointestinal adverse effects (including diarrhoea and nausea). In September 2003, Biogen (now Biogen Idec) licensed exclusive worldwide rights (excluding Germany) from Fumapharm to develop and market BG 12. Biogen plans to collaborate with Fumapharm to accelerate phase III development for psoriasis and the registration programme worldwide. Financial terms of the agreement were not disclosed. Development plans for BG 12 include other autoimmune and inflammatory disorders, such as multiple sclerosis. In November 2003, Biogen and IDEC Pharmaceuticals merged to form Biogen Idec. Fumapharm completed phase II trials of this second-generation fumarate derivative for psoriasis prior to licensing of the product to Biogen, also with positive results.

  13. 27 CFR 4.93 - Approval of grape variety names.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Approval of grape variety..., DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE American Grape Variety Names § 4.93 Approval of grape variety names. (a) Any interested person may petition the Administrator for the approval...

  14. 27 CFR 4.93 - Approval of grape variety names.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Approval of grape variety..., DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE American Grape Variety Names § 4.93 Approval of grape variety names. (a) Any interested person may petition the Administrator for the approval...

  15. 27 CFR 4.93 - Approval of grape variety names.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Approval of grape variety..., DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF WINE American Grape Variety Names § 4.93 Approval of grape variety names. (a) Any interested person may petition the Administrator for the approval...

  16. 27 CFR 4.93 - Approval of grape variety names.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Approval of grape variety..., DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF WINE American Grape Variety Names § 4.93 Approval of grape variety names. (a) Any interested person may petition the Administrator for the approval...

  17. 30 CFR 20.0 - Compliance with the requirements necessary for obtaining approval.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.0 Compliance with the requirements necessary for obtaining approval. To receive approval of MSHA for any electric mine lamps other than standard cap lamps a manufacturer must comply with the...

  18. 30 CFR 20.0 - Compliance with the requirements necessary for obtaining approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.0 Compliance with the requirements necessary for obtaining approval. To receive approval of MSHA for any electric mine lamps other than standard cap lamps a manufacturer must comply with the...

  19. 30 CFR 20.0 - Compliance with the requirements necessary for obtaining approval.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.0 Compliance with the requirements necessary for obtaining approval. To receive approval of MSHA for any electric mine lamps other than standard cap lamps a manufacturer must comply with the...

  20. 30 CFR 20.0 - Compliance with the requirements necessary for obtaining approval.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.0 Compliance with the requirements necessary for obtaining approval. To receive approval of MSHA for any electric mine lamps other than standard cap lamps a manufacturer must comply with the...

  1. 46 CFR 160.076-17 - Approval of design or material changes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... approval before changing PFD production methods. (b) Determinations of equivalence of design, construction... 46 Shipping 6 2010-10-01 2010-10-01 false Approval of design or material changes. 160.076-17... Flotation Devices § 160.076-17 Approval of design or material changes. (a) The manufacturer must submit any...

  2. 30 CFR 22.8 - Material required for MSHA records.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.8 Material required for MSHA... manufacturer must submit to MSHA before the approval is granted to show the details of the detector as approved, are retained. These drawings are used to identify the detector in the approval and as a means of...

  3. 30 CFR 22.8 - Material required for MSHA records.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.8 Material required for MSHA... manufacturer must submit to MSHA before the approval is granted to show the details of the detector as approved, are retained. These drawings are used to identify the detector in the approval and as a means of...

  4. 30 CFR 22.8 - Material required for MSHA records.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.8 Material required for MSHA... manufacturer must submit to MSHA before the approval is granted to show the details of the detector as approved, are retained. These drawings are used to identify the detector in the approval and as a means of...

  5. 30 CFR 22.8 - Material required for MSHA records.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.8 Material required for MSHA... manufacturer must submit to MSHA before the approval is granted to show the details of the detector as approved, are retained. These drawings are used to identify the detector in the approval and as a means of...

  6. 9 CFR 592.180 - Suspension of plant approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Suspension of plant approval. 592.180... Suspension of plant approval. (a) Any plant approval pursuant to the regulations in this part may be suspended for: (1) Failure to maintain plant and equipment in a satisfactory state of repairs; (2) The use...

  7. 9 CFR 354.38 - Suspension of plant approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Suspension of plant approval. 354.38... Inspection Service § 354.38 Suspension of plant approval. (a) Any plant approval given pursuant to the regulations in this part may be suspended by the Administrator for: (1) Failure to maintain plant and...

  8. 9 CFR 354.38 - Suspension of plant approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Suspension of plant approval. 354.38... Inspection Service § 354.38 Suspension of plant approval. (a) Any plant approval given pursuant to the regulations in this part may be suspended by the Administrator for: (1) Failure to maintain plant and...

  9. 9 CFR 592.180 - Suspension of plant approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Suspension of plant approval. 592.180... Suspension of plant approval. (a) Any plant approval pursuant to the regulations in this part may be suspended for: (1) Failure to maintain plant and equipment in a satisfactory state of repairs; (2) The use...

  10. 9 CFR 354.38 - Suspension of plant approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Suspension of plant approval. 354.38... Inspection Service § 354.38 Suspension of plant approval. (a) Any plant approval given pursuant to the regulations in this part may be suspended by the Administrator for: (1) Failure to maintain plant and...

  11. 9 CFR 590.161 - Termination of plant approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Termination of plant approval. 590.161... Service § 590.161 Termination of plant approval. When inspection service is not performed at any plant for a period of at least 90 days, plant approval shall terminate upon notice by the Administrator...

  12. 9 CFR 592.180 - Suspension of plant approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Suspension of plant approval. 592.180... Suspension of plant approval. (a) Any plant approval pursuant to the regulations in this part may be suspended for: (1) Failure to maintain plant and equipment in a satisfactory state of repairs; (2) The use...

  13. 9 CFR 354.38 - Suspension of plant approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Suspension of plant approval. 354.38... Inspection Service § 354.38 Suspension of plant approval. (a) Any plant approval given pursuant to the regulations in this part may be suspended by the Administrator for: (1) Failure to maintain plant and...

  14. 9 CFR 354.38 - Suspension of plant approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Suspension of plant approval. 354.38... Inspection Service § 354.38 Suspension of plant approval. (a) Any plant approval given pursuant to the regulations in this part may be suspended by the Administrator for: (1) Failure to maintain plant and...

  15. 9 CFR 590.161 - Termination of plant approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Termination of plant approval. 590.161... Service § 590.161 Termination of plant approval. When inspection service is not performed at any plant for a period of at least 90 days, plant approval shall terminate upon notice by the Administrator...

  16. 9 CFR 592.180 - Suspension of plant approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Suspension of plant approval. 592.180... Suspension of plant approval. (a) Any plant approval pursuant to the regulations in this part may be suspended for: (1) Failure to maintain plant and equipment in a satisfactory state of repairs; (2) The use...

  17. 9 CFR 590.161 - Termination of plant approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Termination of plant approval. 590.161... Service § 590.161 Termination of plant approval. When inspection service is not performed at any plant for a period of at least 90 days, plant approval shall terminate upon notice by the Administrator...

  18. 9 CFR 590.161 - Termination of plant approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Termination of plant approval. 590.161... Service § 590.161 Termination of plant approval. When inspection service is not performed at any plant for a period of at least 90 days, plant approval shall terminate upon notice by the Administrator...

  19. 7 CFR 58.122 - Approved plants under USDA inspection and grading service.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Approved plants under USDA inspection and grading... FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Purpose § 58.122 Approved plants under USDA inspection and grading service. (a...

  20. 7 CFR 58.122 - Approved plants under USDA inspection and grading service.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Approved plants under USDA inspection and grading... FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Purpose § 58.122 Approved plants under USDA inspection and grading service. (a...

  1. 7 CFR 58.122 - Approved plants under USDA inspection and grading service.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Approved plants under USDA inspection and grading... FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Purpose § 58.122 Approved plants under USDA inspection and grading service. (a...

  2. 7 CFR 58.122 - Approved plants under USDA inspection and grading service.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Approved plants under USDA inspection and grading... FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Purpose § 58.122 Approved plants under USDA inspection and grading service. (a...

  3. 7 CFR 58.122 - Approved plants under USDA inspection and grading service.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Approved plants under USDA inspection and grading... FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Purpose § 58.122 Approved plants under USDA inspection and grading service. (a...

  4. Jefferson Lab 12 GEV Cebaf Upgrade

    NASA Astrophysics Data System (ADS)

    Rode, C. H.

    2010-04-01

    The existing continuous electron beam accelerator facility (CEBAF) at Thomas Jefferson National Accelerator Facility (TJNAF) is a 5-pass, recirculating cw electron Linac operating at ˜6 GeV and is devoted to basic research in nuclear physics. The 12 GeV CEBAF Upgrade is a 310 M project, sponsored by the Department of Energy (DOE) Office of Nuclear Physics, that will expand its research capabilities substantially by doubling the maximum energy and adding major new experimental apparatus. The project received construction approval in September 2008 and has started the major procurement process. The cryogenic aspects of the 12 GeV CEBAF Upgrade includes: doubling the accelerating voltages of the Linacs by adding ten new high-performance, superconducting radiofrequency (SRF) cryomodules (CMs) to the existing 42 1/4 cryomodules; doubling of the 2 K cryogenics plant; and the addition of eight superconducting magnets.

  5. 30 CFR 20.12 - How approvals are granted.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.12 How approvals are... part only when the testing engineers judge that the lamp has met the requirements of this part and...

  6. 30 CFR 20.12 - How approvals are granted.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.12 How approvals are... part only when the testing engineers judge that the lamp has met the requirements of this part and...

  7. 30 CFR 20.12 - How approvals are granted.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.12 How approvals are... part only when the testing engineers judge that the lamp has met the requirements of this part and...

  8. 30 CFR 20.12 - How approvals are granted.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.12 How approvals are... part only when the testing engineers judge that the lamp has met the requirements of this part and...

  9. 30 CFR 20.12 - How approvals are granted.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... APPROVAL OF MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.12 How approvals are... part only when the testing engineers judge that the lamp has met the requirements of this part and...

  10. Market withdrawal of new molecular entities approved in the United States from 1980 to 2009.

    PubMed

    Qureshi, Zaina P; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Stevenson, Kurt B; Szeinbach, Sheryl L

    2011-07-01

    Economic factors, market dynamics, and safety issues are largely responsible for decisions to withdraw pharmaceutical products from the market. In this study, new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) were examined in the USA from 1980 to 2009. Data were obtained from the FDA, Micromedex, Medline, and Lexis-Nexis. Descriptive analyses were used to classify product discontinuations by therapeutic category, time frame for discontinuation, and reason for withdrawal. There were 740 NMEs approved by the FDA during the study period. As of 1 December 2010, the number of drugs discontinued was 118 (15.9%). Discontinuations were the highest for antiparasitic products, insecticides, and repellents (6, 33.3% of approvals), systemic hormonal preparations excluding sex hormones and insulins (5, 33.3%), musculo-skeletal system (11, 32.4%), diagnostic agents (16, 28.1%), and anti-infectives for systemic use (27, 25.2%). Safety was the primary reason for withdrawing 26 drugs (3.5% of approvals). Approximately one in seven approved NMEs were discontinued from the market in the period of 1980-2009. Less than one-quarter (22%) of the total withdrawals were attributed to safety reasons. An ongoing evaluation of new drugs throughout their product life cycle is important to determine their efficacy, safety, and value to society. Copyright © 2011 John Wiley & Sons, Ltd.

  11. 2015 Fermilab Laboratory Directed Research & Development Annual Report

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

    Wester, W.

    2016-05-26

    The Fermi National Accelerator Laboratory (FNAL) is conducting a Laboratory Directed Research and Development (LDRD) program. Fiscal year 2015 represents the first full year of LDRD at Fermilab and includes seven projects approved mid-year in FY14 and six projects approved in FY15. One of the seven original projects has been completed just after the beginning of FY15. The implementation of LDRD at Fermilab is captured in the approved Fermilab 2015 LDRD Annual Program Plan. In FY15, the LDRD program represents 0.64% of Laboratory funding. The scope of the LDRD program at Fermilab will be established over the next couple ofmore » years where a portfolio of about 20 on-going projects representing approximately between 1% and 1.5% of the Laboratory funding is anticipated. This Annual Report focuses on the status of the current projects and provides an overview of the current status of LDRD at Fermilab.« less

  12. 9 CFR 590.411 - Requirement of formulas and approval of labels for use in official egg products plants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION... distributor. When the distributor is shown, it shall be qualified by such terms as “packed for,” “distributed... the reasons for the denial on a form approved by the Administrator. If the person using or proposing...

  13. 9 CFR 590.411 - Requirement of formulas and approval of labels for use in official egg products plants.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION... distributor. When the distributor is shown, it shall be qualified by such terms as “packed for,” “distributed... the reasons for the denial on a form approved by the Administrator. If the person using or proposing...

  14. 75 FR 61497 - Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ..., whereas small molecule drugs are typically manufactured through chemical synthesis. Section 351(k) of the... provision for protein products that have been or will be approved under section 505 of the FD&C Act (21 U.S... certain protein products during the 10-year transition period following enactment of the BPCI Act; and the...

  15. Companion diagnostics: a regulatory perspective from the last 5 years of molecular companion diagnostic approvals.

    PubMed

    Roscoe, Donna M; Hu, Yun-Fu; Philip, Reena

    2015-01-01

    Companion diagnostics are essential for the safe and effective use of the corresponding therapeutic products. The US FDA has approved a number of companion diagnostics used to select cancer patients for treatment with contemporaneously approved novel therapeutics. The processes of co-development and co-approval of a therapeutic product and its companion diagnostic have been a learning experience that continues to evolve. Using several companion diagnostics as examples, this article describes the challenges associated with the scientific, clinical and regulatory hurdles faced by FDA and industry alike. Taken together, this discussion is intended to assist manufacturers toward a successful companion diagnostics development plan.

  16. 5 CFR 1305.2 - Production prohibited unless approved.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Production prohibited unless approved. 1305.2 Section 1305.2 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET ADMINISTRATIVE PROCEDURES RELEASE OF OFFICIAL INFORMATION, AND TESTIMONY BY OMB PERSONNEL AS WITNESSES, IN LITIGATION § 1305...

  17. 75 FR 18558 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Accelerated Approval of a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    .... Information regarding the market price and trading volume of the Shares will be continually available on a... trading volume information for the Shares will be published daily in the financial sections of newspapers...), name of security or financial instrument, number of shares or dollar value of financial instruments...

  18. 77 FR 63908 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... Accelerated Approval of Proposed Rule Change To Amend NASD Rule 2711 and Incorporated NYSE Rule 472 To Conform With the Requirements of the Jumpstart Our Business Startups Act and Related Changes October 11, 2012... rule change as described in Items I, II, and III below, which Items have substantially been prepared by...

  19. 76 FR 11303 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Granting Accelerated Approval of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-01

    ..., 2011. I. Introduction On January 14, 2011, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'') filed...\\ pursuant to which, among other things, short sale orders in covered securities \\6\\ generally cannot be... the current national best bid (``NBB'') when a short sale circuit breaker is in effect for the covered...

  20. 76 FR 11301 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Granting Accelerated Approval of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-01

    ... 23, 2011. I. Introduction On January 14, 2011, BATS Y-Exchange, Inc. (the ``Exchange'' or ``BYX... Rule 201,\\5\\ pursuant to which, among other things, short sale orders in covered securities \\6... the current national best bid (``NBB'') when a short sale circuit breaker is in effect for the covered...

  1. 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...

  2. 77 FR 22372 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Filing and Order...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... Organizations; Chicago Mercantile Exchange Inc.; Notice of Filing and Order Granting Accelerated Approval of... Organizations April 9, 2012. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act'') \\1...). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of Terms of Substance of the...

  3. 78 FR 22011 - Self-Regulatory Organizations; NYSE MKT LLC; Order Approving, on an Accelerated Basis, Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... Treat Orders, Market-Making Quoting Obligations, and Errors in Response to the Regulation NMS Plan To..., market-making quoting obligations, and errors in response to the Regulation NMS Plan to Address... Specialist has met its market-making quoting requirement pursuant to Rule 925.1NY(b) or a Market Maker has...

  4. 76 FR 70799 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice and Order Granting Accelerated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ... the applicable quantitative and liquidity measures contained in the Rule 5300, 5400 and 5500 Series... July 25, 2011, the Commission extended the time period in which to either approve the proposed rule... length of time before applying to list; (iv) applying the price requirement using closing prices, both...

  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. 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...

  8. Human Short-Latency Somatosensory Evoked Potentials in Impact Acceleration Research: Equipment, Procedures and Techniques

    DTIC Science & Technology

    1990-10-01

    New Orleans, LA 70189-0407 Approved for public release; distribution is unlimited. Reproduction in whole or in part is permitted for any purpose of...have the subject supine on a bed with pillows at the head to minimize neck muscle tone. The room is kept quiet and a mild hypnotic , such as chloral

  9. 75 FR 1678 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Order...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-12

    ... Accelerated Approval to a Proposed Rule Change Relating to the Amounts That Direct Edge ECN, in Its Capacity... Substance of the Proposed Rule Change The Exchange proposes to modify the amounts that Direct Edge ECN... immediate effectiveness a proposed rule change to amend Direct Edge ECN's (``DECN'') fee schedule for ISE...

  10. 75 FR 62466 - Delegation of Authority to the Director of the Division of Trading and Markets

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... 19(b) and publish the reasons for such determination as well as to effect any such extension; to... SRO notice of the grounds for disapproval under consideration; to find good cause to approve a proposal on an accelerated basis and to publish the reasons for such determination; and to extend the...

  11. 78 FR 75435 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-11

    ... Accelerated Approval of Proposed Rule Change To Amend CBOE Rule 18.2 (Procedures in Trading Permit Holder... of the Terms of Substance of the Proposed Rule Change The Exchange proposes to amend CBOE Rule 18.2.... Purpose The Exchange seeks to amend Rule 18.2 (Procedures in Trading Permit Holder Controversies) to...

  12. 78 FR 21653 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving, on an Accelerated Basis...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... time period before suddenly reversing to prices consistent with their pre-decline levels.\\5\\ This... implemented through a series of rule filings by the equity exchanges and by FINRA.\\6\\ The single-stock circuit breaker was designed to reduce extraordinary market volatility in NMS stocks by imposing a five-minute...

  13. Approval of the first biosimilar antibodies in Europe: a major landmark for the biopharmaceutical industry.

    PubMed

    Beck, Alain; Reichert, Janice M

    2013-01-01

    In a defining moment for the European Medicines Agency (EMA) and the biopharmaceutical industry, on June 27, 2013 EMA's Committee for Medicinal Products for Human Use adopted a positive opinion for two biosimilar infliximab products (Celltrion's Remsima® and Hospira's Inflectra®), and recommended that they be approved for marketing in the European Union (EU). The European Commission's decision on an application is typically issued 67 d after an opinion is provided; thus, decisions are expected in early September 2013. If approved, the products will comprise the first biosimilar antibody made available to patients in a highly regulated market, although launch may be delayed due to an extension of the reference product's (Remicade®) patent in the EU.

  14. Concerns about the safety of obesity agents from a manufacturing perspective.

    PubMed

    Kanfer, Isadore

    2008-07-01

    Salt derivatives of active pharmaceutical ingredients (API), such as hydrochloride and mesylate salts, are frequently used during drug product development. Compared with the underivatized API, salt derivatives are often associated with beneficial properties, including improved solubility and better absorption. Although the obesity agent sibutramine was initially approved as the hydrochloride salt, it has also been formulated as a mesylate salt (sibutramine mesylate). In order to qualify as interchangeable, generic products generally must be both pharmaceutically equivalent and bioequivalent to an approved reference product. Because generic versions of hydrochloride salt formulations that have been reformulated as mesylate salts are not pharmaceutically equivalent to the approved reference products, they would not be interchangeable, even if bioequivalent. The safety of APIs and drug products manufactured outside the United States in non-Food and Drug Administration-regulated facilities are of concern, particularly agents that may contain harmful impurities, such as obesity products formulated as mesylate salts.

  15. 76 FR 16533 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-24

    ... portions that reflect approval of eight new animal drug applications. The final rule inadvertently failed... approval of eight new animal drug applications. The final rule inadvertently failed to add conforming...

  16. How to Seek EPA Approval for Pesticide Applicator Soil Fumigation Exams

    EPA Pesticide Factsheets

    Registrants of soil fumigant products offer EPA-approved training for certified pesticide applicators. Although not required, state lead agencies (SLAs) may seek EPA’s approval and provide applicators with an alternative to registrant-sponsored training.

  17. 7 CFR 58.443 - Whey handling.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Operations and Operating... objectionable odors. (b) Whey or whey products intended for human food shall at all times be handled in a...

  18. 48 CFR 9.308-2 - Testing performed by the Government.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS First Article Testing and Approval 9.308-2 Testing performed by... produce the first article and the production quantity at the same facility, the contracting officer shall... purchase material or to commence production before first article approval, the contracting officer shall...

  19. 48 CFR 9.308-2 - Testing performed by the Government.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS First Article Testing and Approval 9.308-2 Testing performed by... produce the first article and the production quantity at the same facility, the contracting officer shall... purchase material or to commence production before first article approval, the contracting officer shall...

  20. 48 CFR 9.308-2 - Testing performed by the Government.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS First Article Testing and Approval 9.308-2 Testing performed by... produce the first article and the production quantity at the same facility, the contracting officer shall... purchase material or to commence production before first article approval, the contracting officer shall...

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