Regulatory administrative databases in FDA's Center for Biologics Evaluation and Research: convergence toward a unified database.

PubMed

Smith, Jeffrey K

2013-04-01

Regulatory administrative database systems within the Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) are essential to supporting its core mission, as a regulatory agency. Such systems are used within FDA to manage information and processes surrounding the processing, review, and tracking of investigational and marketed product submissions. This is an area of increasing interest in the pharmaceutical industry and has been a topic at trade association conferences (Buckley 2012). Such databases in CBER are complex, not for the type or relevance of the data to any particular scientific discipline but because of the variety of regulatory submission types and processes the systems support using the data. Commonalities among different data domains of CBER's regulatory administrative databases are discussed. These commonalities have evolved enough to constitute real database convergence and provide a valuable asset for business process intelligence. Balancing review workload across staff, exploring areas of risk in review capacity, process improvement, and presenting a clear and comprehensive landscape of review obligations are just some of the opportunities of such intelligence. This convergence has been occurring in the presence of usual forces that tend to drive information technology (IT) systems development toward separate stovepipes and data silos. CBER has achieved a significant level of convergence through a gradual process, using a clear goal, agreed upon development practices, and transparency of database objects, rather than through a single, discrete project or IT vendor solution. This approach offers a path forward for FDA systems toward a unified database.

FDA, CE mark or something else?-Thinking fast and slow.

PubMed

Mishra, Sundeep

There is a robust debate going on among the Medical Device stake-holders whether FDA is better or CE mark or something else. Currently process of obtaining an FDA approval is bogged down by ever-increasing unpredictability, inconsistency, prolonged time, and huge expense but CE mark has its own problems. Historically, the Japanese review process has tended to be the slowest among the big three but recently with the introduction of accelerated review process there has been a significant progress. While the goal of an innovator/manufacturer is to develop, manufacture and market a medical device that addresses an unmet clinical need, the requisite regulatory approval process can be very confusing. Not only there is a whole lot of jargon tossed around by regulatory affair professionals: "substantial equivalence," "PMDA," "CE mark," "Notified body," "510K" and "PMA" but the actual approval process can also be very tardy, inconsistent and expensive. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

FDA use of international standards in the premarket review process.

PubMed

Rechen, E; Barth, D J; Marlowe, D; Kroger, L

1998-01-01

"This is an exciting time," says Eric Rechen, policy analyst in the U.S. Food and Drug Administration's (FDA) Office of Device Evaluation (ODE). "We're entering an era in which standards will have a more prominent role in the review of medical devices than ever before." During the past 10 years, there has been significant growth in the importance of standards in regulatory processes, as Donald J. Barth, regulatory staff manager for the Medical Products Group at Hewlett Packard Company, notes in setting the stage for discussion of the latest developments. Donald Marlowe, director of the FDA's Office of Science and Technology, and Rechen explain the use of standards in the regulatory review process as part of FDA efforts to ensure public safety in a time of shrinking agency resources. Marlowe discusses provisions of the FDA Modernization Act of 1997 that allow manufacturers to submit a declaration of conformity to a standard to satisfy premarket review requirements. A guidance on the recognition and use of consensus standards, a list of recognized standards, and a list of frequently asked questions are available at the Web site of the Center for Devices and Radiological Health (CDRH) at www.fda.gov/cdrh and via the AAMI Web site at www.aami.org. The information is also available by telephone via CDRH Facts on Demand at 800-899-0381. Rechen provides details about the two new approaches for premarket notifications available under the new 510(k) paradigm. Manufacturers may demonstrate substantial equivalence through special and abbreviated 510(k)s in addition to traditional 510(k)s. A copy of the new 510(k) paradigm is available at the AAMI and CDRH Web sites and through Facts on Demand. As the FDA and many manufacturers enter the new world of abbreviated and special 510(k)s, Larry Kroger, GE Medical Systems, provides his comments based on the 4 years of experience manufacturers of diagnostic x-ray products have had with simplified 510(k)s. A comparison of the European conformity assessment procedures with the new 510(k) paradigm will appear in an upcoming issue of BI&T.

The Prescription Drug User Fee Act: Cause for Concern?

PubMed

Gabay, Michael

2018-04-01

The Prescription Drug User Fee Act (PDUFA) was originally enacted into law in 1992. PDUFA provides the Food and Drug Administration (FDA) with needed revenue in the form of various fees paid by drug and biologic manufacturers. The FDA utilizes this revenue to streamline the review and approval process for medications. Since the enactment of PDUFA, the median approval time for priority new drug applications and biologics license applications has reduced significantly. The FDA views PDUFA as a successful program that provides a consistent revenue stream to the agency, improves access to medications for patients, and allows industry to have a more predictable product review timeline. However, critics of PDUFA cite concerns including the potential for a lack of FDA independence and medication safety issues involving drugs approved after the existence of PDUFA.

Medical Device Regulation: A Comparison of the United States and the European Union.

PubMed

Maak, Travis G; Wylie, James D

2016-08-01

Medical device regulation is a controversial topic in both the United States and the European Union. Many physicians and innovators in the United States cite a restrictive US FDA regulatory process as the reason for earlier and more rapid clinical advances in Europe. The FDA approval process mandates that a device be proved efficacious compared with a control or be substantially equivalent to a predicate device, whereas the European Union approval process mandates that the device perform its intended function. Stringent, peer-reviewed safety data have not been reported. However, after recent high-profile device failures, political pressure in both the United States and the European Union has favored more restrictive approval processes. Substantial reforms of the European Union process within the next 5 to 10 years will result in a more stringent approach to device regulation, similar to that of the FDA. Changes in the FDA regulatory process have been suggested but are not imminent.

Food irradiation—US regulatory considerations

NASA Astrophysics Data System (ADS)

Morehouse, Kim M.

2002-03-01

The use of ionizing radiation in food processing has received increased interest as a means of reducing the level of foodborne pathogens. This overview discusses the regulatory issues connected with the use of this technology in the United States. Several recent changes in the FDA's review process are discussed. These include the current policy that utilizes an expedited review process for petitions seeking approval of additives and technologies intended to reduce pathogen levels in food, and the recent USDA rule that eliminates the need for a separate rulemaking process by USDA for irradiation of meat and poultry. Recently promulgated rules and pending petitions before the FDA associated with the use of ionizing radiation for the treatment of foods are also discussed along with the current FDA labeling requirements for irradiated foods and the 1999 advanced notice of proposed rule on labeling. Another issue that is presented is the current status of the approval of packaging materials intended for food contact during irradiation treatment of foods.

Development of an automated assessment tool for MedWatch reports in the FDA adverse event reporting system.

PubMed

Han, Lichy; Ball, Robert; Pamer, Carol A; Altman, Russ B; Proestel, Scott

2017-09-01

As the US Food and Drug Administration (FDA) receives over a million adverse event reports associated with medication use every year, a system is needed to aid FDA safety evaluators in identifying reports most likely to demonstrate causal relationships to the suspect medications. We combined text mining with machine learning to construct and evaluate such a system to identify medication-related adverse event reports. FDA safety evaluators assessed 326 reports for medication-related causality. We engineered features from these reports and constructed random forest, L1 regularized logistic regression, and support vector machine models. We evaluated model accuracy and further assessed utility by generating report rankings that represented a prioritized report review process. Our random forest model showed the best performance in report ranking and accuracy, with an area under the receiver operating characteristic curve of 0.66. The generated report ordering assigns reports with a higher probability of medication-related causality a higher rank and is significantly correlated to a perfect report ordering, with a Kendall's tau of 0.24 ( P  = .002). Our models produced prioritized report orderings that enable FDA safety evaluators to focus on reports that are more likely to contain valuable medication-related adverse event information. Applying our models to all FDA adverse event reports has the potential to streamline the manual review process and greatly reduce reviewer workload. Published by Oxford University Press on behalf of the American Medical Informatics Association 2017. This work is written by US Government employees and is in the public domain in the United States.

A Comparative Review of Waivers Granted in Pediatric Drug Development by FDA and EMA from 2007-2013.

PubMed

Egger, Gunter F; Wharton, Gerold T; Malli, Suzanne; Temeck, Jean; Murphy, M Dianne; Tomasi, Paolo

2016-09-01

The European Union and the United States have different legal frameworks in place for pediatric drug development, which can potentially lead to different pediatric research requirements for the pharmaceutical industry. This manuscript compares pediatric clinical trial waivers granted by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). This is a retrospective review comparing EMA's Paediatric Committee (PDCO) decisions with FDA's Pediatric Review Committee (PeRC) recommendations for all product-specific pediatric full waiver applications submitted to EMA from January 2007 through December 2013. Using baseline data from EMA, we matched product-specific waivers with their FDA equivalents during the study period. For single active substance products, PDCO and PeRC adopted similar opinions in 42 of 49 indications (86%). For fixed-dose combinations, PDCO and PeRC adopted similar opinions in 24 of 31 indications (77%). Despite the different legal frameworks, criteria, and processes of determination, the waiver decisions of the 2 agencies were similar in the majority of cases.

78 FR 310 - Draft Revision of Guidance for Industry on Providing Regulatory Submissions in Electronic Format...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-03

...ApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm253101.htm , http://www.regulations.../Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm253101.htm , http...), in a format that FDA can process, review, and archive. Currently, the Agency can process, review, and...

Pharmacogenomics in the assessment of therapeutic risks versus benefits: inside the United States Food and Drug Administration.

PubMed

Zineh, Issam; Pacanowski, Michael A

2011-08-01

Pharmacogenomics is the study of how genetic variations influence responses to drugs, diagnostics, or biologic agents. The field of pharmacogenomics has significant potential to enhance drug development and aid in making regulatory decisions. The United States Food and Drug Administration (FDA) has supported pharmacogenomics for nearly a decade by providing regulatory advice and reviewing applications, with the intent of discovering and applying genetic determinants of treatment effects. The FDA will continue to develop policies and processes centered on genomics and individualized therapeutics to guide rational drug development. It will also continue to inform the public of clinically relevant pharmacogenomic issues through various mechanisms of communication, such as drug labeling. In this review, we provide a perspective on several pharmacogenomic activities at the FDA. In addition, we attempt to clarify what we believe are several misperceptions regarding the FDA's pharmacogenomic initiatives. We hope this perspective provides a window into some ways in which the FDA is enabling individualized therapeutics through its mission-critical activities.

77 FR 34958 - Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... the Agency considers your comment on this draft guidance before it begins work on the final version of... the regulated entities under FDA's and OHRP's jurisdiction. The Agencies wish to stress, however, that... other entities involved in the study oversight transfer process. FDA and OHRP will continue to work...

75 FR 57962 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-23

... identified in FDA's official establishment inventory plus 1,220 very small apple juice manufacturers and 230... Importing of Juice AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... Sanitary Processing and Importing of Juice--(OMB Control Number 0910-0466)--Extension FDA's regulations in...

78 FR 77686 - Agency Information Collection Activities; Proposed Collection; Comment Request; Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... and review process. FDA's regulations governing application for Agency approval to market a new drug... Agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of... submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

75 FR 10294 - Strengthening the Center for Devices and Radiological Health's 510(k) Review Process; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

...] Strengthening the Center for Devices and Radiological Health's 510(k) Review Process; Public Meeting; Extension...). In the notice, FDA requested comments on a number of identified challenges associated with the 510(k... premarket notification (or 510(k)) process for the review of medical devices. Specific questions for comment...

A review of the progress and pitfalls of FDA policy process: Planning a pathway for pharmaceutical interventions for hearing loss development.

PubMed

Hammill, Tanisha L

2017-06-01

The Federal Food and Drug Administration, or FDA is generally considered a powerful gatekeeper, able to deliver or withhold life-saving cures and create or destroy economic windfalls. As the decades go by, and technologies, diseases, public health demands, and politics evolve, we can identify patterns of change, action and inter-action among some of these traditional stakeholders in the FDA's policy sphere. A careful examination of this agency's colorful history can shed light on central features of the agency's policy process, which has been quite receptive to its stakeholders and adaptive to change over the decades and, in turn, show the way for development in lanes which do not fit neatly into the current paradigms offered by the agency. This paper will explore the history of FDA policy process, through examination of seminal moments in FDA history, the prominent actors and focusing events within them, and the outcomes of those events, in an attempt to illuminate a pattern of behavior or processes by which a struggling field of pharmaceutical development such as interventions for hearing loss can advance. Copyright © 2016 Elsevier B.V. All rights reserved.

75 FR 4402 - Strengthening the Center for Devices and Radiological Health's 510(k) Review Process; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

..., clinical studies conducted to demonstrate superiority to a control, instead of non- inferiority to a... will include no more than 10 non-FDA participants. Only one participant from an organization or company will be assigned to the discussion group. FDA will attempt to have a range of constituencies...

78 FR 35273 - Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

..., to FDA for approval to market a product in interstate commerce. The container and package labeling... be in electronic format and in a form that FDA can process, review, and archive. This requirement is... 356h ``Application to Market a New Drug, Biologic, or an Antibiotic Drug for Human Use'' to harmonize...

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.

Development and approval of vaccines in the United States.

PubMed

Botstein, P

1986-01-01

In the United States, vaccines and the establishments in which they are manufactured are required to be licensed by the Food and Drug Administration (FDA) before the vaccine can be marketed. This licensing process, as well as the development and investigation of vaccines, is regulated by the FDA's Office of Biologics Research and Review. An application for licensing must contain information supporting the safety, effectiveness, purity and potency of the product. These are data obtained during the investigational phase and then submitted by a commercial sponsor for review and approval. Inspections, surveillance and laboratory testing are performed by the FDA before and after issuance of a license for marketing. The procedures and policies in the investigational and licensing phases of vaccine development are described.

78 FR 11204 - Accreditation and Reaccreditation Process for Firms Under the Third Party Review Program: Part I...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

...] Accreditation and Reaccreditation Process for Firms Under the Third Party Review Program: Part I; Draft Guidance... announcing the availability of the draft guidance entitled ``Accreditation and Reaccreditation Process for... Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA), requires FDA...

78 FR 10179 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... for Devices and Radiological Health (CDRH) Appeals Processes'' revises, updates, and combines two... regarding CDRH's appeal processes. Individuals outside of FDA who disagree with a decision or action taken by CDRH and wish to have it reviewed or reconsidered have several processes for resolution from which...

Drug interactions evaluation: An integrated part of risk assessment of therapeutics

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

Zhang, Lei; Reynolds, Kellie S.; Zhao, Ping

2010-03-01

Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance ( (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf)) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industrymore » and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a 'Drug Development and Drug Interactions' website to provide up-to-date information regarding evaluation of drug interactions ( (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm)). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process.« less

76 FR 11783 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-N-0265... and Budget Review; Comment Request; Food Canning Establishment Registration, Process Filing, and Recordkeeping for Acidified Foods and Thermally Processed Low-Acid Foods in Hermetically Sealed Containers...

Case studies with new excipients: development, implementation and regulatory approval.

PubMed

Koo, Otilia M Y; Varia, Sailesh A

2011-07-01

The purpose of this article is to describe the process whereby new excipients become accepted and to describe three case studies to illustrate the process. New excipients are defined according to the 2005 FDA Guidance on Nonclinical Safety Evaluation of New Excipients. The requirements for safety data submission for new excipients used in different classes of products for different durations are outlined in the guidance. Currently, the development of new excipients is linked to the development and approval of new drug products that contain them. New excipients that are used in US-approved drug products become listed in the FDA Inactive Ingredients Guide (IIG) database. Thereafter, US Pharmacopeia monographs for the new excipients are proposed. New excipients are reviewed and become accepted in the same way in Europe and Japan, except that there is no equivalent IIG database. Therefore, the focus of this article will be on the FDA review process. Three case studies, polyoxyl 15 hydroxystearate, sulfobutyl ether cyclodextrin and silicified microcrystalline cellulose, are used to illustrate how new excipients are accepted and implemented.

Current FDA directives for promoting public health

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

Hayes, A.H. Jr.

1982-03-01

The current directions of the FDA are outlined. The underlying philosophy of the FDA under the Reagan Administration is that both the private sector and the government must address the responsibilities to which they are best suited for the health-care system to work more efficiently. To facilitate this, FDA is conducting comprehensive reviews of FDA regulations and the drug-evaluation process. There are many dimensions to promoting public health, and the FDA alone cannot assure an adequate supply of safe and effective drugs. Innovative science and technology are needed to develop new drugs, followed by maximum potentiation (maximum good and leastmore » harm) after FDA approval. Hospital pharmacists have a role in maximizing the potential benefits of drugs through pharmacy and therapeutics committees. The current status of the pilot program for patient package inserts is described. The response at a recent hearing on the program indicates that the responsibility to protect the public health is shared by the government, health professions, industry, and the public. The FDA's campaign on sodium is based on that shared responsibility. By improving communication and building upon their common objections, both pharmacy and the FDA can do their jobs successfully.« less

Quantifying The Food And Drug Administration's rulemaking delays highlights the need for transparency.

PubMed

Hwang, Thomas J; Avorn, Jerry; Carpenter, Daniel; Kesselheim, Aaron S

2014-02-01

The Food and Drug Administration (FDA) frequently uses its rulemaking process to establish or modify the way it regulates drugs, medical devices, and other medical products. The federal agency's rulemaking is controversial because of its perceived complexity, lack of transparency, and lengthy duration. To shed light on the FDA's rulemaking process, we examined the evolution of significant rules that the agency published during 2000-12 for drugs, devices, and other medical products. We found that the rules' median time to finalization was 7.3 years, with the pre-rule phase and postreview deliberation within the FDA accounting for the majority of that time. Rules that involved mandatory cost-benefit analyses were associated with an additional delay of approximately two years. We also found that longer review times were significantly associated with a reduction in the stringency of final rules, compared to the originally proposed versions. We recommend improving FDA's rulemaking by allocating additional resources to increase efficiency and by embarking on initiatives to promote transparency by the FDA and other parts of the executive branch.

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

Removal of Review and Reclassification Procedures for Biological Products Licensed Prior to July 1, 1972. Final rule.

PubMed

2016-02-12

The Food and Drug Administration (FDA, the Agency, or we) is removing two regulations that prescribe procedures for FDA's review and classification of biological products licensed before July 1, 1972. FDA is taking this action because the two regulations are obsolete and no longer necessary in light of other statutory and regulatory authorities established since 1972, which allow FDA to evaluate and monitor the safety and effectiveness of all biological products. In addition, other statutory and regulatory authorities authorize FDA to revoke a license for biological products because they are not safe and effective, or are misbranded. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation.

Translating New Science Into the Drug Review Process

PubMed Central

Rouse, Rodney; Kruhlak, Naomi; Weaver, James; Burkhart, Keith; Patel, Vikram; Strauss, David G.

2017-01-01

In 2011, the US Food and drug Administration (FDA) developed a strategic plan for regulatory science that focuses on developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. In line with this, the Division of Applied Regulatory Science was created to move new science into the Center for Drug Evaluation and Research (CDER) review process and close the gap between scientific innovation and drug review. The Division, located in the Office of Clinical Pharmacology, is unique in that it performs mission-critical applied research and review across the translational research spectrum including in vitro and in vivo laboratory research, in silico computational modeling and informatics, and integrated clinical research covering clinical pharmacology, experimental medicine, and postmarket analyses. The Division collaborates with Offices throughout CDER, across the FDA, other government agencies, academia, and industry. The Division is able to rapidly form interdisciplinary teams of pharmacologists, biologists, chemists, computational scientists, and clinicians to respond to challenging regulatory questions for specific review issues and for longer-range projects requiring the development of predictive models, tools, and biomarkers to speed the development and regulatory evaluation of safe and effective drugs. This article reviews the Division’s recent work and future directions, highlighting development and validation of biomarkers; novel humanized animal models; translational predictive safety combining in vitro, in silico, and in vivo clinical biomarkers; chemical and biomedical informatics tools for safety predictions; novel approaches to speed the development of complex generic drugs, biosimilars, and antibiotics; and precision medicine. PMID:29568713

The ABCs of the FDA: A Primer on the Role of the United States Food and Drug Administration in Medical Device Approvals and IR Research.

PubMed

Adamovich, Ashley; Park, Susie; Siskin, Gary P; Englander, Meridith J; Mandato, Kenneth D; Herr, Allen; Keating, Lawrence J

2015-09-01

The role of the US Food and Drug Administration (FDA) in medical device regulation is important to device-driven specialties such as interventional radiology. Whether it is through industry-sponsored trials during the approval process for new devices or investigator-initiated research prospectively evaluating the role of existing devices for new or established procedures, interaction with the FDA is an integral part of performing significant research in interventional radiology. This article reviews the potential areas of interface between the FDA and interventional radiology, as understanding these areas is necessary to continue the innovation that is the hallmark of this specialty. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Interagency Oncology Task Force Fellowship

Cancer.gov

In collaboration with FDA, these fellowships train scientists in research and research-related regulatory review, policies, and regulations to develop a skill set that bridges the two disparate processes.

75 FR 32479 - Determination of Regulatory Review Period for Purposes of Patent Extension; ABLAVAR

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket Nos. FDA-2009-E-0165 and FDA-2009-E-0169] Determination of Regulatory Review Period for Purposes of Patent Extension... Administration (FDA) has determined the regulatory review period for ABLAVAR (previously the trade name of the...

21 CFR 314.100 - Timeframes for reviewing applications and abbreviated applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.100 Timeframes for reviewing... application for a new drug under section 505(j) of the act, FDA will review it and send the applicant either...

21 CFR 314.100 - Timeframes for reviewing applications and abbreviated applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.100 Timeframes for reviewing... application for a new drug under section 505(j) of the act, FDA will review it and send the applicant either...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.100 - Timeframes for reviewing applications and abbreviated applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.100 Timeframes for reviewing... application for a new drug under section 505(j) of the act, FDA will review it and send the applicant either...

21 CFR 314.100 - Timeframes for reviewing applications and abbreviated applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.100 Timeframes for reviewing... application for a new drug under section 505(j) of the act, FDA will review it and send the applicant either...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

21 CFR 314.100 - Timeframes for reviewing applications and abbreviated applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.100 Timeframes for reviewing... application for a new drug under section 505(j) of the act, FDA will review it and send the applicant either...

21 CFR 314.60 - Amendments to an unapproved application, supplement, or resubmission.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW...) FDA generally assumes that when an original application, supplement to an approved application, or... the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review...

Agenda: EDRN FDA Education Workshop — EDRN Public Portal

Cancer.gov

The purpose of this workshop was to open dialogue between FDA staff that provide oversight for review of in vitro diagnostic applications and EDRN scientists currently performing clinical validation studies on cancer biomarkers. Issues related to FDA review of diagnostic tests were presented by FDA personnel. Representatives from EDRN provided details on supporting data of their validation studies and the resources developed within EDRN to facilitate such research for FDA compliance. The agenda provided here provides links to the presentations by each speaker.

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.

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

Spin in RCTs of anxiety medication with a positive primary outcome: a comparison of concerns expressed by the US FDA and in the published literature.

PubMed

Beijers, Lian; Jeronimus, Bertus F; Turner, Erick H; de Jonge, Peter; Roest, Annelieke M

2017-03-29

This study aimed to determine the presence of spin in papers on positive randomised clinical trials (RCTs) of antidepressant medication for anxiety disorders by comparing concerns expressed in the Food and Drug Administration (FDA) reviews with those expressed in the published paper. For every positive anxiety medication trial with a matching publication (n=41), two independent reviewers identified the concerns raised in the US FDA reviews and those in the published literature. Spin was identified when concerns or limitations were expressed by the FDA (about the efficacy of the study drug) but not in the corresponding published paper. Concerns mentioned in the papers but not by the FDA were scored as 'non-FDA' concerns. Only six out of 35 (17%) of the FDA concerns pertaining to drug efficacy were reported in the papers. Two papers mentioned a concern that fit the FDA categories, but was not mentioned in the corresponding FDA review. Eighty-seven non-FDA concerns were counted, which often reflected general concerns or concerns related to the study design. Results indicate the presence of substantial spin in the clinical trial literature on drugs for anxiety disorders. In papers describing RCTs on anxiety medication, the concerns raised by the authors differed from those raised by the FDA. Published papers mentioned a large number of generic concerns about RCTs, such as a lack of long-term research and limited generalisability, while they mentioned few concerns about drug efficacy. These results warrant the promotion of independent statistical review, reporting of patient-level data, more study of spin, and an increased expectation that authors report FDA concerns. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Gaps, tensions, and conflicts in the FDA approval process: implications for clinical practice.

PubMed

Deyo, Richard A

2004-01-01

Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.

The use of compound topical anesthetics: a review.

PubMed

Kravitz, Neal D

2007-10-01

The author reviewed the history of, federal regulations regarding, risks of and adverse drug reactions of five compound topical anesthetics: tetracaine, adrenaline/epinephrine and cocaine (TAC); lidocaine, adrenaline/epinephrine and tetracaine (LET); lidocaine, tetracaine and phenylephrine (TAC 20 percent Alternate); lidocaine, prilocaine and tetracaine (Profound); and lidocaine, prilocaine, tetracaine and phenylephrine with thickeners (Profound PET). The author reviewed clinical trials, case reports, descriptive articles, and U.S. Food and Drug Administration (FDA) regulations and recent public advisory warnings regarding the federal approval of and risks associated with the use of compound topical anesthetics. Compound topical anesthetics are neither FDA-regulated nor -unregulated. Some compounding pharmacies bypass the new FDA drug approval process, which is based on reliable scientific data and ensures that a marketed drug is safe, effective, properly manufactured and accurately labeled. Two deaths have been attributed to the lay use of compound topical anesthetics. In response, the FDA has announced the strengthening of its efforts against unapproved drug products. Compound topical anesthetics may be an effective alternative to local infiltration for some minimally invasive dental procedures; however, legitimate concerns exist in regard to their safety. Until they become federally regulated, compound topical anesthetics remain unapproved drug products whose benefits may not outweigh their risks for dental patients.

New orthopedic devices and the FDA.

PubMed

Sheth, Ujash; Nguyen, Nhu-An; Gaines, Sean; Bhandari, Mohit; Mehlman, Charles T; Klein, Guy

2009-01-01

Each year the field of orthopedics is introduced to an influx of new medical devices. Each of these medical devices has faced certain hurdles prior to being approved for marketing by the U.S. Food and Drug Administration (FDA). Among the regulatory pathways available, the 510(k) premarket notification is by far the one most commonly used. The 510(k) premarket notification allows the manufacturer to receive prompt approval of their device by demonstrating that it is "substantially equivalent" to an existing legally marketed device. In most instances, this proof of substantial equivalence allows manufacturers of medical devices to bypass the use of clinical trials, which are a hallmark of the approval process for new drugs. As a result, most medical devices are approved without demonstrating safety or effectiveness. This article reviews the regulatory processes used by the FDA to evaluate new orthopedic devices.

Evidentiary Support in Public Comments to the FDA's Center for Tobacco Products.

PubMed

Hemmerich, Natalie; Klein, Elizabeth G; Berman, Micah

2017-08-01

Electronic Nicotine Delivery Systems (ENDS) were introduced into the US market in 2007, and until recently these devices were unregulated at the federal level. In 2014, the US Food and Drug Administration (FDA) published a Notice of Proposed Rulemaking asserting its intention to regulate ENDS and requesting public comments on numerous related issues, including potential limits on the sale of flavored ENDS. This article analyzes key comments submitted to the FDA on the issue of flavor regulation in ENDS and examines the weight and credibility of the evidence presented by both supporters and opponents of regulation. It also describes the final deeming rule, published in May 2016, and the FDA's response to the evidence submitted. This is the first study to examine public comments submitted to the FDA's Center for Tobacco Products, and it concludes that opponents of regulation were more likely to rely on sources that were not peer reviewed and that were affected by conflicts of interest. In light of these findings, the FDA and the research community should develop processes to carefully and critically analyze public comments submitted to the FDA on issues of tobacco regulation. Copyright © 2017 by Duke University Press.

21 CFR 814.44 - Procedures for review of a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.44 Procedures for review of a PMA. (a) FDA will begin substantive review of a PMA after the PMA is accepted for filing under § 814.42. FDA may refer the PMA to a panel on its own initiative, and will do so upon request of an...

Life cycle of medical product rules issued by the US Food and Drug Administration.

PubMed

Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

2014-08-01

The US Food and Drug Administration (FDA) uses rulemaking as one of its primary tools to protect the public health and implement laws enacted by Congress and the president. Because of the many effects that these rules have on social welfare and the economy, the FDA and other executive agencies receive input from the executive branch, the public, and in some cases, the courts, during the process of rulemaking. In this article, we examine the life cycle of FDA regulations concerning medical products and review notable features of the rulemaking process. The current system grants substantial opportunities for diverse stakeholders to participate in and influence how rules are written and implemented. However, the duration, complexity, and adversarial qualities of the rulemaking process can hinder the FDA's ability to achieve its policy and public health goals. There is considerable variation in the level of transparency at different stages in the process, ranging from freely accessible public comments to undisclosed internal agency deliberations. In addition, significant medical product rules are associated with lengthy times to finalization, in some cases for unclear reasons. We conclude by identifying potential areas for reform on the basis of transparency and efficiency. Copyright © 2014 by Duke University Press.

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting.

PubMed

Phillips, Adam T; Desai, Nihar R; Krumholz, Harlan M; Zou, Constance X; Miller, Jennifer E; Ross, Joseph S

2017-07-18

Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry. Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation. Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive. FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

21 CFR 814.44 - Procedures for review of a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.44 Procedures for review of a PMA. Link to an amendment published at 75 FR 16351, Apr. 1, 2010. (a) FDA will begin substantive review of a PMA after the PMA is accepted for filing under § 814.42. FDA may refer the PMA to a panel on...

21 CFR 814.44 - Procedures for review of a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.44 Procedures for review of a PMA. Link to an amendment published at 79 FR 1740, Jan. 10, 2014. (a) FDA will begin substantive review of a PMA after the PMA is accepted for filing under § 814.42. FDA may refer the PMA to a panel on...

76 FR 45271 - Review and Qualification of Clinical Outcome Assessments; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-28

... announcing a public workshop to discuss measurement principles for clinical outcome assessments (COAs) for... appropriate drug development program. Because the qualification process is separate from the drug marketing... other DDTs. This workshop will focus on FDA review principles specific to all type of COAs, i.e., PRO...

A Comparative Review of Waivers Granted in Pediatric Drug Development by FDA and EMA from 2007-2013

PubMed Central

Egger, Gunter F.; Wharton, Gerold T.; Malli, Suzanne; Temeck, Jean; Murphy, M. Dianne; Tomasi, Paolo

2016-01-01

Background The European Union and the United States have different legal frameworks in place for pediatric drug development, which can potentially lead to different pediatric research requirements for the pharmaceutical industry. This manuscript compares pediatric clinical trial waivers granted by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Methods This is a retrospective review comparing EMA’s Paediatric Committee (PDCO) decisions with FDA’s Pediatric Review Committee (PeRC) recommendations for all product-specific pediatric full waiver applications submitted to EMA from January 2007 through December 2013. Using baseline data from EMA, we matched product-specific waivers with their FDA equivalents during the study period. Results For single active substance products, PDCO and PeRC adopted similar opinions in 42 of 49 indications (86%). For fixed-dose combinations, PDCO and PeRC adopted similar opinions in 24 of 31 indications (77%). Conclusion Despite the different legal frameworks, criteria, and processes of determination, the waiver decisions of the 2 agencies were similar in the majority of cases. PMID:27274951

The debate on FDA reform: a view from the U.S. Senate. Food and Drug Administration.

PubMed

Baker, R

1995-09-01

The recently released concept paper on Food and Drug Administration (FDA) reform from Republican Senator, Nancy Kassebaum, is reviewed. Senator Kassebaum chairs the Senate Committee on Labor and Human Resources that will influence the Senate's action on FDA reform. The paper outlines the Senator's priorities for Congressional legislation on FDA reform in the following areas: the FDA mission and its accountability; creation of a Performance Review Panel and Industry Advisory Council; approval and access of products for seriously ill patients; the FDA's responsibility for good manufacturing practices; establishment of an Ombudsman Office for resolving disputes; dissemination of information on unapproved uses of approved products; and approval standards for new drugs.

A review of the FDA draft guidance document for software validation: guidance for industry.

PubMed

Keatley, K L

1999-01-01

A Draft Guidance Document (Version 1.1) was issued by the United States Food and Drug Administration (FDA) to address the software validation requirement of the Quality System Regulation, 21 CFR Part 820, effective June 1, 1997. The guidance document outlines validation considerations that the FDA regards as applicable to both medical device software and software used to "design, develop or manufacture" medical devices. The Draft Guidance is available at the FDA web site http:@www.fda.gov/cdrh/comps/swareval++ +.html. Presented here is a review of the main features of the FDA document for Quality System Regulation (QSR), and some guidance for its implementation in industry.

21 CFR 814.40 - Time frames for reviewing a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.40 Time frames for... the applicant does not submit a major amendment, FDA will review the PMA and, after receiving the report and recommendation of the appropriate FDA advisory committee, send the applicant an approval order...

21 CFR 814.40 - Time frames for reviewing a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.40 Time frames for... the applicant does not submit a major amendment, FDA will review the PMA and, after receiving the report and recommendation of the appropriate FDA advisory committee, send the applicant an approval order...

21 CFR 814.40 - Time frames for reviewing a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.40 Time frames for... the applicant does not submit a major amendment, FDA will review the PMA and, after receiving the report and recommendation of the appropriate FDA advisory committee, send the applicant an approval order...

78 FR 65329 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... Safety Testing of Sunlamp Products'' Form FDA 3632 ``Guide for Preparing Product Reports on Lasers and Products Containing Lasers'' Form FDA 3633''General Variance Request'' Form FDA 3634 ``Television Products Annual Report'' Form FDA 3635 ``Laser Light Show Notification'' Form FDA 3636 ``Guide for Preparing...

75 FR 26964 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

... of Sunlamps and Sunlamp Products'' FDA Form 3632 ``Guide for Preparing Product Reports on Lasers and Products Containing Lasers'' FDA Form 3633 ``General Variance Request'' FDA Form 3634 ``Television Products Annual Report'' FDA Form 3635 ``Laser Light Show Notification'' FDA Form 3636 ``Guide for Preparing...

Central site monitoring: results from a test of accuracy in identifying trials and sites failing Food and Drug Administration inspection.

PubMed

Lindblad, Anne S; Manukyan, Zorayr; Purohit-Sheth, Tejashri; Gensler, Gary; Okwesili, Paul; Meeker-O'Connell, Ann; Ball, Leslie; Marler, John R

2014-04-01

Site monitoring and source document verification account for 15%-30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification. To determine whether a central review by statisticians using data submitted to the Food and Drug Administration (FDA) by clinical trial sponsors can identify problem sites and trials that failed FDA site inspections. An independent Analysis Center (AC) analyzed data from four anonymous new drug applications (NDAs) where FDA had performed site inspections overseen by FDA's Office of Scientific Investigations (OSI). FDA team members in the OSI chose the four NDAs from among all NDAs with data in Study Data Tabulation Model (SDTM) format. Two of the NDAs had data that OSI had deemed unreliable in support of the application after FDA site inspections identified serious data integrity problems. The other two NDAs had clinical data that OSI deemed reliable after site inspections. At the outset, the AC knew only that the experimental design specified two NDAs with significant problems. FDA gave the AC no information about which NDAs had problems, how many sites were inspected, or how many were found to have problems until after the AC analysis was complete. The AC evaluated randomization balance, enrollment patterns, study visit scheduling, variability of reported data, and last digit reference. The AC classified sites as 'High Concern', 'Moderate Concern', 'Mild Concern', or 'No Concern'. The AC correctly identified the two NDAs with data deemed unreliable by OSI. In addition, central data analysis correctly identified 5 of 6 (83%) sites for which FDA recommended rejection of data and 13 of 15 sites (87%) for which any regulatory deviations were identified during inspection. Of the six sites for which OSI reviewed inspections and found no deviations, the central process flagged four at the lowest level of concern, one at a moderate level, and one was not flagged. Central data monitoring during the conduct of a trial while data checking was in progress was not evaluated. Systematic central monitoring of clinical trial data can identify problems at the same trials and sites identified during FDA site inspections. Central data monitoring in conjunction with an overall monitoring process that adapts to identify risks as a trial progresses has the potential to reduce the frequency of site visits while increasing data integrity and decreasing trial costs compared to processes that are dependent primarily on source documentation.

76 FR 61565 - Preemption Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

.... FDA-2011-N-0527] Preemption Review AGENCY: Food and Drug Administration, HHS. ACTION: Notification of preemption review. SUMMARY: The Food and Drug Administration (FDA) is announcing that it has determined, after conducting a review of its existing regulations issued within the past 10 years that contain...

From bench to FDA to bedside: US regulatory trends for new stem cell therapies.

PubMed

Knoepfler, Paul S

2015-03-01

The phrase "bench-to-bedside" is commonly used to describe the translation of basic discoveries such as those on stem cells to the clinic for therapeutic use in human patients. However, there is a key intermediate step in between the bench and the bedside involving governmental regulatory oversight such as by the Food and Drug Administration (FDA) in the United States (US). Thus, it might be more accurate in most cases to describe the stem cell biological drug development process in this way: from bench to FDA to bedside. The intermediate development and regulatory stage for stem cell-based biological drugs is a multifactorial, continually evolving part of the process of developing a biological drug such as a stem cell-based regenerative medicine product. In some situations, stem cell-related products may not be classified as biological drugs in which case the FDA plays a relatively minor role. However, this middle stage is generally a major element of the process and is often colloquially referred to in an ominous way as "The Valley of Death". This moniker seems appropriate because it is at this point, and in particular in the work that ensues after Phase 1, clinical trials that most drug product development is terminated, often due to lack of funding, diseases being refractory to treatment, or regulatory issues. Not surprisingly, workarounds to deal with or entirely avoid this difficult stage of the process are evolving both inside and outside the domains of official regulatory authorities. In some cases these efforts involve the FDA invoking new mechanisms of accelerating the bench to beside process, but in other cases these new pathways bypass the FDA in part or entirely. Together these rapidly changing stem cell product development and regulatory pathways raise many scientific, ethical, and medical questions. These emerging trends and their potential consequences are reviewed here. Copyright © 2014 Elsevier B.V. All rights reserved.

76 FR 72712 - Agency Emergency Processing Under the Office of Management and Budget Review; Submission for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

... Management and Budget Review; Comment Request; Food and Drug Administration Food Safety Modernization Act...., Office of Information Management, Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0841...

TU-AB-204-00: CDRH/FDA Regulatory Processes and Device Science Activities

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

NONE

The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) andmore » the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC), Image Gently, and the Quantitative Imaging Biomarkers Alliance (QIBA) among others, to fulfill FDA’s mission will be discussed. Learning Objectives: Understand FDA’s pre-market and post-market review processes for medical devices Understand FDA’s current regulatory research activities in the areas of medical physics and imaging products Understand how being involved with AAPM and other organizations can also help to promote innovative, safe and effective medical devices J. Delfino, nothing to disclose.« less

Applications of functional data analysis: A systematic review.

PubMed

Ullah, Shahid; Finch, Caroline F

2013-03-19

Functional data analysis (FDA) is increasingly being used to better analyze, model and predict time series data. Key aspects of FDA include the choice of smoothing technique, data reduction, adjustment for clustering, functional linear modeling and forecasting methods. A systematic review using 11 electronic databases was conducted to identify FDA application studies published in the peer-review literature during 1995-2010. Papers reporting methodological considerations only were excluded, as were non-English articles. In total, 84 FDA application articles were identified; 75.0% of the reviewed articles have been published since 2005. Application of FDA has appeared in a large number of publications across various fields of sciences; the majority is related to biomedicine applications (21.4%). Overall, 72 studies (85.7%) provided information about the type of smoothing techniques used, with B-spline smoothing (29.8%) being the most popular. Functional principal component analysis (FPCA) for extracting information from functional data was reported in 51 (60.7%) studies. One-quarter (25.0%) of the published studies used functional linear models to describe relationships between explanatory and outcome variables and only 8.3% used FDA for forecasting time series data. Despite its clear benefits for analyzing time series data, full appreciation of the key features and value of FDA have been limited to date, though the applications show its relevance to many public health and biomedical problems. Wider application of FDA to all studies involving correlated measurements should allow better modeling of, and predictions from, such data in the future especially as FDA makes no a priori age and time effects assumptions.

Applications of functional data analysis: A systematic review

PubMed Central

2013-01-01

Background Functional data analysis (FDA) is increasingly being used to better analyze, model and predict time series data. Key aspects of FDA include the choice of smoothing technique, data reduction, adjustment for clustering, functional linear modeling and forecasting methods. Methods A systematic review using 11 electronic databases was conducted to identify FDA application studies published in the peer-review literature during 1995–2010. Papers reporting methodological considerations only were excluded, as were non-English articles. Results In total, 84 FDA application articles were identified; 75.0% of the reviewed articles have been published since 2005. Application of FDA has appeared in a large number of publications across various fields of sciences; the majority is related to biomedicine applications (21.4%). Overall, 72 studies (85.7%) provided information about the type of smoothing techniques used, with B-spline smoothing (29.8%) being the most popular. Functional principal component analysis (FPCA) for extracting information from functional data was reported in 51 (60.7%) studies. One-quarter (25.0%) of the published studies used functional linear models to describe relationships between explanatory and outcome variables and only 8.3% used FDA for forecasting time series data. Conclusions Despite its clear benefits for analyzing time series data, full appreciation of the key features and value of FDA have been limited to date, though the applications show its relevance to many public health and biomedical problems. Wider application of FDA to all studies involving correlated measurements should allow better modeling of, and predictions from, such data in the future especially as FDA makes no a priori age and time effects assumptions. PMID:23510439

US Food and Drug Administration draft recommendations on radioactive contamination of food

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

Thompson, D.L.

Recommendations on accidental radioactive contamination of human food were issued in 1982 by the Food and Drug Administration (FDA). The recommendations provided guidance to State and local government officials in the exercise of their respective authorities, and were applicable to emergency response planning and to the conduct of radiation protection activities associated with the production, processing, distribution, and use of human food accidentally contaminated with radioactive material. Review of the 1982 FDA recommendations, stimulated by the events following the 1986 accident at Chernobyl, indicated that it would be appropriate to update the recommendations to incorporate newer scientific information and radiationmore » protection philosophy, to include experience gained since 1982, and to take into account international advances. This paper presents a brief outline of the FDA`s approach to its draft revision. the most recent draft was circulated for interagency review in November 1994. Modification made in response to the comments received are included in this paper. 20 refs., 6 tabs.« less

76 FR 27062 - Biologics Price Competition and Innovation Act of 2009; Options for a User Fee Program for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

... under the Public Health Service Act (PHS Act). FDA is requesting input on the identified principles for... adhere to these principles, and performance goals for this program. FDA plans to review the comments... drug marketing applications were submitted each year for FDA review. The number of participants in the...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

76 FR 5179 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

... decisionmaking processes will provide the better understanding of target audiences that FDA needs to design... give their reaction to the messages in either individual or group settings. Third, as evaluative...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

Current good manufacturing practice and investigational new drugs intended for use in clinical trials. Final rule.

PubMed

2008-07-15

The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most phase 1 investigational drugs from complying with the regulatory CGMP requirements. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of the investigational new drug applications (IND). In addition, elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: CGMP for Phase 1 Investigational Drugs" dated November 2007 (the companion guidance). This guidance document sets forth recommendations on approaches to compliance with statutory CGMP for the exempted phase 1 investigational drugs. FDA is taking this action to focus a manufacturer's effort on applying CGMP that is appropriate and meaningful for the manufacture of the earliest stage investigational drug products intended for use in phase 1 clinical trials while ensuring safety and quality. This action will also streamline and promote the drug development process.

Some Non-FDA Approved Uses for Neuromodulation: A Review of the Evidence.

PubMed

Lee, Samuel; Abd-Elsayed, Alaa

2016-09-01

Neuromodulation, including spinal cord stimulation and peripheral nerve field stimulation, has been used with success in treating several painful conditions. The FDA approved the use of neuromodulation for a few indications. We review evidence for neuromodulation in treating some important painful conditions that are not currently FDA approved. This review included an online web search for only clinical trials testing the efficacy of neuromodulation in treating coronary artery disease, peripheral vascular disease (PVD), headache, and peripheral field stimulation. Our systematic literature search found 10, 6, and 3 controlled studies relating to coronary artery disease, PVD, and headache, respectively. Our review also included 5 noncontrolled studies relating to peripheral field stimulation, as no controlled studies had been completed. This review article shows compelling evidence based on clinical trials that neuromodulation can be of benefit for patients with serious painful conditions that are not currently approved by the FDA. © 2015 World Institute of Pain.

High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

PubMed

Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

2007-01-01

Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

Internet Database Review: The FDA BBS.

ERIC Educational Resources Information Center

Tomaiuolo, Nicholas G.

1993-01-01

Describes the electronic bulletin board system (BBS) of the Food and Drug Administration (FDA) that is accessible through the Internet. Highlights include how to gain access; the menu-driven software; other electronic sources of FDA information; and adding value. Examples of the FDA BBS menu and the help screen are included. (LRW)

Radiopharmaceutical regulation and Food and Drug Administration policy.

PubMed

Rotman, M; Laven, D; Levine, G

1996-04-01

The regulatory policy of the Food and Drug Administration (FDA) on radiopharmaceuticals flows from a rigid, traditional, drug-like interpretation of the FDC Act on the licensing of radiopharmaceuticals. This contributes to significant delays in the drug-approval process for radiopharmaceuticals, which are very costly to the nuclear medicine community and the American public. It seems that radiopharmaceuticals would be better characterized as molecular devices. Good generic rule-making principles include: use of a risk/benefit/cost analysis; intent based on sound science; performance standards prepared by outside experts; a definite need shown by the regulatory agency; to live with the consequences of any erroneous cost estimates; and design individual credential requirements so that additional training results in enhanced professional responsibility. When these common elements are applied to current FDA policy, it seems that the agency is out of sync with the stated goals for revitalizing federal regulatory policies as deemed necessary by the Clinton administration. Recent FDA rulings on positron-emission tomography, Patient Package inserts, and on medical device service accentuate the degree of such asynchronization. Radiopharmaceutical review and licensing flexibility could be dramatically improved by excluding radiopharmaceuticals from the drug category and reviewing them as separate entities. This new category would take into account their excellent record of safety and their lack of pharmacological action. Additionally, their evaluation of efficacy should be based on their ability to provide useful scintiphotos, data, or responses of the physiological system it portends to image, quantitate, or describe. To accomplish the goal of transforming the FDA's rigid, prescriptive policy into a streamlined flexible performance-based policy, the Council on Radionuclides and Radiopharmaceuticals proposal has been presented. In addition, it is suggested that the United States Pharmacopeia write radiopharmaceutical review standards, that an independent scientific body review the data submitted, and that the FDA either accept or reject the recommendation.

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.

Retrospective review of the performance standard for diagnostic x-ray equipment; availability of report--FDA. Notice; final rule-related.

PubMed

1985-11-12

The Food and Drug Administration (FDA) is announcing the availability of a report prepared by the X-Ray Standard Review Group (XSRG) in FDA's Center for Devices and Radiological Health (CDRH). The report contains the review group's assessment of the performance standard for diagnostic x-ray systems and their major components. It contains recommendations for changes in the standard with respect to the need to ensure that regulatory controls keep pace with developing technology and the needs of the radiological community. In addition, FDA is inviting interested persons to submit written comments, data, or information regarding the report for the agency's consideration in deciding whether to initiate any changes in the performance standard.

Anti-Obesity Agents and the US Food and Drug Administration.

PubMed

Casey, Martin F; Mechanick, Jeffrey I

2014-09-01

Despite the growing market for obesity care, the US Food and Drug Administration (FDA) has approved only two new pharmaceutical agents-lorcaserin and combination phentermine/topiramate-for weight reduction since 2000, while removing three agents from the market in the same time period. This article explores the FDA's history and role in the approval of anti-obesity medications within the context of a public health model of obesity. Through the review of obesity literature and FDA approval documents, we identified two major barriers preventing fair evaluation of anti-obesity agents including: (1) methodological pitfalls in clinical trials and (2) misaligned values in the assessment of anti-obesity agents. Specific recommendations include the use of adaptive (Bayesian) design protocols, value-based analyses of risks and benefits, and regulatory guidance based on a comprehensive, multi-platform obesity disease model. Positively addressing barriers in the FDA approval process of anti-obesity agents may have many beneficial effects within an obesity disease model.

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 320.30 - Inquiries regarding bioavailability and bioequivalence requirements and review of protocols by...

Code of Federal Regulations, 2012 CFR

2012-04-01

... bioequivalence requirements and review of protocols by the Food and Drug Administration. 320.30 Section 320.30... requirements and review of protocols by the Food and Drug Administration. (a) The Commissioner of Food and... for the study to FDA for review prior to the initiation of the study. (b) FDA may review a proposed...

21 CFR 320.30 - Inquiries regarding bioavailability and bioequivalence requirements and review of protocols by...

Code of Federal Regulations, 2014 CFR

2014-04-01

... bioequivalence requirements and review of protocols by the Food and Drug Administration. 320.30 Section 320.30... requirements and review of protocols by the Food and Drug Administration. (a) The Commissioner of Food and... for the study to FDA for review prior to the initiation of the study. (b) FDA may review a proposed...

21 CFR 320.30 - Inquiries regarding bioavailability and bioequivalence requirements and review of protocols by...

Code of Federal Regulations, 2013 CFR

2013-04-01

... bioequivalence requirements and review of protocols by the Food and Drug Administration. 320.30 Section 320.30... requirements and review of protocols by the Food and Drug Administration. (a) The Commissioner of Food and... for the study to FDA for review prior to the initiation of the study. (b) FDA may review a proposed...

TU-AB-204-01: Device Approval Process

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

Delfino, J.

The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) andmore » the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC), Image Gently, and the Quantitative Imaging Biomarkers Alliance (QIBA) among others, to fulfill FDA’s mission will be discussed. Learning Objectives: Understand FDA’s pre-market and post-market review processes for medical devices Understand FDA’s current regulatory research activities in the areas of medical physics and imaging products Understand how being involved with AAPM and other organizations can also help to promote innovative, safe and effective medical devices J. Delfino, nothing to disclose.« less

Chromium picolinate intake and risk of type 2 diabetes: an evidence-based review by the United States Food and Drug Administration.

PubMed

Trumbo, Paula R; Ellwood, Kathleen C

2006-08-01

The labeling of both health claims that meet significant scientific agreement (SSA) and qualified health claims on conventional foods and dietary supplements requires pre-market approval by the US Food and Drug Administration (FDA). Approval by the FDA involves, in part, a thorough review of the scientific evidence to support an SSA or a qualified health claim. This article discusses FDA's evidence-based review of the scientific evidence on the role of chromium picolinate supplements in reducing the risk of type 2 diabetes. Based on this evidence-based review, FDA issued a letter of enforcement discretion for one qualified health claim on chromium picolinate and risk of insulin resistance, a surrogate endpoint for type 2 diabetes. The agency concluded that the relationship between chromium picolinate intake and insulin resistance is highly uncertain.

78 FR 5463 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... currently assessing any additional data requirements. In this regard, FDA published an Advance Notice of... report. Here, e-form FDA 3744a and reporting via the Electronic Submission Gateway are provided by FDA... January 17, 2012 (77 FR 2302), FDA published a 60-day notice requesting public comment on the proposed...

76 FR 81511 - Draft Guidance for Industry and Food and Drug Administration Staff; Center for Devices and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

... ``Center for Devices and Radiological Health (CDRH) Appeals Processes.'' This document describes the processes available to outside stakeholders to request additional review of decisions and actions by CDRH... submit related requests to CDRH and FDA. This draft guidance is not final nor is it in effect at this...

Evaluation of efficacy of heartworm preventive products at the FDA.

PubMed

Hampshire, Victoria A

2005-10-24

The Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA/CVM) has authority under the United States Code 21 under Section 514.80 to monitor for adverse experiences of approved animal products. Although veterinarians voluntarily report suspect drug-related events to manufacturers, firms that market FDA-approved animal products must report serious events to the FDA within 15 working days of the veterinarian or pet-owner's call to them. Under the present regulations, canine heartworm preventatives are approved for 100% efficacy after testing in laboratory and field conditions. The report of lack of efficacy against heartworm larvae is a serious adverse drug event because the resulting condition or the treatment of the condition is life threatening. Information on lack of effect that are deemed possibly, probably, or definitely drug-related available for review under generic product on the FDA/CVM website Surveillance of these reports indicates there are some failures for virtually all heartworm prevention product categories. Most failures have been reported in heartworm-endemic states. At this time, it is unclear whether these are representative of the rare occurrences of failure that have been in existence for a long time, but not reported regularly or promptly, or whether there is a true increase in complaints of ineffectiveness and real variability between products. This paper discusses methods, personnel, and procedures in place in the Division of Surveillance that will aid the FDA to better assess heartworm preventive treatment failures. It discusses scoring paradigms presently utilized by FDA/CVM to assess severity of complaints of lack of efficacy against heartworms, and welcomes audience input as to how to improve existing processes. Results suggest that more comprehensive reporting will provide FDA/CVM more accurate surveillance information regarding efficacy problems. Such practices will permit FDA/CVM to better interpret both incidence and severity of in-effect and possible patterns of emerging resistance and to convey this in any necessary updated labeling. It also indicates that as part of that process, practitioners should return to a more conservative testing schedule.

A safety review of the medications used to treat atopic dermatitis.

PubMed

Shukla, Shweta; Feldman, Steven R; Strowd, Lindsay C

2018-02-01

Atopic dermatitis (AD) is a common disease in children and adults which causes severe physical discomfort and psychosocial distress. Recently novel therapies for AD have been FDA approved for use which creates the need to review the safety surrounding current FDA approved AD medications. Areas covered: Published clinical studies involving topical and oral FDA approved medications for AD are included in this review. Authors used PubMed research database to search for clinical trials involving AD patients. Expert opinion: AD is a common disease which currently has limited FDA approved medications. Given the chronicity of this disease, medications are needed which control disease while minimizing side effects to allow for long term use. Newer approved medications show promise but safety data is limited given their relatively new utilization for AD.

Therapeutic vaccines in renal cell carcinoma.

PubMed

Schwaab, Thomas; Ernstoff, Marc S

2011-07-01

Metastatic renal cell carcinoma (mRCC) is a lethal disease. The advent of tyrosine kinase inhibitors (TKIs) has changed the disease process, yet the majority of patients will develop treatment-resistant disease. IL-2 based immunotherapy in mRCC is the only US FDA-approved treatment with curative results. Immunotherapeutic vaccine approaches to mRCC have been under investigation for several decades with mixed results. The recent FDA-approval of the first cellular immunotherapy in prostate cancer (Provenge(®)) has reinvigorated the search for similar vaccines approaches in mRCC. This review introduces the concepts and different features required for a successful anticancer vaccine approach.

A new chapter in pharmaceutical manufacturing: 3D-printed drug products.

PubMed

Norman, James; Madurawe, Rapti D; Moore, Christine M V; Khan, Mansoor A; Khairuzzaman, Akm

2017-01-01

FDA recently approved a 3D-printed drug product in August 2015, which is indicative of a new chapter for pharmaceutical manufacturing. This review article summarizes progress with 3D printed drug products and discusses process development for solid oral dosage forms. 3D printing is a layer-by-layer process capable of producing 3D drug products from digital designs. Traditional pharmaceutical processes, such as tablet compression, have been used for decades with established regulatory pathways. These processes are well understood, but antiquated in terms of process capability and manufacturing flexibility. 3D printing, as a platform technology, has competitive advantages for complex products, personalized products, and products made on-demand. These advantages create opportunities for improving the safety, efficacy, and accessibility of medicines. Although 3D printing differs from traditional manufacturing processes for solid oral dosage forms, risk-based process development is feasible. This review highlights how product and process understanding can facilitate the development of a control strategy for different 3D printing methods. Overall, the authors believe that the recent approval of a 3D printed drug product will stimulate continual innovation in pharmaceutical manufacturing technology. FDA encourages the development of advanced manufacturing technologies, including 3D-printing, using science- and risk-based approaches. Published by Elsevier B.V.

76 FR 66309 - Pilot Program for Parallel Review of Medical Products; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare and Medicaid Services [CMS-3180-N2] Food and Drug Administration [Docket No. FDA-2010-N-0308] Pilot Program for Parallel Review of Medical... technologies to participate in a program of parallel FDA-CMS review. The document was published with an...

Warning letters to sponsor-investigators at academic health centres - the regulatory "canaries in a coal mine".

PubMed

O'Reilly, Erin K; Blair Holbein, M E; Berglund, Jelena P; Parrish, Amanda B; Roth, Mary-Tara; Burnett, Bruce K

2013-12-01

This study highlights Warning Letter (WL) findings issued to sponsor-investigators (S-Is) by the Food and Drug Administration (FDA). The online index of WLs issued from October 1, 2007 through September 30, 2012 was reviewed [1]. Through a manual screening process, letters were evaluated if specifically issued to 'clinical investigators', 'sponsors' or 'sponsor-investigators'. A particular focus was given to S-Is at Academic Health Centres (AHCs). Each letter was scored for the presence of violations in 40 general regulatory categories. A review of FDA WLs issued over a five-year period (FDA Fiscal Years 2008-2012) revealed that WLs to S-Is represent half of the WLs issued to all sponsors (16 of 32 letters). A review of these letters indicates that S-Is are not aware of, or simply do not meet, their regulatory responsibilities as either investigators or sponsors. In comparing total sponsor letters to those of S-Is, the most cited violation was the same: a lack of monitoring. A review of publicly available inspection data indicates that these 16 letters merely represent the tip of the iceberg. This review of the WL database reveals the potential for serious regulatory violations among S-Is at AHCs. Recent translational funding initiatives may serve to increase the number of S-Is, especially among Academic Health Centres (AHCs) [2]; thus, AHCs must become aware of this S-I role and work to support investigators who assume both roles in the course of their research.

Some Non-FDA Approved Uses for Neuromodulation in Treating Autonomic Nervous System Disorders: A Discussion of the Preliminary Support.

PubMed

Lee, Samuel; Abd-Elsayed, Alaa

2016-12-01

Neuromodulation, including cavernous nerve stimulation, gastric electrical stimulation, deep brain stimulation, and vagus nerve stimulation, has been used with success in treating several functional disease conditions. The FDA has approved the use of neuromodulation for a few indications. We discuss in our review article the evidence of using neuromodulation for treating some important disorders involving the autonomic nervous system that are not currently FDA approved. This was a review article that included a systematic online web search for human clinical studies testing the efficacy of neuromodulation in treating erectile dysfunction, gastroparesis, gastroesophageal reflux disease, obesity, asthma, and heart failure. Our review includes all feasibility studies, nonrandomized clinical trials, and randomized controlled trials. Our systematic literature search found 3, 4, 5, 4, 1, and 4 clinical studies relating to erectile dysfunction, gastroparesis, gastroesophageal reflux disease, obesity, asthma, and heart failure, respectively. This review article shows preliminary support based on clinical studies that neuromodulation can be of benefit for patients with important autonomic nervous system disease conditions that are not currently approved by the FDA. All of these investigational uses are encouraging; further studies are necessary and warranted for all indications discussed in this review before achieving FDA approval. © 2016 International Neuromodulation Society.

Biomedical applications of tissue engineering technology: regulatory issues.

PubMed

Hellman, K B

1995-01-01

Novel emerging technologies such as tissue engineering, which utilize the approaches of molecular and cell biology, biotechnology, as well as materials science and engineering, are being used in the development of a wide range of biomedical products developed by industries regulated by the U.S. Food and Drug Administration (FDA). The FDA's mission is to promote and protect the public health by ensuring the safety and effectiveness of pharmaceuticals and medical devices, including those manufactured by novel technology, as assessed by scientific principles and methods. Regulatory review is conducted on a product-by-product basis. To accomplish its mission over the wide range of products in its regulatory purview, the FDA has six centers, each staffed with the scientific and regulatory expertise to evaluate the products in the center's jurisdiction. Recent legislative and regulatory changes are designed to simplify and facilitate the administrative process for evaluating novel combination products emanating from such interdisciplinary technology as tissue engineering and to resolve questions of product regulatory jurisdiction. Under the new procedures, the FDA may designate a lead FDA center for product review based on the primary mode of action of the combination product, with additional center(s) designated to assist in the evaluation in a collaborative or consultative capacity. In addition, FDA centers have increased their cooperation and information sharing with regard to evolving interdisciplinary technology. The FDA InterCenter Tissue Engineering Initiative was established to develop information on intercenter efforts in the evaluation of tissue engineering applications and to identify areas for further consideration. The FDA InterCenter Tissue Engineering Working Group, comprised of staff from the Center for Biologies Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), Center for Drug Evaluation and Research (CDER), and Center for Veterinary Medicine (CVM) has developed a Draft Report considering recent developments in tissue engineering and scientific and regulatory issues in the product application areas. The Working Group has identified generic safety and effectiveness issues for consideration by the research and development community in its development of products. The FDA centers are using multiple approaches at their disposal in the evaluation of tissue engineered products including research, data and information monitoring, regulatory guidance, training and education, and cooperation with public and private groups.

Development times, clinical testing, postmarket follow-up, and safety risks for the new drugs approved by the US food and drug administration: the class of 2008.

PubMed

Moore, Thomas J; Furberg, Curt D

2014-01-01

The US Food and Drug Administration (FDA) has advanced multiple proposals to promote biomedical innovation by making new drugs available more quickly but with shorter, smaller, and more selective clinical trials and less rigorous end points. To inform the debate about appropriate standards, we studied the development times, clinical testing, postmarket follow-up, and safety risks for the new drugs approved by the FDA in 2008, when most provisions of current law, regulation, and policies were in effect. Descriptive study of the drugs classified as new molecular entities using preapproval FDA evaluation documents, agency drug information databases, prescribing information, and other primary data sources. Comparison of drugs that received standard review and those deemed sufficiently innovative to receive expedited review with regard to clinical development and FDA review time, the size and duration of efficacy trials, safety issues, and postmarket follow-up. In 2008, the FDA approved 20 therapeutic drugs, 8 with expedited review and 12 with standard review. The expedited drugs took a median of 5.1 years (range, 1.6-10.6 years) of clinical development to obtain marketing approval compared with 7.5 years (range, 4.7-19.4 years) for the standard review drugs (P = .05). The expedited drugs were tested for efficacy in a median of 104 patients receiving the active drug (range, 23-599), compared with a median of 580 patients (range, 75-1207) for standard review drugs (P = .003). Nonclinical testing showed that 6 therapeutic drugs were animal carcinogens, 5 were in vitro mutagens, and 14 were animal teratogens. Other safety concerns resulted in 5 Boxed Warnings; 8 drugs required risk management plans. The FDA required 85 postmarket commitments. By 2013, 5 drugs acquired a new or expanded Boxed Warning; 26 of 85 (31%) of the postmarketing study commitments had been fulfilled, and 8 (9%) had been submitted for agency review. For new drugs approved by the FDA in 2008, those that received expedited review were approved more rapidly than those that received standard review. However, considerably fewer patients were studied prior to approval, and many safety questions remained unanswered. By 2013, many postmarketing studies had not been completed.

75 FR 69093 - Prescription Drug User Fee Act; Reopening of the Comment Period

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-10

... review program after negotiations with the regulated industry conclude. FDA expects that this additional...)(2) (21 U.S.C. 379h-2(d)(2)) of the FD&C Act requires that before FDA begins negotiations with the... requires public review of the recommendations for the human drug review program after negotiations with the...

78 FR 29141 - Center for Devices and Radiological Health Appeals Processes; Guidance for Industry and FDA Staff...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0893] Center for Devices and Radiological Health Appeals Processes; Guidance for Industry and FDA Staff... Administration (FDA) is announcing the availability of the guidance entitled ``Center for Devices and...

Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches.

PubMed

Cardot, J-M; Garcia Arieta, A; Paixao, P; Tasevska, I; Davit, B

2016-07-01

The US-FDA recently posted a draft guideline for industry recommending procedures necessary to obtain a biowaiver for immediate-release oral dosage forms based on the Biopharmaceutics Classification System (BCS). This review compares the present FDA BCS biowaiver approach, with the existing European Medicines Agency (EMA) approach, with an emphasis on similarities, difficulties, and shared challenges. Some specifics of the current EMA BCS guideline are compared with those in the recently published draft US-FDA BCS guideline. In particular, similarities and differences in the EMA versus US-FDA approaches to establishing drug solubility, permeability, dissolution, and formulation suitability for BCS biowaiver are critically reviewed. Several case studies are presented to illustrate the (i) challenges of applying for BCS biowaivers for global registration in the face of differences in the EMA and US-FDA BCS biowaiver criteria, as well as (ii) challenges inherent in applying for BCS class I or III designation and common to both jurisdictions.

A Critical Review of Methods to Evaluate the Impact of FDA Regulatory Actions

PubMed Central

Briesacher, Becky A.; Soumerai, Stephen B.; Zhang, Fang; Toh, Sengwee; Andrade, Susan E.; Wagner, Joann L.; Shoaibi, Azadeh; Gurwitz, Jerry H.

2013-01-01

Purpose To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions, and identify best practices for future evaluations. Methods We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity, and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations. Results We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions. Conclusions Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies. PMID:23847020

Building a roadmap to biomarker qualification: challenges and opportunities.

PubMed

Amur, Shashi G; Sanyal, Sarmistha; Chakravarty, Aloka G; Noone, Marianne H; Kaiser, James; McCune, Susan; Buckman-Garner, ShaAvhree Y

2015-01-01

The traditional route for regulatory acceptance of biomarkers in drug development is through submission of biomarker data in drug approval submissions in the context of a single drug development program. The US FDA's Critical Path Initiative called for establishment of a biomarker qualification process to enable progress in the drug development paradigm. In response to this, the Center for Drug Evaluation and Research (CDER) established a Biomarker Qualification Program (BQP) to qualify a biomarker for a specific context of use (COU). The qualified biomarker can then be used in multiple drug development programs for this COU without re-review. Here, we describe some of the features of the BQP and two new initiatives that have the potential to aid biomarker development through early interactions with the FDA. Finally, we discuss some of the feedback the FDA has received from submitters and the BQP's actions to strengthen the program.

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status.

PubMed

Singh, Vijay K; Garcia, Melissa; Seed, Thomas M

2017-09-01

The threat of a radiological/nuclear event is a critical concern for all government agencies involved in national security and public health preparedness. Countermeasures that are safe, easily administered, and effective at diminishing or eliminating adverse health effects to individuals and the overall public health impact of radiation exposure are urgently needed. Radiation countermeasures included in this three-part series have been classified under various subheadings based specifically on their developmental stages for United States Food and Drug Administration (FDA) approval. We have included FDA-approved agents for acute radiation syndrome (ARS) in part I. This is part II in which we have reviewed FDA-approved agents for limited indications, internalized radionuclides, emesis, late effects, radiomitigators available in the strategic national stockpile (SNS), agents with FDA investigational new drug (IND) status, and those with NHP efficacy data without FDA IND. Agents discussed in part III are those agents that have been peer reviewed, published, and have demonstrated significant survival benefits in animal models of ARS. Agents investigated in in vitro models only or studied in animal models without peer-reviewed publications have not been included. The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. A number of promising radiation countermeasures are currently moving forward with continued support and effort by both governmental agencies and by publicly and privately held pharmaceutical companies. There is a limited number of countermeasures which are progressing well following the Animal Rule and may get approved in the near future, thus serving to close the gap of this critically important, unmet radiobiomedical need.

Peer Review for EPA’s Biologically Based Dose-Response (BBDR) Model for Perchlorate

EPA Science Inventory

EPA is developing a regulation for perchlorate in drinking water. As part the regulatory process EPA must develop a Maximum Contaminant Level Goal (MCLG). FDA and EPA scientists developed a biologically based dose-response (BBDR) model to assist in deriving the MCLG. This mode...

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

75 FR 47599 - Agency Information Collection Activities; Proposed Collection; Comment Request; Generic Food and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... premarket notification and review process. FDA's regulations governing application for agency approval to...-3520), Federal agencies must obtain approval from the Office of Management and Budget (OMB) for each... collection of information, before submitting the collection to OMB for approval. To comply with this...

75 FR 12768 - Blood Products Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

...] Blood Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION... Administration (FDA). At least one portion of the meeting will be closed to the public. Name of Committee: Blood... Biochemistry and Vascular Biology, Division of Hematology, Office of Blood Research and Review, CBER, FDA. FDA...

Research misconduct identified by the US Food and Drug Administration: out of sight, out of mind, out of the peer-reviewed literature.

PubMed

Seife, Charles

2015-04-01

Every year, the US Food and Drug Administration (FDA) inspects several hundred clinical sites performing biomedical research on human participants and occasionally finds evidence of substantial departures from good clinical practice and research misconduct. However, the FDA has no systematic method of communicating these findings to the scientific community, leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature. To identify published clinical trials in which an FDA inspection found significant evidence of objectionable conditions or practices, to describe violations, and to determine whether the violations are mentioned in the peer-reviewed literature. Cross-sectional analysis of publicly available documents, dated from January 1, 1998, to September 30, 2013, describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found. For each inspection document that could be linked to a specific published clinical trial, the main measure was a yes/no determination of whether there was mention in the peer-reviewed literature of problems the FDA had identified. Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published. When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.

Lessons Learned From The Investigational Device Exemption (IDE) Review of Children's Oncology Group Trial AAML1031

PubMed Central

Meshinchi, Soheil; Hunger, Stephen P.; Aplenc, Richard; Adamson, Peter C.; Jessup, J. Milburn

2012-01-01

The FDA is now exerting its regulatory authority over molecular diagnostics and their assays used for medical-decision making in clinical trials by performing pre-Investigational Device Exemption (IDE) reviews in all phases of clinical trials. This review assesses the analytical performance of the assay for the diagnostic and considers how that performance affects the diagnostic and the patient and their risks and benefits from treatment. This manuscript reviews the process of the first review that was performed on a new Children's Oncology Group (COG) Phase III trial in Acute Myelogenous Leukemia. The lessons learned and recommendations for how to prepare for and incorporate this new level of regulatory review into the protocol development process are presented. PMID:22422407

TU-AB-204-04: Partnerships

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

Ochs, R.

The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) andmore » the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC), Image Gently, and the Quantitative Imaging Biomarkers Alliance (QIBA) among others, to fulfill FDA’s mission will be discussed. Learning Objectives: Understand FDA’s pre-market and post-market review processes for medical devices Understand FDA’s current regulatory research activities in the areas of medical physics and imaging products Understand how being involved with AAPM and other organizations can also help to promote innovative, safe and effective medical devices J. Delfino, nothing to disclose.« less

Meeting the challenges of medical countermeasure development

PubMed Central

Maher, Carmen; Hu‐Primmer, Jean; MacGill, Tracy; Courtney, Brooke; Borio, Luciana

2012-01-01

Summary Despite substantial investments since the events of 2001, much work remains to prepare the nation for a chemical, biological, radiological or nuclear (CBRN) attack or to respond to an emerging infectious disease threat. Following a 2010 review of the US Public Health Emergency Medical Countermeasures Enterprise, FDA launched its Medical Countermeasures initiative (MCMi) to facilitate the development and availability of medical products to counter CBRN and emerging disease threats. As a regulatory agency, FDA has a unique and critical part to play in this national undertaking. Using a three‐pillar approach, FDA is addressing key challenges associated with the regulatory review process for medical countermeasures; gaps in regulatory science for MCM development and evaluation; and issues related to the legal, regulatory and policy framework for an effective public health response. Filling the gaps in the MCM Enterprise is a huge national undertaking, requiring the collaboration of all stakeholders, including federal partners, current and prospective developers of medical countermeasures, relevant research organizations, and state and local responders. Especially critical to success are an appreciation of the long timelines, risks and high costs associated with developing medical countermeasures – and the systems to deliver them – and the requisite support of all stakeholders, including national leadership. PMID:22925432

77 FR 17483 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0776] Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment... based upon estimates by FDA administrative and technical staff who: (1) Are familiar with the...

78 FR 65667 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... Request; Guidance for Industry on Chemistry, Manufacturing, and Controls Postapproval Manufacturing... chemistry, manufacturing, and controls (CMC) postapproval manufacturing changes that FDA has determined will... Pharmaceutical Product Quality Initiative and its risk-based approach to CMC review, FDA has evaluated the types...

78 FR 65588 - Medical Gas Regulation Review; Announcement of Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket No. FDA-2013-N-0001] Medical Gas Regulation Review; Announcement of Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting. The Food and Drug Administration (FDA) is announcing a...

75 FR 47820 - Generic Drug User Fee; Public Meeting; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0381... fee program. The number of human generic drug applications awaiting FDA action and the median review... needed for presentations, FDA reserves the right to terminate the meeting early. If you need special...

21 CFR 814.42 - Filing a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.42 Filing a PMA. (a) The filing of an application means that FDA has made a threshold determination that the application is sufficiently complete to permit a substantive review. Within 45 days after a PMA is received by FDA, the agency will notify the...

75 FR 27790 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0057... Veterinary Medicine Using the FDA Electronic Submission Gateway AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection...

77 FR 36279 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0194... Request; Biosimilars User Fee Cover Sheet; Form FDA 3792 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of...

76 FR 15321 - SEDASYS Computer-Assisted Personalized Sedation System; Ethicon Endo-Surgery, Inc.'s, Petition...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-P-0176... of FDA's Denial of Premarket Approval AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that it intends to refer for review before...

76 FR 38186 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0502... Request; National Consumer Surveys on Understanding the Risks and Benefits of FDA--Regulated Medical... Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of...

21 CFR 814.42 - Filing a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.42 Filing a PMA. (a) The filing of an application means that FDA has made a threshold determination that the application is sufficiently complete to permit a substantive review. Within 45 days after a PMA is received by FDA, the agency will notify the...

78 FR 8543 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0536... Request; Medical Device User Fee Cover Sheet, Form FDA 3601 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection...

78 FR 65332 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0530... Request; Guidance on Medical Devices: The Pre-Submission Program and Meetings With FDA Staff AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

78 FR 27969 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1131... Request; New Animal Drug Applications and Supporting Regulations and Form FDA 356V AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a...

75 FR 2865 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0488... on Forms FDA 1932, 1932a, and 2301 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of information has...

75 FR 27347 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0545... Cellular and Tissue-Based Product Deviations in Manufacturing; Form FDA 3486 and Addendum 3486A AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

78 FR 72893 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0579... Cellular and Tissue-Based Product Deviations in Manufacturing; Forms FDA 3486 and 3486A AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing...

77 FR 64523 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0471... Request; Prescription Drug User Fee Cover Sheet; Form FDA 3397 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection...

77 FR 41984 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0708... Request; Form FDA 3728, Animal Generic Drug User Fee Act Cover Sheet AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed...

76 FR 59401 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0275... FDA 3674) AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of...

78 FR 6822 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0324... Request; Guidance for Industry, FDA Staff, and Foreign Governments: Fiscal Year 2012 Medical Device User...: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of...

78 FR 950 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0530... Request; Guidance on Medical Devices: The Pre-Submission Program and Meetings With FDA Staff; Withdrawal... a Food and Drug Administration (FDA) notice that published in the Federal Register of December 11...

21 CFR 814.42 - Filing a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.42 Filing a PMA. (a) The filing of an application means that FDA has made a threshold determination that the application is sufficiently complete to permit a substantive review. Within 45 days after a PMA is received by FDA, the agency will notify the...

75 FR 2874 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0486... Request; Guidance for Industry, FDA, and Foreign Governments: Fiscal Year 2010 Medical Device User Fee.... SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of information...

77 FR 66620 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0748... Request; Generic Drug User Fee Cover Sheet; Form FDA 3794 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection...

75 FR 2866 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0483... Request; Medical Device User Fee Cover Sheet--Form FDA 3601 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection...

75 FR 32786 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0019..., Labeling, Revocation and Suspension, Postmarketing Studies Status Reports, and Forms FDA 356h and 2567 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

78 FR 63217 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

... Division of Dockets Management and on the Internet at http://www.fda.gov/Food/IngredientsPackagingLabeling... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0730] Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment...

New aquaculture drugs under FDA review

USGS Publications Warehouse

Bowker, James D.; Gaikowski, Mark P.

2012-01-01

Only eight active pharmaceutical ingredients available in 18 drug products have been approved by the U.S. Food and Drug Administration for use in aquaculture. The approval process can be lengthy and expensive, but several new drugs and label claims are under review. Progress has been made on approvals for Halamid (chloramine-T), Aquaflor (florfenicol) and 35% PeroxAid (hydrogen peroxide) as therapeutic drugs. Data are also being generated for AQUI-S 20E, a fish sedative.

Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.

PubMed

McCall, W Vaughn; Benca, Ruth M; Rosenquist, Peter B; Riley, Mary Anne; McCloud, Laryssa; Newman, Jill C; Case, Doug; Rumble, Meredith; Krystal, Andrew D

2017-01-01

Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

Hypnotic medications and suicide: risk, mechanisms, mitigation, and the FDA

PubMed Central

McCall, W. Vaughn; Benca, Ruth M.; Rosenquist, Peter B.; Riley, Mary Anne; McCloud, Laryssa; Newman, Jill C.; Case, Doug; Rumble, Meredith; Krystal, Andrew D.

2016-01-01

Objective Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has warnings regarding suicide in the prescribing information of hypnotics. We conducted a review of the evidence for and against hypnotics increasing the risk of suicide. Method This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms ‘suicide’ and ‘suicidal’ with each of the modern FDA-approved hypnotics. The FDA website was searched for post-marketing safety reviews, and the FDA was contacted to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Report system. Results The epidemiological studies show that hypnotics are associated with increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be previously suicidal. On the other hand, ongoing research is testing whether treatment of insomnia might reduce suicidality in depressed adults. Conclusions This review indicates hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess both types of possible effects: 1) an increase in suicidality due to central nervous system impairments from a given hypnotic medication; and 2) a decrease in suicidality due to improving insomnia. PMID:27609243

Enrollment and Monitoring of Women in Post-Approval Studies for Medical Devices Mandated by the Food and Drug Administration

PubMed Central

Herz, Naomi; Loyo-Berrios, Nilsa; Tarver, Michelle

2014-01-01

Abstract Background: Disease presentation, prevalence, and treatment effects vary by sex, thus it is important to ensure adequate participation of both sexes in medical device post-approval studies (PAS). Methods: The goals of this study were to determine the participation rate of women in PAS mandated by the Food and Drug Administration (FDA) and if participation varied by clinical area. The study also evaluated the frequency in which enrollment by sex is reported by applicant reports and FDA reviews, as well as the frequency in which final study reports analyze whether outcomes differ by sex. Results: Of 89 studies with enrollment completed, data on sex of participants were available in 93% of submitted reports, while data on enrollment by sex was evaluated and noted in 43% of FDA review memos. Study participation varied by clinical area, with female participation ranging from 32% in cardiovascular PAS to 90% in PAS for reconstructive devices. Of 53 completed studies, data on enrollment by sex was provided in 49 of the final reports. Of these 14% included a multivariate analysis that included sex as a covariate and 4% included a subgroup analysis for female participants. Conclusions: Data on sex was not routinely assessed in FDA reviews. Based on these findings, FDA implemented new procedures to ensure participation by sex is evaluated in PAS reviews. FDA will continue working with applicants to develop PAS that enroll and retain proportions of women consistent with the sex-specific prevalence for the disease or condition the device is used to treat. PMID:24405314

The Use of Published Clinical Study Reports to Support U.S. Food and Drug Administration Approval of Imaging Agents.

PubMed

Rieves, Dwaine; Jacobs, Paula

2016-12-01

Pharmaceutical companies typically perform prospective, multicenter phase 3 clinical studies to support approval of a new imaging agent by the U.S. Food and Drug Administration (FDA). In uncommon situations, the FDA has approved imaging agents based solely, or in large part, on the clinical study experience described in published reports, including reports of exploratory (i.e., phase 1 or 2) studies performed at a single clinical site. We performed a survey of published reports to assess the potential of the reported information to support FDA approval of a commonly cited investigational imaging agent. Our survey revealed critical data limitations in most publications, all of which reported exploratory clinical studies. Here we summarize the precedent for FDA approval of imaging agents using effectiveness data from publications, FDA guidance, and our experience in reviewing publications. We also present a key-data checklist for investigators to consider in the design, conduct, and reporting of exploratory clinical studies for publication. We encourage editors and peer reviewers to consider requiring these key data when reviewing these reports for publication. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

78 FR 5462 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... these decisionmaking processes will be applied by FDA to help design effective communication strategies..., beliefs, and behaviors--and use risk communications; (2) more efficiently and effectively design messages... provided about the design and methodology of the pretests and the studies to effectively comment on the...

78 FR 3433 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... and by educating the public, especially young people, about tobacco products and the dangers their use... identified. When FDA receives tobacco-specific adverse event and product problem information, it will use the... quality problem, or product use error occurs. This risk identification process is the first necessary step...

Safety and Procedural Success of Left Atrial Appendage Exclusion With the Lariat Device: A Systematic Review of Published Reports and Analytic Review of the FDA MAUDE Database.

PubMed

Chatterjee, Saurav; Herrmann, Howard C; Wilensky, Robert L; Hirshfeld, John; McCormick, Daniel; Frankel, David S; Yeh, Robert W; Armstrong, Ehrin J; Kumbhani, Dharam J; Giri, Jay

2015-07-01

The Lariat device has received US Food and Drug Administration (FDA) 510(k) clearance for soft-tissue approximation and is being widely used off-label for left atrial appendage (LAA) exclusion. A comprehensive analysis of safety and effectiveness has not been reported. To perform a systematic review of published literature to assess safety and procedural success, defined as successful closure of the LAA during the index procedure, of the Lariat device. We performed a formal analytic review of the FDA MAUDE (Manufacturer and User Facility Device Experience) database to compile adverse event reports from real-world practice with the Lariat. For the systematic review, PubMed, EMBASE, CINAHL, and the Cochrane Library were searched from January 2007 through August 2014 to identify all studies reporting use of the Lariat device in 3 or more patients. The FDA MAUDE database was queried for adverse events reports related to Lariat use. Data were abstracted in duplicate by 2 physician reviewers. Events from published literature were pooled using a generic inverse variance weighting with a random effects model. Cumulative and individual adverse events were also reported using the FDA MAUDE data set. Procedural adverse events and procedural success. In the systematic review, 5 reports of Lariat device use in 309 participants were identified. Specific complications weighted for inverse of variance of individual studies were urgent need for cardiac surgery (2.3%; 7 of 309 procedures) and death (0.3%; 1 of 309 procedures). Procedural success was 90.3% (279 of 309 procedures). In the FDA MAUDE database, there were 35 unique reports of adverse events with use of the Lariat device. Among these, we identified 5 adverse event reports that noted pericardial effusion and death and an additional 23 reported urgent cardiac surgery without mention of death. This review of published reports and case reports identified risks of adverse events with off-label use of the Lariat device for LAA exclusion. Formal, controlled investigations into the safety and efficacy of the device for this indication are warranted.

Environmental assessments and findings of no significant impact--FDA. Notice.

PubMed

1998-05-18

The Food and Drug Administration (FDA) is announcing that it has reviewed environmental assessments (EA's) and issued findings of no significant impact (FONSI's) relating to the 167 new drug applications (NDA's) and supplemental applications listed in this document. FDA is publishing this notice because Federal regulations require public notice of the availability of environmental documents.

77 FR 59287 - National Organic Program (NOP); Sunset Review (2012) for Nutrient Vitamins and Minerals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-27

... Value (DRV). FDA stated that substances such as omega-3 and omega-6 fatty acids, inositol, choline....\\3\\ The reference to 21 CFR 104.20 refers to the fortification policy for food under the FDA's... those nutrients. \\3\\ FDA Response to NOP--Questions and Answers Regarding Nutrient Fortification of...

21 CFR 314.94 - Content and format of an abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... the application are required, an archival copy, a review copy, and a field copy. FDA will maintain... application based on an approved petition under § 10.30 of this chapter or § 314.93, a reference to FDA...

21 CFR 314.94 - Content and format of an abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... the application are required, an archival copy, a review copy, and a field copy. FDA will maintain... application based on an approved petition under § 10.30 of this chapter or § 314.93, a reference to FDA...

Concise Review: The U.S. Food and Drug Administration and Regenerative Medicine.

PubMed

Witten, Celia M; McFarland, Richard D; Simek, Stephanie L

2015-12-01

Regenerative medicine (RM) is a popular term for a field of scientific and medical research. There is not one universally accepted definition of RM, but it is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. RM products have the potential to provide treatments for a number of unmet needs but have substantial scientific and regulatory challenges that need to be addressed for this potential to be fully realized. FDA has established formal regulatory definitions for biologics, medical devices, and combination products, as well as human cells and tissues. Regenerative medicine products regulated by FDA are classified on the basis of these definitions, and the classification forms the basis for determining the regulatory requirements to each specific product. FDA regulations are generally written to allow the agency flexibility to accommodate new scientific questions raised by novel and evolving technologies. FDA efforts to facilitate product development in this novel and promising area include working with individual sponsors, interacting with the scientific and industry communities, participating in standards development, and developing policy and guidance. Regenerative medicine is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. This article provides an overview of the efforts of the U.S. Food and Drug Administration (FDA) to facilitate product development in the field commonly known was regenerative medicine. It provides an introduction to the processes by which FDA works with individual sponsors, interacts with the scientific and industry communities, participates in standards development, and develops formal FDA policy and guidance. ©AlphaMed Press.

Regulatory Forum Opinion Piece: Review of FDA Draft Guidance Testicular Toxicity-Evaluation during Drug Development Guidance for Industry.

PubMed

Hukkanen, Renee R; Halpern, Wendy G; Vidal, Justin D

2016-10-01

In July 2015, the U.S. Food and Drug Administration (FDA) posted a new draft guidance entitled "Testicular Toxicity: Evaluation during Drug Development Guidance for Industry," with a 90-day public comment period. As the nonclinical assessment of testicular toxicity often relies on the expert interpretation of pathology affecting the male reproductive tract, this draft guidance is considered directly relevant to the toxicologic pathology community. Therefore, a working group was formed through the Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathologists (STPs) to provide a detailed review of the draft guidance. Specific comments on the guidance were submitted to the FDA by the STP. The draft guidance and all comments received are currently under review with the FDA. This commentary provides a summary of the components of the draft guidance and the comments submitted by the STP with acknowledgment of different perspectives reflected in comments from other respondents. © The Author(s) 2016.

FDA marketing claims, and the practitioner.

PubMed

Runner, Susan

2006-03-01

The Food and Drug Administration (FDA) is the federal agency that is tasked with regulating market entry for medical devices. The laws that govern this process are codified in the Federal Food Drug and Cosmetic Act (the Act) and the regulations are based on this law. The medical device amendments to the Act were instituted in 1976, instituting the methods for classification of medical devices and the format for the premarket review of devices. Information for practitioners on how medical devices come to market, what data are required, how specific claims are cleared, and how the practitioner can give input to the system are critical for the further development of safe and effective medical devices.

75 FR 55589 - Fee for Using a Priority Review Voucher in Fiscal Year 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0463] Fee for Using a Priority Review Voucher in Fiscal Year 2011 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the fee rates for using a...

Urogynecologic Surgical Mesh Implants

MedlinePlus

... FDA collected samples during the inspections, and reviewed mechanical performance testing and sterility testing of the final ... characterization of the polypropylene resin, and biocompatibility and mechanical performance testing on the final product. The FDA ...

No longer "if," but "when": the coming abbreviated approval pathway for follow-on biologics.

PubMed

Kelly, Jeremiah J; David, Michael

2009-01-01

Abbreviated approval of follow-on biologics involves answering complex scientific, legal, and policy questions. The Food and Drug Administration (FDA or the Agency) asserts that it lacks the statutory authority to approve follow-on versions of biologics licensed under Section 351 of the Public Health Service Act (PHSA). Despite persuasive arguments to the contrary the one hundred and tenth Congress entertained four legislative proposals to give FDA this authority, each markedly different. It is no longer a question of "if," but "when" FDA will receive authority to review and license abbreviated applications for follow-on biologics. Any legislation in the one hundred and eleventh Congress must determine: (1) if FDA should be granted authority to develop an abbreviated pathway through rulemaking or guidance; (2) if human clinical trials should be mandatory or discretionary; (3) the feasibility of interchangeability determinations in light of patient safety concerns; (4) the duration of marketing exclusivity for associated products; (5) which products are eligible for follow-on approval; and (6) the degree to which uniformity is achievable between the FD&C Act and the PHSA. This paper recommends the one hundred and eleventh Congress strike a balance between patient safety, incentives for product innovation, price competition, and the need for a flexible, transparent process that capitalizes on FDA's growing expertise with follow-on biologics approvals under Section 505(b)(2) of the FD&C Act.

Patient Reported Outcome (PRO) assessment in epilepsy: a review of epilepsy-specific PROs according to the Food and Drug Administration (FDA) regulatory requirements.

PubMed

Nixon, Annabel; Kerr, Cicely; Breheny, Katie; Wild, Diane

2013-03-11

Despite collection of patient reported outcome (PRO) data in clinical trials of antiepileptic drugs (AEDs), PRO results are not being routinely reported on European Medicines Agency (EMA) and Food and Drug Administration (FDA) product labels. This review aimed to evaluate epilepsy-specific PRO instruments against FDA regulatory standards for supporting label claims. Structured literature searches were conducted in Embase and Medline databases to identify epilepsy-specific PRO instruments. Only instruments that could potentially be impacted by pharmacological treatment, were completed by adults and had evidence of some validation work were selected for review. A total of 26 PROs were reviewed based on criteria developed from the FDA regulatory standards. The ability to meet these criteria was classified as either full, partial or no evidence, whereby partial reflected some evidence but not enough to comprehensively address the FDA regulatory standards. Most instruments provided partial evidence of content validity. Input from clinicians and literature was common although few involved patients in both item generation and cognitive debriefing. Construct validity was predominantly compromised by no evidence of a-priori hypotheses of expected relationships. Evidence for test-retest reliability and internal consistency was available for most PROs although few included complete results regarding all subscales and some failed to reach recommended thresholds. The ability to detect change and interpretation of change were not investigated in most instruments and no PROs had published evidence of a conceptual framework. The study concludes that none of the 26 have the full evidence required by the FDA to support a label claim, and all require further research to support their use as an endpoint. The Subjective Handicap of Epilepsy (SHE) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) have the fewest gaps that would need to be addressed through additional research prior to any FDA regulatory submission, although the NDDI-E was designed as a screening tool and is therefore unlikely to be suitable as an instrument for capturing change in a clinical trial and the SHE lacks the conceptual focus on signs and symptoms favoured by the FDA.

Tattoo Removal: Options and Results

MedlinePlus

... tattoos. In recent years, FDA has cleared for marketing several types of lasers for tattoo lightening or ... Mehmet Kosoglu, Ph.D., who reviews applications for marketing clearances of laser-devices. There are several FDA- ...

77 FR 73662 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-11

... received by the Agency under the Pre-IDE program over the past 10 years. Based on FDA's experience with the... rate and reach a steady state of approximately 2,544 submissions per year. FDA estimates from past... annual estimate of 2,544 submissions is based on experienced trends over the past several years. FDA's...

Adverse drug events and the Freedom of Information Act: an apple in Eden.

PubMed

Stang, P E; Fox, J L

1992-02-01

To review some of the abuses and proper uses of the Food and Drug Administration's (FDA's) spontaneous adverse-reaction reporting system, as a way of educating the reader to its strengths and limitations. Published literature and reports based on information obtained from the FDA's database of spontaneous adverse drug-event reports. The Freedom of Information Act has increased public access to the FDA's database of spontaneous adverse drug reaction reports. As these reports are voluntarily received and reported to the FDA, their use for comparisons of drug safety is severely limited. Despite these limitations and the FDA's caveats for use of these data, consumer advocacy groups, researchers, and various pharmaceutical marketing groups have used this source to project the incidence of adverse drug reactions. The FDA's spontaneous adverse-event reporting system is designed to generate signals of unexpected adverse drug events. Use of the data gathered by this system to make drug safety comparisons is beyond their credible scope because many factors influence the reporting of adverse events. Researchers and peer reviewers should place these data in the proper perspective and support sound research into questions of drug safety.

Scouting For Approval: Lessons on Medical Device Regulation in an Era of Crowdfunding from Scanadu's "Scout".

PubMed

Smith, Colleen

2015-01-01

Internet crowdfunding, a new and increasingly popular method of raising capital to develop products and businesses, has recently come into conflict with the Food and Drug Administration's (FDA's) regulation of medical devices. This Article examines the issues that arise when companies pre-sell medical devices via crowdfunding campaigns before gaining FDA approval of the devices. Because Internet crowdfunding has only been in use for a few years, little has been written about it academically, particularly about its interaction with FDA regulations. The rising interest in crowdfunding, coupled with the downturn in investment in the American medical device industry, make this a salient issue that is ripe for FDA review. This Article uses the crowdfunding campaign Scanadu, a medical device company, conducted in 2013 to raise money to develop its in-home diagnostic device, the "Scout," as a starting point for this analysis. Because it is extremely costly to develop a device and obtain FDA approval, medical device companies should be able to utilize crowdfunding to raise the necessary capital. However, because of the possible dangers medical devices pose, FDA needs to review the risks created by allowing companies to crowdfund medical devices and should issue guidance to help companies comply with FDA regulations while still allowing them to take advantage of the benefits of crowdfunding. This guidance should ensure the continued commitment to consumer safety that is at the core of FDA regulation.

Dietary Supplements: What You Need to Know

MedlinePlus

... must notify FDA about that ingredient prior to marketing. However, the notification will only be reviewed by FDA (not approved) and only for safety, not effectiveness. Manufacturers are required to produce dietary supplements in ...

An integrated bioinformatics infrastructure essential for advancing pharmacogenomics and personalized medicine in the context of the FDA's Critical Path Initiative.

PubMed

Tong, Weida; Harris, Stephen C; Fang, Hong; Shi, Leming; Perkins, Roger; Goodsaid, Federico; Frueh, Felix W

2007-01-01

Pharmacogenomics (PGx) is identified in the FDA Critical Path document as a major opportunity for advancing medical product development and personalized medicine. An integrated bioinformatics infrastructure for use in FDA data review is crucial to realize the benefits of PGx for public health. We have developed an integrated bioinformatics tool, called ArrayTrack, for managing, analyzing and interpreting genomic and other biomarker data (e.g. proteomic and metabolomic data). ArrayTrack is a highly flexible and robust software platform, which allows evolving with technological advances and changing user needs. ArrayTrack is used in the routine review of genomic data submitted to the FDA; here, three hypothetical examples of its use in the Voluntary eXploratory Data Submission (VXDS) program are illustrated.: © Published by Elsevier Ltd.

Comparison of oncology drug approval between Health Canada and the US Food and Drug Administration.

PubMed

Ezeife, Doreen A; Truong, Tony H; Heng, Daniel Y C; Bourque, Sylvie; Welch, Stephen A; Tang, Patricia A

2015-05-15

The drug approval timeline is a lengthy process that often varies between countries. The objective of this study was to delineate the Canadian drug approval timeline for oncology drugs and to compare the time to drug approval between Health Canada (HC) and the US Food and Drug Administration (FDA). In total, 54 antineoplastic drugs that were approved by the FDA between 1989 and 2012 were reviewed. For each drug, the following milestones were determined: the dates of submission and approval for both the FDA and HC and the dates of availability on provincial drug formularies in Canadian provinces and territories. The time intervals between the aforementioned milestones were calculated. Of 54 FDA-approved drugs, 49 drugs were approved by HC at the time of the current study. The median time from submission to approval was 9 months (interquartile range [IQR], 6-14.5 months) for the FDA and 12 months (IQR, 10-21.1 months) for HC (P < .0006). The time from HC approval to the placement of a drug on a provincial drug formulary was a median of 16.7 months (IQR, 5.9-27.2 months), and there was no interprovincial variability among the 5 Canadian provinces that were analyzed (P = .5). The time from HC submission to HC approval takes 3 months longer than the same time interval for the FDA. To the authors' knowledge, this is the first documentation of the time required to bring an oncology drug from HC submission to placement on a provincial drug formulary. © 2015 American Cancer Society.

Patient-Focused Drug Development: A New Direction for Collaboration.

PubMed

Perfetto, Eleanor M; Burke, Laurie; Oehrlein, Elisabeth M; Epstein, Robert S

2015-01-01

Patient-Focused Drug Development (PFDD) is a new initiative from the Food and Drug Administration (FDA) intended to bring patient perspectives into an earlier stage of product development. The goal is that patients will be able to provide context for benefit-risk assessments and input to review divisions, and also aid in the development of new assessment tools, study endpoints, and risk communications. This paper provides a summary on what is known to date about FDA's PFDD initiative and describes implications for patients, researchers, payers, and the biopharmaceutical industry. It also provides a roadmap for stakeholders to consider in defining their role in and in shaping PFDD's direction, and for expanding PFDD principles to conditions beyond the current 20 under FDA consideration. A search was conducted of the peer-reviewed and gray literature using PubMed and Google. This included laws, FDA guidance documents, the peer-reviewed literature, and FDA presentations for content relevant to the search term "patient-focused drug development." Currently, FDA activities within PFDD are limited to gaining patient insights through 20 disease-specific meetings. However, many stakeholders see the initiative much more generally as representing a broad shift toward patient centeredness in biopharmaceutical product development. Depending upon the trajectory taken and whether or not all PFDD aims are eventually addressed, the initiative has the potential to change product development in fundamental ways. Further research should explore how patient input on disease manifestation and treatment options is best ascertained from patients and documented before initiating and during drug development.

Environmental Impact Analysis Process. Environmental Assessment for Defense Satellite Communications System III With Integrated Apogee Boost System

DTIC Science & Technology

1995-07-01

spectabilis Royal fern C FDA n/o Remirea maritima Beach star E FDA, FNAI o Scaevola plumeria Scaevola T FDA o Tillandsia simulata Wildpine; air plant...unnamed) T FDA n/o Tillandsia utriculata Giant wildpine; giant air plant C FDA o 1 E = Endangered; T = Threatened; T(S/A) = Threatened due to

Meeting the challenges of medical countermeasure development.

PubMed

Maher, Carmen; Hu-Primmer, Jean; MacGill, Tracy; Courtney, Brooke; Borio, Luciana

2012-09-01

Despite substantial investments since the events of 2001, much work remains to prepare the nation for a chemical, biological, radiological or nuclear (CBRN) attack or to respond to an emerging infectious disease threat. Following a 2010 review of the US Public Health Emergency Medical Countermeasures Enterprise, FDA launched its Medical Countermeasures initiative (MCMi) to facilitate the development and availability of medical products to counter CBRN and emerging disease threats. As a regulatory agency, FDA has a unique and critical part to play in this national undertaking. Using a three-pillar approach, FDA is addressing key challenges associated with the regulatory review process for medical countermeasures; gaps in regulatory science for MCM development and evaluation; and issues related to the legal, regulatory and policy framework for an effective public health response. Filling the gaps in the MCM Enterprise is a huge national undertaking, requiring the collaboration of all stakeholders, including federal partners, current and prospective developers of medical countermeasures, relevant research organizations, and state and local responders. Especially critical to success are an appreciation of the long timelines, risks and high costs associated with developing medical countermeasures - and the systems to deliver them - and the requisite support of all stakeholders, including national leadership. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Prescription for change: an interview with FDA Commissioner Dr. David Kessler.

PubMed

Kessler, D

1992-07-01

Dr David A. Kessler took over as Commissioner of the Food and Drug Administration in December 1990. Since then, he has initiated many changes to improve the structure and efficiency of the agency. In this interview, he describes some of the problems and challenges associated with the process of reviewing and approving new drugs.

76 FR 59407 - Center for Biologics Evaluation and Research Report of Scientific and Medical Literature and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... test data in the studies: Obtained positive skin tests in index cases by either skin prick or... 20852- 1448. Send one self-addressed adhesive label to assist the office in processing your requests... list of reviewed literature associated with each product. FDA's approach to creating this data file was...

[Twenty-year History and Future Challenges in Transparency Enhancement of Review Process for Approval: Focus on Public Release of Review Reports regarding New Drugs and Medical Devices].

PubMed

Morimoto, Kazushige; Kawasaki, Satoko; Yoshida, Yasunori

2015-01-01

For 20 years, the Ministry of Health, Labour and Welfare (MHLW, formerly Ministry of Health and Welfare (MHW)) has been trying to increase transparency of the review process for approving reports in order to promote the rational use of newly approved drugs and medical devices. The first Summary Basis of Approval (SBA) was published by MHW in 1994. In 1999, evaluation reports were prepared by MHW and the Pharmaceuticals and Medical Devices Evaluation Center to make them available to the public. In 2005, a notice from the Chief Executive of the Pharmaceuticals and Medical Devices Agency (PMDA) made procedures for public release of information on reviewing applications for new drugs. In 2006, 90 review reports of newly approved drugs and eight medical devices were revealed on PMDA websites. The dissemination of information by the United States Food and Drug Administration (FDA) and that of the European Medicines Agency (EMA) were studied and compared with that of the MHLW and PMDA. While common technical documents (CTD) for new drugs and summary technical documents (STED) for new medical devices have been released by PMDA, such documents are not released by the FDA and EMA. The European Public Assessment Report (EAPR) summary for the public is an interesting questionnaire approach that uses the "What," "How" and "Why" format. Finally, future proposals for the next decade are also outlined.

TU-AB-204-03: Research Activities in Medical Physics

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

Badano, A.

The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) andmore » the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC), Image Gently, and the Quantitative Imaging Biomarkers Alliance (QIBA) among others, to fulfill FDA’s mission will be discussed. Learning Objectives: Understand FDA’s pre-market and post-market review processes for medical devices Understand FDA’s current regulatory research activities in the areas of medical physics and imaging products Understand how being involved with AAPM and other organizations can also help to promote innovative, safe and effective medical devices J. Delfino, nothing to disclose.« less

TU-AB-204-02: Device Adverse Events and Compliance

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

Gonzales, S.

The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) andmore » the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC), Image Gently, and the Quantitative Imaging Biomarkers Alliance (QIBA) among others, to fulfill FDA’s mission will be discussed. Learning Objectives: Understand FDA’s pre-market and post-market review processes for medical devices Understand FDA’s current regulatory research activities in the areas of medical physics and imaging products Understand how being involved with AAPM and other organizations can also help to promote innovative, safe and effective medical devices J. Delfino, nothing to disclose.« less

Reflections on the US FDA's Warning on Direct-to-Consumer Genetic Testing.

PubMed

Yim, Seon-Hee; Chung, Yeun-Jun

2014-12-01

In November 2013, the US Food and Drug Administration (FDA) sent a warning letter to 23andMe, Inc. and ordered the company to discontinue marketing of the 23andMe Personal Genome Service (PGS) until it receives FDA marketing authorization for the device. The FDA considers the PGS as an unclassified medical device, which requires premarket approval or de novo classification. Opponents of the FDA's action expressed their concerns, saying that the FDA is overcautious and paternalistic, which violates consumers' rights and might stifle the consumer genomics field itself, and insisted that the agency should not restrict direct-to-consumer (DTC) genomic testing without empirical evidence of harm. Proponents support the agency's action as protection of consumers from potentially invalid and almost useless information. This action was also significant, since it reflected the FDA's attitude towards medical application of next-generation sequencing techniques. In this review, we followed up on the FDA-23andMe incident and evaluated the problems and prospects for DTC genetic testing.

21 CFR 1.282 - What must you do if information changes after you have received confirmation of a prior notice...

Code of Federal Regulations, 2011 CFR

2011-04-01

... have received confirmation of a prior notice from FDA? 1.282 Section 1.282 Food and Drugs FOOD AND DRUG... changes after you have received confirmation of a prior notice from FDA? (a)(1) If any of the information... information), changes after you receive notice that FDA has confirmed your prior notice submission for review...

21 CFR 1.282 - What must you do if information changes after you have received confirmation of a prior notice...

Code of Federal Regulations, 2012 CFR

2012-04-01

... have received confirmation of a prior notice from FDA? 1.282 Section 1.282 Food and Drugs FOOD AND DRUG... changes after you have received confirmation of a prior notice from FDA? (a)(1) If any of the information... information), changes after you receive notice that FDA has confirmed your prior notice submission for review...

21 CFR 1.282 - What must you do if information changes after you have received confirmation of a prior notice...

Code of Federal Regulations, 2013 CFR

2013-04-01

... have received confirmation of a prior notice from FDA? 1.282 Section 1.282 Food and Drugs FOOD AND DRUG... changes after you have received confirmation of a prior notice from FDA? (a)(1) If any of the information... information), changes after you receive notice that FDA has confirmed your prior notice submission for review...

21 CFR 1.282 - What must you do if information changes after you have received confirmation of a prior notice...

Code of Federal Regulations, 2014 CFR

2014-04-01

... have received confirmation of a prior notice from FDA? 1.282 Section 1.282 Food and Drugs FOOD AND DRUG... changes after you have received confirmation of a prior notice from FDA? (a)(1) If any of the information... information), changes after you receive notice that FDA has confirmed your prior notice submission for review...

21 CFR 1.282 - What must you do if information changes after you have received confirmation of a prior notice...

Code of Federal Regulations, 2010 CFR

2010-04-01

... have received confirmation of a prior notice from FDA? 1.282 Section 1.282 Food and Drugs FOOD AND DRUG... changes after you have received confirmation of a prior notice from FDA? (a)(1) If any of the information... information), changes after you receive notice that FDA has confirmed your prior notice submission for review...

Supplemental calcium and risk reduction of hypertension, pregnancy-induced hypertension, and preeclampsia: an evidence-based review by the US Food and Drug Administration.

PubMed

Trumbo, Paula R; Ellwood, Kathleen C

2007-02-01

The labeling of health claims that meet the significant scientific agreement (SSA) standard (authorized health claims) and qualified health claims on conventional foods and dietary supplements requires premarket approval by the US Food and Drug Administration (FDA). FDA conducts an evidence-based review to determine whether there is sufficient evidence to support an authorized or qualified health claim. An evidence-based review was conducted on the human intervention and observational studies evaluating the role of supplemental calcium in reducing the risk of hypertension, pregnancy-induced hypertension, and preeclampsia. This review provides FDA's evaluation of the current scientific evidence on the role of supplemental calcium in reducing the risk of these three end points. Based on this evidence-based review, the agency concluded that the relationship between calcium and risk of hypertension is inconsistent and inconclusive, and the relationship between calcium and risk of pregnancy-induced hypertension and preeclampsia is highly unlikely.

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.

76 FR 45825 - Center for Devices and Radiological Health 510(k) Clearance Process; Institute of Medicine Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0556...: ``Medical Devices and the Public's Health, The FDA 510(k) Clearance Process at 35 Years;'' Request for... Drug Administration (FDA) is requesting comments on the Institute of Medicine (IOM) report entitled...

76 FR 54777 - Center for Devices and Radiological Health 510(k) Clearance Process; Recommendations Proposed in...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0556... Institute of Medicine Report: ``Medical Devices and the Public's Health, The FDA 510(k) Clearance Process at...; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared in the...

2017 in review: FDA approvals of new molecular entities.

PubMed

Kinch, Michael S; Griesenauer, Rebekah H

2018-05-08

An overview of drugs approved by the FDA in 2017 reflected a reversion to the mean after a low number of NME approvals in 2016. This reversal was largely driven by the largest number of biologics-based NMEs recorded to date, which offset an average number of small-molecule approvals. Oncology indications continued to dominate followed by novel treatments for infectious, immunologic and neurologic diseases. From a mechanistic standpoint, the industry has continued a trend of target diversification, reflecting advances in scientific understanding of disease processes. Finally, 2017 continued a period of relatively few mergers and acquisitions, which broke a more-than-a-decade-long decline in the number of organizations contributing to research and development. Copyright © 2018 Elsevier Ltd. All rights reserved.

Addressing the immunopathogenesis of atopic dermatitis: advances in topical and systemic treatment.

PubMed

Eichenfield, Lawrence F; Stein Gold, Linda F

2017-03-01

Several immunologic mediators-phosphodiesterase (PDE), interleukin (IL), small molecules, and Janus kinase-have been implicated in the pathogenesis of atopic dermatitis, and evidence has shown that blocking these mediators can help modify the disease process. Several new topical medications have been developed that target the enzyme PDE; crisaborole was recently approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis, and phase II studies have been completed on OPA-15406. The phase III clinical trial results of the systemic medication dupilumab, an inhibitor of the IL-4 receptor α subunit (which inhibits both IL-4 and IL-13 signaling), are currently being reviewed by the FDA. ©2017 Frontline Medical Communications.

A review of complications associated with vertebroplasty and kyphoplasty as reported to the Food and Drug Administration medical device related web site.

PubMed

Nussbaum, David A; Gailloud, Philippe; Murphy, Kieran

2004-11-01

In 2002, approximately 38,000 vertebroplasties and 16,000 kyphoplasties were performed in the United States. As the use of both modalities for the treatment of vertebral compression fractures has increased, so have questions regarding safety and efficacy. The authors addressed this by reviewing both the current literature and complications data reported to the Food and Drug Administration (FDA) Center for Devices and Radiological Health through the on-line database (http://www.fda.gov/cdrh/maude.html) and through the Office of the Freedom of Information Act at the FDA. Although both procedures are largely safe, the FDA data highlight two main concerns: reactions to the use of acrylic (polymethylmethacrylate) bone cement, including hypotension and, in some cases, death, especially when multiple vertebral levels are treated in one setting; and a possible increased risk with kyphoplasty of pedicle fracture and cord compression.

Annual update: drugs, diagnostics and devices.

PubMed

Berardinelli, Candace; Kupecz, Deborah

2003-03-01

As NPs continue to play an important role in health care as administers of prescriptions, the value of reviewing the latest Food and Drug Administration (FDA) approvals for new drugs and devices is immeasurable. In 2002, the FDA approved several new drugs and devices, as well as monitored previously approved drugs for adverse reactions and untoward events. This article provides a brief review of relevant primary care topics.

77 FR 11553 - Draft Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``FDA... that address nearly all aspects of the FDA approval and surveillance processes, including application...

77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... and Drug Administration (FDA) is announcing the availability of a guidance entitled ``FDA Oversight of... nearly all aspects of the FDA approval and surveillance processes, including application submission...

76 FR 56205 - Request for Notification From Industry Organizations Interested in Participating in the Selection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... Products Scientific Advisory Committee, notify FDA in writing. FDA is also requesting nominations for... letters stating interest in participating in the selection process to FDA by October 12, 2011 (see... candidates should be sent to FDA by October 12, 2011. ADDRESSES: All letters of interest and nominations...

The impact of the written request process on drug development in childhood cancer.

PubMed

Snyder, Kristen M; Reaman, Gregory; Avant, Debbie; Pazdur, Richard

2013-04-01

The Food and Drug Administration (FDA) Modernization Act, enacted in 1997, created a pediatric exclusivity incentive allowing sponsors to qualify for an additional 6 months of marketing exclusivity after satisfying the requirements outlined in the Written Request (WR). This review evaluates the impact of the WR mechanism on the development of oncology drugs in children. A search of the FDA document archiving, reporting, and regulatory tracking system was performed for January 1, 2000 to December 31, 2010. Drugs were identified and pediatric-specific labeling information was obtained from Drugs@fda.gov and FDA Pediatric Labeling Changes Table. Fifty WRs have been issued for oncology drugs. Pediatric studies have been submitted for 14 drugs. Thirteen received pediatric exclusivity. As of December 31, 2010, labeling changes have been made for 11 drugs. Three drugs were approved for pediatric use. WRs have provided a mechanism to promote the study of drugs in pediatric malignancies. Information from studies resulting from the WRs regarding safety, pharmacokinetics, and tolerability of oncology drugs has been incorporated into pediatric labeling for 11/14 of the drugs. Earlier communication and collaboration between the FDA, National Cancer Institute, clinical investigators, and commercial sponsors are envisioned to facilitate the identification and prioritization of emerging new drugs of interest for WR consideration. Since this is the only regulatory mechanism, resulting from specific legislative initiatives relevant to cancer drug development for children, efforts to enhance its impact on increasing drug approval for pediatric cancer indications are warranted. Copyright © 2013 Wiley Periodicals, Inc.

Concerns regarding a new culture method for Borrelia burgdorferi not approved for the diagnosis of Lyme disease.

PubMed

Nelson, Christina; Hojvat, Sally; Johnson, Barbara; Petersen, Jeannine; Schriefer, Marty; Beard, C Ben; Petersen, Lyle; Mead, Paul

2014-04-18

In 2005, CDC and the Food and Drug Administration (FDA) issued a warning regarding the use of Lyme disease tests whose accuracy and clinical usefulness have not been adequately established. Often these are laboratory-developed tests (also known as "home brew" tests) that are manufactured and used within a single laboratory and have not been cleared or approved by FDA. Recently, CDC has received inquiries regarding a laboratory-developed test that uses a novel culture method to identify Borrelia burgdorferi, the spirochete that causes Lyme disease. Patient specimens reportedly are incubated using a two-step pre-enrichment process, followed by immunostaining with or without polymerase chain reaction (PCR) analysis. Specimens that test positive by immunostaining or PCR are deemed "culture positive". Published methods and results for this laboratory-developed test have been reviewed by CDC. The review raised serious concerns about false-positive results caused by laboratory contamination and the potential for misdiagnosis.

Medicare covers the majority of FDA-approved devices and Part B drugs, but restrictions and discrepancies remain.

PubMed

Chambers, James D; May, Katherine E; Neumann, Peter J

2013-06-01

The Food and Drug Administration (FDA) and Medicare use different standards to determine, first, whether a new drug or medical device can be marketed to the public and, second, if the federal health insurance program will pay for use of the drug or device. This discrepancy creates hurdles and uncertainty for drug and device manufacturers. We analyzed discrepancies between FDA approval and Medicare national coverage determinations for sixty-nine devices and Part B drugs approved during 1999-2011. We found that Medicare covered FDA-approved drugs or devices 80 percent of the time. However, Medicare often added conditions beyond FDA approval, particularly for devices and most often restricting coverage to patients with the most severe disease. In some instances, Medicare was less restrictive than the FDA. Our findings highlight the importance for drug and device makers of anticipating Medicare's needs when conducting clinical studies to support their products. Our findings also provide important insights for the FDA's and Medicare's pilot parallel review program.

Interview with Janet Woodcock: progress on the FDA's critical path initiative.

PubMed

Woodcock, Janet

2009-12-01

Janet Woodcock is the Director of the US FDA's Center for Drug Evaluation and Research. Dr Woodcock has held various positions within the FDA's Office of the Commissioner from October 2003 until 1 April, 2008, as Deputy Commissioner and Chief Medical Officer, Deputy Commissioner for Operations and Chief Operating Officer and Director of the Critical Path Programs. She oversaw scientific and medical regulatory operations for the FDA. Dr Woodcock served as Director of the Center for Drug Evaluation and Research at the FDA from 1994 to 2005. She previously served in other positions at the FDA including Director of the Office of Therapeutics Research and Review and Acting Deputy Director of the Center for Biologics Evaluation and Research. Dr Woodcock received her MD from Northwestern Medical School (IL, USA), and completed further training and held teaching appointments at the Pennsylvania State University (PA, USA)and the University of California in San Francisco (CA, USA). She joined the FDA in 1986.

Regulatory aspects of noninvasive glucose measurements.

PubMed

Gutman, Steve; Bernhardt, Patricia; Pinkos, Arleen; Moxey-Mims, Marva; Knott, Thomas; Cooper, Jean

2002-01-01

The Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act (the Act) established three regulatory classes for medical devices. Section 513 of the Act specifies three classes based upon the degree of control and Food and Drug Administration (FDA) oversight that is necessary to assure that the various types of devices are safe and effective. High-risk devices are placed into the most regulated device class, Class III. Under Section 515 of the Act, all devices placed in Class III are subject to premarket approval (PMA) requirements. PMA by FDA is the required process of scientific review to ensure the safety and effectiveness of Class III devices. Advisory panel review is required of virtually all original submissions. Manufacturing facilities of devices requiring PMA approval are also subject to preapproval inspection to assure data integrity and compliance with good manufacturing practices. An approved PMA is granted for marketing a particular medical device for a particular intended use. FDA considers noninvasive and minimally invasive glucose devices that are intended to measure, monitor, or predict blood glucose levels in diabetics to be high-risk medical devices. These devices will have a significant potential impact on the medical care of people with diabetes. The technology offers potential improvements in the quality of life, enhanced blood glucose control through increased frequency of testing, or access to testing, in a broader range of patients. However, the technology is not yet well understood, and the information obtained from these devices is often different from the information that has been the traditional base for the management of diabetes. As a result, FDA requires both analytical and clinical studies to support the intended claims for these new devices.

ClinicalTrials.gov and Drugs@FDA: A comparison of results reporting for new drug approval trials

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A.

2016-01-01

Background Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose To validate results posted on ClinicalTrials.gov against publicly-available FDA reviews on Drugs@FDA. Data sources ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical/statistical reviews). Study selection 100 parallel-group, randomized trials for new drug approvals (1/2013 – 7/2014) with results posted on ClinicalTrials.gov (3/15/2015). Data extraction Two assessors systematically extracted, and another verified, trial design, primary/secondary outcomes, adverse events, and deaths. Results The 100 trials were mostly phase 3 (90%) double-blind (92%), placebo-controlled (73%), representing 32 drugs from 24 companies. Of 137 primary outcomes from ClinicalTrials.gov, 134 (98%) had corresponding data in Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results; most differences were nominal (i.e. relative difference < 10%). Of 100 trials, primary outcome results in 14 could not be validated . Of 1,927 secondary outcomes from ClinicalTrials.gov, 1,061 (55%) definitions could be validated and 367 (19%) had results. Of 96 trials with ≥ 1 serious adverse event in either source, 14 could be compared and 7 were discordant. Of 62 trials with ≥ 1 death in either source, 25 could be compared and 17 were discordant. Limitations Unknown generalizability to uncontrolled or crossover trial results. Conclusion Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half of secondary outcomes could not be validated because Drugs@FDA only includes “key outcomes” for regulatory decision-making; nor could serious adverse events and deaths because Drugs@FDA frequently only includes results aggregated across multiple trials. PMID:27294570

Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy

PubMed Central

Pinkerton, JoAnn V.; Pickar, James H.

2016-01-01

Abstract Objective: We review the historical regulation of drug compounding, concerns about widespread use of non-Food and Drug Admiistration (FDA)-approved compounded bioidentical hormone therapies (CBHTs), which do not have proper labeling and warnings, and anticipated impact of the 2013 Drug Quality and Security Act (DQSA) on compounding. Methods: US government websites were searched for documents concerning drug compounding regulation and oversight from 1938 (passage of Federal Food, Drug, and Cosmetic Act [FDCA]) through 2014, including chronologies, Congressional testimony, FDA guidelines and enforcements, and reports. The FDCA and DQSA were reviewed. PubMed and Google were searched for articles on compounded drugs, including CBHT. Results: Congress explicitly granted the FDA limited oversight of compounded drugs in a 1997 amendment to the FDCA, but the FDA has encountered obstacles in exercising that authority. After 64 patient deaths and 750 adversely affected patients from the 2012 meningitis outbreak due to contaminated compounded steroid injections, Congress passed the DQSA, authorizing the FDA to create a voluntary registration for facilities that manufacture and distribute sterile compounded drugs in bulk and reinforcing FDCA regulations for traditional compounding. Given history and current environment, concerns remain about CBHT product regulation and their lack of safety and efficacy data. Conclusions: The DQSA and its reinforcement of §503A of the FDCA solidifies FDA authority to enforce FDCA provisions against compounders of CBHT. The new law may improve compliance and accreditation by the compounding industry; support state and FDA oversight; and prevent the distribution of misbranded, adulterated, or inconsistently compounded medications, and false and misleading claims, thus reducing public health risk. PMID:26418479

Interview with Janet Woodcock.

PubMed

Woodcock, Janet

2010-09-01

Dr Janet Woodcock is the Director of the US FDA's Center for Drug Evaluation and Research. Dr Woodcock has held various positions within the FDA's Office of the Commissioner from October 2003 until 1 April 2008, as Deputy Commissioner and Chief Medical Officer, Deputy Commissioner for Operations and Chief Operating Officer and Director of the Critical Path Programs. She oversaw scientific and medical regulatory operations for the FDA. Dr Woodcock served as Director of the Center for Drug Evaluation and Research at the FDA from 1994 to 2005. She previously served in other positions at the FDA, including Director of the Office of Therapeutics Research and Review and Acting Deputy Director of the Center for Biologics Evaluation and Research. Dr Woodcock received her MD from Northwestern Medical School (IL, USA), and completed further training and held teaching appointments at the Pennsylvania State University (PA, USA) and the University of California in San Francisco (CA, USA). She joined the FDA in 1986.

Why European and United States drug regulators are not speaking with one voice on anti-influenza drugs: regulatory review methodologies and the importance of 'deep' product reviews.

PubMed

Mulinari, Shai; Davis, Courtney

2017-11-09

Relenza represents the first neuraminidase inhibitor (NI), a class of drugs that also includes the drug Tamiflu. Although heralded as breakthrough treatments in influenza, NI efficacy has remained highly controversial. A key unsettled question is why the United States Food and Drug Administration (FDA) has approved more cautious efficacy statements in labelling than European regulators for both drugs. We conducted a qualitative analysis of United States and European Union regulatory appraisals for Relenza to investigate the reasons for divergent regulatory interpretations, pertaining to Relenza's capacity to alleviate symptoms and reduce frequency of complications of influenza. In Europe, Relenza was evaluated via the so-called national procedure with Sweden as the reference country. We show that FDA reviewers, unlike their European (i.e. Swedish) counterpart, (1) rejected the manufacturer's insistence on pooling efficacy data, (2) remained wary of subgroup analyses, and (3) insisted on stringent statistical analyses. These differences meant that the FDA was less likely to depart from prevailing regulatory and scientific standards in interpreting trial results. We argue that the differences are explained largely by divergent institutionalised review methodologies, i.e. the European regulator's reliance on manufacturer-compiled summaries compared to the FDA's examination of original data and documentation from trials. The FDA's more probing and meticulous evaluative methodology allowed its reviewers to develop 'deep' knowledge concerning the clinical and statistical facets of trials, and more informed opinions regarding suitable methods for analysing trial results. These findings challenge the current emphasis on evaluating regulatory performance mainly in terms of speed of review. We propose that persistent uncertainty and knowledge deficits regarding NIs could have been ameliorated had regulators engaged in the public debates over the drugs' efficacy and explained their contrasting methodologies and judgments. Regulators use major resources to evaluate drugs, but if regulators' assessments are not effectively disseminated and used, resources are used inefficiently.

FDA toxicity databases and real-time data entry.

PubMed

Arvidson, Kirk B

2008-11-15

Structure-searchable electronic databases are valuable new tools that are assisting the FDA in its mission to promptly and efficiently review incoming submissions for regulatory approval of new food additives and food contact substances. The Center for Food Safety and Applied Nutrition's Office of Food Additive Safety (CFSAN/OFAS), in collaboration with Leadscope, Inc., is consolidating genetic toxicity data submitted in food additive petitions from the 1960s to the present day. The Center for Drug Evaluation and Research, Office of Pharmaceutical Science's Informatics and Computational Safety Analysis Staff (CDER/OPS/ICSAS) is separately gathering similar information from their submissions. Presently, these data are distributed in various locations such as paper files, microfiche, and non-standardized toxicology memoranda. The organization of the data into a consistent, searchable format will reduce paperwork, expedite the toxicology review process, and provide valuable information to industry that is currently available only to the FDA. Furthermore, by combining chemical structures with genetic toxicity information, biologically active moieties can be identified and used to develop quantitative structure-activity relationship (QSAR) modeling and testing guidelines. Additionally, chemicals devoid of toxicity data can be compared to known structures, allowing for improved safety review through the identification and analysis of structural analogs. Four database frameworks have been created: bacterial mutagenesis, in vitro chromosome aberration, in vitro mammalian mutagenesis, and in vivo micronucleus. Controlled vocabularies for these databases have been established. The four separate genetic toxicity databases are compiled into a single, structurally-searchable database for easy accessibility of the toxicity information. Beyond the genetic toxicity databases described here, additional databases for subchronic, chronic, and teratogenicity studies have been prepared.

Biotechnology stock prices before public announcements: evidence of insider trading?

PubMed

Overgaard, C B; van den Broek, R A; Kim, J H; Detsky, A S

2000-03-01

Unique financial challenges faced by biotechnology companies developing therapeutics have contributed to the creation of a highly sensitive market, where stock prices are capable of great fluctuation. The potential for significant financial reward and the nature of the scientific review process make this industry susceptible to illegal share trading on nonpublic information. We examined stock prices of biotechnology products before and after announcement of Phase III clinical trial and Food and Drug Administration (FDA) Advisory Panel results for indirect evidence of insider trading. Biotechnology stock prices were recorded for 98 products undergoing Phase III clinical trials and 49 products undergoing FDA Advisory Panel review between 1990 and 1998. Prices were recorded for 120 consecutive trading days before and after public announcement of these two events. We compared the average change in stock price of successful products ('winners') with unsuccessful products ('losers') before the public announcement of results for both critical events. The difference between average stock price change from 120 to 3 days before public announcement of results of Phase III clinical trial winners (+27%) and losers (-4%) was highly significant (P = 0.0007). A similar but non-significant difference was observed between the average stock price of winning (+27%) and losing products (+13%) before FDA Advisory Panel review announcements (P = 0.25). Our results provide indirect evidence that insider trading may be common in the biotechnology industry. Clinical investigators may wish to consider this issue before participating in any equity position in the biotechnology industry, especially if they are going to perform research for those companies.

21 CFR 514.5 - Presubmission conferences.

Code of Federal Regulations, 2013 CFR

2013-04-01

... resolution. FDA is committed to resolving differences between a potential applicant and FDA reviewing... communication. (b) Requesting a presubmission conference. A potential applicant is entitled to one or more... establishing part or all of a submission or investigational requirement. A potential applicant's request for a...

21 CFR 514.5 - Presubmission conferences.

Code of Federal Regulations, 2012 CFR

2012-04-01

... resolution. FDA is committed to resolving differences between a potential applicant and FDA reviewing... communication. (b) Requesting a presubmission conference. A potential applicant is entitled to one or more... establishing part or all of a submission or investigational requirement. A potential applicant's request for a...

21 CFR 514.5 - Presubmission conferences.

Code of Federal Regulations, 2010 CFR

2010-04-01

... resolution. FDA is committed to resolving differences between a potential applicant and FDA reviewing... communication. (b) Requesting a presubmission conference. A potential applicant is entitled to one or more... establishing part or all of a submission or investigational requirement. A potential applicant's request for a...

21 CFR 514.5 - Presubmission conferences.

Code of Federal Regulations, 2011 CFR

2011-04-01

... resolution. FDA is committed to resolving differences between a potential applicant and FDA reviewing... communication. (b) Requesting a presubmission conference. A potential applicant is entitled to one or more... establishing part or all of a submission or investigational requirement. A potential applicant's request for a...

21 CFR 514.5 - Presubmission conferences.

Code of Federal Regulations, 2014 CFR

2014-04-01

... resolution. FDA is committed to resolving differences between a potential applicant and FDA reviewing... communication. (b) Requesting a presubmission conference. A potential applicant is entitled to one or more... establishing part or all of a submission or investigational requirement. A potential applicant's request for a...

FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR Staging

Cancer.gov

An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

The regulation of patient-reported outcome claims: need for a flexible standard.

PubMed

Morris, Louis A; Miller, David W

2002-01-01

We review the FDA's policies for the regulation of patient-reported outcome (PRO) claims such as quality of life, productivity, satisfaction and symptom reports and suggest alternative standards for substantiation. We base our review on FDA regulatory activities and public statements in the field of advertising substantiation. We compare these activities to the FDA's label substantiation policies and policies for health-economic (HE) claim substantiation. There is an overt inconsistency between the FDA's policies for substantiation of PRO claims in product labels and substantiation for such claims in advertising materials. This results in a higher standard for PRO claims in promotional vehicles than in product labels. Rather than relying on a "substantial evidence" standard, the FDA should consider a more flexible standard, such as the one currently applied to information included in the Clinical Trials section of product labels, or adopting a "competent and reliable scientific evidence" standard as set forth in Section 114 of the Food and Drug Administration Modernization Act (FDAMA) for HE data. We conclude that there needs to be greater consistency for substantiation in product labels and promotional materials. Furthermore, reconceptualizing most PRO claims as benefit extrapolations as opposed to efficacy information suggests a less rigorous standard is necessary.

Decision support environment for medical product safety surveillance.

PubMed

Botsis, Taxiarchis; Jankosky, Christopher; Arya, Deepa; Kreimeyer, Kory; Foster, Matthew; Pandey, Abhishek; Wang, Wei; Zhang, Guangfan; Forshee, Richard; Goud, Ravi; Menschik, David; Walderhaug, Mark; Woo, Emily Jane; Scott, John

2016-12-01

We have developed a Decision Support Environment (DSE) for medical experts at the US Food and Drug Administration (FDA). The DSE contains two integrated systems: The Event-based Text-mining of Health Electronic Records (ETHER) and the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment (PANACEA). These systems assist medical experts in reviewing reports submitted to the Vaccine Adverse Event Reporting System (VAERS) and the FDA Adverse Event Reporting System (FAERS). In this manuscript, we describe the DSE architecture and key functionalities, and examine its potential contributions to the signal management process by focusing on four use cases: the identification of missing cases from a case series, the identification of duplicate case reports, retrieving cases for a case series analysis, and community detection for signal identification and characterization. Published by Elsevier Inc.

Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.

PubMed

Esensten, Jonathan H; Bluestone, Jeffrey A; Lim, Wendell A

2017-01-24

Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

Medtronic, Inc.; premarket approval of the Interstim Sacral Nerve Stimulation (SNS) System--FDA. Notice.

PubMed

1998-01-29

The Food and Drug Administration (FDA) is announcing its approval of the application by Medtronic, Inc., Minneapolis, MN, for premarket approval, under the Federal Food, Drug, and Cosmetic Act (the act), of the Interstim Sacral Nerve Stimulation (SNS) System. After reviewing the recommendation of the Gastroenterology and Urology Devices Panel, FDA's Center for Devices and Radiological Health (CDRH) notified the applicant, by letter of September 29, 1997, of the approval of the application.

Regulating biopharmaceuticals under CDER versus CBER: an insider's perspective.

PubMed

Schwieterman, William D

2006-10-01

The FDA has recently transferred jurisdiction for the regulation of certain biopharmaceuticals from the Center for Biologics, Evaluation and Research to the Center for Drugs, Evaluation and Research, where they will be reviewed in the same FDA divisions as are traditional pharmaceutical agents. With this transfer, sponsors of investigational biopharmaceuticals should expect changes in the regulatory requirements the FDA imposes on the clinical development plans, including an increase in the size and number of pivotal studies; more consistent requirements for conducting preclinical tests in two animal species; increased emphasis on organ structure and function as components of primary endpoints; more emphasis on characterizing dose-ranging and pharmacology; more intense scrutinizing of product advertising; and decreased direct communication with the review team.

Registering medicines for low-income countries: how suitable are the stringent review procedures of the World Health Organisation, the US Food and Drug Administration and the European Medicines Agency?

PubMed

Doua, Joachim Y; Van Geertruyden, Jean-Pierre

2014-01-01

New medicines are registered after a resource-demanding process. Unfortunately, in low-income countries (LICs), demand outweighs resources. To facilitate registration in LICs, stringent review procedures of the European Medicines Agency (EMA Article-58), Food and Drug Administration (FDA PEPFAR-linked review) and WHO Prequalification programme have been established. Only the PEPFAR-linked review gives approval, while the others make recommendations for approval. This study assessed the performance and discussed the challenges of these three stringent review procedures. Data from WHO, FDA, EMA, Medline and Internet were analysed. Over 60% of medicines reviewed by stringent review procedures are manufactured in India. Until 2012, WHO prequalified 400 medicines (211 vaccines, 130 antiretrovirals, 29 tuberculostatics, 15 antimalarials and 15 others). PEPFAR-linked review approved 156 antiretrovirals, while EMA Article 58 recommended approval of 3 antiretrovirals, 1 vaccine and 1 antimalarial. WHO Prequalification and PEPFAR-linked review are free of charge and as a result have accelerated access to antiretrovirals. They both built capacity in sub-Saharan Africa, although WHO prequalification relies technically on stringent regulatory authorities and financially on donors. Article-58 offers the largest disease coverage and strongest technical capacities, is costly and involves fewer LICs. To meet the high demand for quality medicines in LICs, these stringent review procedures need to enlarge their disease coverage. To improve registration, EMA Article 58 should actively involve LICs. Furthermore, LIC regulatory activities must not be fully resigned to stringent review procedure. © 2013 John Wiley & Sons Ltd.

The Food and Drug Administration and pragmatic clinical trials of marketed medical products

PubMed Central

Anderson, Monique L; Griffin, Joseph; Goldkind, Sara F; Zeitler, Emily P; Wing, Liz; Al-Khatib, Sana M; Sherman, Rachel E

2015-01-01

Pragmatic clinical trials (PCTs) can help answer questions of comparative effectiveness for interventions routinely used in medical practice. PCTs may examine outcomes of one or more marketed medical products, and they are heterogeneous in design and risk. The Food and Drug Administration (FDA) is charged with protecting the rights, safety, and welfare of individuals enrolled in clinical investigations, as well as assuring the integrity upon which approval of medical products are made. The FDA has broad jurisdiction over drugs and medical devices (whether or not they are approved for marketing), and as such, clinical investigations of these products are subject to applicable FDA regulations. While many PCTs will meet the criteria for an exemption from the requirements for an investigational new drug application (IND) or investigational device exemption (IDE), in general all clinical investigations of medical products that fall under FDA jurisdiction must adhere to regulations for informed consent and review by an institutional review board (IRB). We are concerned that current FDA requirements for obtaining individual informed consent may deter or delay the conduct of PCTs intended to develop reliable evidence of comparative safety and effectiveness of approved medical products that are regulated by the FDA. Under current regulations, there are no described mechanisms to alter or waive informed consent to make it less burdensome or more practicable for low-risk PCTs. We recommend that the FDA establish a risk-based approach to obtaining informed consent in PCTs that would facilitate the conduct of PCTs without compromising the protection of enrolled individuals or the integrity of the resulting data. PMID:26374684

Participation of Women and Sex Analyses in Late-Phase Clinical Trials of New Molecular Entity Drugs and Biologics Approved by the FDA in 2007–2009

PubMed Central

Poon, Rita; Khanijow, Keshav; Umarjee, Sphoorti; Yu, Monica; Zhang, Lei; Parekh, Ameeta

2013-01-01

Abstract Background Biological sex differences may contribute to differential treatment outcomes for therapeutic products. This study tracks women's participation in late-phase clinical trials (LPCTs), where efficacy and safety of drugs and biologics are evaluated, of new molecular entity (NME) drugs and biologics approved by the U.S. Food and Drug Administration (FDA) in 2007–2009. Furthermore, presentations of sex-based analyses were assessed from the FDA reviews. Methods New drug applications (NDAs) and biologics license applications (BLAs) were accessed from the U.S. FDA database and evaluated for women's participation in LPCTs. Sex-based analyses for efficacy and safety contained in FDA reviews were surveyed. Ratios for women's LPCT participation (PROPORTION OF STUDY SUBJECTS) to their proportion in the disease population were calculated for each approved therapeutic product and grouped into therapeutic categories. Results Sex-specific (n=5) and pediatric (n=3) drug applications were excluded. Women's participation in LPCTs was 39%, 48%, and 42% in NDAs (n=50) and 49%, 62%, and 58% in BLAs (n=11) for 2007, 2008, and 2009, respectively. Sixty-four percent of NDAs and 91% of BLAs had participation to proportion ratios of ≥0.80. Seventy-four percent of NDA reviews and 64% of BLA reviews included safety and efficacy sex analysis. Ninety-six percent of NDA reviews and 100% of BLA reviews included efficacy sex analysis. Conclusion Women's participation in LPCTs averaged 43% for NDAs and 57% for BLAs in 2007–2009 and varied widely by indication. As a comparison, the 2001 U.S. Government Accountability Office (GAO) reported 52% of women's participation for drug clinical trials in1998–2000 and an FDA study reported 45% for BLAs approved from 1995 to 1999. This study showed that sex-analysis of both safety and efficacy in NDA has increased to 74% since the GAO report of 72%, while those for BLAs increased to 64% from 37% reported for therapeutic biologics approved in 1995–1999. Knowledge of disease prevalence and participation in clinical trials provides an understanding of recruitment and retention patterns of patients in these trials. PMID:23768021

A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience.

PubMed

Goldkind, Lawrence; Laine, Loren

2006-04-01

Drug-induced hepatotoxicity is the leading cause of acute liver failure (ALF) in the US and the most common adverse event causing drug non-approval and drug withdrawal by the U.S. Food and Drug Administration (FDA). Three different nonsteroidal anti-inflammatory drugs (NSAIDs) have been withdrawn in the UK and/or the US due to hepatotoxicity (bromfenac, ibufenac, and benoxaprofen). A systematic review of clinical trials data for these drugs was performed in an effort to identify possible early signals that could have predicted post-marketing serious hepatoxicity. There were very limited published data on benoxaprofen and none on ibufenac or bromfenac. The publicly accessible archives of the FDA provided information on bromfenac. Flu-like symptoms associated with hepatic enzyme elevation and a case of possible drug-related hepatocellular jaundice may in retrospect have been signals for serious hepatotoxicity in the database of 1195 subjects reviewed by the FDA. Following approval, rates of acute liver failure for bromfenac were estimated to be in the range of 1:10 000. In addition, the safety databases of several drugs also accessed through FDA archives have been reviewed (simvastatin, tacrine, troglitazone, and ximelagatran). These data suggest that while ALT elevations alone do not reliably signal serious hepatotoxicity, elevated transaminases in association with symptomatic hepatitis or jaundice may be predictors of an increased risk of ALF. At present, however, pre-approval databases are generally not large enough to rule out low rates of serious hepatotoxicity. Therefore, it remains critical that clinicians report such cases to the FDA through the MEDWATCH system and that active post-marketing monitoring studies be used to identify potential rare cases of hepatotoxicity. Copyright (c) 2006 John Wiley & Sons, Ltd.

A Tale of Two Citizens: A State Attorney General and a Hematologist Facilitate Translation of Research Into US Food and Drug Administration Actions—A SONAR Report

PubMed Central

Chen, Brian; Restaino, John; Norris, LeAnn; Xirasagar, Sudha; Qureshi, Zaina P.; McKoy, June M.; Lopez, Isaac S.; Trenery, Alyssa; Murday, Alanna; Kahn, Adam; Mattison, Donald R.; Ray, Paul; Sartor, Oliver; Bennett, Charles L.

2012-01-01

Purpose: Pharmaceutical safety is a public health issue. In 2005, the Connecticut Attorney General (AG) raised concerns over adverse drug reactions in off-label settings, noting that thalidomide was approved to treat a rare illness, but more than 90% of its use was off label. A hematologist had reported thalidomide with doxorubicin or dexamethasone was associated with venous thromboembolism (VTE) rates of 25%. We review US Food and Drug Administration (FDA) and manufacturer responses to a citizen petition filed to address these thalidomide safety issues. Methods: Case study. Results: The AG petitioned the FDA requesting thalidomide-related safety actions. Coincidentally, the manufacturer submitted a supplemental New Drug Approval (sNDA), requesting approval to treat multiple myeloma with thalidomide-dexamethasone. FDA safety officers reviewed the petition and the literature and noted that VTE risks with thalidomide were not appropriately addressed in the existing package insert. In the sNDA application, the manufacturer reported thalidomide-associated toxicities for multiple myeloma were primarily somnolence and neurotoxicity, and a proposed package insert did not focus on VTE risks. In October, the FDA informed the Oncology Drug Division that VTE risks with thalidomide were poorly addressed in the existing label. After reviewing this memorandum, an Oncology Drug Division reviewer informed the manufacturer that approval of the sNDA would be delayed until several thalidomide-associated VTE safety actions, including revisions of the package insert, were implemented. The manufacturer and FDA agreed on these actions, and the sNDA was approved. Conclusion: New approaches addressing off-label safety are needed. The conditions that facilitated the successful response to this citizen petition are uncommon. PMID:23598851

A tale of two citizens: a State Attorney General and a hematologist facilitate translation of research into US Food and Drug Administration actions--a SONAR report.

PubMed

Chen, Brian; Restaino, John; Norris, LeAnn; Xirasagar, Sudha; Qureshi, Zaina P; McKoy, June M; Lopez, Isaac S; Trenery, Alyssa; Murday, Alanna; Kahn, Adam; Mattison, Donald R; Ray, Paul; Sartor, Oliver; Bennett, Charles L

2012-11-01

Pharmaceutical safety is a public health issue. In 2005, the Connecticut Attorney General (AG) raised concerns over adverse drug reactions in off-label settings, noting that thalidomide was approved to treat a rare illness, but more than 90% of its use was off label. A hematologist had reported thalidomide with doxorubicin or dexamethasone was associated with venous thromboembolism (VTE) rates of 25%. We review US Food and Drug Administration (FDA) and manufacturer responses to a citizen petition filed to address these thalidomide safety issues. Case study. The AG petitioned the FDA requesting thalidomide-related safety actions. Coincidentally, the manufacturer submitted a supplemental New Drug Approval (sNDA), requesting approval to treat multiple myeloma with thalidomide-dexamethasone. FDA safety officers reviewed the petition and the literature and noted that VTE risks with thalidomide were not appropriately addressed in the existing package insert. In the sNDA application, the manufacturer reported thalidomide-associated toxicities for multiple myeloma were primarily somnolence and neurotoxicity, and a proposed package insert did not focus on VTE risks. In October, the FDA informed the Oncology Drug Division that VTE risks with thalidomide were poorly addressed in the existing label. After reviewing this memorandum, an Oncology Drug Division reviewer informed the manufacturer that approval of the sNDA would be delayed until several thalidomide-associated VTE safety actions, including revisions of the package insert, were implemented. The manufacturer and FDA agreed on these actions, and the sNDA was approved. New approaches addressing off-label safety are needed. The conditions that facilitated the successful response to this citizen petition are uncommon.

Biomarkers as drug development tools: discovery, validation, qualification and use.

PubMed

Kraus, Virginia B

2018-06-01

The 21st Century Cures Act, approved in the USA in December 2016, has encouraged the establishment of the national Precision Medicine Initiative and the augmentation of efforts to address disease prevention, diagnosis and treatment on the basis of a molecular understanding of disease. The Act adopts into law the formal process, developed by the FDA, of qualification of drug development tools, including biomarkers and clinical outcome assessments, to increase the efficiency of clinical trials and encourage an era of molecular medicine. The FDA and European Medicines Agency (EMA) have developed similar processes for the qualification of biomarkers intended for use as companion diagnostics or for development and regulatory approval of a drug or therapeutic. Biomarkers that are used exclusively for the diagnosis, monitoring or stratification of patients in clinical trials are not subject to regulatory approval, although their qualification can facilitate the conduct of a trial. In this Review, the salient features of biomarker discovery, analytical validation, clinical qualification and utilization are described in order to provide an understanding of the process of biomarker development and, through this understanding, convey an appreciation of their potential advantages and limitations.

EBOLA and FDA: reviewing the response to the 2014 outbreak, to find lessons for the future

PubMed Central

Largent, Emily A.

2016-01-01

Abstract In 2014, West Africa confronted the most severe outbreak of Ebola virus disease (EVD) in history. At the onset of the outbreak—as now—there were no therapies approved by the U.S. Food and Drug Administration (FDA) for prevention of, post-exposure prophylaxis against, or treatment of EVD. As a result, the outbreak spurred interest in developing novel treatments, sparked calls to use experimental interventions in the field, and highlighted challenges to the standard approach to FDA approval of new drugs. Although the outbreak was geographically centered in West Africa, it showcased FDA's global role in drug development, approval, and access. FDA's response to EVD highlights the panoply of agency powers and demonstrates the flexibility of FDA's regulatory framework. This paper evaluates the strengths and weaknesses of FDA's response and makes policy recommendations regarding how FDA should respond to new and re-emerging public health threats. In particular, it argues that greater emphasis should be placed on drug development in interoutbreak periods and on assuring access to approved products. The current pandemic of Zika virus infection is but one example of an emerging health threat that will require FDA involvement in order to achieve a successful response. PMID:28852537

Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges

PubMed Central

2013-01-01

Tremendous efforts have been made over the past few decades to discover novel cancer biomarkers for use in clinical practice. However, a striking discrepancy exists between the effort directed toward biomarker discovery and the number of markers that make it into clinical practice. One of the confounding issues in translating a novel discovery into clinical practice is that quite often the scientists working on biomarker discovery have limited knowledge of the analytical, diagnostic, and regulatory requirements for a clinical assay. This review provides an introduction to such considerations with the aim of generating more extensive discussion for study design, assay performance, and regulatory approval in the process of translating new proteomic biomarkers from discovery into cancer diagnostics. We first describe the analytical requirements for a robust clinical biomarker assay, including concepts of precision, trueness, specificity and analytical interference, and carryover. We next introduce the clinical considerations of diagnostic accuracy, receiver operating characteristic analysis, positive and negative predictive values, and clinical utility. We finish the review by describing components of the FDA approval process for protein-based biomarkers, including classification of biomarker assays as medical devices, analytical and clinical performance requirements, and the approval process workflow. While we recognize that the road from biomarker discovery, validation, and regulatory approval to the translation into the clinical setting could be long and difficult, the reward for patients, clinicians and scientists could be rather significant. PMID:24088261

Responding rapidly to FDA drug withdrawals: design and application of a new approach for a consumer health website.

PubMed

Embi, Peter J; Acharya, Prasad; McCuistion, Mark; Kishman, Charles P; Haag, Doris; Marine, Stephen

2006-09-06

Information about drug withdrawals may not reach patients in a timely manner, and this could result in adverse events. Increasingly, the public turns to consumer health websites for health information, but such sites may not update their content for days or weeks following important events like Food and Drug Administration (FDA) drug withdrawal actions. There is no recognized standard for how quickly consumer health websites should respond to such events, and reports addressing this issue are lacking. The objective of this study was to develop and implement an approach to enhance the efficiency with which a consumer health website (NetWellness.org) responds to FDA drug withdrawal actions. Evaluation of the current approach used by NetWellness staff to update content affected by FDA action revealed a slow process driven by the goal of performing thorough and comprehensive review and editing. To achieve our desired goal of accurately updating affected content within 24 hours of FDA action, we developed a strategy that included rapid updating of affected Web pages with warning boxes and hyperlinks to the information about the withdrawal. With the next FDA withdrawal event, that of valdecoxib (Bextra) on April 7, 2005, we applied this new approach, observed the time and resource requirements, and monitored the rate at which consumers viewed the updated information to gauge its potential impact. Application of the new approach allowed one person to modify the affected Web pages in less than 1 hour and within 18 hours of the FDA announcement. Using the old strategy, response to a similar event, the withdrawal of rofecoxib (Vioxx) 6 months earlier, had taken over 3 weeks and the efforts of several personnel. Updated valdecoxib content received 188 hits within the first month and 4285 hits within 1 year. Rapid updating of a consumer health website's content in response to an FDA drug withdrawal event was easily accomplished by applying the approach described. This allowed consumers to view accurate information regarding the withdrawn drug much sooner than would otherwise have been the case. Given that consumers increasingly turn to websites for their health information, adoption of a rapid response standard for important health events like FDA drug withdrawals should be considered by the consumer health informatics community.

Paving the critical path: how can clinical pharmacology help achieve the vision?

PubMed

Lesko, L J

2007-02-01

It has been almost 3 years since the launch of the FDA critical path initiative following the publication of the paper "Innovation or Stagnation: Challenges and Opportunities on the Critical Path of New Medical Product Development." The initiative was intended to create an urgency with the drug development enterprise to address the so-called "productivity problem" in modern drug development. Clinical pharmacologists are strategically aligned with solutions designed to reduce late phase clinical trial failures to show adequate efficacy and/or safety. This article reviews some of the ways that clinical pharmacologists can lead and implement change in the drug development process. It includes a discussion of model-based, semi-mechanistic drug development, drug/disease models that facilitate informed clinical trial designs and optimal dosing, the qualification process and criteria for new biomarkers and surrogate endpoints, approaches to streamlining clinical trials and new types of interaction between industry and FDA such as the end-of-phase 2A and voluntary genomic data submission meetings respectively.

FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | Frederick National Laboratory for Cancer Research

Cancer.gov

An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

21 CFR 312.48 - Dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... division in FDA's Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research which is responsible for review of the IND, beginning with the consumer safety officer assigned to the... director of the division in FDA's Center for Drug Evaluation and Research or Center for Biologics...

21 CFR 814.39 - PMA supplements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... which does not affect the safety or effectiveness of the device. (c) All procedures and actions that... copies and additional information if requested by FDA. The time frames for review of, and FDA action on... strengthen a contraindication, warning, precaution, or information about an adverse reaction for which there...

76 FR 80948 - Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

...The Food and Drug Administration (FDA) is extending the comment period for the notice that appeared in the Federal Register of Thursday, November, 10, 2011 (76 FR 70151). In the notice, FDA requested comments on the draft guidance that has been developed to promote the initiation of clinical investigations to evaluate the medical devices under FDA's Investigational Device Exemptions (IDE) regulations. The Agency is taking this action to allow interested persons additional time to submit comments.

Peer-Reviewed Publication of Clinical Trials Completed for Pediatric Exclusivity

PubMed Central

Benjamin, Daniel Kelly; Smith, Philip Brian; Murphy, M. Dianne; Roberts, Rosemary; Mathis, Lisa; Avant, Debbie; Califf, Robert M; Li, Jennifer S.

2009-01-01

Context Much of pediatric drug use is “off-label” because appropriate pediatric studies have not been conducted and the drugs have not been labeled by the US Food and Drug Administration (FDA) for use in children. In 1997, Congress authorized FDA to grant extensions of marketing rights known as “pediatric exclusivity” if FDA-requested pediatric trials were conducted. As a result, there have been over 100 product labeling changes. The publication status of studies completed for pediatric exclusivity has not been evaluated. Objective To quantify the dissemination of results of studies conducted for pediatric exclusivity into the peer-review literature. Design Cohort study of all trials conducted for Pediatric Exclusivity, the subsequent labeling changes, and the publication of those studies in peer-reviewed journals. We categorized each study in the exclusivity application as ”successful” or “unsuccessful” based on FDA approval of the indication sought by the sponsor. We categorized any labeling changes resulting from the studies as ”positive” or “negative” for the drug under study. We then evaluated aspects of the studies and product label changes that were associated with subsequent publication in peer-reviewed medical journals. Main Outcome Measures Publication of the trial data in peer-reviewed journals. Results Between 1998 and 2004, 253 studies were submitted to FDA for pediatric exclusivity: 50% evaluated efficacy, 20% were multi-dose pharmacokinetic, 13% were single-dose pharmacokinetic, and 17% were safety studies. Labeling changes were positive for 127/253 (50%) of studies; only 112/253 (44%) were published. Efficacy studies and those with a favorable labeling change were more likely to be published. Of 100 studies resulting in important labeling changes, only 33 were published. Conclusions The pediatric exclusivity program has been successful in encouraging drug studies in children. However, the dissemination of these results in the peer-reviewed literature is limited. The results of these trials and future studies conducted for pediatric exclusivity should be published in peer-reviewed journals. Mechanisms to more widely disperse this information warrant further evaluation. PMID:16968851

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.

Accounting for heterogeneous treatment effects in the FDA approval process.

PubMed

Malani, Anup; Bembom, Oliver; van der Laan, Mark

2012-01-01

The FDA employs an average-patient standard when reviewing drugs: it approves a drug only if is safe and effective for the average patient in a clinical trial. It is common, however, for patients to respond differently to a drug. Therefore, the average-patient standard can reject a drug that benefits certain patient subgroups (false negatives) and even approve a drug that harms other patient subgroups (false positives). These errors increase the cost of drug development - and thus health care - by wasting research on unproductive or unapproved drugs. The reason why the FDA sticks with an average patient standard is concern about opportunism by drug companies. With enough data dredging, a drug company can always find some subgroup of patients that appears to benefit from its drug, even if the subgroup truly does not. In this paper we offer alternatives to the average patient standard that reduce the risk of false negatives without increasing false positives from drug company opportunism. These proposals combine changes to institutional design - evaluation of trial data by an independent auditor - with statistical tools to reinforce the new institutional design - specifically, to ensure the auditor is truly independent of drug companies. We illustrate our proposals by applying them to the results of a recent clinical trial of a cancer drug (motexafin gadolinium). Our analysis suggests that the FDA may have made a mistake in rejecting that drug.

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

The use of cimetidine in hospitalized patients.

PubMed

Kopala, L

1984-01-01

Cimetidine is the most commonly prescribed drug in North America. A clinical review was conducted to identify physicians' prescribing habits. From September 1, 1981 to March 31, 1982, the charts were reviewed of 50 patients receiving cimetidine in an isolated coastal community hospital in British Columbia. It was discovered that physicians prescribed the drug for reasons approved by the Food and Drug Administration (FDA) only 14% of the time. The FDA guidelines approve cimetidine for duodenal ulcer, Zollinger-Ellison syndrome, and other hypersecretory states. A literature review was conducted, and guidelines on prescribing cimetidine were given to all members of the hospital's medical staff.

A brave new beef: The US Food and Drug Administration's review of the safety of cloned animal products.

PubMed

Solomon, Louis M; Noll, Rebekka C; Mordkoff, David S; Murphy, Patrick; Rolerson, Marcy

2009-09-01

To meet its public mandate, the US Food and Drug Administration (FDA) collected studies on the potential health hazards of eating or drinking cloned food products. Based on an earlier National Academy of Sciences study that, on closer analysis, was not nearly as sanguine, the FDA's report found no evidence of a health risk from the public's ingestion of cloned food products. This article analyzes the risks the FDA considered, and concludes that there is a disconnect between the risks the FDA assessed in these studies and the risks that might arise from cloned food products. The FDA should consider instituting effective tracking mechanisms and other diagnostics that would permit scientists and the public to answer the question of health risks posed by cloned food products.

78 FR 72895 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0797... Request; Human Tissue Intended for Transplantation AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of...

75 FR 45127 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0066... Request; Human Tissue Intended for Transplantation AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of...

76 FR 6142 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0598... Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing... CONTACT: Johnny Vilela, Office of Information Management, Food and Drug Administration, 1350 Piccard Dr...

78 FR 60883 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0545... Request; Infant Formula Requirements AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of information has...

75 FR 48350 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0190... Request; Infant Formula Requirements AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of information has...

78 FR 25746 - Agency Information Collection Activities; Proposed Collection; Comment Request; Product...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0380...: Assignment of Agency Component for Review of Premarket Applications AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing an opportunity for public...

78 FR 16401 - Institutional Review Boards; Correcting Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-15

... Administration, HHS. ACTION: Final rule; correcting amendments. SUMMARY: The Food and Drug Administration (FDA... the regulatory text and to update contact information. This action is editorial in nature and is... action under the Administrative Procedures Act (5 U.S.C. 553). FDA has determined that notice and public...

78 FR 33847 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0172... Request; Foreign Clinical Studies Not Conducted Under an Investigational New Drug Application AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

76 FR 82301 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0619... Request; Medical Devices: Humanitarian Use Devices AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of...

78 FR 20663 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function..., Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. FDA intends to...

75 FR 47600 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... (Tobacco Control Act), FDA must conduct research and studies relating to the control and prevention of... such research, FDA will employ formative pretests to assess the likely effectiveness of tobacco..., formative research will provide critical knowledge about target audiences such as adolescents, adults...

76 FR 60052 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

... Request; Current Good Manufacturing Practice Regulations for Finished Pharmaceuticals AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0362...

75 FR 39537 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0101...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... CONTACT: Elizabeth Berbakos, Office of Information Management, Food and Drug Administration, 1350 Piccard...

ClinicalTrials.gov, stem cells and 'pay-to-participate' clinical studies.

PubMed

Turner, Leigh

2017-09-01

Numerous US businesses that engage in direct-to-consumer advertising of stem cell interventions that are not US FDA-approved also recruit clients by listing 'pay-to-participate' studies listed on ClinicalTrials.gov . Individuals considering enrolling in such studies and NIH officials responsible for overseeing the database need to be aware that some businesses are using the registry to promote unapproved stem cell interventions that study subjects are charged to receive. Inclusion of such studies in ClinicalTrials.gov reveals that the database needs better screening tools. In particular, screening should evaluate whether studies submitted to the registry have been reviewed and permitted to proceed by the FDA in the case of clinical studies requiring FDA clearance in addition to institutional review board approval.

76 FR 24494 - Draft Guidance for Industry and FDA Staff: Processing/Reprocessing Medical Devices in Health Care...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-02

...] Draft Guidance for Industry and FDA Staff: Processing/ Reprocessing Medical Devices in Health Care... Devices in Health Care Settings: Validation Methods and Labeling.'' The recommendations in this guidance... Staff: Processing/Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling...

FDA & digital mammography: why has FDA required full field digital mammography systems to be regulated as potentially dangerous devices for more than 10 years?

PubMed

Nields, Morgan W

2010-05-01

Digital mammography is routinely used in the US to screen asymptomatic women for breast cancer and currently over 50% of US screening centers employ the technology. In spite of FDAs knowledge that digital mammography requires less radiation than film mammography and that its equivalence has been proven in a prospective randomized trial, the agency has failed to allow the technology market access via the 510(k) pre market clearance pathway. As a result of the restrictive Pre Market Approval process, only four suppliers have received FDA approval. The resulting lack of a competitive market has kept costs high, restricted technological innovation, and impeded product improvements as a result of PMA requirements. Meanwhile, at least twelve companies are on the market in the EU and the resulting competitive market has lowered costs and provided increased technological choice. A cultural change with new leadership occurred in the early 90's at FDA. The historical culture at the Center for Devices and Radiological Health of collaboration and education gave way to one characterized by a lack of reliance on outside scientific expertise, tolerance of decision making by unqualified reviewers, and an emphasis on enforcement and punishment. Digital mammography fell victim to this cultural change and as a result major innovations like breast CT and computer aided detection technologies are also withheld from the market. The medical device law, currently under review by the Institute of Medicine, should be amended by the Congress so that new technologies can be appropriately classified in accordance with the risk based assessment classification system detailed in Chapter V of the Federal Food, Drug, and Cosmetic Act. A panel of scientific experts chartered by the NIH or IOM should determine the classification appropriate for new technologies that have no historical regulatory framework. This would be binding on FDA. Unless the law is changed we will likely again experience additional debacles similar to that of digital mammography where important technology has been withheld from millions of women for more than a decade. Copyright 2010 AUR. Published by Elsevier Inc. All rights reserved.

Current FDA regulatory guidance on the conduct of drug discrimination studies for NDA review: Does the scientific literature support recent recommendations?

PubMed

Gauvin, David V; Zimmermann, Zachary J; Kallman, Mary Jeanne

2016-11-01

The Controlled Substances Staff of the Center for Drug Evaluation and Research at the US Food and Drug Administration and the Pharmaceutical Research Manufacturers Association (PhRMA) conducted a series of open forum dialog sessions between 2006 and 2016. A Cross Company Abuse Liability Council (CCALC) was formed during the process of this unique collaborative effort between Industry and Federal Regulators whose goals were to establish the development of standards for the preclinical screening of new molecular entities for schedule control actions required as part of every New Drug Application process. The draft guidance document was published and disseminated in 2010, which allowed for alternative approaches to each study protocol requirement needed for NDA review, if the approach satisfied the requirements of the applicable statutes and regulations (i.e., the controlled substance act). In a series of recent pre-study protocol reviews requested by confidential Pharmaceutical Sponsors of MPI Research, the CSS staff appeared to change its policy and set forth to require all drug discrimination study data to be generated under "extinction" test sessions. MPI Research is a Contract Research Organization acting on behalf of pharmaceutical companies and bound under separate confidentiality agreements. The purpose of this review is to highlight the data appearing in peer-reviewed scientific journals that do not support the regulatory administrative constraints on one specific testing methodology (extinction) to the exclusion of another (reinforced test sessions). This mind shift represents a restrictive administrative policy by the FDA that is not supported by the published data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Regulatory issues for computerized electrocardiographic devices.

PubMed

Muni, Neal I; Ho, Charles; Mallis, Elias

2004-01-01

Computerized electrocardiogram (ECG) devices are regulated in the U.S. by the FDA Center for Devices and Radiological Health (CDRH). This article aims to highlight the salient points of the FDA regulatory review process, including the important distinction between a "tool" claim and a "clinical" claim in the intended use of a computerized ECG device. Specifically, a tool claim relates to the ability of the device to accurately measure a certain ECG parameter, such as T-wave alternans (TWA), while a clinical claim imputes a particular health hazard associated with the identified parameter, such as increased risk of ventricular tachyarrhythmia or sudden death. Given that both types of claims are equally important and receive the same regulatory scrutiny, the manufacturer of a new ECG diagnostic device should consider the distinction and regulatory pathways for approval between the two types of claims discussed in this paper.

Dental radiographic guidelines: a review.

PubMed

Kim, Irene H; Mupparapu, Muralidhar

2009-05-01

The 2004 American Dental Association (ADA)/US Food and Drug Administration (FDA) radiographic selection criteria and guidelines were reviewed and compared with the prior radiographic selection criteria and guidelines. The authors reviewed the publications from the US FDA, US Department of Health and Human Services, and National Council on Radiation Protection and Measurements. The positions outlined by the Canadian Dental Association and the European Commission were also reviewed and compared to US guidelines. The FDA guidelines were first published in 1987, and several changes have been made to them over the years. Recent literature reveals that the general compliance of these guidelines is very low, especially within dental schools in the United States and Canada. Little is known about the compliance outside of the dental school environment; however, it is expected to be low for various reasons. In 2007, the International Commission on Radiological Protection (ICRP) revised its estimates of tissue radiosensitivity, which resulted in effective doses of dental radiographs 32% to 422% higher than the 1990 ICRP guidelines. Flow charts summarizing the latest guidelines were developed to facilitate general compliance among practitioners. Based on the literature reviewed and the recent ICRP findings, it would be prudent for dental health care professionals to follow dental radiographic guidelines.

The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis.

PubMed

Adil, Areej; Godwin, Marshall

2017-07-01

Androgenetic alopecia, or male pattern hair loss, is a hair loss disorder mediated by dihydrotestosterone, the potent form of testosterone. Currently, minoxidil and finasteride are Food and Drug Administration (FDA)-approved, and HairMax LaserComb, which is FDA-cleared, are the only treatments recognized by the FDA as treatments of androgenetic alopecia. This systematic review and meta-analysis assesses the efficacy of nonsurgical treatments of androgenetic alopecia in comparison to placebo for improving hair density, thickness, growth (defined by an increased anagen:telogen ratio), or subjective global assessments done by patients and investigators. A systematic review of randomized controlled trials was conducted. PubMed, Embase, and Cochrane were searched up to December 2016, with no lower limit on the year. We included only randomized controlled trials of good or fair quality based on the US Preventive Services Task Force quality assessment process. A meta-analysis was conducted separately for 5 groups of studies that tested the following hair loss treatments: low-level laser light therapy in men, 5% minoxidil in men, 2% minoxidil in men, 1 mg finasteride in men, and 2% minoxidil in women. All treatments were superior to placebo (P < .00001) in the 5 meta-analyses. Other treatments were not included because the appropriate data were lacking. High heterogeneity in most studies. This meta-analysis strongly suggests that minoxidil, finasteride, and low-level laser light therapy are effective for promoting hair growth in men with androgenetic alopecia and that minoxidil is effective in women with androgenetic alopecia. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

FDA toxicity databases and real-time data entry

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

Arvidson, Kirk B.

Structure-searchable electronic databases are valuable new tools that are assisting the FDA in its mission to promptly and efficiently review incoming submissions for regulatory approval of new food additives and food contact substances. The Center for Food Safety and Applied Nutrition's Office of Food Additive Safety (CFSAN/OFAS), in collaboration with Leadscope, Inc., is consolidating genetic toxicity data submitted in food additive petitions from the 1960s to the present day. The Center for Drug Evaluation and Research, Office of Pharmaceutical Science's Informatics and Computational Safety Analysis Staff (CDER/OPS/ICSAS) is separately gathering similar information from their submissions. Presently, these data are distributedmore » in various locations such as paper files, microfiche, and non-standardized toxicology memoranda. The organization of the data into a consistent, searchable format will reduce paperwork, expedite the toxicology review process, and provide valuable information to industry that is currently available only to the FDA. Furthermore, by combining chemical structures with genetic toxicity information, biologically active moieties can be identified and used to develop quantitative structure-activity relationship (QSAR) modeling and testing guidelines. Additionally, chemicals devoid of toxicity data can be compared to known structures, allowing for improved safety review through the identification and analysis of structural analogs. Four database frameworks have been created: bacterial mutagenesis, in vitro chromosome aberration, in vitro mammalian mutagenesis, and in vivo micronucleus. Controlled vocabularies for these databases have been established. The four separate genetic toxicity databases are compiled into a single, structurally-searchable database for easy accessibility of the toxicity information. Beyond the genetic toxicity databases described here, additional databases for subchronic, chronic, and teratogenicity studies have been prepared.« less

Analysis of US Food and Drug Administration Warning Letters: False Promotional Claims Relating to Prescription and Over-the-Counter Medications.

PubMed

Salas, Maribel; Martin, Michelle; Pisu, Maria; McCall, Erin; Zuluaga, Alvaro; Glasser, Stephen P

2008-03-01

Recent studies have suggested that there has been an increase in the number of 'warning letters' issued by the US Food and Drug Administration (FDA) despite the publication of the FDA advertising guidelines. However, limited information is available on the description of warning letters. The objective of this study was to analyse the frequency and content of FDA warning letters in relation to promotional claims and discuss the influence of regulatory and industry constraints on promotion. All warning letters published by the FDA between 5 May 1995 and 11 June 2007 were reviewed. Warning letters related to promotional issues were included and analysed. Information related to the identification number, date of the warning letter, FDA division that issued the letter, drug name, manufacturer, specific warning problem, type of promotional material and requested action was extracted. Two independent investigators reviewed and classified each PDF file, any differences were discussed until a consensus was reached. Between May 1995 and June 2007 a total of 8692 warning letters were issued, of which 25% were related to drugs. Of these, 206 warning letters focused on drug promotion and were included in this study: 23% were issued in 2005, 15% in 2004 and 14% in 1998. In total, 47% of the warning letters were issued because of false or misleading unapproved doses and uses, 27% failed to disclose risks, 15% cited misleading promotion, 8% related to misleading labelling and 3% promoted false effectiveness claims. There is an important variation in the number of warning letters issued in the last decade, probably because of the increasing number of drugs approved by the FDA, drug withdrawal scandals, and the publication of the FDA and the Pharmaceutical Research and Manufacturers of America (PhRMA) guidelines. We found that benefit-related claims, such as unapproved uses or doses of drugs, and failure to disclose risks, are the main causes of FDA issued warning letters for promotional claims related to medications.

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

2016-09-20

Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

Bone morphogenetic protein use in spine surgery-complications and outcomes: a systematic review.

PubMed

Faundez, Antonio; Tournier, Clément; Garcia, Matthieu; Aunoble, Stéphane; Le Huec, Jean-Charles

2016-06-01

Because of significant complications related to the use of autologous bone grafts in spinal fusion surgery, bone substitutes and growth factors such as bone morphogenetic protein (BMP) have been developed. One of them, recombinant human (rh) BMP-2, has been approved by the Food and Drug Administration (FDA) for use under precise conditions. However, rhBMP-2-related side effects have been reported, used in FDA-approved procedures, but also in off-label use.A systematic review of clinical data was conducted to analyse the rhBMP-2-related adverse events (AEs), in order to assess their prevalence and the associated surgery practices. Medline search with keywords "bone morphogenetic protein 2", "lumbar spine", "anterolateral interbody fusion" (ALIF) and the filter "clinical trial". FDA published reports were also included. Study assessment was made by authors (experienced spine surgeons), based on quality of study designs and level of evidence. Extensive review of randomised controlled trials (RCTs) and controlled series published up to the present point, reveal no evidence of a significant increase of AEs related to rhBMP-2 use during ALIF surgeries, provided that it is used following FDA guidelines. Two additional RCTs performed with rhBMP-2 in combination with allogenic bone dowels reported increased bone remodelling in BMP-treated patients. This AE was transient and had no consequence on the clinical outcome of the patients. No other BMP-related AEs were reported in these studies. This literature review confirms that the use of rhBMP-2 following FDA-approved recommendations (i.e. one-level ALIF surgery with an LT-cage) is safe. The rate of complications is low and the AEs had been identified by the FDA during the pre-marketing clinical trials. The clinical efficiency of rhBMP-2 is equal or superior to that of allogenic or autologous bone graft in respect to fusion rate, low back pain disability, patient satisfaction and rate of re-operations. For all other off-label use, the safety and effectiveness of rhBMP-2 have not been established, and further RCTs with high level of evidence are required.

Marketing approval for the lithotripter.

PubMed

Nightingale, S L; Young, F E

1986-01-01

In December 1984, the Food and Drug Administration (FDA) granted Dornier Systems (FRG) approval to market the external shock wave lithotripter (ESWL) in the USA. The Medical Device Amendments of the Food, Drug, and Cosmetic Act require that the FDA evaluate the safety and effectiveness of medical devices intended for commercial distribution in the U.S. Such evaluation includes basic scientific studies, animal testing, and investigational studies in human subjects, culminating in a judgment concerning acceptable risks in terms of anticipated benefits, and whether the device is effective for its intended use. Prior to human studies in West Germany, Dornier had evaluated the destruction of stones of varying composition, measured the rate and energy of stone destruction, and tested blood samples and lymphocyte cultures exposed to shock waves. In addition, studies in both rats and dogs had demonstrated the feasibility of the technique and evidence of safety. Such data are provided by manufacturers when applying for an investigational device exemption (IDE) from the FDA, which permits clinical studies in humans; such studies also require the approval of an Institutional Review Board. The FDA approved Dornier's IDE, allowing human investigational use of the ESWL in facilities in the U.S., conducted concurrently with similar studies in West Germany. Upon completion of clinical trials, data acquired in vitro, in laboratory animals, and in human investigations are submitted to the FDA for a premarked approval application (PMAA). The Agency was given 6 months to make a decision, taking into consideration the recommendation of an advisory panel of experts from outside the Agency who had reviewed the same data. In its evaluation of the ESWL for safety and effectiveness, the FDA considered the question of alternative practices and procedures to treat nephrolithiasis, including percutaneous nephrolithotomy and open surgical procedures, and the adverse effects of such procedures. Clinical data available at the time of review for approval included reports of treatment of 667 patients in West German centers, and 327 patients treated in three U.S. facilities. Dornier and the FDA initiated discussions concerning the labeling of the device and a postmarketing surveillance plan. These were completed and marketing approval for the ESWL was granted.

Your business in court and at federal agencies: 2010 - 2011.

PubMed

Reiss, John B; Crowder, Dawn; Simons, Brian; Pleskov, Igor; Davis, Tiffany; Nugent, Patrick

2012-01-01

This year the government aggressively pursued Manufacturers under the enhanced provisions of the False Claims Act (FCA), as well as under the provisions of the Food, Drug and Cosmetics Act (FDCA). In addition, the government pursued actions against individual executives under the Responsible Corporate Officer Doctrine ("RCO Doctrine") because it does not believe sanctions against the companies provide sufficient deterrence to inappropriate behavior. Companies need to focus on implementing effective compliance programs in order to prevent the occurrence of allegedly improper activity. It should be noted that the existence of an effective program will not protect executives from liability under the RCO Doctrine if improper behavior takes place. The Food and Drug Administration's (FDA's) has undertaken a number of initiatives during the past year in an attempt to counter claims that its review processes for domestic products is driving the development of drugs and devices to overseas markets. The Agency also has improved its capacity to review products imported from overseas by undertaking initiatives with foreign agencies and stationing more FDA employees in foreign countries. The FDA increased the number of warning letters and other enforcement actions. The FDA added two new topics of enhanced authority during the year. One was an expansion of its regulatory authority over foods, and the second was new authority to regulate certain tobacco products. The former is being subjected to some review by the courts, and the scope of its authority over tobacco is the subject of ongoing major litigation. The Federal Trade Commission (FTC) and Securities and Exchange Commission (SEC) are unlikely to experience significant change regarding their regulation of Manufacturers. The FTC, as it has for many years, continues to try to prevent "reverse" payments to generic drug manufacturers by Innovator Manufacturers to diminish generic drug competition, and proposed legislation is before Congress. The SEC still appears focused on the Foreign Corporate Practices Act with respect to enforcement against pharmaceutical and device manufacturers. Federal preemption of State law continues to be a topic of concern, with Court's taking different positions on the effect of the various Supreme Court decisions made in the last two years.

76 FR 71575 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0492... Request; Class II Special Controls Guidance Document: Labeling for Natural Rubber Latex Condoms AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

78 FR 21613 - Prescription Drug User Fee Act Patient-Focused Drug Development; Announcement of Disease Areas...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

... syndrome; narcolepsy; neurological manifestations of inborn errors of metabolism; Parkinson's disease and... available therapies. Patients who live with a disease have a direct stake in the outcome of FDA's decisions... of applications for new drugs in certain disease areas. For FDA's review divisions, this kind of...

78 FR 6824 - Considerations Regarding Food and Drug Administration Review and Regulation of Drugs for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... Amyotrophic Lateral Sclerosis; Public Hearing AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public hearing; request for comments. SUMMARY: The Food and Drug Administration (FDA or the Agency) is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0035...

78 FR 44126 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

... for products regulated by FDA, including foods and dietary supplements that bear a nutrient content... applications for research or marketing permits for products regulated by FDA, including foods and dietary supplements, that bear a nutrient content claim or a health claim, infant formulas, food and color additives...

77 FR 57092 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... to FDA's decision not to authorize four dietary supplement health claims that failed to meet the SSA... study is to collect quantitative data to examine consumer interpretations of two dietary supplement... Conventional Human Foods and Human Dietary Supplements,'' 2003, available at http://www.fda.gov/Food/Guidance...

75 FR 65636 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0541... Request; Guidance for Industry on Special Protocol Assessment AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection...

76 FR 6475 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0603... Request; Animal Drug User Fees and Fee Waivers and Reductions AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection...

75 FR 70266 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... Nutrition Facts label format to require, the Agency undertook consumer research to evaluate alternatives (Refs. 1, 2, and 3). More recently, FDA conducted qualitative consumer research on the format of the.... 5). In addition to conducting consumer research, in response to the OWG plan FDA issued two advance...

78 FR 50064 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0380...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... CONTACT: Jonna Capezzuto, Office of Operations, Food and Drug Administration, 1350 Piccard Dr., PI50-400B...

75 FR 59721 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0356... Request; Designated New Animal Drugs for Minor Use and Minor Species AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed...

77 FR 33746 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0110...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... CONTACT: Daniel Gittleson, Office of Information Management, Food and Drug Administration, 1350 Piccard Dr...

78 FR 71623 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0716... Request; Designated New Animal Drugs for Minor Use and Minor Species AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed...

77 FR 46441 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0386... Establishments and Listing of Ingredients in Tobacco Products AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of...

75 FR 80825 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... pet food, and that FDA conducts inspections of pet food manufacturing establishments. However, USDA is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0368... Request; Pet Event Tracking Network--State, Federal Cooperation To Prevent Spread of Pet Food Related...

75 FR 65491 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0411... Request; Guide To Minimize Microbial Food Safety Hazards of Fresh-Cut Fruits and Vegetables AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

76 FR 51986 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0410... Request; Premarket Notification for a New Dietary Ingredient AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection...

75 FR 8957 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

....fda.gov/ScienceResearch/SpecialTopics/WomensHealthResearch/ucm134844.htm . FDA regulations (21 CFR 201... ``mental modeling,'' a qualitative research method that compares a model of the priorities, perceptions... are rarely included in experimental research studies of the medication because of concerns that the...

76 FR 56201 - Prescription Drug User Fee Act; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... PDUFA expires in September 2012. At that time, new legislation will be required for FDA to collect... and upgrade its information technology systems. At the same time, FDA committed to complete reviews in...\\ Since PDUFA was enacted, the median approval time of original NDAs and BLAs has been reduced by about 50...

Antiperspirant drug products for over-the-counter human use; final monograph. Final rule.

PubMed

2003-06-09

The Food and Drug Administration (FDA) is issuing a final rule in the form of a final monograph establishing conditions under which over-the-counter (OTC) antiperspirant drug products are generally recognized as safe and effective and not misbranded as part of FDA's ongoing review of OTC drug products. FDA is issuing this final rule after considering public comments on its proposed regulation, issued as a tentative final monograph (TFM), and all new data and information on antiperspirant drug products that have come to the agency's attention.

Obesity and Pediatric Drug Development.

PubMed

Vaughns, Janelle D; Conklin, Laurie S; Long, Ying; Zheng, Panli; Faruque, Fahim; Green, Dionna J; van den Anker, John N; Burckart, Gilbert J

2018-05-01

There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies. FDA labels were also reviewed for statements addressing obesity in pediatric patients. Forty-five drugs studied in pediatric patients under the FDA Amendments Act were found to have statements and key words in the medical and clinical pharmacology reviews and labels related to obesity. Forty-four products were identified similarly with pediatric studies under FDASIA. Of the 89 product labels identified, none provided dosing information related to obesity. The effect of body mass index on drug pharmacokinetics was mentioned in only 4 labels. We conclude that there is little information presently available to provide guidance related to dosing in obese pediatric patients. Moving forward, regulators, clinicians, and the pharmaceutical industry should consider situations in drug development in which the inclusion of obese patients in pediatric trials is necessary to facilitate the safe and effective use of new drug products in the obese pediatric population. © 2018, The American College of Clinical Pharmacology.

Conflicts of interest in approvals of additives to food determined to be generally recognized as safe: out of balance.

PubMed

Neltner, Thomas G; Alger, Heather M; O'Reilly, James T; Krimsky, Sheldon; Bero, Lisa A; Maffini, Maricel V

Food and Drug Administration (FDA) guidance allows food manufacturers to determine whether additives to food are "generally recognized as safe" (GRAS). Manufacturers are not required to notify the FDA of a GRAS determination, although in some instances they notify the agency. The individuals that companies select to make these determinations may have financial conflicts of interest. To determine the extent to which individuals selected by manufacturers to make GRAS determinations have conflicts of interest between their obligations to ensure that the use of the additive is safe and their financial relationships to the company. DESIGN Using conflict of interest criteria developed by a committee of the Institute of Medicine, we analyzed 451 GRAS notifications that were voluntarily submitted to the FDA between 1997 and 2012. Number of GRAS notices submitted to the FDA; frequency of various types of relationships between decision maker and additive manufacturer; frequency of participation on GRAS panels by individuals; and number of GRAS safety determinations identified by the FDA that were not submitted to the agency. For the 451 GRAS notifications, 22.4% of the safety assessments were made by an employee of an additive manufacturer, 13.3% by an employee of a consulting firm selected by the manufacturer, and 64.3% by an expert panel selected by either a consulting firm or the manufacturer. A standing expert panel selected by a third party made none of these safety assessments. The 290 panels that made GRAS determinations had an average of 3.5 members, with a maximum of 7. Ten individuals served on 27 or more panels; 1 individual served on 128 panels (44.1%). At least 1 of the 10 individuals with the most frequent service was a member of 225 panels (77.6%). Between 1997 and 2012, financial conflicts of interest were ubiquitous in determinations that an additive to food was GRAS. The lack of independent review in GRAS determinations raises concerns about the integrity of the process and whether it ensures the safety of the food supply, particularly in instances where the manufacturer does not notify the FDA of the determination. The FDA should address these concerns.

Patient-Reported Outcomes in Cancer Drug Development and US Regulatory Review: Perspectives From Industry, the Food and Drug Administration, and the Patient.

PubMed

Basch, Ethan; Geoghegan, Cindy; Coons, Stephen Joel; Gnanasakthy, Ari; Slagle, Ashley F; Papadopoulos, Elektra J; Kluetz, Paul G

2015-06-01

Data reported directly by patients about how they feel and function are rarely included in oncology drug labeling in the United States, in contrast to Europe and to nononcology labeling in the United States, where this practice is more common. Multiple barriers exist, including challenges unique to oncology trials, and industry's concerns regarding cost, logistical complexities, and the Food and Drug Administration's (FDA's) rigorous application of its 2009 guidance on the use of patient-reported outcome (PRO) measures. A panel consisting of representatives of industry, FDA, the PRO Consortium, clinicians, and patients was assembled at a 2014 workshop cosponsored by FDA to identify practical recommendations for overcoming these barriers. Key recommendations included increasing proactive encouragement by FDA to clinical trial sponsors for including PROs in drug development programs; provision of comprehensive PRO plans by sponsors to FDA early in drug development; promotion of an oncology-specific PRO research agenda; development of an approach to existing ("legacy") PRO measures, when appropriate (focused initially on symptoms and functional status); and increased FDA and industry training in PRO methodology. FDA has begun implementing several of these recommendations.

Use of surrogate outcomes in US FDA drug approvals, 2003-2012: a survey.

PubMed

Yu, Tsung; Hsu, Yea-Jen; Fain, Kevin M; Boyd, Cynthia M; Holbrook, Janet T; Puhan, Milo A

2015-11-27

To evaluate, across a spectrum of diseases, how often surrogate outcomes are used as a basis for drug approvals by the US Food and Drug Administration (FDA), and whether and how the rationale for using treatment effects on surrogates as predictors of treatment effects on patient-centred outcomes is discussed. We used the Drugs@FDA website to identify drug approvals produced from 2003 to 2012 by the FDA. We focused on four diseases (chronic obstructive pulmonary disease (COPD), type 1 or 2 diabetes, glaucoma and osteoporosis) for which surrogates are commonly used in trials. We reviewed the drug labels and medical reviews to provide empirical evidence on how surrogate outcomes are handled by the FDA. Of 1043 approvals screened, 58 (6%) were for the four diseases of interest. Most drugs for COPD (7/9, 78%), diabetes (26/26, 100%) and glaucoma (9/9, 100%) were approved based on surrogates while for osteoporosis, most drugs (10/14, 71%) were also approved for patient-centred outcomes (fractures). The rationale for using surrogates was discussed in 11 of the 43 (26%) drug approvals based on surrogates. In these drug approvals, we found drug approvals for diabetes are more likely than the other examined conditions to contain a discussion of trial evidence demonstrating that treatment effects on surrogate outcomes predict treatment effects on patient-centred outcomes. Our results suggest that the FDA did not use a consistent approach to address surrogates in assessing the benefits and harms of drugs for COPD, type 1 or 2 diabetes, glaucoma and osteoporosis. For evaluating new drugs, patient-centred outcomes should be chosen whenever possible. If the use of surrogate outcomes is necessary, then a consistent approach is important to review the evidence for surrogacy and consider surrogate's usage in the treatment and population under study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Use of Cimetidine in Hospitalized Patients

PubMed Central

Kopala, Lili

1984-01-01

Cimetidine is the most commonly prescribed drug in North America. A clinical review was conducted to identify physicians' prescribing habits. From September 1, 1981 to March 31, 1982, the charts were reviewed of 50 patients receiving cimetidine in an isolated coastal community hospital in British Columbia. It was discovered that physicians prescribed the drug for reasons approved by the Food and Drug Administration (FDA) only 14% of the time. The FDA guidelines approve cimetidine for duodenal ulcer, Zollinger-Ellison syndrome, and other hypersecretory states. A literature review was conducted, and guidelines on prescribing cimetidine were given to all members of the hospital's medical staff. PMID:21283494

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.

Review of Usnic Acid and Usnea Barbata Toxicity

PubMed Central

Guo, Lei; Shi, Qiang; Fang, Jia-Long; Mei, Nan; Ali, A. Afshan; Lewis, Sherry M.; Leakey, Julian E.A.; Frankos, Vasilios H.

2017-01-01

Usnic acid is a prominent secondary lichen metabolite that has been used for various purposes worldwide. Crude extracts of usnic acid or pure usnic acid have been marketed in the United States as dietary supplements to aid in weight loss. The US Food and Drug Administration (FDA) received 21 reports of liver toxicity related to the ingestion of dietary supplements that contain usnic acid. This prompted the FDA to issue a warning about one such supplement, LipoKinetix, in 2001 (http://www.cfsan.fda.gov/~dms/ds-lipo.html). Subsequently, usnic acid and Usnea barbata lichen were nominated by the National Toxicology Program (NTP) for toxicity evaluations. At present, a toxicological evaluation of usnic acid is being conducted by the NTP. This review focuses on the recent findings of usnic acid-induced toxicities and their underlying mechanisms of action. PMID:19034791

Medical devices; hematology and pathology devices; classification of cord blood processing system and storage container. Final rule.

PubMed

2007-02-01

The Food and Drug Administration (FDA) is classifying a cord blood processing system and storage container into class II (special controls). The special control that will apply to this device is the guidance document entitled "Class II Special Controls Guidance Document: Cord Blood Processing System and Storage Container." FDA is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of this device. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of the guidance document that will serve as the special control for this device.

Advances in downstream processing of biologics - Spectroscopy: An emerging process analytical technology.

PubMed

Rüdt, Matthias; Briskot, Till; Hubbuch, Jürgen

2017-03-24

Process analytical technologies (PAT) for the manufacturing of biologics have drawn increased interest in the last decade. Besides being encouraged by the Food and Drug Administration's (FDA's) PAT initiative, PAT promises to improve process understanding, reduce overall production costs and help to implement continuous manufacturing. This article focuses on spectroscopic tools for PAT in downstream processing (DSP). Recent advances and future perspectives will be reviewed. In order to exploit the full potential of gathered data, chemometric tools are widely used for the evaluation of complex spectroscopic information. Thus, an introduction into the field will be given. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

78 FR 25749 - Submission of New Drug Application/Abbreviated New Drug Application Field Alert Reports: Notice...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-02

... language)-enabled Adobe PDF form, Form FDA 3331--Automated to submit new drug application (NDA) and...-enabled Adobe PDF form, Form FDA 3331--Automated, will be available for piloting between May 1, 2013, and... modernize the FAR submission and review pathway using an XML-enabled PDF form to enable integration with...

77 FR 14018 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-08

... Smoking Prevention and Tobacco Control Act (the Tobacco Control Act) (Pub. L. 111-31) into law. The... 3734 for Cigarette Flavor Ban Violations. This new form will be posted on FDA's Web site, and... similar type of reporting went into effect for the cigarette flavor ban, FDA has received several reports...

76 FR 62810 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-11

... partnership between FDA and the University of Maryland. The CRCR will design and administer the study. FDA is... in the article. To help design and refine the questionnaire, we will recruit 25 participants in order...-four participants (20 consumers, 2 growers, 2 retailers) will complete the pretest. Each pretest will...

76 FR 20990 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

... Communication Research will design and administer the study. The proposed study will assess consumers' emotional... will help FDA to design more effective consumer food recall messages during and after a recall. FDA... collection of information is 354 hours (table 1 of this document). To help design and refine the...

76 FR 6620 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

... violative drug residues in products from treated animals and to investigate product defects when a drug is... medicated feeds for which FDA has determined that the drugs used in their manufacture need less control... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0601...

78 FR 17932 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

... Federal Food, Drug, and Cosmetic Act (21 U.S.C. 342(a)(3)). In addition, the current good manufacturing... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0033... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

76 FR 7866 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... with the OMB control number 0910-0539. Also include the FDA docket number found in brackets in the..., Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville, MD 20850, 301-796-7651, [email protected] . SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has...

76 FR 12975 - Determination of Regulatory Review Period for Purposes of Patent Extension; CERVARIX

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

... in situ; and cervical intraepithelial neoplasia grade 1. Subsequent to this approval, the Patent and... testing phase and approval phase as specified in 35 U.S.C. 156(g)(1)(B). FDA recently approved for...) from MedImmune, LLC., and the Patent and Trademark Office requested FDA's assistance in determining...

Development of a patient-reported outcome measure of recovery after abdominal surgery: a hypothesized conceptual framework.

PubMed

Alam, Roshni; Figueiredo, Sabrina M; Balvardi, Saba; Nauche, Bénédicte; Landry, Tara; Lee, Lawrence; Mayo, Nancy E; Feldman, Liane S; Fiore, Julio F

2018-05-17

We initiated a research program to develop a novel patient-reported outcome measure (PROM) to assess postoperative recovery from the perspective of abdominal surgery patients. In light of FDA recommendations, the first stage of our program aimed to, based on previous literature and expert input, develop a hypothesized conceptual framework portraying the health domains that are potentially relevant to the process of recovery after abdominal surgery. This study was conducted in three phases: (1) systematic review to identify PROMs with measurement properties appraised in the context of recovery after abdominal surgery, (2) content analysis to categorize the health domains covered by the PROMs according to the ICF, and (3) two-round Delphi study to gain expert input regarding which of these health domains are relevant to the process of recovery. Participants were experts in perioperative care identified through two major surgical societies (35 invited). The systematic review identified 19 PROMs covering 66 ICF domains. 23 experts (66%) participated in the Delphi process. After Round 2, experts agreed that 22 health domains (8 body functions, 14 activities and participation) are potentially relevant to the process of recovery after abdominal surgery. These domains were organized into a diagram, representing our hypothesized conceptual framework. This hypothesized conceptual framework is an important first step in our research program and will be further refined based on in-depth qualitative interviews with patients. The sound methodological approach used to derive this framework may be valuable for studies aimed to develop PROMs according to FDA standards.

Assessment of Apixaban Prescribing Patterns for Nonvalvular Atrial Fibrillation in Hospitalized Patients.

PubMed

Gibson, Caitlin M; Smith, Carmen B; Davis, Sondra; Scalese, Michael J

2018-01-01

Apixaban is a direct oral anticoagulant (DOAC) for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Other DOACs require renal dose adjustments based solely on creatinine clearance. Apixaban differs in that its dose adjustments are more complex, potentially leading to prescribing errors. To determine if adherence to Food and Drug Administration (FDA)-approved dosing for apixaban is maintained in hospitalized patients with NVAF. Patients ≥18 years old with NVAF who received apixaban during admission to 1 of 3 hospitals were evaluated. The primary outcome was to determine if providers order apixaban in accordance with FDA-approved dosages. Secondary outcomes included determining if pharmacist review increased the number of orders in accordance with FDA-approved dosing, which of the 3 criteria (age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) were met in patients receiving off-label dosing, and the rationale for off-label prescribing. A total of 556 patients met inclusion criteria. Apixaban was dosed according to FDA labeling by providers in 83.4% (n = 464) of orders. After pharmacist review, 87.0% (n = 484) of orders were at the approved dose, 12.2% (n = 68) were underdosed, and 0.7% (n = 4) were overdosed. Most patients who were underdosed met only 1 dose reduction criterion-most commonly age ≥80 years (56.0%). Reasons for off-label dosing included home dose continuation (39.0%), history of or perceived bleeding risk (30.5%), or unspecified/other (30.5%). The majority of apixaban orders for NVAF were based on FDA-approved dosages after provider entry and pharmacist review.

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.

Dandruff, seborrheic dermatitis, and psoriasis drug products containing coal tar and menthol for over-the-counter human use; amendment to the monograph. Final rule

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

NONE

2006-03-15

The Food and Drug Administration (FDA) is issuing a final rule amending the final monograph (FM) for over-the-counter (OTC) dandruff, seborrheic dermatitis, and psoriasis drug products to include the combination of 1.8 percent coal tar solution and 1.5 percent menthol in a shampoo drug product to control dandruff. FDA did not receive any comments or data in response to its previously proposed rule to include this combination. This final rule is part of FDA's ongoing review of OTC drug products.

Recent strategies for drug development in fibromyalgia syndrome.

PubMed

Blumenthal, David E; Malemud, Charles J

2016-12-01

The US Federal Drug Administration (FDA) approved 3 medications for treating fibromyalgia syndrome (FMS). There have been no additional FDA approvals since January 2009 and the efficacy of the FDA-approved medications for FMS has been questioned. Areas covered: The "search for studies" tool using clinicaltrials.gov and PubMed were employed. The term, "fibromyalgia" was used for clinicaltrials.gov. The terms employed for PubMed were "Name-of-Drug Fibromyalgia", "Fibromyalgia Treatment" or "Fibromyalgia Drug Treatment." Clinical trials were reviewed if they were prospective and blinded, and if they employed a comparator, either placebo or another pharmaceutical. Expert commentary: Progress toward standardizing the outcome measures for FMS clinical trials have been made but challenges remain. Several pharmaceutical candidates for FMS have been tested since 2009. The results of these studies with potential novel targets for drug development for FMS were reviewed including the results of trials with sodium oxybate, quetiapine, esreboxetine, nabilone, memantine, naltrexone, and melatonin.

The first FDA marketing authorizations of next-generation sequencing technology and tests: challenges, solutions and impact for future assays.

PubMed

Bijwaard, Karen; Dickey, Jennifer S; Kelm, Kellie; Težak, Živana

2015-01-01

The rapid emergence and clinical translation of novel high-throughput sequencing technologies created a need to clarify the regulatory pathway for the evaluation and authorization of these unique technologies. Recently, the US FDA authorized for marketing four next generation sequencing (NGS)-based diagnostic devices which consisted of two heritable disease-specific assays, library preparation reagents and a NGS platform that are intended for human germline targeted sequencing from whole blood. These first authorizations can serve as a case study in how different types of NGS-based technology are reviewed by the FDA. In this manuscript we describe challenges associated with the evaluation of these novel technologies and provide an overview of what was reviewed. Besides making validated NGS-based devices available for in vitro diagnostic use, these first authorizations create a regulatory path for similar future instruments and assays.

Safety assessments and public concern for genetically modified food products: the American view.

PubMed

Harlander, Susan K

2002-01-01

In the relatively short time since their commercial introduction in 1996, genetically modified (GM) crops have been rapidly adopted in the United States GM crops are regulated through a coordinated framework developed in 1992 and administered by three agencies-the US Department of Agriculture (USDA) that ensures the products are safe to grow, the Environmental Protection Agency (EPA) that ensures the products are safe for the environment, and the Food and Drug Administration (FDA) that ensures the products are safe to eat. Rigorous food and environmental safety assessments must be completed before GM crops can be commercialized. Fifty-one products have been reviewed by the FDA, including several varieties of corn, soybeans, canola, cotton, rice, sugar beets, potatoes, tomatoes, squash, papaya, and flax. Because FDA considers these crops "substantially equivalent" to their conventional counterparts, no special labeling is required for GM crops in the United States and they are managed as commodities with no segregation or identity preservation. GM crops have thus made their way through commodity distribution channels into thousands of ingredients used in processed foods. It has been estimated that 70% to 85% of processed foods on supermarket shelves in the United States today contain one or more ingredients potentially derived from GM crops. The food industry and retail industry have been monitoring the opinions of their consumers on the GM issue for the past several years. Numerous independent groups have also surveyed consumer concerns about GM foods. The results of these surveys are shared and discussed here.

Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov, Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional Analysis.

PubMed

Pradhan, Richeek; Singh, Sonal

2018-04-11

Inconsistencies in data on serious adverse events (SAEs) and mortality in ClinicalTrials.gov and corresponding journal articles pose a challenge to research transparency. The objective of this study was to compare data on SAEs and mortality from clinical trials reported in ClinicalTrials.gov and corresponding journal articles with US Food and Drug Administration (FDA) medical reviews. We conducted a cross-sectional study of a randomly selected sample of new molecular entities approved during the study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding journal articles (the two index resources), and FDA medical reviews (reference standard). We estimated the magnitude of deviations in rates of SAEs and mortality between the index resources and the reference standard. We found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53% in corresponding journal articles) when compared with the reference standard. The intra-class correlation coefficient between the three resources was 0.99 (95% confidence interval [CI] 0.98-0.99) for SAE rates and 0.99 (95% CI 0.97-0.99) for mortality rates. There are differences in data on rates of SAEs and mortality in randomized clinical trials in both ClinicalTrials.gov and journal articles compared with FDA reviews. Further efforts should focus on decreasing existing discrepancies to enhance the transparency and reproducibility of data reporting in clinical trials.

Effect of warning placement on the information processing of college students reading an OTC drug facts panel.

PubMed

Bhansali, Archita H; Sangani, Darshan S; Mhatre, Shivani K; Sansgiry, Sujit S

2018-01-01

To compare three over-the-counter (OTC) Drug Facts panel versions for information processing optimization among college students. University of Houston students (N = 210) participated in a cross-sectional survey from January to May 2010. A current FDA label was compared to two experimental labels developed using the theory of CHREST to test information processing by re-positioning the warning information within the Drug Facts panel. Congruency was defined as placing like information together. Information processing was evaluated using the OTC medication Label Evaluation Process Model (LEPM): label comprehension, ease-of-use, attitude toward the product, product evaluation, and purchase intention. Experimental label with chunked congruent information (uses-directions-other information-warnings) was rated significantly higher than the current FDA label and had the best average scores among the LEPM information processing variables. If replications uphold these findings, the FDA label design might be revised to improve information processing.

Access to Investigational Drugs: FDA Expanded Access Programs or “Right‐to‐Try” Legislation?

PubMed Central

Berglund, Jelena P.; Weatherwax, Kevin; Gerber, David E.; Adamo, Joan E.

2015-01-01

Abstract Purpose The Food and Drug Administration Expanded Access (EA) program and “Right‐to‐Try” legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. Methods FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. Results The FDA EA program includes Single Patient‐Investigational New Drug (SP‐IND), Emergency SP‐IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. “Right‐to‐Try” legislation bypasses some of these steps, but provides no regulatory or safety oversight. Conclusion The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP‐IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements. PMID:25588691

Access to Investigational Drugs: FDA Expanded Access Programs or "Right-to-Try" Legislation?

PubMed

Holbein, M E Blair; Berglund, Jelena P; Weatherwax, Kevin; Gerber, David E; Adamo, Joan E

2015-10-01

The Food and Drug Administration Expanded Access (EA) program and "Right-to-Try" legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. The FDA EA program includes Single Patient-Investigational New Drug (SP-IND), Emergency SP-IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. "Right-to-Try" legislation bypasses some of these steps, but provides no regulatory or safety oversight. The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP-IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements. © 2015 Wiley Periodicals, Inc.

78 FR 64220 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0804... Section 510(k) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360(k)) and the... sheet form, assists respondents in categorizing administrative 510(k) information for submission to FDA...

Taxane anticancer agents: a patent perspective

PubMed Central

Ojima, Iwao; Lichtenthal, Brendan; Lee, Siyeon; Wang, Changwei; Wang, Xin

2016-01-01

Introduction Paclitaxel and docetaxel were two epoch-making anticancer drugs and have been successfully used in chemotherapy for a variety of cancer types. In 2010, a new taxane, cabazitaxel, was approved by FDA for use in combination with prednisone for the treatment of metastatic hormone-refractory prostate cancer. Albumin-bound paclitaxel (nab™-paclitaxel; abraxane) nanodroplet formulation was another notable invention (FDA approval 2005 for refractory, metastatic, or relapsed breast cancer). Abraxane in combination with gemcitabine for the treatment of pancreatic cancer was approved by FDA in 2013. Accordingly, there have been a huge number of patent applications dealing with taxane anticancer agents in the last five years. Thus, it is a good time to review the progress in this area and find the next wave for new developments. Area covered This review article covers the patent literature from 2010 to early 2015 on various aspects of taxane-based chemotherapies and drug developments. Expert opinion Three FDA-approved taxane anticancer drugs will continue to expand their therapeutic applications, especially through drug combinations and new formulations. Inspired by the success of abraxane, new nano-formulations are emerging. Highly potent new-generation taxanes will play a key role in the development of efficacious tumor-targeted drug delivery systems. PMID:26651178

Peer Review for EPA's Biologically Based Dose-Response ...

EPA Pesticide Factsheets

EPA is developing a regulation for perchlorate in drinking water. As part the regulatory process EPA must develop a Maximum Contaminant Level Goal (MCLG). FDA and EPA scientists developed a biologically based dose-response (BBDR) model to assist in deriving the MCLG. This model is designed to determine under what conditions of iodine nutrition and exposure to perchlorate across sensitive lifestages would result in low serum free and total thyroxine (hypothyroxinemia). EPA is undertaking a peer review to provide a focused, objective independent peer evaluation of the draft model and its model results report. EPA is undertaking a peer review to provide a focused, objective independent peer evaluation of the draft model and its model results report. Peer review is an important component of the scientific process. The criticism, suggestions, and new ideas provided by the peer reviewers stimulate creative thought, strengthen the interpretation of the reviewed material, and confer credibility on the product. The peer review objective is to provide advice to EPA on steps that will yield a highly credible scientific product that is supported by the scientific community and a defensible perchlorate MCLG.

Design control considerations for biologic-device combination products.

PubMed

Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

2017-03-01

Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting development of innovative, safe and effective combination products. It remains the manufacturer's responsibility to comply with the relevant requirements and regulations, and develop good business practices that clearly describe how these practices comply with FDA's final rule (21 CFR Part 4) and aligns with the company's already established quality system. Copyright © 2017 Elsevier B.V. All rights reserved.

Digital management and regulatory submission of medical images from clinical trials: role and benefits of the core laboratory

NASA Astrophysics Data System (ADS)

Robbins, William L.; Conklin, James J.

1995-10-01

Medical images (angiography, CT, MRI, nuclear medicine, ultrasound, x ray) play an increasingly important role in the clinical development and regulatory review process for pharmaceuticals and medical devices. Since medical images are increasingly acquired and archived digitally, or are readily digitized from film, they can be visualized, processed and analyzed in a variety of ways using digital image processing and display technology. Moreover, with image-based data management and data visualization tools, medical images can be electronically organized and submitted to the U.S. Food and Drug Administration (FDA) for review. The collection, processing, analysis, archival, and submission of medical images in a digital format versus an analog (film-based) format presents both challenges and opportunities for the clinical and regulatory information management specialist. The medical imaging 'core laboratory' is an important resource for clinical trials and regulatory submissions involving medical imaging data. Use of digital imaging technology within a core laboratory can increase efficiency and decrease overall costs in the image data management and regulatory review process.

OpenFDA: an innovative platform providing access to a wealth of FDA's publicly available data.

PubMed

Kass-Hout, Taha A; Xu, Zhiheng; Mohebbi, Matthew; Nelsen, Hans; Baker, Adam; Levine, Jonathan; Johanson, Elaine; Bright, Roselie A

2016-05-01

The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs). Using cutting-edge technologies deployed on FDA's new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges. Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event. With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved.

Assessing new developments in the pre-market regulatory process of medical devices in the People's Republic of China.

PubMed

Zhang, Shixuan; Kriza, Christine; Kolominsky-Rabas, Peter L

2014-09-01

The objective of this paper is to provide a systematic overview of the Chinese medical device registration processes, identify challenges and suggest how these can be addressed. In addition, the paper will outline the impact of new policies and regulations since the restructuring of the China FDA. A systematic review was performed for journal articles between the year of 2009 and 2013 in the following databases: PubMed, ScienceDirect and Zhongguozhiwang. The review has identified 184 papers which were potentially relevant. Seventeen articles were included in the review, which highlights the challenges and opportunities related to the medical device registration process. In order to understand the actual impact of the regulation environment and its policies including the lack of regulatory guidance regular assessment updates are crucial. The results of this paper are aimed at informing regulatory bodies, health policy decision makers, national and international Health Technology Assessment networks as well as medical devices manufacturers.

Price, performance, and the FDA approval process: the example of home HIV testing.

PubMed

Paltiel, A David; Pollack, Harold A

2010-01-01

The Food and Drug Administration (FDA) is considering approval of an over-the-counter, rapid HIV test for home use. To support its decision, the FDA seeks evidence of the test's performance. It has asked the manufacturer to conduct field studies of the test's sensitivity and specificity when employed by untrained users. In this article, the authors argue that additional information should be sought to evaluate the prevalence of undetected HIV in the end-user The analytic framework produces the elementary but counterintuitive finding that the performance of the home HIV test- measured in terms of its ability to correctly detect the presence and absence of HIV infection among the people who purchase it-depends critically on the manufacturer's retail price. This finding has profound implications for the FDA's approval process.

77 FR 11555 - Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Institutional...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... either http://www.regulations.gov or http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinical...] Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Institutional Review Board Continuing Review After Clinical Investigation Approval; Availability AGENCY: Food and Drug Administration...

FDA Regulation of Clinical Applications of CRISPR-CAS Gene-Editing Technology.

PubMed

Grant, Evita V

Scientists have repurposed an adaptive immune system of single cell organisms to create a new type of gene-editing tool: CRISPR (clustered regularly interspaced short palindromic repeats)-Cas technology. Scientists in China have reported its use in the genome modification of non-viable human embryos. This has ignited a spirited debate about the moral, ethical, scientific, and social implications of human germline genome engineering. There have also been calls for regulations; however, FDA has yet to formally announce its oversight of clinical applications of CRISPR-Cas systems. This paper reviews FDA regulation of previously controversial biotechnology breakthroughs, recombinant DNA and human cloning. It then shows that FDA is well positioned to regulate CRISPR-Cas clinical applications, due to its legislative mandates, its existing regulatory frameworks for gene therapies and assisted reproductive technologies, and other considerations.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

PubMed

Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

2018-02-01

This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

Anterior pelvic organ prolapse repair using synthetic mesh.

PubMed

Patel, Bhavin N; Lucioni, Alvaro; Kobashi, Kathleen C

2012-06-01

Since the U.S. Food and Drug Administration (FDA) statement on mesh in July of 2011, there has been controversy regarding synthetic mesh repairs for vaginal prolapse. In this article, we review the biochemical basis for the use of synthetic mesh in prolapse repair as well as clinical results of anterior compartment prolapse repair with synthetic mesh. Finally, we discuss the FDA warning regarding mesh.

78 FR 66746 - Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

...] Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal Year 2014... and Drug Administration (FDA or the Agency) is announcing the Web site location where the Agency will... documents, FDA has committed to updating its Web site in a timely manner to reflect the Agency's review of...

21 CFR 60.26 - Final action on regulatory review period determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... final upon expiration of the 180-day period for filing a due diligence petition under § 60.30 unless FDA... determination; (3) A due diligence petition filed under § 60.30; or (4) A request for a hearing filed under § 60... expiration of the 180-day period for filing a due diligence petition; or (2) If FDA has received a request...

Topical antifungal drug products for over-the-counter human use; amendment of final monograph. Final rule.

PubMed

2002-02-08

The Food and Drug Administration (FDA) is issuing a final rule amending the final monograph for over-the-counter (OTC) topical antifungal drug products to add the ingredient clotrimazole as generally recognized as safe and effective for the treatment of athlete's foot, jock itch, and ringworm. This final rule is part of FDA's ongoing review of OTC drug products.

Aripiprazole for irritability associated with autistic disorder in children and adolescents aged 6–17 years

PubMed Central

Blankenship, Kelly; Erickson, Craig A; Stigler, Kimberly A; Posey, David J; McDougle, Christopher J

2011-01-01

Aripiprazole was recently US FDA-approved to treat irritability in children and adolescents with autistic disorder aged 6–17 years. There are currently only two psychotropics approved by the FDA to treat irritability in the autistic population. This drug profile will discuss available studies of aripiprazole in individuals with pervasive developmental disorders, two of which led to its recent FDA approval. We will discuss the efficacy, as well as the safety and tolerability of the drug documented in these studies. In addition, the chemistry, pharmacokinetics, metabolism and mechanism of action of aripiprazole will be reviewed. PMID:21359119

U.S. Food and Drug Administration approval summary: Eltrombopag for the treatment of pediatric patients with chronic immune (idiopathic) thrombocytopenia.

PubMed

Ehrlich, Lori A; Kwitkowski, Virginia E; Reaman, Gregory; Ko, Chia-Wen; Nie, Lei; Pazdur, Richard; Farrell, Ann T

2017-12-01

The U.S. Food and Drug Administration (FDA) approved eltrombopag for pediatric patients with chronic immune (idiopathic) thrombocytopenia (ITP) ages ≥6 on June 11, 2015, and ages ≥1 on August 24, 2015. Approval was based on the FDA review of two randomized trials that included 159 pediatric patients with chronic ITP who had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This manuscript describes the basis for approval of these applications. The FDA concluded that eltrombopag has shown efficacy and a favorable benefit to risk profile for pediatric patients with chronic ITP. © 2017 Wiley Periodicals, Inc.

Evaluation of genotoxicity testing of FDA approved large molecule therapeutics.

PubMed

Sawant, Satin G; Fielden, Mark R; Black, Kurt A

2014-10-01

Large molecule therapeutics (MW>1000daltons) are not expected to enter the cell and thus have reduced potential to interact directly with DNA or related physiological processes. Genotoxicity studies are therefore not relevant and typically not required for large molecule therapeutic candidates. Regulatory guidance supports this approach; however there are examples of marketed large molecule therapeutics where sponsors have conducted genotoxicity studies. A retrospective analysis was performed on genotoxicity studies of United States FDA approved large molecule therapeutics since 1998 identified through the Drugs@FDA website. This information was used to provide a data-driven rationale for genotoxicity evaluations of large molecule therapeutics. Fifty-three of the 99 therapeutics identified were tested for genotoxic potential. None of the therapeutics tested showed a positive outcome in any study except the peptide glucagon (GlucaGen®) showing equivocal in vitro results, as stated in the product labeling. Scientific rationale and data from this review indicate that testing of a majority of large molecule modalities do not add value to risk assessment and support current regulatory guidance. Similarly, the data do not support testing of peptides containing only natural amino acids. Peptides containing non-natural amino acids and small molecules in conjugated products may need to be tested. Copyright © 2014 Elsevier Inc. All rights reserved.

FDA approval of cardiac implantable electronic devices via original and supplement premarket approval pathways, 1979-2012.

PubMed

Rome, Benjamin N; Kramer, Daniel B; Kesselheim, Aaron S

The US Food and Drug Administration (FDA) evaluates high-risk medical devices such as cardiac implantable electronic devices (CIEDs), including pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, via the premarket approval (PMA) process, during which manufacturers submit clinical data demonstrating safety and effectiveness. Subsequent changes to approved high-risk devices are implemented via "supplements," which may not require additional clinical testing. To characterize the prevalence and characteristics of changes to CIEDs made through the PMA supplement process. Using the FDA's PMA database, we reviewed all CIEDs approved as original PMAs or supplements from 1979 through 2012. For each supplement, we collected the date approved, type of supplement (panel-track, 180-day, real-time, special, and 30-day notice), and the nature of the changes. We calculated the number of supplements approved per PMA and analyzed trends relating to different supplement regulatory categories over time. For supplements approved via the 180-day regulatory pathway, which often involve significant design changes, from 2010-2012, we identified how often additional clinical data were collected. From 1979-2012, the FDA approved 77 original and 5829 supplement PMA applications for CIEDs, with a median of 50 supplements per original PMA (interquartile range [IQR], 23-87). Excluding manufacturing changes that do not alter device design, the number of supplements approved each year was stable around a mean (SD) of 2.6 (0.9) supplements per PMA per year. Premarket approvals remained active via successive supplements over a median period of 15 years (IQR, 8-20), and 79% of the 77 original PMAs approved during our study period were the subject of at least 1 supplement in 2012. Thirty-seven percent of approved supplements involved a change to the device's design. Among 180-day supplements approved from 2010-2012, 23% (15/64) included new clinical data to support safety and effectiveness. Many CIED models currently used by clinicians were approved via the PMA supplement process, not as original PMAs. Most new device models are deemed safe and effective without requiring new clinical data, reinforcing the importance of rigorous postapproval surveillance of these devices.

78 FR 34565 - Irradiation in the Production, Processing, and Handling of Animal Feed and Pet Food; Electron...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-10

.... FDA-2012-F-0178] Irradiation in the Production, Processing, and Handling of Animal Feed and Pet Food; Electron Beam and X-Ray Sources for Irradiation of Poultry Feed and Poultry Feed Ingredients; Correction... Administration (FDA) is correcting a document amending the regulations for irradiation of animal feed and pet...

Postmarketing Surveillance for “Modified-Risk” Tobacco Products

PubMed Central

2012-01-01

Introduction: The U.S. Food and Drug Administration (FDA) acquired authority to regulate tobacco products in 2009. This authority will provide a structured process for manufacturers to introduce products that may have “modified-risk” for morbidity or mortality relative to traditional tobacco products, with postmarketing surveillance and studies a condition of marketing. Method: A narrative review approach was taken. The author searched and integrated publicly accessible literature on tobacco product surveillance as well as drug and medical device postmarket activities currently performed by FDA. Results: FDA relies on active and passive methods for postmarket surveillance and can require specific studies and risk evaluation and mitigation strategies for certain products, including those with abuse liability. Past efforts at examining the individual and population effects of reduced harm tobacco products provide an example of integrating different data streams. Discussion: Postmarket surveillance can be viewed in terms of the Agent–Host–Vector–Environment model, and concepts from diffusion of innovations are relevant to understanding factors associated with the adoption of new products by the population. Given that active and passive surveillance approaches have different strengths and weaknesses, multiple approaches may be necessary to evaluate population-level effects. Assuring that required studies are properly conducted and reported and that data indicating significant public health harms are quickly recognized will be important going forward. Conclusions: The advent of broad regulatory authority over tobacco provides opportunities for policy evaluation research. The research community can provide FDA with the independent science it needs to evaluate the public health impact of novel tobacco products. PMID:21330282

The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration to Accelerate Diagnosis and Treatment of Traumatic Brain Injury.

PubMed

Manley, Geoffrey T; MacDonald, Christine L; Markowitz, Amy; Stephenson, Diane; Robbins, Ann; Gardner, Raquel C; Winkler, Ethan A; Bodien, Yelena; Taylor, Sabrina; Yue, John K; Kannan, Lakshmi; Kumar, Allison; McCrea, Michael; Wang, Kevin K W

2017-03-31

The Traumatic Brain Injury Endpoints Development (TED) Initiative is a 5-year, Department of Defense (DoD) funded project that is working toward the ultimate goal of developing better designed clinical trials, leading to more precise diagnosis, and effective treatments for traumatic brain injury (TBI). TED is comprised of leading academic clinician-scientists, along with innovative industry leaders in biotechnology and imaging technology, patient advocacy organizations, and philanthropists, working collaboratively with regulatory authorities, specifically the US Food and Drug Administration (FDA). The goals of the TED Initiative are to gain consensus and validation of TBI clinical outcome assessment measures and biomarkers for endorsement by global regulatory agencies for use in drug and device development processes. This manuscript summarizes the Initiative's Stage 1 progress over the first 18 months, including intensive engagement with a number of FDA divisions responsible for review and validation of biomarkers and clinical outcome assessments, progression into the prequalification phase of FDA's Medical Device Development Tool program for a candidate set of neuroimaging biomarkers, and receipt of FDA's Recognition of Research Importance Letter regarding TBI. Other signal achievements relate to the creation of the TED Metadataset, harmonizing study measures across eight major TBI studies, and the leadership role played by TED investigators in the conversion of the NINDS TBI Common Data Elements (CDEs) to Clinical Data Interchange Standards Consortium (CDISC) standards. This paper frames both the near-term expectations and the Initiative's long-term vision to accelerate approval of treatments for patients affected by TBI in urgent need of effective therapies.

The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

PubMed

Ciociola, Arthur A; Karlstadt, Robyn G; Pambianco, Daniel J; Woods, Karen L; Ehrenpreis, Eli D

2014-10-01

Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDA's decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the public's interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

Substantial Equivalence Standards in Tobacco Governance: Statutory Clarity and Regulatory Precedent for the FSPTCA.

PubMed

Carpenter, Daniel; Connolly, Gregory N; Lempert, Lauren Kass

2017-08-01

The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 creates the first national system of premarket regulation of tobacco products in American history. The FDA must now review and give marketing authorization to all new tobacco products, based on a public health standard, before they can be legally marketed. Yet the law also contains an alternative pathway for market entry-the substantial equivalence (SE) clause-by which novel and altered tobacco products can be marketed by demonstrating their substantial equivalence to existing products. Over 99 percent of tobacco product applications sent to the FDA under the new law have used this mechanism, and loose application of the SE mechanism carries the risk of undoing the FDA's gatekeeping power under the law. We review the statutory and regulatory precedent for SE, examining the FSPTCA itself as well as regulatory precedent from drug and device regulation (from which the term substantial equivalence and much of the associated statutory language was derived). Our review of standards and scientific precedent demonstrates that exacting scrutiny under the public health standard should govern all SE reviews and that clinical data incorporating social scientific evidence should be routinely required for SE claims by tobacco product sponsors. Copyright © 2017 by Duke University Press.

Trials of transvaginal mesh devices for pelvic organ prolapse: a systematic database review of the US FDA approval process.

PubMed

Heneghan, Carl J; Goldacre, Ben; Onakpoya, Igho; Aronson, Jeffrey K; Jefferson, Tom; Pluddemann, Annette; Mahtani, Kamal R

2017-12-06

Transvaginal mesh devices are approved in the USA by the Food and Drug Administration (FDA), through the 510(k) system. However, there is uncertainty about the benefit to harm balance of mesh approved for pelvic organ prolapse. We, therefore, assessed the evidence at the time of approval for transvaginal mesh products and the impact of safety studies the FDA mandated in 2012 because of emerging harms. We used FDA databases to determine the evidence for approval of transvaginal mesh. To create a 'family tree' of device equivalence, we used the 510(k) regulatory approval of the 1985 Mersilene Mesh (Ethicon) and the 1996 ProteGen Sling (Boston Scientific), searched for all subsequently related device approvals, and for the first published randomised trial evidence. We assessed compliance with all FDA 522 orders issued in 2012 requiring postmarketing surveillance studies. We found 61 devices whose approval ultimately relied on claimed equivalence to the Mersilene Mesh and the ProteGen Sling. We found no clinical trials evidence for these 61 devices at the time of approval. Publication of randomised clinical trials occurred at a median of 5 years after device approval (range 1-14 years). Analysis of 119 FDA 522 orders revealed that in 79 (66%) the manufacturer ceased market distribution of the device, and in 26 (22%) the manufacturer had changed the indication. Only seven studies (six cohorts and new randomised controlled trial) covering 11 orders were recruiting participants (none had reported outcomes). Transvaginal mesh products for pelvic organ prolapse have been approved on the basis of weak evidence over the last 20 years. Devices have inherited approval status from a few products. A publicly accessible registry of licensed invasive devices, with details of marketing status and linked evidence, should be created and maintained at the time of approval. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prior notice of imported food under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002. Final rule.

PubMed

2008-11-07

The Food and Drug Administration (FDA) is issuing a final regulation that requires the submission to FDA of prior notice of food, including animal feed, that is imported or offered for import into the United States. The final rule implements the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (the Bioterrorism Act), which required prior notification of imported food to begin on December 12, 2003. The final rule requires that the prior notice be submitted to FDA electronically via either the U.S. Customs and Border Protection (CBP or Customs) Automated Broker Interface (ABI) of the Automated Commercial System (ACS) or the FDA Prior Notice System Interface (FDA PNSI). The information must be submitted and confirmed electronically as facially complete by FDA for review no less than 8 hours (for food arriving by water), 4 hours (for food arriving by air or land/rail), and 2 hours (for food arriving by land/road) before the food arrives at the port of arrival. Food imported or offered for import without adequate prior notice is subject to refusal and, if refused, must be held. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a draft compliance policy guide (CPG) entitled "Sec. 110.310 Prior Notice of Imported Food Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002."

An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation.

PubMed

Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

2015-03-01

The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA's authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

76 FR 78931 - Food and Drug Administration Rare Disease Patient Advocacy Day; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-20

... Administration, HHS. ACTION: Notice. The Food and Drug Administration's (FDA) Office of Orphan Products... educate the rare disease community on the FDA regulatory processes. This educational meeting will consist...

21 CFR 900.4 - Standards for accreditation bodies.

Code of Federal Regulations, 2014 CFR

2014-04-01

... image quality, or upon request by FDA, the accreditation body shall review a facility's clinical images... review by the accreditation body demonstrates that a problem does exist with respect to image quality or... program shall: (i) Include requirements for clinical image review and phantom image review; (ii) Ensure...

21 CFR 900.4 - Standards for accreditation bodies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... image quality, or upon request by FDA, the accreditation body shall review a facility's clinical images... review by the accreditation body demonstrates that a problem does exist with respect to image quality or... program shall: (i) Include requirements for clinical image review and phantom image review; (ii) Ensure...

21 CFR 900.4 - Standards for accreditation bodies.

Code of Federal Regulations, 2012 CFR

2012-04-01

... image quality, or upon request by FDA, the accreditation body shall review a facility's clinical images... review by the accreditation body demonstrates that a problem does exist with respect to image quality or... program shall: (i) Include requirements for clinical image review and phantom image review; (ii) Ensure...

21 CFR 900.4 - Standards for accreditation bodies.

Code of Federal Regulations, 2013 CFR

2013-04-01

... image quality, or upon request by FDA, the accreditation body shall review a facility's clinical images... review by the accreditation body demonstrates that a problem does exist with respect to image quality or... program shall: (i) Include requirements for clinical image review and phantom image review; (ii) Ensure...

Physicians' Trust in the FDA's Use of Product-Specific Pathways for Generic Drug Approval.

PubMed

Kesselheim, Aaron S; Eddings, Wesley; Raj, Tara; Campbell, Eric G; Franklin, Jessica M; Ross, Kathryn M; Fulchino, Lisa A; Avorn, Jerry; Gagne, Joshua J

2016-01-01

Generic drugs are cost-effective versions of brand-name drugs approved by the Food and Drug Administration (FDA) following proof of pharmaceutical equivalence and bioequivalence. Generic drugs are widely prescribed by physicians, although there is disagreement over the clinical comparability of generic drugs to brand-name drugs within the physician community. The objective of this survey was to assess physicians' perceptions of generic drugs and the generic drug approval process. A survey was administered to a national sample of primary care internists and specialists between August 2014 and January 2015. In total, 1,152 physicians comprising of internists with no reported specialty certification and those with specialty certification in hematology, infectious diseases, and endocrinology were surveyed. The survey assessed physicians' perceptions of the FDA's generic drug approval process, as well as their experiences prescribing six generic drugs approved between 2008 and 2012 using product-specific approval pathways and selected comparator drugs. Among 718 respondents (62% response rate), a majority were comfortable with the FDA's process in ensuring the safety and effectiveness of generic drugs overall (91%) and with letting the FDA determine which tests were necessary to determine bioequivalence in a particular drug (92%). A minority (13-26%) still reported being uncomfortable prescribing generic drugs approved using product-specific pathways. Overall, few physicians heard reports of concerns about generic versions of the study drugs or their comparators, with no differences between the two groups. Physicians tended to hear about concerns about the safety or effectiveness of generic drugs from patients, pharmacists, and physician colleagues. Physicians hold largely positive views of the FDA's generic drug approval process even when some questioned the performance of certain generic drugs in comparison to brand-name drugs. Better education about the generic drug approval process and standards may alleviate concerns among the physician community and support the delivery of cost-effective health care.

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

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.

77 FR 38301 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... valid import milk permit (21 U.S.C. 141). Before such permit is issued: (1) All cows from which import... imported raw, all such cows must pass a tuberculin test; (3) the dairy farm and each plant in which the... examination of cows. 1210.13....... FDA 1994/ 1 1 1 0.5 0.5 Tuberculin test. 1210.14....... FDA 1997/ 2 1 2 2...

Medical countermeasures for unwanted CBRN exposures: part II radiological and nuclear threats with review of recent countermeasure patents

PubMed Central

Singh, Vijay K.; Romaine, Patricia L.P.; Newman, Victoria L.; Seed, Thomas M.

2016-01-01

ABSTRACT Introduction: The global threat of a chemical, biological, radiological, or nuclear (CBRN) disaster is an important priority for all government agencies involved in domestic security and public health preparedness. Radiological/nuclear (RN) attacks or accidents have become a larger focus of the United States Food and Drug administration (US FDA) over time because of their increased likeliness. Clinical signs and symptoms of a developing acute radiation syndrome (ARS) are grouped into three sub-syndromes named for the dominant organ system affected, namely the hematopoietic (H-ARS), gastrointestinal (GI-ARS), and neurovascular systems. The availability of safe and effective countermeasures against radiological/nuclear threats currently represents a significant unmet medical need. Areas covered: This article reviews the development of RN threat medical countermeasures and highlights those specific countermeasures that have been recently patented and approved following the FDA Animal Rule. Patents for such agents from 2015 have been presented. Expert opinion: Two granulocyte colony-stimulating factor (G-CSF)-based radiation countermeasures (Neupogen® (Amgen, Thousand Oaks, CA) and Neulasta® (Amgen, Thousand Oaks, CA)) have recently been approved by the FDA for treatment of H-ARS and both these agents are radiomitigators, used after radiation exposure. To date, there are no FDA-approved radioprotectors for ARS. PMID:27610458

Dihydroxyacetone: A Review.

PubMed

Braunberger, Taylor L; Nahhas, Amanda F; Katz, Linda M; Sadrieh, Nakissa; Lim, Henry W

2018-04-01

The sunless tanning industry has experienced rapid growth due to public education on the dangers of ultraviolet radiation on skin and improvements in products. Dihydroxyacetone (DHA) is a 3-carbon sugar allowed by the Food and Drug Administration (FDA) as a color additive in sunless tanning products. Bronzers, a product removed with soap and water, may also contain DHA. We aim to review the literature on DHA. DHA is intended for external application, not including the mucous membranes or in or around the eye area. DHA has been used in spray-tan booths and by airbrushing it onto consumers, although these are unapproved uses, as contact with the color additive is not restricted to the external part of the body. Consequently, the FDA recommends customers shield their eyes, lips, and mucous membranes, as well as refrain from ingestion or inhalation of DHA. Unlike sunscreens, products that protect against ultraviolet radiation and are regulated by the FDA as non-prescription drugs, sunless tanning products are regulated as cosmetics and cannot provide any protection from exposure to ultraviolet radiation. There are reports of non-cosmetic uses of DHA that are not FDA approved. With the wide-spread use of DHA, additional studies on its safety are warranted.

J Drugs Dermatol. 2018;17(4):387-391.

Medical countermeasures for unwanted CBRN exposures: Part I chemical and biological threats with review of recent countermeasure patents.

PubMed

Singh, Vijay K; Garcia, Melissa; Wise, Stephen Y; Seed, Thomas M

2016-12-01

The threat of chemical, biological, radiological, and nuclear (CBRN) warfare has been addressed as the uppermost risk to national security since the terrorist attacks on 11 September 2001. Despite significant scientific advances over the past several decades toward the development of safe, non-toxic and effective countermeasures to combat CBRN threats, relatively few countermeasures have been approved by the US Food and Drug Administration (US FDA). Therefore, countermeasures capable of protecting the population from the effects of CBRN attack remain a significant unmet medical need. Chemical and biological (CB) threat agents can be particularly hazardous due to their effectiveness in small quantities and ease of distribution. Area covered: This article reviews the development of countermeasures for CB threats and highlights specific threats for which at least one countermeasure has been approved following the FDA Animal Rule. Patents of CB countermeasures since 2010 have been included. Expert opinion: Nine CB countermeasures have received FDA approval for use in humans following the Animal Rule, and a number of promising CB countermeasures are currently under development. In the next few years, we should expect to have multiple countermeasures approved by the FDA for each indication allowing for more flexible and effective treatment options.

"The Google of Healthcare": enabling the privatization of genetic bio/databanking.

PubMed

Spector-Bagdady, Kayte

2016-07-01

23andMe is back on the market as the first direct-to-consumer genetic testing company that "includes reports that meet Food and Drug Administration (FDA) standards…." But, whereas its front-end product is selling individual genetic tests online, its back-end business model is amassing one of the largest privately owned genetic databases in the world. What is the effect, however, of the private control of bio/databases on genetic epidemiology and public health research? The recent federal government notices of proposed rulemaking for: (1) revisions to regulations governing human subjects research and (2) whether certain direct-to-consumer genetic tests should require premarket FDA review, were reviewed and related to the 23andMe product, business model, and consumer agreements. FDA regulatory action so far has focused on the return of consumer test reports but it should also consider the broader misuse of data and information not otherwise protected by human subjects research regulations. As the federal government revises its decades-old human subjects research structure, the Executive Office of the President (EOP) should consider a cohesive approach to regulating private genetic bio/databanks. This strategy should allow the FDA and other agencies to play a role in expanding current regulatory coverage. Copyright © 2016 Elsevier Inc. All rights reserved.

Food and Drug Administration: Insufficient Planning for Field Laboratory Consolidation Decisions.

DTIC Science & Technology

1987-12-04

adequately 5 address whether FDA could meet its current and future laboratory needs if the five laboratories were closed or whether cost- effective ...pie transit and laboratory processing times would lessen FDA’S regula- tory effectiveness . Moreover, 61 percent of the excess laboratory capacity...FDA believes that it can ship sam- pies from across the nation to almost any location for analysis without reducing its regulatory effectiveness . (See

Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.

PubMed

Sellers, Edward M

2018-02-01

This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.

Primaquine in vivax malaria: an update and review on management issues

PubMed Central

2011-01-01

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs. PMID:22152065

Primaquine in vivax malaria: an update and review on management issues.

PubMed

Fernando, Deepika; Rodrigo, Chaturaka; Rajapakse, Senaka

2011-12-12

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs.

An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation

PubMed Central

Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

2015-01-01

The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA’s authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules. PMID:25550419

76 FR 62808 - Pilot Program for Parallel Review of Medical Products

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-11

... voluntary participation in the pilot program, as well as the guiding principles the Agencies intend to... 57045), parallel review is intended to reduce the time between FDA marketing approval and CMS national...

Software-Related Recalls of Health Information Technology and Other Medical Devices: Implications for FDA Regulation of Digital Health.

PubMed

Ronquillo, Jay G; Zuckerman, Diana M

2017-09-01

Policy Points: Medical software has become an increasingly critical component of health care, yet the regulation of these devices is inconsistent and controversial. No studies of medical devices and software assess the impact on patient safety of the FDA's current regulatory safeguards and new legislative changes to those standards. Our analysis quantifies the impact of software problems in regulated medical devices and indicates that current regulations are necessary but not sufficient for ensuring patient safety by identifying and eliminating dangerous defects in software currently on the market. New legislative changes will further deregulate health IT, reducing safeguards that facilitate the reporting and timely recall of flawed medical software that could harm patients. Medical software has become an increasingly critical component of health care, yet the regulatory landscape for digital health is inconsistent and controversial. To understand which policies might best protect patients, we examined the impact of the US Food and Drug Administration's (FDA's) regulatory safeguards on software-related technologies in recent years and the implications for newly passed legislative changes in regulatory policy. Using FDA databases, we identified all medical devices that were recalled from 2011 through 2015 primarily because of software defects. We counted all software-related recalls for each FDA risk category and evaluated each high-risk and moderate-risk recall of electronic medical records to determine the manufacturer, device classification, submission type, number of units, and product details. A total of 627 software devices (1.4 million units) were subject to recalls, with 12 of these devices (190,596 units) subject to the highest-risk recalls. Eleven of the devices recalled as high risk had entered the market through the FDA review process that does not require evidence of safety or effectiveness, and one device was completely exempt from regulatory review. The largest high-risk recall categories were anesthesiology and general hospital, with one each in cardiovascular and neurology. Five electronic medical record systems (9,347 units) were recalled for software defects classified as posing a moderate risk to patient safety. Software problems in medical devices are not rare and have the potential to negatively influence medical care. Premarket regulation has not captured all the software issues that could harm patients, evidenced by the potentially large number of patients exposed to software products later subject to high-risk and moderate-risk recalls. Provisions of the 21st Century Cures Act that became law in late 2016 will reduce safeguards further. Absent stronger regulations and implementation to create robust risk assessment and adverse event reporting, physicians and their patients are likely to be at risk from medical errors caused by software-related problems in medical devices. © 2017 Milbank Memorial Fund.

Pharmacogenomic biomarker information in drug labels approved by the United States food and drug administration: prevalence of related drug use.

PubMed

Frueh, Felix W; Amur, Shashi; Mummaneni, Padmaja; Epstein, Robert S; Aubert, Ronald E; DeLuca, Teresa M; Verbrugge, Robert R; Burckart, Gilbert J; Lesko, Lawrence J

2008-08-01

To review the labels of United States Food and Drug Administration (FDA)-approved drugs to identify those that contain pharmacogenomic biomarker information, and to collect prevalence information on the use of those drugs for which pharmacogenomic information is included in the drug labeling. Retrospective analysis. The Physicians' Desk Reference Web site, Drugs@FDA Web site, and manufacturers' Web sites were used to identify drug labels containing pharmacogenomic information, and the prescription claims database of a large pharmacy benefits manager (insuring > 55 million individuals in the United States) was used to obtain drug utilization data. Pharmacogenomic biomarkers were defined, FDA-approved drug labels containing this information were identified, and utilization of these drugs was determined. Of 1200 drug labels reviewed for the years 1945-2005, 121 drug labels contained pharmacogenomic information based on a key word search and follow-up screening. Of those, 69 labels referred to human genomic biomarkers, and 52 referred to microbial genomic biomarkers. Of the labels referring to human biomarkers, 43 (62%) pertained to polymorphisms in cytochrome P450 (CYP) enzyme metabolism, with CYP2D6 being most common. Of 36.1 million patients whose prescriptions were processed by a large pharmacy benefits manager in 2006, about 8.8 million (24.3%) received one or more drugs with human genomic biomarker information in the drug label. Nearly one fourth of all outpatients received one or more drugs that have pharmacogenomic information in the label for that drug. The incorporation and appropriate use of pharmacogenomic information in drug labels should be tested for its ability to improve drug use and safety in the United States.

The return to the USA of doxylamine-pyridoxine delayed release combination (Diclegis®) for morning sickness--a new morning for American women.

PubMed

Koren, Gideon

2013-01-01

The US FDA approval in April 2013 of Diclegis®, the doxylamine-pyridoxine combination for morning sickness, is a major milestone, particularly since it is indicated for use in pregnancy and the FDA has labeled it a pregnancy category A drug the strongest evidence of fetal safety. After thirty years of being orphaned from an FDA-labeled drug for the most common medical condition in pregnancy, American women and their health care providers have a therapeutic solution that is likely to positively impact millions of women each year. This review highlights the milestones of this antiemetic agent over the last 40 years.

Preapproval and postapproval availability of published comparative efficacy research on biological agents.

PubMed

Thomas, Rachel Hutchins; Freeman, Maisha Kelly; Hughes, Peter J

2013-07-15

Preapproval and postapproval availability of published comparative efficacy studies on biological agents approved between 2000 and 2010 was investigated. Approval packages published on the Food and Drug Administration (FDA) website were examined for all biological agents approved between 2000 and 2010 to determine if comparative efficacy studies were available at the time of FDA approval. The availability of comparative efficacy studies published subsequent to approval was determined by searching PubMed for randomized, active-controlled experimental or observational study designs that measured efficacy as the primary endpoint and were relevant to the original FDA-approved indication. From 2000 to 2010, 107 biological agents were approved by FDA. Of the biological agents with alternative treatments, 54.6% had comparative efficacy data available at the time of approval. Although standard-reviewed biological agents were more likely to have comparative efficacy trials included in the FDA approval packages than priority-reviewed biological agents, statistically significant differences are unlikely. Subsequent to approval, 58.1% of biological agents had at least one published comparative efficacy trial, representing a 3.5% absolute increase in the availability of comparative efficacy studies since the time of approval. Vaccines and biological agents in the hematologic diseases, oncology, and miscellaneous diseases classes had fewer published postapproval comparative efficacy studies per agent compared with the overall group of biological agents. Nearly half of all biological agents approved for marketing between 2000 and 2010 lacked publicly accessible, active-controlled efficacy studies at the time of drug approval; a slightly greater proportion of biological agents had comparative efficacy data published subsequent to their approval.

Participation of the elderly, women, and minorities in pivotal trials supporting 2011-2013 U.S. Food and Drug Administration approvals.

PubMed

Downing, Nicholas S; Shah, Nilay D; Neiman, Joseph H; Aminawung, Jenerius A; Krumholz, Harlan M; Ross, Joseph S

2016-04-14

Pivotal trials, the clinical studies that inform U.S. Food and Drug Administration (FDA) approval decisions, provide the foundational evidence supporting the safety and efficacy of novel therapeutics. We determined the representation of the elderly, women, and patients from racial and ethnic minorities in pivotal trials and whether the FDA is making subgroup efficacy analyses among these subpopulations available to the public. We conducted a cross-sectional study of novel therapeutics approved by the FDA between 2011 and 2013. Using publicly available FDA documents, we collected information on the demographic characteristics of pivotal trial participants (age ≥65 years, sex [male, female], race [white, black, Asian, other], and ethnicity [Hispanic, non-Hispanic]) and determined the availability of subgroup analyses by age, sex, race, and ethnicity. We identified 86 novel therapeutic that were approved by the FDA between 2011 and 2013 for 92 indications on the basis of 206 pivotal trials. The median age of pivotal trial patients was 53.1 years (interquartile range 40.6-60.6), and the mean proportion of patients ≥65 years of age was 28.9 % (95 % CI 23.5-34.4 %). Similar proportions of pivotal trial participants were male (mean 50.3 %, 95 % CI 45.3-55.2 %) and female (mean 49.7 %, 95 % CI 44.7-54.7 %). Most participants were white (mean 79.2 %, 95 % CI 75.9-82.6 %), while the mean proportion of black patients was 7.4 % (95 % CI 5.5-9.3 %), that of Asian patients was 7.4 % (95 % CI 5.2-9.7 %), and that of patients of other races was 5.9 % (95 % CI 4.4-7.5 %). Information about ethnicity was available for only 59.8 % of indications, and where such data were available, the mean proportion of Hispanic participants was 13.3 % (95 % CI 10.3-16.3 %). FDA reviewers performed and made available subgroup efficacy analyses by age, sex, and race for at least one of the pivotal trials used as the basis of approval for over 80 % of indications. Although women are equally represented in pivotal trials supporting recent novel therapeutic approvals by the FDA, elderly patients and those from racial and ethnic minorities are underrepresented. FDA reviewers generally perform subgroup efficacy analyses by age, sex, and race and make these subgroup analyses available to the public.

Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000-2012.

PubMed

Sacks, Leonard V; Shamsuddin, Hala H; Yasinskaya, Yuliya I; Bouri, Khaled; Lanthier, Michael L; Sherman, Rachel E

Some new drug applications fail because of inadequate drug performance and others are not approved because the information submitted to the US Food and Drug Administration (FDA) is unsatisfactory to make that determination. Resubmission of failed applications is costly, delaying marketing approval and the availability of new drugs to patients. To identify the reasons that FDA marketing approval for new drugs was delayed or denied. A retrospective review of FDA documents and extraction of data were performed. We examined all drug applications first submitted to the FDA between 2000 and 2012 for new molecular entities (NMEs), which are active ingredients never before marketed in the United States in any form. Using FDA correspondence and reviews, we investigated the reasons NMEs failed to obtain FDA approval. Reasons for delayed FDA approval or nonapproval of NME applications. Of the 302 identified NME applications, 151 (50%) were approved when first submitted and 222 (73.5%) were ultimately approved. Seventy-one applications required 1 or more resubmissions before approval, with a median delay to approval of 435 days following the first unsuccessful submission. Of the unsuccessful first-time applications, 24 (15.9%) included uncertainties related to dose selection, 20 (13.2%) choice of study end points that failed to adequately reflect a clinically meaningful effect, 20 (13.2%) inconsistent results when different end points were tested, 17 (11.3%) inconsistent results when different trials or study sites were compared, and 20 (13.2%) poor efficacy when compared with the standard of care. The frequency of safety deficiencies was similar among never-approved drugs compared with those with delayed approval (43 of 80 never approved [53.8%] vs 37 of 71 eventually approved [52.1%]; difference, 1.7% [95% CI, -14.86% to 18.05%]; P = .87). However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals (61 of 80 never approved [76.3%] vs 28 of 71 eventually approved [39.4%]; difference, 36.9% [95% CI, 20.25% to 50.86%]; P < .001). Several potentially preventable deficiencies, including failure to select optimal drug doses and suitable study end points, accounted for significant delays in the approval of new drugs. Understanding the reasons for previous failures is helpful to improve the efficiency of clinical development for new drugs.

Challenges in orphan drug development and regulatory policy in China.

PubMed

Cheng, Alice; Xie, Zhi

2017-01-18

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

Science, practice, and human errors in controlling Clostridium botulinum in heat-preserved food in hermetic containers.

PubMed

Pflug, Irving J

2010-05-01

The incidence of botulism in canned food in the last century is reviewed along with the background science; a few conclusions are reached based on analysis of published data. There are two primary aspects to botulism control: the design of an adequate process and the delivery of the adequate process to containers of food. The probability that the designed process will not be adequate to control Clostridium botulinum is very small, probably less than 1.0 x 10(-6), based on containers of food, whereas the failure of the operator of the processing equipment to deliver the specified process to containers of food may be of the order of 1 in 40, to 1 in 100, based on processing units (retort loads). In the commercial food canning industry, failure to deliver the process will probably be of the order of 1.0 x 10(-4) to 1.0 x 10(-6) when U.S. Food and Drug Administration (FDA) regulations are followed. Botulism incidents have occurred in food canning plants that have not followed the FDA regulations. It is possible but very rare to have botulism result from postprocessing contamination. It may thus be concluded that botulism incidents in canned food are primarily the result of human failure in the delivery of the designed or specified process to containers of food that, in turn, result in the survival, outgrowth, and toxin production of C. botulinum spores. Therefore, efforts in C. botulinum control should be concentrated on reducing human errors in the delivery of the specified process to containers of food.

Current and future bioanalytical approaches for stroke assessment.

PubMed

Pullagurla, Swathi R; Baird, Alison E; Adamski, Mateusz G; Soper, Steven A

2015-01-01

Efforts are underway to develop novel platforms for stroke diagnosis to meet the criteria for effective treatment within the narrow time window mandated by the FDA-approved therapeutic (<3 h). Blood-based biomarkers could be used for rapid stroke diagnosis and coupled with new analytical tools, could serve as an attractive platform for managing stroke-related diseases. In this review, we will discuss the physiological processes associated with stroke and current diagnostic tools as well as their associated shortcomings. We will then review information on blood-based biomarkers and various detection technologies. In particular, point of care testing that permits small blood volumes required for the analysis and rapid turn-around time measurements of multiple markers will be presented.

An Assessment of Concerns Regarding New Regulatory Guidance for Combination Products: A Review of the Submissions Made to the FDA Regarding Their Proposed Draft New Guidance on Human Factors Studies for a Combination Product in an Abbreviated New Drug Application.

PubMed

Lance, Philip T; Greenaway, Ruth V; Edwards, Brian

2018-01-01

The US Food and Drug Administration (FDA) put out a call for comments on new draft guidance for industry "Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA." This call for comments elicited 7 submissions from various organizations in the field of health care products. This article reports on a review conducted on these 7 submissions. The purpose of this review was to identify any commonalities across the different submissions and determine if there was consensus on any point or aspect of the draft guidance. To identify any commonalities, a heat map plotting the lines of the draft guidance that had raised a comment/suggestion was produced. Also, a thematic analysis was conducted on the comments/suggestions. In total the 7 submissions produced 137 suggestions. The heat map revealed that these suggestions did not focus on any single part of the guidance but were spread throughout the guidance. The thematic analysis conducted on the suggestions found a number of distinct trends. These trends were grouped into 10 primary themes, each with a number of subthemes. It was concluded that guidance from the FDA on this matter is warranted and would be appreciated. However, it was also concluded that based on the distinct trends identified in the suggestions, there are issues that the FDA may wish to consider before publishing their final guidance.

Progress in the Fight Against Multidrug-Resistant Bacteria? A Review of U.S. Food and Drug Administration-Approved Antibiotics, 2010-2015.

PubMed

Deak, Dalia; Outterson, Kevin; Powers, John H; Kesselheim, Aaron S

2016-09-06

A weak antibiotic pipeline and the increase in drug-resistant pathogens have led to calls for more new antibiotics. Eight new antibiotics were approved by the U.S. Food and Drug Administration (FDA) between January 2010 and December 2015: ceftaroline, fidaxomicin, bedaquiline, dalbavancin, tedizolid, oritavancin, ceftolozane-tazobactam, and ceftazidime-avibactam. This study evaluates the development course and pivotal trials of these antibiotics for their innovativeness, development process, documented patient outcomes, and cost. Data sources were FDA approval packages and databases (January 2010 to December 2015); the Red Book (Truven Health Analytics); Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (FDA); and supplementary information from company filings, press releases, and media reports. Four antibiotics were approved for acute bacterial skin and skin-structure infection. Seven had similar mechanisms of action to those of previously approved drugs. Six were initially developed by small to midsized companies, and 7 are currently marketed by 1 of 3 large companies. The drugs spent a median of 6.2 years in clinical trials (interquartile range [IQR], 5.4 to 8.8 years) and 8 months in FDA review (IQR, 7.5 to 8 months). The median number of patients enrolled in the pivotal trials was 666 (IQR, 553 to 739 patients; full range, 44 to 1005 patients), and median trial duration was 18 months (IQR, 15 to 22 months). Seven drugs were approved on the basis of pivotal trials evaluating noninferiority. One drug demonstrated superiority on an exploratory secondary end point, 2 showed decreased efficacy in patients with renal insufficiency, and 1 showed increased mortality compared with older drugs. Seven of the drugs are substantially more expensive than their trial comparators. Limitations are that future research may show benefit to patients, new drugs from older classes may show superior effectiveness in specific patient populations, and initial U.S. prices for each new antibiotic were obtained from public sources. Recently marketed antibiotics are more expensive but have been approved without evidence of clinical superiority.

OpenFDA: an innovative platform providing access to a wealth of FDA’s publicly available data

PubMed Central

Kass-Hout, Taha A; Mohebbi, Matthew; Nelsen, Hans; Baker, Adam; Levine, Jonathan; Johanson, Elaine; Bright, Roselie A

2016-01-01

Objective The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs). Materials and Methods Using cutting-edge technologies deployed on FDA’s new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges. Results Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event. Conclusion With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products. PMID:26644398

Mitigation Strategies To Protect Food Against Intentional Adulteration. Final rule.

PubMed

2016-05-27

The Food and Drug Administration (FDA or we) is issuing this final rule to require domestic and foreign food facilities that are required to register under the Federal Food, Drug, and Cosmetic Act (the FD&C Act) to address hazards that may be introduced with the intention to cause wide scale public health harm. These food facilities are required to conduct a vulnerability assessment to identify significant vulnerabilities and actionable process steps and implement mitigation strategies to significantly minimize or prevent significant vulnerabilities identified at actionable process steps in a food operation. FDA is issuing these requirements as part of our implementation of the FDA Food Safety Modernization Act (FSMA).

77 FR 69631 - Draft Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

...://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ProposedRegulationsandDraftGuidances...] Draft Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing the... IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing the Qualifications of...

Public voices in pharmaceutical deliberations: negotiating "clinical benefit" in the FDA's Avastin Hearing.

PubMed

Teston, Christa B; Graham, S Scott; Baldwinson, Raquel; Li, Andria; Swift, Jessamyn

2014-06-01

This article offers a hybrid rhetorical-qualitative discourse analysis of the FDA's 2011 Avastin Hearing, which considered the revocation of the breast cancer indication for the popular cancer drug Avastin. We explore the multiplicity of stakeholders, the questions that motivated deliberations, and the kinds of evidence presented during the hearing. Pairing our findings with contemporary scholarship in rhetorical stasis theory, Mol's (2002) construct of multiple ontologies, and Callon, Lascoumes, and Barthe's (2011) "hybrid forums," we demonstrate that the FDA's deliberative procedures elides various sources of evidence and the potential multiplicity of definitions for "clinical benefit." Our findings suggest that while the FDA invited multiple stakeholders to offer testimony, there are ways that the FDA might have more meaningfully incorporated public voices in the deliberative process. We conclude with suggestions for how a true hybrid forum might be deployed.

The evolution of FDA policy on silicone breast implants: a case study of politics, bureaucracy, and business in the process of decision-making.

PubMed

Palley, H A

1995-01-01

The central issue facing federal regulation of breast implants is that while such devices are not functionally necessary or needed for survival, the side effects may be harmful and have not been proven unharmful. The Medical Device Amendments of 1976 appear to require such evidence prior to the FDA permitting the unrestricted marketing of these devices. However, only recently have such requirements been imposed by the FDA. The author examines the FDA's decision-making process, particularly as applied to silicone breast implants, and the factors that appears to have affected such decisions. In pursuing this study, the activities of a number of interest-group actors, as well as congressional responses and the role of federal bureaucratic actors, were examined. In 1992, the FDA established a regulatory protocol that effectively withdrew most silicone breast implants from the market for the purpose of breast augmentation and allows for the monitoring of the impact of new implants on women's health. This increase concern for determining the safety of breast implants is due to a number of factors, which are examined in this article.

Patient-Reported Outcome (PRO) Consortium translation process: consensus development of updated best practices.

PubMed

Eremenco, Sonya; Pease, Sheryl; Mann, Sarah; Berry, Pamela

2017-01-01

This paper describes the rationale and goals of the Patient-Reported Outcome (PRO) Consortium's instrument translation process. The PRO Consortium has developed a number of novel PRO measures which are in the process of qualification by the U.S. Food and Drug Administration (FDA) for use in clinical trials where endpoints based on these measures would support product labeling claims. Given the importance of FDA qualification of these measures, the PRO Consortium's Process Subcommittee determined that a detailed linguistic validation (LV) process was necessary to ensure that all translations of Consortium-developed PRO measures are performed using a standardized approach with the rigor required to meet regulatory and pharmaceutical industry expectations, as well as having a clearly defined instrument translation process that the translation industry can support. The consensus process involved gathering information about current best practices from 13 translation companies with expertise in LV, consolidating the findings to generate a proposed process, and obtaining iterative feedback from the translation companies and PRO Consortium member firms on the proposed process in two rounds of review in order to update existing principles of good practice in LV and to provide sufficient detail for the translation process to ensure consistency across PRO Consortium measures, sponsors, and translation companies. The consensus development resulted in a 12-step process that outlines universal and country-specific new translation approaches, as well as country-specific adaptations of existing translations. The PRO Consortium translation process will play an important role in maintaining the validity of the data generated through these measures by ensuring that they are translated by qualified linguists following a standardized and rigorous process that reflects best practice.

Can claims, misleading information, and manufacturing issues regarding dietary supplements be improved in the United States?

PubMed

Gibson, James E; Taylor, David A

2005-09-01

The safety and effectiveness of over-the-counter (OTC) drugs are assessed through the Food and Drug Administration's (FDA's) OTC drug review. Prescription drugs are approved through the rigorous new drug application (NDA) process. In contrast, dietary supplements are regulated as foods, and the FDA must determine that a dietary supplement ingredient poses a "significant or unreasonable risk of illness or injury" instead of requiring the manufacturer to provide safety data. According to the FDA, there are more than 29,000 different dietary supplements available to consumers today. This momentum has its roots in consumer interest in health and self-care and suggests that Americans are searching for alternatives to conventional foods for physical and mental well being. The Committee on the Framework for Evaluating the Safety of Dietary Supplements was formed under the auspices of the Food and Nutrition Board that produced a report entitled Dietary Supplements: A Framework for Evaluating Safety. Categories of specific information identified for use are 1) human data, 2) animal studies, 3) in vitro experiments, and 4) information on related substances. Several factors were identified to guide the FDA in applying the framework. Two of these factors are expressed as follows: 1) "the appropriate scientific standard to be used to overturn this basic assumption of safety is to demonstrate significant or unreasonable risk, not prove that an ingredient is unsafe"; and 2) "approaches taken by diverse organizations and governmental bodies, both within and outside the United States, which evaluate the safety and at times efficacy of dietary supplement ingredients, vary in their relevance to the protection of the American public from risks associated with consumption of dietary supplement ingredients".

The US Food and Drug Administration's Risk Evaluation and Mitigation Strategy (REMS) Program - Current Status and Future Direction.

PubMed

Wu, Jasmanda; Juhaeri, Juhaeri

2016-12-01

The US Food and Drug Administration (FDA) Amendments Act of 2007 granted the FDA new authorities to enhance drug safety by requiring application holders to submit a proposed Risk Evaluation and Mitigation Strategy (REMS). A REMS is a required risk management plan that uses tools beyond the package insert. REMS elements may include a medication guide and patient package insert for patients and a communication plan focused on health care professionals. Elements to assure safe use (ETASUs) are put in place to mitigate a specific known serious risk when other less restrictive elements of a REMS are not sufficient to mitigate such risk. An implementation system is required for an REMS that includes the ETASUs. With approximately eight years of experience with REMS programs, many health care settings have created systems to manage REMS and also to integrate REMS into their practice settings. At the same time, there are issues associated with the development and implementation of REMS. In 2011, FDA created the REMS Integration Initiative to develop guidance on how to apply statutory criteria to determine when a REMS is required, to improve standardization and assessment of REMS, and to improve integration of REMS into the existing healthcare system. A key component of the REMS Integration Initiative is stakeholder outreach to better understand how existing REMS programs are working and to identify opportunities for improvement. This review attempts to share our company's experience with the REMS program, and to provide updates on FDA's efforts to improve REMS communication, to standardize REMS process, to reduce REMS program burdens and to build a common REMS platform. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Febuxostat: drug review and update.

PubMed

Grewal, Harmanjot K; Martinez, Joseph R; Espinoza, Luis R

2014-05-01

Gouty arthritis and hyperuricemia have ailed humans for centuries. Recent advances in understanding of the mechanism(s) of their development have changed our perception of the disease process. Despite these gains, the treatment options available are limited. The FDA approval of febuxostat for the treatment of hyperuricemia in gout has been a significant step forward. Since its approval in 2009, febuxostat has proven to be safe and efficacious although concerns remain regarding its long-term effects and superiority to other uricosuric agents, such as allopurinol. A comprehensive literature review of PubMed and Ovid examining clinical trials and post-marketing studies yielded congruent findings on efficacy and safety in elderly populations and those with mild-to-moderate renal/hepatic impairment. A lack of literature and clinical studies was found with regard to comparison of febuxostat to FDA-approved high-dose allopurinol (> 300 mg), the safety of febuxostat in the treatment of severe renal/hepatic impairment and the benefit in the treatment of secondary cases of hyperuricemia. Febuxostat is effective in the treatment of mild-to-moderate renal/hepatic impairment with dramatic effects on the serum urate level. It can be used safely in patients with hypersensitivity reactions to allopurinol. Further research is needed to determine the long-term benefits and risks.

78 FR 72894 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0795] Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Medical Devices; Third-Party Review Under the Food and Drug Administration Modernization Act...

21 CFR 56.104 - Exemptions from IRB requirement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... INSTITUTIONAL REVIEW BOARDS General Provisions § 56.104 Exemptions from IRB requirement. The following categories of clinical investigations are exempt from the requirements of this part for IRB review: (a) Any investigation which commenced before July 27, 1981 and was subject to requirements for IRB review under FDA...

21 CFR 56.104 - Exemptions from IRB requirement.

Code of Federal Regulations, 2012 CFR

2012-04-01

... INSTITUTIONAL REVIEW BOARDS General Provisions § 56.104 Exemptions from IRB requirement. The following categories of clinical investigations are exempt from the requirements of this part for IRB review: (a) Any investigation which commenced before July 27, 1981 and was subject to requirements for IRB review under FDA...

21 CFR 56.104 - Exemptions from IRB requirement.

Code of Federal Regulations, 2014 CFR

2014-04-01

... INSTITUTIONAL REVIEW BOARDS General Provisions § 56.104 Exemptions from IRB requirement. The following categories of clinical investigations are exempt from the requirements of this part for IRB review: (a) Any investigation which commenced before July 27, 1981 and was subject to requirements for IRB review under FDA...

21 CFR 56.104 - Exemptions from IRB requirement.

Code of Federal Regulations, 2013 CFR

2013-04-01

... INSTITUTIONAL REVIEW BOARDS General Provisions § 56.104 Exemptions from IRB requirement. The following categories of clinical investigations are exempt from the requirements of this part for IRB review: (a) Any investigation which commenced before July 27, 1981 and was subject to requirements for IRB review under FDA...

Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals.

PubMed

Schick, Andreas; Miller, Kathleen L; Lanthier, Michael; Dal Pan, Gerald; Nardinelli, Clark

2017-06-01

An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions. We study this question using an internal FDA database containing every new small molecule drug submitted to the FDA's Center for Drug Evaluation and Research (CDER) on or after November 21, 1997, and approved and commercially launched before December 31, 2009. Serious post-marketing safety actions include whether these drugs ever experienced either a post-marketing boxed warning or a withdrawal from the market due to safety concerns. A random effects logistic regression model was used to test whether any pre-marketing characteristics were associated with either post-marketing safety action. A total of 219 new molecular entities were analyzed. Among these drugs, 11 experienced a safety withdrawal and 30 received boxed warnings by July 31, 2016. Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing boxed warning or safety withdrawal. However, we do find that new drugs approved with either a boxed warning or priority review are more likely to experience post-marketing boxed warnings. Furthermore, drugs approved with boxed warnings tend to receive post-marketing boxed warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a boxed warning are 3.88 times more likely to receive a post-marketing boxed warning, while drugs approved with a priority review are 3.51 times more likely to receive a post-marketing boxed warning. Although drugs approved with a boxed warning or priority review are more likely to experience serious post-marketing safety events, other information provided during the FDA drug review that is easy to quantify is generally not associated with post-marketing safety events. It appears that these post-marketing events are not discernible during a pre-marketing review and therefore might not be avoidable using current review data.

Advancing regulatory science to bring novel medical devices for use in emergency care to market: the role of the Food and Drug Administration.

PubMed

Scully, Christopher G; Forrest, Shawn; Galeotti, Loriano; Schwartz, Suzanne B; Strauss, David G

2015-04-01

The Food and Drug Administration (FDA) performs regulatory science to provide science-based medical product regulatory decisions. This article describes the types of scientific research the FDA's Center for Devices and Radiological Health performs and highlights specific projects related to medical devices for emergency medicine. In addition, this article discusses how results from regulatory science are used by the FDA to support the regulatory process as well as how the results are communicated to the public. Regulatory science supports the FDA's mission to assure safe, effective, and high-quality medical products are available to patients. Published by Elsevier Inc.

Drug safety: Pregnancy rating classifications and controversies.

PubMed

Wilmer, Erin; Chai, Sandy; Kroumpouzos, George

2016-01-01

This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

Subarray-based FDA radar to counteract deceptive ECM signals

NASA Astrophysics Data System (ADS)

Abdalla, Ahmed; Wang, Wen-Qin; Yuan, Zhao; Mohamed, Suhad; Bin, Tang

2016-12-01

In recent years, the frequency diverse array (FDA) radar concept has attracted extensive attention, as it may benefit from a small frequency increment, compared to the carrier frequency across the array elements and thereby achieve an array factor that is a function of the angle, the time, and the range which is superior to the conventional phase array radar (PAR). However, limited effort on the subject of FDA in electronic countermeasure scenarios, especially in the presence of mainbeam deceptive jamming, has been published. Basic FDA is not desirable for anti-jamming applications, due to the range-angle coupling response of targets. In this paper, a novel method based on subarrayed FDA signal processing is proposed to counteract deceptive ECM signals. We divide the FDA array into multiple subarrays, each of which employs a distinct frequency increment. As a result, in the subarray-based FDA, the desired target can be distinguished at subarray level in joint range-angle-Doppler domain by utilizing the fact that the jammer generates false targets with the same ranges to each subarray without reparations. The performance assessment shows that the proposed solution is effective for deceptive ECM targets suppression. The effectiveness is verified by simulation results.

Advertising and promotion of medical devices.

PubMed

Portnoy, Stuart

2006-01-01

Dr. Portnoy, a former senior clinical reviewer and manager for the FDA's Center for Devices and Radiological Health, provides guidance for determining acceptable practices for the claims, content, and appearance of advertising and promotional materials for medical devices. In the course of doing so, he discusses important regulatory and legal precedents, and provides examples of successful and problematic advertising and promotion strategies including those that resulted in FDA Warning Letters, enforcement activities, and in some cases, monetary and criminal penalties.

Innovating by developing new uses of already-approved drugs: trends in the marketing approval of supplemental indications.

PubMed

DiMasi, Joseph A

2013-06-01

Much of the literature on trends and factors affecting biopharmaceutical innovation has focused overwhelmingly on the development and approval of never-before approved drugs and biologics. Little attention has been paid to new uses for already-approved compounds, which can be an important form of innovation. This paper aimed to determine and analyze recent trends in the number and type of new or modified US indication approvals for drugs and biologics. We also examine regulatory approval-phase times for new-use efficacy supplements and compare them to approval-phase times for original-use approvals over the same period. We developed a data set of efficacy supplements approved by the US Food and Drug Administration (FDA) from 1998 to 2011 that includes information on the type, approval-phase time (time from submission to the FDA of an application for marketing approval to approval of the application), and FDA therapeutic-significance rating for the approved application, which we obtained from an FDA Web site. This data set was merged with a Tufts Center for the Study of Drug Development (CSDD) data set of US new drug and biologics approvals. We developed descriptive statistics on trends in the number and type of new-use efficacy supplements, on US regulatory approval-phase times for the supplements, and on original new drug and biologics approvals over the study period and for the time from original- to new-use approval. The total number of new-use efficacy-supplement approvals did not exhibit a marked trend, but the number of new pediatric-indication approvals increased substantially. Approval-phase times for new-use supplements varied by therapeutic class and FDA therapeutic-significance rating. Mean approval-phase times were highest for central nervous system compounds (13.8 months) and lowest for antineoplastics (8.9 months). The mean time from original to supplement approval was substantially longer for new pediatric indications than for other new uses. Mean approval-phase time during the study period for applications that received a standard review rating from the FDA was substantially shorter for supplements compared to original uses, but the differences for applications that received a priority review rating from the FDA were negligible. Development of and regulatory approval for new uses of already-approved drugs and biologics is an important source of innovation by biopharmaceutical firms. Despite rising development costs, the output of new-use approvals has remained stable in recent years, driven largely by the pursuit of new pediatric indications. FDA approval-phase times have generally declined substantially for all types of applications since the mid-1990s following legislation that provided a new source of income for the agency. However, while the resources needed to review supplemental applications are likely lower in general than for original-use approvals, the approval-phase times for important new uses are no lower than for important original-use applications. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Preliminary investigation into the analytical potential of a multiwavelength fiber drop analyzer with special reference to applications in medical diagnostics

NASA Astrophysics Data System (ADS)

McMillan, Norman D.; O'Mongain, Eon; Walsh, James E.; Breen, Liam; McMillan, Duncan G.; Power, Michael J.; O'Dea, John P.; Kinsella, Seamus M.; Kelly, Mairead P.; Hammil, Conor; Orr, Dermot

1994-12-01

A preliminary investigation into the use of multiwavelength fiber drop analyzer (FDA) for the measurement of viscosity, spectral absorbance and refractive index is made with a view to obtaining conservative estimates of the instrumental capability of the FDA for these measurands. Some important new insights into drop vibrations are made from studies on the fiber drop traces (FDTs) of mechanically excited damped vibrations in drops with a set volume. A brief description of the feasibility measurements on the first application of the FDA in the diagnosis of disease in synovial fluid is given. Strong experimental evidence is reported for the existence of the surface-guided wave peak of the fiber drop trace and some new insights into the nature of the FDT are suggested based on a comparative study of the FDTs from a multiple-wavelength and a single-wavelength FDA. The earlier reported drop period dependence on applied electric field is critically reexamined, a new interpretation of this effect, is suggested, and an experimental study of clarification is given. Finally, a brief review of the projected capabilities of the FDA based on the work reported here is provided.

Surrogate endpoints and emerging surrogate endpoints for risk reduction of cardiovascular disease.

PubMed

Rasnake, Crystal M; Trumbo, Paula R; Heinonen, Therese M

2008-02-01

This article reviews surrogate endpoints and emerging biomarkers that were discussed at the annual "Cardiovascular Biomarkers and Surrogate Endpoints" symposium cosponsored by the US Food and Drug Administration (FDA) and the Montreal Heart Institute. The FDA's Center for Food Safety and Applied Nutrition (CFSAN) uses surrogate endpoints in its scientific review of a substance/disease relationship for a health claim. CFSAN currently recognizes three validated surrogate endpoints: blood pressure, blood total cholesterol, and blood low-density lipoprotein (LDL) concentration in its review of a health claim for cardiovascular disease (CVD). Numerous potential surrogate endpoints of CVD are being evaluated as the pathophysiology of heart disease is becoming better understood. However, these emerging biomarkers need to be validated as surrogate endpoints before they are used by CFSAN in the evaluation of a CVD health claim.

The Drug Safety and Risk Management Advisory Committee: a case study of meeting frequency, content, and outcomes before and after FDAAA.

PubMed

Morrato, Elaine H; Ling, Sarah B

2012-11-01

The Food and Drug Administration Amendments Act (FDAAA) of 2007 granted FDA-expanded drug safety authority. We hypothesized that meetings involving the FDA Drug Safety and Risk Management (DSaRM) Advisory Committee might serve as a barometer for the impact of FDAAA on drug safety regulatory decision making. We conducted a case study analysis of 42 DSaRM advisory committee meetings held between 2002 and 2011. Publicly available sources (FDA meeting minutes and materials, safety alerts, and drug manufacturer Web sites) were reviewed to describe and compare DSaRM meeting frequency, content and outcomes between the pre-FDAAA (2002-2007) and post-FDAAA (2008-2011) periods. DSaRM meeting frequency increased after FDAAA (from 2.7 to 6.5 meetings per year). DSaRM meetings were more likely to be held jointly with other drug advisory committees after FDAAA (from 68% to 92% of meetings). DSaRM members were invited participants in 35 additional meetings of other drug advisory committees (2007-2011). DSaRM meetings were more likely to review issues of approvability (eg, new drugs, new indications, and new product formulations) after FDAAA. FDA questions to the committee were more likely to request an explicit drug safety assessment after FDAAA (from 31% to 76% of meetings). Content analysis of meeting outcomes and subsequent FDA regulatory decisions did not suggest a more or less risk aversive climate after FDAAA. Increased DSaRM advisory committee activity indicates its advice was being sought more broadly for drug regulatory decision making and at earlier stages of drug development after FDAAA was enacted.

78 FR 55081 - Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-09

... measurements to a database for review by medical professionals. The database is a Web-based server that... review by medical professionals. FDA intends to make background material available to the public no later...

US FDA perspective on regulatory issues affecting circulatory assist devices.

PubMed

Sapirstein, Wolf; Chen, Eric; Swain, Julie; Zuckerman, Bram

2006-11-01

There has been a rapid development in mechanical circulatory support systems in the decade since the US FDA first approved a mechanical device to provide the circulatory support lacking from a failing heart. Devices are presently approved for marketing by the FDA to replace a failing ventricle, the Ventricular Assist Device or the entire heart, Total Artificial Heart. Contemporaneous with, and permitted by, improvement in technology and design, devices have evolved from units located extracorporeally to paracorporeal systems and totally implanted devices. Clinical studies have demonstrated a parallel improvement in the homeostatic adequacy of the circulatory support provided. Thus, while the circulatory support was initially tolerated for short periods to permit recovery of cardiac function, this technology eventually provided effective circulatory support for increasing periods that permitted the FDA to approve devices for bridging patients in end-stage cardiac failure awaiting transplant and eventually a device for destination therapy where patients in end-stage heart failure are not cardiac transplant candidates. The approved devices have relied on displacement pumps that mimic the pulsatility of the physiological system. Accelerated development of more compact devices that rely on alternative pump mechanisms have challenged both the FDA and device manufacturers to assure that the regulatory requirements for safety and effectiveness are met for use of mechanical circulatory support systems in expanded target populations. An FDA regulatory perspective is reviewed of what can be a potentially critical healthcare issue.

Uncharted territories of the patent-restoration due-diligence challenge.

PubMed

Gaudry, Kate S

2011-01-01

The innovation and development incentives offered by the patent system are mitigated if a substantial portion of the patent term is lost while obtaining product approval through the Food and Drug Administration (FDA). The Drug Price Competition and Patent Restoration Act was enacted to return some of the lost patent term to the patentee. However, any person can petition the FDA, contending that the patentee did not act with due diligence in seeking FDA approval of the product during the regulatory review period. A successful challenge will reduce the restored term, such that the patentee is not compensated for time lost due to his own non-diligent actions. While the current due-diligence regulations provide a vague and flexible standard, earlier drafts of the regulations and FDA responses to comments provide insight as to the types of factors the FDA is likely to consider when assessing an applicant's diligence. A due-diligence petition has only been filed three times, and in none of these cases did the FDA issue a decision based on substantive diligence matters. Still, detailed examination of these petitions is also instructive in predicting the success of due-diligence challenges. Statute-imposed maximums and applicants' own incentives to act diligently may minimize the utility of the due-diligence challenges in some contexts. However, in other contexts, I propose that these petitions offer a feasible approach towards limiting pharmaceutical monopolies.

Food Irradiation Research and Technology

USDA-ARS?s Scientific Manuscript database

Food Irradiation is a safe and effective U.S. Food and Drug Administration (FDA) approved process that can be used to disinfest or delay the maturation of fruits and vegetables, improve the microbiological safety of shellfish, eggs, raw meat and poultry, spices, and seeds used for sprouting. FDA ap...

Food irradiation research and technology

USDA-ARS?s Scientific Manuscript database

Food Irradiation is a safe and effective U.S. Food and Drug Administration (FDA) approved process that can be used to disinfest or delay the maturation of fruits and vegetables, improve the microbiological safety of shellfish, eggs, raw meat and poultry, spices, and seeds used for sprouting. FDA ap...

Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis.

PubMed

Shashaty, George; Frankewich, Raymond; Chakraborti, Tamal; Choudary, Jasti; Al-Fayoumi, Suliman; Kacuba, Alice; Castillo, Sonia; Robie-Suh, Kathy; Rieves, Dwaine; Weiss, Karen; Pazdur, Richard

2006-12-01

This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis. The FDA reviewed findings of a controlled, open-label, randomized multicenter phase III study of deferasirox vs. deferoxamine in 586 patients with beta-thalessemia and transfusional hemosiderosis. The study results as well as the results of the FDA review of chemistry, preclinical pharmacology, and supportive studies are described. Following 48 weeks of treatment in the phase III study, patients' liver iron concentrations (a key endpoint variable) had decreased an average of 2.4 mg of iron (Fe)/g dry weight (dw) and 2.9 mg Fe/g dw in the deferasirox and deferoxamine groups, respectively, despite continued blood transfusions in both cohorts. Deferasirox was associated with serum creatinine increases in approximately a third of patients. Common adverse events included gastrointestinal symptoms and skin rash. Other data provided supportive evidence of deferasirox safety and efficacy. The FDA granted deferasirox accelerated approval on November 2, 2005, for use in treating chronic iron overload due to transfusional hemosiderosis in patients > or =2 years of age. The sponsor must obtain clinical data demonstrating the drug's long-term safety and effectiveness.

Interpreting labels of abuse-deterrent opioid analgesics.

PubMed

Webster, Lynn R

To provide an overview of available abuse-deterrent opioids (ADOs) and the labeling text that describes abuse-deterrent (AD) properties. A nonsystematic review of ADO literature and regulatory documents guiding their development. A critical assessment and discussion of common routes of opioid abuse, AD methods and properties, US Food and Drug Administration (FDA) study requirements to achieve AD labeling, and brief guide to understanding AD labels. The FDA has issued guidance as incentive and direction to industry to develop ADOs as one component of a multi-pronged public-health strategy to combat opioid abuse and misuse. The guidance describes separate categories of premarket and postmarket studies and makes recommendations for claims that may be made based on study findings. Ten ADOs have FDA-approved labeling attesting to AD properties. Available formulations that fail to conform to FDA guidance in study and labeling recommendations cannot be considered ADO. Formulations with AD properties are expected to reduce risk compared to the same agents without AD properties but cannot prevent all abuse and adverse clinical outcomes.

New FDA draft guidance on immunogenicity.

PubMed

Parenky, Ashwin; Myler, Heather; Amaravadi, Lakshmi; Bechtold-Peters, Karoline; Rosenberg, Amy; Kirshner, Susan; Quarmby, Valerie

2014-05-01

A "Late Breaking" session was held on May 20 at the 2013 American Association of Pharmaceutical Scientists-National Biotech Conference (AAPS-NBC) to discuss the US Food and Drug Administration's (FDA) 2013 draft guidance on Immunogenicity Assessment for Therapeutic Protein Products. The session was initiated by a presentation from the FDA which highlighted several key aspects of the 2013 draft guidance pertaining to immunogenicity risk, the potential impact on patient safety and product efficacy, and risk mitigation. This was followed by an open discussion on the draft guidance which enabled delegates from biopharmaceutical companies to engage the FDA on topics that had emerged from their review of the draft guidance. The multidisciplinary audience fostered an environment that was conducive to scientific discussion on a broad range of topics such as clinical impact, immune mitigation strategies, immune prediction and the role of formulation, excipients, aggregates, and degradation products in immunogenicity. This meeting report highlights several key aspects of the 2013 draft guidance together with related dialog from the session.

Animal models for acute radiation syndrome drug discovery.

PubMed

Singh, Vijay K; Newman, Victoria L; Berg, Allison N; MacVittie, Thomas J

2015-05-01

Although significant scientific advances have been made over the past six decades in developing safe, nontoxic and effective radiation/medical countermeasures (MCMs) for acute radiation syndrome (ARS), no drug has been approved by the US FDA. The availability of adequate animal models is a prime requisite under the criteria established by the FDA 'animal rule' for the development of novel MCMs for ARS and the discovery of biomarkers for radiation exposure. This article reviews the developments of MCMs to combat ARS, with particular reference to the various animal models (rodents: mouse and rat; canine: beagle; minipigs and nonhuman primates [NHPs]) utilized for the in-depth evaluation. The objective, pathways and challenges of the FDA Animal Efficacy Rule are also discussed. There are a number of well-defined animal models, the mouse, canine and NHP, that are being used for the development of MCMs. Additional animal models, such as the minipig, are under development to further assist in the identification, efficacy testing and approval of MCMs under the FDA Animal Efficacy Rule.

Proceedings of the Food and Drug Administration's public workshop on new red blood cell product regulatory science 2016.

PubMed

Vostal, Jaroslav G; Buehler, Paul W; Gelderman, Monique P; Alayash, Abdu I; Doctor, Alan; Zimring, James C; Glynn, Simone A; Hess, John R; Klein, Harvey; Acker, Jason P; Spinella, Philip C; D'Alessandro, Angelo; Palsson, Bernhard; Raife, Thomas J; Busch, Michael P; McMahon, Timothy J; Intaglietta, Marcos; Swartz, Harold M; Dubick, Michael A; Cardin, Sylvain; Patel, Rakesh P; Natanson, Charles; Weisel, John W; Muszynski, Jennifer A; Norris, Philip J; Ness, Paul M

2018-01-01

The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulatory science on October 6 and 7, 2016, at the Natcher Conference Center on the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop was supported by the National Heart, Lung, and Blood Institute, NIH; the Department of Defense; the Office of the Assistant Secretary for Health, Department of Health and Human Services; and the Center for Biologics Evaluation and Research, FDA. The workshop reviewed the status and scientific basis of the current regulatory framework and the available scientific tools to expand it to evaluate innovative and future RBC transfusion products. A full record of the proceedings is available on the FDA website (http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm507890.htm). The contents of the summary are the authors' opinions and do not represent agency policy. © 2017 AABB.

FDA pregnancy risk categories and the CPS

PubMed Central

Law, Ruth; Bozzo, Pina; Koren, Gideon; Einarson, Adrienne

2010-01-01

ABSTRACT QUESTION My patient is taking a medication for a chronic condition and has just found out that she is 6 weeks pregnant. The US Food and Drug Administration (FDA) has assigned this medication to pregnancy risk category D, and the Compendium of Pharmaceuticals and Specialties provides no additional data. How should I interpret this information, and how does the Motherisk Program evaluate the safety or risks of drug use in pregnancy? ANSWER Pregnancy safety data provided by the FDA pregnancy risk categories and the Compendium of Pharmaceuticals and Specialties are insufficient to guide clinical decisions on how to proceed with a pregnancy following exposure to a category D medication. The Motherisk Program creates peer-reviewed statements derived from the primary literature, and we examine fetal outcomes as well as the risk-benefit profile of maternal treatment when evaluating the safety of medication use in pregnancy. The FDA announced in May 2008 that it is dropping its pregnancy risk categories and adopting a method similar to the one we use at Motherisk. PMID:20228306

A United States regulator's perspective on the ongoing chlorofluorocarbon transition.

PubMed

Meyer, R J

1999-12-01

The Food and Drug Administration (FDA) put in place a general ban on the use of chlorofluorocarbons for the products it regulates (medical devices, drugs, and foods) in 1978, exempting those products where chlorofluorocarbon use was determined to be essential for the public health. In the intervening years, as the international commitment to a full transition away from all chlorofluorocarbon use took shape under the Montreal Protocol, the FDA has worked with industry to facilitate the development and testing of alternative technologies and products for inhalation drug products. As these alternative products begin to move from testing through the approval process and into marketing, the FDA is working collaboratively with the Environmental Protection Agency, other governmental agencies, and nongovernmental stakeholders to develop a transition policy for the United States. The transition policy for metered dose inhalers must be one that achieves the dual aims of first protecting the patients who rely on these vital medical products, while also achieving the public health need of protecting the ozone layer. As a part of developing such a transition strategy, the FDA published an advance notice of proposed rulemaking (ANPRM) in March 1997. The ANPRM proposed mechanisms by which the FDA could determine when chlorofluorocarbon use in a drug product could no longer be considered essential. The ANPRM resulted in a large amount of valuable public debate and input. The FDA is now working to incorporate the knowledge gained from these public comments as it continues the rule-making process.

How Many Batches Are Needed for Process Validation under the New FDA Guidance?

PubMed

Yang, Harry

2013-01-01

The newly updated FDA Guidance for Industry on Process Validation: General Principles and Practices ushers in a life cycle approach to process validation. While the guidance no longer considers the use of traditional three-batch validation appropriate, it does not prescribe the number of validation batches for a prospective validation protocol, nor does it provide specific methods to determine it. This potentially could leave manufacturers in a quandary. In this paper, I develop a Bayesian method to address the issue. By combining process knowledge gained from Stage 1 Process Design (PD) with expected outcomes of Stage 2 Process Performance Qualification (PPQ), the number of validation batches for PPQ is determined to provide a high level of assurance that the process will consistently produce future batches meeting quality standards. Several examples based on simulated data are presented to illustrate the use of the Bayesian method in helping manufacturers make risk-based decisions for Stage 2 PPQ, and they highlight the advantages of the method over traditional Frequentist approaches. The discussions in the paper lend support for a life cycle and risk-based approach to process validation recommended in the new FDA guidance. The newly updated FDA Guidance for Industry on Process Validation: General Principles and Practices ushers in a life cycle approach to process validation. While the guidance no longer considers the use of traditional three-batch validation appropriate, it does not prescribe the number of validation batches for a prospective validation protocol, nor does it provide specific methods to determine it. This potentially could leave manufacturers in a quandary. In this paper, I develop a Bayesian method to address the issue. By combining process knowledge gained from Stage 1 Process Design (PD) with expected outcomes of Stage 2 Process Performance Qualification (PPQ), the number of validation batches for PPQ is determined to provide a high level of assurance that the process will consistently produce future batches meeting quality standards. Several examples based on simulated data are presented to illustrate the use of the Bayesian method in helping manufacturers make risk-based decisions for Stage 2 PPQ, and THEY highlight the advantages of the method over traditional Frequentist approaches. The discussions in the paper lend support for a life cycle and risk-based approach to process validation recommended in the new FDA guidance.

JCL roundtable: Risk evaluation and mitigation strategy.

PubMed

Brown, W Virgil; Bramlet, Dean A; Ross, Joyce L; Underberg, James A

Many factors enter into the decision by the Food and Drug Administration (FDA) to approve a new drug for use by physicians and other health care providers in treating diseases. Initially, the FDA authority was restricted to issues of safety and only later did the documentation of efficacy become part of the review process required for approval. However, all drugs have the potential for causing harm at some dose level to all and at lower doses in certain patients with vulnerability to the particular pharmacology of the agent. As new drugs have been designed to manage disorders that are uncommon, but of significant consequence, they may have adverse effects that are acceptable only because they are so uniquely beneficial to these specific conditions. The risk of these adverse effects may be acceptable since the benefit can outweigh the harm in most patients and the adversity can be predicted and managed. The approval of this category of drugs has grown rapidly since definition of a mechanism of action to manage and modify the risk has been provided by a process known as known as Risk Evaluation and Mitigation Strategy or "REMS." In 2007, the Food and Drug Administration Amendments Act (FDAAA) allowed the FDA to require postmarketing studies and the authority to mandate the implementation of a REMS for drugs with efficacy but documented potential for harm. Two relatively new drugs useful in the management of severe elevations of low-density lipoprotein cholesterol have been approved under a requirement for a REMS. These are lomitapide, an inhibitor of microsomal triglyceride transfer protein and mipomersen, an antisense oligonucleotide which reduces the synthesis of apolipoprotein B. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Agency perspectives on food safety for the products of animal biotechnology.

PubMed

Howard, H J; Jones, K M; Rudenko, L

2012-08-01

Animal biotechnology represents one subset of tools among a larger set of technologies for potential use to meet increasing world demands for food. Assisted reproductive technologies (ART) such as artificial insemination and embryo transfer continue to make positive contributions in food animal production. The US Food and Drug Administration (FDA) performed a comprehensive risk assessment to identify potential food consumption or animal health risks associated with animal cloning, an emerging ART. At that time, FDA concluded that animal cloning posed no unique risks either to animal health or to food consumption, and food from animal clones and their sexually reproduced offspring required no additional federal regulation beyond that applicable to conventionally bred animals of the species examined. At this time, no new information has arisen that would necessitate a change in FDA's conclusions on food from animal clones or their sexually reproduced offspring. Use of recombinant DNA technologies to produce genetically engineered (GE) animals represents another emerging technology with potential to impact food animal production. In its regulation of GE animals, FDA follows a cumulative, risk-based approach to address scientific questions related to the GE animals. FDA evaluates data and information on the safety, effectiveness and stability of the GE event. FDA carries out its review at several levels (e.g. molecular biology, animal safety, food safety, environmental safety and claim validation). GE animal sponsors provide data to address risk questions for each level. This manuscript discusses FDA's role in evaluation of animal cloning and GE animals. © 2012 Blackwell Verlag GmbH.

Intragastric Balloon Treatment for Obesity: Review of Recent Studies.

PubMed

Tate, Chinara M; Geliebter, Allan

2017-08-01

The FDA recently approved three intragastric balloon (IGB) devices, ReShape, ORBERA™, and Obalon for treatment of obesity. Given the high cost, complication risk, and invasiveness of bariatric surgery, IGB treatment may present a safer and lower cost option for weight reduction. IGBs are generally placed in the stomach endoscopically for up to 6 months to reduce gastric capacity, enhance feelings of fullness, and induce weight loss. The mechanism of action likely involves stimulation of gastric mechanoreceptors triggering short-acting vagal signals to brain regions implicated in satiety. Balloon efficacy may be influenced by balloon volume, patient gastric capacity, and treatment duration. This review focused on eight recent (2006-present) randomized controlled trials (RCTs) comparing percentage total body weight loss (%TBWL) between IGB and control groups including three reviewed by the FDA. %TBWL based on the reviewed studies was also compared with bariatric surgery and pharmacotherapy. Of the eight IGB studies, five had balloon treatment duration of 6 months. Efficacy at 6 months, based on a pooled weighted-mean %TBWL, was 9.7%, and the control-subtracted %TBWL was 5.6%. When one study without SDs was removed, the weighted mean %TBWL was 9.3 ± 5.7% SD, and control-subtracted %TBWL was 5.5 ± 7.8%, which was statistically greater than controls. IGB showed lower efficacy than bariatric surgery (median weight loss of 27% for Rouen-Y gastric bypass (RYGB). The control-subtracted %TBWL over 6 months of 5.5-5.6% is less than the most efficacious FDA-approved weight loss drug, Qsymia. At the recommended dose, Qsymia has a placebo-subtracted %TBWL at 6 months of approximately 6.6%. The weighted mean reported incidence of serious adverse events (SAEs) in the IGB group across all eight studies was 10.5%. Only six of the eight reviewed studies reported adverse events (AEs) in the IGB group, with a pooled reported incidence of 28.2%. Recently, the FDA reported new AEs including acute pancreatitis with ReShape and ORBERA™. Based on the available evidence, it is unlikely that IGB use will supplant other forms of obesity treatment. The estimated cost of endoscopic balloon implantation and retrieval is US $8,150. Collectively, a relatively small control-subtracted %TBWL and the potential for serious complications makes IGB unlikely to become widely adopted. Given the recent FDA warning, IGB longevity on the market is questionable.

75 FR 78252 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-15

... Review Boards--OMB Control Number 0910-0130--Extension When reviewing clinical research studies regulated... participating in clinical research. In the Federal Register of August 17, 2010 (75 FR 50766), FDA published a 60... IRB will use in performing its functions; the research protocols, informed consent documents, progress...

76 FR 30176 - Expedited Review for New Animal Drug Applications for Human Pathogen Reduction Claims; Withdrawal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2001-D-0066] (Formerly Docket No. 2001D-0107) Expedited Review for New Animal Drug Applications for Human Pathogen... Review for New Animal Drug Applications for Human Pathogen Reduction Claims.'' The guidance predates the...

76 FR 23520 - Periodic Review of Existing Regulations; Retrospective Review Under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... reviews that regulation to determine if the underlying science and policy are still valid and whether the regulations should be updated based on current science, policy, data, or technology. The third mechanism is... charged FDA with encouraging more research and development for treatments specifically for children. In...

77 FR 40072 - Assessment of the Program for Enhanced Review Transparency and Communication for New Molecular...

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2012-07-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0603] Assessment of the Program for Enhanced Review Transparency and Communication for New Molecular Entity New... statement of work for an assessment of the Program for Enhanced Review Transparency and Communication for...

Ionizing Solutions to Future Processor Demands for Safe Food

USDA-ARS?s Scientific Manuscript database

Food Irradiation is a safe and effective U.S. Food and Drug Administration (FDA) approved process that can be used to disinfest or delay the maturation of fruits and vegetables, improve the microbiological safety of shellfish, eggs, raw meat and poultry, spices, and seeds used for sprouting. FDA ap...

78 FR 69689 - Agency Information Collection Activities; Proposed Collection; Comment Request; Hazard Analysis...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-1427... Critical Control Point Procedures for the Safe and Sanitary Processing and Importing of Juice AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

Brief report: investigation into recalled human tissue for transplantation--United States, 2005-2006.

PubMed

2006-05-26

On September 29, 2005, a human tissue-processing company discovered inaccuracies in donor records forwarded from a tissue-recovery firm and notified the Food and Drug Administration (FDA). An FDA investigation determined that the recovery firm, Biomedical Tissue Services, Ltd. (BTS) (Fort Lee, New Jersey), recovered tissues from human donors who might not have met donor eligibility requirements and who were not screened properly for certain infectious diseases. In October 2005, BTS and the five processors that had received the tissues, working with FDA, issued a recall for all tissues recovered by BTS. The continuing FDA investigation determined that information for some donors (e.g., cause, place, or time of death) was not consistent with death certificate data obtained from the states where the deaths occurred. The investigation also determined that BTS had failed to recover tissues in a manner that would prevent contamination or cross-contamination and failed to control environmental conditions adequately during tissue recovery. These failures were violations of the Current Good Tissue Practice Rules (effective May 25, 2005), which require manufacturers to recover, process, store, label, package, and distribute human cells, tissue, and cellular and tissue-based products (HCT/Ps) to prevent introduction, transmission, or spread of communicable diseases. In January 2006, FDA ordered BTS to cease manufacturing and to retain all HCT/Ps.

Development of pediatric vaccine recommendations and policies.

PubMed

Pickering, Larry K; Orenstein, Walter A

2002-07-01

A significant decrease in each vaccine-preventable disease has occurred since the introduction of the respective immunizations now included in the recommended childhood immunization schedule. The process through which a vaccine must travel from development to approval and implementation is complex. Hurdles include receiving approval from several advisory committees, government agencies, and professional organizations. At each step in the process, data regarding safety, immunogenicity, and efficacy are evaluated continuously and rigorously. Once a vaccine is approved by the Food and Drug Administration (FDA) and incorporated into the recommended childhood immunization schedule, continuing issues include those that deal with supply, safety, effectiveness, and financing. The logistics of development and implementation of pediatric vaccine recommendations and policies are reviewed.

Validation of gamma irradiator controls for quality and regulatory compliance

NASA Astrophysics Data System (ADS)

Harding, Rorry B.; Pinteric, Francis J. A.

1995-09-01

Since 1978 the U.S. Food and Drug Administration (FDA) has had both the legal authority and the Current Good Manufacturing Practice (CGMP) regulations in place to require irradiator owners who process medical devices to produce evidence of Irradiation Process Validation. One of the key components of Irradiation Process Validation is the validation of the irradiator controls. However, it is only recently that FDA audits have focused on this component of the process validation. What is Irradiator Control System Validation? What constitutes evidence of control? How do owners obtain evidence? What is the irradiator supplier's role in validation? How does the ISO 9000 Quality Standard relate to the FDA's CGMP requirement for evidence of Control System Validation? This paper presents answers to these questions based on the recent experiences of Nordion's engineering and product management staff who have worked with several US-based irradiator owners. This topic — Validation of Irradiator Controls — is a significant regulatory compliance and operations issue within the irradiator suppliers' and users' community.

76 FR 35448 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

...The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.

76 FR 4117 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-24

...The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.

29 CFR 1987.112 - Judicial review.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false Judicial review. 1987.112 Section 1987.112 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) PROCEDURES FOR HANDLING RETALIATION COMPLAINTS UNDER SECTION 402 OF THE FDA FOOD SAFETY...

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Federal Register 2010, 2011, 2012, 2013, 2014

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...The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.

78 FR 39731 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

...The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.

Just a Spoonful of Sugar Will Land You Six Feet Underground: Should the Food and Drug Administration Revoke Added Sugar's GRAS Status?

PubMed

Card, Melissa Marie; Abela, John Francis

2015-01-01

This article assesses whether added sugar meets FDA's standard to be generally recognized as safe ("GRAS"). If added sugar is not GRAS, then manufacturers are subject to premarket approval prior to using added sugar in their products. This article advocates that FDA should issue a Federal Register notice determining that added sugar is not GRAS, allowing FDA to regulate the amount of added sugar used in processed foods, decreasing the health adversities that stem from added sugar consumption.

NCI, NHLBI, FDA, AACC, and CMS Collaborate in Advancing Proteomics Regulatory Science | Office of Cancer Clinical Proteomics Research

Cancer.gov

Despite great strides in proteomics and the growing number of articles citing the discovery of potential biomarkers, the actual rate of introduction of Food and Drug Administration (FDA) approved protein analytes has been relatively unchanged over the past 10 years. One of reasons for the lack of new protein-based biomarkers approved has been a lack of information and understanding by the proteomics research community to the regulatory process used by the FDA. To address this issue, Dr.

Enhancing the incorporation of the patient's voice in drug development and evaluation.

PubMed

Chalasani, Meghana; Vaidya, Pujita; Mullin, Theresa

2018-01-01

People living with a condition are uniquely positioned to inform the understanding of the therapeutic context for drug development and evaluation. In 2012, the U.S. Food and Drug Administration (FDA) established the Patient-Focused Drug Development (PFDD) initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. PFDD meetings are unique among FDA public meetings, with a format designed to engage patients and elicit their perspectives on two topic areas: (1) the most significant symptoms of their condition and the impact of the condition on daily life; and, (2) their current approaches to treatment. FDA has conducted 24 disease-specific PFDD meetings to date. The lessons learned from PFDD meetings range from experiences common across rare diseases to more disease specific experiences that matter most to patients. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Patient-focused drug development is an ongoing effort and FDA looks forward to the next steps in advancing the science and the utilization of patient input throughout drug development and evaluation. The U.S. Food and Drug Administration (FDA) has multiple mechanisms for its regulators and staff to interact with patients -- but none quite like its novel Patient-Focused Drug Development (PFDD) initiative. FDA established the PFDD initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. Since the initiative's inception in 2012, FDA has held 24 PFDD meetings, covering a range of disease areas and hearing directly from thousands of patients and caregivers. FDA's PFDD meetings have also provided key stakeholders, including patient advocates, researchers, drug developers, healthcare providers, and other government officials, an opportunity to hear the patient's voice. The lessons learned include but are not limited to specific experiences that matter most to patients, patient perspectives on meaningful treatment benefits and how patients want to be engaged in the drug development process. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Further enhancing the incorporation of the patient's voice in drug development and evaluation continues to be a priority for FDA.

The nightmare of FDA clearance/approval to market: perception or reality?

PubMed

Tylenda, C A

1996-09-01

Over the last few years the Center for Device Evaluation and Research (CDRH) at the Food and Drug Administration (FDA) has received annually over 16 thousand submissions related to medical devices. Over 10,000 of these are major submissions which include applications to conduct clinical trials and applications to market medical devices for a specified indication for use. Each application is carefully considered. FDA personnel work closely with applicants to ensure that clinical trial design minimizes risk to the patients and maximizes benefit with respect to addressing the safety and effectiveness of the device being tested. Applicants are given every opportunity to provide additional information when necessary to assure that applications to market medical devices are complete. Applicants have the opportunity to meet with FDA staff prior to submitting applications in cases where the application is other than a straight forward, uncomplicated submission. In addition, FDA assists applicants through the development of guidance documents, which discuss the type of information that would be beneficial to include in a submission. The Division of Small Manufacturers Assistance at FDA is dedicated to helping interested persons understand the clearance/approval process. This paper will discuss the role of FDA in the regulation of medical devices, with an emphasis on the pathway to obtaining permission to market medical devices in the United States.

75 FR 13766 - Food and Drug Administration and Process Analytical Technology for Pharma Manufacturing: Food and...

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76 FR 24495 - Reprocessing of Reusable Medical Devices; Public Workshop

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... workshop will be held in the Great Room at the FDA White Oak Conference Center, Bldg. 31, Rm. 1503, 10903... requests to make oral presentations, as well as presentation materials, must be sent to the contact person... sterilization process, potentially resulting in HAIs or other adverse patient outcomes. FDA receives reports of...

75 FR 65495 - Draft Guidance for Industry on Qualification Process for Drug Development Tools; Availability

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2010-10-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0529...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... framework for interactions between the Center for Drug Evaluation and Research (CDER) and DDT sponsors to...

78 FR 68705 - Premerger Notification; Reporting and Waiting Period Requirements

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2013-11-15

....\\6\\ An exclusive license is substantively the same as buying the patent or part of the patent... through the FDA approval process, nor to effectively market or promote it in drug form after FDA approval... promotion of the drug. There is a great deal of uncertainty involved because the transfer takes place very...

21 CFR 822.17 - How long will your review of my submission take?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false How long will your review of my submission take? 822.17 Section 822.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE FDA Review and Action § 822.17 How long will...

21 CFR 822.17 - How long will your review of my submission take?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false How long will your review of my submission take? 822.17 Section 822.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE FDA Review and Action § 822.17 How long will...

21 CFR 822.17 - How long will your review of my submission take?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false How long will your review of my submission take? 822.17 Section 822.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE FDA Review and Action § 822.17 How long will...

21 CFR 822.17 - How long will your review of my submission take?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false How long will your review of my submission take? 822.17 Section 822.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE FDA Review and Action § 822.17 How long will...

21 CFR 822.17 - How long will your review of my submission take?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false How long will your review of my submission take? 822.17 Section 822.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE FDA Review and Action § 822.17 How long will...

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

PubMed

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

2015-01-01

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

Regulation of prescription drug promotion: direct-to-consumer advertising.

PubMed

Baylor-Henry, M; Drezin, N A

1998-01-01

The US Food and Drug Administration (FDA) is responsible for regulating the information on prescription drugs disseminated by sponsors to health care providers and consumers to ensure that it is truthful and not misleading, and that it presents a fair balance of benefit and risk information. Thus the public health is both protected and promoted by the dissemination of honest, accurate information about regulated products. This paper discusses the regulatory requirements for promotional materials for prescription drugs and the standards used by the FDA to evaluate these materials. It also discusses the agency's views on direct-to-consumer advertising, the enforcement actions that are available to the FDA, the process used by the FDA to determine what action should be taken and when, and what remedies are available.

Adolescent dosing and labeling since the Food and Drug Administration Amendments Act of 2007.

PubMed

Momper, Jeremiah D; Mulugeta, Yeruk; Green, Dionna J; Karesh, Alyson; Krudys, Kevin M; Sachs, Hari C; Yao, Lynn P; Burckart, Gilbert J

2013-10-01

During pediatric drug development, dedicated pharmacokinetic studies are generally performed in all relevant age groups to support dose selection for subsequent efficacy trials. To our knowledge, no previous assessments regarding the need for an intensive pharmacokinetic study in adolescents have been performed. To compare U.S. Food and Drug Administration (FDA)-approved adult and adolescent drug dosing and to assess the utility of allometric scaling for the prediction of drug clearance in the adolescent population. Adult and adolescent dosing and drug clearance data were obtained from FDA-approved drug labels and publicly available databases containing reviews of pediatric trials submitted to the FDA. Dosing information was compared for products with concordant indications for adolescent and adult patients. Adolescent drug clearance was predicted from adult pharmacokinetic data by using allometric scaling and compared with observed values. Adolescent and adult dosing information and drug clearance. There were 126 unique products with pediatric studies submitted to the FDA since the FDA Amendments Act of 2007, of which 92 had at least 1 adolescent indication concordant with an adult indication. Of these 92 products, 87 (94.5%) have equivalent dosing for adults and adolescent patients. For 18 of these 92 products, a minimum weight or body surface area threshold is recommended for adolescents to receive adult dosing. Allometric scaling predicted adolescent drug clearance with an overall mean absolute percentage error of 17.0%. Approved adult and adolescent drug dosing is equivalent for 94.5% of products with an adolescent indication studied since the FDA Amendments Act of 2007. Allometric scaling may be a useful tool to avoid unnecessary dedicated pharmacokinetic studies in the adolescent population during pediatric drug development, although each development program in adolescents requires a full discussion of drug dosing with the FDA.

Standards for Lithotripter Performance

NASA Astrophysics Data System (ADS)

Schultheiss, Reiner; Doerffel, Michael

2008-09-01

Standards for lithotripsy have been developed by the International Electrotechnical Commission (IEC) and the FDA. In addition to the existing regulations and norms for the manufacturers, special standards were developed to address a treatment method developed in the early 1980's using extracorporeal shock waves. Initially, the FDA regulated the premarket approval process for lithotripters as a Class III device but reclassified lithotripters in 2000 to a Class II device. The corresponding guidance document for showing the substantial equivalence of new devices with predicate devices will be described in detail. The FDA guidance document is very useful in helping device manufacturers: (i) develop technical performance testing for a shock wave lithotripter within the parameters of an FDA submission, and (ii) conduct clinical performance testing via at least one clinical confirmation study with a small number of subjects. Unfortunately although the submitted data are available at the FDA they are not available in the marketplace and this causes difficulties for physicians in deciding which device to use. The results of the technical performance testing of the LithoGold™ are provided.

Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

PubMed Central

Miller, Jennifer E; Korn, David; Ross, Joseph S

2015-01-01

Objective To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Conclusions Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge. PMID:26563214

Report on cancer risks associated with the ingestion of asbestos

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

Lemen, R.; Meinhardt, T.; Becking, G.

Cancer risks associated with ingestion of asbestos are discussed. Asbestos contamination of drinking water is considered. At least 66.5% of the United States water systems are capable of eroding asbestos cement pipes. The ability of water to leach asbestos from asbestos cement pipes can be modified by coatings applied to the inside pipe surface. Asbestos contamination in foods or pharmaceuticals is discussed. Asbestos fibers at concentrations of 1.1 to 172.7 million fibers per liter have been found in beverages. To date, studies supported by the Food and Drug Administration (FDA) have provided no evidence that ingesting asbestos results in anmore » increased cancer risk. The FDA has determined that no prohibition on using asbestos filters in processing food, beverages, and non-parenteral drugs is needed. Toxicological studies on asbestos ingestion and carcinogenicity are reviewed. Epidemiological evaluations of the association between drinking-water supplies containing asbestos and cancer mortality are discussed. It is concluded that the available information is insufficient for assessing the risk of cancer associated with ingesting asbestos.« less

Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history

PubMed Central

Nagaich, Upendra; Sadhna, Divya

2015-01-01

There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to company's discovery, customer's complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firm's recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing affined and safety/efficacy affined. It is essential to follow all the guidelines related to drug development and manufacturing procedure so as to minimize drug recall. PMID:25599028

US Food and Drug Administration Clearance of Moderate-Risk Otolaryngologic Devices via the 510(k) Process, 1997-2016.

PubMed

Rathi, Vinay K; Gadkaree, Shekhar K; Ross, Joseph S; Kozin, Elliott D; Sethi, Rosh K; Naunheim, Matthew R; Puram, Sidharth V; Gray, Stacey T

2017-10-01

Objective The US Food and Drug Administration (FDA) clears moderate-risk devices via the 510(k) process based on substantial equivalence to previously cleared devices; evidence of safety and effectiveness is not required. We characterized the premarket evidence supporting FDA clearance of otolaryngologic devices. Study Design Retrospective cross-sectional analysis. Setting Publicly available FDA documents. Subjects and Methods Recently cleared (1997-2016) moderate-risk otolaryngologic devices were categorized by type (diagnostic/therapeutic), subspecialty, implantable designation (yes/no), and recall history (yes/no). Supporting evidence was categorized by type (clinical/nonclinical/none; nonclinical and clinical mutually inclusive) and public availability of nonclinical and clinical performance data (available/not provided/not applicable). Results Between 1997 and 2016, the FDA cleared 377 moderate-risk otolaryngologic devices. The majority were therapeutic (n = 240/377 [63.7%]) and otologic (n = 311/377 [82.5%]); roughly one-third (n = 121/377 [32.1%]) were implantable. Few (n = 10/377 [2.7%]) devices were subject to recall. FDA documents summarizing premarket evidence were accessible for two-thirds (n = 247/377 [65.5%]) of devices. Among these devices, one-quarter (n = 66/247 [26.7%]) were supported by clinical evidence. The majority (n = 177/247 [71.7%]) were supported by nonclinical evidence, although nearly one-quarter (n = 58/247 [23.5%]) were cleared without supporting evidence. Therapeutic devices were more often cleared without supporting evidence (therapeutic: n = 53/170 [31.2%]; diagnostic: n = 5/77 [6.5%]; P < .0001). Nonclinical and clinical performance data were rarely available (nonclinical: n = 49/247 [19.8%]; clinical: n = 32/247 [13.0%]) within public summaries. Conclusion The FDA cleared most moderate-risk otolaryngologic devices for marketing via the 510(k) process without clinical evidence of safety and effectiveness. Otolaryngologists should be aware of limitations in premarket evidence when considering the adoption of new devices into clinical practice.

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

PubMed Central

Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

2017-01-01

Objectives To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Design Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data sources Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Outcome measures Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. Results The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Conclusions Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress. PMID:29208616

New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process.

PubMed

Huang, Shiew-Mei; Strong, John M; Zhang, Lei; Reynolds, Kellie S; Nallani, Srikanth; Temple, Robert; Abraham, Sophia; Habet, Sayed Al; Baweja, Raman K; Burckart, Gilbert J; Chung, Sang; Colangelo, Philip; Frucht, David; Green, Martin D; Hepp, Paul; Karnaukhova, Elena; Ko, Hon-Sum; Lee, Jang-Ik; Marroum, Patrick J; Norden, Janet M; Qiu, Wei; Rahman, Atiqur; Sobel, Solomon; Stifano, Toni; Thummel, Kenneth; Wei, Xiao-Xiong; Yasuda, Sally; Zheng, Jenny H; Zhao, Hong; Lesko, Lawrence J

2008-06-01

Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling.

FDA has the legal authority to adopt a threshold of toxicological concern (TTC) for substances in food at trace levels.

PubMed

Hahn, Martin J

2010-01-01

It now is possible to detect many substances in the parts per trillion and further advances will allow for even lower levels of detection. Many of these substances may always have been present in the food supply, but escaped detection. Others may have been introduced through environmental contamination, changes in food processing, sourcing of ingredients from different manufacturers or countries, and a myriad of other reasons. The adulteration and various safety provisions of the Federal Food, Drug, and Cosmetic Act (FDCA), principles of statutory construction, and case law, provide FDA with the legal authority to adopt the threshold concept. FDA and the courts have long recognized it is possible to establish safe levels of poisonous or deleterious substances found in foods. FDA routinely conducts such an analysis under the general adulteration provisions of the FDCA and has identified safe levels for numerous environmental contaminants found in food. The courts have recognized that through its exercise of enforcement discretion, FDA has the legal authority to establish non-binding defect action levels for contaminants. FDA similarly could implement the Threshold of Toxicological Concern (TTC) through its exercise of enforcement discretion.

Methylmercury in fish: a review of residue levels, fish consumption and regulatory action in the United States

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

Tollefson, L.; Cordle, F.

1986-09-01

The dangers associated with the consumption of large amounts of methylmercury in fish are well recognized, and there is some evidence to suggest that methylmercury may be the cause of subtle neurological impairments when ingested at even low to moderate levels, particularly the prenatal and early childhood periods. This concern has prompted a continuing assessment of the risk of methylmercury toxicity among fish consumers in the US as well as other countries. The toxicokinetics of methylmercury in humans are reviewed and used to estimate body burdens associated with toxic effects. To determine seafood consumption patterns among the continental US populationmore » the Food and Drug Administration (FDA) has analyzed data from a diary study commissioned by the Tuna Research Foundation. Mercury residue levels in domestic fish sampled by the FDA were used to determine the level of exposure to methylmercury. Until evidence is presented that substantially lowers the known body burden of methylmercury which causes toxicity, calculations indicate that the current 1.0 ppm regulatory level provides adequate protection for the average fish consumer, for young children, and for a significant number of consumers exceeding the acceptable daily intake. However, additional studies are being carried out in a continuing process to ensure that safe levels of prenatal exposure to mercury residues in fish are maintained.« less

The FDA's decision-making process: isn't it time to temper the principle of protective paternalism?

PubMed

Brandt, Lawrence J

2008-05-01

The authors conducted a well-designed, multinational, large study of women younger than 65 yr of age with irritable bowel syndrome (IBS) with a mixed pattern of diarrhea and constipation (IBS-M) or constipation (IBS-C) and showed that a statistically greater percentage of patients in each group responded to tegaserod compared with patients treated with placebo. Practicality looms large, however, in that the Food and Drug Administration (FDA) disallowed the continued marketing of tegaserod because of cardiovascular safety concerns, and it now is only available under a restricted access program. The wisdom of this decision aside, it is disturbing that the FDA revealed a zero-tolerance for any significant risk of disease when a drug (e.g., tegaserod) was used for a nonlife-threatening condition; the FDA chose to neglect any potential benefit of significant improvement in quality of life, while at the same time allowing the continued availability of sildenifil for erectile dysfunction and other medications (e.g., rosiglitazone and nonsteroidal anti-inflammatory drugs [NSAIDs]), each with a far greater risk of cardiovascular complications. Whether tegaserod will be re-released and, if so, under what conditions, is yet to be determined, as is the question of whether the FDA will decide to allow a more transparent decision-making process with input from all interested parties affected by their decision.