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.

77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

Media Coverage of FDA Drug Safety Communications about Zolpidem: A Quantitative and Qualitative Analysis.

PubMed

Woloshin, Steve; Schwartz, Lisa M; Dejene, Sara; Rausch, Paula; Dal Pan, Gerald J; Zhou, Esther H; Kesselheim, Aaron S

2017-05-01

FDA issues Drug Safety Communications (DSCs) to alert health care professionals and the public about emerging safety information affecting prescription and over-the-counter drugs. News media may amplify DSCs, but it is unclear how DSC messaging is transmitted through the media. We conducted a content analysis of the lay media coverage reaching the broadest audience to characterize the amount and content of media coverage of two zolpidem DSCs from 2013. After the first DSC, zolpidem news stories increased from 19 stories/week in the preceding 3 months to 153 following its release. Most (81%) appeared in the lay media, and 64% focused on the DSC content. After the second DSC, news stories increased from 24 stories/week in the preceding 3 months to 39 following. Among the 100 unique lay media news stories, at least half correctly reported three key DSC messages: next-day impairment and drowsiness as common safety hazards, lower doses for some but not all zolpidem products, and women's higher risk for impairment. Other DSC messages were reported in fewer than one-third of stories, such as the warning that impairment can happen even when people feel fully awake. The first-but not the second-zolpidem DSC generated high-profile news coverage. The finding that some messages were widely reported but others were not emphasizes the importance of ensuring translation of key DSC content.

OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

PubMed

Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

2016-01-01

Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

PubMed

Wang, Bo; Franklin, Jessica M; Eddings, Wesley; Landon, Joan; Kesselheim, Aaron S

2016-01-01

Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children. Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone. During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79). The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

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

Improving the effect of FDA-mandated drug safety alerts with Internet-based continuing medical education.

PubMed

Kraus, Carl N; Baldwin, Alan T; McAllister, R G

2013-02-01

The US Food and Drug Administration (FDA) requires risk communication as an element of Risk Evaluation and Mitigation Strategies (REMS) to alert and educate healthcare providers about severe toxicities associated with approved drugs. The educational effectiveness of this approach has not been evaluated. To support the communication plan element of the ipilimumab REMS, a Medscape Safe Use Alert (SUA) letter was distributed by Medscape via email and mobile device distribution to clinicians specified in the REMS. This alert contained the FDA-approved Dear Healthcare Provider (DHCP) letter mandated for distribution. A continuing medical education (CME) activity describing ipilimumab toxicities and the appropriate management was simultaneously posted on the website and distributed to Medscape members. Data were collected over a 6-month period regarding the handling of the letter and the responses to pre- and post-test questions for those who participated in the CME activity. Analysis of the answers to the pre- and posttest questions showed that participation in the CME activity resulted in an improvement in correct answer responses of 47%. Our experience shows that there are likely distinct information sources that are utilized by different HCP groups. The ready availability of a brief CME activity was utilized by 24,063 individuals, the majority of whom showed enhanced understanding of ipilimumab toxicity by improvement in post-test scores, educational data that are not available via implementation of standard safety alert communications. These results demonstrate that improvement in understanding of specific drug toxicities is enhanced by a CME intervention.

76 FR 13643 - FDA Food Safety Modernization Act: Title III-A New Paradigm for Importers; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... Act: Title III--A New Paradigm for Importers; Public Meeting AGENCY: Food and Drug Administration, HHS... announcing a public meeting entitled ``FDA Food Safety Modernization Act: Title III--A New Paradigm for.... In particular, title III of FSMA significantly enhances FDA's authority for oversight of the millions...

FDA working to ensure the safety of medical devices used in the pediatric population.

PubMed

Flack, Marilyn Neder; Gross, Thomas P; Reid, Joy Samuels; Mills, Thalia T; Francis, Jacqueline

2012-12-01

Special initiatives exist in FDA's Center for Devices and Radiological Health (CDRH), the Center for Drug Evaluation and Research, and the Center for Biologics Evaluation and Research to ensure the safety and effectiveness of medical products used in the vulnerable pediatric population. This article focuses on the special programs, projects, and special studies implemented by CDRH to ensure this safety and effectiveness in devices used in pediatric patients throughout the devices' total product life-cycles. Pediatricians play a major role in keeping medical devices safe for use in children by reporting device problems to FDA. Published by Elsevier Inc.

Interchangeability, Safety and Efficacy of Modified-Release Drug Formulations in the USA: The Case of Opioid and Other Nervous System Drugs.

PubMed

Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Hansen, Richard

2016-04-01

Modified-release drugs may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes. Concerns have been raised regarding interchangeability, efficacy, and safety of modified-release formulations. This study analyses all US Food and Drug Administration (FDA)-approved modified-release formulations and market trends, and illustrates how bioequivalence and safety of generic modified-release products compare to their respective brand name drugs and other generic drugs with different formulation design characteristics. This study also examines major concerns related to modified-release formulations: safety of opioids and bioequivalence of generic bupropion and methylphenidate. Study data were derived from the FDA electronic versions of the FDA's Orange Book (OB) and the FDA safety communications web page. Medicare Part D utilization and expenditures data were extracted from the Centers for Medicare and Medicaid. In May 2015, 276 (11.9 %) of the 2325 active ingredients and fixed-dose combinations listed in the FDA's Orange Book had at least one modified-release form approved by the FDA. The number of approvals increased over time; 52.5 % of modified releases were approved in the period 2000-May 2015. The FDA required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended-release opioids outweighed its risks of overdose and abuse. The REMS involved 16 new drug applications and 25 abbreviated new drug applications. The FDA addressed interchangeability problems with generic modified-release alternatives of bupropion and methylphenidate including lack of bioequivalence, reduced efficacy, and increased incidence of adverse events. Systematic post-marketing surveillance studies are needed to assess differences in safety, interchangeability, and efficacy of drugs with modified- and immediate-release formulations.

Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

PubMed

2010-09-29

The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

76 FR 19375 - Safety and Efficacy of Hypnotic Drugs; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Safety and Efficacy of Hypnotic Drugs; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting. The Food and Drug Administration (FDA) is announcing a public meeting to...

The role of quantitative safety evaluation in regulatory decision making of drugs.

PubMed

Chakravarty, Aloka G; Izem, Rima; Keeton, Stephine; Kim, Clara Y; Levenson, Mark S; Soukup, Mat

2016-01-01

Evaluation of safety is a critical component of drug review at the US Food and Drug Administration (FDA). Statisticians are playing an increasingly visible role in quantitative safety evaluation and regulatory decision-making. This article reviews the history and the recent events relating to quantitative drug safety evaluation at the FDA. The article then focuses on five active areas of quantitative drug safety evaluation and the role Division of Biometrics VII (DBVII) plays in these areas, namely meta-analysis for safety evaluation, large safety outcome trials, post-marketing requirements (PMRs), the Sentinel Initiative, and the evaluation of risk from extended/long-acting opioids. This article will focus chiefly on developments related to quantitative drug safety evaluation and not on the many additional developments in drug safety in general.

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

76 FR 37131 - Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management...: Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. General...

Characteristics of FDA drug recalls: A 30-month analysis.

PubMed

Hall, Kelsey; Stewart, Tyler; Chang, Jongwha; Freeman, Maisha Kelly

2016-02-15

The characteristics of drug recalls issued over 30 months by the Food and Drug Administration (FDA) were analyzed. All FDA-issued recalls for drugs (prescription and nonprescription, including dietary supplements) and biological products issued from June 20, 2012, to December 31, 2014, were included in this retrospective analysis. Data for all drug recalls were downloaded and sorted by the inclusion criteria from weekly FDA enforcement reports. The following data were analyzed: product type, recall firm, type of recall firm (compounding or noncompounding), country, voluntary or involuntary recall, method of communication of recall, recall number, FDA recall classification (class I, II, or III), product availability (prescription or nonprescription), reason for recall, recall initiation date, and recall report date. A total of 21,120 products were recalled during the 30-month study period. Of these, 3,045 drug products (14.4%) met the inclusion criteria and were analyzed. A total of 348 total manufacturers were associated with recalled drug products. The 5 firms most frequently involved in recalls accounted for 299, 273, 212, 118, and 112 recalls. The most common reasons for recalls were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. There was a significant association between FDA recall classification and the following outcomes: reasons for recall, product availability, type of recall firm, and form of communication. An investigation of FDA drug recalls revealed that the five most common recall reasons were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. Compounding firms were associated more frequently with contamination than were noncompounding firms. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

The FDA Unapproved Drugs Initiative: An Observational Study of the Consequences for Drug Prices and Shortages in the United States.

PubMed

Gupta, Ravi; Dhruva, Sanket S; Fox, Erin R; Ross, Joseph S

2017-10-01

Hundreds of drug products are currently marketed in the United States without approval from the FDA. The 2006 Unapproved Drugs Initiative (UDI) requires manufacturers to remove these drug products from the market or obtain FDA approval by demonstrating evidence of safety and efficacy. Once the FDA acts against an unapproved drug, fewer manufacturers remain in the market, potentially enabling drug price increases and greater susceptibility to drug shortages. There is a need for systematic study of the UDI's effect on prices and shortages of all targeted drugs. To examine the clinical evidence for approval and association with prices and shortages of previously unapproved prescription drugs after being addressed by the UDI. Previously unapproved prescription drugs that faced UDI regulatory action or with at least 1 product that received FDA approval through manufacturers' voluntary compliance with the UDI between 2006 and 2015 were identified. The clinical evidence was categorized as either newly conducted clinical trials or use of previously published literature and/or bioequivalence studies to demonstrate safety and efficacy. We determined the change in average wholesale price, presence of shortage, and duration of shortage for each drug during the 2 years before and after UDI regulatory action or approval through voluntary compliance. Between 2006 and 2015, 34 previously unapproved prescription drugs were addressed by the UDI. Nearly 90% of those with a drug product that received FDA approval were supported by literature reviews or bioequivalence studies, not new clinical trial evidence. Among the 26 drugs with available pricing data, average wholesale price during the 2 years before and after voluntary approval or UDI action increased by a median of 37% (interquartile range [IQR] = 23%-204%; P < 0.001). The number of drugs in shortage increased from 17 (50.0%) to 25 (73.5%) during the 2 years before and after, respectively (P = 0.046). The median shortage

78 FR 64957 - Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management... Committee and the Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To...

Right to experimental treatment: FDA new drug approval, constitutional rights, and the public's health.

PubMed

Leonard, Elizabeth Weeks

2009-01-01

On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Eschenbach, held that terminally ill patients who have exhausted all other available options have a constitutional right to experimental treatment that FDA has not yet approved. Although ultimately overturned by the full court, Abigail Alliance generated considerable interest from various constituencies. Meanwhile, FDA proposed similar regulatory amendments, as have lawmakers on both sides of the aisle in Congress. But proponents of expanded access fail to consider public health and consumer safety concerns. In particular, allowing patients to try unproven treatments, outside of controlled clinical trials risks both the study's outcome and the health of patients who might benefit from the deliberate, careful process of new drug approval as it currently operates under FDA's auspices.

MedWatch, the FDA Safety Information and Adverse Event Reporting Program

MedlinePlus

... Information and Adverse Event Reporting Program MedWatch: The FDA Safety Information and Adverse Event Reporting Program Share ... use. [Posted 06/01/2018] More What's New FDA Approved Safety Information DailyMed (National Library of Medicine) ...

75 FR 10490 - Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management Advisory... Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To provide...

Regulatory and scientific issues regarding use of foreign data in support of new drug applications in the United States: an FDA perspective.

PubMed

Khin, N A; Yang, P; Hung, H M J; Maung-U, K; Chen, Y-F; Meeker-O'Connell, A; Okwesili, P; Yasuda, S U; Ball, L K; Huang, S-M; O'Neill, R T; Temple, R

2013-08-01

Globalization of clinical research has led to an increase in clinical trials conducted outside of the United States that are submitted to the US Food and Drug Administration (FDA) in new drug applications. This article discusses the FDA's experience with these submissions in specific therapeutic areas, including the extent of this practice, differences between the effectiveness and safety outcomes of studies conducted inside and outside the United States, and the FDA's approach to acceptance of these trials.

FDA preemption of drug and device labeling: who should decide what goes on a drug label?

PubMed

Valoir, Tamsen; Ghosh, Shubha

2011-01-01

The Supreme Court decided an issue that is critical to consumer health and safety last year. In April 2009, the Supreme Court held that extensive FDA regulation of drugs did not preempt a state law claim that an additional warning on the label was necessary to make the drug reasonably safe for use. Thus, states--and even courts and juries--are now free to cast their vote on what a drug label should say. This is in direct contrast to medical devices, where the federal statute regulating medical devices expressly provides that state regulations are preempted. This Article discusses basic preemption principles and drugs, and explores the policy ramifications of pro- and anti-preemption policy in the healthcare industry.

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.

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

[Topics from "Overseas Drug Safety Information" in the past five years].

PubMed

Amanuma, Kimiko

2013-01-01

The Drug Safety Information Section of the Division of Safety Information on Drug, Food and Chemicals has been providing bulletins titled "Overseas Drug Safety Information" in Japanese since 2003. These bulletins comprise summarized and translated reports of important post-marketing drug safety information that are published by foreign regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medical Agency. A new issue of the bulletin is posted every two weeks on the website of the National Institute of Health Sciences, Japan; to date (May 2013), a total of 280 issues have been posted, covering approximately 2400 foreign news items and articles since its inception. Recently, visits to the bulletin website have been increasing: the number of hits for each issue totaled 570,000 in fiscal 2012. Among the "Overseas Drug Safety Information" issued in the past five years, I briefly describe here several topics which interested me: erythropoietin-stimulating agents in chronic kidney disease and their cardiovascular risk; bisphosphonates and atypical femur fracture; effectiveness of oral liquid cough medicines containing codeine in children; bevacizumab for metastatic breast cancer; and congenital abnormality associated with the use of antiepileptic drugs by pregnant women. I also describe the potential safety signals identified by FDA using its Adverse Event Reporting System, and their importance in ensuring the safe use of drugs in the post-marketing phase.

A comparison of new drugs approved by the FDA, the EMA, and Swissmedic: an assessment of the international harmonization of drugs.

PubMed

Zeukeng, Minette-Joëlle; Seoane-Vazquez, Enrique; Bonnabry, Pascal

2018-06-01

This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016. The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 2007 to 2016 was collected from websites of those agencies. The study included regulatory information, approval date, and indication for each drug. Descriptive statistical t tests and x 2 -tests were performed for the analysis. From 2007 to 2016, 134 new drugs were approved by all three regulatory agencies. Overall, 66.4% of the drugs were first approved by the FDA, 30.6% by the EMA, and 3.0% by SMC. The difference in approval dates between SMC and the EMA, SMC and the FDA, and the FDA and the EMA were statistically significant. The indications approved by the FDA, the EMA, and SMC for the same drugs were similar in content for 23.1% drugs and different in 76.9% of the drugs. Significant differences in indications existed between the FDA and SMC and the FDA and the EMA, but not between the EMA and SMC. There were differences in the characteristics of new drugs approved by the EMA, the FDA, and SMC in the period 2007-2016. Overall, two thirds of the new drugs were first approved by the FDA. Differences in indications were found in three out of four new drugs approved by the three regulatory agencies. Despite international drug regulation harmonization efforts, significant differences in the characteristics of new drugs approved by different agencies persist.

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

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.

Exploring Machine Learning Techniques Using Patient Interactions in Online Health Forums to Classify Drug Safety

ERIC Educational Resources Information Center

Chee, Brant Wah Kwong

2011-01-01

This dissertation explores the use of personal health messages collected from online message forums to predict drug safety using natural language processing and machine learning techniques. Drug safety is defined as any drug with an active safety alert from the US Food and Drug Administration (FDA). It is believed that this is the first…

Science, law, and politics in the Food and Drug Administration's genetically engineered foods policy: FDA's 1992 policy statement.

PubMed

Pelletier, David L

2005-05-01

The US Food and Drug Administration's (FDA's) 1992 policy statement was developed in the context of critical gaps in scientific knowledge concerning the compositional effects of genetic transformation and severe limitations in methods for safety testing. FDA acknowledged that pleiotropy and insertional mutagenesis may cause unintended changes, but it was unknown whether this happens to a greater extent in genetic engineering compared with traditional breeding. Moreover, the agency was not able to identify methods by which producers could screen for unintended allergens and toxicants. Despite these uncertainties, FDA granted genetically engineered foods the presumption of GRAS (Generally Recognized As Safe) and recommended that producers use voluntary consultations before marketing them.

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

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.

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

Discovery of FDA-Approved Drugs that Promote Retinal Cell Survival or Regeneration

DTIC Science & Technology

2015-10-01

1 AD______________ AWARD NUMBER: W81XWH-14-1-0407 TITLE:Discovery of FDA-Approved Drugs that Promote Retinal Cell Survival or Regeneration...SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0407Discovery of FDA-Approved Drugs that Promote Retinal Cell Survival or Regeneration 5c...vivo drug discovery platform named Automated Reporter Quantification in vivo (ARQiv). ARQiv quantifies reporter activity in transgenic zebrafish at

78 FR 36194 - Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0490] Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

IDAAPM: integrated database of ADMET and adverse effects of predictive modeling based on FDA approved drug data.

PubMed

Legehar, Ashenafi; Xhaard, Henri; Ghemtio, Leo

2016-01-01

The disposition of a pharmaceutical compound within an organism, i.e. its Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties and adverse effects, critically affects late stage failure of drug candidates and has led to the withdrawal of approved drugs. Computational methods are effective approaches to reduce the number of safety issues by analyzing possible links between chemical structures and ADMET or adverse effects, but this is limited by the size, quality, and heterogeneity of the data available from individual sources. Thus, large, clean and integrated databases of approved drug data, associated with fast and efficient predictive tools are desirable early in the drug discovery process. We have built a relational database (IDAAPM) to integrate available approved drug data such as drug approval information, ADMET and adverse effects, chemical structures and molecular descriptors, targets, bioactivity and related references. The database has been coupled with a searchable web interface and modern data analytics platform (KNIME) to allow data access, data transformation, initial analysis and further predictive modeling. Data were extracted from FDA resources and supplemented from other publicly available databases. Currently, the database contains information regarding about 19,226 FDA approval applications for 31,815 products (small molecules and biologics) with their approval history, 2505 active ingredients, together with as many ADMET properties, 1629 molecular structures, 2.5 million adverse effects and 36,963 experimental drug-target bioactivity data. IDAAPM is a unique resource that, in a single relational database, provides detailed information on FDA approved drugs including their ADMET properties and adverse effects, the corresponding targets with bioactivity data, coupled with a data analytics platform. It can be used to perform basic to complex drug-target ADMET or adverse effects analysis and predictive modeling. IDAAPM is

The effect of globalization of drug manufacturing, production, and sourcing and challenges for American drug safety.

PubMed

Woo, J; Wolfgang, S; Batista, H

2008-03-01

Americans benefit from one of the safest drug supplies and one of the highest standards of consumer protection in the world. Over the past decade, though, a general trend toward globalization of the supply chains for finished pharmaceutical products and active pharmaceutical ingredients has created new challenges for the Food and Drug Administration (FDA) in ensuring the safety and quality of the drug supply. Explosive growth in pharmaceutical manufacturing for the US market is particularly evident in the developing regions of Asia. Manufacturing sites in China and India now comprise approximately 40% of all FDA-registered foreign sites, having increased from 30% in 2002. (In 2001, when legislation first went into effect requiring registration of all foreign drug manufacturing sites, 140 registered sites in China listed 797 drug items for potential importation; as of 1 October 2007, that number had grown to 815 registered sites and well over 3,000 listed items.) In total in 2006, the United States received >145,000 line entries of imported drug products from >160 countries, up from only 1,300 line entries in 2000. FDA regulatory oversight resources (e.g., those allocated to inspection and testing of imports) are being challenged to keep up with the explosive growth of imported drugs. (In 2006, the FDA performed inspections at 212 foreign drug firms. This number has remained relatively consistent over the past 6 years, starting at 249 in 2001 and ranging from 190 to 260 on an annual basis.)

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.

Automatic signal extraction, prioritizing and filtering approaches in detecting post-marketing cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS).

PubMed

Xu, Rong; Wang, Quanqiu

2014-02-01

Targeted drugs dramatically improve the treatment outcomes in cancer patients; however, these innovative drugs are often associated with unexpectedly high cardiovascular toxicity. Currently, cardiovascular safety represents both a challenging issue for drug developers, regulators, researchers, and clinicians and a concern for patients. While FDA drug labels have captured many of these events, spontaneous reporting systems are a main source for post-marketing drug safety surveillance in 'real-world' (outside of clinical trials) cancer patients. In this study, we present approaches to extracting, prioritizing, filtering, and confirming cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS). The dataset includes records of 4,285,097 patients from FAERS. We first extracted drug-cardiovascular event (drug-CV) pairs from FAERS through named entity recognition and mapping processes. We then compared six ranking algorithms in prioritizing true positive signals among extracted pairs using known drug-CV pairs derived from FDA drug labels. We also developed three filtering algorithms to further improve precision. Finally, we manually validated extracted drug-CV pairs using 21 million published MEDLINE records. We extracted a total of 11,173 drug-CV pairs from FAERS. We showed that ranking by frequency is significantly more effective than by the five standard signal detection methods (246% improvement in precision for top-ranked pairs). The filtering algorithm we developed further improved overall precision by 91.3%. By manual curation using literature evidence, we show that about 51.9% of the 617 drug-CV pairs that appeared in both FAERS and MEDLINE sentences are true positives. In addition, 80.6% of these positive pairs have not been captured by FDA drug labeling. The unique drug-CV association dataset that we created based on FAERS could facilitate our understanding and prediction of cardiotoxic events associated with

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

Development of a Course of Study in FDA Drug Regulatory Procedures

ERIC Educational Resources Information Center

Jacobs, Robin Wills; King, James C.

1977-01-01

It is evident that more colleges of pharmacy should establish some major course of study in the area of governmental drug regulatory procedures. This study is aimed at expanding cooperative educational programs through an FDA residency for pharmacy students and preparing a didactic course in FDA procedures. (LBH)

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

PubMed

Berlin, Robert J

2009-09-01

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

The impact of Wyeth v. Levine on FDA regulation of prescription drugs.

PubMed

Ausness, Richard C

2010-01-01

In Wyeth v. Levine, decided in March, 2009, the United States Supreme Court concluded that the plaintiff's failure to warn claim against the makers of the drug Phenergan was not impliedly preempted by the Food, Drug and Cosmetic Act. In doing so, the Court rejected the argument of the U.S. Food and Drug Administration (FDA) that tort claims of this nature stand as an obstacle to federal regulatory objectives. This Article evaluates the Court's opinion in Wyeth and examines that decision's impact on subsequent litigation in the area of prescription drug labeling. The Article first discusses the preemption doctrine and its application to state law tort claims against product manufacturers. It then reviews the history of implied preemption of tort claims against manufacturers of FDA-approved prescription drugs prior to Wyeth and then discusses the Wyeth decisions in the Vermont Supreme Court and the United States Supreme Court. Finally, the Article evaluates some of the prescription drug preemption cases that have been decided in the lower federal courts since Wyeth and suggests that these courts are now reluctant to preempt failure to warn claims unless a manufacturer affirmatively seeks permission from FDA to change a drug's labeling.

ADHD medication use following FDA risk warnings.

PubMed

Barry, Colleen L; Martin, Andres; Busch, Susan H

2012-09-01

In 2006, the U.S. Food and Drug Administration (FDA) investigated cardiac and psychiatric risks associated with attention deficit/hyperactivity disorder (ADHD) medication use. To examine how disclosure of safety risks affected pediatric ADHD use, and to assess news media coverage of the issue to better understand trends in treatment patterns. We used the AHRQ's Medical Expenditure Panel Survey (MEPS), a nationally representative household panel survey, to calculate unadjusted rates of pediatric ADHD use from 2002 to 2008 overall and by parents' education. We examined whether children (ages 0 to 20) filled a prescription for any ADHD medication during the calendar year. Next, we used content analysis methods to analyze news coverage of the issue in 10 high-circulation newspapers, the 3 major television networks and a major cable news network in the U.S. We examined 6 measures capturing information conveyed on risk and benefits of ADHD medication use. No declines in medication use following FDA safety warnings overall or by parental education level were observed. News media coverage was relatively balanced in its portrayal of the risks and benefits of ADHD medication use by children. ADHD risk warnings were not associated with large declines in medication use, and balanced news coverage may have contributed to the treatment patterns observed. Self-reported surveys like the MEPS rely on the recall of respondents and may be subject to reporting bias. However, the validity of these data is supported by their consistency with other data on drug use from other sources. These findings are in direct contrast to the substantial declines in use observed after pediatric antidepressant risk warnings in the context of a news media environment that emphasized risks over benefits. Our findings are relevant to the ongoing discussion about improving the FDA's ability to monitor drug safety. Safety warnings occur amid ongoing concern that the agency has insufficient authority and

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/

Evaluating oversight of human drugs and medical devices: a case study of the FDA and implications for nanobiotechnology.

PubMed

Paradise, Jordan; Tisdale, Alison W; Hall, Ralph F; Kokkoli, Efrosini

2009-01-01

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration (FDA) using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Criteria assessment and expert elicitation are combined with existing literature, case law, and regulations in an integrative historical case studies approach. We then use our findings as a tool to explore possibilities for effective oversight and regulatory mechanisms for nanobiotechnology. Section I describes oversight mechanisms for human drugs and medical devices and presents current nanotechnology products. Section II describes the results of expert elicitation research. Section III highlights key criteria and relates them to the literature and larger debate. We conclude with broad lessons for the oversight of nanobiotechnology informed by Sections I-III in order to provide useful analysis from multiple disciplines and perspectives to guide discussions regarding appropriate FDA oversight.

77 FR 14402 - Draft Guidance on Classifying Significant Postmarket Drug Safety Issues; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

....'' This draft guidance describes FDA's current approach to classifying a significant postmarket drug... elevating some priority TSIs to an ``emergency'' status. The draft guidance was developed in connection with... guidance describes CDER's current approach to determining whether a significant postmarket drug safety...

New and incremental FDA black box warnings from 2008 to 2015.

PubMed

Solotke, Michael T; Dhruva, Sanket S; Downing, Nicholas S; Shah, Nilay D; Ross, Joseph S

2018-02-01

The boxed warning (also known as 'black box warning [BBW]') is one of the strongest drug safety actions that the U.S. Food & Drug Administration (FDA) can implement, and often warns of serious risks. The objective of this study was to comprehensively characterize BBWs issued for drugs after FDA approval. We identified all post-marketing BBWs from January 2008 through June 2015 listed on FDA's MedWatch and Drug Safety Communications websites. We used each drug's prescribing information to classify its BBW as new, major update to a preexisting BBW, or minor update. We then characterized these BBWs with respect to pre-specified BBW-specific and drug-specific features. There were 111 BBWs issued to drugs on the US market, of which 29% (n = 32) were new BBWs, 32% (n = 35) were major updates, and 40% (n = 44) were minor updates. New BBWs and major updates were most commonly issued for death (51%) and cardiovascular risk (27%). The new BBWs and major updates impacted 200 drug formulations over the study period, of which 64% were expected to be used chronically and 58% had available alternatives without a BBW. New BBWs and incremental updates to existing BBWs are frequently added to drug labels after regulatory approval.

A Good Year: FDA Approved Nine New Cancer Drugs in 2014

Cancer.gov

In 2014, the Food and Drug Administration (FDA) approved 41 drugs that had not been approved previously for any indication, the most in nearly 20 years. Of these 41 novel drugs, 9 were approved for the treatment of cancer or cancer-related conditions.

Online availability and safety of drugs in shortage: a descriptive study of internet vendor characteristics.

PubMed

Liang, Bryan A; Mackey, Tim K

2012-02-09

Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. We performed a descriptive study of the prevalence of online marketing for shortage drugs-that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing.

Online Availability and Safety of Drugs in Shortage: A Descriptive Study of Internet Vendor Characteristics

PubMed Central

Mackey, Tim K

2012-01-01

Background Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. Objective To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. Methods We performed a descriptive study of the prevalence of online marketing for shortage drugs—that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Results Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. Conclusions FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing. PMID:22321731

Bisphosphonates and Nonhealing Femoral Fractures: Analysis of the FDA Adverse Event Reporting System (FAERS) and International Safety Efforts

PubMed Central

Edwards, Beatrice J.; Bunta, Andrew D.; Lane, Joseph; Odvina, Clarita; Rao, D. Sudhaker; Raisch, Dennis W.; McKoy, June M.; Omar, Imran; Belknap, Steven M.; Garg, Vishvas; Hahr, Allison J.; Samaras, Athena T.; Fisher, Matthew J.; West, Dennis P.; Langman, Craig B.; Stern, Paula H.

2013-01-01

Background: In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts. Methods: We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012). Results: The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [CI], 3.44 to 5.92) for bisphosphonate use and nonhealing femoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures. Conclusions: Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing. PMID:23426763

Food and drug administration regulation of drugs that raise blood pressure.

PubMed

Blankfield, Robert P; Iftikhar, Imran H

2015-01-01

Although it is recognized that a systolic blood pressure (SBP) increase ≥ 2 mm Hg or a diastolic blood pressure (DBP) increase ≥ 1 mm Hg increases the risk of heart attacks and strokes in middle-aged adults, the Food and Drug Administration (FDA) lacks an adequate policy for regulating medications that increase blood pressure (BP). Some FDA reviewers consider a clinically significant increase in BP to occur only if a drug raises SBP ≥ 20 mm Hg or if a drug raises DBP ≥ 10 to 15 mm Hg. In recent years, numerous drugs have been regulated or taken off the market due to cardiovascular safety concerns. The list includes rofecoxib (Vioxx), valdecoxib (Bextra), nonselective nonsteroidal anti-inflammatory drugs, sibutramine (Meridia), and phenylpropanolamine. It is probable that the hypertensive effect of these drugs explains why they increase the risk of adverse cardiovascular events. Other drugs, notably serotonin-norepinephrine reuptake inhibitors and drugs used to treat attention deficit hyperactivity disorder, were approved without cardiovascular safety data despite the fact that they raise BP comparable to valdecoxib and sibutramine. It is the responsibility of the FDA to ensure that drugs are properly labeled regarding risk. Even if a drug raises BP only modestly, FDA guidelines for new drug approvals should include a requirement for cardiovascular safety data. However, such guidelines will not address the problem of how to obtain cardiovascular safety data for the many already approved drugs that increase BP. The FDA should play a role in obtaining cardiovascular safety data for such drugs. © The Author(s) 2014.

Ensuring that consumers receive appropriate information from drug ads: what is the FDA's role?

PubMed

Waxman, Henry A

2004-01-01

The promise of direct-to-consumer (DTC) prescription drug advertisements lies in their potential to educate consumers about medical conditions and the possibility of treatment. But this promise can only be fulfilled if consumers are given clear and accurate information. The responsibility for ensuring that this occurs falls on the Food and Drug Administration (FDA). Recent congressional investigations have indicated that the agency is failing at this task, as FDA enforcement actions against false and misleading ads have declined precipitously in recent years. Other FDA efforts, such as its recently released guidelines on prescription drugs, do not appear to be helpful, potentially confusing consumers more than helping them.

Medical devices; exemptions from premarket notification; class II devices--FDA, Final rule.

PubMed

1998-11-03

The Food and Drug Administration (FDA) is codifying the exemption from premarket notification of all 62 class II (special controls) devices listed as exempt in a January 21, 1998, Federal Register notice, subject to the limitations on exemptions. FDA has determined that for these exempted devices, manufacturers' submissions of premarket notifications are unnecessary to provide a reasonable assurance of safety and effectiveness. These devices will remain subject to current good manufacturing practice (CGMP) regulations and other general controls. This rulemaking implements new authorities delegated to FDA under the Food and Drug Administration Modernization Act (FDAMA).

FDA actions against health economic promotions, 2002-2011.

PubMed

Neumann, Peter J; Bliss, Sarah K

2012-01-01

To investigate Food and Drug Administration (FDA) regulatory actions against drug companies' health economic promotions from 2002 through 2011 to understand how frequently and in what circumstances the agency has considered such promotions false or misleading. We reviewed all warning letters and notices of violation ("untitled letters") issued by the FDA's Division of Drug Marketing, Advertising and Communications (DDMAC) to pharmaceutical companies from January 2002 through December 2011. We analyzed letters containing a violation related to "health economic promotion," defined according to one of several categories (e.g., implied claims of cost savings due to work productivity or economic claims containing unsupported statements about effectiveness or safety). We also collected information on factors such as the indication and type of media involved and whether the letter referenced Section 114 of the Food and Drug Administration Modernization Act. Of 291 DDMAC letters sent to pharmaceutical companies during the study period, 35 (12%) cited a health economic violation. The most common type of violation cited was an implied claim of cost savings due to work productivity or functioning (found in 20 letters) and economic claims containing unsubstantiated comparative claims of effectiveness, safety, or interchangeability (7 letters). The violations covered various indications, mostly commonly psychiatric disorders (6 letters) and pain (6 letters). No DDMAC letter pertained to Food and Drug Administration Modernization Act Section 114. The FDA has cited inappropriate health economic promotions in roughly 12% of the letters issued by the DDMAC. The letters highlight drug companies' interest in promoting the value of their products and the FDA's concerns in certain cases about the lack of supporting evidence. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Combination products regulation at the FDA.

PubMed

Lauritsen, K J; Nguyen, T

2009-05-01

The US Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, efficacy, and security of drugs, biological products, and medical devices. As single-entity products, drugs are generally regulated by the Center for Drug Evaluation and Research (CDER), devices by the Center for Devices and Radiological Health (CDRH), and biologics by the Center for Biologics Evaluation and Research (CBER). In recent years, technological advances have led to a blurring of the historical lines of separation between the centers.

FDA Kids' Home Page

MedlinePlus

... and Drug Administration A to Z Index Follow FDA En Español Search FDA Submit search Popular Content Home Food Drugs Medical ... 日本語 | فارسی | English FDA Accessibility Careers FDA Basics FOIA No FEAR Act ...

International Conference on Harmonisation; Electronic Transmission of Postmarket Individual Case Safety Reports for Drugs and Biologics, Excluding Vaccines; Availability of Food and Drug Administration Regional Implementation Specifications for ICH E2B(R3) Reporting to the Food and Drug Administration Adverse Event Reporting System. Notice of Availability.

PubMed

2016-06-23

The Food and Drug Administration (FDA) is announcing the availability of its FDA Adverse Event Reporting System (FAERS) Regional Implementation Specifications for the International Conference on Harmonisation (ICH) E2B(R3) Specification. FDA is making this technical specifications document available to assist interested parties in electronically submitting individual case safety reports (ICSRs) (and ICSR attachments) to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). This document, entitled "FDA Regional Implementation Specifications for ICH E2B(R3) Implementation: Postmarket Submission of Individual Case Safety Reports (ICSRs) for Drugs and Biologics, Excluding Vaccines" supplements the "E2B(R3) Electronic Transmission of Individual Case Safety Reports (ICSRs) Implementation Guide--Data Elements and Message Specification" final guidance for industry and describes FDA's technical approach for receiving ICSRs, for incorporating regionally controlled terminology, and for adding region-specific data elements when reporting to FAERS.

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false The Food and Drug Administration's (FDA's... (CONTINUED) FOOD ADDITIVES Premarket Notifications § 170.105 The Food and Drug Administration's (FDA's... data or other information available to FDA, including data not submitted by the manufacturer or...

Impact of biomarker development on drug safety assessment

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

Marrer, Estelle, E-mail: estelle.marrer@novartis.co; Dieterle, Frank

2010-03-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative andmore » 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.« less

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

Industry funding of the FDA: effects of PDUFA on approval times and withdrawal rates.

PubMed

Berndt, Ernst R; Gottschalk, Adrian H B; Philipson, Tomas J; Strobeck, Matthew W

2005-07-01

The development of new therapies is a crucial component of efforts to improve healthcare. Because drug development and FDA regulatory review have historically been lengthy and costly processes, the US Congress passed a series of legislative acts, beginning in 1992, known collectively as the Prescription Drug User Fee Acts (PDUFA), which sought to expedite the FDA drug-review process. Here, we review data on drug approvals and drug-approval times, both as a whole and by therapeutic class, which demonstrate that implementation of the PDUFAs led to substantial incremental reductions in approval times beyond what would have been observed in the absence of these legislative acts. In addition, our preliminary examination of the trends in the number of new molecular entity withdrawals, frequently used as a proxy to assess the FDA's safety record, suggests that the proportion of approvals ultimately leading to safety withdrawals prior to PDUFA and during PDUFA I and II were not statistically different.

Deficiencies in the reporting of VD and t1/2 in the FDA approved chemotherapy drug inserts

PubMed Central

D’Souza, Malcolm J.; Alabed, Ghada J.

2011-01-01

Since its release in 2006, the US Food and Drug Administration (FDA) final improved format for prescription drug labeling has revamped the comprehensiveness of drug inserts, including chemotherapy drugs. The chemotherapy drug “packets”, retrieved via the FDA website and other accredited drug information reporting agencies such as the Physician Drug Reference (PDR), are practically the only available unbiased summary of information. One objective is to impartially evaluate the reporting of useful pharmacokinetic parameters, in particular, Volume of Distribution (VD) and elimination half-life (t1/2), in randomly selected FDA approved chemotherapy drug inserts. The web-accessible portable document format (PDF) files for 30 randomly selected chemotherapy drugs are subjected to detailed search and the two parameters of interest are tabulated. The knowledge of the two parameters is essential in directing patient care as well as for clinical research and since the completeness of the core FDA recommendations has been found deficient, a detailed explanation of the impact of such deficiencies is provided. PMID:21643531

Doctors, drugs, and the FDA.

PubMed

Shanklin, D R

1972-11-01

This communication is directed to obstetricians, to the Food and Drug Administration (FDA), and to those individuals who might want to impose possibly unnecessary external structures on the practice of medicine. It is considered a positive that the patients of today are well informed and are more actively participating in therapeutic design. There is more veto power on the part of the patient and more concern over the trained ability of the physician. In the past physicians frequently made judgements individually, applying isolated and at times random standards for their decisions. Such actions were inevitable in an era when neither pathogenesis nor treatment was well understood. Now there is no excuse for such actions. Communication is easy, journals are widely circulated, and there are numerous refresher seminars. Increased specialization of knowledge has meant more corporate or group decisions for therapy. Current trends will continue to offer both opportunities and responsibilities. The opportunities are for better diffusion of knowledge, and the responsibility is to be informed. There can be a high level national standard for medical practice. As a beginning, the medical practice laws could use some uniform decisions. The FDA needs to show more responsiveness to changing knowledge and increased willingness to reconsider indications and contraindications in the light of newer experience. There is sufficient information available now to support the revocation of the approval of the use of diuretics in the management of human pregnancy. Another role of the FDA is the approval of new substances or new uses of old substances. The prostaglandins appear in this category, and the December 1972 issue will include the recent Brook Lodge Symposium on prostaglandins. The individual physician requires journal articles, individual experience, and designed trials in order to make judgements on patients who may have some factors not accounted for by groupthink or regulations.

Geographic Variation in Rosiglitazone Use Surrounding FDA Warnings in the Department of Veterans Affairs.

PubMed

Ahuja, Vishal; Sohn, Min-Woong; Birge, John R; Syverson, Chad; Budiman-Mak, Elly; Emanuele, Nicholas; Cooper, Jennifer M; Huang, Elbert S

2015-12-01

Geographic variation in the use of prescription drugs, particularly those deemed harmful by the FDA, may lead to variation in patient exposure to adverse drug events. One such drug is the glucose-lowering drug rosiglitazone, for which the FDA issued a safety alert on May 21, 2007, following the publication of a meta-analysis that suggested a 43% increase in the risk of myocardial infarction with the use of rosiglitazone. This alert was followed by a black box warning on August 14, 2007, that was updated 3 months later. While large declines have been documented in rosiglitazone use in clinical practice, little is known about how the use of rosiglitazone and other glucose-lowering drugs varied within the Department of Veterans Affairs (VA), surrounding the FDA alerts. Understanding this variation within integrated health care systems is essential to formulating policies that enhance patient protection and quality of care. To document variation in the use of rosiglitazone and other glucose- lowering drugs across 21 Veterans Integrated Service Networks (VISNs). We conducted a retrospective analysis of drug use patterns for all major diabetes drugs in a national cohort of 550,550 veterans with diabetes from 2003 to 2008. This included the time periods when rosiglitazone was added to (November 2003) and removed from (October 2007) the VA national formulary (VANF). We employed multivariable logistic regression models to statistically estimate the association between a patient's location and the patient's odds of using rosiglitazone. Aggregate rosiglitazone use increased monotonically from 7.7%, in the quarter it was added to the VANF (November 4, 2003), to a peak of 15.3% in the quarter when the FDA issued the safety alert. Rosiglitazone use decreased sharply afterwards, reaching 3.4% by the end of the study period (September 30, 2008). The use of pioglitazone, another glucose-lowering drug in the same class as rosiglitazone, was low when the FDA issued the safety alert

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.

Efficacy, Safety, and Regulatory Approval of Food and Drug Administration-Designated Breakthrough and Nonbreakthrough Cancer Medicines.

PubMed

Hwang, Thomas J; Franklin, Jessica M; Chen, Christopher T; Lauffenburger, Julie C; Gyawali, Bishal; Kesselheim, Aaron S; Darrow, Jonathan J

2018-04-24

Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non-breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non-breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non-breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non-breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy-designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non-breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy

FDA approves efavirenz. Food and Drug Administration.

PubMed

Highleyman, L

1998-10-01

The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

76 FR 30727 - Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0366] Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments. SUMMARY: The...

FDA's perspectives on cardiovascular devices.

PubMed

Chen, Eric A; Patel-Raman, Sonna M; O'Callaghan, Kathryn; Hillebrenner, Matthew G

2009-06-01

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, Section 903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA's review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.

Association of Attorney Advertising and FDA Action with Prescription Claims: A Time Series Segmented Regression Analysis.

PubMed

Tippett, Elizabeth C; Chen, Brian K

2015-12-01

Attorneys sponsor television advertisements that include repeated warnings about adverse drug events to solicit consumers for lawsuits against drug manufacturers. The relationship between such advertising, safety actions by the US Food and Drug Administration (FDA), and healthcare use is unknown. To investigate the relationship between attorney advertising, FDA actions, and prescription drug claims. The study examined total users per month and prescription rates for seven drugs with substantial attorney advertising volume and FDA or other safety interventions during 2009. Segmented regression analysis was used to detect pre-intervention trends, post-intervention level changes, and changes in post-intervention trends relative to the pre-intervention trends in the use of these seven drugs, using advertising volume, media hits, and the number of Medicare enrollees as covariates. Data for these variables were obtained from the Center for Medicare and Medicaid Services, Kantar Media, and LexisNexis. Several types of safety actions were associated with reductions in drug users and/or prescription rates, particularly for fentanyl, varenicline, and paroxetine. In most cases, attorney advertising volume rose in conjunction with major safety actions. Attorney advertising volume was positively correlated with prescription rates in five of seven drugs, likely because advertising volume began rising before safety actions, when prescription rates were still increasing. On the other hand, attorney advertising had mixed associations with the number of users per month. Regulatory and safety actions likely reduced the number of users and/or prescription rates for some drugs. Attorneys may have strategically chosen to begin advertising adverse drug events prior to major safety actions, but we found little evidence that attorney advertising reduced drug use. Further research is needed to better understand how consumers and physicians respond to attorney advertising.

Maternal characteristics associated with pregnancy exposure to FDA category C, D, and X drugs in a Canadian population.

PubMed

Yang, Tubao; Walker, Mark C; Krewski, Daniel; Yang, Qiuying; Nimrod, Carl; Garner, Peter; Fraser, William; Olatunbosun, Olufemi; Wen, Shi Wu

2008-03-01

To estimate the frequency of exposure to prescription Food and Drug Administration (FDA) category C, D, and X drugs in pregnant women, and to analyze the maternal characteristics associated with such an exposure. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 was chosen for the study. The rate of exposure to FDA category C, D, or X drugs recorded in the pharmacist database was estimated. Associations of exposure to FDA category C, D, and X drugs with maternal characteristics were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 575 women were included in this study. Among them, 3604 (19.4%) had exposure to one or more FDA category C, D, and X drugs during pregnancy. Category C drugs were the most frequently used drugs (15.8%), followed by D drugs (5.2%), and X drugs (3.9%). Women with chronic health conditions had fourfold at increased risk of exposure than women without. Regardless of health status, women who were <20 years of age, who had a parity > or =3, and who were on social assistance plan were at increased risk of pregnancy exposure to these drugs. About 19.4% pregnant women are exposed to FDA C, D or X drugs during pregnancy. Women with chronic diseases, younger age, increased parity, and under social assistance are at increased risk of exposure to FDA C, D, or X drugs. Copyright 2008 John Wiley & Sons, Ltd.

Food and Drug Administration (FDA) drug approval end points for chronic cutaneous ulcer studies.

PubMed

Eaglstein, William H; Kirsner, Robert S; Robson, Martin C

2012-01-01

The rising costs of caring for chronic cutaneous ulcers (CCUs) and recent appreciation of the mortality of CCUs have led to consideration of the reasons for the failure to have new drug therapies. No new chemical entities to heal CCUs have been approved by the Food and Drug Administration (FDA) in over a decade, in part due to an inability to reach the FDA accepted end point of "complete wound closure." The frequent failure to reach the complete closure end point brings forward the question of the relevance of other healing end points such as improved quality of life, or partial healing. Because CCUs carry a prognosis and mortality rate worse than many cancers, it is reasonable to compare the FDA trial end points for cancer drug approval with those for CCUs. And the difference is quite striking. While there is only one end point for CCUs, there are five surrogate and three direct end points for cancers. In contrast to cancer, surrogate end points and partial healing are not acceptable for therapies aimed at CCUs. For example, making tumors smaller is an acceptable end point, but making CCUs smaller is not and improvement in the signs and symptoms of cancer is an acceptable end point for cancers but not CCUs. As CCUs carry a prognosis and mortality rate worse than many cancers, we believe a reconsideration of end points for CCUs is highly warranted. © 2012 by the Wound Healing Society.

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

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

Patterns of pregnancy exposure to prescription FDA C, D and X drugs in a Canadian population.

PubMed

Wen, S W; Yang, T; Krewski, D; Yang, Q; Nimrod, C; Garner, P; Fraser, W; Olatunbosun, O; Walker, M C

2008-05-01

To examine prescription Food and Drug Administration (FDA) C, D and X drugs in general obstetric population. Historical cohort study. A total of 18 575 women who gave a birth in Saskatchewan between January 1997 and December 2000 were included. Among them, 3604 (19.4%) received FDA C, D or X drugs at least once during pregnancy. The pregnancy exposure rates were 15.8, 5.2 and 3.9%, respectively, for category C, D and X drugs, and were 11.2, 7.3 and 8.2%, respectively, in the first, second and third trimesters. Salbutamol (albuterol), trimethoprim/sulfamethoxazole (co-trimoxazole), ibuprofen, naproxen and oral contraceptives were the most common C, D, X drugs used during pregnancy. About one in every five women uses FDA C, D and X drugs at least once during pregnancy, and the most common prescription drugs in pregnancy are antiasthmatic, antibiotics, nonsteroid anti-inflammation drugs, antianxiety or antidepressants and oral contraceptives.

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

PubMed

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

2015-07-01

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

76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notice; extension of comment...

76 FR 20686 - Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0164] Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

PubMed

Planer, Joseph D; Hulverson, Matthew A; Arif, Jennifer A; Ranade, Ranae M; Don, Robert; Buckner, Frederick S

2014-07-01

An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper) have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's) in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM), a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM), and an antifolate drug (pyrimethamine, EC50 of 3.8 µM) and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

Synergy Testing of FDA-Approved Drugs Identifies Potent Drug Combinations against Trypanosoma cruzi

PubMed Central

Ranade, Ranae M.; Don, Robert; Buckner, Frederick S.

2014-01-01

An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper) have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's) in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM), a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM), and an antifolate drug (pyrimethamine, EC50 of 3.8 µM) and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease. PMID:25033456

Regulatory aspects of oncology drug safety evaluation: past practice, current issues, and the challenge of new drugs.

PubMed

Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M Stacey; McGuinn, W David; Verbois, S Leigh

2010-03-01

The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

Comparison of content of FDA letters not approving applications for new drugs and associated public announcements from sponsors: cross sectional study

PubMed Central

Chahal, Harinder S; Sigelman, Daniel W; Stacy, Sylvie; Sclar, Joshua; Ddamulira, Barbara

2015-01-01

Objectives To describe the content of non-public complete response letters issued by the US Food and Drug Administration (FDA) when they do not approve marketing applications from sponsors (drug companies) and to compare them with the content any subsequent press releases issued by those sponsors Design Cross sectional study. Data sources All applications for which FDA’s Center for Drug Evaluation and Research initially issued complete response letters (n=61) from 11 August 2008 to 27 June 2013. Complete response letters and press releases were divided into discrete statements related to seven domains and 64 subdomains and assessed to determine whether they matched. Results 48% (29) of complete response letters cited deficiencies in both the safety and efficacy domains, and only 13% cited neither safety nor efficacy deficiencies. No press release was issued for 18% (11) of complete response letters, and 21% (13) of press releases did not match any statements from the letters. Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements. Of 32 complete response letters that called for a new clinical trial for safety or efficacy, 59% (19) had matching press release statements. Seven complete response letters reported higher mortality rates in treated participants; only one associated press release mentioned this fact. Conclusions FDA generally issued complete response letters to sponsors for multiple substantive reasons, most commonly related to safety and/or efficacy deficiencies. In many cases, press releases were not issued in response to those letters and, when they were, omitted most of the statements in the complete response letters. Press releases are incomplete substitutes for the detailed information contained in complete response letters. PMID:26063327

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.

Clinical benefit, price and approval characteristics of FDA-approved new drugs for treating advanced solid cancer, 2000-2015.

PubMed

Vivot, A; Jacot, J; Zeitoun, J-D; Ravaud, P; Crequit, P; Porcher, R

2017-05-01

Prices of anti-cancer drugs are skyrocking. We aimed to assess the clinical benefit of new drugs for treating advanced solid tumors at the time of their approval by the US Food and Drug Administration (FDA) and to search for a relation between price and clinical benefit of drugs. We included all new molecular entities and new biologics for treating advanced solid cancer that were approved by the FDA between 2000 and 2015. The clinical benefit of drugs was graded based on FDA medical review of pivotal clinical trials using the 2016-updated of the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Characteristics of drugs and approvals were obtained from publicly available FDA documents and price was evaluated according to US Medicare, US Veterans Health Administration and United Kingdom market systems. The FDA approved 51 new drugs for advanced solid cancer from 2000 to 2015; we could evaluate the value of 37 drugs (73%). By the ESMO-MCBS, five drugs (14%) were grade one (the lowest), nine (24%) grade two, 10 (27%) grade three, 11 (30%) grade four and two (5%) grade five (the highest). Thus, 13 drugs (35%) showed a meaningful clinical benefit (scale levels 4 and 5). By the ASCO-VF which had a range of 3.4-67, the median drug value was 37 (interquartile range 20-52). We found no relationship between clinical benefit and drug price (P = 0.9). No characteristic of drugs and of approval was significantly associated with clinical benefit. Many recently FDA-approved new cancer drugs did not have high clinical benefit as measured by current scales. We found no relation between the price of drugs and benefit to society and patients. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Comparative Assessment of Off-label and Unlicensed Drug Prescriptions in Children: FDA Versus ANSM Guidelines.

PubMed

Berdkan, Sandra; Rabbaa, Lara; Hajj, Aline; Eid, Bassam; Jabbour, Hicham; Osta, Nada El; Karam, Latife; Khabbaz, Lydia Rabbaa

2016-08-01

The main objectives of this study were to assess the incidence of off-label (OL) and/or unlicensed (UL) prescriptions in a sample of pediatric Lebanese patients by using US Food and Drug Administration (FDA) and the French Medical Regulatory Authority (ANSM) regulations. The goal was to analyze the divergences between regulations and to identify those drugs most commonly involved in OL-UL utilization. This study was a retrospective analysis (500 pediatric files) conducted in a Lebanese University hospital in 3 pediatric wards (chronic diseases, acute diseases, and the pediatric intensive care unit). The frequency of OL-UL drug use was significantly different between pediatric wards (P < 0.001), with the highest incidence occurring in the intensive care unit. The most frequent OL-UL prescriptions occurred with cancer (oncology) admissions. Age was significantly related to OL-UL frequency (highest incidence in children aged between 0 and 1 year). The number of drugs prescribed per patient ranged between 1 and 20 (mean [SD], 4.13 [2.6]). The incidence of OL-UL prescriptions was significantly higher in patients treated with a greater number of medicines (P < 0.001). Overall, 58.9% of drug prescriptions were authorized according to ANSM and 50.7% according to FDA regulations; 11.1% (ANSM) and 15.8% (FDA) were UL, and 30.2% (ANSM) and 33.5% (FDA), respectively, were OL use (where OL for the indication were the most common). The highest percentage of OL-UL prescriptions was seen with the following groups: blood and blood-forming organs, genitourinary system, and sex hormones. Divergence between FDA and ANSM was mainly observed for OL medicines. UL prescriptions assessed according to both regulations showed similar results. This study highlights the need for prescribers to continuously examine updates to official regulations to avoid using an OL-UL drug whenever possible. It also calls for better harmonization between worldwide official guidelines concerning drugs used in

Risk management policy and black-box warnings: a qualitative analysis of US FDA proceedings.

PubMed

Cook, Daniel M; Gurugubelli, Rama K; Bero, Lisa A

2009-01-01

The US FDA increasingly applies risk management to drug safety policy. Little is known about the process by which the FDA approves labelling changes. Although advisory committees can recommend any of the risk management tools, including the use of 'black-box warnings', it is unknown whether they deliberate on these questions or how they apply the principles of risk minimization or management during their considerations of drug licensing. To examine the process by which risk management is considered by the FDA, including the role of FDA advisory committees. We also aimed to identify and describe drug labelling changes and additions, including the prevalence of black-box warnings. We electronically obtained publicly available information regarding drug approvals, drug revisions and advisory committee meetings over 3 years (2004-6) from the FDA. Data in the form of meeting transcripts and full histories of labelling changes were collected on drugs discussed by advisory committees. We then searched and qualitatively analysed the meeting transcripts to identify themes in the discussion. We also created a database of all prescription drug labelling changes for 3 years and examined which drugs have had the most changes. We describe the risk management consideration process and report the frequency and characteristics of labelling changes. Excerpts from the transcripts are selected to illustrate both typical and atypical features of the discussion. A total of 174 black-box changes were made in the 3-year period of our study, of which 77 were new black-box warnings and 97 were revisions in black-box warnings. Of 77 new black-box warning additions, only 11 drugs were discussed by the advisory committees. Of the 17 most frequently revised drug labels in these 3 years, two were discussed in the advisory committee meetings. Advisory meeting discussions revealed confusion about black-box warnings and emphasized potential consequences of the warnings rather than their content

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 FDA alert on suicidality and antiepileptic drugs: Fire or false alarm?

PubMed

Hesdorffer, Dale C; Kanner, Andres M

2009-05-01

In January 2008, the U.S. Food and Drug Administration (FDA) issued an alert about an increased risk for suicidality in 199 clinical trials of 11 antiepileptic drugs (AEDs) for three different indications, including epilepsy. An advisory panel voted against a black-box warning on AED labels, and the FDA has accepted this recommendation. We discuss three potential problems with the alert. First, adverse event data were used rather than systematically collected data. Second, the 11 drugs grouped together as a single class of AEDs have different mechanisms of action and very different relative risks, many of which were not statistically significant and some of which were smaller than one. These facts suggest that they should not be grouped as a class. Third, the risk of adverse effects from uncontrolled seizures almost certainly outweighs the small risk of suicidality. We place our comments in the context of a review of the literature on suicidality and depression in epilepsy and the sparse literature on AEDs and suicidality. We recommend that all patients with epilepsy be routinely evaluated for depression, anxiety, and suicidality, and that future clinical trials include validated instruments to systematically assess these conditions to determine whether the possible signal observed by the FDA is real.

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.

A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus.

PubMed

Ekins, Sean; Freundlich, Joel S; Coffee, Megan

2014-01-01

We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.

A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus

PubMed Central

Ekins, Sean; Freundlich, Joel S.; Coffee, Megan

2014-01-01

We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested. PMID:25653841

75 FR 76992 - Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0072] (formerly Docket No. 2005D-0042) Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing at FDA Advisory Committee Meetings; Availability AGENCY: Food and Drug...

The FDA's role in medical device clinical studies of human subjects

NASA Astrophysics Data System (ADS)

Saviola, James

2005-03-01

This paper provides an overview of the United States Food and Drug Administration's (FDA) role as a regulatory agency in medical device clinical studies involving human subjects. The FDA's regulations and responsibilities are explained and the device application process discussed. The specific medical device regulatory authorities are described as they apply to the development and clinical study of retinal visual prosthetic devices. The FDA medical device regulations regarding clinical studies of human subjects are intended to safeguard the rights and safety of subjects. The data gathered in pre-approval clinical studies provide a basis of valid scientific evidence in order to demonstrate the safety and effectiveness of a medical device. The importance of a working understanding of applicable medical device regulations from the beginning of the device development project is emphasized particularly for novel, complex products such as implantable visual prosthetic devices.

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

PubMed

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

2016-06-01

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

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

A Guide to the FDA.

ERIC Educational Resources Information Center

Miller, Annetta K.

The United States Food and Drug Administration (FDA) collects information in seven areas: foods, cosmetics, human drugs, animal drugs and feeds, medical devices, biologics, and electronic radiological products. By using procedures outlined in the Freedom of Information Act, the public may get specific information from such FDA files as inspection…

Data Sets Representative of the Structures and Experimental Properties of FDA-Approved Drugs.

PubMed

Douguet, Dominique

2018-03-08

Presented here are several data sets that gather information collected from the labels of the FDA approved drugs: their molecular structures and those of the described active metabolites, their associated pharmacokinetics and pharmacodynamics data, and the history of their marketing authorization by the FDA. To date, 1852 chemical structures have been identified with a molecular weight less than 2000 of which 492 are or have active metabolites. To promote the sharing of data, the original web server was upgraded for browsing the database and downloading the data sets (http://chemoinfo.ipmc.cnrs.fr/edrug3d). It is believed that the multidimensional chemistry-oriented collections are an essential resource for a thorough analysis of the current drug chemical space. The data sets are envisioned as being used in a wide range of endeavors that include drug repurposing, drug design, privileged structures analyses, structure-activity relationship studies, and improving of absorption, distribution, metabolism, and elimination predictive models.

AACR-FDA-NCI Cancer Biomarkers Collaborative consensus report: advancing the use of biomarkers in cancer drug development.

PubMed

Khleif, Samir N; Doroshow, James H; Hait, William N

2010-07-01

Recent discoveries in cancer biology have greatly increased our understanding of cancer at the molecular and cellular level, but translating this knowledge into safe and effective therapies for cancer patients has proved to be challenging. There is a growing imperative to modernize the drug development process by incorporating new techniques that can predict the safety and effectiveness of new drugs faster, with more certainty, and at lower cost. Biomarkers are central to accelerating the identification and adoption of new therapies, but currently, many barriers impede their use in drug development and clinical practice. In 2007, the AACR-FDA-NCI Cancer Biomarkers Collaborative stepped into the national effort to bring together disparate stakeholders to clearly delineate these barriers, to develop recommendations for integrating biomarkers into the cancer drug development enterprise, and to set in motion the necessary action plans and collaborations to see the promise of biomarkers come to fruition, efficiently delivering quality cancer care to patients.

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

ADHD Medication Use Following FDA Risk Warnings

PubMed Central

Barry, Colleen L.; Martin, Andres; Busch, Susan H.

2013-01-01

Background In 2006, the U.S. Food and Drug Administration (FDA) investigated cardiac and psychiatric risks associated with attention deficit/hyperactivity disorder (ADHD) medication use. Aims of the Study To examine how disclosure of safety risks affected pediatric ADHD use, and to assess news media coverage of the issue to better understand trends in treatment patterns. Methods We used the AHRQ’s Medical Expenditure Panel Survey (MEPS), a nationally representative household panel survey, to calculate unadjusted rates of pediatric ADHD use from 2002 to 2008 overall and by parents’ education. We examined whether children (ages 0 to 20) filled a prescription for any ADHD medication during the calendar year. Next, we used content analysis methods to analyze news coverage of the issue in 10 high-circulation newspapers, the 3 major television networks and a major cable news network in the U.S. We examined 6 measures capturing information conveyed on risk and benefits of ADHD medication use. Results No declines in medication use following FDA safety warnings overall or by parental education level were observed. News media coverage was relatively balanced in its portrayal of the risks and benefits of ADHD medication use by children. Discussion ADHD risk warnings were not associated with large declines in medication use, and balanced news coverage may have contributed to the treatment patterns observed. Self-reported surveys like the MEPS rely on the recall of respondents and may be subject to reporting bias. However, the validity of these data is supported by their consistency with other data on drug use from other sources. Implications for Health Care Provision and Use These findings are in direct contrast to the substantial declines in use observed after pediatric antidepressant risk warnings in the context of a news media environment that emphasized risks over benefits. Implications for Health Policies Our findings are relevant to the ongoing discussion about

Regulating nanomedicine - can the FDA handle it?

PubMed

Bawa, Raj

2011-05-01

There is enormous excitement and expectation surrounding the multidisciplinary field of nanomedicine - the application of nanotechnology to healthcare - which is already influencing the pharmaceutical industry. This is especially true in the design, formulation and delivery of therapeutics. Currently, nanomedicine is poised at a critical stage. However, regulatory guidance in this area is generally lacking and critically needed to provide clarity and legal certainty to manufacturers, policymakers, healthcare providers as well as public. There are hundreds, if not thousands, of nanoproducts on the market for human use but little is known of their health risks, safety data and toxicity profiles. Less is known of nanoproducts that are released into the environment and that come in contact with humans. These nanoproducts, whether they are a drug, device, biologic or combination of any of these, are creating challenges for the Food and Drug Administration (FDA), as regulators struggle to accumulate data and formulate testing criteria to ensure development of safe and efficacious nanoproducts (products incorporating nanoscale technologies). Evidence continues to mount that many nanoproducts inherently posses novel size-based properties and toxicity profiles. Yet, this scientific fact has been generally ignored by the FDA and the agency continues to adopt a precautionary approach to the issue in hopes of countering future potential negative public opinion. As a result, the FDA has simply maintained the status quo with regard to its regulatory policies pertaining to nanomedicine. Therefore, there are no specific laws or mechanisms in place for oversight of nanomedicine and the FDA continues to treat nanoproducts as substantially equivalent ("bioequivalent") to their bulk counterparts. So, for now nanoproducts submitted for FDA review will continue to be subjected to an uncertain regulatory pathway. Such regulatory uncertainty could negatively impact venture funding, stifle

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.

NIEHS/FDA CLARITY-BPA research program update.

PubMed

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

2015-12-01

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

NIEHS/FDA CLARITY-BPA research program update

PubMed Central

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

2016-01-01

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

Consumer Understanding, Preferences, and Responses to Different Versions of Drug Safety Messages in the United States: A Randomized Controlled Trial.

PubMed

McCormack, Lauren; Craig Lefebvre, R; Bann, Carla; Taylor, Olivia; Rausch, Paula

2016-02-01

As part of its mission, the US Food and Drug Administration (FDA) communicates with the public regularly about the benefits and risks of prescription and over-the-counter (OTC) drugs. Effectively communicating risk, however, is a significant public health challenge. To better understand how different populations understand information communicated by the FDA about drug safety, we conducted a randomized experiment to examine comprehension and other measures of effectiveness of drug safety messages that occurred in a post-market surveillance phase. We used an Internet panel survey of 1244 consumers, of whom 58% used prescription drugs in the past year. Half of the sample panel was randomized to read a previous FDA Drug Safety Communication (DSC) with the drug name changed, and the other half was randomized to read a revised version of the same DSC. We examined how making certain modifications to the way drug risk information is communicated has an impact on comprehension and behavioral intentions, including the user's likelihood of discontinuing the drug. We also studied how comprehension varied by respondent characteristics, health literacy skills, risk perceptions, and trust in the message. Based on a five-item comprehension index, the revised version of the message was associated with significantly greater comprehension of the information relative to the standard version (63 vs 52% correct, p < 0.001). Significantly more respondents found the revised version to be clear (82 vs 73%, p < 0.000), while fewer in that group reported learning something new (78% vs 84%, p = 0.015). No significant differences emerged between the two groups in terms of the message being informative, convincing, or helpful. We found no significant differences between the two groups in terms of behavioral intentions, risk perception, and trust. We found that making plain language changes to the DSC significantly increased consumers' level of comprehension of its content, providing support

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis

PubMed Central

Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry

2018-01-01

Background The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. Objective The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. Methods We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between –0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes “Related queries” during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website’s editorial history, which lists all revisions to a given page and the editor’s identity. Results In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC

Sanofi Pharmaceuticals, Inc., et al.; withdrawal of approval of 21 new drug applications and 62 abbreviated new drug applications--FDA. Notice.

PubMed

1998-05-12

The Food and Drug Administration (FDA) is withdrawing approval of 21 new drug applications (NDA's) and 62 abbreviated new drug applications (ANDA's). The holders of the applications notified the agency in writing that the drug products were no longer marketed and requested that the approval of the applications be withdrawn.

RU 486, the FDA and free enterprise.

PubMed

Buc, N L

1992-01-01

The legal question whether RU-486 can meet the standards for US Food and Drug Administration (FDA) approval for a drug indicated for abortion can be answered in the affirmative. Under the Food, Drug, and Cosmetic Act, efficacy must be demonstrated by evidence consisting of adequate and well-controlled investigations to show that a drug is safe and effective for its intended use. The FDA will approve it if on the basis of the clinical trials it could be concluded that the drug will have the effect it purports as prescribed in the labeling, and if the drug is safe. In congressional hearings and in the newspapers the so-called import alert issued by the FDA to prevent the importing of RU-486 under certain circumstances has been publicized. The import alert is no bar to conducting clinical studies in the US under an investigational new drug application (IND) nor is the import alert a bar to the filing and the pursuit of a new drug application (NDA) to allow marketing in the US. The import alert is no bar to anything except importation without an IND or NDA. The real problem is that there is no seller of RU-486 in the US and no sponsor of an NDA offering clinical evidence of safety and efficacy as well as the ability to manufacture the drug and the necessary prostaglandins properly. In additions to abortion, other uses of RU-486 include contraception, breast cancer, and Cushing syndrome. Some limited research could be done under INDs with small supplies of the drug obtained elsewhere on the world market. There are only 2 solutions to this problem. One is that Roussel must change its mind or have its mind changed as the example of the AIDS community showed, which has managed to induce the development of drugs that were impossible 8 or 10 years ago. The other solution is to found a pharmaceutical company that could induce competition for manufacturing RU-486.

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.

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

PubMed

KuKanich, Butch; Warner, Matt; Hahn, Kevin

2017-02-01

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

21 CFR 314.162 - Removal of a drug product from the list.

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 and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.162 - Removal of a drug product from the list.

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 and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.162 - Removal of a drug product from the list.

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 and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.162 - Removal of a drug product from the list.

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 and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.162 - Removal of a drug product from the list.

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 and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

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.

Statistical, epidemiological, and risk-assessment approaches to evaluating safety of vaccines throughout the life cycle at the Food and Drug Administration.

PubMed

Ball, Robert; Horne, Dale; Izurieta, Hector; Sutherland, Andrea; Walderhaug, Mark; Hsu, Henry

2011-05-01

The public health community faces increasing demands for improving vaccine safety while simultaneously increasing the number of vaccines available to prevent infectious diseases. The passage of the US Food and Drug Administration (FDA) Amendment Act of 2007 formalized the concept of life-cycle management of the risks and benefits of vaccines, from early clinical development through many years of use in large numbers of people. Harnessing scientific and technologic advances is necessary to improve vaccine-safety evaluation. The Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research is working to improve the FDA's ability to monitor vaccine safety by improving statistical, epidemiologic, and risk-assessment methods, gaining access to new sources of data, and exploring the use of genomics data. In this article we describe the current approaches, new resources, and future directions that the FDA is taking to improve the evaluation of vaccine safety.

Permitting product liability litigation for FDA-approved drugs and devices promotes patient safety.

PubMed

Kesselheim, A S

2010-06-01

In 2008 and 2009, the Supreme Court reviewed the question of whether patients injured by dangerous prescription drugs or medical devices can bring tort lawsuits against pharmaceutical and device manufacturers. The Court ruled that claims against device manufacturers were preempted while claims against pharmaceutical manufacturers were not. The threat of product liability lawsuits promotes patient safety by encouraging manufacturers to take greater responsibility in providing clear warnings about known adverse effects of their products.

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

Adverse drug event monitoring at the Food and Drug Administration.

PubMed

Ahmad, Syed Rizwanuddin

2003-01-01

The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk.

Adverse Drug Event Monitoring at the Food and Drug Administration

PubMed Central

Ahmad, Syed Rizwanuddin

2003-01-01

The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk. PMID:12534765

A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents

PubMed Central

Madrid, Peter B.; Chopra, Sidharth; Manger, Ian D.; Gilfillan, Lynne; Keepers, Tiffany R.; Shurtleff, Amy C.; Green, Carol E.; Iyer, Lalitha V.; Dilks, Holli Hutcheson; Davey, Robert A.; Kolokoltsov, Andrey A.; Carrion, Ricardo; Patterson, Jean L.; Bavari, Sina; Panchal, Rekha G.; Warren, Travis K.; Wells, Jay B.; Moos, Walter H.; Burke, RaeLyn L.; Tanga, Mary J.

2013-01-01

Background The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. Methodology/Principal Findings A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. Conclusions/Significance The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses. PMID:23577127

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

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

Wang, Kejian, E-mail: kejian.wang.bio@gmail.com; Weng, Zuquan; Sun, Liya

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. Inmore » the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.« less

Dynamic enhancement of drug product labels to support drug safety, efficacy, and effectiveness.

PubMed

Boyce, Richard D; Horn, John R; Hassanzadeh, Oktie; Waard, Anita de; Schneider, Jodi; Luciano, Joanne S; Rastegar-Mojarad, Majid; Liakata, Maria

2013-01-26

Out-of-date or incomplete drug product labeling information may increase the risk of otherwise preventable adverse drug events. In recognition of these concerns, the United States Federal Drug Administration (FDA) requires drug product labels to include specific information. Unfortunately, several studies have found that drug product labeling fails to keep current with the scientific literature. We present a novel approach to addressing this issue. The primary goal of this novel approach is to better meet the information needs of persons who consult the drug product label for information on a drug's efficacy, effectiveness, and safety. Using FDA product label regulations as a guide, the approach links drug claims present in drug information sources available on the Semantic Web with specific product label sections. Here we report on pilot work that establishes the baseline performance characteristics of a proof-of-concept system implementing the novel approach. Claims from three drug information sources were linked to the Clinical Studies, Drug Interactions, and Clinical Pharmacology sections of the labels for drug products that contain one of 29 psychotropic drugs. The resulting Linked Data set maps 409 efficacy/effectiveness study results, 784 drug-drug interactions, and 112 metabolic pathway assertions derived from three clinically-oriented drug information sources (ClinicalTrials.gov, the National Drug File - Reference Terminology, and the Drug Interaction Knowledge Base) to the sections of 1,102 product labels. Proof-of-concept web pages were created for all 1,102 drug product labels that demonstrate one possible approach to presenting information that dynamically enhances drug product labeling. We found that approximately one in five efficacy/effectiveness claims were relevant to the Clinical Studies section of a psychotropic drug product, with most relevant claims providing new information. We also identified several cases where all of the drug-drug

Larval Zebrafish Model for FDA-Approved Drug Repositioning for Tobacco Dependence Treatment

PubMed Central

Cousin, Margot A.; Ebbert, Jon O.; Wiinamaki, Amanda R.; Urban, Mark D.; Argue, David P.; Ekker, Stephen C.; Klee, Eric W.

2014-01-01

Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA) may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation. PMID:24658307

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

FDA recognition of consensus standards in the premarket notification program.

PubMed

Marlowe, D E; Phillips, P J

1998-01-01

"The FDA has long advocated the use of standards as a significant contributor to safety and effectiveness of medical devices," Center for Devices and Radiological Health's (CDRH) Donald E. Marlowe and Philip J. Phillips note in the following article, highlighting the latest U.S. Food and Drug Administration (FDA) plans for use of standards. They note that the important role standards can play has been reinforced as part of FDA reengineering efforts undertaken in anticipation of an increased regulatory work-load and declining agency resources. As part of its restructuring effort, the FDA announced last spring that it would recognize some consensus standards for use in the device approval process. Under the new 510(k) paradigm--the FDA's proposal to streamline premarket review, which includes incorporating the use of standards in the review of 510(k) submissions--the FDA will accept proof of compliance with standards as evidence of device safety and effectiveness. Manufacturers may submit declarations of conformity to standards instead of following the traditional review process. The International Electrotechnical Commission (IEC) 60601 series of consensus standards, which deals with many safety issues common to electrical medical devices, was the first to be chosen for regulatory review. Other standards developed by nationally or internationally recognized standards development organizations, such as AAMI, may be eligible for use to ensure review requirements. In the following article, Marlowe and Phillips describe the FDA's plans to use standards in the device review process. The article focuses on the use of standards for medical device review, the development of the standards recognition process for reviewing devices, and the anticipated benefits of using standards to review devices. One important development has been the recent implementation of the FDA Modernization Act of 1997 (FDAMA), which advocates the use of standards in the device review process. In

Dynamic enhancement of drug product labels to support drug safety, efficacy, and effectiveness

PubMed Central

2013-01-01

Out-of-date or incomplete drug product labeling information may increase the risk of otherwise preventable adverse drug events. In recognition of these concerns, the United States Federal Drug Administration (FDA) requires drug product labels to include specific information. Unfortunately, several studies have found that drug product labeling fails to keep current with the scientific literature. We present a novel approach to addressing this issue. The primary goal of this novel approach is to better meet the information needs of persons who consult the drug product label for information on a drug’s efficacy, effectiveness, and safety. Using FDA product label regulations as a guide, the approach links drug claims present in drug information sources available on the Semantic Web with specific product label sections. Here we report on pilot work that establishes the baseline performance characteristics of a proof-of-concept system implementing the novel approach. Claims from three drug information sources were linked to the Clinical Studies, Drug Interactions, and Clinical Pharmacology sections of the labels for drug products that contain one of 29 psychotropic drugs. The resulting Linked Data set maps 409 efficacy/effectiveness study results, 784 drug-drug interactions, and 112 metabolic pathway assertions derived from three clinically-oriented drug information sources (ClinicalTrials.gov, the National Drug File – Reference Terminology, and the Drug Interaction Knowledge Base) to the sections of 1,102 product labels. Proof-of-concept web pages were created for all 1,102 drug product labels that demonstrate one possible approach to presenting information that dynamically enhances drug product labeling. We found that approximately one in five efficacy/effectiveness claims were relevant to the Clinical Studies section of a psychotropic drug product, with most relevant claims providing new information. We also identified several cases where all of the drug-drug

Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters.

PubMed

Kim, Hyosun

2015-08-25

For the purpose of understanding the Food and Drug Administration's (FDA's) concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs) and warning letters issued by the FDA to pharmaceutical manufacturers. The FDA's warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014) regarding online promotional activities, were content-analyzed. Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA) of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the FDA has thus begun to keep tabs on social media promotions of

FDA direct-to-consumer advertising for prescription drugs: what are consumer preferences and response tendencies?

PubMed

Khanfar, Nile; Loudon, David; Sircar-Ramsewak, Feroza

2007-01-01

The effect of direct-to-consumer (DTC) television advertising of prescription medications is a growing concern of the United States (U.S.) Congress, state legislatures, and the Food and Drug Administration (FDA). This research study was conducted in order to examine consumers' perceived preferences of DTC television advertisement in relation to "reminder" "help-seeking," and "product-claim" FDA-approved advertisement categories. An additional objective was to examine the influence of DTC television advertising of prescription drugs on consumers' tendency to seek more information about the medication and/or the medical condition. The research indicates that DTC television drug ads appear to be insufficient for consumers to make informed decisions. Their mixed perception and acceptance of the advertisements seem to influence them to seek more information from a variety of medical sources.

Association between change of health care providers and pregnancy exposure to FDA category C, D and X drugs.

PubMed

Yang, Jianzhou; Xie, Rihua; Krewski, Daniel; Wang, Yongjin; Walker, Mark; Cao, Wenjun; Wen, Shi Wu

2014-01-01

Changing health care providers frequently breaks the continuity of care, which is associated with many health care problems. The purpose of this study was to examine the association between a change of health care providers and pregnancy exposure to FDA category C, D and X drugs. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 were chosen for this study. The association between the number of changes in health care providers and with pregnancy exposure to category C, D, and X drugs for those women with and without chronic diseases were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 568 women were included in this study. Rates of FDA C, D, and X drug uses were 14.35%, 17.07%, 21.72%, and 31.14%, in women with no change of provider, 1-2 changes, 3-5 changes, and more than 5 changes of health care providers. An association between the number of changes of health care providers and pregnancy exposure to FDA C, D, and X drugs existed in women without chronic diseases but not in women with chronic disease. Change of health care providers is associated with pregnancy exposure to FDA category C, D and X drugs in women without chronic diseases.

Impact of the 2011 FDA transvaginal mesh safety update on AUGS members' use of synthetic mesh and biologic grafts in pelvic reconstructive surgery.

PubMed

Clemons, Jeffrey L; Weinstein, Milena; Guess, Marsha K; Alperin, Marianna; Moalli, Pamela; Gregory, William Thomas; Lukacz, Emily S; Sung, Vivian W; Chen, Bertha H; Bradley, Catherine S

2013-01-01

To describe the frequency of use and recent change in use of synthetic mesh and biologic grafts in pelvic organ prolapse (POP) and stress urinary incontinence surgery by American Urogynecology Society (AUGS) members. An electronic survey of AUGS members was conducted between December 2011 and January 2012. Frequency of graft use in POP (overall and by transvaginal and transabdominal approaches) and stress urinary incontinence surgery was queried relative to the timing of the 2011 Food and Drug Administration (FDA) safety update. Rates of materials' use before and after the statement were compared using Wilcoxon signed rank test. Fifty-three percent (507/962) of AUGS members responded and were included in analysis; 79% were urogynecologists. Before the FDA warning, in POP surgery, most (90%) used synthetic mesh and fewer (34%) used biologic grafts; 99% used synthetic mesh slings. After the FDA statement, respondents reported an overall decrease in the percent of POP cases in which they used synthetic mesh (P < 0.001) but no change in biologic graft use for POP (P = 0.37) or synthetic mesh sling use (P = 0.10). Specifically, transvaginal mesh use decreased: 40% reported decreased use and 12% stopped use. However, transvaginal mesh was still used by 61% of respondents in at least some cases. No change (62%) or increased use (12%) of mesh was reported for transabdominal POP procedures. Synthetic mesh use in transvaginal POP surgery decreased after the 2011 FDA safety update, but synthetic mesh use for transabdominal POP repair and sling procedures and overall biologic graft use in POP surgery did not decrease.

75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

Revisiting financial conflicts of interest in FDA advisory committees.

PubMed

Pham-Kanter, Genevieve

2014-09-01

The Food and Drug Administration (FDA) Safety and Innovation Act has recently relaxed conflict-of-interest rules for FDA advisory committee members, but concerns remain about the influence of members' financial relationships on the FDA's drug approval process. Using a large newly available data set, this study carefully examined the relationship between the financial interests of FDA Center for Drug Evaluation and Research (CDER) advisory committee members and whether members voted in a way favorable to these interests. The study used a data set of voting behavior and reported financial interests of 1,379 FDA advisory committee members who voted in CDER committee meetings that were convened during the 15-year period of 1997-2011. Data on 1,168 questions and 15,739 question-votes from 379 meetings were used in the analyses. Multivariable logit models were used to estimate the relationship between committee members' financial interests and their voting behavior. Individuals with financial interests solely in the sponsoring firm were more likely to vote in favor of the sponsor than members with no financial ties (OR = 1.49, p = 0.03). Members with interests in both the sponsoring firm and its competitors were no more likely to vote in favor of the sponsor than those with no financial ties to any potentially affected firm (OR = 1.16, p = 0.48). Members who served on advisory boards solely for the sponsor were significantly more likely to vote in favor of the sponsor (OR = 4.97, p = 0.005). There appears to be a pro-sponsor voting bias among advisory committee members who have exclusive financial relationships with the sponsoring firm but not among members who have nonexclusive financial relationships (ie, those with ties to both the sponsor and its competitors). These findings point to important heterogeneities in financial ties and suggest that policymakers will need to be nuanced in their management of financial relationships of FDA advisory committee members. �

THE IMPACT OF EMERGING SAFETY AND EFFECTIVENESS EVIDENCE ON THE USE OF PHYSICIAN-ADMINISTERED DRUGS: THE CASE OF BEVACIZUMAB FOR BREAST CANCER

PubMed Central

Conti, Rena M.; Dusetzina, Stacie B.; Herbert, Ann C.; Berndt, Ernst R.; Huskamp, Haiden A.; Keating, Nancy L.

2014-01-01

Background Spending on physician-administered drugs is high and uses not approved by the U.S. Food and Drug Administration (FDA) are frequent. While these drugs may be targets of future policy efforts to rationalize use, little is known regarding how physicians respond to emerging safety and effectiveness evidence. Study objective We analyzed changes in bevacizumab (Avastin™) use for breast cancer in response to its market launch (Feb-2008), two FDA meetings reviewing data suggesting that its risks exceed its benefits (July-2010, June-2011), and the FDA’s withdrawal of approval (Nov-2011). Data Data from a population-based audit of oncologists’ prescribing (IntrinsiQ Intellidose) were used to measure the monthly number of breast cancer patients treated with bevacizumab January, 2008-April,2012. Methods The number of bevacizumab patients following each regulatory action was estimated using negative binomial regression, compared with patients before the first FDA meeting, adjusting for cancer stage, treatment line, patient age and outpatient office affiliation. Results Bevacizumab use for breast cancer increased significantly after FDA approval. Following all regulatory actions, there was a 65% decline (95%CI=64%-65%) in use compared with the period before the first meeting. The largest decline was in the six-month period following the first meeting (37%, 95%CI=28%-47%). The rate of decline did not differ by patient or cancer characteristics and differed minimally by office affiliation. Discussion Bevacizumab use for breast cancer declined dramatically after FDA meetings and regulatory actions, a period without changes in guideline recommendations or insurance coverage. Physicians appear responsive to emerging evidence concerning physician-administered drug safety and effectiveness. PMID:23604014

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.

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

FDA's Approach to Regulating Biosimilars.

PubMed

Lemery, Steven J; Ricci, M Stacey; Keegan, Patricia; McKee, Amy E; Pazdur, Richard

2017-04-15

The Biologics Price Competition and Innovation (BPCI) Act, enacted as part of the Affordable Care Act, created a new licensure pathway for biological products demonstrated to be biosimilar with or interchangeable with an FDA-licensed biological product (the "reference product"). The FDA's approach to the regulation of biosimilars is based on the requirements set forth in the BPCI Act. A biosimilar product is highly similar to the reference product, notwithstanding minor differences in clinically inactive components, and there are no clinically meaningful differences between products in terms of safety, purity, and potency. The foundation of a biosimilar development program is an analytic similarity assessment that directly compares the structural/physiochemical and functional properties of the proposed biosimilar with the reference product. Data from clinical studies, which include an assessment of immunogenicity and pharmacokinetics/pharmacodynamics, are used to assess for clinically meaningful differences and not to independently establish the safety and effectiveness of the biosimilar. Like all products that the FDA regulates, the FDA requires that biosimilar products meet the agency's rigorous standards of safety and efficacy for approval. That means patients and health care professionals are able to rely upon the safety and effectiveness of biosimilar products in the same manner as for the reference product. Clin Cancer Res; 23(8); 1882-5. ©2016 AACR . ©2016 American Association for Cancer Research.

78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

...: Food and Drug Administration, HHS. ACTION: Notification of public meeting; request for comments. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing a public meeting regarding FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket Nos...

Trends in internet search activity, media coverage, and patient-centered health information after the FDA safety communications on surgical mesh for pelvic organ prolapse.

PubMed

Stone, Benjamin V; Forde, James C; Levit, Valerie B; Lee, Richard K; Te, Alexis E; Chughtai, Bilal

2016-11-01

In July 2011, the US Food and Drug Administration (FDA) issued a safety communication regarding serious complications associated with surgical mesh for pelvic organ prolapse, prompting increased media and public attention. This study sought to analyze internet search activity and news article volume after this FDA warning and to evaluate the quality of websites providing patient-centered information. Google Trends™ was utilized to evaluate search engine trends for the term "pelvic organ prolapse" and associated terms between 1 January 2004 and 31 December 2014. Google News™ was utilized to quantify the number of news articles annually under the term "pelvic organ prolapse." The search results for the term "pelvic organ prolapse" were assessed for quality using the Health On the Net Foundation (HON) certification. There was a significant increase in search activity from 37.42 in 2010 to 57.75 in 2011, at the time of the FDA communication (p = 0.021). No other annual interval had a statistically significant increase in search activity. The single highest monthly search activity, given the value of 100, was August 2011, immediately following the July 2011 notification, with the next highest value being 98 in July 2011. Linear regression analysis of news articles per year since the FDA communication revealed r 2  = 0.88, with a coefficient of 186. Quality assessment demonstrated that 42 % of websites were HON-certified, with .gov sites providing the highest quality information. Although the 2011 FDA safety communication on surgical mesh was associated with increased public and media attention, the quality of relevant health information on the internet remains of poor quality. Future quality assurance measures may be critical in enabling patients to play active roles in their own healthcare.

Petitioning the FDA to Improve Pharmaceutical, Device and Public Health Safety by Ordinary Citizens: A Descriptive Analysis

PubMed Central

Yang, Y. Tony; Cheng, Xi; Bian, John; Bennett, Charles L.

2016-01-01

The United States Constitution protects the right of citizens to petition the government for “a redress of grievances.” This right has important implications for citizens desiring to advance the public health by petitioning administrative agencies, such as the Food and Drug Administration, to take safety actions. We examined a total of 1,915 petitions filed between 2001 and 2013 to investigate the outcomes of citizen petitions that address public health concerns. We found that most petitions were filed by manufacturers against other manufacturers. Only 346 (18%) of all petitions were submitted by individuals and non-profit organizations, and 178 (87.3%) of these petitions with a final response were denied. On average, these petitions required 2.85 years for a final agency decision, and many decisions remain pending 10–13 years after their initial submission. The great majority of the approved requests included some form of risk communication, such as labeling changes, boxed warnings or placement of a drug into a Risk Evaluation and Mitigation Strategy. As a policy instrument to improve the safety of medical and food products, the citizen petition process requires sophisticated legal and scientific expertise, and may not represent a viable route for ordinary citizens to petition the FDA to “redress grievances.” PMID:27171162

Petitioning the FDA to Improve Pharmaceutical, Device and Public Health Safety by Ordinary Citizens: A Descriptive Analysis.

PubMed

Chen, Brian K; Yang, Y Tony; Cheng, Xi; Bian, John; Bennett, Charles L

2016-01-01

The United States Constitution protects the right of citizens to petition the government for "a redress of grievances." This right has important implications for citizens desiring to advance the public health by petitioning administrative agencies, such as the Food and Drug Administration, to take safety actions. We examined a total of 1,915 petitions filed between 2001 and 2013 to investigate the outcomes of citizen petitions that address public health concerns. We found that most petitions were filed by manufacturers against other manufacturers. Only 346 (18%) of all petitions were submitted by individuals and non-profit organizations, and 178 (87.3%) of these petitions with a final response were denied. On average, these petitions required 2.85 years for a final agency decision, and many decisions remain pending 10-13 years after their initial submission. The great majority of the approved requests included some form of risk communication, such as labeling changes, boxed warnings or placement of a drug into a Risk Evaluation and Mitigation Strategy. As a policy instrument to improve the safety of medical and food products, the citizen petition process requires sophisticated legal and scientific expertise, and may not represent a viable route for ordinary citizens to petition the FDA to "redress grievances."

75 FR 48352 - Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The... were not withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA... approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the...

Impact of the FDA warning of potential ceftriaxone and calcium interactions on drug use policy in clinical practice.

PubMed

Esterly, John S; Steadman, Emily; Scheetz, Marc H

2011-06-01

In September 2007, the FDA issued an alert recommending that ceftriaxone and calcium-containing solutions should not be administered to any patient within 48 h of each other. Due to the widespread use of ceftriaxone, significant concern was expressed by the greater healthcare community about the warning, which the FDA eventually retracted in April of 2009. We sought to quantify the impact of the warning on healthcare institutions. A survey was administered to the membership of the Society of Infectious Diseases Pharmacists to quantify perceived changes in ceftriaxone use among healthcare institutions across the United States. A survey of Infectious Diseases experts was conducted. Participants were queried for hospital policies/drug use statistics during two times: immediately after the FDA warning and approximately 13 months post warning (preceding the FDA retraction). Related changes in formulary, drug-use policy, and the number of employee hours that were devoted to addressing the FDA warning were assessed. Ninety-four surveys representing 94 hospital systems were included in the analysis. Approximately half (n = 49, 52%) of respondent institutions enacted at least one drug-use policy change based on the warning; one institution removed ceftriaxone from a clinical protocol. Institutions' final interpretations of the warning differed slightly from initial understanding of the warning, and there was an overall minor decrease in the perceived use of ceftriaxone. The majority of those surveyed (n = 70, 74%) estimated that their respective institutions devoted between 1 and 49 employee hours to address the warning. Hospitals with ID pharmacists had minimal changes to ceftriaxone use after the 2007 FDA warning. Specialized pharmacists may be uniquely situated to help hospitals interpret global recommendations locally.

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.

State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines.

PubMed

Dawidczyk, Charlene M; Kim, Chloe; Park, Jea Ho; Russell, Luisa M; Lee, Kwan Hyi; Pomper, Martin G; Searson, Peter C

2014-08-10

The ability to efficiently deliver a drug to a tumor site is dependent on a wide range of physiologically imposed design constraints. Nanotechnology provides the possibility of creating delivery vehicles where these design constraints can be decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing targeting efficiency and efficacy. Here we review the design strategies of the two FDA-approved antibody-drug conjugates (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and Abraxane) in the context of the challenges associated with systemic targeted delivery of a drug to a solid tumor. The lessons learned from these nanomedicines provide an important insight into the key challenges associated with the development of new platforms for systemic delivery of anti-cancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

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)

Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

PubMed

Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

2018-01-05

The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the

New initiatives for pharmacovigilance in South Korea: introducing the Korea Institute of Drug Safety and Risk Management (KIDS).

PubMed

Shin, Ju-Young; Jung, Sun-Young; Ahn, So-Hyeon; Lee, Shin Haeng; Kim, Su-Jin; Seong, Jong-Mi; Chung, Soo-Youn; Park, Byung-Joo

2014-11-01

Pharmacovigilance plays a vital role in ensuring that patients receive appropriate medical products that are safe and effective. This paper aims to describe the history of pharmacovigilance in Korea and introduce the establishment and goal of the KIDS. In Korea, the adverse drug reactions (ADR) reporting system was launched in 1988 by the Korea Ministry of Food and Drug Safety (MFDS) and spontaneous ADR reports have been collected from health care professionals and the general public. Although the ADR reporting system has begun, the reporting rate was very low in the first 10 years, and safety actions were done passively in response to the US Food and Drug Administration (FDA) or European Medicines Agency (EMA)'s safety alert and communications. Therefore, the Korea Institute of Drug Safety and Risk Management (KIDS) was established in April 2012 as a new initiative for pharmacovigilance. The KIDS will continue to contribute to the improvement of Korean pharmacovigilance by collecting, managing, and analyzing consumer-centered drug safety information. Copyright © 2014 John Wiley & Sons, Ltd.

Network Analysis of Drug-target Interactions: A Study on FDA-approved New Molecular Entities Between 2000 to 2015.

PubMed

Lin, Hui-Heng; Zhang, Le-Le; Yan, Ru; Lu, Jin-Jian; Hu, Yuanjia

2017-09-25

The U.S. Food and Drug Administration (FDA) approves new drugs every year. Drug targets are some of the most important interactive molecules for drugs, as they have a significant impact on the therapeutic effects of drugs. In this work, we thoroughly analyzed the data of small molecule drugs approved by the U.S. FDA between 2000 and 2015. Specifically, we focused on seven classes of new molecular entity (NME) classified by the anatomic therapeutic chemical (ATC) classification system. They were NMEs and their corresponding targets for the cardiovascular system, respiratory system, nerve system, general anti-infective systemic, genito-urinary system and sex hormones, alimentary tract and metabolisms, and antineoplastic and immunomodulating agents. To study the drug-target interaction on the systems level, we employed network topological analysis and multipartite network projections. As a result, the drug-target relations of different kinds of drugs were comprehensively characterized and global pictures of drug-target, drug-drug, and target-target interactions were visualized and analyzed from the perspective of network models.

78 FR 17933 - Determination That BENADRYL (diphenhydramine hydrochloride) Injection and Two Other Drug Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

... Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... effectiveness. This determination means that FDA will not begin procedures to withdraw approval of abbreviated... withdraws or suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness, or if FDA...

ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy.

PubMed

Ottesen, Eric W

2017-01-01

Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children and infants. SMA is caused by deletions or mutations of Survival Motor Neuron 1 ( SMN1 ) gene. SMN2 , a nearly identical copy of SMN1 , cannot compensate for the loss of SMN1 due to predominant skipping of exon 7. While various regulatory elements that modulate SMN2 exon 7 splicing have been proposed, intronic splicing silencer N1 (ISS-N1) has emerged as the most promising target thus far for antisense oligonucleotide-mediated splicing correction in SMA. Upon procuring exclusive license from the University of Massachussets Medical School in 2010, Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical development of Spinraza ™ (synonyms: Nusinersen, IONIS-SMN RX , ISIS-SMN RX ), an antisense drug based on ISS-N1 target. Spinraza ™ showed very promising results at all steps of the clinical development and was approved by US Food and Drug Administration (FDA) on December 23, 2016. Spinraza ™ is the first FDA-approved treatment for SMA and the first antisense drug to restore expression of a fully functional protein via splicing correction. The success of Spinraza ™ underscores the potential of intronic sequences as promising therapeutic targets and sets the stage for further improvement of antisense drugs based on advanced oligonucleotide chemistries and delivery protocols.

ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy

PubMed Central

Ottesen, Eric W.

2017-01-01

Abstract Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children and infants. SMA is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, cannot compensate for the loss of SMN1 due to predominant skipping of exon 7. While various regulatory elements that modulate SMN2 exon 7 splicing have been proposed, intronic splicing silencer N1 (ISS-N1) has emerged as the most promising target thus far for antisense oligonucleotide-mediated splicing correction in SMA. Upon procuring exclusive license from the University of Massachussets Medical School in 2010, Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical development of Spinraza™ (synonyms: Nusinersen, IONIS-SMNRX, ISIS-SMNRX), an antisense drug based on ISS-N1 target. Spinraza™ showed very promising results at all steps of the clinical development and was approved by US Food and Drug Administration (FDA) on December 23, 2016. Spinraza™ is the first FDA-approved treatment for SMA and the first antisense drug to restore expression of a fully functional protein via splicing correction. The success of Spinraza™ underscores the potential of intronic sequences as promising therapeutic targets and sets the stage for further improvement of antisense drugs based on advanced oligonucleotide chemistries and delivery protocols. PMID:28400976

21 CFR 5.1110 - FDA public information offices.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA public information offices. 5.1110 Section 5.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ORGANIZATION Organization § 5.1110 FDA public information offices. (a) Division of Dockets Management. The...

21 CFR 5.1110 - FDA public information offices.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA public information offices. 5.1110 Section 5.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ORGANIZATION Organization § 5.1110 FDA public information offices. (a) Division of Dockets Management. The...

21 CFR 5.1110 - FDA public information offices.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA public information offices. 5.1110 Section 5.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ORGANIZATION Organization § 5.1110 FDA public information offices. (a) Division of Dockets Management. The...

21 CFR 5.1110 - FDA public information offices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA public information offices. 5.1110 Section 5.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ORGANIZATION Organization § 5.1110 FDA public information offices. (a) Division of Dockets Management. The...

21 CFR 5.1110 - FDA public information offices.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA public information offices. 5.1110 Section 5.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ORGANIZATION Organization § 5.1110 FDA public information offices. (a) Division of Dockets Management. The...

Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme.

PubMed

Ourso, André

2012-01-01

Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety.

Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice.

PubMed

Li, Chunfeng; Zhu, Xingliang; Ji, Xue; Quanquin, Natalie; Deng, Yong-Qiang; Tian, Min; Aliyari, Roghiyh; Zuo, Xiangyang; Yuan, Ling; Afridi, Shabbir Khan; Li, Xiao-Feng; Jung, Jae U; Nielsen-Saines, Karin; Qin, Frank Xiao-Feng; Qin, Cheng-Feng; Xu, Zhiheng; Cheng, Genhong

2017-10-01

Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public. Copyright © 2017. Published by Elsevier B.V.

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

Can Disproportionality Analysis of Post-marketing Case Reports be Used for Comparison of Drug Safety Profiles?

PubMed

Michel, Christiane; Scosyrev, Emil; Petrin, Michael; Schmouder, Robert

2017-05-01

Clinical trials usually do not have the power to detect rare adverse drug reactions. Spontaneous adverse reaction reports as for example available in post-marketing safety databases such as the FDA Adverse Event Reporting System (FAERS) are therefore a valuable source of information to detect new safety signals early. To screen such large data-volumes for safety signals, data-mining algorithms based on the concept of disproportionality have been developed. Because disproportionality analysis is based on spontaneous reports submitted for a large number of drugs and adverse event types, one might consider using these data to compare safety profiles across drugs. In fact, recent publications have promoted this practice, claiming to provide guidance on treatment decisions to healthcare decision makers. In this article we investigate the validity of this approach. We argue that disproportionality cannot be used for comparative drug safety analysis beyond basic hypothesis generation because measures of disproportionality are: (1) missing the incidence denominators, (2) subject to severe reporting bias, and (3) not adjusted for confounding. Hypotheses generated by disproportionality analyses must be investigated by more robust methods before they can be allowed to influence clinical decisions.

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.

Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

NASA Technical Reports Server (NTRS)

Das, H.; Daniels, V. R.; Vaksman, Z.; Boyd, J. L.; Buckey, J. C.; Locke, J. P.; Putcha, L.

2007-01-01

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training

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

Examination of pharmacists' intention to report serious adverse drug events (ADEs) to the FDA using the theory of planned behavior.

PubMed

Gavaza, Paul; Brown, Carolyn M; Lawson, Kenneth A; Rascati, Karen L; Wilson, James P; Steinhardt, Mary

2011-12-01

Adverse drug event (ADE) reporting by pharmacists is an indispensable part of the drug safety system. U.S. pharmacists may submit reports of serious ADEs that they encounter to the Food and Drug Administration (FDA) through MedWatch. However, underreporting of serious ADEs is a common problem. Little is known about pharmacists' decision making with respect to ADE reporting. This study explored the utility of the theory of planned behavior (TPB) model in predicting Texas pharmacists' intention to report serious ADEs to the FDA. Data were collected from practicing Texas pharmacists using a mail questionnaire. A total of 1500 surveys were mailed, and 377 usable responses were obtained for a response rate of 26.4%. A majority (70.2%) of the 377 respondents were white/Caucasian, and 52.9% were male. Overall, pharmacists intended to report serious ADEs (mean=15.87±4.22; possible range: 3-21), had a positive attitude toward reporting (mean=4.62±4.92; possible range: -15 to +15), perceived that important others wanted them to report (subjective norm [SN] score=5.65±2.99; possible range: -9 to +9), and believed that they had control over their reporting behavior (perceived behavioral control [PBC] score=3.54±2.69; possible/actual range: -6 to +6). Attitude (β=0.221, P<.001) and SN (β=0.438, P<.001) significantly predicted intent; however, PBC (β=0.028, P>.05) did not. Attitude, SN, and PBC together accounted for 34.0% of the variance in intention to report serious ADEs (P<.001). The addition of past reporting behavior (P=.021) and perceived moral obligation (P<.001) significantly increased the variance in intention explained by the TPB model. Pharmacists showed a strong positive intent to report serious ADEs to the FDA. Strategies to increase pharmacists' intentions to report serious ADEs should focus on helping them see the value of reporting and altering their perception of social pressure toward reporting. The TPB may have utility in predicting ADE

76 FR 1180 - FDA Transparency Initiative: Improving Transparency to Regulated Industry

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

...] FDA Transparency Initiative: Improving Transparency to Regulated Industry AGENCY: Food and Drug... the Transparency Initiative, the Food and Drug Administration (FDA) is announcing the availability of a report entitled ``FDA Transparency Initiative: Improving Transparency to Regulated Industry.'' The...

FDA's proposed rules on patent listing requirements for new drug and 30-month stays on ANDA approval (proposed Oct. 24, 2002).

PubMed

Hui, Yuk Fung

2003-01-01

In order to close the loophole in the generic drug approval process that allows a brand name drug patent holder to delay or defeat generic drug application merely by technicality, the FDA recently proposed to modify its regulations. Those proposals affect the patent listing requirements of a new drug application, and the duration of time that a generic drug application could be put on hold in the event of a patent infringement suit. With the modified rules, the FDA expects to see an increase in the availability of generic drugs, which eventually will lead to lower drug costs. Ms. Hui discusses the contents of the proposed regulations and provides an analysis of the proposed rule's legal authority, implications on patent rights, and impact on the pharmaceutical industry.

Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies.

PubMed

Palos, Isidro; Lara-Ramirez, Edgar E; Lopez-Cedillo, Julio Cesar; Garcia-Perez, Carlos; Kashif, Muhammad; Bocanegra-Garcia, Virgilio; Nogueda-Torres, Benjamin; Rivera, Gildardo

2017-06-18

Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi , which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate) and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin) showed better trypanocidal effects (LC 50 range 15.8-26.1 μg/mL) in comparison with benznidazole and nifurtimox (LC 50 range 33.1-46.7 μg/mL). A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90-60%) at 6 h, but this was low compared to benznidazole (50%). This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents.

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

The Pharmaceutical Industry in 2016. An Analysis of FDA Drug Approvals from a Perspective of the Molecule Type.

PubMed

Torre, Beatriz G de la; Albericio, Fernando

2017-02-27

This is an analysis from a chemical point of view of the 22 drugs accepted by the FDA during 2016. The different drugs from the 2016 "harvest" have been classified according to their chemical structure: antibodies; TIDES (oligonucleotides and peptides); amino acids and natural products; drug combination; and small molecules.

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...

Structure-activity relationship for FDA approved drugs as inhibitors of the human sodium taurocholate cotransporting polypeptide (NTCP).

PubMed

Dong, Zhongqi; Ekins, Sean; Polli, James E

2013-03-04

The hepatic bile acid uptake transporter sodium taurocholate cotransporting polypeptide (NTCP) is less well characterized than its ileal paralog, the apical sodium dependent bile acid transporter (ASBT), in terms of drug inhibition requirements. The objectives of this study were (a) to identify FDA approved drugs that inhibit human NTCP, (b) to develop pharmacophore and Bayesian computational models for NTCP inhibition, and (c) to compare NTCP and ASBT transport inhibition requirements. A series of NTCP inhibition studies were performed using FDA approved drugs, in concert with iterative computational model development. Screening studies identified 27 drugs as novel NTCP inhibitors, including irbesartan (Ki = 11.9 μM) and ezetimibe (Ki = 25.0 μM). The common feature pharmacophore indicated that two hydrophobes and one hydrogen bond acceptor were important for inhibition of NTCP. From 72 drugs screened in vitro, a total of 31 drugs inhibited NTCP, while 51 drugs (i.e., more than half) inhibited ASBT. Hence, while there was inhibitor overlap, ASBT unexpectedly was more permissive to drug inhibition than was NTCP, and this may be related to NTCP possessing fewer pharmacophore features. Findings reflected that a combination of computational and in vitro approaches enriched the understanding of these poorly characterized transporters and yielded additional chemical probes for possible drug-transporter interaction determinations.

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.

A pre-marketing ALT signal predicts post-marketing liver safety.

PubMed

Moylan, Cynthia A; Suzuki, Ayako; Papay, Julie I; Yuen, Nancy A; Ames, Michael; Hunt, Christine M

2012-08-01

Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-marketing clinical trials predicted post-marketing hepatotoxicity. Incidence of ALT elevations (ALT ≥ 3 times upper limits normal [× ULN]) for drug and placebo of new chemical entities and approved drugs associated with hepatotoxicity was calculated using the Food and Drug Administration (FDA) website. Post-marketing liver safety events were identified using the FDA Adverse Event Reporting System (AERS). The association of FDA AERS signal score (EB05 ≥ 2) and excess risk of pre-marketing ALT elevation (difference in incidence of ALT ≥ 3× ULN in treated versus placebo) was examined. An ALT signal of ≥ 1.2% was significantly associated with a post-marketing liver safety signal (p ≤ 0.013) and a 71.4% positive predictive value. An absent ALT signal was associated with a high likelihood of post-marketing liver safety; negative predictive value of 89.7%. Daily drug dose information improved the prediction of post-marketing liver safety. A cut-off of 1.2% increase in ALT ≥ 3× ULN in treated versus placebo groups provides an easily calculated method for predicting post-marketing liver safety. Published by Elsevier Inc.

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.

No sisyphean task: how the FDA can regulate electronic cigarettes.

PubMed

Paradise, Jordan

2013-01-01

The adverse effects of smoking have fostered a natural market for smoking cessation and smoking reduction products. Smokers attempting to quit or reduce consumption have tried everything: "low" or "light" cigarettes; nicotine-infused chewing gum, lozenges, and lollipops; dermal patches; and even hypnosis. The latest craze in the quest to find a safer source of nicotine is the electronic cigarette. Electronic cigarettes (e-cigarettes) have swept the market, reaching a rapidly expanding international consumer base. Boasting nicotine delivery and the tactile feel of a traditional cigarette without the dozens of other chemical constituents that contribute to carcinogenicity, e-cigarettes are often portrayed as less risky, as a smoking reduction or even a complete smoking cessation product, and perhaps most troubling for its appeal to youth, as a flavorful, trendy, and convenient accessory. The sensationalism associated with e-cigarettes has spurred outcry from health and medical professional groups, as well as the Food and Drug Administration (FDA), because of the unknown effects on public health. Inhabiting a realm of products deemed "tobacco products" under recent 2009 legislation, e-cigarettes pose new challenges to FDA regulation because of their novel method of nicotine delivery, various mechanical and electrical parts, and nearly nonexistent safety data. Consumer use, marketing and promotional claims, and technological characteristics of e-cigarettes have also raised decades old questions of when the FDA can assert authority over products as drugs or medical devices. Recent case law restricting FDA enforcement efforts against e-cigarettes further confounds the distinction among drugs and medical devices, emerging e-cigarette products, and traditional tobacco products such as cigarettes, cigars, and smokeless tobacco. This Article investigates the e-cigarette phenomenon in the wake of the recently enacted Family Smoking Prevention and Tobacco Control Act of 2009

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.

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.630 - Postmarketing safety reporting.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 314.630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.630 Postmarketing safety reporting. Drug...

21 CFR 314.630 - Postmarketing safety reporting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 314.630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.630 Postmarketing safety reporting. Drug...

21 CFR 314.630 - Postmarketing safety reporting.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 314.630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.630 Postmarketing safety reporting. Drug...

21 CFR 314.630 - Postmarketing safety reporting.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 314.630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.630 Postmarketing safety reporting. Drug...

21 CFR 314.630 - Postmarketing safety reporting.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 314.630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.630 Postmarketing safety reporting. Drug...

Closing the information gap: informing better medical decisionmaking through the use of post-market safety and comparative effectiveness information.

PubMed

Fox, Bethany

2012-01-01

While FDA gathers vast amounts of data about prescription drugs prior to their marketing approval, important information about the relative effectiveness and long term safety of products is not required for approval, and often is never collected. Increased postmarket research on the safety and comparative effectiveness of products would improve medical decisionmaking and lead to better clinical outcomes. Fortunately, Congress has recognized the value of this information for healthcare professionals. In response to a congressional mandate in the FDA Amendments Act (FDAAA), FDA is developing the Sentinel Initiative, an active surveillance system for monitoring postmarket drug safety issues. FDAAA also authorized FDA to require a drug sponsor to conduct postmarket safety studies or clinical trials to address a specific safety concern. To increase the repository of comparative effectiveness information, Congress established the Patient-Centered Outcomes Research Institute (PCORI) in the Patient Protection and Affordable Care Act (PPACA), directing it to manage comparative effectiveness research (CER). This article discusses the need for better safety and comparative effectiveness information and outlines methods to efficiently conduct the research and communicate it effectively to healthcare professionals. Coordination between FDA and the PCORI in gathering and communicating postmarket information is recommended. Medical source data collected by the Sentinel Initiative should be used for CER in addition to postmarket safety surveillance, and FDA and the PCORI should adopt identical standards for the distribution and communication of CER. Coordination between the two entities is recommended to save costs, reduce duplication of efforts, and to generate and communicate more information on prescription drugs for medical decisionmakers.

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.

Have antiepileptic drug prescription claims changed following the FDA suicidality warning? An evaluation in a state Medicaid program.

PubMed

Mittal, Manish; Harrison, Donald L; Miller, Michael J; Farmer, Kevin C; Thompson, David M; Ng, Yu-Tze

2014-05-01

In January 2008, the Food and Drug Administration (FDA) communicated concerns and, in May 2009, issued a warning about an increased risk of suicidality for all antiepileptic drugs (AEDs). This research evaluated the association between the FDA suicidality communications and the AED prescription claims among members with epilepsy and/or psychiatric disorder. A longitudinal interrupted time-series design was utilized to evaluate Oklahoma Medicaid claims data from January 2006 through December 2009. The study included 9289 continuously eligible members with prevalent diagnoses of epilepsy and/or psychiatric disorder and at least one AED prescription claim. Trends, expressed as monthly changes in the log odds of AED prescription claims, were compared across three time periods: before (January 2006 to January 2008), during (February 2008 to May 2009), and after (June 2009 to December 2009) the FDA warning. Before the FDA warning period, a significant upward trend of AED prescription claims of 0.01% per month (99% CI: 0.008% to 0.013%, p<0.0001) was estimated. In comparison to the prewarning period, no significant change in trend was detected during (-20.0%, 99% CI: -70.0% to 30.0%, p=0.34) or after (80.0%, 99% CI: -20.0% to 200.0%, p=0.03) the FDA warning period. After stratification, no diagnostic group (i.e., epilepsy alone, epilepsy and comorbid psychiatric disorder, and psychiatric disorder alone) experienced a significant change in trend during the entire study period (p>0.01). During the time period considered, the FDA AED-related suicidality warning does not appear to have significantly affected prescription claims of AED medications for the study population. Copyright © 2014 Elsevier Inc. All rights reserved.

76 FR 38184 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0439] Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall Regulations AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: Teaching Drug Marketers How to Inform Better or Spin Better? Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Doran, Evan

2016-02-21

Hyosun Kim's report "Trouble Spots in Online Direct to Consumer Prescription Drug Promotion: A content Analysis of FDA Warning Letters" aims to teach marketers how to avoid breaching current Food and Drug Administration (FDA) guidelines in their online drug promotion. While Kim hopes to minimise the potential for online promotion to misinform consumers and the study is carefully conducted, teaching drug marketers how to avoid the common mistakes in online drug promotion is more likely to make marketers more adept at spinning information than appropriately balancing it. © 2016 by Kerman University of Medical Sciences.

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

Examining the FDA's oversight of direct-to-consumer advertising.

PubMed

Gahart, Martin T; Duhamel, Louise M; Dievler, Anne; Price, Roseanne

2003-01-01

Our analysis examined the effects of the Food and Drug Administration's (FDA's) 1997 draft guidance regarding advertisements for prescription drugs broadcast directly to consumers. We found that although direct-to-consumer (DTC) advertising spending by pharmaceutical companies has increased, more than 80 percent of their promotional spending is directed to physicians. DTC advertising appears to increase the use of prescription drugs among consumers. The FDA's oversight has not prevented companies from making misleading claims in subsequent advertisements, and a recent policy change has lengthened the FDA's review process, raising the possibility that some misleading campaigns could run their course before review.

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

Structure Activity Relationship for FDA Approved Drugs as Inhibitors of the Human Sodium Taurocholate Co-transporting Polypeptide (NTCP)

PubMed Central

Dong, Zhongqi; Ekins, Sean; Polli, James E.

2013-01-01

The hepatic bile acid uptake transporter Sodium Taurocholate Cotransporting Polypeptide (NTCP) is less well characterized than its ileal paralog, the Apical Sodium Dependent Bile Acid Transporter (ASBT), in terms of drug inhibition requirements. The objectives of this study were a) to identify FDA approved drugs that inhibit human NTCP, b) to develop pharmacophore and Bayesian computational models for NTCP inhibition, and c) to compare NTCP and ASBT transport inhibition requirements. A series of NTCP inhibition studies were performed using FDA approved drugs, in concert with iterative computational model development. Screening studies identified 27 drugs as novel NTCP inhibitors, including irbesartan (Ki =11.9 μM) and ezetimibe (Ki = 25.0 μM). The common feature pharmacophore indicated that two hydrophobes and one hydrogen bond acceptor were important for inhibition of NTCP. From 72 drugs screened in vitro, a total of 31 drugs inhibited NTCP, while 51 drugs (i.e. more than half) inhibited ASBT. Hence, while there was inhibitor overlap, ASBT unexpectedly was more permissive to drug inhibition than was NTCP, and this may be related to NTCP’s possessing fewer pharmacophore features. Findings reflected that a combination of computational and in vitro approaches enriched the understanding of these poorly characterized transporters and yielded additional chemical probes for possible drug-transporter interaction determinations. PMID:23339484

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

Regulatory Underpinnings of Global Health Security: FDA's Roles in Preventing, Detecting, and Responding to Global Health Threats

PubMed Central

Bond, Katherine C.; Maher, Carmen

2014-01-01

In February 2014, health officials from around the world announced the Global Health Security Agenda, a critical effort to strengthen national and global systems to prevent, detect, and respond to infectious disease threats and to foster stronger collaboration across borders. With its increasing global roles and broad range of regulatory responsibilities in ensuring the availability, safety, and security of medical and food products, the US Food and Drug Administration (FDA) is engaged in a range of efforts in support of global health security. This article provides an overview of FDA's global health security roles, focusing on its responsibilities related to the development and use of medical countermeasures (MCMs) for preventing, detecting, and responding to global infectious disease and other public health emergency threats. The article also discusses several areas—antimicrobial resistance, food safety, and supply chain integrity—in which FDA's global health security roles continue to evolve and extend beyond MCMs and, in some cases, beyond traditional infectious disease threats. PMID:25254912

Regulatory underpinnings of Global Health security: FDA's roles in preventing, detecting, and responding to global health threats.

PubMed

Courtney, Brooke; Bond, Katherine C; Maher, Carmen

2014-01-01

In February 2014, health officials from around the world announced the Global Health Security Agenda, a critical effort to strengthen national and global systems to prevent, detect, and respond to infectious disease threats and to foster stronger collaboration across borders. With its increasing global roles and broad range of regulatory responsibilities in ensuring the availability, safety, and security of medical and food products, the US Food and Drug Administration (FDA) is engaged in a range of efforts in support of global health security. This article provides an overview of FDA's global health security roles, focusing on its responsibilities related to the development and use of medical countermeasures (MCMs) for preventing, detecting, and responding to global infectious disease and other public health emergency threats. The article also discusses several areas-antimicrobial resistance, food safety, and supply chain integrity-in which FDA's global health security roles continue to evolve and extend beyond MCMs and, in some cases, beyond traditional infectious disease threats.

21 CFR 315.6 - Evaluation of safety.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Evaluation of safety. 315.6 Section 315.6 Food and... USE DIAGNOSTIC RADIOPHARMACEUTICALS § 315.6 Evaluation of safety. (a) Factors considered in the safety...)(1) To establish the safety of a diagnostic radiopharmaceutical, FDA may require, among other...

FDA plan for statutory compliance. Notice of availability.

PubMed

1998-11-24

The Food and Drug Administration (FDA) is announcing the availability of a document entitled "FDA Plan for Statutory Compliance" (the plan). This document is the agency's response to section 406(b) of the Food and Drug Administration Modernization Act of 1997 (FDAMA), which requires the Secretary of the Department of Health and Human Services (the Secretary) to develop a plan bringing the agency into compliance with the requirements of the Federal Food, Drug, and Cosmetic Act (the act).

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

77 FR 70166 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-23

...; Establishment of a Public Docket AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket for information pertaining to FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1090...

How are drugs approved? Part 1: the evolution of the Food and Drug Administration.

PubMed

Howland, Robert H

2008-01-01

The discovery, development, and marketing of drugs for clinical use is a process that is complex, arduous, expensive, highly regulated, often criticized, and sometimes controversial. In the United States, the Food and Drug Administration (FDA) is the governmental agency responsible for regulating the development and marketing of drugs, medical devices, biologics, foods, cosmetics, radiation-emitting electronic devices, and veterinary products, with the objective of ensuring their safety and efficacy. As part of a broad overview of the drug development process, this article will describe the historical evolution of the FDA. This will provide background for two subsequent articles in this series, which will describe the ethical foundations of clinical research and hethe stages of drug development.

Teaching the science of safety in US colleges and schools of pharmacy.

PubMed

Holdford, David A; Warholak, Terri L; West-Strum, Donna; Bentley, John P; Malone, Daniel C; Murphy, John E

2011-05-10

This paper provides baseline information on integrating the science of safety into the professional degree curriculum at colleges and schools of pharmacy. A multi-method examination was conducted that included a literature review, key informant interviews of 30 individuals, and in-depth case studies of 5 colleges and schools of pharmacy. Educators believe that they are devoting adequate time to science of safety topics and doing a good job teaching students to identify, understand, report, manage, and communicate medication risk. Areas perceived to be in need of improvement include educating pharmacy students about the Food and Drug Administration's (FDA's) role in product safety, how to work with the FDA in post-marketing surveillance and other FDA safety initiatives, teaching students methods to improve safety, and educating students to practice in interprofessional teams. The report makes 10 recommendations to help pharmacy school graduates be more effective in protecting patients from preventable drug-related problems.

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.

Access to F.D.A. Information.

ERIC Educational Resources Information Center

Sinovic, Dianna

Prior to the enactment of the Freedom of Information Act (FOIA), little of the data collected by the Food and Drug Administration (FDA) was made public or could be obtained from the agency. Although the FDA files are now open, information is considered exempt from public disclosure when it involves regulatory procedures, program guidelines, work…

Summary of safety and effectiveness data from FDA: a valuable source of information on the performance of global endometrial ablation devices.

PubMed

Cooper, Jay; Gimpelson, Richard J

2004-04-01

To provide an overview of the approved second-generation endometrial ablation technologies. Data from the FDA Summary of Safety and Effectiveness Data were compared for Thermachoice, HydroThermablator, Her Option and Novasure devices. At 12 months' follow-up, Novasure and HydroThermablator had the highest amenorrhea rates. Thermochoice and Novasure had the highest success rates at 12 months. Novasure had the lowest adverse event rates in the first 24 hours, between 24 hours and 2 weeks and between 2 weeks and 1 year of follow-up. Summary of Safety and Effectiveness Data, obtainable on the FDA Web site, offers objective data for comparing second-generation endometrial ablation technologies.

Influence of kidney disease on drug disposition: An assessment of industry studies submitted to the FDA for new chemical entities 1999-2010.

PubMed

Matzke, Gary R; Dowling, Thomas C; Marks, Samantha A; Murphy, John E

2016-04-01

In 1998, the United States Food and Drug Administration (FDA) released the first guidance for industry regarding pharmacokinetic (PK) studies in renally impaired patients. This study aimed to determine if the FDA renal PK guidance influenced the frequency and rigor of renal studies conducted for new chemical entities (NCEs). FDA-approved package inserts (APIs) and clinical pharmacology review documents were analyzed for 194 NCEs approved from 1999 to 2010. Renal studies were conducted in 71.6% of NCEs approved from 1999 to 2010, a significant increase over the 56.3% conducted from 1996 to 1997 (P = .0242). Renal studies were more likely to be completed in highly renally excreted drugs (fe ≥ 30%) compared with drugs with low renal excretion, fe < 30% (89.6% vs 65.8%, P = .0015). PK studies to assess the impact of dialysis were conducted for 31.7% of NCEs that had a renal study: a greater proportion of high fe NCEs were studied (44.2% vs 26.0%, P = .0335). No significant change in frequency or rigor of PK studies was detected over time. The majority of NCEs (76.3%) with a renal study provided specific dosing recommendations in the API. The adoption of the 1998 FDA guidance has resulted in improved availability of PK and drug-dosing recommendations, particularly for high fe drugs. © 2015, The American College of Clinical Pharmacology.

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.

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

Year 2000 (Y2K) computer compliance guide; guidance for FDA personnel. Food and Drug Administration. Notice.

PubMed

1999-05-14

The Food and Drug Administration (FDA) is announcing the availability of a new compliance policy guide (CPG) entitled "Year 2000 (Y2K) Computer Compliance" (section 160-800). This guidance document represents the agency's current thinking on the manufacturing and distribution of domestic and imported products regulated by FDA using computer systems that may not perform properly before, or during, the transition to the year 2000 (Y2K). The text of the CPG is included in this notice. This compliance guidance document is an update to the Compliance Policy Guides Manual (August 1996 edition). It is a new CPG, and it will be included in the next printing of the Compliance Policy Guides Manual. This CPG is intended for FDA personnel, and it is available electronically to the public.

Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies.

PubMed

Nguyen, Diane; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Montagne, Michael

2013-01-22

The United States (US) Food and Drug Administration (FDA) is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA) and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation) to pharmaceutical companies. A regulatory letter represents the FDA's first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA.This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997-2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total), followed by the Office of Scientific Investigations (131; 5.3%), and the Office of Compliance (105; 4.3%). During the 2nd Clinton Administration (1997-2000) the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001-2008) it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009-2011) it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by administration: Clinton (122.3 ± 36.4), Bush (29.5�

76 FR 53912 - FDA's Public Database of Products With Orphan-Drug Designation: Replacing Non-Informative Code...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

...] FDA's Public Database of Products With Orphan-Drug Designation: Replacing Non-Informative Code Names... replaced non- informative code names with descriptive identifiers on its public database of products that... on our public database with non-informative code names. After careful consideration of this matter...

Pharmacogenetics and pharmacogenomics in drug development and regulatory decision making: report of the first FDA-PWG-PhRMA-DruSafe Workshop.

PubMed

Lesko, Lawrence J; Salerno, Ronald A; Spear, Brian B; Anderson, Donald C; Anderson, Timothy; Brazell, Celia; Collins, Jerry; Dorner, Andrew; Essayan, David; Gomez-Mancilla, Baltazar; Hackett, Joseph; Huang, Shiew-Mei; Ide, Susan; Killinger, Joanne; Leighton, John; Mansfield, Elizabeth; Meyer, Robert; Ryan, Stephen G; Schmith, Virginia; Shaw, Peter; Sistare, Frank; Watson, Mark; Worobec, Alexandra

2003-04-01

The use of pharmacogenetics and pharmacogenomics in the drug development process, and in the assessment of such data submitted to regulatory agencies by industry, has generated significant enthusiasm as well as important reservations within the scientific and medical communities. This situation has arisen because of the increasing number of exploratory and confirmatory investigations into variations in RNA expression patterns and DNA sequences being conducted in the preclinical and clinical phases of drug development, and the uncertainty surrounding the acceptance of these data by regulatory agencies. This report summarizes the outcome of a workshop cosponsored by the Food and Drug Administration (FDA), the Pharmacogenetics Working Group (PWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the PhRMA Preclinical Safety Committee (DruSafe). The specific aim of the workshop was to identify key issues associated with the application of pharmacogenetics and pharmacogenomics, including the feasibility of a regulatory "safe harbor" for exploratory genome-based data, and to provide a forum for industry-regulatory agency dialogue on these important issues.

21 CFR 830.100 - FDA accreditation of an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA accreditation of an issuing agency. 830.100... (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency § 830.100 FDA... issuing agency. (b) Accreditation criteria. FDA may accredit an organization as an issuing agency, if the...

Practice patterns and postoperative complications before and after US Food and Drug Administration safety communication on power morcellation.

PubMed

Harris, John A; Swenson, Carolyn W; Uppal, Shitanshu; Kamdar, Neil; Mahnert, Nichole; As-Sanie, Sawsan; Morgan, Daniel M

2016-01-01

In April 2014, the US Food and Drug Administration (FDA) published its first safety communication discouraging "the use of laparoscopic power morcellation during hysterectomy or myomectomy for the treatment of women with uterine fibroids." Due to the concern of worsening outcomes for patients with occult uterine malignancy, specifically uterine leiomyosarcoma, the FDA recommended a significant change to existing surgical planning, patient consent, and surgical technique in the United States. We sought to report temporal trends in surgical approach to hysterectomy and postoperative complications before and after the April 17, 2014, FDA safety communication concerning the use of power morcellation during myomectomy or hysterectomy. A retrospective cohort study was performed with patients undergoing hysterectomy for benign indications in the Michigan Surgical Quality Collaborative from Jan. 1, 2013, through Dec. 31, 2014. The rates of abdominal, laparoscopic, and vaginal hysterectomy, as well as the rates of major postoperative complications and 30-day hospital readmissions and reoperations, were compared before and after April 17, 2014, the date of the original FDA safety communication. Major postoperative complications included blood transfusions, vaginal cuff infection, vaginal cuff dehiscence, ureteral obstruction, vesicovaginal fistula, deep and organ space surgical site infection, acute renal failure, respiratory failure, sepsis, pulmonary embolism, deep vein thrombosis requiring therapy, cerebral vascular accident, cardiac arrest, and death. We calculated the median episode cost related to hysterectomy readmissions using Michigan Value Collaborative data. Analyses were performed using robust multivariable multinomial and logistic regression models. There were 18,299 hysterectomies available for analysis during the study period. In all, 2753 cases were excluded due to an indication for cancer, cervical dysplasia, or endometrial hyperplasia, and 174 cases were

Evaluation of the Safety of Drugs and Biological Products Used During Lactation: Workshop Summary

PubMed Central

Wang, J; Johnson, T; Sahin, L; Tassinari, MS; Anderson, PO; Baker, TE; Bucci-Rechtweg, C; Burckart, GJ; Chambers, CD; Hale, TW; Johnson-Lyles, D; Nelson, RM; Nguyen, C; Pica-Branco, D; Ren, Z; Sachs, H; Sauberan, J; Zajicek, A; Ito, S; Yao, LP

2017-01-01

This report serves as a summary of a 2-day public workshop sponsored by the US Food and Drug Administration (FDA) to discuss the safety of drugs and biological products used during lactation. The aim of the workshop was to provide a forum to discuss the collection of data to inform the potential risks to breastfed infants with maternal use of medications during lactation. Discussions included the review of current approaches to collect data on medications used during lactation, and the considerations for future approaches to design and guide clinical lactation studies. This workshop is part of continuing efforts to raise the awareness of the public for women who choose to breastfeed their infants. PMID:28510297

Adherence of Pharmaceutical Advertisements in Medical Journals to FDA Guidelines and Content for Safe Prescribing

PubMed Central

Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S.

2011-01-01

Background Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Methods and Findings Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1–14). Six “teaser” advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Conclusions Few

Adherence of pharmaceutical advertisements in medical journals to FDA guidelines and content for safe prescribing.

PubMed

Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S

2011-01-01

Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1-14). Six "teaser" advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Few physician-directed print pharmaceutical advertisements

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.

New technology in electrophysiology: FDA process and perspective.

PubMed

Selzman, Kimberly A; Fellman, Mark; Farb, Andrew; de Del Castillo, Sergio; Zuckerman, Bram

2016-10-01

The Food and Drug Administration (FDA) is a large regulatory agency that monitors everything from food, tobacco, and veterinary medicine to pharmaceutical drugs and medical devices. The Mission statement of the CDRH, one of the Centers of the FDA, in its most succinct form is to protect and promote public health. This is accomplished through timely and continued access to safe, effective, and high quality medical devices. This paper aims to review the overarching principles of the Agency's review process for cardiac devices as well as highlight some of the newer programs that FDA has engaged in to facilitate innovation, device development, research, and timely market approval.

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.

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

Amendment to examination and investigation sample requirements--FDA. Direct final rule.

PubMed

1998-09-25

The Food and Drug Administration (FDA) is amending its regulations regarding the collection of twice the quantity of food, drug, or cosmetic estimated to be sufficient for analysis. This action increases the dollar amount that FDA will consider to determine whether to routinely collect a reserve sample of a food, drug, or cosmetic product in addition to the quantity sufficient for analysis. Experience has demonstrated that the current dollar amount does not adequately cover the cost of most quantities sufficient for analysis plus reserve samples. This direct final rule is part of FDA's continuing effort to achieve the objectives of the President's "Reinventing Government" initiative, and is intended to reduce the burden of unnecessary regulations on food, drugs, and cosmetics without diminishing the protection of the public health. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule under FDA's usual procedures for notice and comment to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comment and withdraws this direct final rule.

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2011 CFR

2011-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2012 CFR

2012-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0792] (Formerly FDA-1999-D-0792) Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial.... SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance...

The analysis of the market success of FDA approvals by probing top 100 bestselling drugs.

PubMed

Polanski, Jaroslaw; Bogocz, Jacek; Tkocz, Aleksandra

2016-05-01

Target-oriented drug discovery is the main research paradigm of contemporary drug discovery. In target-oriented approaches, we attempt to maximize in vitro drug potency by finding the optimal fit to the target. This can result in a higher molecular complexity, in particular, the higher molecular weight (MW) of the drugs. However, a comparison of the successful developments of pharmaceuticals with the general trends that can be observed in medicinal chemistry resulted in the conclusion that the so-called molecular obesity is an important reason for the attrition rate of drugs. When analyzing the list of top 100 drug bestsellers versus all of the FDA approvals, we discovered that on average lower-complexity (MW, ADMET score) drugs are winners of the top 100 list in terms of numbers but that, especially, up to some optimal MW value, a higher molecular complexity can pay off with higher incomes. This indicates that slim drugs are doing better but that fat drugs are bigger fishes to catch.

The analysis of the market success of FDA approvals by probing top 100 bestselling drugs

NASA Astrophysics Data System (ADS)

Polanski, Jaroslaw; Bogocz, Jacek; Tkocz, Aleksandra

2016-05-01

Target-oriented drug discovery is the main research paradigm of contemporary drug discovery. In target-oriented approaches, we attempt to maximize in vitro drug potency by finding the optimal fit to the target. This can result in a higher molecular complexity, in particular, the higher molecular weight (MW) of the drugs. However, a comparison of the successful developments of pharmaceuticals with the general trends that can be observed in medicinal chemistry resulted in the conclusion that the so-called molecular obesity is an important reason for the attrition rate of drugs. When analyzing the list of top 100 drug bestsellers versus all of the FDA approvals, we discovered that on average lower-complexity (MW, ADMET score) drugs are winners of the top 100 list in terms of numbers but that, especially, up to some optimal MW value, a higher molecular complexity can pay off with higher incomes. This indicates that slim drugs are doing better but that fat drugs are bigger fishes to catch.

The safety and regulation of natural products used as foods and food ingredients.

PubMed

Abdel-Rahman, Ali; Anyangwe, Njwen; Carlacci, Louis; Casper, Steve; Danam, Rebecca P; Enongene, Evaristus; Erives, Gladys; Fabricant, Daniel; Gudi, Ramadevi; Hilmas, Corey J; Hines, Fred; Howard, Paul; Levy, Dan; Lin, Ying; Moore, Robert J; Pfeiler, Erika; Thurmond, T Scott; Turujman, Saleh; Walker, Nigel J

2011-10-01

The use of botanicals and dietary supplements derived from natural substances as an adjunct to an improved quality of life or for their purported medical benefits has become increasingly common in the United States. This review addresses the safety assessment and regulation of food products containing these substances by the U.S. Food and Drug Administration (FDA). The issue of safety is particularly critical given how little information is available on the toxicity of some of these products. The first section uses case studies for stevia and green tea extracts as examples of how FDA evaluates the safety of botanical and herbal products submitted for consideration as Generally Recognized as Safe under the Federal Food, Drug, and Cosmetics Act. The 1994 Dietary Supplement Health Education Act (DSHEA) created a regulatory framework for dietary supplements. The article also discusses the regulation of this class of dietary supplements under DSHEA and addresses the FDA experience in analyzing the safety of natural ingredients described in pre-market safety submissions. Lastly, we discuss an ongoing interagency collaboration to conduct safety testing of nominated dietary supplements.

FDA Approval for Imiquimod

Cancer.gov

On July 15, 2004, the U.S. Food and Drug Administration (FDA) announced the approval of a new indication for Aldara® (imiquimod) topical cream for the treatment of superficial basal cell carcinoma (sBCC), a type of skin cancer.

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

[U.S. Food and Drug Administration (FDA) strengthens warning that non-aspirin non steroidal anti-inflammatory drugs (NSAIDs) can cause myocardial infarctions or strokes: the dentist's perspective].

PubMed

Rosen, E; Tsesis, I; Vered, M

2015-10-01

This short communication is aimed to update dental practitioners regarding the recently published warning of the U.S. Food and Drug Administration (FDA) regarding the risk for severe cardiovascular complications such as myocardial infarction or stroke following the use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs).

The FDA role in contact lens development and safety.

PubMed

Lippman, R E

1990-01-01

The Food and Drug Administration (FDA) exercises a multifaceted role in fulfilling its mission of enforcing the Federal Food, Drug and Cosmetic Act (Act), functioning not only as industry regulator and consumer protector, but also as scientific advisor and consumer educator regarding medical devices, drugs, foods, cosmetics, and veterinary medicine. Medical devices are regulated within the Center for Devices and Radiological Health. Contact lenses are regulated under the authority of the medical device amendments. The Center is responsible for promulgating regulations, publishing guidelines, and developing written guidance in enforcing the Act, and also for guiding manufacturers of medical devices in safe and effective product development. Other components deal with the compliance of manufacturers with the marketing of medical devices within the meaning of the Act, and through labeling requirements of the Act and consumer education and informational activities. As for contact lenses, the process of updating product development regulations and guidelines is an ongoing activity. The most recent version of the Contact Lens Guideline Document, issued in April 1988, contains two major revisions involving preclinical and clinical testing. The first redefines plastics into one materials category, thus reducing testing requirements with respect to animal toxicology studies and other preclinical areas. The second revision restricts clinical testing requirements to allow confirmatory trials in applications for new daily wear lenses. The intention was to maintain the ability of studies to detect major material or design flaws in lenses, thus boosting confidence in their performance while eliminating unnecessary trials.(ABSTRACT TRUNCATED AT 250 WORDS)

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

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.

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

76 FR 61709 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Form 3728...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0708] Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Form 3728, Animal...: The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed...

A Drug Safety Rating System Based on Postmarketing Costs Associated with Adverse Events and Patient Outcomes.

PubMed

Hoffman, Keith B; Dimbil, Mo; Kyle, Robert F; Tatonetti, Nicholas P; Erdman, Colin B; Demakas, Andrea; Chen, Dingguo; Overstreet, Brian M

2015-12-01

Given the multiple limitations associated with relatively homogeneous preapproval clinical trials, inadequate data disclosures, slow reaction times from regulatory bodies, and deep-rooted bias against disclosing and publishing negative results, there is an acute need for the development of analytics that reflect drug safety in heterogeneous, real-world populations. To develop a drug safety statistic that estimates downstream medical costs associated with serious adverse events (AEs) and unfavorable patient outcomes associated with the use of 706 FDA-approved drugs. All primary suspect case reports for each drug were collected from the FDA's Adverse Event Reporting System database (FAERS) from 2010-2014. The Medical Dictionary for Regulatory Activities (MedDRA) was used to code serious AEs and outcomes, which were tallied for each case report. Medical costs associated with AEs and poor patient outcomes were derived from Agency for Healthcare Research and Quality (AHRQ) survey data, and their corresponding ICD-9-CM codes were mapped to MedDRA terms. Nonserious AEs and outcomes were not included. For each case report, either the highest AE cost or, if no eligible AE was listed, the highest outcome cost was used. All costed cases were aggregated for each drug and divided by the number of patients exposed to obtain a downstream estimated direct medical cost burden per exposure. Each drug was assigned a corresponding 1-100 point total. The 706 drugs showed an exponential distribution of downstream costs, and the data were transformed using the natural log to approximate a normal distribution. The minimum score was 8.29, and the maximum score was 99.25, with a mean of 44.32. Drugs with the highest individual scores tended to be kinase inhibitors, thalidomide analogs, and endothelin receptor antagonists. When scores were analyzed across Established Pharmacologic Class (EPC), the kinase inhibitor and endothelin receptor antagonist classes had the highest total. However

Drugs and Diseases Interacting with Cigarette Smoking in US Prescription Drug Labelling.

PubMed

Li, Haibo; Shi, Qiang

2015-05-01

The US Food and Drug Administration (FDA) draft guidance for industry on drug interaction studies recommends, but does not mandate, that both cigarette smokers and non-smokers can be used to study drug metabolism in clinical trials, and that important results related to smoking should be included in drug labelling to guide medication usage. This study aimed to provide a comprehensive review of drugs or diseases interacting with smoking, as presented in all US drug labelling. The 62,857 drug labels deposited in the FDA Online Label Repository were searched using the keywords 'smoke', 'smoker(s)', 'smoking', 'tobacco' and 'cigarette(s)' on 19 June 2014. The resultant records were refined to include only human prescription drug labelling, for manual examination. For 188 single-active-ingredient drugs and 36 multiple-active-ingredient drugs, the labelling was found to contain smoking-related information. The pharmacokinetics of 29 and 21 single-active-ingredient drugs were affected and unaffected, respectively, by smoking. For the remaining drugs, the provided information related to smoking affecting efficacy, safety or diseases but not pharmacokinetics. Depending on the nature of specific drugs, the perturbation in pharmacokinetic parameters in smokers ranged from 13 to 500%, in comparison with non-smokers. Dosage modifications in smokers are necessary for four drugs and may be necessary for six drugs, but are unnecessary for seven drugs although the pharmacokinetic parameters of four of them are affected by smoking. Cigarette smoking is a risk factor for 16 types of diseases or adverse drug reactions. For one single-active-ingredient contraceptive drug and 10 multiple-active-ingredient contraceptive drugs, a black box warning (the FDA's strongest safety warning) is included in the labelling for increased risks of heart attacks and strokes in female smokers, and "women are strongly advised not to smoke" when using these drugs. This study presents the first

76 FR 67461 - Cosmetic Microbiological Safety Issues; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0770] Cosmetic Microbiological Safety Issues; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments and opening of a docket. SUMMARY: The Food and Drug...

FDA: Evidentiary Standards for Drug Development and Approval

PubMed Central

Katz, Russell

2004-01-01

Summary: The United States Food and Drug Administration is charged with approving drug treatments that have been shown to be safe and effective. Relevant statutes and regulations provide a legal framework for establishing safety and effectiveness that is sufficiently flexible to ensure that appropriate scientific data are collected for specific treatments targeted to particular diseases. Nonetheless, all clinical trials proposed to establish effectiveness must incorporate common elements in order for the appropriate legal and scientific standards of drug approval to be met. This article will discuss the relevant laws and regulations pertaining to the current effectiveness standard and will discuss the most important clinical trial design elements currently considered acceptable for applications for treatments of neurologic and psychiatric illness. PMID:15717032

76 FR 31615 - Draft Guidance for Industry and FDA Staff: Commercially Distributed In Vitro Diagnostic Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0305] Draft Guidance for Industry and FDA Staff: Commercially Distributed In Vitro Diagnostic Products Labeled...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

Food and Drug Administration Evaluation and Cigarette Smoking Risk Perceptions

ERIC Educational Resources Information Center

Kaufman, Annette R.; Waters, Erika A.; Parascandola, Mark; Augustson, Erik M.; Bansal-Travers, Maansi; Hyland, Andrew; Cummings, K. Michael

2011-01-01

Objectives: To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…

Drug Labeling and Exposure in Neonates

PubMed Central

Laughon, Matthew M.; Avant, Debbie; Tripathi, Nidhi; Hornik, Christoph P.; Cohen-Wolkowiez, Michael; Clark, Reese H.; Smith, P. Brian; Rodriguez, William

2014-01-01

Importance Federal legislation has led to a notable increase in pediatric studies submitted to the Food and Drug Administration (FDA), resulting in new pediatric information in product labeling. However, approximately 50% of drug labels still have insufficient information on safety, efficacy, or dosing in children. Neonatal information in labeling is even scarcer because neonates comprise a vulnerable subpopulation for which end point development is lagging and studies are more challenging. Objective To quantify progress made in neonatal studies and neonatal information in product labeling as result of recent legislation. Design 1. Cohort of neonatal drug studies; and 2. Cohort of infants exposed to these drugs.. Setting 1. Neonatal drug studies: FDA website; 2. National review: infants admitted to a neonatal intensive care unit (NICU) Participants 1) We identified drug studies between 1997 and 2010 that included neonates as a result of pediatric legislation using information available on the FDA website. We determined what studies were published in the medical literature, the legislation responsible for the studies, and the resulting neonatal labeling changes. 2) We then examined the use of these drugs in neonates admitted to 290 NICUs (the Pediatrix Data Warehouse) in the United States from 2005–2010. Exposures Infants exposed to a drug studied in neonates as identified by the FDA website Main outcome measures Number of drug studies with neonates and rate of exposure per 1000 admission among infants admitted to a NICU Results In a review of the FDA databases, we identified 28 drugs studied in neonates and 24 related labeling changes. Forty-one studies encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of the 24 neonatal labeling changes established safety and effectiveness. In a review of a cohort of 446,335 hospitalized infants, we identified 399 drugs used and 1,525,739 drug exposures in the first 28 postnatal days. Thirteen (46%) of

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...

Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library.

PubMed

Pascoalino, Bruno S; Courtemanche, Gilles; Cordeiro, Marli T; Gil, Laura H V G; Freitas-Junior, Lucio

2016-01-01

Background The recent epidemics of Zika virus (ZIKV) implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account. Thus, antiviral chemotherapy should be pursued as a priority strategy to control the spread of the virus and prevent the complications associated with Zika. Methods Here we describe a fast and reliable cell-based, high-content screening assay for discovery of anti-ZIKV compounds. This methodology has been used to screen the National Institute of Health Clinical Collection compound library, a small collection of FDA-approved drugs. Results and conclusion From 725 FDA-approved compounds triaged, 29 (4%) were found to have anti-Zika virus activity, of which 22 had confirmed (76% of confirmation) by dose-response curves. Five candidates presented selective activity against ZIKV infection and replication in a human cell line. These hits have abroad spectrum of chemotypes and therapeutic uses, offering valuable opportunities for selection of leads for antiviral drug discovery.

The Conundrum of Online Prescription Drug Promotion Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Wanasika, Isaac

2016-03-26

This commentary discusses pertinent issues from Hyosun Kim's paper on online prescription drug promotion. The study is well-designed and the findings highlight some of the consequences of the Food and Drug Administration's (FDA's) decision to deregulate online advertising of prescription drugs. While Kim's findings confirm some of the early concerns, they also provide a perspective of implementation challenges in the ever-changing technological environment. © 2016 by Kerman University of Medical Sciences.

Clinical Evidence Supporting US Food and Drug Administration Approval of Otolaryngologic Prescription Drug Indications, 2005-2014.

PubMed

Rathi, Vinay K; Wang, Bo; Ross, Joseph S; Downing, Nicholas S; Kesselheim, Aaron S; Gray, Stacey T

2017-04-01

Objective The US Food and Drug Administration (FDA) approves indications for prescription drugs based on premarket pivotal clinical studies designed to demonstrate safety and efficacy. We characterized the pivotal studies supporting FDA approval of otolaryngologic prescription drug indications. Study Design Retrospective cross-sectional analysis. Setting Publicly available FDA documents. Subjects Recently approved (2005-2014) prescription drug indications for conditions treated by otolaryngologists or their multidisciplinary teams. Drugs could be authorized for treatment of otolaryngologic disease upon initial approval (original indications) or thereafter via supplemental applications (supplemental indications). Methods Pivotal studies were categorized by enrollment, randomization, blinding, comparator type, and primary endpoint. Results Between 2005 and 2014, the FDA approved 48 otolaryngologic prescription drug indications based on 64 pivotal studies, including 21 original indications (19 drugs, 31 studies) and 27 supplemental indications (18 drugs, 33 studies). Median enrollment was 299 patients (interquartile range, 198-613) for original indications and 197 patients (interquartile range, 64-442) for supplemental indications. Most indications were supported by ≥1 randomized study (original: 20/21 [95%], supplemental: 21/27 [78%]) and ≥1 double-blinded study (original: 14/21 [67%], supplemental: 17/27 [63%]). About half of original indications (9/21 [43%]) and one-quarter of supplemental indications (7/27 [26%]) were supported by ≥1 active-controlled study. Nearly half (original: 8/21 [38%], supplemental: 14/27 [52%]) of all indications were approved based exclusively on studies using surrogate markers as primary endpoints. Conclusion The quality of clinical evidence supporting FDA approval of otolaryngologic prescription drug indications varied widely. Otolaryngologists should consider limitations in premarket evidence when helping patients make informed

[Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

PubMed

Li, Yuanyuan; Xie, Yanming

2011-10-01

The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

21 CFR 830.120 - Responsibilities of an FDA-accredited issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Responsibilities of an FDA-accredited issuing... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency § 830.120 Responsibilities of an FDA-accredited issuing agency. To maintain its accreditation, an...

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.

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.

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

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

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

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...

21 CFR 830.220 - Termination of FDA service as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Termination of FDA service as an issuing agency... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA as an Issuing Agency § 830.220 Termination of FDA service as an issuing agency. (a) FDA may end our services as an issuing agency if we...

FDA Benchmark Medical Device Flow Models for CFD Validation.

PubMed

Malinauskas, Richard A; Hariharan, Prasanna; Day, Steven W; Herbertson, Luke H; Buesen, Martin; Steinseifer, Ulrich; Aycock, Kenneth I; Good, Bryan C; Deutsch, Steven; Manning, Keefe B; Craven, Brent A

Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation. In addition, computational simulations were performed by more than 20 independent groups to assess current CFD techniques. The primary goal of this article is to summarize the FDA initiative and to report recent findings from the benchmark blood pump model study. Discrepancies between CFD predicted velocities and those measured using particle image velocimetry most often occurred in regions of flow separation (e.g., downstream of the nozzle throat, and in the pump exit diffuser). For the six pump test conditions, 57% of the CFD predictions of pressure head were within one standard deviation of the mean measured values. Notably, only 37% of all CFD submissions contained hemolysis predictions. This project aided in the development of an FDA Guidance Document on factors to consider when reporting computational studies in medical device regulatory submissions. There is an accompanying podcast available for this article. Please visit the journal's Web site (www.asaiojournal.com) to listen.

76 FR 32367 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0742 (formerly Docket No. 1999D-4396)] Draft Guidance for Clinical Investigators, Industry, and FDA Staff...: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared...

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.

Stimulated reporting: the impact of US food and drug administration-issued alerts on the adverse event reporting system (FAERS).

PubMed

Hoffman, Keith B; Demakas, Andrea R; Dimbil, Mo; Tatonetti, Nicholas P; Erdman, Colin B

2014-11-01

The US Food and Drug Administration (FDA) uses the Adverse Event Reporting System (FAERS) to support post-marketing safety surveillance programs. Currently, almost one million case reports are submitted to FAERS each year, making it a vast repository of drug safety information. Sometimes cited as a limitation of FAERS, however, is the assumption that "stimulated reporting" of adverse events (AEs) occurs in response to warnings, alerts, and label changes that are issued by the FDA. To determine the extent of "stimulated reporting" in the modern-day FAERS database. One hundred drugs approved by the FDA between 2001 and 2010 were included in this analysis. FDA alerts were obtained by a comprehensive search of the FDA's MedWatch and main websites. Publicly available FAERS data were used to assess the "primary suspect" AE reporting pattern for up to four quarters before, and after, the issuance of an FDA alert. A few drugs did demonstrate "stimulated reporting" trends. A majority of the drugs, however, showed little evidence for significant reporting changes associated with the issuance of alerts. When we compared the percentage changes in reporting after an FDA alert with those after a sham "control alert", the overall reporting trends appeared to be quite similar. Of 100 drugs analyzed for short-term reporting trends, 21 real alerts and 25 sham alerts demonstrated an increase (greater than or equal to 1 %) in reporting. The long-term analysis of 91 drugs showed that 24 real alerts and 28 sham alerts demonstrated a greater than or equal to 1 % increase. Our results suggest that most of modern day FAERS reporting is not significantly affected by the issuance of FDA alerts.

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.

Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters

PubMed Central

Kim, Hyosun

2015-01-01

Background: For the purpose of understanding the Food and Drug Administration’s (FDA’s) concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs) and warning letters issued by the FDA to pharmaceutical manufacturers. Methods: The FDA’s warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014) regarding online promotional activities, were content-analyzed. Results: Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA) of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. Conclusion: Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the FDA has thus

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.

76 FR 41506 - Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215] Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

78 FR 20926 - Draft Guidance for Industry on Providing Postmarket Periodic Safety Reports in the International...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-08

...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Providing Postmarket Periodic Safety Reports in the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report).'' This guidance is intended to inform applicants of the conditions under which FDA will exercise its waiver authority to permit applicants to submit an International Conference on Harmonisation (ICH) E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER) in place of the ICH E2C(R1) Periodic Safety Update Report (PSUR), U.S. periodic adverse drug experience report (PADER), or U.S. periodic adverse experience report (PAER), to satisfy the periodic safety reporting requirements in FDA regulations. The guidance describes the steps applicants can take to submit the PBRER, and discusses the format, content, submission deadline, and frequency of reporting for the PBRER.

75 FR 56112 - Integrated Food Safety System Online Collaboration Development-Cooperative Agreement With the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

... unintentional contamination of food at each of these points. FDA has worked with other Federal, State, local... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0480] Integrated Food Safety System Online Collaboration Development-- Cooperative Agreement With the National...

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.

Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients.

PubMed

Maxey, Dawn M; Ivy, D Dunbar; Ogawa, Michelle T; Feinstein, Jeffrey A

2013-10-01

Because most medications for pediatric pulmonary hypertension (PH) are used off label and based on adult trials, little information is available on pediatric-specific adverse events (AEs). Although drug manufacturers are required to submit postmarket AE reports to the Food and Drug Administration (FDA), this information is rarely transmitted to practitioners. In the setting of a recent FDA warning for sildenafil, the authors sought to give a better description of the AEs associated with current therapies in pediatric PH. In January 2010, a written request was made to the Food and Drug Administration for AE records of commonly used PH medications. Reports were screened for pediatric patients, analyzed in terms of AEs, and compared with the medical literature. Arbitrarily, AEs that could be attributed to concomitant medications were not attributed to the PH medication in question. Adverse events occurring in more than 5 % of events for each drug were assumed to be associated with the targeted PH medication. Between November 1997 and December 2009, 588 pediatric AE reports (death in 257 cases) were reported for the three most commonly used therapies: bosentan, epoprostenol, and sildenafil. Many of the AEs were similar to those reported previously. However, 27 AEs not previously reported in the literature (e.g., pulmonary hemorrhage, hemoptysis, and pneumonia) were found. The FDA postmarket records for PH medications in pediatric patients show a significant number of AEs. The discovery of AEs not previously reported will better inform those caring for these complex and critically ill children, and the large number of deaths suggest they may be underreported in current literature.

Pharmacogenomic Biomarkers: an FDA Perspective on Utilization in Biological Product Labeling.

PubMed

Schuck, Robert N; Grillo, Joseph A

2016-05-01

Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities. Since pharmacogenomic biomarker information can help inform drug dosing, efficacy, and safety, pharmacogenomic data are critically reviewed by FDA staff to ensure effective use of pharmacogenomic strategies in drug development and appropriate incorporation into product labels. Pharmacogenomic information may be provided in drug or biological product labeling to inform health care providers about the impact of genotype on response to a drug through description of relevant genomic markers, functional effects of genomic variants, dosing recommendations based on genotype, and other applicable genomic information. The format and content of labeling for biologic drugs will generally follow that of small molecule drugs; however, there are notable differences in pharmacogenomic information that might be considered useful for biologic drugs in comparison to small molecule drugs. Furthermore, the rapid entry of biologic drugs for treatment of rare genetic diseases and molecularly defined subsets of common diseases will likely lead to increased use of pharmacogenomic information in biologic drug labels in the near future. In this review, we outline the general principles of therapeutic product labeling and discuss the utilization of pharmacogenomic information in biologic drug labels.

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

An analysis of the FDA Food Safety Modernization Act: protection for consumers and boon for business.

PubMed

Strauss, Debra M

2011-01-01

This article analyzes components of the FDA Food Safety Modernization Act, which was prompted by incidents of food contamination, exploring the history of its passage and explaining its significance, as well as its limitations. As the first time in 70 years that food law has been changed substantially, this new law represents only an initial but significant step in the direction of improving food safety. With bipartisan support from both Congress and the President, this legislation embodies a mandate that food safety is at this moment becoming a priority. As a result, the time is ripe for a reassessment of other areas of food laws--particularly genetically modified foods and the use of milk and meat from cloned animals and their progeny--which are allowed under current U.S. law with no labeling, preapprovals, or post-market monitoring. These areas warrant special regulation consistent with the new proactive policy towards securing the safety of the food supply.

Trial endpoints for drug approval in oncology: Chemoprevention.

PubMed

Beitz, J

2001-04-01

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

76 FR 59141 - Determination That LOXITANE (Loxapine Succinate) Capsules and Three Other Drug Products Were Not...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice... document were not withdrawn from sale for reasons of safety or effectiveness. This determination means that... approval of the drug's NDA or ANDA for reasons of safety or effectiveness, or if FDA determines that the...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Utilization of an advisory committee on the initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any...

The history and contemporary challenges of the US Food and Drug Administration.

PubMed

Borchers, Andrea T; Hagie, Frank; Keen, Carl L; Gershwin, M Eric

2007-01-01

The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on pre-market control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false How does FDA define the terms used in this part... § 803.3 How does FDA define the terms used in this part? Some of the terms we use in this part are..., repairs, or upgrades, for an estimated period of time. FDA, we, or us means the Food and Drug...

Drug labeling and exposure in neonates.

PubMed

Laughon, Matthew M; Avant, Debbie; Tripathi, Nidhi; Hornik, Christoph P; Cohen-Wolkowiez, Michael; Clark, Reese H; Smith, P Brian; Rodriguez, William

2014-02-01

Federal legislation has led to a notable increase in pediatric studies submitted to the Food and Drug Administration (FDA), resulting in new pediatric information in product labeling. However, approximately 50% of drug labels still have insufficient information on safety, efficacy, or dosing in children. Neonatal information in labeling is even scarcer because neonates comprise a vulnerable subpopulation for which end-point development is lagging and studies are more challenging. To quantify progress made in neonatal studies and neonatal information in product labeling as a result of recent legislation. We identified a cohort of drug studies between 1997 and 2010 that included neonates as a result of pediatric legislation using information available on the FDA website. We determined what studies were published in the medical literature, the legislation responsible for the studies, and the resulting neonatal labeling changes. We then examined the use of these drugs in a cohort of neonates admitted to 290 neonatal intensive care units (NICUs) (the Pediatrix Data Warehouse) in the United States from 2005 to 2010. Infants exposed to a drug studied in neonates as identified by the FDA website. Number of drug studies with neonates and rate of exposure per 1000 admissions among infants admitted to an NICU. In a review of the FDA databases, we identified 28 drugs studied in neonates and 24 related labeling changes. Forty-one studies encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of the 24 neonatal labeling changes established safety and effectiveness. In a review of a cohort of 446,335 hospitalized infants, we identified 399 drugs used and 1,525,739 drug exposures in the first 28 postnatal days. Thirteen (46%) of the 28 drugs studied in neonates were not used in NICUs; 8 (29%) were used in fewer than 60 neonates. Of the drugs studied, ranitidine was used most often (15,627 neonates, 35 exposures per 1000 admissions). Few drug labeling changes

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

The legal and scientific basis for FDA's assertion of jurisdiction over cigarettes and smokeless tobacco.

PubMed

Kessler, D A; Barnett, P S; Witt, A; Zeller, M R; Mande, J R; Schultz, W B

1997-02-05

On August 28, 1996, the US Food and Drug Administration (FDA) asserted jurisdiction over cigarettes and smokeless tobacco under the Federal Food, Drug, and Cosmetic Act. Under this Act, a product is a "drug" or "device" subject to FDA jurisdiction if it is "intended to affect the structure or any function of the body." The FDA determined that nicotine in cigarettes and smokeless tobacco does "affect the structure or any function of the body" because nicotine causes addiction and other pharmacological effects. The FDA then determined that these pharmacological effects are "intended" because (1) a scientific consensus has emerged that nicotine is addictive; (2) recent studies have shown that most consumers use cigarettes and smokeless tobacco for pharmacological purposes, including satisfying their addiction to nicotine; and (3) newly disclosed evidence from the tobacco manufacturers has revealed that the manufacturers know that nicotine causes pharmacological effects, including addiction, and design their products to provide pharmacologically active doses of nicotine. The FDA thus concluded that cigarettes and smokeless tobacco are subject to FDA jurisdiction because they contain a "drug," nicotine, and a "device" for delivering this drug to the body.

78 FR 19492 - Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0286] Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product Sponsors or... Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled...

Considering the Future of Pharmaceutical Promotions in Social Media Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Carpentier, Francesca Renee Dillman

2016-02-09

This commentary explores the implications of increased social media marketing by drug manufacturers, based on findings in Hyosun Kim's article of the major themes in recent Food and Drug Administration (FDA) warning letters and notices of violation regarding online direct-to-consumer promotions of pharmaceuticals. Kim's rigorous analysis of FDA letters over a 10-year span highlights a relative abundance of regulatory action toward marketer-controlled websites and sponsored advertisements, compared to branded and unbranded social media messaging. However, social media marketing efforts are increasing, as is FDA attention to these efforts. This commentary explores recent developments and continuing challenges in the FDA's attempts to provide guidance and define pharmaceutical company accountability in marketer-controlled and -uncontrolled claims disseminated through social media. © 2016 by Kerman University of Medical Sciences.

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

Safety Assessment of Alumina and Aluminum Hydroxide as Used in Cosmetics.

PubMed

Becker, Lillian C; Boyer, Ivan; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2016-11-01

This is a safety assessment of alumina and aluminum hydroxide as used in cosmetics. Alumina functions as an abrasive, absorbent, anticaking agent, bulking agent, and opacifying agent. Aluminum hydroxide functions as a buffering agent, corrosion inhibitor, and pH adjuster. The Food and Drug Administration (FDA) evaluated the safe use of alumina in several medical devices and aluminum hydroxide in over-the-counter drugs, which included a review of human and animal safety data. The Cosmetic Ingredient Review (CIR) Expert Panel considered the FDA evaluations as part of the basis for determining the safety of these ingredients as used in cosmetics. Alumina used in cosmetics is essentially the same as that used in medical devices. This safety assessment does not include metallic or elemental aluminum as a cosmetic ingredient. The CIR Expert Panel concluded that alumina and aluminum hydroxide are safe in the present practices of use and concentration described in this safety assessment. © The Author(s) 2016.

75 FR 28622 - FDA Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] FDA Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of the U.S. Food and Drug Administration; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

Use of data mining at the Food and Drug Administration.

PubMed

Duggirala, Hesha J; Tonning, Joseph M; Smith, Ella; Bright, Roselie A; Baker, John D; Ball, Robert; Bell, Carlos; Bright-Ponte, Susan J; Botsis, Taxiarchis; Bouri, Khaled; Boyer, Marc; Burkhart, Keith; Condrey, G Steven; Chen, James J; Chirtel, Stuart; Filice, Ross W; Francis, Henry; Jiang, Hongying; Levine, Jonathan; Martin, David; Oladipo, Taiye; O'Neill, Rene; Palmer, Lee Anne M; Paredes, Antonio; Rochester, George; Sholtes, Deborah; Szarfman, Ana; Wong, Hui-Lee; Xu, Zhiheng; Kass-Hout, Taha

2016-03-01

This article summarizes past and current data mining activities at the United States Food and Drug Administration (FDA). We address data miners in all sectors, anyone interested in the safety of products regulated by the FDA (predominantly medical products, food, veterinary products and nutrition, and tobacco products), and those interested in FDA activities. Topics include routine and developmental data mining activities, short descriptions of mined FDA data, advantages and challenges of data mining at the FDA, and future directions of data mining at the FDA. Published by Oxford University Press on behalf of the American Medical Informatics Association 2015. This work is written by US Government employees and is in the public domain in the US.