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...

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.

Drugs@FDA: FDA Approved Drug Products

MedlinePlus

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

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

Frequency and level of evidence used in recommendations by the National Comprehensive Cancer Network guidelines beyond approvals of the US Food and Drug Administration: retrospective observational study.

PubMed

Wagner, Jeffrey; Marquart, John; Ruby, Julia; Lammers, Austin; Mailankody, Sham; Kaestner, Victoria; Prasad, Vinay

2018-03-07

To determine the differences between recommendations by the National Comprehensive Cancer Network (NCNN) guidelines and Food and Drug Administration approvals of anticancer drugs, and the evidence cited by the NCCN to justify recommendations where differences exist. Retrospective observational study. National Comprehensive Cancer Network and FDA. 47 new molecular entities approved by the FDA between 2011 and 2015. Comparison of all FDA approved indications (new and supplemental) with all NCCN recommendations as of 25 March 2016. When the NCCN made recommendations beyond the FDA's approvals, the recommendation was classified and the cited evidence noted. 47 drugs initially approved by the FDA between 2011 and 2015 for adult hematologic or solid cancers were examined. These 47 drugs were authorized for 69 FDA approved indications, whereas the NCCN recommended these drugs for 113 indications, of which 69 (62%) overlapped with the 69 FDA approved indications and 44 (39%) were additional recommendations. The average number of recommendations beyond the FDA approved indications was 0.92. 23% (n=10) of the additional recommendations were based on evidence from randomized controlled trials, and 16% (n=7) were based on evidence from phase III studies. During 21 months of follow-up, the FDA granted approval to 14% (n=6) of the additional recommendations. The NCCN frequently recommends beyond the FDA approved indications even for newer, branded drugs. The strength of the evidence cited by the NCCN supporting such recommendations is weak. Our findings raise concern that the NCCN justifies the coverage of costly, toxic cancer drugs based on weak evidence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Review of Patient-Reported Outcome Labeling in the United States (2011-2015).

PubMed

Gnanasakthy, Ari; Mordin, Margaret; Evans, Emily; Doward, Lynda; DeMuro, Carla

2017-03-01

A review of new drug approvals (NDAs) by the Food and Drug Administration (FDA) for 2006 to 2010 showed that 24.1% of new drugs had patient-reported outcome (PRO) labeling. To review PRO labeling for NDAs for 2011 to 2015 and to compare key findings reported previously. A review of the FDA drug approval reports for NDAs was conducted using the FDA Web site to determine the number of NDAs for the period 2011 to 2015. For all identified NDAs, drug approval package and product labeling were reviewed to identify PRO end-point status and PRO labeling. NDAs for the period 2006 to 2015 were grouped by disease category as per the International Classification of Diseases, Tenth Revision. Data were summarized for all NDAs and for approvals in diseases that traditionally rely on PROs for evaluating treatment benefit (PRO-dependent). Results were compared with NDAs for the period 2006 to 2010. In the period 2011 to 2015, 16.5% of the 182 NDAs had PRO labeling. For PRO-dependent NDAs, this figure was 46.9% and 46.0% for the period 2006 to 1010 and the period 2011 to 2015, respectively. Most of the PRO labeling for the period 2011 to 2015 was based on primary end points (76.7%). Almost all PRO labeling was for concepts proximal to the disease. There is potential for increased PRO labeling, especially for drug approvals in diseases that traditionally rely on PROs for evaluating treatment benefit to satisfy regulatory needs. Less PRO labeling based on secondary end points may be indicative of drug manufacturers' reluctance to aid and enhance the value propositions of their products to all stakeholders, including patients. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

How drugs are developed and approved by the FDA: current process and future directions.

PubMed

Ciociola, Arthur A; Cohen, Lawrence B; Kulkarni, Prasad

2014-05-01

This article provides an overview of FDA's regulatory processes for drug development and approval, and the estimated costs associated with the development of a drug, and also examines the issues and challenges facing the FDA in the near future. A literature search was performed using MEDLINE to summarize the current FDA drug approval processes and future directions. MEDLINE was further utilized to search for all cost analysis studies performed to evaluate the pharmaceutical industry R&D productivity and drug development cost estimates. While the drug approval process remains at high risk and spans over multiple years, the FDA drug review and approval process has improved, with the median approval time for new molecular drugs been reduced from 19 months to 10 months. The overall cost to development of a drug remains quite high and has been estimated to range from $868M to $1,241M USD. Several new laws have been enacted, including the FDA Safety and Innovation Act (FDASIA) of 2013, which is designed to improve the drug approval process and enhance access to new medicines. The FDA's improved processes for drug approval and post-market surveillance have achieved the goal of providing patients with timely access to effective drugs while minimizing the risk of drug-related harm. The FDA drug approval process is not without controversy, as a number of well-known gastroenterology drugs have been withdrawn from the US market over the past few years. With the approval of the new FDASIA law, the FDA will continue to improve their processes and, working together with the ACG through the FDA-Related Matters Committee, continue to develop safe and effective drugs for our patients.

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

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 314.125 - Refusal to approve an application.

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... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given 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 314.125 - Refusal to approve an application.

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... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 314.125 - Refusal to approve an application.

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... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 314.125 - Refusal to approve an application.

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... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given 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 314.125 - Refusal to approve an application.

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... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 814.45 - Denial of approval of a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.45 Denial of approval of a PMA. (a) FDA may issue an order denying approval of a PMA if the applicant fails to follow the... information before the agency, FDA determines that any of the grounds for denying approval of a PMA specified...

21 CFR 814.45 - Denial of approval of a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.45 Denial of approval of a PMA. (a) FDA may issue an order denying approval of a PMA if the applicant fails to follow the... information before the agency, FDA determines that any of the grounds for denying approval of a PMA specified...

21 CFR 814.45 - Denial of approval of a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.45 Denial of approval of a PMA. (a) FDA may issue an order denying approval of a PMA if the applicant fails to follow the... information before the agency, FDA determines that any of the grounds for denying approval of a PMA specified...

Could FDA approval of pre-exposure prophylaxis make a difference? A qualitative study of PrEP acceptability and FDA perceptions among men who have sex with men.

PubMed

Underhill, Kristen; Morrow, Kathleen M; Operario, Don; Mayer, Kenneth H

2014-02-01

The FDA has approved tenofovir-emtricitabine for use as HIV pre-exposure prophylaxis, but it is unknown how approval may affect PrEP acceptability among US men who have sex with men. We conducted 8 focus groups among 38 Rhode Island MSM, including 3 groups among 16 male sex workers and 5 groups among 22 men in the general MSM community. Participants reported wide-ranging beliefs regarding consequences and meanings of FDA approval. Some participants would not use PrEP without approval, while others perceived approval as irrelevant or less significant than other sources of information. Our results suggest that FDA approval sends a signal that directly shapes PrEP acceptability among some MSM, while indirect influences of approval may affect uptake by others. Efforts to educate MSM about PrEP can increase acceptability by incorporating information about FDA approval, and outreach strategies should consider how this information may factor into personal decisions about PrEP use.

FDA: polyurethane condom carries "extremely misleading" label. Federal agency allows distribution for public health's sake.

PubMed

1995-02-01

The labeling of the Avanti polyurethane condom selling in 10 Western states makes misleading claims about protection from pregnancy and sexually transmitted diseases (STDs) according to officials at the US Food and Drug Administration (FDA). Avanti is sold in a foil package printed with the claim that it is effective against pregnancy, HIV, and STDs. However, polyurethane condoms have not undergone clinical efficacy testing for contraception or STDs, according to officials. The manufacturer of the condom refuted this allegation, stating that latex condoms have the same claims on them. In early 1995 the FDA met with the manufacturer and other companies developing plastic condoms, and concluded that these condoms could not make such claims, nor any claims about slippage and breakage rates. Despite warnings in 1993 to the manufacturer of Avanti about labeling restrictions, the company printed pregnancy and STD efficacy claims on the boxes and individual packages. The FDA later worked out a compromise with the firm in which only the boxes had to be reprinted with the generic label. The FDA had to weigh the risk of the public health cost of delaying sale of the condom, which is the first impermeable condom proven safe for people with latex allergies. In 1991 the FDA was defining standards for clinical testing and labeling of polyurethane condoms under congressional mandate, but the manufacturer of Avanti began mass production based on a preliminary approval determining that the condom was equivalent to latex condoms already on the market. 7000 Avanti condoms were subsequently tested in five countries, but these user tests did not compare Avanti to latex condoms and did not test for pregnancy and STD protection. Test results submitted to the FDA by the company indicated that, although Avanti is more than 1/3 less elastic than latex condoms, it did not break more frequently in an in-use study involving 187 couples.

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

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.

FDA Approves Lutathera for Neuroendocrine Tumors

Cancer.gov

FDA has approved Lutathera® for some people with neuroendocrine tumors (NETs) that affect the digestive tract. On January 29, FDA approved Lutathera® for adult patients with advanced NETs that affect the pancreas or gastrointestinal tract, known as GEP-NETs.

Application of FDA-Approved Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in Rodent Models of Tuberous Sclerosis Complex

DTIC Science & Technology

2015-06-01

AWARD NUMBER: W81XWH-13-1-0053 TITLE: Application of FDA-Approved Memantine and Newer NitroMemantine Derivatives to Treat Neurological...2015 Final 1 May 2013 - 30 Apr 2015 Application of FDA-Approved Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in...FDA-approved drug, Memantine , an uncompetitive/fast off-rate antagonist of the Nmethyl-D-aspartate-type glutamate receptor, and its improved

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

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.

21 CFR 814.46 - Withdrawal of approval of a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.46 Withdrawal of approval of a PMA. (a) FDA may issue an order withdrawing approval of a PMA if, from any information available to the agency, FDA determines that: (1) Any of the grounds under section 515(e)(1) (A)-(G) of the act...

21 CFR 814.46 - Withdrawal of approval of a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.46 Withdrawal of approval of a PMA. (a) FDA may issue an order withdrawing approval of a PMA if, from any information available to the agency, FDA determines that: (1) Any of the grounds under section 515(e)(1) (A)-(G) of the act...

21 CFR 814.46 - Withdrawal of approval of a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.46 Withdrawal of approval of a PMA. (a) FDA may issue an order withdrawing approval of a PMA if, from any information available to the agency, FDA determines that: (1) Any of the grounds under section 515(e)(1) (A)-(G) of the act...

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

PubMed

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

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

"Off Label" Use of FDA-Approved Devices and Digital Breast Tomosynthesis.

PubMed

Kopans, Daniel B

2015-11-01

The purpose of this article is to clarify for radiologists the meaning of U.S. Food and Drug Administration (FDA) approval with respect to Digital Breast Tomosynthesis (DBT). DBT is a major improvement over 2D mammography in the detection of cancers (sensitivity) and the reduction in recalls resulting from screening (specificity). Most imaging systems that have been approved by the FDA are used "off label" for breast imaging. Although the FDA determines which claims a manufacturer can make for a device, physicians may use approved devices, such as DBT, off label to provide better patient care.

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.

21 CFR 314.150 - Withdrawal of approval of an application or abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.150 Withdrawal of approval of an... abbreviated application for a new drug on a finding that there is an imminent hazard to the public health. FDA...

21 CFR 314.150 - Withdrawal of approval of an application or abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.150 Withdrawal of approval of an... abbreviated application for a new drug on a finding that there is an imminent hazard to the public health. FDA...

21 CFR 814.47 - Temporary suspension of approval of a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.47 Temporary suspension of approval of a PMA. (a) Scope. (1) This section describes the procedures that FDA will follow in... the original PMA, as well as any PMA supplement(s), for a medical device. (2) FDA will issue an order...

21 CFR 814.47 - Temporary suspension of approval of a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.47 Temporary suspension of approval of a PMA. (a) Scope. (1) This section describes the procedures that FDA will follow in... the original PMA, as well as any PMA supplement(s), for a medical device. (2) FDA will issue an order...

21 CFR 314.150 - Withdrawal of approval of an application or abbreviated application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.150 Withdrawal of approval of an... abbreviated application for a new drug on a finding that there is an imminent hazard to the public health. FDA...

21 CFR 314.150 - Withdrawal of approval of an application or abbreviated application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.150 Withdrawal of approval of an... abbreviated application for a new drug on a finding that there is an imminent hazard to the public health. FDA...

21 CFR 814.47 - Temporary suspension of approval of a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) MEDICAL DEVICES PREMARKET APPROVAL OF MEDICAL DEVICES FDA Action on a PMA § 814.47 Temporary suspension of approval of a PMA. (a) Scope. (1) This section describes the procedures that FDA will follow in... the original PMA, as well as any PMA supplement(s), for a medical device. (2) FDA will issue an order...

21 CFR 314.150 - Withdrawal of approval of an application or abbreviated application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.150 Withdrawal of approval of an... abbreviated application for a new drug on a finding that there is an imminent hazard to the public health. FDA...

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.

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

PubMed

Park, Glen D; Mitchel, Jules T

2016-06-01

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

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

PubMed

Sasinowski, Frank J; Varond, Alexander J

2016-08-01

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

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

PubMed

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

2015-05-15

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

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.152 - Notice of withdrawal of approval of an application or abbreviated application for a new drug.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.152 Notice of... Administration withdraws approval of an application or abbreviated application for a new drug, FDA will publish a...

21 CFR 314.152 - Notice of withdrawal of approval of an application or abbreviated application for a new drug.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.152 Notice of... Administration withdraws approval of an application or abbreviated application for a new drug, FDA will publish a...

21 CFR 314.152 - Notice of withdrawal of approval of an application or abbreviated application for a new drug.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.152 Notice of... Administration withdraws approval of an application or abbreviated application for a new drug, FDA will publish a...

21 CFR 314.152 - Notice of withdrawal of approval of an application or abbreviated application for a new drug.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.152 Notice of... Administration withdraws approval of an application or abbreviated application for a new drug, FDA will publish a...

21 CFR 314.152 - Notice of withdrawal of approval of an application or abbreviated application for a new drug.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.152 Notice of... Administration withdraws approval of an application or abbreviated application for a new drug, FDA will publish a...

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

PubMed

1998-01-29

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

Regulatory Challenges for Cartilage Repair Technologies.

PubMed

McGowan, Kevin B; Stiegman, Glenn

2013-01-01

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

Regulatory Challenges for Cartilage Repair Technologies

PubMed Central

Stiegman, Glenn

2013-01-01

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

Incentives for orphan drug research and development in the United States.

PubMed

Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Szeinbach, Sheryl L; Visaria, Jay

2008-12-16

The Orphan Drug Act (1983) established several incentives to encourage the development of orphan drugs (ODs) to treat rare diseases and conditions. This study analyzed the characteristics of OD designations, approvals, sponsors, and evaluated the effective patent and market exclusivity life of orphan new molecular entities (NMEs) approved in the US between 1983 and 2007. Primary data sources were the FDA Orange Book, the FDA Office of Orphan Drugs Development, and the US Patent and Trademark Office. Data included all orphan designations and approvals listed by the FDA and all NMEs approved by the FDA during the study period. The FDA listed 1,793 orphan designations and 322 approvals between 1983 and 2007. Cancer was the main group of diseases targeted for orphan approvals. Eighty-three companies concentrated 67.7% of the total orphan NMEs approvals. The average time from orphan designation to FDA approval was 4.0 +/- 3.3 years (mean +/- standard deviation). The average maximum effective patent and market exclusivity life was 11.7 +/- 5.0 years for orphan NME. OD market exclusivity increased the average maximum effective patent and market exclusivity life of ODs by 0.8 years. Public programs, federal regulations, and policies support orphan drugs R&D. Grants, research design support, FDA fee waivers, tax incentives, and orphan drug market exclusivity are the main incentives for orphan drug R&D. Although the 7-year orphan drug market exclusivity provision had a positive yet relatively modest overall effect on effective patent and market exclusivity life, economic incentives and public support mechanisms provide a platform for continued orphan drug development for a highly specialized market.

Innovating by developing new uses of already-approved drugs: trends in the marketing approval of supplemental indications.

PubMed

DiMasi, Joseph A

2013-06-01

Much of the literature on trends and factors affecting biopharmaceutical innovation has focused overwhelmingly on the development and approval of never-before approved drugs and biologics. Little attention has been paid to new uses for already-approved compounds, which can be an important form of innovation. This paper aimed to determine and analyze recent trends in the number and type of new or modified US indication approvals for drugs and biologics. We also examine regulatory approval-phase times for new-use efficacy supplements and compare them to approval-phase times for original-use approvals over the same period. We developed a data set of efficacy supplements approved by the US Food and Drug Administration (FDA) from 1998 to 2011 that includes information on the type, approval-phase time (time from submission to the FDA of an application for marketing approval to approval of the application), and FDA therapeutic-significance rating for the approved application, which we obtained from an FDA Web site. This data set was merged with a Tufts Center for the Study of Drug Development (CSDD) data set of US new drug and biologics approvals. We developed descriptive statistics on trends in the number and type of new-use efficacy supplements, on US regulatory approval-phase times for the supplements, and on original new drug and biologics approvals over the study period and for the time from original- to new-use approval. The total number of new-use efficacy-supplement approvals did not exhibit a marked trend, but the number of new pediatric-indication approvals increased substantially. Approval-phase times for new-use supplements varied by therapeutic class and FDA therapeutic-significance rating. Mean approval-phase times were highest for central nervous system compounds (13.8 months) and lowest for antineoplastics (8.9 months). The mean time from original to supplement approval was substantially longer for new pediatric indications than for other new uses. Mean approval-phase time during the study period for applications that received a standard review rating from the FDA was substantially shorter for supplements compared to original uses, but the differences for applications that received a priority review rating from the FDA were negligible. Development of and regulatory approval for new uses of already-approved drugs and biologics is an important source of innovation by biopharmaceutical firms. Despite rising development costs, the output of new-use approvals has remained stable in recent years, driven largely by the pursuit of new pediatric indications. FDA approval-phase times have generally declined substantially for all types of applications since the mid-1990s following legislation that provided a new source of income for the agency. However, while the resources needed to review supplemental applications are likely lower in general than for original-use approvals, the approval-phase times for important new uses are no lower than for important original-use applications. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Understanding risk evaluation and mitigation strategies in organ transplantation.

PubMed

Gabardi, Steven

2011-07-01

The United States Food and Drug Administration (FDA) Amendments Act of 2007 mandated that Risk Evaluation and Mitigation Strategies (REMS) be required of manufacturers. These REMS are strategies implemented to manage known or potential risks associated with drugs and to ensure ongoing pharmacovigilance throughout the life of a pharmaceutical product, including once the product becomes available as generic. The elements of an individual REMS program consist of three levels: medication guide or patient package insert, communication plan, and elements to assure safe use (ETASU). A medication guide or patient package insert is used to help prevent serious adverse events, aid in patient decision making, and enhance drug adherence. Communication plans are used to educate health care providers and to encourage their compliance with REMS. The ETASU is a restrictive process that is implemented when it is deemed necessary to ensure that patients have safe access to products with known serious risks that would otherwise be unavailable. To review the components of REMS and specifically assess their impact on health care providers practicing within the organ transplantation arena, a literature search of the MEDLINE database (January 2007-December 2010) was performed, and published materials from the FDA and its Web site were also reviewed. In transplantation, REMS programs exist for both everolimus (medication guide and communication plan) and sirolimus (medication guide). The FDA has stated that all mycophenolic acid derivatives will be subject to a proposed REMS that has not yet been approved; however, both branded mycophenolic acid agents already have approved medication guides. The REMS are a permanent fixture in the development and marketing of pharmaceutical agents, and their further implementation in solid organ transplantation is inevitable. Transplantation providers should take a proactive role in patient education and implementation of REMS within the therapeutic area. It is imperative for health care providers to realize that the ultimate goals of REMS are to reduce the potential for serious risks and to make outcomes from the treatment of disease more predictable.

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

PubMed

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

2016-06-01

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

Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease.

PubMed

Boyiadzis, Michael M; Kirkwood, John M; Marshall, John L; Pritchard, Colin C; Azad, Nilofer S; Gulley, James L

2018-05-14

The U.S. Food and Drug Administration (FDA) recently approved pembrolizumab, an anti- programmed cell death protein 1 cancer immunotherapeutic, for use in advanced solid tumors in patients with the microsatellite-high/DNA mismatch repair-deficient biomarker. This is the first example of a tissue-agnostic FDA approval of a treatment based on a patient's tumor biomarker status, rather than on tumor histology. Here we discuss key issues and implications arising from the biomarker-based disease classification implied by this historic approval.

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

PubMed Central

Largent, Emily A.

2016-01-01

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

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

PubMed

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

2018-02-01

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

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.

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.

Improving the postmarket surveillance of total joint arthroplasty devices.

PubMed

Mahomed, Nizar N; Syed, Khalid; Sledge, Clement B; Brennan, Troyen A; Liang, Matthew H

2008-01-01

To evaluate the FDA's approval process and postmarket surveillance strategies for THR devices. The FDA Center for Devices and Radiological Health (CDRH) 510k releasable database was used to document approved THR devices. The CDRH Medical Device Reporting data files were used to study the efficiency of the FDA's post-market surveillance system. Manufacturers were contacted to supply information regarding their implants. Medline was searched between 1966-1996 to determine the percentage of THR devices with published data on clinical outcomes. Between 1976 and 1996, 701 new THR devices were approved by the Substantial Equivalent (SE) route and 34 were approved on the basis of Premarket Approval PMA. The number of approvals doubled between 1991-1995 compared to 1976-1990. Seventy-four different manufacturers obtained approval to market THR devices. Only four manufacturers obtained approval via the PMA application. Under Mandatory Device Reporting all revision arthroplasties should be reported. Using data from 2 independent services for which we had US hospital discharge data in 1993 we estimate that only 3% of all revision THR were reported to the FDA. Manufacturers of hip implants failed to provide useful information. Medline search revealed only 15% of the approved THR devices had published data on outcomes. Current FDA premarket approval and postmarket surveillance strategies fail to provide information for evidence-based selection of THR devices. Recommendations are made to avert problems with device failures.

Deficiencies of product labeling directions for the preparation of radiopharmaceuticals.

PubMed

Hung, Joseph C; Ponto, James A; Gadient, Katie R; Frie, Julia A; Aksamit, Carolyn M; Enquist, Cassandra L; Carrels, Katie E

2004-01-01

To identify potential deficiencies in product labeling (package insert) instructions for the preparation of radiopharmaceuticals. Preparation instructions, which include both reconstitution and quality control (QC) directions, as stated in the package inserts were evaluated for all commercially available reconstituted radiopharmaceuticals. Reviews of the package inserts were initially performed by each author, and then all identified deficiencies were compiled and evaluated by all authors. The preparation scenario for each package insert evaluated was based on a centralized nuclear pharmacy operation assuming typical support personnel, standard operating equipment, and workload. The instructions as stated in each package insert for the preparation (including QC) were rated as inadequate if a satisfactory preparation could not be prepared by a nuclear pharmacist or physician when instructions were followed exactly. Identified deficiencies in package insert instructions for the preparation of radiopharmaceuticals fell into the following five categories: (1) absent or incomplete directions (especially with regard to QC procedures); (2) restrictive directions (e.g., specific requirement to use designated needles, chromatography solvents, counting devices), (3) inconsistent directions (e.g., different reconstituted volumes for the same final drug product, unworkable expiration times); (4) impractical directions (e.g., unrealistically low reconstituted activity limits, dangerously high number of radiolabeled particles); and (5) vague directions (e.g., use of the words "should," "may," "recommend"). Manufacturers' directions for the preparation of radiopharmaceuticals often contain deficiencies and should be viewed as standard guidance rather than as requirements. Just as physicians are permitted to use U.S. Food and Drug Administration (FDA)-approved drugs for off-label indications, nuclear pharmacists should be allowed to use alternative methods for preparing radiopharmaceuticals, provided those methods have been validated to be as good as the stated directions and that the nuclear pharmacists do not engage in activities that fall outside the normal practice of pharmacy. Manufacturers, FDA, nuclear pharmacists, and nuclear physicians should work together to address identified deficiencies in package insert directions.

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

PubMed Central

Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

2017-01-01

Objectives To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Design Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data sources Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Outcome measures Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. Results The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Conclusions Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress. PMID:29208616

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

Incremental Revisions across the Life Span of Ophthalmic Devices after Initial Food and Drug Administration Premarket Approval, 1979-2015.

PubMed

Gopal, Anand D; Rathi, Vinay K; Teng, Christopher C; Del Priore, Lucian; Ross, Joseph S

2017-08-01

To characterize the frequency, nature, and regulatory mechanisms by which ophthalmic devices are iteratively modified after initial Food and Drug Administration (FDA) Premarket Approval (PMA). Retrospective cross-sectional analysis using publicly available FDA data. Ophthalmic devices initially approved via the FDA's PMA pathway between January 1, 1979 and December 31, 2015. We used the FDA's PMA Database to identify and characterize initial approvals and subsequent postmarket modifications to Class III ophthalmic devices. The FDA Recalls Database was used to identify associated safety events. Median iterated life span (timespan across which modifications occurred after initial PMA) and median number of supplements approved per device, by device type, and overall, stratified by regulatory pathway and modification type. Between 1979 and 2015, the FDA approved 168 original ophthalmic devices via the PMA pathway and 2813 subsequent modifications. More than one third (n = 64; 38%) of original approvals were intraocular lenses. Overall, devices underwent a median of 11 postmarket modifications (interquartile range [IQR], 3-24.8) across a median 10.0-year iterated life span (IQR, 4.1-16.7). The majority of devices (n = 144; 86%) underwent more than 1 postapproval modification, including more than 1 design modification (n = 84; 50%). The median number of changes altering device design or labeling was 3.5 (IQR, 1-9). Although manufacturing alterations (n = 834 of 2813; 30%) were the most frequent type of revision, changes involving device design (n = 667; 24%) and labeling (n = 417; 15%) were common. Recalled devices underwent more frequent postapproval modifications per year (median, 1.4; IQR, 0.7-2.3; mean, 1.5; 95% confidence interval, 1.1-1.9) in the period preceding recall than did nonrecalled devices (median, 0.5; IQR, 0.2-1.1; mean, 0.8; 95% confidence interval, 0.7-1.0) across their market approval period (P < 0.001). Most ophthalmic devices approved via the FDA's PMA pathway have undergone extensive revisions, including serial design and labeling changes, since their initial approvals, often without supporting clinical data. Ophthalmologists should take into consideration that cumulative revisions may render the clinical evidence that supported an original FDA approval less relevant to newer device models. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Contrasting clinical evidence for market authorisation of cardio-vascular devices in Europe and the USA: a systematic analysis of 10 devices based on Austrian pre-reimbursement assessments.

PubMed

Wild, Claudia; Erdös, Judit; Zechmeister, Ingrid

2014-11-04

European medical device regulation is under scrutiny and will be re-regulated with stricter rules concerning requirements for clinical evidence for high-risk medical devices. It is the aim of this study to analyse the differences between Europe and USA in dealing with risks and benefits of new cardio-vascular devices. Since no information is available on clinical data used by the Notified Body for CE-marking, data from Austrian pre-reimbursement assessments close to European market approval were used as proxy and compared with clinical data available at time of market approval by FDA in the USA. 10 cardio-vascular interventions with 27 newly CE approved medical devices were analysed. The time lag between market authorisation in Europe and in the USA is 3 to 7 years. Only 7 CE-marked devices also hold a FDA market approval, 7 further devices are in FDA approved ongoing efficacy trials. For 4 of the CE-marked devices the FDA market application or the approval-trial was either suspended due to efficacy or safety concerns or the approval was denied. Evidence available at time of CE-marking are most often case-series or small feasibility RCTs, while large RCTs and only in rare cases prospective cohort studies are the basis of FDA approvals. Additionally, the FDA often requires post-approval studies for high-risk devices. Market authorisation based on mature clinical data deriving from larger RCTs and longer follow-ups do not only change the perspective on the risk-benefit ratio, but also secures real patient benefit and safety and assures payers of investing only in truly innovative devices.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

PubMed

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2015-01-01

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

21 CFR 314.93 - Petition to request a change from a listed drug.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... listed combination drug, must first obtain permission from FDA to submit such an abbreviated application... petition that is permitted under paragraph (a) of this section is submitted, FDA will approve or disapprove...

21 CFR 314.93 - Petition to request a change from a listed drug.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... listed combination drug, must first obtain permission from FDA to submit such an abbreviated application... petition that is permitted under paragraph (a) of this section is submitted, FDA will approve or disapprove...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

21 CFR 814.40 - Time frames for reviewing a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

21 CFR 814.40 - Time frames for reviewing a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

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

Code of Federal Regulations, 2010 CFR

2010-04-01

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

21 CFR 314.93 - Petition to request a change from a listed drug.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... listed combination drug, must first obtain permission from FDA to submit such an abbreviated application... petition that is permitted under paragraph (a) of this section is submitted, FDA will approve or disapprove...

21 CFR 814.40 - Time frames for reviewing a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

Assessing the potential clinical impact of reciprocal drug approval legislation on access to novel therapeutics in the USA: a cohort study.

PubMed

Larochelle, Matthieu; Downing, Nicholas S; Ross, Joseph S; David, Frank S

2017-02-08

To quantify the potential effect of reciprocal approval legislation on access to clinically impactful therapeutics in the USA. A cohort study. New therapeutics approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and/or Health Canada between 2000 and 2010. Characteristics of new therapeutics approved by the EMA and/or Health Canada before the FDA, including mechanistic novelty, likely clinical impact, size of the affected population and FDA review outcome. From 2001 to 2010, 282 drugs were approved in the USA, Europe or Canada, including 172 (61%) first approved in the USA, 24 (9%) never approved in the USA, and 86 (30%) approved in the USA after Europe and/or Canada. Of the 110 new drugs approved in Europe and/or Canada before the USA, 37 (34%) had a novel mechanisms of action compared with drugs already approved by the FDA, but only 10 (9%) were for conditions lacking alternate available therapies in the USA at the time of ex-US approval-of which the majority (9/10; 90%) were indicated for rare diseases. 12 of the 37 agents with novel mechanisms of action approved first in Europe and/or Canada (32%) had their initial FDA submissions rejected for safety reasons-including 2 drugs that were ultimately withdrawn from the market in Europe due to safety concerns. If enacted, reciprocal approval legislation would most likely benefit only a small number of US patients receiving treatment for rare diseases, and the benefit may be somewhat mitigated by an increased exposure to harms. 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/.

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

PubMed

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

2012-08-01

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

FDA Expands Abiraterone Approval for Prostate Cancer

Cancer.gov

The FDA has expanded the approval of abiraterone (Zytiga) to treat men with metastatic prostate cancer. The agency approved abiraterone, in combination with prednisone, for men whose cancer that is responsive to hormone-blocking treatments (also known as castration-sensitive) and is at high risk of progressing.

Assessing the potential clinical impact of reciprocal drug approval legislation on access to novel therapeutics in the USA: a cohort study

PubMed Central

Larochelle, Matthieu; Downing, Nicholas S; Ross, Joseph S; David, Frank S

2017-01-01

Objective To quantify the potential effect of reciprocal approval legislation on access to clinically impactful therapeutics in the USA. Design A cohort study. Setting New therapeutics approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and/or Health Canada between 2000 and 2010. Main outcome measures Characteristics of new therapeutics approved by the EMA and/or Health Canada before the FDA, including mechanistic novelty, likely clinical impact, size of the affected population and FDA review outcome. Results From 2001 to 2010, 282 drugs were approved in the USA, Europe or Canada, including 172 (61%) first approved in the USA, 24 (9%) never approved in the USA, and 86 (30%) approved in the USA after Europe and/or Canada. Of the 110 new drugs approved in Europe and/or Canada before the USA, 37 (34%) had a novel mechanisms of action compared with drugs already approved by the FDA, but only 10 (9%) were for conditions lacking alternate available therapies in the USA at the time of ex-US approval—of which the majority (9/10; 90%) were indicated for rare diseases. 12 of the 37 agents with novel mechanisms of action approved first in Europe and/or Canada (32%) had their initial FDA submissions rejected for safety reasons—including 2 drugs that were ultimately withdrawn from the market in Europe due to safety concerns. Conclusions If enacted, reciprocal approval legislation would most likely benefit only a small number of US patients receiving treatment for rare diseases, and the benefit may be somewhat mitigated by an increased exposure to harms. PMID:28179418

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

PubMed

Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

2017-12-05

To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies' transparency records and recognise exemplary companies may encourage further progress. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

21 CFR 514.80 - Records and reports concerning experience with approved new animal drugs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... and 2301? How can I get them? Can I use computer-generated equivalents? 514.80(d) Reporting forms. How... provided on the forms. Computer-generated equivalents of Form FDA 1932 or Form FDA 2301, approved by FDA... Medicine, Division of Surveillance (HFV-210), 7500 Standish Pl., Rockville, MD 20855-2764. (e) Records to...

21 CFR 514.80 - Records and reports concerning experience with approved new animal drugs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and 2301? How can I get them? Can I use computer-generated equivalents? 514.80(d) Reporting forms. How... provided on the forms. Computer-generated equivalents of Form FDA 1932 or Form FDA 2301, approved by FDA... Medicine, Division of Surveillance (HFV-210), 7500 Standish Pl., Rockville, MD 20855-2764. (e) Records to...

21 CFR 514.80 - Records and reports concerning experience with approved new animal drugs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... and 2301? How can I get them? Can I use computer-generated equivalents? 514.80(d) Reporting forms. How... provided on the forms. Computer-generated equivalents of Form FDA 1932 or Form FDA 2301, approved by FDA... Medicine, Division of Surveillance (HFV-210), 7500 Standish Pl., Rockville, MD 20855-2764. (e) Records to...

21 CFR 514.80 - Records and reports concerning experience with approved new animal drugs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and 2301? How can I get them? Can I use computer-generated equivalents? 514.80(d) Reporting forms. How... provided on the forms. Computer-generated equivalents of Form FDA 1932 or Form FDA 2301, approved by FDA... Medicine, Division of Surveillance (HFV-210), 7500 Standish Pl., Rockville, MD 20855-2764. (e) Records to...

21 CFR 514.80 - Records and reports concerning experience with approved new animal drugs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and 2301? How can I get them? Can I use computer-generated equivalents? 514.80(d) Reporting forms. How... provided on the forms. Computer-generated equivalents of Form FDA 1932 or Form FDA 2301, approved by FDA... Medicine, Division of Surveillance (HFV-210), 7500 Standish Pl., Rockville, MD 20855-2764. (e) Records to...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

21 CFR 314.70 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... application. (1)(i) Except as provided in paragraph (a)(1)(ii) of this section, the applicant must notify FDA... of change, the applicant must notify FDA about the change in a supplement under paragraph (b) or (c...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

21 CFR 314.70 - Supplements and other changes to an approved application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... application. (1)(i) Except as provided in paragraph (a)(1)(ii) of this section, the applicant must notify FDA... of change, the applicant must notify FDA about the change in a supplement under paragraph (b) or (c...

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-05-09

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

78 FR 70062 - Withdrawal of Approval of New Animal Drug Applications; Carbarsone; Roxarsone

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0002] Withdrawal of Approval of New Animal Drug Applications; Carbarsone; Roxarsone AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of...

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

PubMed

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

2017-12-06

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

FDA Approves Apalutamide for Prostate Cancer

Cancer.gov

Apalutamide (Erleada) is a hormone therapy that counteracts resistance to androgen deprivation therapy. Learn more about the FDA approval of apalutamide for men with castration-resistant nonmetastatic prostate cancer in this Cancer Currents blog post.

Verification of performance specifications for a US Food and Drug Administration-approved molecular microbiology test: Clostridium difficile cytotoxin B using the Becton, Dickinson and Company GeneOhm Cdiff assay.

PubMed

Schlaberg, Robert; Mitchell, Michael J; Taggart, Edward W; She, Rosemary C

2012-01-01

US Food and Drug Administration (FDA)-approved diagnostic tests based on molecular genetic technologies are becoming available for an increasing number of microbial pathogens. Advances in technology and lower costs have moved molecular diagnostic tests formerly performed for research purposes only into much wider use in clinical microbiology laboratories. To provide an example of laboratory studies performed to verify the performance of an FDA-approved assay for the detection of Clostridium difficile cytotoxin B compared with the manufacturer's performance standards. We describe the process and protocols used by a laboratory for verification of an FDA-approved assay, assess data from the verification studies, and implement the assay after verification. Performance data from the verification studies conducted by the laboratory were consistent with the manufacturer's performance standards and the assay was implemented into the laboratory's test menu. Verification studies are required for FDA-approved diagnostic assays prior to use in patient care. Laboratories should develop a standardized approach to verification studies that can be adapted and applied to different types of assays. We describe the verification of an FDA-approved real-time polymerase chain reaction assay for the detection of a toxin gene in a bacterial pathogen.

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

PubMed

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

2017-12-01

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

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

PubMed

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

2017-09-01

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

Biologics as countermeasures for acute radiation syndrome: where are we now?

PubMed

Singh, Vijay K; Romaine, Patricia L P; Newman, Victoria L

2015-04-01

Despite significant scientific advances toward the development of a safe, nontoxic and effective radiation countermeasure for acute radiation syndrome (ARS) over the past six decades, no drug has been approved by the US FDA. Several biologics are currently under development as radiation countermeasures for ARS, of which three have received FDA Investigational New Drug (IND) status for clinical investigation. Presently, two of these agents, entolimod (CBLB502) and HemaMax (recombinant human IL-12) are progressing with large animal studies and clinical trials. Neupogen (G-CSF, filgrastim) has recently been recommended for approval by an FDA Advisory Committee. Filgrastim, GM-CSF (Leukine, sargramostim), and PEGylated G-CSF (Neulasta) have high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the FDA in the future. The former two biologics are available in the US Strategic National Stockpile (SNS) for use in the event of nuclear or radiological emergency. The Emergency Use Authorization (EAU) application for entolimod may be filed soon with the FDA. Biologics are attractive agents that are progressing along the path for FDA approval, to fill the unmet need for ARS countermeasures.

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

PubMed

Rieves, Dwaine; Jacobs, Paula

2016-12-01

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

The rise (and decline?) of biotechnology.

PubMed

Kinch, Michael S

2014-11-01

Since the 1970s, biotechnology has been a key innovator in drug development. An analysis of FDA-approved therapeutics demonstrates pharmaceutical companies outpace biotechs in terms of new approvals but biotechnology companies are now responsible for earlier-stage activities (patents, INDs or clinical development). The number of biotechnology organizations that contributed to an FDA approval began declining in the 2000s and is at a level not seen since the 1980s. Whereas early biotechnology companies had a decade from first approval until acquisition, the average acquisition of a biotechnology company now occurs months before their first FDA approval. The number of hybrid organizations that arise when pharmaceutical companies acquire biotechnology is likewise declining, raising questions about the sustainability of biotechnology. Copyright © 2014 Elsevier Ltd. All rights reserved.

FDA Approves First Immunotherapy for Lymphoma

Cancer.gov

The FDA has approved nivolumab (Opdivo®) for the treatment of patients with classical Hodgkin lymphoma whose disease has relapsed or worsened after receiving an autologous hematopoietic stem cell transplantation followed by brentuximab vedotin (Adcetris®)

FDA Approves First Therapeutic Cancer Vaccine

Cancer.gov

Sipuleucel-T (Provenge) is a relatively nontoxic treatment option for men with hormone-resistant or castration-resistant prostate cancer. The FDA's approval of the vaccine represented the first proof of principle that immunotherapy can work in cancer.

78 FR 70566 - Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0002] Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of a new...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

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

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.

Quality investigation of hydroxyprogesterone caproate active pharmaceutical ingredient and injection

PubMed Central

Chollet, John L.; Jozwiakowski, Michael J.

2012-01-01

The purpose of this study was to investigate the quality of hydroxyprogesterone caproate (HPC) active pharmaceutical ingredient (API) sources that may be used by compounding pharmacies, compared to the FDA-approved source of the API; and to investigate the quality of HPC injection samples obtained from compounding pharmacies in the US, compared to the FDA-approved product (Makena®). Samples of API were obtained from every source confirmed to be an original manufacturer of the drug for human use, which were all companies in China that were not registered with FDA. Eight of the ten API samples (80%) did not meet the impurity specifications required by FDA for the API used in the approved product. One API sample was found to not be HPC at all; additional laboratory testing showed that it was glucose. Thirty samples of HPC injection obtained from com pounding pharmacies throughout the US were also tested, and eight of these samples (27%) failed to meet the potency requirement listed in the USP monograph for HPC injection and/or the HPLC assay. Sixteen of the thirty injection samples (53%) exceeded the impurity limit setforthe FDA-approved drug product. These results confirm the inconsistency of compounded HPC Injections and suggest that the risk-benefit ratio of using an unapproved compounded preparation, when an FDA-approved drug product is available, is not favorable. PMID:22329865

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

PubMed

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

2016-01-01

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

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/

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

PubMed

Burton, J H; Stanley, S D; Knych, H K; Rodriguez, C O; Skorupski, K A; Rebhun, R B

2016-01-01

Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products. The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies. Thirty-seven dogs treated with FDA-approved or compounded lomustine. Dogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. Twenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration. These data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

FDA Expands Approval of Venetoclax for CLL

Cancer.gov

FDA expanded the approval of venetoclax (Venclexta) for people with chronic lymphocytic leukemia (CLL) to include those whose cancer has progressed after previous treatment, regardless of whether their cancer cells have the deletion 17p gene alteration.

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.

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

PubMed

Lee, Samuel; Abd-Elsayed, Alaa

2016-09-01

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

78 FR 24425 - Assay Migration Studies for In Vitro Diagnostic Devices; Guidance for Industry and Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... approach to gain FDA approval of Class III or certain licensed in vitro diagnostic devices in cases when a... approach to gain FDA approval of Class III or certain licensed in vitro diagnostic devices in cases when a... fulfilled in order for a sponsor to utilize the migration study approach in support of the change. The FDA...

78 FR 52429 - New Animal Drugs; Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-23

... 558 [Docket No. FDA-2013-N-0839] New Animal Drugs; Withdrawal of Approval of New Animal Drug...: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect the withdrawal of approval of three new animal drug applications (NADAs) at the sponsors' request...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

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

21 CFR 314.153 - Suspension of approval of an abbreviated new drug application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Suspension of approval of an abbreviated new drug application. 314.153 Section 314.153 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 FDA...

21 CFR 314.153 - Suspension of approval of an abbreviated new drug application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Suspension of approval of an abbreviated new drug application. 314.153 Section 314.153 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 FDA...

21 CFR 314.153 - Suspension of approval of an abbreviated new drug application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Suspension of approval of an abbreviated new drug application. 314.153 Section 314.153 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 FDA...

21 CFR 314.153 - Suspension of approval of an abbreviated new drug application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Suspension of approval of an abbreviated new drug application. 314.153 Section 314.153 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 FDA...

21 CFR 314.153 - Suspension of approval of an abbreviated new drug application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Suspension of approval of an abbreviated new drug application. 314.153 Section 314.153 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 FDA...

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.

Price analysis of multiple sclerosis disease-modifying therapies marketed in the United States.

PubMed

Bin Sawad, Aseel; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Turkistani, Fatema

2016-11-01

This study assessed trends in the average wholesale price (AWP) at the market entry of disease-modifying therapies (DMTs) approved by Food and Drug Administration (FDA) in the period 1987-2014. DMT regulatory information was derived from the FDA website. The AWPs per unit at market entry data were derived from the Red Book (Truven Health Analytics Inc.). The AWP history for each DMT was collected from its date of approval to 31 December 2014. The FDA approved label defined daily dose (DDD) for adult patients was obtained from FDA approved labels. The AWP per DDD and the AWP/DDD per year of therapy were computed. Descriptive statistics, Wilcoxon tests, t-test, and multiple linear regression were performed. The statistical significance level was set at 0.05. The FDA approved 12 multiple sclerosis (MS) DMTs, including five new drug applications (NDAs) and seven biologic license applications (BLAs) as of 31 December 2014. The FDA granted orphan designation to five DMTs. There was one DMT approved by the FDA in the 1980s, three in the 1990s, three in 2000s, and five in the period 2010-2014. The market entry inflation-adjusted AWP per DDD was $10.23 for the first DMT (mitoxantrone hydrochloride) that was approved in the 1980s. The median market entry inflation-adjusted AWP per DDD was $12.41 (interquartile range [IQR] = 4.51) for DMTs approved in the 1990s, $71.26 (IQR = 58.35) in the 2000s, and $172.56 (IQR = 84.97) in the period 2010-2014. The median AWP per DDD was statistically significantly different (p = 0.011) for orphan (median = $41.82, IQR = 56.077) compared to non-orphan drugs (median = $171.32, IQR = 199.29). Year of market entry was positively associated with DMT prices at US market entry (p = 0.01). The AWP per DDD for DMTs at market entry increased substantially over time. The increase in DMTs prices exceeded the general consumer price index.

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 treatment decisions about newly approved drugs.

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.

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...

78 FR 18233 - Medical Devices; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... the right column: Section Remove Add 814.20 http://www.fda.gov/ http://www.fda.gov/ cdrh/devadvice.../ PremarketApproval PMA/default.htm. 822.7 http://www.fda.gov/ http://www.fda.gov/ cdrh/ombudsman/ AboutFDA/ dispute.html. CentersOffices/ OfficeofMedicalPr oductsandTobacco/ CDRH/ CDRHOmbudsman/ default.htm. 822.15...

FDA Expands Approval of Brentuximab for Hodgkin Lymphoma

Cancer.gov

The FDA has expanded the approved uses of brentuximab (Adcetris) in people with Hodgkin lymphoma. As this Cancer Currents post explains, it can now be used in combination with three chemotherapy drugs as an initial treatment in patients with advanced disease.

78 FR 950 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

..., FDA- 2012-M-0965, FDA-2012-M-0968, FDA-2012-M-1011, and FDA-2012-M-1013] Medical Devices; Availability...\\ February 16, 2011. Adjustable Gastric Banding System. P100049, FDA-2012-M-0893....... Torax Medical, Inc.... Trabecular Micro- Bypass Stent and Inserter. P110007, FDA-2012-M-0734....... Abbott Medical Healon[supreg...

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

PubMed

Lee, Samuel; Abd-Elsayed, Alaa

2016-12-01

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

Characteristics of Clinical Studies Used for US Food and Drug Administration Approval of High-Risk Medical Device Supplements.

PubMed

Zheng, Sarah Y; Dhruva, Sanket S; Redberg, Rita F

2017-08-15

High-risk medical devices often undergo modifications, which are approved by the US Food and Drug Administration (FDA) through various kinds of premarket approval (PMA) supplements. There have been multiple high-profile recalls of devices approved as PMA supplements. To characterize the quality of the clinical studies and data (strength of evidence) used to support FDA approval of panel-track supplements (a type of PMA supplement pathway that is used for significant changes in a device or indication for use and always requires clinical data). Descriptive study of clinical studies supporting panel-track supplements approved by the FDA between April 19, 2006, and October 9, 2015. Panel-track supplement approval. Methodological quality of studies including randomization, blinding, type of controls, clinical vs surrogate primary end points, use of post hoc analyses, and reporting of age and sex. Eighty-three clinical studies supported the approval of 78 panel-track supplements, with 71 panel-track supplements (91%) supported by a single study. Of the 83 studies, 37 (45%) were randomized clinical trials and 25 (30%) were blinded. The median number of patients per study was 185 (interquartile range, 75-305), and the median follow-up duration was 180 days (interquartile range, 84-270 days). There were a total of 150 primary end points (mean [SD], 1.8 [1.2] per study), and 57 primary end points (38%) were compared with controls. Of primary end points with controls, 6 (11%) were retrospective controls and 51 (89%) were active controls. One hundred twenty-one primary end points (81%) were surrogate end points. Thirty-three studies (40%) did not report age and 25 (30%) did not report sex for all enrolled patients. The FDA required postapproval studies for 29 of 78 (37%) panel-track supplements. Among clinical studies used to support FDA approval of high-risk medical device modifications, fewer than half were randomized, blinded, or controlled, and most primary outcomes were based on surrogate end points. These findings suggest that the quality of studies and data evaluated to support approval by the FDA of modifications of high-risk devices should be improved.

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.

Delegations of authority and organization; Center for Devices and Radiological Health--FDA. Final rule.

PubMed

1998-05-18

The Food and Drug Administration (FDA) is amending the regulations for delegations of authority to reflect a new delegation that authorizes the Division Directors, Office of Device Evaluation (ODE), Center for Devices and Radiological Health (CDRH) to approve, disapprove, or withdraw approval of product development protocols and applications for premarket approval for medical devices.

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.

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2012 CFR

2012-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2013 CFR

2013-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2010 CFR

2010-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2011 CFR

2011-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2014 CFR

2014-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.151 - Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.151 Withdrawal...

21 CFR 314.151 - Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.151 Withdrawal...

21 CFR 314.151 - Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.151 Withdrawal...

21 CFR 314.151 - Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.151 Withdrawal...

21 CFR 314.151 - Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.151 Withdrawal...

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.

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

PubMed

Casey, Martin F; Mechanick, Jeffrey I

2014-09-01

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

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

Annual update: drugs, diagnostics and devices.

PubMed

Berardinelli, Candace; Kupecz, Deborah

2003-03-01

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

Marketing approval for the lithotripter.

PubMed

Nightingale, S L; Young, F E

1986-01-01

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

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

PubMed Central

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

2011-01-01

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

Overcoming obstacles to repurposing for neurodegenerative disease

PubMed Central

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

2014-01-01

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

Characteristics of Clinical Studies Conducted Over the Total Product Life Cycle of High-Risk Therapeutic Medical Devices Receiving FDA Premarket Approval in 2010 and 2011.

PubMed

Rathi, Vinay K; Krumholz, Harlan M; Masoudi, Frederick A; Ross, Joseph S

2015-08-11

The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle. To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014. Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator-initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer/investigator-initiated postmarket studies, respectively. Approximately half of all studies used no comparator (pivotal: 13/30 [43.3%]; completed postmarket: 16/26 [61.5%]; ongoing postmarket: 70/153 [45.8%]). Median duration of primary effectiveness end point follow-up was 3.0 months (IQR, 3.0-12.0), 9.0 months (IQR, 0.3-12.0), and 12.0 months (IQR, 7.0-24.0) for pivotal, completed postmarket, and ongoing postmarket studies, respectively. Among high-risk therapeutic devices approved via the FDA PMA pathway, total product life cycle evidence generation varied in both the number and quality of premarket and postmarket studies, with approximately 13% of initiated postmarket studies completed between 3 and 5 years after FDA approval.

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

PubMed

Paltiel, A David; Pollack, Harold A

2010-01-01

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

Is It a Cosmetic, a Drug, or Both? (or Is It Soap?)

MedlinePlus

... of product. Firms sometimes violate the law by marketing a cosmetic with a drug claim or by marketing a drug as if it were a cosmetic, ... that FDA approve a pharmaceutical for sale and marketing in the United States. FDA only approves an ...

21 CFR 314.54 - Procedure for submission of an application requiring investigations for approval of a new...

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.54... effectiveness of the drug product. (iii) Identification of the listed drug for which FDA has made a finding of...

21 CFR 314.54 - Procedure for submission of an application requiring investigations for approval of a new...

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.54... effectiveness of the drug product. (iii) Identification of the listed drug for which FDA has made a finding of...

21 CFR 314.54 - Procedure for submission of an application requiring investigations for approval of a new...

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.54... effectiveness of the drug product. (iii) Identification of the listed drug for which FDA has made a finding of...

21 CFR 314.54 - Procedure for submission of an application requiring investigations for approval of a new...

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.54... effectiveness of the drug product. (iii) Identification of the listed drug for which FDA has made a finding of...

US FDA perspective on regulatory issues affecting circulatory assist devices.

PubMed

Sapirstein, Wolf; Chen, Eric; Swain, Julie; Zuckerman, Bram

2006-11-01

There has been a rapid development in mechanical circulatory support systems in the decade since the US FDA first approved a mechanical device to provide the circulatory support lacking from a failing heart. Devices are presently approved for marketing by the FDA to replace a failing ventricle, the Ventricular Assist Device or the entire heart, Total Artificial Heart. Contemporaneous with, and permitted by, improvement in technology and design, devices have evolved from units located extracorporeally to paracorporeal systems and totally implanted devices. Clinical studies have demonstrated a parallel improvement in the homeostatic adequacy of the circulatory support provided. Thus, while the circulatory support was initially tolerated for short periods to permit recovery of cardiac function, this technology eventually provided effective circulatory support for increasing periods that permitted the FDA to approve devices for bridging patients in end-stage cardiac failure awaiting transplant and eventually a device for destination therapy where patients in end-stage heart failure are not cardiac transplant candidates. The approved devices have relied on displacement pumps that mimic the pulsatility of the physiological system. Accelerated development of more compact devices that rely on alternative pump mechanisms have challenged both the FDA and device manufacturers to assure that the regulatory requirements for safety and effectiveness are met for use of mechanical circulatory support systems in expanded target populations. An FDA regulatory perspective is reviewed of what can be a potentially critical healthcare issue.

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.

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

PubMed

Kelly, Jeremiah J; David, Michael

2009-01-01

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

Oncologic Drugs Advisory Committee Recommendations and Approval of Cancer Drugs by the US Food and Drug Administration.

PubMed

Tibau, Ariadna; Ocana, Alberto; Anguera, Geòrgia; Seruga, Bostjan; Templeton, Arnoud J; Barnadas, Agustí; Amir, Eitan

2016-06-01

The US Food and Drug Administration (FDA) advisory committees influence decisions relating to the regulatory approval of drugs in the United States. Outside of the field of oncology, prosponsor voting bias has been observed among members with financial conflicts of interest (FCOIs). To explore factors associated with Oncologic Drugs Advisory Committee (ODAC) recommendations and the influence ODAC members' FCOIs on the drug approval process. Retrospective analysis of 82 ODAC meeting transcripts between January 2000 and December 2014. Analysis was restricted to meetings at which votes were cast relating to oncologic drugs. The influence of methodology of trials supporting approval and frequency and type of self-reported FCOIs of voting members was explored using logistic regression. ODAC recommendation for drug approval and subsequent FDA approval. Eighty-two transcripts of ODAC meetings between January 2000 and December 2014 were available for analysis. During the time period analyzed, ODAC members voted on 68 applications in 79 meetings (the remaining 3 meetings included voting questions regarding postmarketing safety or trial design). There was agreement between ODAC recommendations and final FDA approval; FDA approval was received for all 41 drugs that ODAC recommended approval. Additionally, the FDA approved 7 out of 41 agents that were not recommended for approval by ODAC (κ = 0.83). In 51 of 79 meetings, more than 1 trial was available to support the indication of a particular drug, and favorable ODAC recommendations were more likely when this was the case (odds ratio [OR], 1.82; 95% CI, 1.19-2.78; P = .01). Availability of randomized data did not appear to be important with selected single-arm phase 2 trials leading to recommendations for approval, especially in rare diseases. There has been a significant reduction in FCOIs over time (31 of 77 voting members [40%] in 2000 vs 0 of 20 voting members in 2014 [0%]; P < .001). Recommendations for approval were made in 28 of 47 meetings with members reporting FCOIs while among meetings with no reported FCOIs, recommendations for approval were made in 13 of 35 meetings (OR, 1.19; 95% CI, 0.97-1.46; P = .10). No significant association between ODAC recommendations and FDA approval was observed for members with FCOIs with the sponsor (OR, 1.79; 95% CI, 0.97-1.46; P = .19 and OR, 3.48; 95% CI, 0.84-14.35; P = .09, respectively) compared with members with FCOIs with competitors (OR, 1.06; 95% CI, 0.78-1.44; P = .72 and OR, 0.94; 95% CI, 0.69-1.28; P = .69, respectively). Availability of multiple trials is associated with higher odds of ODAC recommendation and drug approval. Availability of randomized data appears less important. Declaration of FCOIs among ODAC members was frequent during the time period of interest but has decreased significantly over time. There is no apparent association between FCOIs and ODAC recommendations and subsequent FDA approval.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-10-01

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

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.

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.

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

PubMed

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

2015-09-23

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

21 CFR 314.650 - Termination of requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

....650 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 § 314.650 Termination of requirements. If FDA determines after...

21 CFR 314.650 - Termination of requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

....650 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 § 314.650 Termination of requirements. If FDA determines after...

21 CFR 314.650 - Termination of requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

....650 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 § 314.650 Termination of requirements. If FDA determines after...

21 CFR 314.650 - Termination of requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

....650 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 § 314.650 Termination of requirements. If FDA determines after...

21 CFR 314.650 - Termination of requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

....650 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 § 314.650 Termination of requirements. If FDA determines after...

FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | FNLCR Staging

Cancer.gov

The U.S. Food and Drug Administration (FDA) has approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected.  The National Cancer In

77 FR 60442 - Withdrawal of Approval of New Animal Drug Applications; Butorphanol; Doxapram; Triamcinolone...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0981] Withdrawal of Approval of New Animal Drug Applications; Butorphanol; Doxapram; Triamcinolone; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

21 CFR 310.515 - Patient package inserts for estrogens.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Patient package inserts for estrogens. 310.515... package inserts for estrogens. (a) Requirement for a patient package insert. FDA concludes that the safe... patient package insert containing information concerning the drug's benefits and risks. An estrogen drug...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

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 314.108 - New drug product exclusivity.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... investigation means that before or during the investigation, the applicant was named in Form FDA-1571 filed with FDA as the sponsor of the investigational new drug application under which the investigation was...

21 CFR 314.96 - Amendments to an unapproved abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... applicant on the same drug product formulation, unless the information has previously been submitted to FDA... and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may...

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 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

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...

21 CFR 314.96 - Amendments to an unapproved abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... applicant on the same drug product formulation, unless the information has previously been submitted to FDA... and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may...

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 freely accessible at http://idaapm.helsinki.fi and can be exploited through a KNIME workflow connected to the database.Graphical abstractFDA approved drug data integration for predictive modeling.

Safety and Efficacy of the BrainPort V100 Device in Individuals Blinded by Traumatic Injury

DTIC Science & Technology

2016-12-01

the functional performance of the BrainPort® V200 device, a non-surgical, FDA approved, sensory substitution system, in persons who are profoundly...The BrainPort V200 device is a wearable, non-surgical, FDA approved, prosthetic device intended for people who are profoundly blind. The BrainPort...BrainPort V200 electronic vision aid (described previously) has been developed under this research. FDA clearance to market the V200 in the US is expected

Patient-reported outcome labeling claims and measurement approach for metastatic castration-resistant prostate cancer treatments in the United States and European Union

PubMed Central

2014-01-01

Background Metastatic castration-resistant prostate cancer (mCRPC) and its treatment significantly affect health-related quality of life (HRQOL). Our objectives were to evaluate and compare patient-reported outcome (PRO) claims granted by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for 5 recently approved mCRPC treatments and to examine key characteristics, development, and measurement properties of the PRO measures supporting these claims against current regulatory standards. Methods Five products approved for treatment of mCRPC by the FDA and the EMA (2010–2013) were examined: enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and radium Ra 223 dichloride. United States (US) drug approval packages and European Public Assessment Reports were reviewed. PRO claims in the US labels and European Summaries of Product Characteristics and supporting measures were identified. For PRO measures supporting claims, a targeted literature review was conducted to identify information on key characteristics and measurement properties; this information was compared against FDA PRO guidance criteria. Results Nine PRO “claims” were granted across 4 of 5 products reviewed. The EMA granted more claims (7 claims—4 for pain, 3 for HRQOL) than the FDA (2 claims, both for pain). The Brief Pain Inventory–Short Form (BPI-SF) worst pain item supported most pain claims and was the only measure supporting US claims. EMA pain claims were supported by BPI-SF worst pain (n = 2) and average pain (n = 1) items and the McGill Pain Questionnaire Present Pain Intensity component (n = 1). EMA HRQOL claims were supported by the Functional Assessment of Cancer Therapy–Prostate Module (n = 2) and the EuroQol 5 Dimensions with visual analogue scale (n = 1). Pain and prostate cancer–specific HRQOL measures supporting claims met US regulatory standards for construct validity, reliability, and responsiveness; these properties were strongest for the BPI-SF worst pain item. Only the BPI-SF worst pain item has documented content validity in mCRPC. Conclusions PRO label claims were commonly granted across the mCRPC products reviewed. Among the measures reviewed, only the BPI-SF worst pain item supported US label claims. The BPI-SF worst pain item is recommended for pain assessment for the evaluation of new mCRPC treatments. PMID:24989428

Tasimelteon (Hetlioz™): A New Melatonin Receptor Agonist for the Treatment of Non-24-Hour Sleep-Wake Disorder.

PubMed

Bonacci, Janene M; Venci, Jineane V; Gandhi, Mona A

2015-10-01

In January 2014, the US Food and Drug Administration approved tasimelteon (Hetlioz™), a melatonin-receptor agonist for the treatment of non-24-hour sleep-wake disorder. This article provides an overview of the mechanism of action, pharmacokinetic properties, as well as the clinical efficacy, safety, and tolerability of tasimelteon. Relevant information was identified through a comprehensive literature search of several databases using the key words tasimelteon, Non-24-hour Sleep-Wake disorder, Non-24, and melatonin. Further information was obtained from the tasimelteon package insert, fda.gov, clinicaltrials.gov, briefing materials provided by Vanda Pharmaceuticals, and posters from scientific meetings. © The Author(s) 2014.

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.

FDA approval of expanded age indication for a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine.

PubMed

2011-09-23

On July 8, 2011, the Food and Drug Administration (FDA) approved an expanded age indication for the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) Boostrix (GlaxoSmithKline Biologicals, Rixensart, Belgium). Originally, Boostrix was licensed in 2005 for persons aged 10 through 18 years, but in 2008, FDA approved an expanded age indication for Boostrix to include persons aged 19 through 64 years. FDA has now expanded the age indication to include persons aged 65 years and older. Boostrix is now licensed for use in persons aged 10 years and older as a single-dose booster vaccination. This notice summarizes the indications for use of Boostrix. Recommendations of the Advisory Committee on Immunization Practices (ACIP) for Tdap vaccines have been published previously. Publication of revised Tdap recommendations within the next year is anticipated.

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... that FDA can process, review, and archive. FDA will periodically issue guidance on how to provide the...

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.

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.

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.

75 FR 55796 - Determination That VESANOID (Tretinoin) Capsules, 10 Milligrams, Were Not Withdrawn From Sale for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-14

...] Determination That VESANOID (Tretinoin) Capsules, 10 Milligrams, Were Not Withdrawn From Sale for Reasons of... Drug Administration (FDA) has determined that VESANOID (tretinoin) Capsules, 10 milligrams (mg), were... approved. FDA may not approve an ANDA that does not refer to a listed drug. VESANOID (tretinoin) Capsules...

78 FR 70496 - Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 [Docket No. FDA-2013-N-0002] Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is...

77 FR 29665 - Determination That PITRESSIN TANNATE IN OIL (Vasopressin Tannate) Injection, 5 Pressor Units...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications... suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines...

75 FR 14444 - Determination That DIDREX (Benzphetamine Hydrochloride) Tablets, 25 Milligrams, Were Not...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

... Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug... safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications... or suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA...

75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug Application; Buquinolate; Coumaphos AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations by...

FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | Frederick National Laboratory for Cancer Research

Cancer.gov

The U.S. Food and Drug Administration (FDA) has approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected.  The National Cancer In

78 FR 68705 - Premerger Notification; Reporting and Waiting Period Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

....\\6\\ An exclusive license is substantively the same as buying the patent or part of the patent... through the FDA approval process, nor to effectively market or promote it in drug form after FDA approval... promotion of the drug. There is a great deal of uncertainty involved because the transfer takes place very...

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.

Clinical Evidence Supporting US Food and Drug Administration Premarket Approval of High-Risk Otolaryngologic Devices, 2000-2014.

PubMed

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

2017-02-01

The US Food and Drug Administration (FDA) approves high-risk medical devices based on premarket pivotal clinical studies demonstrating reasonable assurance of safety and effectiveness and may require postapproval studies (PAS) to further inform benefit-risk assessment. We conducted a cross-sectional analysis using publicly available FDA documents to characterize industry-sponsored pivotal studies and PAS of high-risk devices used in the treatment of otolaryngologic diseases. Between 2000 and 2014, the FDA approved 23 high-risk otolaryngologic devices based on 28 pivotal studies. Median enrollment was 118 patients (interquartile range, 67-181), and median duration of longest primary effectiveness end point follow-up was 26 weeks (interquartile range, 16-96). Fewer than half were randomized (n = 13, 46%), blinded (n = 12, 43%), or controlled (n = 10, 36%). The FDA required 23 PASs for 16 devices (70%): almost two-thirds (n = 15, 65%) monitored long-term performance, and roughly one-third (n = 8, 35%) focused on subgroups. Otolaryngologists should be aware of limitations in the strength of premarket evidence when considering the use of newly approved devices.

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

PubMed

Smith, Colleen

2015-01-01

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

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

PubMed

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

2016-04-14

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

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

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

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

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

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

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) ...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

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

PubMed

Moore, Thomas J; Furberg, Curt D

2014-01-01

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

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 advantage when compared with non-breakthrough-designated drugs.

Application of FDA-Approved Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in Rodent Models of Tuberous Sclerosis Complex

DTIC Science & Technology

2014-05-01

Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in Rodent Models of Tuberous Sclerosis Complex PRINCIPAL...Approved Memantine and Newer NitroMemantine Derivatives to Treat 5a. CONTRACT NUMBER W81XWH-13-1-0053 Neurological Manifestations in Rodent Models of...to investigate if administration of the FDA-approved drug, Memantine , an uncompetitive/fast off-rate antagonist of the N- methyl-D-aspartate-type

NCI, NHLBI, FDA, AACC, and CMS Collaborate in Advancing Proteomics Regulatory Science | Office of Cancer Clinical Proteomics Research

Cancer.gov

Despite great strides in proteomics and the growing number of articles citing the discovery of potential biomarkers, the actual rate of introduction of Food and Drug Administration (FDA) approved protein analytes has been relatively unchanged over the past 10 years. One of reasons for the lack of new protein-based biomarkers approved has been a lack of information and understanding by the proteomics research community to the regulatory process used by the FDA. To address this issue, Dr.

Guidance for the emergency use of unapproved medical devices; availability--FDA. Notice.

PubMed

1985-10-22

The Food and Drug Administration (FDA) is announcing guidance, developed by FDA's Center for Devices and Radiological Health (CDRH), with respect to those emergency situations in which the agency would not object to a physician's using a potentially life-saving medical device for a use for which the device ordinarily is required to have, but does not have, an approved application for premarket approval or an investigational device exemption. The guidance is contained in a document entitled "guidance for the Emergency Use of Unapproved Medical Devices."

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

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

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

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

26 CFR 51.2T - Explanation of terms (temporary).

Code of Federal Regulations, 2014 CFR

2014-04-01

... approved the drug for marketing for any indication other than the treatment of a rare disease or condition... for treatment of another rare disease or condition. If a drug has prior FDA marketing approval for the treatment of a rare disease or condition for which a section 45C credit was allowed, and the FDA...

26 CFR 51.2T - Explanation of terms (temporary).

Code of Federal Regulations, 2012 CFR

2012-04-01

... approved the drug for marketing for any indication other than the treatment of a rare disease or condition... for treatment of another rare disease or condition. If a drug has prior FDA marketing approval for the treatment of a rare disease or condition for which a section 45C credit was allowed, and the FDA...

26 CFR 51.2T - Explanation of terms (temporary).

Code of Federal Regulations, 2013 CFR

2013-04-01

... approved the drug for marketing for any indication other than the treatment of a rare disease or condition... for treatment of another rare disease or condition. If a drug has prior FDA marketing approval for the treatment of a rare disease or condition for which a section 45C credit was allowed, and the FDA...

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...

75 FR 81617 - Determination That TRANDATE (Labetalol Hydrochloride) Tablets, 300 Milligrams and 400 Milligrams...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... 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...

Center for Cancer Research plays key role in first FDA-approved drug for treatment of Merkel cell carcinoma | Center for Cancer Research

Cancer.gov

The Center for Cancer Research’s ability to rapidly deploy integrated basic and clinical research teams at a single site facilitated the rapid FDA approval of the immunotherapy drug avelumab for metastatic Merkel cell carcinoma, a rare, aggressive form of skin cancer. Learn more...  

Captopril and losartan for mitigation of renal injury caused by single-dose total-body irradiation.

PubMed

Moulder, John E; Cohen, Eric P; Fish, Brian L

2011-01-01

It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) "Animal Efficacy Rule", we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m(2)/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed.

Captopril and Losartan for Mitigation of Renal Injury Caused by Single-Dose Total-Body Irradiation

PubMed Central

Moulder, John E.; Cohen, Eric P.; Fish, Brian L.

2011-01-01

It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) “Animal Efficacy Rule”, we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m2/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed. PMID:21175344

Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications.

PubMed

Halpern, Bruno; Halpern, Alfredo

2015-02-01

Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.

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...

Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

DTIC Science & Technology

2016-10-01

consensus meeting, with input from investigators in the Prostate Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study...Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study Endpoint and Label Development Team, and FDA Division of...Abstract. American Society of Clinical Oncology . Chicago IL, June 1-5, 2013. INVENTIONS, PATENTS AND LICENSES None 11 REPORTABLE OUTCOMES

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

PubMed Central

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

2013-01-01

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

The Orphan Drug Act: Restoring the Mission to Rare Diseases.

PubMed

Daniel, Michael G; Pawlik, Timothy M; Fader, Amanda N; Esnaola, Nestor F; Makary, Martin A

2016-04-01

The Orphan Drug Act has fostered drug development for patients with rare cancers and other diseases; however, current data suggest that companies are gaming the system to use the law for mainstream drugs. We identify a pattern of pharmaceutical companies submitting drugs to the Food and Drug Administration (FDA) as orphan drugs but once approved, the drugs are used broadly off-label with the lucrative orphan drug protections and exclusivity benefits. Since the law was passed, the proportion of new FDA-approved drugs that were submitted as orphan drugs has increased with a peak last year of 41% of all FDA-approved drugs approved as orphan drugs. On the basis of the current data, we suggest that patients with rare cancers and other diseases may suffer due to dilution of the incentives and benefits. We propose reform to increase submission scrutiny, decrease benefits based on off-label use, and increase price transparency.

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.

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.

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

PubMed

Maak, Travis G; Wylie, James D

2016-08-01

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

Fixed-dose combination and single active ingredient drugs: a comparative cost analysis.

PubMed

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2016-01-01

Fixed-dose combination (FDC) drugs are formulations of two or more active ingredients. To assess the pricing structure and price difference of all US FDA-approved FDCs and single drugs included in the combination. Data were collected from the FDA Orange Book and Drugs@FDA. Average Wholesale Price (AWP) unit price data were derived from The Red Book. The FDA approved 117 FDC. The average AWP difference percentage between the FDC and the sum of the single drugs in the FDC is 84.9 ± 26.2%, and varied by therapeutic class (p < 0.001). The FDC AWP averaged 83.3 ± 23.4% of the single drug AWP sum when there are no generics, and 95.1 ± 42.3% (p < 0.01) when there are two generic single active ingredients in the FDC. The price difference between FDC and single active ingredients in the combination is correlated with the therapeutic class, the year of FDC approval, and the number of single ingredients in the combination that have generics.

78 FR 65334 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... information, including certain labeling information, to FDA for approval to market a product in interstate... and in a form that FDA can process, review, and archive. This requirement is in addition to the....12(b) in table 1 of this document. In July 1997, FDA revised Form FDA 356h ``Application to Market a...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

Nods for Atezolizumab and Nivolumab from FDA.

PubMed

2016-08-01

The FDA has conditionally approved atezolizumab, the first PD-L1 inhibitor, for metastatic urothelial carcinoma, along with a companion diagnostic, the Ventana PD-L1 (SP142) assay. The agency has also expanded nivolumab's indications to include classical Hodgkin lymphoma, making this PD-1 inhibitor the first to be approved for a hematologic malignancy. ©2016 American Association for Cancer Research.

78 FR 66742 - Determination That MOBAN (Molindone Hydrochloride) Tablets (5 Milligrams, 10 Milligrams, 25...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

... regulatory requirements are met. FOR FURTHER INFORMATION CONTACT: Emily Helms Williams, Center for Drug... now section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)), which requires FDA to publish a list of all approved drugs. FDA publishes this list as part of the ``Approved...

FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | Poster

Cancer.gov

By Frank Blanchard, Staff Writer The U.S. Food and Drug Administration (FDA) recently approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected. The National Cancer Institute’s (NCI) Biopharmaceutical Development Program (BDP) at the Frederick National

Taxane anticancer agents: a patent perspective

PubMed Central

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

2016-01-01

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

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

PubMed

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

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

Zohydro approval by food and drug administration: controversial or frightening?

PubMed

Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

2014-01-01

The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health consequences, despite numerous regulations enforced by multiple organizations. The approval of Zohydro and its defense from the FDA were based on a misunderstanding of the prevalence of chronic severe disabling pain. Based on inaccurate data from the Institute of Medicine, in part caused by conflicts of interest, 100 million persons have been described to suffer from severe pain - the correct number is 22.6 million. This manuscript analyzes 3 important principles of drug approval and utilization based on safety, efficacy, and medical necessity. Based on the limited literature that the authors were able to review including that which was submitted to the FDA by the manufacturers, it appears the safety, efficacy, and medical necessity were not demonstrated. In fact, the study submitted to the FDA showed a 50% pain improvement in only 48% of the patients in the treatment group and 21% of the patients in the placebo group at 85 day follow-up. This is a statistically significant result but its clinical relevance is unknown. The FDA approval decision occurring against the backdrop of the advisory panel recommendation is concerning and may result in serious consequences in the future.

Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

PubMed

Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

2018-03-21

The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95% CI -0.15-0.16). Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers.

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

PubMed

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

2015-08-15

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

77 FR 26161 - New Animal Drugs; Ceftiofur Crystalline Free Acid; Gamithromycin; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

... [Docket No. FDA-2012-N-0002] New Animal Drugs; Ceftiofur Crystalline Free Acid; Gamithromycin; Tylosin... (FDA) is amending the animal drug regulations to reflect approval actions for new animal drug applications (NADAs) and abbreviated new animal drug applications (ANADAs) during February 2012. FDA is also...

78 FR 25182 - New Animal Drugs; Dexmedetomidine; Lasalocid; Melengestrol; Monensin; and Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... [Docket No. FDA-2013-N-0002] New Animal Drugs; Dexmedetomidine; Lasalocid; Melengestrol; Monensin; and... Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval actions for new animal drug applications and abbreviated new animal drug applications during March 2013. FDA...

77 FR 76862 - New Animal Drugs; Enrofloxacin; Melengestrol; Meloxicam; Pradofloxacin; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-31

..., and 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Enrofloxacin; Melengestrol; Meloxicam... Administration (FDA) is amending the animal drug regulations to reflect approval actions for new animal drug applications (NADAs) and abbreviated new animal drug applications (ANADAs) during November 2012. FDA is also...

21 CFR 314.91 - Obtaining a reduction in the discontinuance notification period.

Code of Federal Regulations, 2013 CFR

2013-04-01

... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG... manufacturer of certain products notifies FDA that it will discontinue manufacturing the product. The discontinuance notification period ends when manufacturing ceases. (b) When can FDA reduce the discontinuance...

21 CFR 314.122 - Submitting an abbreviated application for, or a 505(j)(2)(C) petition that relies on, a listed...

Code of Federal Regulations, 2012 CFR

2012-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... petition FDA for a determination whether the drug product was withdrawn from the market for safety or...

21 CFR 314.91 - Obtaining a reduction in the discontinuance notification period.

Code of Federal Regulations, 2011 CFR

2011-04-01

... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG... manufacturer of certain products notifies FDA that it will discontinue manufacturing the product. The discontinuance notification period ends when manufacturing ceases. (b) When can FDA reduce the discontinuance...

21 CFR 314.122 - Submitting an abbreviated application for, or a 505(j)(2)(C) petition that relies on, a listed...

Code of Federal Regulations, 2010 CFR

2010-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... petition FDA for a determination whether the drug product was withdrawn from the market for safety or...

21 CFR 314.122 - Submitting an abbreviated application for, or a 505(j)(2)(C) petition that relies on, a listed...

Code of Federal Regulations, 2014 CFR

2014-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... petition FDA for a determination whether the drug product was withdrawn from the market for safety or...

21 CFR 314.91 - Obtaining a reduction in the discontinuance notification period.

Code of Federal Regulations, 2012 CFR

2012-04-01

... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG... manufacturer of certain products notifies FDA that it will discontinue manufacturing the product. The discontinuance notification period ends when manufacturing ceases. (b) When can FDA reduce the discontinuance...

21 CFR 314.122 - Submitting an abbreviated application for, or a 505(j)(2)(C) petition that relies on, a listed...

Code of Federal Regulations, 2011 CFR

2011-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... petition FDA for a determination whether the drug product was withdrawn from the market for safety or...

21 CFR 314.91 - Obtaining a reduction in the discontinuance notification period.

Code of Federal Regulations, 2010 CFR

2010-04-01

... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG... manufacturer of certain products notifies FDA that it will discontinue manufacturing the product. The discontinuance notification period ends when manufacturing ceases. (b) When can FDA reduce the discontinuance...

21 CFR 314.122 - Submitting an abbreviated application for, or a 505(j)(2)(C) petition that relies on, a listed...

Code of Federal Regulations, 2013 CFR

2013-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... petition FDA for a determination whether the drug product was withdrawn from the market for safety or...

Coming Soon to a Pharmacy Near You.

PubMed

Dubois, Wil

2016-01-01

Recent FDA approvals introduce both cheaper insulin in the form of a biosimilar and lipid-lowering agents with prices that rival the cost of cancer drugs. They also give us brand new ways to lower blood glucose and repair the damage done when glucose control fails. Hundreds more are in the pipeline, of which one or two per year will win marketing approval from the FDA.

Three Drugs Approved for Urothelial Carcinoma by FDA.

PubMed

2017-07-01

The FDA has approved one PD-1 checkpoint inhibitor, pembrolizumab, and two PD-L1 checkpoint inhibitors, avelumab and durvalumab, to treat metastatic urothelial carcinoma in patients whose disease continues to progress despite platinum-based chemotherapy. This brings the total number of checkpoint inhibitors for the disease to five, prompting questions about how best to use them. ©2017 American Association for Cancer Research.

Health Reports

DTIC Science & Technology

1992-11-01

Food and Drug Recombinant Bovine Growth Hormone: FDA Approval Should Be Withheld Administration Until the Mastitis Issue Is Resolved (Report, Aug. 6...Care: Demonstration Project Concerning Future Structure of Veterans’ Health Program (Testimony, Aug. 11, 1992, GA(Yr-HRD-92-53). Recombinant Bovine ...Growth Hormone: FDA Approval Should Be Withheld Until the Mastitis Issue Is Resolved (Report, Aug. 6, 1992, GAO/PEMD-92-26). Page 10 GAD/RRD-98-38 Health

Companion diagnostics: a regulatory perspective from the last 5 years of molecular companion diagnostic approvals.

PubMed

Roscoe, Donna M; Hu, Yun-Fu; Philip, Reena

2015-01-01

Companion diagnostics are essential for the safe and effective use of the corresponding therapeutic products. The US FDA has approved a number of companion diagnostics used to select cancer patients for treatment with contemporaneously approved novel therapeutics. The processes of co-development and co-approval of a therapeutic product and its companion diagnostic have been a learning experience that continues to evolve. Using several companion diagnostics as examples, this article describes the challenges associated with the scientific, clinical and regulatory hurdles faced by FDA and industry alike. Taken together, this discussion is intended to assist manufacturers toward a successful companion diagnostics development plan.

Digital mammography. Why hasn't it been approved for U.S. hospitals?

PubMed

2000-01-01

Mammography is the only major imaging technique still unavailable in the United States in digital form. This is because the Food and Drug Administration (FDA) has been unable to devise an effective method for manufacturers to demonstrate the safety and efficacy of digital mammography systems. As a result, the agency has been unable to approve any of those systems for marketing in the United States. In this Regulatory Update, we describe FDA's recent efforts to help manufacturers obtain approval and the reasons those efforts have so far proved ineffective.

Delegations of authority and organization; Center for Biologics Evaluation and Research, Center for Devices and Radiological Health, and Center for Drug Evaluation and Research--FDA. Final rule.

PubMed

1991-11-21

The Food and Drug Administration (FDA) is amending the regulations for delegations of authority relating to premarket approval of products that are or contain a biologic, a device, or a drug. The amendment grants directors, deputy directors, and certain other supervisory personnel in the Center for Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and the Center for Drug Evaluation and Research (CDER) reciprocal premarket approval authority to approve such products.

21 CFR 1141.1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... CIGARETTE PACKAGE AND ADVERTISING WARNINGS General Provisions § 1141.1 Scope. (a) This part sets forth the requirements for the display of health warnings on cigarette packages and in advertisements for cigarettes. FDA... manufacturers or distributors of cigarettes that do not manufacture, package, or import cigarettes for sale or...

Drug Safety

MedlinePlus

... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

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

PubMed

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

2015-09-01

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

2016 in review: FDA approvals of new molecular entities.

PubMed

Griesenauer, Rebekah H; Kinch, Michael S

2017-11-01

An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of mergers and acquisitions decreased the total number of organizations with past approval experience and continued research and development (R&D) activities to 102, divided evenly between more established pharmaceutical and newer biotechnology companies. Despite these substantial differences, the industry continued to pursue regulatory incentives, as evidenced by a continued increase in the fraction of NMEs approved using an orphan or priority designation, and almost all oncology drugs approved in 2016 utilized these mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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

PubMed

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

2015-01-01

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

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

PubMed

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

2018-01-01

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

Evaluation of drug content (potency) for compounded and FDA-approved formulations of doxycycline on receipt and after 21 days of storage.

PubMed

KuKanich, Kate; KuKanich, Butch; Slead, Tanner; Warner, Matt

2017-10-01

OBJECTIVE To determine drug content (potency) of compounded doxycycline formulations for veterinary use and of US FDA-approved doxycycline formulations for human use < 24 hours after receipt (day 1) and after 21 days of storage under recommended conditions (day 21). DESIGN Evaluation study. SAMPLE FDA-approved doxycycline tablets (100 mg), capsules (100 mg), and liquid suspension (10 mg/mL) and compounded doxycycline formulations from 3 pharmacies (tablets [25, 100, and 150 mg; 1 product/source], chews [100 mg; 1 product/source], and liquid suspensions or solution [6 mg/mL {2 sources} and 50 mg/mL {1 source}]). PROCEDURES Doxycycline content was measured in 5 samples of each tablet, chew, or capsule formulation and 5 replicates/bottle of liquid formulation on days 1 and 21 by liquid chromatography and compared with US Pharmacopeia acceptable ranges. RESULTS All FDA-approved formulations had acceptable content on days 1 and 21. On day 1, mean doxycycline content for the 3 compounded tablet formulations was 89%, 98%, and 116% (3/5, 5/5, and 1/5 samples within acceptable ranges); day 21 content range was 86% to 112% (1/5, 5/5, and 4/5 samples within acceptable ranges). Day 1 content of chews was 81%, 78%, and 98% (0/5, 0/5, and 5/5 samples within acceptable ranges), and that of compounded liquids was 50%, 52%, and 85% (no results within acceptable ranges). No chews or compounded liquid formulations met USP standards on day 21. CONCLUSIONS AND CLINICAL RELEVANCE FDA-approved doxycycline should be prescribed when possible. Whole tablets yielded the most consistent doxycycline content for compounded formulations.

AIDSinfo Drug Database

MedlinePlus

... HIV/AIDS-related drugs for that condition. OK Filters Approval: What's this? FDA-Approved Investigational Class: What's ... Encephalitis Tuberculosis Varicella-Zoster Virus Diseases Update Loading... Filter by approval status, drug class, and condition Browse ...

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments.

PubMed

2017-03-23

On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. Thereafter, the Department of Health and Human Services (HHS) provided the Drug Enforcement Administration (DEA) with a scheduling recommendation that would result in Syndros (and other oral solutions containing dronabinol) being placed in schedule II of the Controlled Substances Act (CSA). In accordance with the CSA, as revised by the Improving Regulatory Transparency for New Medical Therapies Act, DEA is hereby issuing an interim final rule placing FDA-approved products of oral solutions containing dronabinol in schedule II of the CSA.

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

PubMed Central

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

2015-01-01

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

Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

PubMed

Krentz, A J; Fujioka, K; Hompesch, M

2016-06-01

Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs. © 2016 John Wiley & Sons Ltd.

FDA Approvals - Cancer Currents Blog

Cancer.gov

Blog posts on cancer drugs and devices approved by the Food and Drug Administration—including summaries of the evidence to support the approvals and what they mean for patients—from NCI Cancer Currents.

21 CFR 314.55 - Pediatric use information.

Code of Federal Regulations, 2012 CFR

2012-04-01

... FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.55 Pediatric use... disease and the effects of the drug are sufficiently similar in adults and pediatric patients, FDA may... required. (b) Deferred submission. (1) FDA may, on its own initiative or at the request of an applicant...

21 CFR 314.55 - Pediatric use information.

Code of Federal Regulations, 2011 CFR

2011-04-01

... FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.55 Pediatric use... disease and the effects of the drug are sufficiently similar in adults and pediatric patients, FDA may... required. (b) Deferred submission. (1) FDA may, on its own initiative or at the request of an applicant...

21 CFR 314.95 - Notice of certification of invalidity or noninfringement of a patent.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... this section when it receives from FDA an acknowledgment letter stating that its abbreviated new drug... information: (1) A statement that FDA has received an abbreviated new drug application submitted by the...

21 CFR 814.42 - Filing a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

21 CFR 314.101 - Filing an application and receiving an abbreviated new drug application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.101 Filing an application and receiving an abbreviated new drug application. (a)(1) Within 60 days after FDA receives an...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-21

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

21 CFR 814.42 - Filing a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

21 CFR 314.101 - Filing an application and receiving an abbreviated new drug application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.101 Filing an application and receiving an abbreviated new drug application. (a)(1) Within 60 days after FDA receives an...

21 CFR 314.101 - Filing an application and receiving an abbreviated new drug application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.101 Filing an application and receiving an abbreviated new drug application. (a)(1) Within 60 days after FDA receives an...

21 CFR 314.55 - Pediatric use information.

Code of Federal Regulations, 2013 CFR

2013-04-01

... FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.55 Pediatric use... disease and the effects of the drug are sufficiently similar in adults and pediatric patients, FDA may... required. (b) Deferred submission. (1) FDA may, on its own initiative or at the request of an applicant...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

21 CFR 314.95 - Notice of certification of invalidity or noninfringement of a patent.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... this section when it receives from FDA an acknowledgment letter stating that its abbreviated new drug... information: (1) A statement that FDA has received an abbreviated new drug application submitted by the...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

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

21 CFR 314.101 - Filing an application and receiving an abbreviated new drug application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.101 Filing an application and receiving an abbreviated new drug application. (a)(1) Within 60 days after FDA receives an...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

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

21 CFR 314.101 - Filing an application and receiving an abbreviated new drug application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.101 Filing an application and receiving an abbreviated new drug application. (a)(1) Within 60 days after FDA receives an...

21 CFR 814.42 - Filing a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

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

PubMed

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

2016-12-01

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

Filgrastim for the treatment of hematopoietic acute radiation syndrome.

PubMed

Farese, A M; MacVittie, T J

2015-09-01

The U.S. Food and Drug Administration (FDA) recently approved Neupogen(®) (filgrastim) for the treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident. It is the first medical countermeasure currently approved by the FDA for this indication under the criteria of the FDA "animal rule". This article summarizes the consequences of high-dose radiation exposure, a description of the hematopoietic acute radiation syndrome (H-ARS), the use of hematopoietic growth factors in radiation accident victims and current available treatments for H-ARS with an emphasis on the use of Neupogen in this scenario. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

A new paradigm for obtaining marketing approval for pediatric-sized prosthetic heart valves.

PubMed

Yoganathan, Ajit P; Fogel, Mark; Gamble, Susan; Morton, Michael; Schmidt, Paul; Secunda, Jeff; Vidmar, Sara; Del Nido, Pedro

2013-10-01

Congenital heart valve disease is one of the most common abnormalities in children. There are limited technological solutions available for treating children with congenital heart valve diseases. The aim of this study is to provide the details of the consensus reached in terms of pediatric definitions, design approach, in vitro testing, and clinical trials, which may be used as guidance for developing prosthetic heart valves for the pediatric indication. In stark contrast to the various designs of adult-sized replacement valves available in the market, there are no Food and Drug Administration (FDA)-approved prosthetic heart valves available for use in the pediatric population. There is a pressing need for FDA-approved pediatric valve devices in the United States. The pediatric patient population has been typically excluded from replacement heart valve trials for several reasons. In January 2010, heart valve manufacturers and pediatric clinicians collaborated with academicians and FDA staff in a workshop to suggest ways to successfully evaluate pediatric prosthetic valves and conduct pediatric clinical trials to provide acceptable heart valve replacement options for this patient population. Recommendations, derived from ISO 5840:2005 and the 2010 FDA Draft Replacement Heart Valve Guidance, are provided for hydrodynamic, durability, and fatigue testing. The article specifically addresses in vitro and premarket and postmarket approval clinical studies that should be considered by a heart valve manufacturer for obtaining regulatory approval of pediatric sizes of prosthetic heart valve designs that are already approved for adult clinical use. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Impact of cardiovascular outcomes on the development and approval of medications for the treatment of diabetes mellitus.

PubMed

Joffe, Hylton V; Parks, Mary H; Temple, Robert

2010-03-01

All medications currently approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus are indicated to improve glycemic control. Since 1995, FDA has used HbA1c as the primary basis for approval of these therapies because a reduction in blood glucose lessens the symptoms of hyperglycemia and lowering of HbA1c has been shown to reduce the risk for some of the chronic complications of diabetes. Despite evidence of clinical benefit with therapies that reduce HbA1c, concerns have been raised that some diabetes medications may increase cardiovascular risk in a patient population that is already vulnerable to cardiovascular disease. Therefore, FDA convened a public advisory committee meeting to discuss the role of cardiovascular assessment in the pre-approval and post-approval settings for medications developed for the treatment of type 2 diabetes. After considering the advisory panel's recommendations and other data, FDA published a guidance document requesting evidence showing that new treatments for type 2 diabetes do not result in an unacceptable increase in cardiovascular risk. This review article begins by summarizing the events leading up to publication of this guidance. Subsequent sections discuss the guidance itself as well as general considerations for implementing the new cardiovascular recommendations. The new approach to developing medications for the treatment of type 2 diabetes will lead to evaluation in patients more representative of those who will use these therapies, if approved, and will help healthcare providers make informed decisions when choosing a medication within the growing treatment armamentarium for type 2 diabetes.

Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey.

PubMed

Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

2015-01-01

In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA) pathway. We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives.

Tattoos and Permanent Make-Up

MedlinePlus

... tattoos you have before any medical procedure. FDA's Role FDA-- has not approved any inks for injecting ... International Programs News & Events Training & Continuing Education Inspections & Compliance Federal, State & Local Officials Consumers Health Professionals Science & ...

16 CFR 1702.15 - Petitions alleging the incompatiability of child resistant packaging with the particular...

Code of Federal Regulations, 2010 CFR

2010-01-01

... is based upon the fact that package choice is limited by a new drug application filed with the FDA, the petition shall state the limitation of package choice and a description of a time schedule to revise the NDA in order to allow additional package choice. (c) If the allegation of incompatibility is...

16 CFR 1702.15 - Petitions alleging the incompatiability of child resistant packaging with the particular...

Code of Federal Regulations, 2011 CFR

2011-01-01

... is based upon the fact that package choice is limited by a new drug application filed with the FDA, the petition shall state the limitation of package choice and a description of a time schedule to revise the NDA in order to allow additional package choice. (c) If the allegation of incompatibility is...

16 CFR 1702.15 - Petitions alleging the incompatibility of child resistant packaging with the particular substance...

Code of Federal Regulations, 2012 CFR

2012-01-01

... is based upon the fact that package choice is limited by a new drug application filed with the FDA, the petition shall state the limitation of package choice and a description of a time schedule to revise the NDA in order to allow additional package choice. (c) If the allegation of incompatibility is...

16 CFR 1702.15 - Petitions alleging the incompatibility of child resistant packaging with the particular substance...

Code of Federal Regulations, 2014 CFR

2014-01-01

... is based upon the fact that package choice is limited by a new drug application filed with the FDA, the petition shall state the limitation of package choice and a description of a time schedule to revise the NDA in order to allow additional package choice. (c) If the allegation of incompatibility is...

16 CFR § 1702.15 - Petitions alleging the incompatibility of child resistant packaging with the particular substance...

Code of Federal Regulations, 2013 CFR

2013-01-01

... is based upon the fact that package choice is limited by a new drug application filed with the FDA, the petition shall state the limitation of package choice and a description of a time schedule to revise the NDA in order to allow additional package choice. (c) If the allegation of incompatibility is...

Communicating uncertainties about prescription drugs to the public: a national randomized trial.

PubMed

Schwartz, Lisa M; Woloshin, Steven

2011-09-12

Many new drugs are aggressively promoted. The public may not realize that even with US Food and Drug Administration (FDA) approval, important uncertainties about the benefits and harms of these drugs remain. We assessed the US public's understanding of the meaning of FDA drug approval and tested how brief explanations communicating drug uncertainties affect consumer choices. We conducted an Internet-based randomized controlled trial using a national sample of US adults from a research panel of approximately 30,000 households. A total of 2944 participants were randomized to receive 1 of 3 explanations about a pair of cholesterol drugs (1 approved based only on a surrogate outcome [lower cholesterol] and 1 based on a patient outcome [reduced myocardial infarctions]). Participants were randomized a second time to receive 1 of 3 explanations about a pair of heartburn drugs (1 newly approved and 1 approved 8 years earlier). Controls received no explanation; the nondirective group received explanations (for the cholesterol drugs, surrogates do not always translate into patient outcomes; for the heartburn drugs, it takes time to establish the safety of new drugs); the directive group received explanations plus advice to "Ask for a drug shown to reduce heart attacks or ask for one with a longer track record." The primary outcomes were choice: the cholesterol drug reducing myocardial infarctions, and the older heartburn drug. Thirty-nine percent mistakenly believed that the FDA approves only "extremely effective" drugs; 25% mistakenly believed that the FDA approves only drugs without serious side effects. Explanations affected choices: 71% of those in the directive group, 71% in the nondirective group, and 59% of controls chose the cholesterol drug that reduced myocardial infarctions (absolute difference, 12% [95% confidence interval, 7%-18%] for each explanation vs control). For the heartburn drugs, 53% of the directive group, 53% of the nondirective group, and 34% of controls chose the older drug (absolute difference, 19% [95% confidence interval, 13%-24%] for each explanation vs control). A substantial proportion of the public mistakenly believes that the FDA approves only extremely effective drugs and drugs lacking serious side effects. Brief explanations highlighting uncertainties about the benefit of drugs approved based on surrogate outcomes and the safety of new prescription drugs improved choices. Nondirective explanations worked as well as directive ones. clinicaltrials.gov Identifiers: NCT00950157, NCT00950131.

76 FR 36627 - Required Warnings for Cigarette Packages and Advertisements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

...The Food and Drug Administration (FDA) is amending its regulations to add a new requirement for the display of health warnings on cigarette packages and in cigarette advertisements. This rule implements a provision of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) that requires FDA to issue regulations requiring color graphics, depicting the negative health consequences of smoking, to accompany the nine new textual warning statements required under the Tobacco Control Act. The Tobacco Control Act amends the Federal Cigarette Labeling and Advertising Act (FCLAA) to require each cigarette package and advertisement to bear one of nine new textual warning statements. This final rule specifies the color graphic images that must accompany each of the nine new textual warning statements.

Required warnings for cigarette packages and advertisements. Final rule.

PubMed

2011-06-22

The Food and Drug Administration (FDA) is amending its regulations to add a new requirement for the display of health warnings on cigarette packages and in cigarette advertisements. This rule implements a provision of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) that requires FDA to issue regulations requiring color graphics, depicting the negative health consequences of smoking, to accompany the nine new textual warning statements required under the Tobacco Control Act. The Tobacco Control Act amends the Federal Cigarette Labeling and Advertising Act (FCLAA) to require each cigarette package and advertisement to bear one of nine new textual warning statements. This final rule specifies the color graphic images that must accompany each of the nine new textual warning statements.

The US Food and Drug Administration's tentative approval process and the global fight against HIV.

PubMed

Chahal, Harinder Singh; Murray, Jeffrey S; Shimer, Martin; Capella, Peter; Presto, Ryan; Valdez, Mary Lou; Lurie, Peter G

2017-12-01

In 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource-constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource-constrained settings. Although the tFDA was originally intended to support the United States' President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in-depth review of the relevant legal and regulatory processes. USFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use. In this paper, we describe the importance and implementation of USFDA's tentative approval process to review ARVs for resource-constrained settings. We also highlight the impact of patents and exclusivities on review of HIV drugs under tFDA and illustrate the concepts using a new HIV drug as an example. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Dietary Supplements: What You Need to Know

MedlinePlus

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

21 CFR 314.2 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.2 Purpose. The purpose of this part... safe and effective. These regulations are also intended to establish an effective system for FDA's...

21 CFR 314.2 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.2 Purpose. The purpose of this part... safe and effective. These regulations are also intended to establish an effective system for FDA's...

21 CFR 314.2 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.2 Purpose. The purpose of this part... safe and effective. These regulations are also intended to establish an effective system for FDA's...

21 CFR 314.2 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.2 Purpose. The purpose of this part... safe and effective. These regulations are also intended to establish an effective system for FDA's...

21 CFR 314.2 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.2 Purpose. The purpose of this part... safe and effective. These regulations are also intended to establish an effective system for FDA's...

Mammography: What You Need to Know

MedlinePlus

... changes in how the nipple looks. Why Is Facility Certification Important? The FDA, or an FDA-approved ... for all women.” Where Is the Closest Certified Facility? About 8,700 certified facilities are now in ...

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

Compounding and Extralabel Use of Drugs in Exotic Animal Medicine.

PubMed

Powers, Lauren V; Davidson, Gigi

2018-05-01

Extralabel drug use is the use of a Food and Drug Administration (FDA)-approved drug in a manner different from what is stipulated on the approved label. Compounding is the process of preparing a medication in a manner not indicated on the label to create a formulation specifically tailored to the needs of an individual patient. Extralabel drug use and compounding are vital aspects of safe and effective drug delivery to patients in exotic animal practice. There are few FDA-approved drugs for exotic animal species, and many approved drugs for other species are not available in suitable formulations for use in exotic animals. Copyright © 2018 Elsevier Inc. 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 75936 - Required Warnings for Cigarette Packages and Advertisements; Research Report

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... on consumer attitudes, beliefs, perceptions, and intended behaviors related to cigarette smoking. The... that FDA was conducting research to: (1) Measure consumer attitudes, beliefs, and intended behaviors... warnings on smoking behavior and evaluating the communication effectiveness of such images. FDA worked with...

Opportunities for Data Science in the Pharmaceutical Industry: The Use of Data to Find Efficiencies in Drug Development Can?t Come Too Soon.

PubMed

Keshava, Nirmal

2017-01-01

By the numbers, 2016 was not a good year for the U.S. pharmaceutical industry. As of early December, only 19 new drugs had been approved by the Food and Drug Administration (FDA), fewer than half of those approved in 2015 and the lowest number since 2007. Further, the FDA approved only 61% of submissions in 2016, compared to 95% in 2015 [1]. And, among the largest companies, the return on investment for research and development (R&D) fell to 3.7% [2].

Has the tobacco industry evaded the FDA's ban on ‘Light’ cigarette descriptors?

PubMed Central

Connolly, Gregory N; Alpert, Hillel R

2014-01-01

Background Under the Family Smoking Prevention and Tobacco Control Act (FSPTCA), the Food and Drug Administration (FDA) banned the use of “Lights” descriptors or similar terms on tobacco products that convey messages of reduced risk. Manufacturers eliminated terms explicitly stated and substituted colour name descriptors corresponding to the banned terms. This paper examines whether the tobacco industry complied with or circumvented the law and potential FDA regulatory actions. Methods Philip Morris retailer manuals, manufacturers' annual reports filed with the Massachusetts Department of Public Health, a national public opinion survey, and market-wide cigarette sales data were examined. Results Manufacturers substituted “Gold” for “Light” and “Silver” for “Ultra-light” in the names of Marlboro sub-brands, and “Blue”, “Gold”, and “Silver” for banned descriptors in sub-brand names. Percent filter ventilation levels, used to generate the smoke yield ranges associated with “Lights” categories, appear to have been reassigned to the new colour brand name descriptors. Following the ban, 92% of smokers reported they could easily identify their usual brands, and 68% correctly named the package colour associated with their usual brand, while sales for “Lights” cigarettes remained unchanged. Conclusions Tobacco manufacturers appear to have evaded a critical element of the FSPTCA, the ban on misleading descriptors that convey reduced health risk messages. The FPSTCA provides regulatory mechanisms, including banning these products as adulterated (Section 902). Manufacturers could then apply for pre-market approval as new products and produce evidence for FDA evaluation and determination whether or not sales of these products are in the public health interest. PMID:23485704

A Phase II Immunotherapeutic Trial: Combination Androgen Ablative Therapy Treatment for Advanced Prostate Cancer

DTIC Science & Technology

2008-03-01

two study statisticians; d) the filing of an investigator IND with the FDA; e) procurement of local IRB approvals; f) procurement of FDA-approval to...compromising the interpretation of outcome data pertaining to the treatment of patients with local or advanced prostate cancer receiving treatment on...patients prior treatment (radiation or cryotherapy ) • 1 patient taking Saw Palmetto (before criteria changed) • 5 patients taking Proscar/Avodart • 2

The Oncogenic Palmitoyi-Protein Network in Prostate Cancer

DTIC Science & Technology

2015-06-01

obesity drug, Ortistat, which inhibits the enzyme fatty acid synthase (FASN), has been shown to slow the growth of human prostate tumors in mice...Orlistat, an FDA-approved anti- obesity drug, suppresses the growth of human prostate tumors in nude mice.5 Despite these advances, the role of lipid...We also tested in vivo whether this network is vulnerable to an intervention that employs a dietary strategy in combination with an FDA-approved

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.

THPdb: Database of FDA-approved peptide and protein therapeutics.

PubMed

Usmani, Salman Sadullah; Bedi, Gursimran; Samuel, Jesse S; Singh, Sandeep; Kalra, Sourav; Kumar, Pawan; Ahuja, Anjuman Arora; Sharma, Meenu; Gautam, Ankur; Raghava, Gajendra P S

2017-01-01

THPdb (http://crdd.osdd.net/raghava/thpdb/) is a manually curated repository of Food and Drug Administration (FDA) approved therapeutic peptides and proteins. The information in THPdb has been compiled from 985 research publications, 70 patents and other resources like DrugBank. The current version of the database holds a total of 852 entries, providing comprehensive information on 239 US-FDA approved therapeutic peptides and proteins and their 380 drug variants. The information on each peptide and protein includes their sequences, chemical properties, composition, disease area, mode of activity, physical appearance, category or pharmacological class, pharmacodynamics, route of administration, toxicity, target of activity, etc. In addition, we have annotated the structure of most of the protein and peptides. A number of user-friendly tools have been integrated to facilitate easy browsing and data analysis. To assist scientific community, a web interface and mobile App have also been developed.

Recent strategies for drug development in fibromyalgia syndrome.

PubMed

Blumenthal, David E; Malemud, Charles J

2016-12-01

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

A Pressing Need for Pharmacotherapy Development to Treat Drug Addiction: An Editorial from a Legal Perspective.

PubMed

Andraka-Christou, B

2016-01-01

Only three FDA-approved pharmacological treatments exist for treating opiate dependence, all of which are underprescribed and underused. No FDA-approved pharmacological treatments exist for cocaine or methamphetamine dependence. More evidence-based, FDA-approved treatments are needed for treating drug dependence, but pharmaceutical companies are unlikely to pursue such research without government incentives. Today pharmaceutical companies primarily conduct research and development (R&D) related to "blockbuster" and rare diseases; drug dependence does not fall into either category. Further compounding the problem, pharmaceutical companies have been recently slashing risky areas of research, rather than adopting new areas. Fortunately, the government has a number of options to incentivize pharmaceutical R&D relating to drug dependence treatment, including the following: market exclusivity for new medications, tax breaks, priority review vouchers, liability reduction, and an advanced market commitment. © 2016 Elsevier Inc. All rights reserved.

The "art" of medicine and the "smokescreen" of the randomized trial off-label use of vascular devices.

PubMed

Ansel, Gary M; Jaff, Michael R

2008-12-01

Once a device is approved for sale in the United States by the Food and Drug Administration (FDA), it can legally be used by doctors to treat any condition a physician determines is medically appropriate. Based on postmarket published data and physician procedural experience, this may even become the standard of care when an alternative device either does not exist or is inferior in performance, even before FDA approval. This right of physicians to practice medicine without FDA approval is Federal law. The off-label use of medical devices for the treatment of peripheral vascular disease has recently become the latest target by groups with interests that have little to do with patient care. This interference has begun to negatively impact the latitude necessary for physicians to best treat their patients. Copyright 2008 Wiley-Liss, Inc.

Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis.

PubMed

Wallach, Joshua D; Egilman, Alexander C; Dhruva, Sanket S; McCarthy, Margaret E; Miller, Jennifer E; Woloshin, Steven; Schwartz, Lisa M; Ross, Joseph S

2018-05-24

To characterize postmarketing requirements for new drugs and biologics approved by the US Food and Drug Administration (FDA), and to examine rates and timeliness of registration, results reporting, and publication of required prospective cohort studies, registries, and clinical trials. Cross sectional analysis. Postmarketing requirements for all new drugs and biologics approved by the FDA between 1 January 2009 and 31 December 2012, with follow-up up to 15 November 2017. Postmarketing requirements and their characteristics known at the time of FDA approval, including FDA authority, study design, and study characteristics. Rates and timeliness of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials. Between 2009 and 12, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval, for a total of 437 postmarketing requirements. Postmarket study descriptions were short (median word count 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). 220 (50.3%) postmarketing requirements were for new animal or other studies (including pharmacokinetic studies); 134 (30.7%) were for prospective cohort studies, registries, and clinical trials; and 83 (19.0%) were for secondary analyses or follow-up studies. Of 110 clinical trials, 38 (34.5%), 44 (40.0%), 62 (56.4%), 66 (60.0%), and 98 (89.1%) did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled, respectively. Of 134 required prospective cohort studies, registries, and clinical trials, 102 (76.1%) were registered on ClinicalTrials.gov; of 50 registered and completed studies, 36 (72.0%) had reported results on ClinicalTrials.gov. Among 65 completed studies, 47 (72.3%) had either reported results or were published a median of 47 months (interquartile range 32-67) after FDA approval. 32 (68.1%) of these 47 studies did not report results publicly by the time of their original FDA report submission deadline. Postmarketing requirements for new drugs and biologics were often briefly described and did not contain enough information to characterize study designs. Approximately three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, and nearly three quarters of completed studies reported results or were published, suggesting that at least a quarter of these required studies are not being publicly disseminated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

76 FR 31965 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

.... ENDURANT STENT GRAFT SYSTEM. FDA-2011-M-0040 P100010 Medtronic Cryocath, ARCTIC FRONT December 17, 2010. LP.... Vascular. LX VASCULAR STENT SYSTEMS. FDA-2011-M-0039 P070026 Depuy, Inc......... CERAMAX CERAMIC HIP.... EXPANDABLE RENAL STENT SYSTEM. FDA-2011-M-0056 P090013 Medtronic, Inc..... REVO MRI SURESCAN IPG February 8...

77 FR 60704 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

...] Fenestrated April 4, 2012. AAA Endovascular Graft (with the adjunctive Zenith Alignment Stent). P110029, FDA...\\ plus CoCr April 12, 2012. Coronary Stent on RX System. P110035, FDA-2012-M-0373 Boston Scientific Epic\\TM\\ Vascular Self- April 13, 2012. Corp. Expanding Stent System. P090015, FDA-2012-M-0390 Leica...

77 FR 15779 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... 26, 2011. iliac balloon- expandable stent system. P100042, FDA-2011-M-0792 Gen-Probe APTIMA HPV assay..., 2011. XIENCE PRIME LL EVEROLIMUS-eluting coronary stent system. P100041, FDA-2011-M-0837 Edwards.... EVEROLIMUS-eluting platinum chromium coronary stent system. P100024, FDA-2011-M-0866 Dako Denmark A/S...

21 CFR 314.92 - Drug products for which abbreviated applications may be submitted.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... suitable for an abbreviated new drug application submission by FDA through the petition procedures set forth under § 10.30 of this chapter and § 314.93. (b) FDA will publish in the list listed drugs for...

21 CFR 314.52 - Notice of certification of invalidity or noninfringement of a patent.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... notice required by paragraph (a) of this section when it receives from FDA an acknowledgment letter...) application submitted by the applicant has been filed by FDA. (2) The application number. (3) The established...

21 CFR 314.92 - Drug products for which abbreviated applications may be submitted.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... suitable for an abbreviated new drug application submission by FDA through the petition procedures set forth under § 10.30 of this chapter and § 314.93. (b) FDA will publish in the list listed drugs for...

21 CFR 314.161 - Determination of reasons for voluntary withdrawal of a listed drug.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.161 Determination of reasons for... act, FDA will initiate a proceeding in accordance with § 314.153(b). (e) A drug that the agency...

21 CFR 314.52 - Notice of certification of invalidity or noninfringement of a patent.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... notice required by paragraph (a) of this section when it receives from FDA an acknowledgment letter...) application submitted by the applicant has been filed by FDA. (2) The application number. (3) The established...

21 CFR 99.305 - Exemption from the requirement to file a supplemental application.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., BIOLOGICS, AND DEVICES FDA Action on Submissions, Requests, and Applications § 99.305 Exemption from the... exemption from the requirement of a supplemental application, FDA shall approve or deny the application. (1) If FDA does not act on the application for an exemption within the 60-day period, the application for...

21 CFR 99.305 - Exemption from the requirement to file a supplemental application.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., BIOLOGICS, AND DEVICES FDA Action on Submissions, Requests, and Applications § 99.305 Exemption from the... exemption from the requirement of a supplemental application, FDA shall approve or deny the application. (1) If FDA does not act on the application for an exemption within the 60-day period, the application for...

21 CFR 314.52 - Notice of certification of invalidity or noninfringement of a patent.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... notice required by paragraph (a) of this section when it receives from FDA an acknowledgment letter...) application submitted by the applicant has been filed by FDA. (2) The application number. (3) The established...

21 CFR 314.161 - Determination of reasons for voluntary withdrawal of a listed drug.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.161 Determination of reasons for... act, FDA will initiate a proceeding in accordance with § 314.153(b). (e) A drug that the agency...

21 CFR 314.52 - Notice of certification of invalidity or noninfringement of a patent.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... notice required by paragraph (a) of this section when it receives from FDA an acknowledgment letter...) application submitted by the applicant has been filed by FDA. (2) The application number. (3) The established...

21 CFR 314.52 - Notice of certification of invalidity or noninfringement of a patent.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... notice required by paragraph (a) of this section when it receives from FDA an acknowledgment letter...) application submitted by the applicant has been filed by FDA. (2) The application number. (3) The established...

21 CFR 314.161 - Determination of reasons for voluntary withdrawal of a listed drug.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.161 Determination of reasons for... act, FDA will initiate a proceeding in accordance with § 314.153(b). (e) A drug that the agency...

21 CFR 314.92 - Drug products for which abbreviated applications may be submitted.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... suitable for an abbreviated new drug application submission by FDA through the petition procedures set forth under § 10.30 of this chapter and § 314.93. (b) FDA will publish in the list listed drugs for...

21 CFR 99.305 - Exemption from the requirement to file a supplemental application.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., BIOLOGICS, AND DEVICES FDA Action on Submissions, Requests, and Applications § 99.305 Exemption from the... exemption from the requirement of a supplemental application, FDA shall approve or deny the application. (1) If FDA does not act on the application for an exemption within the 60-day period, the application for...

21 CFR 99.305 - Exemption from the requirement to file a supplemental application.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., BIOLOGICS, AND DEVICES FDA Action on Submissions, Requests, and Applications § 99.305 Exemption from the... exemption from the requirement of a supplemental application, FDA shall approve or deny the application. (1) If FDA does not act on the application for an exemption within the 60-day period, the application for...

21 CFR 314.92 - Drug products for which abbreviated applications may be submitted.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... suitable for an abbreviated new drug application submission by FDA through the petition procedures set forth under § 10.30 of this chapter and § 314.93. (b) FDA will publish in the list listed drugs for...

21 CFR 314.161 - Determination of reasons for voluntary withdrawal of a listed drug.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.161 Determination of reasons for... act, FDA will initiate a proceeding in accordance with § 314.153(b). (e) A drug that the agency...

21 CFR 314.161 - Determination of reasons for voluntary withdrawal of a listed drug.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.161 Determination of reasons for... act, FDA will initiate a proceeding in accordance with § 314.153(b). (e) A drug that the agency...

Fibrin sealants: surgical hemostat, sealant and adhesive.

PubMed

Mandell, Samuel P; Gibran, Nicole S

2014-06-01

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

Tobramycin Ophthalmic

MedlinePlus

... not currently approved by the FDA for safety, effectiveness, and quality. Federal law generally requires that prescription drugs in the U.S. be shown to be both safe and effective prior to marketing. Please see the FDA website for more information ...

Radiopharmaceutical regulation and Food and Drug Administration policy.

PubMed

Rotman, M; Laven, D; Levine, G

1996-04-01

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

76 FR 43847 - Poison Prevention Packaging Requirements; Exemption of Powder Formulations of Colesevelam...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

... FDA-regulated drug, biologic, medical device, dietary supplement, or cosmetic. (See http://www.fda.gov... powders generally present a low risk because they are more difficult to ingest, particularly in large quantities. Generally, with the exception of caustics, the primary exposure risk associated with powders is...

75 FR 78715 - Small Entity Compliance Guide: Current Good Manufacturing Practice in Manufacturing, Packaging...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0605..., or Holding Operations for Dietary Supplements; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a...

Adolescent dosing and labeling since the Food and Drug Administration Amendments Act of 2007.

PubMed

Momper, Jeremiah D; Mulugeta, Yeruk; Green, Dionna J; Karesh, Alyson; Krudys, Kevin M; Sachs, Hari C; Yao, Lynn P; Burckart, Gilbert J

2013-10-01

During pediatric drug development, dedicated pharmacokinetic studies are generally performed in all relevant age groups to support dose selection for subsequent efficacy trials. To our knowledge, no previous assessments regarding the need for an intensive pharmacokinetic study in adolescents have been performed. To compare U.S. Food and Drug Administration (FDA)-approved adult and adolescent drug dosing and to assess the utility of allometric scaling for the prediction of drug clearance in the adolescent population. Adult and adolescent dosing and drug clearance data were obtained from FDA-approved drug labels and publicly available databases containing reviews of pediatric trials submitted to the FDA. Dosing information was compared for products with concordant indications for adolescent and adult patients. Adolescent drug clearance was predicted from adult pharmacokinetic data by using allometric scaling and compared with observed values. Adolescent and adult dosing information and drug clearance. There were 126 unique products with pediatric studies submitted to the FDA since the FDA Amendments Act of 2007, of which 92 had at least 1 adolescent indication concordant with an adult indication. Of these 92 products, 87 (94.5%) have equivalent dosing for adults and adolescent patients. For 18 of these 92 products, a minimum weight or body surface area threshold is recommended for adolescents to receive adult dosing. Allometric scaling predicted adolescent drug clearance with an overall mean absolute percentage error of 17.0%. Approved adult and adolescent drug dosing is equivalent for 94.5% of products with an adolescent indication studied since the FDA Amendments Act of 2007. Allometric scaling may be a useful tool to avoid unnecessary dedicated pharmacokinetic studies in the adolescent population during pediatric drug development, although each development program in adolescents requires a full discussion of drug dosing with the FDA.

AMCP Partnership Forum: Enabling the Exchange of Clinical and Economic Information Pre-FDA Approval.

PubMed

2017-01-01

Current federal laws and FDA regulations have significantly restricted the sharing of clinical and health economic information on biopharmaceuticals that have yet to receive FDA approval. Over the past several years, organizations that make health care coverage decisions, including those that set copayments, premiums, and formulary placement, have expressed a need for receiving this information before approval, as long as appropriate safeguards exist to prevent this information from reaching unintended entities. Population health decision makers have indicated that waiting until FDA approval is often too late for the critical planning, budgeting, and forecasting associated with health benefit design, especially given the recent influx of high-cost medications and scrutiny for better evaluation and preparation. Recognizing that securities laws restrict the disclosure of nonpublic information and may need to be amended, permissible early dissemination would allow population health decision makers to incorporate clinical and economic information for pipeline drugs or expanded indications into financial forecasting for the following year's plan. Access to this information is needed 12-18 months before FDA approval when organizations are deciding on terms of coverage and budgetary assumptions for state health insurance rate filings, Medicare and Medicaid bids, contracts with health care purchasers, and other financial arrangements. The need for exchange of clinical economic information before FDA approval was first introduced at a previous Academy of Managed Care (AMCP) forum in March 2016, which addressed section 114 of the Food and Drug Administration Modernization Act and the communication of such information after FDA approval. To address preapproval information specifically, AMCP convened a Partnership Forum on September 13-14, 2016. This forum included a diverse group of stakeholders representing managed care, the biopharmaceutical industry, providers, patients, health economists, academia, and others. The multistakeholder group represented the key professionals and entities affected by the federal laws and FDA regulations that restrict the sharing of preapproval information and the collective credibility necessary for proposing this new communication process. Forum participants primarily focused on 6 items of discussion: (1) creating and defining new terms for how biopharmaceutical manufacturers may provide clinical and economic information 12-18 months before FDA approval; (2) defining the clinical and scientific standards that this information should meet; (3) determining which entities should have access to this information and the value to each; (4) the format and process by which this information should be disseminated; (5) developing definitions for existing terms referenced in current laws, regulations, or guidance documents that would need to be modernized to align with the identified new term; and (6) providing safeguards to prevent this information from reaching unintended entities. Forum participants selected "preapproval information exchange" (PIE) as the correct term to describe this proposed new communication process and to be inclusive of data from pivotal phase III clinical trials, pharmaco-economic data, and patient-reported outcomes, as well as other relevant items, including anticipated indications, place in therapy, and routes of administration. Stakeholders agreed that PIE should be truthful, non-misleading, and include a broad range of information to meet the needs of population health decision makers and health care technology evolution. Recipients of PIE would be limited to population health decision makers who need this information for coverage decisions. The format and process for PIE disseminated should allow for a bidirectional exchange between manufacturers and population health decision makers but should not be proscribed in legislation. Furthermore, new legislative language may be beneficial, since PIE is a novel category of information. New legislation could provide a safe harbor and clarity that PIE does not violate preapproval promotion and the Federal Food, Drug, and Cosmetic Act and its regulations. The AMCP Partnership Forum on Enabling the Exchange of Clinical and Economic Data Pre-FDA Approval and the development of this proceedings document were supported by AbbVie, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Celgene, Intarcia Therapeutics, Eli Lilly and Company, GlaxoSmithKline, Merck, National Pharmaceutical Council, Novo Nordisk, Pfizer, Pharmaceutical Research and Manufacturers of America, Precision for Value, Sanofi, Takeda Pharmaceuticals, U.S.A., and Xcenda. All sponsors participated in the forum and in revising and approving the manuscript.

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, selection of clinical research operations contractor, data capturing and management, and annual reporting of results to FDA were successfully completed. Protocol 002-A was completed and sample and data analysis is currently in progress. Protocol 002-B is currently in progress at Dartmouth Hitchcock Medical Center and Protocol 002-C has been submitted to the FDA and will be implemented at the same contractor site as 002-A. An annual report was filed as required by FDA on the results of Protocol 002-A. Once all the three Phase II protocols are completed, a New Drug Administration application will be filed with FDA for Phase III clinical assessment and approval for marketing of the formulation. A commercial vendor will be identified for this phase. This is critical for making this available for treatment of SMS in astronauts and military personnel on duty. Once approved by FDA, INSCOP can be also used by civilian population for motion sickness associated with recreational travel and other ailments that require treatment with anticholinergic drugs.

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.

Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

PubMed Central

Miller, Jennifer E; Korn, David; Ross, Joseph S

2015-01-01

Objective To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Conclusions Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge. PMID:26563214

Economics of new oncology drug development.

PubMed

DiMasi, Joseph A; Grabowski, Henry G

2007-01-10

Review existing studies and provide new results on the development, regulatory, and market aspects of new oncology drug development. We utilized data from the US Food and Drug Administration (FDA), company surveys, and publicly available commercial business intelligence databases on new oncology drugs approved in the United States and on investigational oncology drugs to estimate average development and regulatory approval times, clinical approval success rates, first-in-class status, and global market diffusion. We found that approved new oncology drugs to have a disproportionately high share of FDA priority review ratings, of orphan drug designations at approval, and of drugs that were granted inclusion in at least one of the FDA's expedited access programs. US regulatory approval times were shorter, on average, for oncology drugs (0.5 years), but US clinical development times were longer on average (1.5 years). Clinical approval success rates were similar for oncology and other drugs, but proportionately more of the oncology failures reached expensive late-stage clinical testing before being abandoned. In relation to other drugs, new oncology drug approvals were more often first-in-class and diffused more widely across important international markets. The market success of oncology drugs has induced a substantial amount of investment in oncology drug development in the last decade or so. However, given the great need for further progress, the extent to which efforts to develop new oncology drugs will grow depends on future public-sector investment in basic research, developments in translational medicine, and regulatory reforms that advance drug-development science.

Antipyrine-Benzocaine Otic

MedlinePlus

... not currently approved by the FDA for safety, effectiveness, and quality. Federal law generally requires that prescription drugs in the U.S. be shown to be both safe and effective prior to marketing. Please see the FDA website for more information ...

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

PubMed

Trumbo, Paula R; Ellwood, Kathleen C

2006-08-01

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

New Antiretroviral Therapies for Pediatric HIV Infection

PubMed Central

Morris, Jennifer L.; Kraus, Donna M.

2005-01-01

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection. PMID:23118639

21 CFR 314.90 - Waivers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.90 Waivers. (a) An applicant may ask the... under §§ 314.50 through 314.81. An applicant may ask FDA to waive under § 314.126(c) any criteria of an... information justifying a waiver. (b) FDA may grant a waiver if it finds one of the following: (1) The...

21 CFR 314.90 - Waivers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.90 Waivers. (a) An applicant may ask the... under §§ 314.50 through 314.81. An applicant may ask FDA to waive under § 314.126(c) any criteria of an... information justifying a waiver. (b) FDA may grant a waiver if it finds one of the following: (1) The...

21 CFR 314.90 - Waivers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.90 Waivers. (a) An applicant may ask the... under §§ 314.50 through 314.81. An applicant may ask FDA to waive under § 314.126(c) any criteria of an... information justifying a waiver. (b) FDA may grant a waiver if it finds one of the following: (1) The...

21 CFR 814.44 - Procedures for review of a PMA.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

21 CFR 314.90 - Waivers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.90 Waivers. (a) An applicant may ask the... under §§ 314.50 through 314.81. An applicant may ask FDA to waive under § 314.126(c) any criteria of an... information justifying a waiver. (b) FDA may grant a waiver if it finds one of the following: (1) The...

2017 in review: FDA approvals of new molecular entities.

PubMed

Kinch, Michael S; Griesenauer, Rebekah H

2018-05-08

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

75 FR 69523 - Required Warnings for Cigarette Packages and Advertisements

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

...The Food and Drug Administration (FDA) is proposing to amend its regulations to add a new requirement for the display of health warnings on cigarette packages and in cigarette advertisements. The proposed rule would implement a provision of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) that requires FDA to issue regulations requiring color graphics depicting the negative health consequences of smoking to accompany the nine new textual warning statements that will be required under the Tobacco Control Act. The Tobacco Control Act amends the Federal Cigarette Labeling and Advertising Act (FCLAA) to require each cigarette package and advertisement to bear one of nine new textual warning statements. This proposed rule, once finalized, would specify the color graphics that must accompany each of the nine new textual warning statements.

Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database

PubMed Central

Turner, Erick H.; Knoepflmacher, Daniel; Shapley, Lee

2012-01-01

Background Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy. Methods and Findings FDA Drug Approval Packages for eight second-generation antipsychotics—aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection (risperidone LAI), and ziprasidone—were used to identify a cohort of 24 FDA-registered premarketing trials. The results of these trials according to the FDA were compared with the results conveyed in corresponding journal articles. The relationship between study outcome and publication status was examined, and effect sizes derived from the two data sources were compared. Among the 24 FDA-registered trials, four (17%) were unpublished. Of these, three failed to show that the study drug had a statistical advantage over placebo, and one showed the study drug was statistically inferior to the active comparator. Among the 20 published trials, the five that were not positive, according to the FDA, showed some evidence of outcome reporting bias. However, the association between trial outcome and publication status did not reach statistical significance. Further, the apparent increase in the effect size point estimate due to publication bias was modest (8%) and not statistically significant. On the other hand, the effect size for unpublished trials (0.23, 95% confidence interval 0.07 to 0.39) was less than half that for the published trials (0.47, 95% confidence interval 0.40 to 0.54), a difference that was significant. Conclusions The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently. Without increased access to regulatory agency data, publication bias will continue to blur distinctions between effective and ineffective drugs. Please see later in the article for the Editors' Summary PMID:22448149

Immunotherapy Combination Approved for Advanced Kidney Cancer

Cancer.gov

FDA has approved the combination of the immunotherapy drugs nivolumab (Opdivo) and ipilimumab (Yervoy) as an initial treatment for some patients with advanced kidney cancer. The approval is expected to immediately affect patient care, as this Cancer Currents post explains.

HIV Testing in the United States

MedlinePlus

... health facilities ;” May 2007. ← Return to text FDA Consumer Information, “Fourth Generation HIV Diagnostic Test Approved, permitting ... HIV): Screening; ” April 2013. ← Return to text FDA Consumer Information, “First rapid diagnostic test to detect both ...

21 CFR 314.1 - Scope of this part.

Code of Federal Regulations, 2014 CFR

2014-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.1 Scope of this part... postmarketing reports to them. (b) This part does not apply to drug products subject to licensing by FDA under...

21 CFR 314.1 - Scope of this part.

Code of Federal Regulations, 2013 CFR

2013-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.1 Scope of this part... postmarketing reports to them. (b) This part does not apply to drug products subject to licensing by FDA under...

21 CFR 314.99 - Other responsibilities of an applicant of an abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... abbreviated application. (b) An applicant may ask FDA to waive under this section any requirement that applies...

21 CFR 314.1 - Scope of this part.

Code of Federal Regulations, 2012 CFR

2012-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.1 Scope of this part... postmarketing reports to them. (b) This part does not apply to drug products subject to licensing by FDA under...

21 CFR 314.1 - Scope of this part.

Code of Federal Regulations, 2010 CFR

2010-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.1 Scope of this part... postmarketing reports to them. (b) This part does not apply to drug products subject to licensing by FDA under...

21 CFR 314.99 - Other responsibilities of an applicant of an abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW... abbreviated application. (b) An applicant may ask FDA to waive under this section any requirement that applies...

21 CFR 314.1 - Scope of this part.

Code of Federal Regulations, 2011 CFR

2011-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG General Provisions § 314.1 Scope of this part... postmarketing reports to them. (b) This part does not apply to drug products subject to licensing by FDA under...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

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

Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening.

PubMed

Pothineni, Venkata Raveendra; Wagh, Dhananjay; Babar, Mustafeez Mujtaba; Inayathullah, Mohammed; Solow-Cordero, David; Kim, Kwang-Min; Samineni, Aneesh V; Parekh, Mansi B; Tayebi, Lobat; Rajadas, Jayakumar

2016-01-01

Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that >300,000 cases per annum are reported in USA alone. A total of 10%-20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with posttreatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved) that were screened are Library of Pharmacologically Active Compounds (LOPAC1280), the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150 unique compounds, which inhibited >90% of B. burgdorferi growth at a concentration of <25 µM. These 150 unique compounds comprise many safe antibiotics, chemical compounds, and also small molecules from plant sources. Of the 150 unique compounds, 101 compounds are FDA approved. We selected the top 20 FDA-approved molecules based on safety and potency and studied their minimum inhibitory concentration and minimum bactericidal concentration. The promising safe FDA-approved candidates that show low minimum inhibitory concentration and minimum bactericidal concentration values can be chosen as lead molecules for further advanced studies.

Ethical imperatives of timely access to orphan drugs: is possible to reconcile economic incentives and patients' health needs?

PubMed

Rodriguez-Monguio, R; Spargo, T; Seoane-Vazquez, E

2017-01-05

More than 6,800 rare diseases and conditions have been identified in the US, which affect 25-30 million Americans. In 1983, the US Congress enacted the Orphan Drug Act (ODA) to encourage the development and marketing of drugs to treat rare diseases and conditions. This study analyzed all orphan designations and FDA approvals since 1983 through 2015, discussed the effectiveness of incentives for the development of treatments for rare diseases, and reflected on the ethical imperatives for timely access to orphan drugs. Study data were derived from the Food and Drug Administration (FDA) Orange Book and the Office of Orphan Drugs Development. A search was conducted to assess literature on the ethical principles and economic incentives for the development of orphan drugs. In the period 1983-2015, the FDA granted 3,647 orphan drug designations and 554 orphan drug approvals. The orphan drug approvals corresponded to 438 different brand names. Cancer was the therapeutic area with the highest number of approvals. The increased number of patients with rare diseases and the growth in the cost of orphan drugs pose a significant economic burden for patients, public programs and private third party payers. Regulatory differences to qualify for orphan designation and various population thresholds employed by the FDA and the European Medicines Agency lead to further unmet health needs for patients with rare diseases and aggravate health inequities. There is no societal consensus on the population and economic thresholds, the drug effectiveness indicator(s), or the societal value to be placed for the approval and reimbursement of orphan drugs. Orphan drug development and marketing in the US concentrate in few therapeutic areas. Despite the increase in the number of FDA approved orphan drugs, the unmet needs of patients with rare diseases evidence that the current incentives are not efficiently stimulating orphan drug development. There is need to balance economic incentives to stimulate the development and marketing of orphan drugs without jeopardizing patients' access to treatment. Thus, aligning pharmaceutical companies' incentives with societal budgetary constraints is necessary and the ethical imperatives of timely access to orphan drugs need to be agreed upon.

A rational regulatory approach for positron emission tomography imaging probes: from "first in man" to NDA approval and reimbursement.

PubMed

Barrio, Jorge R; Marcus, Carol S; Hung, Joseph C; Keppler, Jennifer S

2004-01-01

We propose a new regulatory approach for positron emission tomography (PET) molecular imaging probes, essential tools in today's medicine. Even though the focus of this paper is on positron-emitting labeled probes, it is also justified to extend this proposed regulatory approach to other diagnostic nuclear medicine radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular imaging probes would be placed in a "no significant risk" category, similar to that category for devices in current Food and Drug Administration (FDA) regulations, based on overwhelming scientific evidence that demonstrates their faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research Committee (RDRC) will oversee all diagnostic research with these probes. The newly defined RDRC should approve "first in man" use; supervise a broader spectrum of diagnostic research protocols, including those looking to demonstrate initial efficacy, as well as multicenter clinical trials and the use of molecular imaging probes as a screening tool in drug discovery. The current investigational new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval (i.e., NDA) will be sought. The review will be done by a newly constituted Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the professional societies, who would provide a binding assessment of the adequacy of the safety and efficacy data. When the RDAC recommends its diagnostic use on scientific and medical grounds, the molecular imaging probe becomes FDA approved. After a molecular imaging probe is approved for a diagnostic indication, the existing mechanism to seek reimbursement will be utilized; and (4) the FDA would retain its direct oversight function for traditional manufacturers engaged in commercial distribution of the approved diagnostic molecular imaging probes (i.e., under NDA) to monitor compliance with existing US Pharmacopeia (USP) requirements. With abbreviated and more appropriate regulations, new PET molecular imaging probes for diagnostic use would be then rapidly incorporated into the mainstream diagnostic medicine. Equally importantly, this approach would facilitate the use of molecular imaging in drug discovery and development, which would substantially reduce the costs and time required to bring new therapeutic drugs to market.

Regulatory perspectives and research activities at the FDA on the use of phantoms with in vivo diagnostic devices

NASA Astrophysics Data System (ADS)

Agrawal, Anant; Gavrielides, Marios A.; Weininger, Sandy; Chakrabarti, Kish; Pfefer, Joshua

2008-02-01

For a number of years, phantoms have been used to optimize device parameters and validate performance in the primary medical imaging modalities (CT, MRI, PET/SPECT, ultrasound). Furthermore, the FDA under the Mammography Quality Standards Act (MQSA) requires image quality evaluation of mammography systems using FDA-approved phantoms. The oldest quantitative optical diagnostic technology, pulse oximetry, also benefits from the use of active phantoms known as patient simulators to validate certain performance characteristics under different clinically-relevant conditions. As such, guidance provided by the FDA to its staff and to industry on the contents of pre-market notification and approval submissions includes suggestions on how to incorporate the appropriate phantoms in establishing device effectiveness. Research at the FDA supports regulatory statements on the use of phantoms by investigating how phantoms can be designed, characterized, and utilized to determine critical device performance characteristics. These examples provide a model for how novel techniques in the rapidly growing field of optical diagnostics can use phantoms during pre- and post-market regulatory testing.

FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | Poster

Cancer.gov

By Frank Blanchard, Staff Writer The U.S. Food and Drug Administration (FDA) recently approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected. The National Cancer Institute’s (NCI) Biopharmaceutical Development Program (BDP) at the Frederick National Laboratory for Cancer Research produced ch14.18 for the NCI-sponsored clinical trials that proved the drug’s effectiveness against the disease.

tetrahydrocannabinol (delta-9-THC)] in Schedule II. Final rule.

PubMed

2017-11-22

This final rule adopts without changes an interim final rule with request for comments published in the Federal Register on March 23, 2017. On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. The Drug Enforcement Administration (DEA) maintains FDA-approved products of oral solutions containing dronabinol in schedule II of the Controlled Substances Act.

As if Biomarker Discovery Isn't Hard Enough: the Consequences of Poorly Characterized Reagents

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

Rodland, Karin D.

The advent of high throughput omic technologies over the past two decades has driven a vast expansion in the search for clinical biomarkers, as manifested by the plethora of publications on biomarker discovery (over 8,600) listed on PubMed since 2000. Unfortunately, the same time period has seen a relative dearth of clinically validated biomarkers that have received FDA approval; only 10 new cancer biomarkers have been approved by the FDA in the same time period [1].

New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals.

PubMed

Stancu, Andreea Lucia; Smith, Mitchell R; Almasan, Alexandru

2014-01-01

Leukemia and lymphoma are systemic malignancies that represent half of all childhood cancers, though 90% occur in adults. Various treatment options are available, but therapy is mainly systemic chemotherapy plus appropriate monoclonal antibodies. In certain situations radiotherapy and bone marrow transplantation play a role. Some types/subtypes of these diseases are potentially curable, yet many leukemias and lymphomas do not properly respond to current therapies. Although the FDA (US Food and Drugs Administration) approvals of new drugs have shown a small increasing trend between 2007-2012, overall, the trend of new approvals remains relatively steady between 2006-2013, with a peak of 39 new drugs approved in 2012 and a drop in the new FDA drug approvals in 2013, to 27. Drugs approved for cancer treatment have shown a similar trend. Between 2006-2013, at least one drug was approved every year for the treatment of particular types of lymphoma or leukemia, except in 2010, with a peak of 5 new approvals in 2012. Between January 2013-March 2014, several important new approvals were made: ibrutinib for the treatment of CLL and mantle cell lymphoma (MCL), obinutuzumab for the treatment of CLL (in combination with chlorambucil), and lenalidomide for the treatment of mantle cell lymphoma. The results, importance, adverse effects and mechanisms of action of these agents are discussed in this review. These results held promise and their discovery and approval for the treatment of CLL and MCL is a major step forward. However, the emergence of resistance and the lack of cures need to be addressed by rational development of combination therapy, as well as development of novel drugs with enhanced potency or different mechanism of action, to achieve better overall and complete response rates with decreased toxicity.

New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals

PubMed Central

Stancu, Andreea Lucia; Smith, Mitchell R.; Almasan, Alexandru

2015-01-01

Leukemia and lymphoma are systemic malignancies that represent half of all childhood cancers, though 90% occur in adults. Various treatment options are available, but therapy is mainly systemic chemotherapy plus appropriate monoclonal antibodies. In certain situations radiotherapy and bone marrow transplantation play a role. Some types/subtypes of these diseases are potentially curable, yet many leukemias and lymphomas do not properly respond to current therapies. Although the FDA (US Food and Drugs Administration) approvals of new drugs have shown a small increasing trend between 2007–2012, overall, the trend of new approvals remains relatively steady between 2006–2013, with a peak of 39 new drugs approved in 2012 and a drop in the new FDA drug approvals in 2013, to 27. Drugs approved for cancer treatment have shown a similar trend. Between 2006–2013, at least one drug was approved every year for the treatment of particular types of lymphoma or leukemia, except in 2010, with a peak of 5 new approvals in 2012. Between January 2013-March 2014, several important new approvals were made: ibrutinib for the treatment of CLL and mantle cell lymphoma (MCL), obinutuzumab for the treatment of CLL (in combination with chlorambucil), and lenalidomide for the treatment of mantle cell lymphoma. The results, importance, adverse effects and mechanisms of action of these agents are discussed in this review. These results held promise and their discovery and approval for the treatment of CLL and MCL is a major step forward. However, the emergence of resistance and the lack of cures need to be addressed by rational development of combination therapy, as well as development of novel drugs with enhanced potency or different mechanism of action, to achieve better overall and complete response rates with decreased toxicity. PMID:26280017

Petition to request an exemption from 100 percent identity testing of dietary ingredients: Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements. Interim final rule.

PubMed

2007-06-25

The Food and Drug Administration (FDA) is issuing an interim final rule (IFR) that sets forth a procedure for requesting an exemption from the requirement in the final rule "Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements," published elsewhere in this issue of the Federal Register, that the manufacturer conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient. This IFR allows for submission to, and review by, FDA of an alternative to the required 100 percent identity testing of components that are dietary ingredients, provided certain conditions are met and establishes a requirement for retention of records relating to the FDA's response to an exemption request.

Market withdrawal of new molecular entities approved in the United States from 1980 to 2009.

PubMed

Qureshi, Zaina P; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Stevenson, Kurt B; Szeinbach, Sheryl L

2011-07-01

Economic factors, market dynamics, and safety issues are largely responsible for decisions to withdraw pharmaceutical products from the market. In this study, new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) were examined in the USA from 1980 to 2009. Data were obtained from the FDA, Micromedex, Medline, and Lexis-Nexis. Descriptive analyses were used to classify product discontinuations by therapeutic category, time frame for discontinuation, and reason for withdrawal. There were 740 NMEs approved by the FDA during the study period. As of 1 December 2010, the number of drugs discontinued was 118 (15.9%). Discontinuations were the highest for antiparasitic products, insecticides, and repellents (6, 33.3% of approvals), systemic hormonal preparations excluding sex hormones and insulins (5, 33.3%), musculo-skeletal system (11, 32.4%), diagnostic agents (16, 28.1%), and anti-infectives for systemic use (27, 25.2%). Safety was the primary reason for withdrawing 26 drugs (3.5% of approvals). Approximately one in seven approved NMEs were discontinued from the market in the period of 1980-2009. Less than one-quarter (22%) of the total withdrawals were attributed to safety reasons. An ongoing evaluation of new drugs throughout their product life cycle is important to determine their efficacy, safety, and value to society. Copyright © 2011 John Wiley & Sons, Ltd.

21 CFR 814.44 - Procedures for review of a PMA.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

21 CFR 814.44 - Procedures for review of a PMA.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

Evaluation of efficacy of heartworm preventive products at the FDA.

PubMed

Hampshire, Victoria A

2005-10-24

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

Development and approval of vaccines in the United States.

PubMed

Botstein, P

1986-01-01

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

Tisagenlecleucel (Kymriah) Approved to Treat Some Lymphomas

Cancer.gov

FDA has approved the CAR T-cell therapy tisagenlecleucel for adults with diffuse large B-cell lymphoma that is relapsed or refractory. Learn more about this new approval and how it may affect patients in this NCI Cancer Currents blog post.

75 FR 38532 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

... LLIAC March 5, FDA-2010-M-0135 Scientific PREMOUNTED STENT SYSTEM 2010 Corp. P090006 Medtronic COMPLETE SE VASCULAR March 17, FDA-2010-M-0158 Vascular STENT SYSTEM 2010 II. Electronic Access Persons with...

The next forum for unraveling FDA off-label marketing rules: State and federal legislatures.

PubMed

Sinha, Michael S; Kesselheim, Aaron S

2018-05-01

In a Guest Editorial, Aaron S. Kesselheim and Michael S. Sinha show how federal and state legislation to allow promotion of drugs for non-approved uses threatens to undermine the FDA's public health mission.

21 CFR 314.65 - Withdrawal by the applicant of an unapproved application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... application and will provide a copy to the applicant on request under the fee schedule in § 20.45 of FDA's...

21 CFR 314.65 - Withdrawal by the applicant of an unapproved application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... application and will provide a copy to the applicant on request under the fee schedule in § 20.45 of FDA's...

21 CFR 314.65 - Withdrawal by the applicant of an unapproved application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... application and will provide a copy to the applicant on request under the fee schedule in § 20.45 of FDA's...

21 CFR 314.65 - Withdrawal by the applicant of an unapproved application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... application and will provide a copy to the applicant on request under the fee schedule in § 20.45 of FDA's...

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

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

PubMed

Mishra, Sundeep

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

Who's guarding what? A poststructural feminist analysis of gardasil discourses.

PubMed

Thompson, Marie

2010-03-01

In May 2006 the Gardasil vaccine was approved for implementation in the United States to prohibit the spread of four strains of the human papillomavirus (HPV) that can lead to cervical cancer. Through a poststructural feminist reading, I critique ideologies at play throughout the Food and Drug Administration (FDA) approval hearing for this vaccine. I explore the conditions that gave rise to the adoption of the Gardasil vaccine as evidenced in the hearing transcript, and probe contradictions between choices the FDA enacted for the feminine body with those recommendations from lead scientists of Merck that urged the inclusion of males in the vaccination process. Along the way, I respond to appeals from scholars to address matters of health policy formation and implementation as critical and underexplored dimensions of health communication. I offer a vision that makes way for proactive engagement of males in reproductive and sexual health, particularly as the FDA delayed vaccine approval for males until 2009.

Amprenavir, new protease inhibitor, approved.

PubMed

James, J S

1999-05-07

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

Drugs Approved for Neuroblastoma

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

An examination of structure-function claims in dietary supplement advertising in the U.S.: 2003-2009.

PubMed

Avery, Rosemary J; Eisenberg, Matthew D; Cantor, Jonathan H

2017-04-01

Dietary supplement advertising cannot claim a causal link between the product and the treatment, prevention, or cure of a disease unless manufacturers seek approval from the FDA for a health claim. Manufacturers can make structure-function (S-F) claims without FDA approval linking a supplement to a body function or system using words such as "may help" or "promotes." These S-F claims are examined in this study in order to determine whether they mimic health claims for which the FDA requires stricter scientific evidence. Data include S-F claims in supplement advertisements (N=6179) appearing in US nationally circulated magazines (N=137) from 2003 to 2009. All advertisements were comprehensively coded for S-F claims, seals of approval, and other claims of guarantee. S-F claims associate supplements with a wide variety of health conditions, many of which are serious diseases and/or ailments. A significant number of the specific verbs used in these S-F claims are indicative of disease treatment/cure effects, thereby possibly mimicking health claims to the average consumer. The strength of the clinical associations made are largely unsubstantiated in the medical literature. Claims that a product is "scientifically proven" or "guaranteed" were largely unsubstantiated by clinical literature. Ads carrying externally validating seals of approval were highly prevalent. S-F claims that strongly mimic FDA-prohibited health claims are likely to create confusion in interpretation and possible public health concerns are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Delegations of authority and organization; Center for Devices and Radiological Health--FDA. Final rule.

PubMed

1991-10-10

The Commissioner of Food and Drugs is redelegating authorities to certain officials of the Food and Drug Administration's (FDA's) Center for Devices and Radiological Health (CDRH) to temporarily suspend premarket approval applications and to recall devices in the event those devices would cause serious adverse consequences to health or death. These authorities were given to the FDA by the Safe Medical Devices Act of 1990.

Clinical study assessing the photosensitizer accumulation and light penetration for esophageal cancer prior to treatment by PDT

NASA Astrophysics Data System (ADS)

Bargo, Paulo R.; Jacques, Steven L.

2001-07-01

The FDA has approved PDT using Photofrin for certain esophageal and lung cancers, specifying an approved prescription of administered drug (mg/kg body weight) and administered light (J/linear cm of cylindrical fiber). This paper describes our development of a multi-optical fiber catheter for endoscopic use which documents the drug accumulated in the target tissues and the light penetration into the target tissues. The catheter uses reflectance to specify the light penetration depth and uses reflectance- corrected fluorescence to document drug accumulation. The goal is to document the variation in drug and light received by patients who are administered the FDA-approved prescription.

Drugs Approved for Pancreatic Cancer

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

Drugs Approved for Lung Cancer

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

Drugs Approved for Retinoblastoma

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

Drugs Approved for Breast Cancer

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for breast cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

Drugs Approved for Bladder Cancer

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

42 CFR 447.502 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) approved by the Food and Drug Administration (FDA), including an authorized generic drug. It includes a... license approval (ELA) or antibiotic drug approval (ADA). Lagged price concession means any discount or... of natural origin, or independently by means of chemical synthesis, or by a combination of extraction...

42 CFR 447.502 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) approved by the Food and Drug Administration (FDA), including an authorized generic drug. It includes a... license approval (ELA) or antibiotic drug approval (ADA). Lagged price concession means any discount or... of natural origin, or independently by means of chemical synthesis, or by a combination of extraction...