Regulatory Update

Regulatory Update, August 2016

Monday, August 1, 2016

FDA Publishes Several Final Guidance Documents

Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices

In the June 21, 2016 Federal Register, the FDA announced the availability of the guidance titled “Leveraging Existing Clin­ical Data for Extrapolation to Pediatric Uses of Medical Devices.” This guidance explains the circumstances in which it may be appropriate to extrapolate existing medical device data to support pediatric device indications in several marketing ap­plications. This guidance also describes the FDA’s approach for determining whether extrapolation may be appropriate and the factors that should be considered within a statistical model for extrapolation. Extrap­olation may be appropriate when there are few differences in safety or effectiveness of the proposed device when used in adult as compared to the intended pediatric popu­lations and the adult data are of high qual­ity for borrowing.

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Regulatory Update, July 2016

Friday, July 1, 2016

NIH Guidelines Amended

In the April 15, 2016 Federal Register, the National Institutes of Health (NIH) Office of Science Policy (OSP) announced it was amending portions of the NIH Guidelines for Research Involving Recombinant or Syn­thetic Nucleic Acid Molecules (NIH Guide­lines) in order to provide investigators with biosafety guidance regarding the standards for containment of non-human primates (NHP) in biosafety level (BL) 4 laboratories and to make such guidance consistent with the expectations articulated in the Centers for Disease Control and Prevention (CDC)/ NIH Biosafety in Microbiological and Bio­medical Laboratories, 5th edition (BMBL).

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Regulatory Update, June 2016

Wednesday, June 1, 2016

FDA Proposed Rule on Administrative Actions for IRB Noncompliance

In the April 4, 2016, Federal Register, the FDA proposed amending the regulations describing lesser administrative actions that may be imposed on an Institutional Re­view Board (IRB) that has failed to comply with applicable IRB regulations. The FDA is taking this action to ensure clarity and ac­curacy of the regulations. The FDA is pro­posing to amend language in 21 CFR 56.120 (b) that describes lesser administrative ac­tions the FDA may impose on an IRB until the IRB takes appropriate action to correct noncompliance identified during an FDA inspection of the IRB. This revision would state that the FDA has authority to require the IRB withhold approval of new FDA-regulated studies conducted at the institu­tion or reviewed by the IRB, to direct the IRB that no new subjects may be enrolled in ongoing studies and to terminate ongoing studies, provided that doing so would not endanger study subjects. Disqualification of the IRB would be used only if the non­compliance adversely affects the validity of the data or the rights or safety of the human subjects and lesser actions (e.g., warnings or rejection of data from individual clinical in­vestigations) have not been or probably will not be adequate in achieving compliance.

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Regulatory Update, May 2016

Sunday, May 1, 2016

Human Factors Take Center Stage in FDA Guidance Documents

In the February 3, 2016 Federal Regis­ter, the FDA issued three guidance docu­ments on human factors engineering (one final and two draft documents). These are relevant to clinical research as medical de­vice manufacturers conduct clinical trials to evaluate human use factors during their device development programs. Human factors/usability engineering consider­ations in the development of medical de­vices involve the three major components of the device-user system: (1) device users, (2) device use environments and (3) device user interfaces.

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Regulatory Update, April 2016

Friday, April 1, 2016

Final FDA Guidance on Safety Data Collection in Late-stage Clinical Investigations

In the February 19, 2016 Federal Register, the FDA announced the availability of a fi­nal guidance document titled “Determining the Extent of Safety Data Collection Needed in Late-Stage Premarket and Postapproval Clinical Investigations.” The guidance is intended to help sponsors determine the amounts and types of safety data to collect in late-stage premarket and post-approval clini­cal investigations (e.g., phase III clinical trials, studies of new uses, long-term outcomes) based on what is al­ready known about a drug’s safety pro­file. Sponsors collect extensive safety data in clinical investiga­tions of drug and biological products conducted to sup­port marketing ap­proval (premarket) and after approval (postapproval). The FDA believes that selective safety data collection may be possible for some late-stage premarket and postapproval clini­cal investigations because certain aspects of a drug’s safety profile will be sufficiently well-established and comprehensive data collec­tion is not needed. This guidance makes final the draft guidance issued in February 2012.

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Regulatory Update, March 2016

Tuesday, March 1, 2016

Final FDA Guidance on Developing Antiretroviral Drugs for HIV-1 Treatment

In the November 3, 2015 Federal Regis­ter, the FDA announced the availability of a final guidance document titled “Hu­man Immunodeficiency Virus-1 Infec­tion: Developing Antiretroviral Drugs for Treatment.” The purpose of this guidance is to assist sponsors in all phases of drug development of antiretroviral drugs and therapeutic biologic products for the treat­ment of human immunodeficiency virus-1 (HIV-1) infection. This includes nonclini­cal development, early phases of clinical development, phase III protocol designs, and endpoints for the treatment of HIV.

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Regulatory Update, February 2016

Monday, February 1, 2016

Draft FDA Guidance on Safety Assessment for IND Safety Reporting

In the Dec. 17, 2015, edition of the Federal Register, the FDA announced the availability of a draft guidance document titled Safety Assess­ment for IND Safety Reporting. The draft guid­ance provides recommendations to sponsors on developing a systematic approach to inves­tigational new drug application (IND) safety reporting for human drugs and biological products developed under an IND. The draft guidance is a follow-on to the 2010 guidance for industry and investigators titled Safety Report­ing Requirements for INDs and BA/BE Studies that provides recommendations for how spon­sors of INDs can identify and evaluate impor­tant safety information that must be submitted to the FDA and all participating investigators, including a recommendation that sponsors de­velop a safety assessment committee.

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Regulatory Update, January 2016

Friday, January 1, 2016

FDA Seeks Comments on ICH’s GCP Guideline Update

In Sept. 29’s Federal Register, the FDA announced the availability of a draft guidance titled “Guideline for Good Clinical Practice” E6 (R2). The draft is an update of the International Conference on Harmonisation’s (ICH) “Guideline for Good Clinical Practice” E6 (R1), in which new information is integrated into the original document. The changes are intended to encourage improved and more efficient approaches to clinical trial design, conduct, oversight, recording, and reporting, and also to update standards regarding electronic records and essential documents. The draft also is intended to improve clinical trial quality and efficiency while maintaining human subject protection. The FDA made the draft guidance available for public comment on the sections added to ICH E6 (R1) and marked as “ADDENDUM.”

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Regulatory Update, December 2015

Tuesday, December 1, 2015

Final FDA Guidance on Product Development under the Animal Rule

In the Oct. 28 Federal Register, the FDA announced the availability of a final guidance document titled “Product Development under the Animal Rule.” When human efficacy studies are not ethical and field trials are not feasible, the FDA may rely on adequate and well-controlled animal efficacy studies to support approval of a new drug or licensure of a new biological product under the Animal Rule. Adequate and well-controlled animal efficacy studies are required under the Animal Rule. The guidance document is intended to help potential stakeholders in industry and academia (as well as the government) understand the FDA’s expectations for product development under the Animal Rule. This guidance makes final a June 3, 2014, revised draft guidance of the same name. The FDA reviewed 26 comments on the draft received; the comments may be read at the website identified below.

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Regulatory Update, November 2015

Sunday, November 1, 2015

CRO Warning Letter From FDA Instructional to Sponsors on Overseeing CROs

On June 16, 2015, a contract research organization (CRO) received a Food and Drug Administration (FDA) Warning Letter (WL) for violations of FDA regulations observed during a September 2014 inspection. Many sponsors lack the resources to fully manage their clinical trials in-house and outsourcing to CROs is common, whether for a few trial activities or a full-service CRO to manage essentially all trial activities. Sponsors are responsible for the adequacy of the CROs they choose and are expected to oversee their performance. Sponsors can review the violations in this WL as a “lessons learned” exercise and use those violations for help in assessing their own CROs. Excerpts are provided below but the entire WL is available for interested readers at The inspection covered three protocols for an investigational drug being studied under an Investigational New Drug (IND) application.

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