In a Good Laboratory Practice (GLP) study, NIAID-funded researchers reported that the growth factor drug filgrastim (trade name Neupogen) nearly doubles survival in radiation-exposed monkeys. Seventy-nine percent of treated animals survived for more than 60 days after radiation exposure, compared to 41 percent of animals that did not receive the drug. Monkeys receiving filgrastim also experienced fewer infections. Based on these study results, an FDA advisory panel concluded, by a 17-1 vote, that filgrastim therapy is likely to benefit humans exposed to radiation. Because human studies of drug efficacy cannot be performed ethically, FDA approved filgrastim as a radiation medical countermeasure under its Animal Rule in 2015. The approval will improve access to this therapy during a public health emergency.
Code of Federal Regulations (CFR) Concerning the FDA Animal Rule
Animal Rule, Drugs (21 CFR Part 314, Subpart I - Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible)
Animal Rule, Biologics (21 CFR Part 601, Subpart H - Approval of Biological Products When Human Efficacy Studies Are Not Ethical or Feasible)
FDA Guidance for Industry: Animal Models – Essential Elements to Address Efficacy Under the Animal Rule (PDF). This guidance focuses on identifying f the critical characteristics (essential data elements) of an animal model to be addressed when developing drug or biological products for approval or licensure, respectively, under the Animal Rule (see 21 CFR 314.600 for drugs; 21 CFR 601.90 for biological products).
FDA 2014 Draft Guidance: Product Development Under the Animal Rule (PDF). This guidance provides information and recommendations on drug and biological product development when human efficacy studies are not ethical or feasible. This draft guidance revises the 2009 guidance for industry Animal Models – Essential Elements to Address Efficacy Under the Animal Rule. While addressing the topics covered in the 2009 draft, this revision covers a broader scope of issues for drugs developed under the Animal Rule. For example, new sections have been added related specifically to study conduct and data quality and integrity (section IV.B); vaccine development (section VII.A); and development of cellular and gene therapies (section VII.B). There are new sections on FDA’s general expectations for animal studies related to; for example, animals used in investigations, types of animal care interventions, and study reports (section IV). There is also a new section on FDA’s general expectations regarding natural history studies (Appendix C).
FDA Guidance for Industry: Internal Radioactive Contamination — Development of Decorporation Agents (PDF). This document provides guidance to industry on the development of decorporation agents for which evidence is needed to demonstrate effectiveness but for which human efficacy studies are unethical or infeasible. In such instances, the Animal Rule, 21 CFR part 314 subpart I, may be invoked to approve new decorporation agents not previously marketed or new indications for previously marketed drug products. Specifically, this document provides guidance on 1) chemistry, manufacturing, and controls (CMC) information; 2) animal efficacy, safety pharmacology, and toxicology studies; 3) clinical pharmacology, biopharmaceutics, and human safety studies; and 4) post-approval commitments for such drug products.
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
Center for Devices and Radiological Health (CDRH)
FDA Animal Model Qualification Program. NIAID currently is working with FDA on qualification of animal models for radiation exposure. Qualification of an animal model through the FDA Animal Model Qualification Program (AMQP), which is jointly supported by CDER and CBER, is voluntary (i.e., not required for product approval or licensure under the Animal Rule). However, the qualification process is limited to animal models used for product approval under the Animal Rule. A qualified model may be used for efficacy testing in development programs for multiple investigational drugs that target the same disease or condition. Such animal models are considered product-independent (i.e., not linked to a specific drug).
To receive copies of any of the available presentations listed below, please send an email to firstname.lastname@example.org. The email should include the name of the slide set(s), as shown below, and the meeting at which the slides were presented.
NIAID/CMCR Workshop on the FDA Pre-Market Regulatory Process: Applications to Technologies for Radiation Biodosimetry After a Large-Scale Radiological Incident, March 27, 2006, Bethesda, Maryland.
Slide SetsThe FDA Pre-Market Regulatory Process (PDF), presented by Mary Pastel, Associate Director for Advanced In Vitro Diagnostics, Office of In Vitro Diagnostic Device Evaluation and Safety and Office of Science and Engineering Laboratories, Center for Devices and Radiological Health (CDRH), FDA.
Pre-IDE Processing (PDF), presented by Sousan Altaie, Scientific Policy Advisor, Office of In Vitro Diagnostic Device Evaluation and Safety, CDRH, FDA.
Data Analysis: Software and Statistics (PDF), presented by Estelle Russek-Cohen, Team Leader and Mathematical Statistician, Diagnostic Devices Branch, Division of Biostatistics, Office of Surveillance and Biometrics, CDRH, FDA.
Role of the Clinical Laboratory Improvement Amendments (CLIA) Program (PDF), presented by James Cometa, Team Leader/Program Analyst, Centers for Medicare & Medicaid Services, Survey and Certification Group, Division of Laboratory Services.
NIAID/CMCR Workshop on the FDA Pre-Market Regulatory Process: Applications to Radiation Countermeasures after a Large-Scale, Radiological Incident, June 9, 2006, Hilton Hotel, Gaithersburg, Maryland.
Slide SetsDrug Development Process and the Role of NIAID Regulatory Affairs (PDF), presented by Jui Shah, Ph.D., Senior Regulatory Officer, Office of Regulatory Affairs, Division of Allergy, Immunology, and Transplantation (DAIT), NIAID, NIH.
Regulatory Pathways for Drug Development (PDF), presented by Joanne Holmes, MBA, Associate Director for Regulatory Affairs, Office of Counter Terrorism and Emergency Coordination (OCTEC), Center for Drug Evaluation and Research (CDER), FDA.
Nonclinical Development of Biotechnology-Derived Products and Small Molecules… What are the Differences (PDF), presented by Melanie Hartsough, Ph.D., Pharmacologist, Office of New Drugs, CDER, FDA.
FDA Overview of Regulatory Expectations for INDs for Cellular and Gene Therapy Products (PDF), presented by Richard McFarland, M.D., Ph.D., Acting Associate Director for Regulatory Policy, Office of Cellular, Tissue, and Gene Therapies, Center for Biologics Evaluation and Research, FDA.
Evidence Needed to Demonstrate Effectiveness of New Drugs When Human Studies Are Not Ethical or Feasible or the "Animal Rule" (PDF), presented by Martin Green, Ph.D., Supervisory Pharmacologist, Office of New Drugs, CDER, FDA.
Last Updated April 27, 2015