Before a medical product can be approved by FDA, the sponsor must prove efficacy—that the product works. In some cases, such as developing medical countermeasures (MCMs) for potential bioterror threats, human challenge studies (exposing people to the threat agent) would not be ethical or feasible.
In these cases, FDA may grant approval based on well-controlled animal studies, when the results of those studies establish that the drug or biologic product is reasonably likely to produce clinical benefit in humans. The product sponsor must still demonstrate the product’s safety in humans.
FDA strongly encourages MCM sponsors to establish early and ongoing communications with FDA.
The Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA) added a new section 565(d) of the FD&C Act to require that FDA establish a procedure for a sponsor or applicant developing “a countermeasure for which human efficacy studies are not ethical or practicable, and that has an approved investigational new drug application or investigational device exemption” (IND and IDE, respectively) to request and receive two meetings with FDA – one meeting to discuss “proposed animal model development activities” and a second meeting prior to initiating pivotal animal studies. More MCM-related counterterrorism legislation
Drug products and biologics
Guidance for Industry: Product Development Under the Animal Rule (PDF, 574 KB)
FDA intends to rely on its existing procedures for arranging formal meetings with sponsors and applicants to enable them to request and receive the meetings provided in section 565(d). Thus, sponsors or applicants developing drug products should consult the following resources for detailed information about the process and expectations for meetings about product development under the Animal Rule, in addition to the guidance linked above:
- Guidance for Industry - Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products (PDF, 156 KB) (December 2017)
- FDA’s Drug Development Tools Qualification Programs
Compliance Program for the Inspection of Nonclinical Laboratories Conducting Animal Rule-Specific Studies
On April 1, 2019, FDA posted a Compliance Program for the Inspection of Nonclinical Laboratories Conducting Animal Rule-Specific Studies (CP 7348.007) (PDF, 173 KB) on its Bioresearch Monitoring Program (BIMO) Compliance Programs web page.
This compliance program provides instructions for the inspection of nonclinical laboratories conducting the Animal Rule-specific studies (i.e., the natural history studies that define the animal model in which the efficacy of an investigational drug or biological product will be tested, the adequate and well-controlled animal efficacy studies intended to provide the primary evidence of effectiveness to support marketing approval of the product, and the pharmacokinetic and/or pharmacodynamic studies in animals used to select a dose and regimen in humans).
Inspections of these studies are conducted to verify, to the extent practicable, the quality and integrity of the data contained in the final reports of the Animal Rule-specific studies submitted to FDA.
FDA has been working with the Critical Path Institute and the Clinical Data Interchange Standards Consortium (CDISC) to develop electronic data standards for the natural history and efficacy studies conducted in animals that support Animal Rule applications. The Standard for Exchange Nonclinical Data (SEND) Implementation Guide for Animal Rule studies (SENDIG Animal Rule) and the last part of the associated controlled terminology were published by CDISC in September 2019.
A recording of a March 5, 2019 webinar providing an overview of the SENDIG-AR is available from CDISC.
- October 28, 2015: Federal Register notice: Product Development Under the Animal Rule; Guidance for Industry
- February 2016: Draft Guidance for Industry - Anthrax: Developing Antibacterial Drugs for Prophylaxis of Inhalational Anthrax (PDF, 116 KB)
- Webcast recording: Product Development Under the Animal Rule - Revised Draft Guidance for Industry (June 3, 2014)
- Activities to Encourage Development, Qualification, and Use of Animal Models
- Animal Rule Summary
- 21 CFR 314.600 (drugs)
- 21 CFR 601.90 (biological products)
- Animal Model Qualification Program
- Animal Model Qualification: Frequently Asked Questions
- Drug Development Tools (DDTs)
- Countering Bioterrorism Questions and Answers from CBER
- June 4, 2021: FDA approved Tembexa (brincidofovir) to treat smallpox
- January 28, 2021: FDA approved a treatment to increase survival in adults and pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [HS-ARS]). For more information about this treatment, please see the NPLATE (romiplostim) product label (PDF, 684 KB).
- July 13, 2018: FDA approves the first drug with an indication for treatment of smallpox (TPOXX (tecovirimat))
- March 29, 2018: FDA approves Leukine for treatment of Acute Radiation Syndrome, adding to the country's available treatments in the event of radiological or nuclear emergency
- March 18, 2016: FDA approves new treatment for inhalation anthrax (Anthim) [ARCHIVED]
- November 23, 2015: FDA approves vaccine for use after known or suspected anthrax exposure (BioThrax) [ARCHIVED]
- November 13, 2015: FDA approves new indication for use of Neulasta (pegfilgrastim) to treat adult and pediatric patients at risk of developing myelosuppression after a radiological/nuclear incident
- May 8, 2015: FDA approves additional antibacterial treatment for plague (Avelox) [ARCHIVED]
- March 30, 2015: FDA approves Neupogen for treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident
- March 25, 2015: FDA approves treatment for inhalation anthrax (Anthrasil, Anthrax Immune Globulin Intravenous (Human)) [ARCHIVED]
- February 2, 2015: Ciprofloxacin - supplemental NDA approved to add indication for treatment and prophylaxis of plague due to Yersinia pestis in adults and pediatric patients
- March 22, 2013: FDA approves first Botulism Antitoxin for use in neutralizing all seven known botulinum nerve toxin serotypes [ARCHIVED]
- December 14, 2012: FDA approves raxibacumab to treat inhalational anthrax [ARCHIVED]
- April 27, 2012: FDA approves new antibacterial treatment for plague (levofloxacin) [ARCHIVED]
- December 15, 2006: FDA approves drug to treat cyanide poisoning (Cyanokit) [ARCHIVED]
- February 5, 2003: FDA approves pyridostigmine bromide as pretreatment against nerve gas [ARCHIVED]
Also see from CDER: Animal Rule Approvals