Description
The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled “Product Development Under the Animal Rule.” When human efficacy studies are not ethical and field trials are not feasible, FDA may rely on adequate and well-controlled animal efficacy studies to support approval of a drug or licensure of a biological product under the Animal Rule. This guidance finalizes the 2014 revised draft guidance for industry “Product Development Under the Animal Rule.” It is intended to help potential stakeholders (industry, academia, and government) understand FDA's expectations for product development under the Animal Rule.
Scope & Applicability
Product Classes
10Regulated under section 351(i) of the PHS Act; Virus, therapeutic serum, toxin, vaccine, or protein applicable to prevention or treatment; Alternative regulation category for products meeting device definition
GT products within the scope of this guidance include products that mediate their effect by the expression of transferred genetic materials.; The main subject of the S12 guidance document
Administration of the cellular therapy product to healthy animals
In vitro studies used to determine PD characteristics like susceptibility.
Product category with specific guidance in section VII.B
Not addressed in this guidance
Generally have lower risk of pharmacokinetic DDIs compared to small molecules.
Applies to drug products including small molecule drugs; assessment of immunosuppression risk
drug where there has been no prior determination of safety or effectiveness
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Stakeholders
5Convened to provide advice on withdrawal issues
Provides adequate veterinary oversight and care
Discusses humane needs and scientific requirements with the veterinarian
Role in providing advice on humane endpoints and adequate veterinary care; Institutional Animal Care and Use Committee.
Entity responsible for submitting applications under section 524B
Regulatory Context
Attributes
10The specific environment and population in which a COA is intended to be used; Selecting fit-for-purpose COAs based on the context of use.; The intended context in which the COA will be used
Critical determinants of disease or condition such as signs, endpoints, or biomarkers.
Requirement for the use of animals in research
Assessment made by investigators regarding the appropriateness of the trial.
A dose that produces the largest effect the investigational drug can have
Cmax may be more informative for safety
AUC or Cmin may correlate with efficacy
Absorption, distribution, metabolism, and excretion characteristics; Absorption, distribution, metabolism, and excretion characteristics.
Biological property that may be altered by manufacturing changes; safety narrative should address bioavailability of the ingredients
Proposed biological activity of the drug
Identified Hazards
Hazards
2Biological agents requiring specific regulatory adherence
Indicator for humane endpoints
Related CFR Sections (11)
- 21CFR314.600§ 314.600 Scope.
This subpart applies to certain new drug products that have been studied for their safety and efficacy in ameliorating or preventing serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances. This subpRead full regulation →
- 21CFR601.91§ 601.91 Approval based on evidence of effectiveness from studies in animals.
(a) FDA may grant marketing approval for a biological product for which safety has been established and for which the requirements of § 601.90 are met based on adequate and well-controlled animal studies when the results of those animal studies establish that the biological product is reasonably likRead full regulation →
- 21CFR314.610§ 314.610 Approval based on evidence of effectiveness from studies in animals.
(a) FDA may grant marketing approval for a new drug product for which safety has been established and for which the requirements of § 314.600 are met based on adequate and well-controlled animal studies when the results of those animal studies establish that the drug product is reasonably likely to Read full regulation →
- 21CFR314.126§ 314.126 Adequate and well-controlled studies.
(a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →
- 21CFR601.40§ 601.40 Scope.
This subpart applies to certain biological products that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit to patients over existing treatments (e.g., ability to treat patients unresponsive to, or inRead full regulation →
- 21CFR314.500§ 314.500 Scope.
This subpart applies to certain new drug products that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit to patients over existing treatments (e.g., ability to treat patients unresponsive to, or intoRead full regulation →
- 21CFR314.650§ 314.650 Termination of requirements.
If FDA determines after approval under this subpart that the requirements established in §§ 314.610(b)(2) , 314.620 , and 314.630 are no longer necessary for the safe and effective use of a drug product, FDA will so notify the applicant. Ordinarily, for drug products approved under § 314.610 , theseRead full regulation →
- 21CFR601.90§ 601.90 Scope.
This subpart applies to certain biological products that have been studied for their safety and efficacy in ameliorating or preventing serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances. This suRead full regulation →
- 21CFR601.95§ 601.95 Termination of requirements.
If FDA determines after approval under this subpart that the requirements established in §§ 601.91(b)(2) , 601.92 , and 601.93 are no longer necessary for the safe and effective use of a biological product, FDA will so notify the applicant. Ordinarily, for biological products approved under § 601.91Read full regulation →
- 21CFR314.630§ 314.630 Postmarketing safety reporting.
Drug products approved under this subpart are subject to the postmarketing recordkeeping and safety reporting requirements applicable to all approved drug products, as provided in §§ 314.80 and 314.81 .Read full regulation →
- 21CFR601.93§ 601.93 Postmarketing safety reporting.
Biological products approved under this subpart are subject to the postmarketing recordkeeping and safety reporting applicable to all approved biological products.Read full regulation →
Related Warning Letters (10)
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Guangdong Renhe Guozhuang Biotechnology Co., Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Medinatura New Mexico, Inc.
- 2025-12-16
CGMP/Finished Pharmaceuticals/Adulterated
Sklar Personal Care Inc.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-11
CGMP/Finished Pharmaceuticals/Adulterated
Catalent Indiana, LLC
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
DeVere Manufacturing Inc.
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
CDL Services, Inc. DBA Technichem
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
Seaway Pharma Inc.
- 2025-12-02
Compounding Pharmacy/Adulterated Drug Products
PQ Pharmacy, LLC
See Also (8)
- Guidance for Industry: Acute Bacterial Otitis Media: Developing Drugs for Treatment (Status: Final)
- Acute Bacterial Sinusitis — Developing Antimicrobial Drugs for Treatment (Status: Final)
- Neglected Tropical Diseases of the Developing World: Developing Drugs for Treatment or Prevention (Status: Final)
- Emergency Use Authorization of Medical Products and Related Authorities: Guidance for Industry and Other Stakeholders (Status: Final)
- Antibacterial Therapies for Patients With an Unmet Medical Need for the Treatment of Serious Bacterial Diseases (Status: Final)
- Complicated Urinary Tract Infections: Developing Drugs for Treatment (Status: Final)
- Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products: Draft Guidance for Industry (Status: Draft)
- Mpox: Development of Drugs and Biological Products; Guidance for Industry (Status: Draft)