IACUC Policy 570 - Use of Pharmaceutical and Non-Pharmaceutical Grade Drugs

Effective Date: August 20, 2025 (revised version; originally adopted on November 17, 2021)

I. Policy Purpose

This policy establishes the hierarchy of use of pharmaceutical and non-pharmaceutical grade drugs for use in vertebrate animals.

II. Policy Definitions

Pharmaceutical grade: a drug approved by the Food and Drug Administration (FDA) with an established level of purity, with defined bioavailability, defined routes, and defined half-life of elimination. The FDA-approved drugs for veterinary use are listed in the Green Book and drugs approved for human use are listed in the Orange Book.

Note: if the researcher purchases a pharmaceutical grade compound, but it must be diluted or compounded with other constituents, this new formulation is NO LONGER pharmaceutical grade.

USP/NF: the United States Pharmacopoeia (USP) National Formulary (NF) is the official public standards-setting authority for prescription and non-prescription drugs in the U.S. These drugs typically have the letters USP/NF after the drug listing. USP/NF grade chemicals may or may not be pharmaceutical grade and researchers should verify their status using the Orange Book or Green Book.

Non-pharmaceutical grade substance: a chemical not formulated for use in animals or humans. Non-pharmaceutical grade substances may be identified as USP/NF grade, analytical grade, reagent grade, USP purity grade, or analytical standards, but are not listed in the Green or Orange Books.

III. Policy Statement

In conformance with Federal regulations by the National Institutes of Health Office of Laboratory Animal Welfare (OLAW) and the United States Department of Agriculture Animal and Plant Health Inspection Service (USDA APHIS), and the best practices as defined by the Association of Assessment and Accreditation of Laboratory Animal Care (AAALAC) International, investigators are expected to use pharmaceutical grade compounds when they are available.

The hierarchy for selection of drug substances is:

1. FDA-approved pharmaceutical substances for veterinary or human use (listed in the Green Book or the Orange Book)
2. FDA-approved pharmaceutical substances for veterinary or human use, used to compound a needed dosage form (drugs listed in the Green or Orange Books, but diluted or compounded with other substances)
3. USP/NF grade substances used in a needed dosage form (includes compounded products from any source)
4. Analytical grade chemical used to compound a needed dosage
5. Other grades and sources of substances

Use of any non-pharmaceutical grade substance – including any pharmaceutical substance diluted or compounded with anything else – must follow accepted procedures to ensure purity, sterility, stability, pH, establish storage date/expiry date, and eliminate pyrogenicity.

IV. Procedures

The Principal Investigator must justify use of non-pharmaceutical grade drugs in their IACUC protocol application. The IACUC must review and approve the use of non-pharmaceutical grade drugs. Examples of justification for the use of non-pharmaceutical substances include:

• No equivalent veterinary or human drug is available for experimental use; thus, a pharmaceutical grade compound must be diluted or compounded for use. Though it is not preferred in this case, a non-pharmaceutical grade compound could also be diluted or compounded for use if justified.
• An equivalent veterinary or human drug IS available, but the project requires a lesser-grade substance to compare or replicate methods from previous studies.
• An equivalent veterinary or human drug is available for experimental use, but it contains preservatives or inactive ingredients which may confound the research goals of the study.

When using non-pharmaceutical grade substances, investigators must ensure their sterility and stability. Provisions for ensuring sterility and stability include:

• Preparing all compounds in a sterile manner.
• Filtering (0.22µ or finer) solutions derived from non-sterile components into sterile, sealed containers.
• Labeling the final product with the following information: compound name, concentration (mg/ml), total volume in vial (ml), preparation date, initials of person compounding the substance, and date of expiration.
• Discarding all reconstituted/compounded substances based upon the component with the shortest expiration date, the manufacturer’s recommendations, or within 30 days, whichever occurs first.
• Storing all compounded substances in appropriate conditions of temperature and light, based on agent-specific stability, compatibility, and the manufacturer’s recommendations.
• Using sterile supplies for the administration of parenteral agents: intravenous, subcutaneous, intramuscular, retro-orbital, intraperitoneal, or intracranial.

Note: pyrogens, such as endotoxins, may cause fever when injected. Pharmaceutical agents undergo testing for pyrogens. When compounding non-pharmaceutical grade substances, be aware that sterility does not assure that pyrogens are not present, and that filtering does not remove pyrogens. It is not practical to test small batches of substances for pyrogens. Thus, pyrogenicity may be a potential experimental variable when using non-pharmaceutical grade compounds.

V. References

FDA Center for Veterinary Medicine. U.S. Food & Drug Administration. https://animaldrugsatfda.fda.gov/

NIH Office of Intramural Research. (2023, April 26). Guidelines for the use of non-pharmaceutical grade compounds in laboratory animals. Animal Research Advisory Committee (ARAC) Guidelines. https://oacu.oir.nih.gov/system/files/media/file/2023-05/b14_pharmaceutical_compounds.pdf

National Research Council (2011). The guide for the care and use of laboratory animals (8th ed.). National Academies Press. https://grants.nih.gov/grants/olaw/guide-for-the-care-and-useof-laboratory-animals.pdf

Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food & Drug Administration. https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm

Tucker, C. B., MacNeil, M. D., Webster, A. B. (Eds.). (2020). The guide for the care and use of agricultural animals in research and teaching (4th ed.). American Society of Animal Science. https://www.asas.org/services/ag-guide