Guidelines

Guidelines on the Preparation of Injectable Substances and Agents Administered to Animals

Unit for Laboratory Animal Medicine

Sep 18, 2023 12:00 am

This guideline outlines the expectations for the preparation of injectable substances and agents intended for use in animals.

Glossary Definitions

Pharmaceutical Grade

A drug, biologic, or reagent that is approved by the Food and Drug Administration (FDA) for use in humans or animals or for which a chemical purity standard has been established by the United States Pharmacopeia-National Formulary (USP-NF), or British Pharmacopeia (BP). These standards are used by manufacturers to help ensure the products are of the appropriate chemical purity and quality, in the appropriate solution or compound, to ensure stability, safety, and efficacy. The FDA maintains a database listing approved commercial formulations for human drugs (the Orange Book) and veterinary drugs (the Green Book). For chemicals, a certificate of analysis is usually available upon request.

Related Terms:
Non-Pharmaceutical Grade USP BP NF FDA

Non-Pharmaceutical Grade

Chemicals or compounds that do not meet or exceed requirements of USP/NF/BP and may have higher levels of impurities that can introduce unwanted variables or toxic effects. Sterile pharmaceutical grade preparations that are reconstituted, diluted, mixed or have other substances added are also considered non-pharmaceutical grade.

Related Terms:
Pharmaceutical Grade USP BP NF

Diluent

An agent that dilutes or renders an active compound less potent or irritant. Example – 0.9% sterile saline or sterile water.

Agent

Agents are drugs intended for use explicitly as an anesthetic, analgesic, sedative, tranquilizer, and/or neuromuscular blocking agent (NMBA).

Related Terms:
Substance

Substance

Substances are all chemicals, drugs, or experimental compounds applied in or on an animal as part of the research activities, other than drugs used as anesthetics, analgesics, sedatives, tranquilizers, and/or neuromuscular blocking agents (NMBA).

Related Terms:
Agent
Preparing substances and agents to be administered to animals
Pharmaceutical Grade drugs should be purchased in sterile, rubber topped vials in the smallest volume available that is appropriate for the intended use.

More information on the use of non-pharmaceutical grade substances or agents in animal can be found in the Policy on the Use of Non-Pharmaceutical Grade Drugs

Prior to preparation, review the EHS safety findings in eRAM to determine if a specific substance or agent must be prepared in a chemical fume hood or biological safety cabinet.

Prepare all agents and substances in a manner that ensures the final product is sterile prior to being used in an animal.

Calculate the weight of the agent or substance needed to prepare the desired volume at the necessary concentration. See Appendix A for example pharmaceutical calculations.

In a sterile container, dissolve the measured amount of substance or agent in the appropriate volume of diluent.

Whenever possible, use a sterile, pH balanced (6.8 – 7.2), osmotically balanced (approx. 300 mOsm, e.g. 0.9% Sodium Chloride, Phosphate Buffered Saline, Balanced Salt Solution), pyrogen-free diluent.

For non-aqueous formulations, the IACUC may request additional information describing assurances for sterility, potential adverse consequences, etc.

If needed, adjust pH close to physiologic pH (7.4).

Dissolve the formulation in an appropriate solvent until particles are not visible. Filter through a 0.2 um filter into a sterile container (a sterile glass vial with a crimped rubber closure is recommended).

Discard any solutions or formulations that show signs of contamination, breach of sterility, or compromised integrity (e.g., cloudiness, precipitation, order, visible growth, color change).
Appendix A: Pharmaceutical Calculations for Diluting and Combining Drugs

Pharmaceutical Calculations.pdf

Pharmaceutical Calculations.pdf
References
Blood DC, Studdert VP. 1999. Saunders comprehensive veterinary dictionary. London ; New York: WB Saunders.

Lake T. 2003. Dosage calculations for veterinary nurses and technicians. Edinburgh ; New York: Butterworth-Heinemann.

Matthews, K. and Taylor, D., Assessment of Sterility in Fluid Bags Maintained For Chronic Use; J. American Association for Laboratory Animal Science, Vol. 50, No. 5, Pages 708-712, September 2001.

Plumb DC. 2005. Plumb's veterinary drug handbook. Stockholm, Wis. Ames, Iowa: PharmaVet ; Distributed by Blackwell Pub.

Office for Animal Care and Use, NIH. Updated February 19, 2009. (http://oacu.od.nih.gov/)

Questions?

Questions or concerns about the content of this document should be directed to the Unit for Laboratory Animal Medicine (ULAM) at (734) 764-0277 or ulam-questions@umich.edu.