The Use of Pharmaceutical and Non-pharmaceutical Grade Compound in Animals and Labeling Expectations

IACUC Policy #045-06, Approved 12/14/2012, Last Revised: 02/18/2026

Background

Federal regulations require Investigators to use pharmaceutical-grade compounds for injection in animals, even in acute procedures including euthanasia. This includes, but is not limited to, medications/drugs, vehicles, and diluents. Pharmaceutical-grade compounds meet established standards of purity and composition helping ensure animal health and experimental results.    

It is recognized that many experimental compounds used in research are not available as pharmaceutical grade, or that pharmaceutical grade compounds may need to be diluted or combined for use in laboratory animal research. The purpose of this policy is to outline the additional justification and details that need to be captured within the animal use protocol when non-pharmaceutical grade or compounded agents are used. In addition, this policy outlines the labeling and storage requirements for compounded agents. The use of chemical grade compounds, compounded drugs, or dilution of drugs can introduce unexpected or even toxic effects and should be avoided when possible.  

Definitions

• Pharmaceutical-grade compounds are any drug, biologic, or reagent that is approved, conditionally approved, or indexed by the Food and Drug Administration (FDA) for human or veterinary use. Alternatively, it is manufactured in compliance with current Good Manufacturing Practice and meets applicable United States Pharmacopeia–National Formulary or British Pharmacopeia standards.
  • USP labeling only defines the purity standard and does not equate to pharmaceutical grade; a product must clearly be labeled "Pharmaceutical Grade".
  • The FDA maintains a list of approved formulations for human drugs (orange book) and veterinary drugs (green book).
• Non-Pharmaceutical-grade (NPG) compounds are substances that do not meet the criteria noted above with respect to pharmaceutical grade compounds.
  • This includes pure chemicals obtained from a chemical supplier (e.g., Sigma-Aldrich) and compounds labeled as “research use only.”
  • Phosphate buffered saline (PBS) is considered non-pharmaceutical grade because it is not labelled for parenteral injection.
• An Injection is a preparation intended for administration through the skin or directly into a blood vessel, organ, tissue, or lesion.
• Compounding is a practice in which a person combines, mixes, or alters ingredients of a drug to create a medication tailored to the needs of an individual patient(s).
• Secondary Containers are vials, bottles, or tubes used for storage of drugs or compounds that have been moved from their original container for purposes of transferring, diluting, or compounding.

Requirements

• All agents used in animals must be listed in the IACUC protocol.
• The use of non-pharmaceutical-grade compounds must be clearly identified in the animal use protocol and approved by the IACUC. In the protocol, investigators should indicate:
  1. Justification for use (e.g., non-availability of an acceptable veterinary or human pharmaceutical-grade compound, formulation limitations, or scientific necessity).
     • Cost saving is not a justification for using non-pharmaceutical-grade compounds, although OLAW and USDA have made exceptions in cases of limited access resulting in exorbitant costs.
  2. Processes that will be used to ensure purity and sterility.
• When compounding drugs for injection into animals, investigators must ensure the following:
  1. Aseptic preparation (compounding) of the drug.
     • Ensure that all compounded drugs intended for injection are prepared using aseptic techniques to maintain sterility throughout the process. Non-sterile components require sterilization, such as filtration or autoclaving, provided the compounded drug is stable under heat.
     • Always inspect injectable drugs before use; do not administer them if there is evidence of particulate matter, precipitates, turbidity, or discoloration, as these signs indicate compromised sterility or stability.
  2. Proper storage of the compounded drug.
     • Use suitable containers and methods that maintain sterility while permitting repeated access, such as using a sterile injection vial with a rubber stopper. For single-use applications, a sterile microfuge tube may be appropriate.
     • The secondary container material must be compatible with the drug or compound and its intended use. Container material requirements:
       • Does not react with the drug or compound (e.g. glass, polypropylene, or polycarbonate plastic). For example, buprenorphine dilutions should not be stored in plastic containers due to decrease in drug concentrations.
       • Opaque if light sensitive material is to be stored (e.g., covered with foil, amber glass).
     • Ensure compounded drugs are stored at appropriate temperatures based on the stock drugs and reagents.
  3. Proper labeling of containers for storage of compounded drugs. Must include:
     1. Name of the drug(s) and diluent (when applicable)
     2. Final concentration (usually mg/mL)
     3. Date of Expiration
        • The assigned expiration date shall not exceed the earliest expiration date of any stock agent or diluent used, the expiration date of the container (e.g., sterile injection vial), or 30 days from preparation of compounding or diluting, whichever occurs first.
        • For experimental compounds, the expiration date should also be based on continuous performance evaluation of the agent(s) efficacy as well as consideration of the frequency of use/method of storage.

For more information, please refer to the IACUC policy “Multi-puncture Drug and Fluid Administration in Animal Research, Testing, and Teaching.”

References

1. FAQs about the PHS Policy on humane care and use of laboratory animals. Wolff A, et al. Lab Animal (NY). 2003 Oct; 32(9):33-6. 
2. National Institutes of Health, Office of Animal Care and Use. Animal Research Advisory Committee Guidelines: Guidelines for the use of non-pharmaceutical grade compounds in laboratory animals. U.S. Department of Health and Human Services.
3. United States Pharmopeia. United States Pharmacopeia-National Formulary 
4. U.S. Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations.
5. U.S. Food and Drug Administration. Approved Animal Drug Products (Green Book). 

Institutional Approved SOP for Use of Non-Pharmaceutical-Grade Compounds: Tribromoethanol (Avertin)

Background

Tribromoethanol (TBE), commonly referred to by the brand name Avertin, has been used as an anesthetic agent for mice. TBE provides rapid induction and recovery for single use, short duration (approximately 15-20 minutes) surgical procedures in rodents. Improper preparation, storage, or use of Tribromoethanol can result in severe side effects including peritonitis, ileus, and death, particularly when repeated doses are administered or ineffective anesthesia. Specifically, TBE degrades in the presence of heat and light, producing toxic byproducts that are potent gastrointestinal irritants. TBE is not available as a pharmaceutical-grade compound and alternative options for rodent anesthesia including both pharmaceutical-grade injectable and inhalation options are readily available. Regulatory agencies have subsequently recommended that the use of TBE be discontinued as an anesthetic in mice when possible. ULAR veterinary staff is available to discuss alternatives to the use of TBE.  

Use

The body of scientific literature on this compound, as well as the regulatory requirement to use pharmaceutical-grade drugs in animals, presents a compelling case for discontinuing the use of TBE. The IACUC will review the continued use of TBE at the time of three-year renewal on a case-by-case basis; researchers will be required to provide justification for the continued use of this agent for survival surgery. 

Storage and Expiration Period

TBE must be stored at 2-8°C in light-protected containers. When stored at this temperature, the solution may be used for up to two weeks. Frozen TBE solution can be stored at -80°C for up to 6 months.

The animal use protocol can reference this SOP or alternatively provide details regarding the preparation of the working solution and proper storage of the stock solution in the animal use protocol.

References

1. Papaioannou, VE and Gox, JG. Efficacy of Tribromoethanol Anesthesia in Mice. Laboratory Animal Science, 1993. April, 43(2): 189-192.
2. Zeller, WM; Burki, G; and Panoussis, B. Adverse Effects of Tribromoethanol as Used in the Production of Transgenic Mice. Laboratory Animal Science, 1998. October, 32(4): 407-413.
3. Kohn, DF; Wixson, SK; White, WJ; and Benson, GJ. Anesthesia and Analgesia in Laboratory Animals, 1997.
4. Lieggi, C.C., et al., Efficacy and safety of stored and newly prepared tribromoethanol in ICR mice. Contemp Top Lab Anim Sci, 2005. 44(1): 17-22.
5. PHS Policy on the Human Care and Use of Laboratory Animals, Frequently Asked Questions
6. Lieggi, C.C., et al., An evaluation of preparation methods and storage conditions of tribromoethanol. Contemp Top Lab Anim Sci, 2005. 44(1): 11-6.
7. Meyer, R.E. and R.E. Fish, A review of tribromoethanol anesthesia for production of genetically engineered mice and rats. Lab Anim (NY), 2005. 34(10): 47-52.
8. Zeller, W., et al., Adverse effects of tribromoethanol as used in the production of transgenic mice. Lab Anim, 1998. 32(4): p 407-13.
9. Koizumi, T., H. Maeda, and K. Hioki, Sleep-time variation for ethanol and the hypnotic drugs tribromoethanol, urethane, pentobarbital, and propofol within outbred ICR mice. Exp Anim, 2002. 51(2): p119-24. National Human Genome Research Institute Guideline 03.2.

Institutional Approved SOP for Use of Non-Pharmaceutical-Grade Compounds: Saturated Potassium Chloride (KCl)

Background

The American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals includes intravenous or intracardiac injection of a solution of supersaturated potassium chloride into an animal under general anesthesia as an acceptable method to enact a quick and humane death consistent with adequate veterinary practices. This method of euthanasia is preferable when euthanizing livestock or wildlife species to reduce environmental exposures and the risk of toxicosis for predators or scavengers in situations where carcasses of euthanized animals may be consumed. Saturated KCl is only available as a non-pharmaceutical-grade compound.

Use

The potassium ion is cardiotoxic, and rapid intravenous or intracardiac administration of 1 to 2 mmol/kg of body weight will cause cardiac arrest. Saturated potassium chloride has been commonly used to euthanize large animals (rabbits, dogs, cats, sheep, pigs, etc.) under general anesthesia as approved in the AVMA Guidelines for the Euthanasia of Animals. Saturated potassium chloride is not available in a pharmaceutical grade form. Scientific justification for the use of this euthanasia method is to accomplish a quick and humane death during a non-survival procedure in an animal that is under general anesthesia and this agent does not contaminate the animal carcass per environmental landfill requirements.

References

1. AVMA [American Veterinary Medical Association]. 2020. Guidelines for the Euthanasia of Animals. Schaumburg, IL: AVMA.
2. U.S. Department of Agriculture, Animal and Plant Health Inspection Service, Animal Care, Policy 3- Veterinary Care, April 14, 1997.
3. Barbiturates. In: Ciganovich E, ed. Field manual of wildlife diseases. US Department of the Interior/US Geological Survey, Biological Resources Division, Information and Technical Report 199-2001.
4. Lumb W. Euthanasia by noninhalent pharmacologic agents. J Am Vet Med Association. 1974; 165: 851-852.

Article ID: 42
Created: May 20, 2024
Last Updated: February 27, 2026

Online URL: https://ohiostateresearch.knowledgebase.co/article/the-use-of-pharmaceutical-and-non-pharmaceutical-grade-compound-in-animals-and-labeling-expectations-42.html