Office of Research Integrity
Use of Non-Pharmaceutical Grade Compounds
Guidance from the National Institutes of Health (NIH) Office of Laboratory Animal Welfare (OLAW) requires that preference be given to “pharmaceutical grade” chemicals and other substances when selecting compounds for use in laboratory animals.1 An OLAW policy statement2 has defined “pharmaceutical grade” compounds as those that have been approved for human or veterinary clinical use by the Food and Drug Administration or those for which a chemical purity standard has been established by the United States Pharmacopeia-National Formulary, or British Pharmacopeia. Just as the delivery of drugs and other substances to laboratory animals must be approved by the IACUC, the choice to use non-pharmaceutical-grade compounds must be approved as well. The IACUC has determined that certain compounds not available in a pharmaceutical grade are generally acceptable for use if their use is appropriately justified and in accordance with the specific details listed in Appendix 5. Proposed use of all other non-pharmaceutical-grade compounds, including uses or formulations differing from those in Appendix 5, will be assessed on a case-by-case basis.
Consistent with OLAW requirements, the MUSC IACUC expects that drugs that meet the OLAW definition of pharmaceutical-grade compounds will be used for sedation/restraint, anesthesia, analgesia, euthanasia, and other clinical purposes in laboratory animals. This policy for use of pharmaceutical-grade compounds for “medications” is also consistent with the policies of the United States Department of Agriculture’s Animal and Plant Health Inspection Service for enforcing the Animal Welfare Act Regulations.3
If a preferred compound is not available as a clinical use formulation, a non-pharmaceutical-grade formulation may be used if approved by the IACUC. This applies as well to compounds that typically are available in a pharmaceutical-grade preparation but become unavailable for some period of time.
The MUSC IACUC recognizes that compounds that fall into the non-pharmaceutical-grade category defined above are essential to basic research in many scientific fields, particularly in the biomedical research that comprises the vast majority of the animal research protocols at MUSC. The MUSC IACUC expects that investigators will consider relevant animal welfare as well as scientific issues in choosing the types and sources of substances to administer to laboratory animals for research purposes. Some of the circumstances that compel use of a non-pharmaceutical-grade compound for research include the following:
- The compound is not available in a clinical use formulation.
- The compound is supplied to the investigator through an NIH Drug Supply Program.
- The compound is supplied to the investigator through an MUSC-negotiated Material Transfer Agreement with a pharmaceutical or biotechnology firm.
- The investigator needs to carry out a pharmacological characterization of novel compounds with potential for therapeutic use.
The MUSC IACUC also recognizes that when a clinical-use formulation has been marketed for a particular compound, it may not be useful for a research purpose due to one or more of the following variables:
- The need to manipulate concentration while holding volume constant. (Adding drug powder or diluting the pharmaceutical grade formulation would obviate its advantage.)
- Lack of the appropriate vehicle control.
- Formulation is inappropriate for the planned route of administration.
- Presence of preservatives or other undesirable components in the formulation.
- The need to hold formulation constant for comparison to previous studies.
The IACUC expects researchers to have the expertise and professional judgment to determine the most appropriate formulation and route of administration for their research. If he/she determines that a non-pharmaceutical-grade substance is needed, the IACUC expects that the researcher will obtain the highest quality/purity and will have the expertise, technical information, and laboratory resources for preparing a formulation that is most suitable for the planned route of administration.
The following variables may be relevant to consider, depending on route of administration, when formulating non-pharmaceutical-grade substances for use in laboratory animals: sterility, acid-base balance, pyrogenicity, osmolality, and compatibility of components.1,2
As in any pharmacology study, researchers are expected to anticipate possible side effects and/or adverse reactions that may be relevant to normal functioning of the animal and state these, along with anticipated duration and/or need for treatment, in the protocol.
The MUSC IACUC expects that the duration of storage and use of a non-pharmaceutical-grade formulation will be compatible with the duration for which the formulation will remain potent, as per technical information available. Methods for preparing and storing formulations must prevent contamination that could adversely affect animal welfare or the interpretation of data. Formulations must be labeled with the name of the compound and the concentration as well as the date of preparation and planned date of disposal.
- Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals 8th edn. 31 (National Academies Press, Washington, DC, 2011).
- Policy statement on Non-pharmaceutical grade substances issued 12/1/2011 in response to public comment period ending 5/24/2011; revised 5/29/2012 in response to the public comment period ending 2/3/2012. http://grants.nih.gov/grants/olaw/positionstatement_guide.htm
- Animal Welfare Act and Animal Welfare Regulations. 9 CFR Ch.1 §3.