In accordance with the NIH Office of Laboratory Animal Welfare, an AAALAC FAQ on the topic, and the Guide for the Care and Use of Laboratory Animals (the Guide, 8th edition, p. 31), the Animal Research Committee (ARC) has established the following policy on the use of pharmaceutical-grade compounds.
Unless approved by the ARC, investigators are expected to use pharmaceutical-grade or veterinary grade substances whenever they are available, even in acute procedures. Anesthetics, analgesics, and sedatives used to treat more than momentary or slight pain or distress, and euthanasia agents, must be pharmaceutical / veterinary grade unless used as investigational agents.
When selecting compounds, the following order of choice should be applied:
- FDA approved veterinary or human pharmaceutical compounds;
- FDA approved veterinary or human pharmaceutical compounds used to compound a needed dosage form;
- USP/NF or other pharmacopeia recognized pharmaceutical grade compounds used in a needed dosage form;
- Analytical grade bulk chemical used to compound a needed dosage form (requires justification);
- Other grades and sources of compounds (requires justification).
Any necessary dilutions must be made using pharmaceutical grade diluents. Refer to the ARC Policy on Use of Fluids and Diluted Drugs in Research Animals for more information.
Use of non-pharmaceutical grade/veterinary grade agents must be justified in the protocol and submitted to the ARC for specific review and approval prior to use. Examples of acceptable justification for use of non-pharmaceutical/veterinary grade investigational agents include:
- the compound is not available in a pharmaceutical-grade preparation and comparable alternative agents available in pharmaceutical grade form cannot be used for scientific reasons;
- it is necessary to compare data with previous experiments using the non-pharmaceutical grade substance;
- it would be necessary to dilute the pharmaceutical grade preparation with a non-pharmaceutical grade solution, thereby compromising the pharmaceutical grade quality of the preparation;
- the vehicle of the pharmaceutical grade preparation cannot be determined, preventing use of an appropriate control.
Cost savings alone is not an adequate justification for using non-pharmaceutical-grade compounds in animals.
ARC approval to use non-pharmaceutical grade / non-veterinary grade substances is conditioned by the following:
- All non-pharmaceutical and/or non-veterinary grade substances and diluents must be sterilized (e.g., autoclaved or filter-sterilized using a 0.22 µm filter prior to administration) wherever this is possible without jeopardizing the activity/stability of the agent.
- The method of preparation, labeling (i.e., preparation and use-by dates), administration, and storage of formulations should be appropriately considered with the aim of maintaining their stability and quality (i.e., to prevent inadvertent co-administration of infectious agents or contaminants).
- Investigators should consider relevant animal welfare and scientific issues including safety, efficacy, and the inadvertent introduction of new variables when using non-pharmaceutical grade compounds.
Approved 11/13/00; Revised 6/02, 7/28/03, 8/10/09, 8/23/10, 1/18/11, 5/23/11, 7/9/12, 9/11/23