The 2012 Institutional Animal Care and Use Committee (IACUC) Conference hosted several forums that provided insight into complex issues in the field of animal care and use.

One such topic that was discussed at the conference was a webinar, Use of Non-Pharmaceutical-Grade Chemicals and Other Substances in Research with Animals, which was held several weeks earlier, on March 1, 2012. The goal of this webinar, jointly presented by the United States Department of Agriculture (USDA), the Office of Laboratory Animal Welfare (OLAW), and the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International, was to clarify the expectations of the three sponsoring organizations regarding the use of non-pharmaceutical grade substances. The discussion on this topic by OLAW, USDA, and AAALAC representatives continued throughout the 2012 IACUC Conference.

Per USDA Animal Care Policy Three, investigators are expected to use up-to-date, pharmaceutical-grade medications whenever they are available, even in acute procedures. The USDA policy further states that the use of non-pharmaceutical-grade compounds should be limited to situations involving scientific necessity, unavailability of acceptable veterinary or human pharmaceutical-grade compounds, or specific review and approval by the IACUC. Cost savings alone are not considered adequate justification for the use of non-pharmaceutical-grade compounds in laboratory animals.

In congruence with the USDA policy, the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) also indicates that pharmaceutical-grade chemicals should be used, when available, for all animal-related procedures. It goes on to recommend that the use of non-pharmaceutical-grade chemicals or substances be described and justified in the animal use protocol and approved by the IACUC. The Guide further indicates that, when establishing and reviewing a proposal, the investigators and the IACUC should consider the grade, purity, sterility, pH, pyrogenicity, osmolality, and pharmacokinetics of the non-pharmaceutical grade substances to be administered, as well as any animal welfare and scientific issues relating to their use.

It is important to understand that these guidelines pertain to both active and inactive components of chemicals administered. Therefore, the vehicle used to facilitate the administration of a compound is just as important as the active ingredient in the compound. In accordance with USDA and OLAW guidance, a pharmaceutical-grade compound is a drug, biologic, or reagent that is approved by the Food and Drug Administration (FDA), or for which a chemical purity standard has been written/established by a pharmacopeia, such as US Pharmacopeia and the National Formulary (USP-NF), British Pharmacopoeia (BP), and/or Pharmacopeia of the Council of Europe (EP).

The emphasis on use of pharmaceutical-grade compounds serves to ensure that substances administered to laboratory animals meet established standards of purity and composition, and ultimately, to assure animal welfare and scientific validity of experimental results. The use of lower grade chemicals or compounds containing higher levels of impurities or poorly formulated preparations may introduce research complications, unanticipated variables, and/or adverse effects. The USDA and OLAW have indicated that the wording of these regulations provide some room for professional judgment. This flexibility establishes an expectation that the IACUC and investigators will work together to determine the best way to conduct experiments within the context of humane animal care.

One of the discussions on this topic that was of particular interest to me at the 2012 IACUC Conference focused on how an IACUC can best meet its responsibilities regarding the use of non-pharmaceutical drugs in research with animals. There are a variety of administrative methods an IACUC may use to review and approve the use of such agents, including the establishment of an institutional set of acceptable scientific criteria, in place of criteria arrived at  on a case-by-case basis. Some institutions address this issue in the IACUC application and/or in the veterinary consultation phase of the proposal review.  An institution may also consider developing an IACUC policy for the use of non-pharmaceutical-grade compounds in laboratory animals. Institutions and organizations are expected to make investigators and research staff aware of the new USDA/OLAW requirements. Whether information is provided through newsletter announcements, policy updates, board meetings, email outreach, online training and/or semi-annual site visits, enhancing awareness is key.

Please feel free to share via this blog platform any protocols, ideas, and/or processes that your organization has developed in order to comply with the new guidelines and regulations regarding the use of non-pharmaceutical grade compounds in laboratory animals. Please don’t hesitate to include information on your experiences, challenges, and solutions.