Non-Pharmaceutical Grade Drugs and Cocktails
Adopted January 11, 2007
I. OLAW (NIH) and USDA Policy
The use of non-pharmaceutical grade chemical compounds in experimental animals under certain circumstances has been, and will continue to be, a necessary and acceptable component of biomedical research. OLAW and USDA have determined that their use should be based upon:
a) Scientific necessity;
b) Nonavailability of acceptable veterinary or human pharmaceutical-grade compound(s); and
c) Specific review and approval by the IACUC.
Although one can assume that issues such as sterility, pyrogenicity, stability, pharmacokinetics and quality control have been addressed during the course of pharmaceutical-grade drug production, one cannot ensure the same for substances produced in the research laboratory using non-pharmaceutical-grade chemical compounds. A number of related animal welfare and scientific issues should be considered by investigators and by IACUCs when use of non-pharmaceutical-grade compounds is proposed. These issues include: a) safety; b) efficacy; and c) the inadvertent introduction of research-complicating variables. Cost savings alone do not adequately justify the use of non-pharmaceutical-grade compounds in animals. Although the potential animal welfare consequences of complications are less evident in non-survival studies, the scientific issues remain the same, and the principles and need for professional judgment outlined above still apply.
II. IACUC Recommendations
A. Pharmaceutical Mixtures (Cocktails, e.g., Ketamine/Xylazine)
1) Should be prepared and used on "acute" basis only (1-7 days)
2) Must be prepared/maintained under sterile conditions
3) MUST be clearly labeled with compound names, concentrations, and date of preparation (expiration date shall be assumed to be 7 days after date of preparation).
4) Should be compounded according to methods of successful use/efficacy in published scientific literature.
B. Non-Pharmaceutical Grade Agents
1) MUST be justified by scientific necessity and/or lack of availability of pharmaceutical-grade, commercially available preparations.
(cost alone is not valid justification for use)
2) MUST be prepared/maintained under sterile conditions.
3) MUST be evaluated to assure physiological compatibility (pH, pyrogenicity, osmolarity, etc.)
4) MUST be clearly labeled with compound names, concentrations, and date of preparation. Since shelf-life of such compounds is unknown, long-term storage (>30 days) is strongly discouraged. Regardless of age, solutions should be discarded if changes in color and/or precipitation occur.
5) Should be documented regarding safety and efficacy consistent with methods of successful use/efficacy in published scientific literature if available.