Use of Expired Drugs and Medical Materials and Non-Pharmaceutical Grade Compounds in Laboratory Animals
- Background and Purpose
- Definitions
- IACUC Policy Statements
- Additional Information and Specific Procedures
- References
Background and Purpose
The Animal Welfare Act and Regulations mandate that all animals in research facilities receive adequate veterinary care and treatment as part of the experimental procedures performed to ensure that pain and distress are minimized. Such care includes appropriate use of anesthetic, analgesic, tranquilizing drugs or euthanasia consistent with accepted standards of veterinary care [1,2].
Definitions
- Medical materials – Items used clinically or for research purposes that may have an expiration date assigned by the vendor for the purpose of guaranteeing sterility.
- Acute/terminal procedure – a procedure, surgical or non-surgical, for which an animal receives an anesthetic agent and is euthanized without recovering from anesthesia.
- Survival procedure – A procedure, surgical or non-surgical, performed on an animal that is subsequently allowed to recover from anesthesia.
- Pharmaceutical Grade – Compounds or agents intended for use in human or veterinary medicine which meet the highest standards for purity and bioavailability.
- Chemical Grade – Compounds or agents which may be chemically identical to their pharmaceutical grade counterparts, but do not conform to recognized standards for purity and bioavailability.
IACUC Policy Statements
Use of Expired Drugs and Medical Materials:
The use of any emergency drug or drug administered to relieve pain or distress (anesthetics and analgesics), including euthanasia agents, beyond its published expiration date is not consistent with acceptable or adequate veterinary practice and is not allowed under any circumstances. Expired medical materials such as saline solution, sutures, medical devices, etc., may be used in animals undergoing acute/terminal procedures if their use does not adversely affect the animal’s well-being or compromise the validity of the study.
Use of Pharmaceutical Grade Compounds:
In compliance with Federal Animal Welfare Regulations and guidance and standard veterinary medical practice the IACUC requires that investigators use pharmaceutical grade medications whenever they are available, even in acute/terminal procedures. Pharmaceutical grade compounds must be used in all situations where the health and well-being of the animal are at risk (anesthesia, analgesia, emergency drugs, euthanasia) and for routine veterinary care (non-research).
Additional Information and Specific Procedures
Expired Drugs and Materials:
Expired drugs and medical materials may be maintained in the laboratory for non-animal use provided they are:
- Clearly labeled “NOT FOR USE IN ANIMALS” and
- Stored in an area physically separate from supplies intended for live-animal use.
Whenever possible, expired materials should be stored in an area where live animals are never used.
Findings of use of expired drugs and materials will be treated as a serious noncompliance in conformance with the campus Policy for Regulatory Noncompliance. Any fines imposed upon the institution by USDA may be transferred to the Lead Researcher. Additionally, the Lead Researcher may be subject to sanctions and protocol suspension by the IACUC.
Proper disposal of expired drugs is the responsibility of the Lead Researcher. If you are unsure of the proper disposal method, please call Environmental Health and Safety at (949) 824-5073 or visit their web page at http://www.ehs.uci.edu.
Use of Non-Pharmaceutical Grade Compounds:
The IACUC acknowledges that, under certain circumstances, the use of non-pharmaceutical grade chemical compounds in experimental animals may be a necessary and acceptable component of biomedical research. Non-pharmaceutical grade chemical compounds may be used for scientific investigation provided that a scientific justification is provided for specific review and approval by the IACUC. Acceptable reasons for use of non-pharmaceutical or chemical grade agents may be:
- Scientific necessity;
- Non-availability of an acceptable veterinary or human pharmaceutical-grade product.
NOTE: Cost savings alone is not an adequate justification for using non-pharmaceutical-grade compounds.
If the use of specific non-pharmaceutical grade drugs is required, the method of preparation of the drug and the storage conditions must be described in the animal use protocol and approved by the IACUC. In particular, a detailed description of the methods used to ensure sterility of the drug must be included (e.g., 0.22 micron filter, storage in sterile vials with rubber septum to maintain sterility). Consultation with campus veterinarians is strongly recommended.
Use of Avertin:
Tribromoethanol (TBE), formerly available commercially as Avertin, is no longer available in a pharmaceutical grade form; it must be prepared in the laboratory using chemical-grade ingredients that have no guarantee of purity or effectiveness. Multiple reports in the scientific literature indicate that Avertin is associated with significant side effects including peritonitis, ileus, and death, particularly when repeated doses are administered [3-6]. In addition, the sleep time associated with Avertin has been shown to be variable even when the dose is kept constant [7]. For most procedures, pharmaceutical-grade anesthetics are available as an alternative to Avertin, such as a combination of ketamine and xylazine.
In developing this policy the IACUC understands that for many investigators, the use of Avertin as a general anesthetic in laboratory animals is a long-standing practice. Furthermore, many investigators are reluctant to change anesthetics because of possible ramifications this change may have to their animal models and operating procedures. Nevertheless, when taken as a whole, 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 a prohibition of its use. The IACUC will review the continuing use of Avertin at the time of three-year renewal on a case-by-case basis; researchers will be required to provide scientific evidence that their research will be seriously compromised by a change in anesthesia regimen. A Standard Operating Procedure for the preparation of the working solution and proper storage of both the stock solution and the working solution of Avertin must be submitted for review and approval by the IACUC [8].
NOTE: The IACUC does not consider the added expense and effort required to switch from Avertin to a pharmaceutical grade agent to be adequate justification.
References
1 Animal Welfare Act, 7 USC Chapter 54, Section 2143(a)(3)(A)
2 Animal Welfare Regulations, 9 CFR Chapter 1, Subchapter A, Part 2, Subpart C, Section 2.33(b)1-5
3 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): p. 17-22.
PHS Policy on the Humane Care and Use of Laboratory Animals, Frequently Asked Questions
4 Lieggi, C.C., et al., An evaluation of preparation methods and storage conditions of tribromoethanol. Contemp Top Lab Anim Sci, 2005. 44(1): p. 11-6.
5 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): p. 47-52.
6 Zeller, W., et al., Adverse effects of tribromoethanol as used in the production of transgenic mice. Lab Anim, 1998. 32(4): p. 407-13.
7 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): p. 119-24.
8 National Human Genome Research Institute Guideline 03.2,, http://www.theodora.com/rodent_laboratory/guideline_03_2.html
