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Use of Drugs and Medical Materials in Animals

Definitions

Policy

Controlled Substances

Expired Drugs and Medical Materials

Non-pharmaceutical Grade Compounds


Background

The Animal Welfare Act and Regulations1 mandate that all animals in research facilities receive adequate veterinary care and treatment 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.2   Policy statements and guidance  have been developed for the following specific issues:

  • Use of Expired Drugs and Medical Materials
  • Use of Non-Pharmaceutical Grade Compounds
  • Use of Controlled Substances
     

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 - Drugs, biologics or reagents approved by the U.S. Food and Drug Administration (FDA) or for which a chemical purity standard that has been established by the United States Pharmacopeia-National Formulary or British Pharmacopeia. Pharmaceutical-grade agents are intended for use in human or veterinary medicine and meet the highest standards for purity and bioavailability.3

Chemical Grade - Compounds or agents which may be chemically identifical to their pharmaceutical grade counterparts, but do not conform to recognized standards for purity and bioavailability.
 


Policy


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.  Experimental diets (e.g. medicated feed, high-fat diets, etc.) should not be used past the expiration date shown on the package, or 6 months past the mill date.


Pharmaceutical Grade Compounds

In compliance with Federal Animal Welfare Regulations and guidance and standard veterinary medical practice the IACUC expects that investigators will use pharmaceutical grade medications whenever they are available, even in acute/terminal procedures. Non-pharmaceutical grade compounds should only be used after specific review and approval by the IACUC for reasons such as scientific necessity or non-availability of an acceptable veterinary or human pharmaceutical-grade product. Cost savings is not a justification for using non-pharmaceutical grade compounds in research animals. 4

 

Controlled Substances

The IACUC works closely with Environmental Health and Safety (EH&S) to ensure that all state and federal requirements for the use, storage and disposal of Controlled Substances and Precursor Chemicals are followed. Failure to follow DEA requirements could result in the loss of UCI’s license to purchase these agents. For more information and the specific requirements associated with the use of Controlled Substances, please refer to the EH&S Controlled Substances page.
 


Additional Information and Specific Procedures:


Expired Drugs and Medical Materials

Expired drugs and medical materials may be maintained in the lab for non-animal/in vitro use provided they are:

  • Clearly labeled "NOT FOR USE IN LIVE 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. EXCEPTION:  Controlled Substances have specific requirements for locked storage; expired controlled substances should be picked up for disposal by EH&S as soon as possible. Submit a Request for EH&S Controlled Substance Pick Up.

CAUTION:  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 uponse 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. For questions about proper disposal methods, please contact EH&S at (949) 824-6200 or see the EH&S website.


Use of Non-Pharmaceutical Grade Compounds

If the use of specific non-pharmaceutical grade drug or chemical compound is required and has been appropriately justified, 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.

All compounded or diluted drugs, whether or not their components are pharmaceutical-grade, must be appropriately labeled at all times. At minimum, storage vials should be labeled with the name of the compound, the date it was mixed, and the name of the person or lab. If possible, an expiration or “use by” date should be included as well.


Use of Avertin® (Tribromoethanol)

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. 5 In addition, the sleep time associated with Avertin® has been shown to be variable even when the dose is kept constant. For most procedures, pharmaceutical-grade anesthetics are available as an alternative to Avertin®, such as a combination of ketamine and xylazine.

Given that, for many investigators, the use of Avertin® as a general anesthetic in laboratory mice is a long-standing practice associated with few negative side effects, the IACUC may approve the use of Avertin® if the following documentation is provided in the approved animal-use protocol:

  • A scientific justification for the use of Avertin® instead of other pharmaceutical-grade anesthesia agents;
  • A detailed Standard Operating Procedure for the preparation of the working solution and proper storage of both the stock solution and the working solution.6

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 for its continued use.


References

1Animal Welfare Regulations, 9 CFR Chapter 1, Subchapter A, Part 2, Subpart C, Section 2.33(b)1-5
2USDA Animal Welfare Policy #3: Veterinary Care, Issue Date 3/25/11
3Guide for the Care and Use of Laboratory Animals, 8th Edition (2011).
4OLAW Frequently Asked Questions – PHS Policy on Humane Care and Use of Laboratory Animals, Use of Non-Pharmaceutical-Grade Compounds in Animals
5Avertin® References:

  • 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.
  • 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.
  • 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.
  • Zeller, W., et al., Adverse effects of tribromoethanol as used in the production of transgenic mice. Lab Anim, 1998. 32(4): p. 407-13.
  • 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.

6National Human Genome Research Institute Guideline for the use of tribromoethanol (Avertin®) in mice

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