Substance Administration - Use of Drugs and Chemicals in Laboratory Animals (Guideline)

Guidelines: The IACUC has provided a set of guidance documents (Policies, Guidelines, and Informational Sheets) for use when planning animal procedures at the University of Iowa. An exception to a Guideline must be described and justified in the Animal Protocol and approved during the normal review process.

Purpose: 

These guidelines describe the use of drugs and other chemicals administered to laboratory animals at the University of Iowa. “ The NIH Office of Laboratory Animal Welfare (OLAW) and the United States Department of Agriculture (USDA) both have determined that the use of non-pharmaceutical-grade compounds should be based on (1) scientific necessity, (2) non-availability of an acceptable veterinary or human pharmaceutical-grade compound, and (3) specific review and approval by the institutional ACUC.”¹ The use of drugs falls into one of two usage categories. These guidelines apply to drugs used for experiments or for therapeutic purposes . Deviation from these guidelines must be described and justified in an IACUC-approved Animal Protocol.  

The use of non-pharmaceutical grade compounds in animals may be necessary and appropriate, but must be scientifically justified in an IACUC-approved Animal Protocol.

Definitions

• FDA – Food and Drug Administration
• USP/NF – United States Pharmacopeia/National Formulary
• BP – British Pharmacopeia
• Pharmaceutical grade compound: Drug, biologic, or reagent which is approved by the FDA or for which a chemical purity standard has been established by USP/NF or BP.
• Phosphate buffered saline (PBS) if tissue culture grade and sterile
• Non-pharmaceutical grade compound:  Any substance which does not meet the above definition of pharmaceutical grade, including:
  • Analytical grade bulk chemical: ~99% purity chemical, Certificate of Analysis typically available
  • Pharmaceutical grade drug compounded with non-pharmaceutical grade vehicle or other substance

Drugs Administered for Therapeutic Purposes

• Current standards for the veterinary therapeutic care of research animals state that pharmaceutical grade medications should be used for routine medical treatment
• Examples of therapeutic purposes include:
  • Sedation and anesthesia for surgery or other procedures
  • Relief or treatment of disease or injury  
  • Pain control (analgesia)
  • Euthanasia
• Drugs used for veterinary care, either as part of an IACUC-approved Animal Protocol or an OAR veterinarian-approved treatment plan, should be obtained from a veterinary supply or from a pharmaceutical supplier licensed by the FDA, if available from such sources

Substances Administered for Experimental Purposes²

When developing a proposal to administer a substance to an animal, the following factors should be considered:

• Purity/grade
  • The following order of choice should be applied:
    1. FDA-approved veterinary or human pharmaceutical compound
    2. FDA-approved pharmaceutical compound used to compound a needed dosage/formulation
    3. USP/NF or BP pharmaceutical grade compound used to compound a needed dosage/formulation
    4. Analytical grade bulk chemical used to compound a needed dosage/formulation
    5. Other grades and sources of compounds
• Safety
• Efficacy
• Sterility
• Pyrogenicity
• Stability
• pH/osmolality
• Site/route of administration
• Pharmacokinetics
• Physiological compatibility
• Quality control

The following questions should be considered when deciding what formulation(s) to use for your animal experiments:

Scientific Justification

• In situations where use of a non-pharmaceutical grade substance is necessary and appropriate, the following sample text may be used and/or modified to illustrate scientific justification in your Animal Protocol:
  • No pharmaceutical-grade human or veterinary drug is available
  • A pharmaceutical-grade drug is available, but is not compatible with the concentration, formulation, delivery, or vehicle requirements of experimental administration
  • A pharmaceutical-grade drug is available, but the use of a non-pharmaceutical grade product is required to replicate methods from previous studies because results must be directly compared to the results of replicated studies

Anesthetic Agents for Aquatic Species

The most commonly used anesthetic agent for fish and frogs in our facilities is tricaine methanesulfonate, or MS-222.  This agent is available as an FDA-approved veterinary drug under the labels Finquel or Tricaine-S. As a result, we recommend the use of these veterinary pharmaceutical-grade products according to the product label, which involves dilution in the appropriate aquatic habitat water from the housing facility, followed by buffering with sodium bicarbonate to an appropriate pH. Benzocaine may also be used. Dosage and storage instructions contained in the IACUC Guidelines on Anesthesia should be followed, unless otherwise described and justified in the Animal Protocol. 

Preparation and Handling of Drugs/Chemical Agents

• Agents to be administered to animals must be handled and stored so as to maintain sterility and efficacy
  • Appropriate closed sterile containers (e.g. injection vials, red-topped blood tubes) must be used, rather than snap-cap or screw-top containers
  • The smallest amount of agent suspension/dilution/mixture should be used to minimize storage time prior to administration
  • The rubber injection port/cap should be swabbed with alcohol prior to insertion of the needle
  • Use a clean, sterile container for each preparation (do not reuse)
  • Use new sterile needles for each entry into a sterile container
  • Maintain needles in a sterile manner prior to injection
    • Do not rest needles on non-sterile surfaces
  • The re-use of needles for multiple animals is strongly discouraged due to loss of sharpness and biosecurity/cross-contamination concerns
• Examine multiple-dose injection vials/tubes prior to use for evidence of physical or chemical contamination
  • Discard any substance meeting any of the following criteria:
    • Particulate matter
    • Precipitation of solids
    • Turbid or discolored appearance
    • Mislabeled or unlabeled container
    • Damage to the rubber stopper compromising integrity
• All containers must be labeled with:
  • Name of the drug(s)/chemical(s) contained
  • Concentration of the drug/chemical
  • Date of expiration (see below)

 Expiration of Drug Dilutions/Mixtures

•  Sterile dilutions or mixtures of drugs may result in a shorter effective expiration date than the expiration date of the individual components, due to risk of contamination and dilution of preservatives
• An expiration date of six (6) months from the date of preparation, or the earliest expiration date for any single component (if less than six months), is recommended unless scientifically justified otherwise³

 Expired Drugs

• Expired drugs must not be administered to any animal without explicit IACUC approval
• All expired drugs, including anesthetics and analgesics, must be segregated and clearly mark “EXPIRED”
• For information on storage and destruction of expired DEA controlled substances, please refer to the controlled substances link below

DEA Controlled Substances

• Information on DEA controlled substances 

References:

1) "Guidelines for the Use of Non-Pharmaceutical Grade Compounds in Laboratory Animals." Oacu.od.nih.gov. 8 Jan. 2010. 

2) OLAW FAQ F.4  Accessed 2/11/13.

3) Beyond-use Dating of Extemporaneously Compounded Ketamine, Acepromazine, and Xylazine: Safety, Stability, and Efficacy over Time. JAALAS 48.6 (2009): 718-26.

Last Reviewed By the IACUC 11/8/2023