​Non-Pharmaceutical Grade Substances in Laboratory Animals

Policy

Any drug used for clinical purposes must be an FDA-approved pharmaceutical grade product for use in humans or animals. This includes all anesthetics, analgesics, euthanasia agents, and antibiotics as well as controlled or legend (prescription) drugs used in veterinary care. Investigators are expected to use pharmaceutical-grade compounds whenever they are available, even in non-survival procedures.

Investigators must use pharmaceutical grade drugs when they are available in the proper formulation for the proposed work. The use of a non-pharmaceutical grade formulation when an appropriate pharmaceutical grade formulation is available may be considered in certain special situations on a case-by-case basis by the IACUC. These need to be clearly listed on the IACUC protocol and approved by the IACUC.

New investigational compounds are considered to be non-pharmaceutical grade with no available human or veterinary pharmaceutical grade equivalent or alternative.

Sterile diluents and non-toxic vehicles must be used in the preparation of all non-pharmaceutical grade compounds. Diluents or vehicles must be specified in the animal use protocol.

The UW IACUC expects researchers to have the expertise and professional judgment to determine the most appropriate formulation and route of administration for their research. For example, drugs that are formulated for oral administration should only be considered for oral administration, not altered for injectable administration. If the researcher determines that a non-pharmaceutical grade substance is needed, the researcher will obtain the highest quality/purity and will have the expertise, technical information, and laboratory resources for preparing a formulation that is most suitable for the planned route of administration. Researchers are expected to be aware of possible side effects and/or adverse reactions and state these, along with anticipated duration and/or need for treatment, in the protocol.

Use of non-pharmaceutical grade MS-222 (tricaine) and other compounds used for immersion of aquatic animals and Avertin (tribromoethanol)

• MS-222 is used in an immersion bath for anesthesia and euthanasia of aquatic animals. The IACUC considers that either pharmaceutical grade or non-pharmaceutical grade formulations of MS-222 may be used for this purpose without additional justification in the protocol. Other compounds that are used to prepare immersion baths for aquatic animals may also be non-pharmaceutical grade.
• As tribromoethanol is not available in a comparable pharmaceutical grade compound, its use as an anesthetic agent should be limited to non-survival procedures. The preparation and use of tribromoethanol for survival procedures must be scientifically necessary, appropriately justified and approved by the IACUC.

Preparation, Storage and Labeling of formulations

• Diluents or vehicles must be specified in the animal use protocol. Use of solvents will be evaluated on a case-by-case basis. Use of such solvents may limit amounts, concentration and routes of administration. Where possible, prepared solutions that will be given parenterally must be passed through a syringe filter (0.22 um or finer) at the time of preparation. This can be done in the process of transfer to an injection vial. If there is any question about the sterility of a stored solution, it should also be filtered at the time of use. If filtering is not possible (e.g., nanoparticles), sterile components should be mixed using sterile technique (e.g., in a laminar flow hood or biosafety cabinet). Compounds for oral administration do not need to be sterile; however, sterility might be warranted depending on the type of solution and how long it will be stored to prevent degradation or contamination. Proper storage of agents is important. Solutions must not be used if they are cloudy, discolored, precipitated, etc.
• The UW IACUC expects that the duration of storage and use of a non-pharmaceutical grade formulation will be compatible with the duration for which the formulation will remain potent, as per technical information available, and also sterile. Methods for preparing and storing formulations must prevent contamination that could adversely affect animal welfare or the interpretation of data. Storage in sterile injection vials is strongly recommended as the best option for storage of most injectable drugs. Storage of diluted drugs in 15 or 50 ml conical vials is not recommended, as it is extremely difficult to maintain sterility when they are repeatedly entered with a syringe and needle, outside of a biosafety cabinet. Sterile vials can be purchased from UW Drug Services (https://depts.washington.edu/drugsvcs/home/).
• Formulations (including secondary containers) must be labeled with the following information: name of the compound, concentration, date of preparation and expiration date. The expiration date must meet the guidelines established in IACUC Policy: Expiration Date Management for Medical Supplies, Equipment, and Substances (generally requiring a month expiration date for dilutions and mixtures unless otherwise approved by IACUC).