IACUC Policy: Non-pharmaceutical Grade Compounds Used in Research
Policy # IBT-201.01 IACUC Approval: February 27, 2014

Purpose: 
The purpose of this document is to define the policy regarding the use of non-pharmaceutical grade drugs and expired materials in research animals. 

Scope:
This policy applies to Animal Use Protocols reviewed by the Texas A&M Health Science Center IACUC. 

Responsibilities:
It is the responsibility of the IACUC to review and approve drugs used on research animals, whether pharmaceutical grade or non-pharmaceutical grade, as submitted by the Principal Investigator.
It is the responsibility of the Attending Veterinarian (AV) and PAR Operations Manager or designee to provide expertise when consulting on drug usage (pharmaceutical or non-pharmaceutical).
It is the responsibility of the Principal Investigator or designee to use pharmaceutical grade drugs, if available, or to provide justification for the use of non-pharmaceutical grade drugs to the IACUC.  In the animal study proposal, the PI must identify any drugs, biologics or reagents that will be administered to animals. If these agents are not human or veterinary pharmaceutical-grade substances, the investigator must provide a scientific justification for their use and describe the methods that will be used to ensure appropriate preparation and administration.

Definitions:
Non-pharmaceutical grade compound - compound is defined as any active or inactive drug, biologic or reagent, for which a chemical purity standard has been established by a recognized national or regional pharmacopeia (e.g., the U.S. Pharmacopeia (USP), British Pharmacopeia (BP), National Formulary (NF), European Pharmacopoeia (EP), Japanese Pharmacopeia (JP), etc.). These standards are used by manufacturers to help ensure the products are of the appropriate chemical purity and quality, in the appropriate solution or compound, to ensure stability, safety, and efficacy. 

Policy:
In an animal care and use program, non-pharmaceutical-grade compounds often are necessary for scientific research. Where the use of non-pharmaceutical-grade substances may be essential for the conduct of science, the goal of the investigator and the IACUC should be to consider the health and well-being of the animals while aiding the researcher in minimizing potentially confounding experimental variables and maximizing reproducibility of the research.

When reviewing a protocol, the IACUC will consider study goals, justification to use the substance, the level of pain and distress and with that will purity differences.  The IACUC should also take into account whether the procedure is survival or a non-survival and if survival then sterility must be considered.  The committee should also consider and unique scientific objectives of the study.  The IACUC process should ensure that applicable regulations and guidelines are taken into consideration during the review.

I. IACUC Guidelines
The IACUC will use the following performance standard criteria for use of such compounds within the institution and for review and approval of their use. Two categories exist for the use of non-pharmaceutical-grade compounds:

  1. Clinical Use - compounds used for the clinical treatment of animals and to prevent or reduce/eliminate animal pain or distress. Whenever possible, pharmaceutical-grade compounds must be used.
  2. Research Use - compounds used to accomplish the scientific aims of the study. If available, and suitable, pharmaceutical-grade compounds are preferred; but when non-pharmaceutical-grade preparations are used, investigators and the IACUC must consider the following factors:

 - Use must be compliant with applicable national or regional regulatory guidelines and requirements and the requirements of relevant funding agencies;

 - A scientific justification is provided;

 - The pharmaceutical-grade compound is not available in the appropriate concentration or formulation or the appropriate vehicle control is unavailable.

 The IACUC is responsible for evaluating the potential adverse consequences of such non-pharmaceutical grade agents when used for research. In making its evaluation, the IACUC may consider factors including, for example:

  • grade,
  • purity,
  • sterility,
  • acid-base balance,
  • pyrogenicity,
  • osmolality,
  • stability,
  • site and route of administration,
  • compatibility of components,
  • side effects and adverse reactions,
  • storage,
  • pharmacokinetics,
  • method of preparation,
  • labeling

II. PI Guidelines

  1. When drugs or chemicals are formulated for injection, they must be prepared in a sterile manner. This requires sterile constituents (e.g. sterile powder, sterile diluents), a sterile container and a means of keeping the preparation sterile. Injection vials are preferred as they make it easier to load a syringe and allow removal of solution without exposing the contents to outside contaminants. 
  2. Diluents or vehicles must be specified in the animal use protocol. Diluents or vehicles need to be pharmaceutical grade where available. Use of solvents will be evaluated on a case-by-case basis. Use of such solvents may limit amounts, concentration and routes of administration. 
  3. Containers must be labeled with the drug, concentration, and dates of preparation and expiration.
  4. Where possible, prepared solutions 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 must also be filtered at the time of use. If filtering is not possible (e.g., nanoparticles), sterile components should be mixed using sterile technique.
  5. Prepare only as much as can be used in a reasonable period of time. Drug solutions prepared and stored properly in a suitable injection vial can be stored for a time frame that is in-line with a similar commercial product. Drugs must be stored properly (e.g., freezer, refrigerator, etc.). Solutions must not be used if they are cloudy, discolored, precipitated, etc.
  6. Expired drugs must be disposed of properly. If not discarded, expired drug containers must be labeled “expired” and stored separate from drugs in use. Controlled substances cannot be discarded without appropriate paperwork. All controlled substances must continue to be stored in an approved secure cabinet or safe.
  7.  pH of solutions must be between pH 4.5 and 8.0.Use of a solution with a pH outside this range must be addressed in the animal use protocol.

References:
1.      Office of Laboratory Welfare (OLAW) webinar “Use of Non-Pharmaceutical-grade Chemicals and other Substances in Research with Animals” broadcast March 1, 2012

2.      Seminar by Dr. Patricia Brown entitled, “Use of Non-Pharmaceutical-Grade Substances in Research with Animals” given at the SCAW Winter Conference, December, 2012 in San Antonio Texas

3.      AAALAC Guidelines 

History:
Version 00 – Initial Approval: January 27, 2014
Version 01 – added references and additional language to the responsibilities and policy: February 27, 2014