Pharmaceutical Grade vs. Non-Pharmaceutical Grade
Pharmaceutical Grade – A compound that is approved by the Food and Drug Administration or for which a chemical purity standard has been established by U.S. Pharmacopeia (USP), British Pharmacopeia (BP), National Formulary (NF), and for which such standard is stated on the label. 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. A certificate of analysis is usually available upon request.
Non-pharmaceutical Grade – Any drug that does not meet the above criteria. These compounds may have higher levels of impurities and can introduce unwanted variables or toxic effects. An example would be chemicals that are obtained through SIGMA. If a powder will be used and is scientifically justified, a description of sterile preparation for parenteral administration should be included in your Application for Vertebrate Animal Use (AVAU) protocol.
Investigators are expected by regulatory authorities to use pharmaceutical grade compounds whenever possible. Non-pharmaceutical-grade chemical compounds should only be used in live vertebrate animals after specific review and approval by the Institutional Animal Care and Use Committee (IACUC) for reasons such as scientific necessity or non-availability of an acceptable veterinary or human pharmaceutical-grade product. Cost savings alone is not an adequate justification for using non-pharmaceutical-grade compounds in live vertebrate animals.
Compound Use Categorization
Clinical Use – Compounds used for the clinical treatment of animals and to prevent, reduce or eliminate animal pain or distress. Investigators are expected to use pharmaceutical-grade medications whenever they are available, even in acute procedures.
Research Use – Compounds used to accomplish the scientific aims of the study. If available and suitable, pharmaceutical-grade compounds are preferred; when non-pharmaceutical-grade preparations are used, the IACUC will expect investigators to include the rationale in their IACUC application and meet the following criteria:
- Use must be compliant with applicable national or regional regulatory guidelines and requirements and the requirements of relevant funding agencies;
- A scientific justification must be provided in the application;
- A pharmaceutical-grade compound is not available in the appropriate concentration or formulation or the appropriate vehicle control is unavailable
- The compound is required to generate data that are part of an ongoing study or that are comparable to previous work;
- The chemical properties of the compound are appropriate for the study and the route of administration (e.g., the purity, grade, stability in and out of solution, solution vehicle properties, pH, osmolality, and compatibility of the solvent and other components of final preparation). In some cases the reagent-grade of the compound may be as pure or purer than the pharmaceutical-grade; and
- The method of preparation, labeling (i.e., preparation and use-by dates), administration and storage of formulations should be appropriately considered with the aim of maintaining their stability and quality (i.e., to prevent inadvertent co-administration of infectious agents or contaminants).
Dilutions and Combinations
Oftentimes, administering anesthetics, analgesics or other drugs to very large or very small animals may necessitate dilution or adulteration of drugs that will cause the drugs to be classified as non-pharmaceutical-grade compounds. The NC State IACUC recognizes that such compounds may be preferable in certain circumstances and approves the use of the following agents without scientific justification for routine anesthesia, analgesia or euthanasia:
- Anesthetic cocktails utilizing pharmaceutical grade compounds such as:
- Tiletamine/ketamine/xylazine combination for large swine
- Rodent “cocktails” that contain mixtures of ketamine, xylazine/dexmedetomidine, and/or acepromazine
- Other cocktail combinations that are considered standard veterinary practice and listed as a combination on your approved IACUC protocol.
- Cocktail combinations consistent with standard veterinary care used for veterinary care procedures
- Dilution of the analgesics such as:
- Carprofen, buprenorphine, and meloxicam or other analgesics with USP-grade saline or water prior to administration to small rodents
- Dilution of sodium pentobarbital euthanasia solutions with USP-grade saline or water prior to administration to small rodents
- Other dilutions consistent with standard veterinary care
In all of the above instances, the adulteration of such substances must be performed sterilely and in accordance with appropriate dosages as dictated by standard of care. Once adulterated, the expiration date must be clearly indicated and must account for stability in the altered conditions. As a rule of thumb, the adulterated drug must not be used after three months of initial dilution or sooner if indicated by the unadulterated formulation.
The waiver of the scientific justification requirement is applicable only if the diluted or adulterated pharmaceutical is pharmaceutical grade. If any component of the adulterated or diluted product is not pharmaceutical grade, scientific justification is necessary for use of that product.
Updated and Approved December 12, 2019