Can I Use Non-Pharmaceutical grade chemicals or compounds in my study?

Please to the text provided below for an explanation of the OLAW and USDA guidelines for the use of non-pharmaceutical grade chemicals or compounds

1.    May investigators use non-pharmaceutical-grade compounds in animals?

OLAW and USDA agree that pharmaceutical-grade1 chemicals and other substances, when available, must be used to avoid toxicity or side effects that may threaten the health and welfare of vertebrate animals and / or interfere with the interpretation of research results. However, it is frequently necessary to use investigational compounds, veterinarian- or pharmacy-compounded2 drugs, and / or Schedule I3 controlled substances to meet scientific and research goals.

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

o    grade,

o    purity,

o    sterility,

o    acid-base balance,

o    pyrogenicity,

o    osmolality,

o    stability,

o    site and route of administration,

o    compatibility of components,

o    side effects and adverse reactions,

o    storage, and

o    pharmacokinetics.

The IACUC may use a variety of administrative methods to review and approve the use of such non-pharmaceutical-grade agents. For example, the IACUC may establish acceptable scientific criteria for use of these agents within the institution, rather than on a case-by-case basis. Investigators and IACUCs should consider relevant animal welfare and scientific issues including safety, efficacy, availability of pharmaceutical-grade compounds, and the inadvertent introduction of new variables. Cost savings alone are not an adequate justification for the use of non-pharmaceutical-grade or compounded drugs in animals.

Although the potential animal welfare consequences of complications are less evident in non-survival studies, the scientific issues remain the same. The principles and need for professional judgment outlined above apply to non-survival studies.

Procedures that may cause more than momentary or slight pain or distress to animals must be relieved by sedation, analgesia, or anesthesia using veterinary or human pharmaceutical-grade compounds, unless the use of an investigational chemical or formulation is scientifically necessary, appropriately justified, and approved by the IACUC. The use of a non-pharmaceutical-grade euthanasia agent must meet the same criteria.

1 A pharmaceutical grade compound is a drug, biologic, or reagent that is approved by the Food and Drug Administration (FDA) or for which a chemical purity standard has been established by the United States Pharmacopeia-National Formulary (USP-NF), or British Pharmacopeia (BP).

2 Veterinary compounding is the customized manipulation of an approved drug by a veterinarian, or by a pharmacist upon the prescription of a veterinarian, to meet the needs of a research study. IACUCs considering the use of veterinary compounding for research purposes are advised to consult:  http://www.avma.org/issues/drugs/compounding/veterinary_compounding_brochure.asp for more information about federal regulations.

3 United States Department of Justice Drug Enforcement Agency controlled substances Schedule I and II-IV drugs may be used in biomedical research according to the standards of the Code of Federal Regulations 1301.13.

http://grants.nih.gov/grants/olaw/faqs.htm#useandmgmt_4   . 

This information is also contained in the document entitled IACUC 119 Non-Pharmaceutical Grade Chemicals.

IACUC 119

Approved by the IACUC on August 18, 2010

IACUC POLICIES, PROCEDURES, and GUIDELINES

The Use of Non-Pharmaceutical-Grade Chemicals/Compounds

in Laboratory Animals

119.1 OBJECTIVE

To remain compliant with the guidance provided by the Office of Laboratory Animal

Welfare (OLAW) and the United States Department of Agriculture – Animal Plant Health

Inspection Service (USDA-APHIS), this document details what is required in regards to

the use of non-pharmaceutical-grade chemicals or compounds in laboratory animals at

the University of Kentucky. Non- parenteral drugs used in agricultural animals are

excluded from this policy.

119.2 DEFINITIONS

1. USP/NF: United States Pharmacopeia/National Formulary

2. BP: British Pharmacopeia

3. Pharmaceutical grade chemical: ~97% purity; a chemical that states it meets the

USP/NF or BP standard on the label. A certificate of analysis is usually available on request.

4. Analytical Standards: “Certificate of Analysis” a document that goes with each

product run. This certificate lists the formula for the ingredients as well as the amount of

each raw material/ingredient. The product name and lot number are listed to avoid

confusion with other batches. The Certificate of Analysis also may contain results of

tests for contaminants.

5. Analytical Grade: ~99% purity; Certificate of Analysis usually available; appropriate preparation is imperative.

6. Reagent ACS: This designates the highest quality commercial chemical. The “ACS”

means the American Chemical Society. A Certificate of Analysis is available upon request.

7. Reagent Grade: The highest quality commercial chemical; However, ACS has not set specifications for materials. A Certificate of Analysis is usually not available

 

119.3 DESCRIPTION OF USE

IACUC 119

Approved by the IACUC on August 18, 2010

The use of pharmaceutical-grade chemicals/compounds in laboratory animals ensures that the chemicals/compounds administered meet the established documentable

standards of purity (~97%) and composition established by the United States

Pharmacopeia National Formulary (USP/NF) or the British Pharmacopoeia (BP). The

indiscriminant use of lower grade chemicals/compounds with higher levels of impurities

or poorly formulated non-commercial preparations can introduce unwanted

experimental variables or even toxic effects. Although pharmaceutical grade

chemicals/compounds should be used in experimental animals whenever possible, the

use of non-pharmaceutical-grade chemicals/compounds in experimental animals is an

acceptable practice under certain circumstances. OLAW and USDA both have

determined that the use of non-pharmaceutical-grade products 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 IACUC.

Cost savings alone is not considered an adequate justification for the use of nonpharmaceutical-grade reagents in laboratory animals. (See USDA Policy 3).

119.4 WHAT SHOULD BE CONSIDERED?

Consideration should be given to the grade/purity of the chemical/compound being

proposed, as well as the formulation of the final product. Issues such as sterility,

pyrogenicity, stability, pH, osmolality, site/route of administration, pharmacokinetics,

physiological compatibility, and quality control should be considered when proposing the

use of a non-pharmaceutical-grade agent. The IACUC will expect these considerations

to be included as justification in IACUC animal care and use protocols. When

developing and reviewing a proposal to use non-pharmaceutical-grade agents the

investigator and the IACUC will also consider animal welfare and scientific issues

related to the use of the agent, including potential for contamination, safety, efficacy,

and the inadvertent introduction of confounding research variables. Whereas, many of

the above issues have been addressed in the commercial manufacturing and

formulation of pharmaceutical-grade products, the same cannot be said for noncommercial

formulations using non-pharmaceutical-grade reagents or those

manufactured in the laboratory.

119.5 WHAT ABOUT USE IN NON-SURVIVAL PROCEDURES?

Although the possible implications of the use of non-pharmaceutical-grade

chemicals/compounds in non-survival studies appears less evident, OLAW has stated

that the scientific issues remain the same and professional judgment, as outlined above,

must still apply. The IACUC will expect a justification for non-survival use applications

and will determine approval on a case-by-case basis. Remember, cost savings alone is

not considered adequate justification.

IACUC 119

Page 3 of 3

Approved by the IACUC on August 18, 2010

119.6 WHAT SPECIFICALLY NEEDS TO BE INCLUDED IN THE PROTOCOL?

The use of non-pharmaceutical-grade agents in laboratory animals should be clearly

delineated and justified in the IACUC Animal Care and Use Protocol. Where possible

the description should include the chemical grade of the agent(s) being used (See

definitions above), source of the reagents, as well as a description of the

appropriateness of the agent, its formulation and vehicle. Formulations and vehicles

may need to be adjusted depending on the route and site of administration, as well as

the species under consideration.

119.7 WHAT DOES THE GUIDE FOR THE CARE AND USE OF LABORATORY

ANIMALS SAY?

“The use of pharmaceutical grade chemicals and other substances ensures that toxic or unwanted side effects are not introduced into studies conducted with experimental

animals. Pharmaceutical grade chemicals should be used, when available, for all

animal-related procedures (NIH 2008; USDA 1997b). There may be circumstances

when the use of a non-pharmaceutical grade chemical or substance is necessary to

meet the scientific goals of a project or when a veterinary or human pharmaceutical

grade product is unavailable. The use of non-pharmaceutical grade chemicals or

substances should be described and justified in the animal use protocol and be

approved by the IACUC (Wolff et al. 2003). Consideration should be given to the grade,

purity, sterility, pH, pyrogenicity, osmolality, stability, site and route of administration,

formulation, compatibility, and pharmacokinetics of the chemical or substance to be

administered, as well as animal welfare and scientific issues relating to its use (NIH

2008).”

Approved and Adopted by the

Institutional Animal Care and Use Committee

August 18, 2010