Effective Date:
Approved Date: 2-5-2014
Revised Date: 1-25-2014
Last Reviewed:
Iowa State University
Institutional Animal Care and Use Committee (IACUC)
SOP ID Number: V300.01
SOP Title: The Use of Non-Pharmaceutical-
Grade Drugs
1. Purpose
Standard Operating Procedure (SOP)
This document describes the expectations that Iowa State University’s IACUC has regarding the use of non-pharmaceutical-grade drugs or compounds in animals used in research or teaching. These expectations were developed to remain compliant with the guidance provided by the Guide for the Care and Use of Laboratory Animals, 2011, PHS
Policy, the Animal Welfare Act, the Office of Laboratory Animal Welfare (OLAW), the position statement from AAALAC, International and the USDA-APHIS.
2. Scope
This SOP is applicable to all ISU staff, research investigators, and technicians who are on an approved IACUC protocol and are responsible for administration of experimental and/or therapeutic compounds to animals.
3. General Requirements
All investigators, staff, veterinarians, and others who will administer drugs to animals for an
IACUC protocol must follow the procedure outlined in this SOP. FDA-approved pharmaceutical-grade drugs must be used if available. When investigational test compounds are being used, it is understood that the compound is not yet FDA-approved.
If FDA-approved drugs are not available, non-FDA-approved drugs may be used only after specific review and approval by the IACUC for reasons such as scientific necessity or nonavailability.
4. Procedure
A.
When a procedure requires the administration of a drug or compound, the following order of choice for selection of the compound must be followed:
1.
FDA-approved veterinary or human pharmaceutical-grade compounds
2.
FDA-approved veterinary or human pharmaceuticals used to compound the required dosage form by a licensed compounding pharmacist, who will ensure the drug formulation is appropriate for the intended use and route of administration.
3.
FDA-approved pharmaceutical compounds diluted in the laboratory to make the required dosage form. Details regarding the method of preparation must be documented in the IACUC protocol and follow the recommendations in this SOP.
4.
USP/NF or BP pharmaceutical-grade compounds diluted in the laboratory to make the required dosage form. Details regarding the method of preparation must be documented in the IACUC protocol and follow the recommendations in this SOP
Office for Responsible Research
Iowa State University
Page 1 of 6

Effective Date:
Approved Date: 2-5-2014
Revised Date: 1-25-2014
Last Reviewed:
Iowa State University
Institutional Animal Care and Use Committee (IACUC)
SOP ID Number: V300.01
SOP Title: The Use of Non-Pharmaceutical-
Grade Drugs
5.
Analytical-grade bulk chemicals compounded in the laboratory to the required dosage (requires justification). Details regarding the method of preparation must be documented in the IACUC protocol and follow the recommendations in this SOP.
6.
Any other grade or source of compounds prepared in the laboratory to the final required dosage and form (requires justification). This includes new investigational test compounds in circumstances when the compound itself is an experimental variable. Details regarding the method of preparation must be documented in the
IACUC protocol and follow the recommendations in this SOP.
B.
If a non-pharmaceutical-grade compound is deemed necessary by an investigator for use in a study with animals, the investigator must request IACUC approval for the compound. This should include information regarding the following:
1.
Scientific issues related to the use of the substance: a.
Potential for contamination b.
Safety c.
Efficacy d.
Possibility of inadvertent introduction of confounding research variables
2.
Compound information including: a.
Grade or purity being proposed b.
Sterility c.
Pyrogenicity d.
Stability e.
pH f.
Osmolality g.
Site and route of administration h.
Pharmacokinetics i.
Physiological compatibility j.
Quality control
C.
Compounds must be labeled to include the following information:
1.
Name of the medication
2.
Date that the product was mixed
3.
Expiration date of the reconstituted compound(s)
4.
Initials of the person who compounded the product if performed outside the pharmacy
D.
Documentation of appropriate methods used to prepare and handle experimental compounds must be included in the IACUC protocol proposal and included in the records by the investigator. This documentation should be available to inspectors and should include the following:
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Iowa State University
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Effective Date:
Approved Date: 2-5-2014
Revised Date: 1-25-2014
Last Reviewed:
Iowa State University
Institutional Animal Care and Use Committee (IACUC)
SOP ID Number: V300.01
SOP Title: The Use of Non-Pharmaceutical-
Grade Drugs
1.
Sterility
2.
Shelf-life
3.
Storage conditions
E.
To determine whether a specific compound is FDA-approved, refer to definitions and resources included.
5. Roles and Responsibilities
This section is in a table format. Each individual participating in the duties outlined in the
SOP (animal caretaker, veterinarian, animal researcher, etc.) will be listed in their own row within the “Roles” column. In the corresponding “Responsibilities” column, the tasks that group of individuals is responsible for are described.
Roles
Investigators,
Staff and
Students
ISU IACUC
ISU Attending
Veterinarian
Responsibilities

Must ensure that pharmaceutical-grade compounds are used if they are available.

If a pharmaceutical-grade compound is not available, must provide the IACUC specific details regarding the nonpharmaceutical compound proposed and give scientific justification for the use of it.

Must provide the IACUC with enough information to allow them to assess the potential of the nonpharmaceutical-grade compound to harm animal health or well-being as outlined in section 4.B of this document.
This information includes items such as toxicity of the drug and other components, details about the preparation including sterility, chemical grade, contaminants, pH, osmolality, storage, and any quality control performed on the final product.

Must evaluate possible detrimental effects of nonpharmaceutical-grade compounds that are proposed to be used in animals.

Must evaluate the appropriateness of the proposed formulation of the final product and consider issues including grade/purity, sterility, pyrogenicity, stability, pH, osmolality, route of administration, pharmacokinetics, physiological compatibility with species under study, storage, and quality control.

The Attending Veterinarian is a consultant for the investigators and will help investigators make sure they are in compliance with this SOP.
Office for Responsible Research
Iowa State University
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Iowa State University
Institutional Animal Care and Use Committee (IACUC)
Effective Date:
Approved Date: 2-5-2014
Revised Date: 1-25-2014
Last Reviewed:
6. Definitions
SOP ID Number: V300.01
SOP Title: The Use of Non-Pharmaceutical-
Grade Drugs

Pharmaceutical-grade compound:

OLAW: 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 (USPNF), or
British Pharmacopeia (BP).

USDA: Pharmaceutical-grade compound is any active or inactive drug, biologic, reagent, etc., which is approved by the FDA for which a chemical purity standard has been written or established by any recognized pharmacopeia, which is a book or a compendia, such as the US Pharmacopeia [USP], the National Formulary
[NF], the British Pharmacopoeia [BP], the Pharmacopoeia of the Council of
Europe [EP]. Note the USP and the NF have combined their standards into one compendium [http://www.usp.org/usp-nf]. Analytical-grade bulk chemical: ~99% purity; Certificate of Analysis is usually available. Proper compounding is imperative.

Non-availability: Not commercially available from an active US vendor; includes formulations supplied as tablet, capsule, injectable, etc. May include drugs where price is prohibitive.

New investigational compound: Supplied by its manufacturer for testing in an experimental setting only and, for this reason would not have chemical purity standards established; by default is considered a non-pharmaceutical-grade compound.

FDA: Food and Drug Administration; FDA-approved compounds are manufactured using USP/NF compounds.

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.

Reagent ACS: This designates the highest quality commercial chemical. The “ACS” means the American Chemical Society. A Certificate of Analysis is available upon request.

Reagent Grade: The highest quality commercial chemical; however, ACS has not set specifications for materials. A Certificate of Analysis is usually not available
7. Appendices n/a
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Iowa State University
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Iowa State University
Institutional Animal Care and Use Committee (IACUC)
Effective Date:
Approved Date: 2-5-2014
Revised Date: 1-25-2014
Last Reviewed:
8. Forms and Templates n/a
9. References
SOP ID Number: V300.01
SOP Title: The Use of Non-Pharmaceutical-
Grade Drugs

PHS Policy on Humane Care and Use of Laboratory Animals http://grants.nih.gov/grants/olaw/references/phspol.htm

The Guide for the Care and Use of Laboratory Animals, 8th Edition http://www.nap.edu/catalog.php?record_id=12910

USDA Policy #3: Veterinary Care http://www.aphis.usda.gov/animal_welfare/policy.php?policy=3

Office of Laboratory Animal Welfare: Educational Resources: Non-Pharm Use http://grants.nih.gov/grants/olaw/educational_resources.htm
10. Contact Information
IACUC will be the contact most frequently used for IACUC SOPs. The following statement can be used in this case: Direct questions about this document to: Institutional Animal Care and Use Committee, Iowa State University, 515-294-9581, iacuc@iastate.edu
.
The Attending Veterinarian will often be the contact: Dr. Mary Sauer, 515-294-0266, msauer@iastate.edu
.
LAR Medical may be the contact. The following statement can be used in this case: Direct questions about this document to: LAR Medical, Laboratory Animal Resources, Iowa State
University, 515-294-8507, larmedical@iastate.edu
.
Office for Responsible Research
Iowa State University
Page 5 of 6

Effective Date:
Approved Date: 2-5-2014
Revised Date: 1-25-2014
Last Reviewed:
Iowa State University
Institutional Animal Care and Use Committee (IACUC)
SOP ID Number: V300.01
SOP Title: The Use of Non-Pharmaceutical-
Grade Drugs
_______________________________
Additional Signee (if applicable)
______________________________
Date Signed
_______________________________
Signature of IACUC Chair or Co-Chair
______________________________
Implementation Date
______________________________
Date Signed
Effective Date
(Type in date)
Document management enters after approval.
Appendix 1
Document History
Version Number
01
Document management enters # (2 digits) before sending for approval.
Author(s)
Jen Walker-
Daniels
Mary Sauer
Name(s) of the author(s)
Description
First Issue
For version 01, enter “First
Issue.” Otherwise, enter
“Replaces [Document Number and
Title].”
Briefly describe revision. (Author is responsible for description of revisions that were made.)
For reissued SOP that has undergone review, indicate that a review was performed and the
SOP was reissued with no significant content change.
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Iowa State University
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