Guidelines on the Preparation, Storage and Expiration of Injectable Medications
This guideline outlines the expectations for the preparation, storage and expiration of injectable medications.
-
Glossary Definitions
Pharmaceutical Grade
A drug, biologic, or reagent that is approved by the Food and Drug Administration (FDA) for use in humans or animals or for which a chemical purity standard has been established by the United States Pharmacopeia-National Formulary (USP-NF), or British Pharmacopeia (BP). 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. The FDA maintains a database listing approved commercial formulations for human drugs (the Orange Book) and veterinary drugs (the Green Book). For chemicals, a certificate of analysis is usually available upon request.
Non-Pharmaceutical Grade
Chemicals or compounds that do not meet or exceed requirements of USP/NF/BP and may have higher levels of impurities that can introduce unwanted variables or toxic effects. Sterile pharmaceutical grade preparations that are reconstituted, diluted, mixed or have other substances added are also considered non-pharmaceutical grade.
Diluent
An agent that dilutes or renders an active compound less potent or irritant. Example – 0.9% sterile saline or sterile water.
Dose
The quantity to be administered at one time as a specified amount of medication.
Parenteral
Administration of substances outside of the gastrointestinal tract. Routes of parenteral administration are listed below.
- Intravenous (IV): Administration of substances into venous circulation.
- Intraperitoneal (IP): Administration of substances into the abdominal cavity.
- Topical (epicutaneous): The application of substances directly to the skin for topical effect.
- Transdermal (percutaneous): The application of substances directly to the skin for systemic effect.
- Subcutaneous (SC): Administration of substances into the subcutaneous space.
- Intradermal (ID): Administration of substances into the dermis.
- Intramuscular (IM): Administration of substances into the muscle
- Intranasal (IN): Administration of substances into the nose.
- Intratracheal (IT): Administration of substances within the trachea.
- Intracranial: Administration of substances into the brain.
- Epidural (ED): Administration of substances into the epidural space.
- Intrathecal (IT): Administration of substances into the subarachnoid space (in the spinal canal but not within the spinal cord).
-
Preparing Injectable Medications
- Pharmaceutical Grade drugs should be purchased in sterile, rubber topped vials in the smallest volume available that is appropriate for the intended use.
- Calculate the weight of the chemical needed to prepare the desired volume of drug at the necessary concentration. See Appendix A for example pharmaceutical calculations.
- Prior to preparation, review the EHS safety findings in eRAM to determine if a specific substance must be prepared in a chemical fume hood or biological safety cabinet
- Dissolve the measured amount of drug in the appropriate volume of diluent in a sterile container. Whenever possible, use a sterile, pH balanced (6.8 – 7.2), osmotically balanced (approx. 300 mOsm, e.g. 0.9% Sodium Chloride, Phosphate Buffered Saline, Balanced Salt Solution), pyrogen-free diluent. Non-aqueous formulations may require additional information describing assurances for sterility, potential adverse consequences, etc. during IACUC review.
- If needed, adjust pH close to physiologic pH (7.4).
- Dissolve drug in an appropriate solvent until particles are not visible. Filter through a 0.2 um filter into a sterile vial with a crimped sterile rubber closure.
- Label the container with the name of the drug, the concentration, and a beyond use date as defined below.
-
Storage and expiration of Injectable Medications
- Prepare and access all medications aseptically and store according to manufacturer guidelines.
- It is best practice to open or prepare the smallest quantity of drug required for that day’s work and discard any remaining drug at the end of the day.
- Use and label all medications in accordance with manufacturer expiration dates, manufacturer beyond use dates (if provided), and the U-M Policy on the Use and Storage of Expired Drugs and Medical Materials of Animals. The following stipulations apply:
- A pharmaceutical grade drug with an added diluent or substance (e.g., combining Ketamine and Xylazine) used as an analgesic, anesthetic, antibiotic, or euthanasia agent expires 30 days beyond the date of preparation, or until the manufacturer expiration date or use-by-date, whichever occurs first.
- Sterile fluids expire on which ever date occurs first:
- The manufacturer expiration date,
- 72 hours after opening when administered intravenously, or
- 30 days after opening when administered via a route other than intravenous
Examples:
Scenario: Last day of acceptable use: The manufacturer guidelines for carprofen (expires 8/5/2023) state the product must be used within 28 days of first puncture. The drug is first accessed on 5/2/2022 The remaining contents of the carprofen stock vial and all dilutions made from that vial cannot be used beyond 5/30/2022 On 5/5/23 Ketamine (Ketamine stock bottle has expiration of 9/6/23) is diluted with Xylazine (Xylazine stock bottle has expiration of 10/6/23) for use as an anesthetic cocktail during surgery In accordance with the policy, the anesthetic cocktail expires 30 days post preparation or when the stock bottle expires (whichever occurs first). Ketamine and Xylazine were combined on 5/5/23 and expires 30 days later on 6/3/23* Sterile fluids from an IV bag (expires 12/2/2025) are opened on 8/9/2024 at 2pm and administered intravenously In accordance with the policy, the IV fluids expire 72 hours after opening and cannot be used beyond 12/4/2024 at 2pm *If the individual Ketamine and/or Xylazine stock bottle had an expiration date prior to 6/3/23, the dilution would expire on that date. For example, if the Ketamine vial had an expiration date of 5/25/23, the mixture would expire on 5/25/23.
-
Appendix A: Pharmaceutical Calculations for Diluting and Combining Drugs
-
References
- Blood DC, Studdert VP. 1999. Saunders comprehensive veterinary dictionary. London ; New York: WB Saunders.
- Lake T. 2003. Dosage calculations for veterinary nurses and technicians. Edinburgh ; New York: Butterworth-Heinemann.
- Matthews, K. and Taylor, D., Assessment of Sterility in Fluid Bags Maintained For Chronic Use; J. American Association for Laboratory Animal Science, Vol. 50, No. 5, Pages 708-712, September 2001.
- Plumb DC. 2005. Plumb's veterinary drug handbook. Stockholm, Wis. Ames, Iowa: PharmaVet ; Distributed by Blackwell Pub.
- Office for Animal Care and Use, NIH. Updated February 19, 2009. (http://oacu.od.nih.gov/)
Questions?
Questions or concerns about the content of this document should be directed to the Unit for Laboratory Animal Medicine (ULAM) at (734) 764-0277 or ulam-questions@umich.edu.
