Guidelines

Guidelines on the Preparation, Storage and Expiration of Injectable Medications

Unit for Laboratory Animal Medicine
Mar 12, 2021 12:00 am

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

    1. Pharmaceutical Grade drugs should be purchased in sterile, rubber topped vials in the smallest volume available that is appropriate for the intended use. 
    2. 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. 
    3. 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. 
    4. If needed, adjust pH close to physiologic pH (7.4). 
    5. Consult with EHS to determine if a specific substance must be prepared in a chemical fume hood or biological safety cabinet. 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.
    6. Label the container with the name of the drug, the concentration, and a beyond use date as defined below. 
    7. Prior to removal of any medication from the vial, swab the rubber port of the vial with 70% alcohol and allow to dry completely.
  • Storing Injectable Medications

    1. It is best practice to open or prepare the smallest quantity of drug required for that day’s work, to discard any remaining drug at the end of the day, or to prepare a stock solution that it aliquot and frozen such that a single day’s requirements can be thawed when needed.
    2. All medications should be prepared and accessed aseptically and stored according to manufacturer guidelines.
    3. All medications should be clearly labeled with an expiration date according to the following guidelines:
      Type of Injectable Medication Expiration Guidelines
      Pharmaceutical grade drug without diluents or added substances Expires according to manufacturer guidelines
      Pharmaceutical grade drug reconstituted according to manufacturer guidelines Expires according to manufacturer guidelines
      Pharmaceutical grade drug with added diluents or substances and intended for  clinical use as an analgesic, anesthetic or antibiotic Expires 30 days beyond the date of preparation or until the manufacturer expiration date, whichever occurs first
      Pharmaceutical grade drug with added diluents or substances and not intended for clinical usage Expires according to manufacturer guidelines
      Sterile fluids provided to patients via the intravenous route Expires after 72 hours
      Sterile fluids provided to patients via routes other than intravenous Expires 30 days after opening
    4. Storage of controlled substances, including storage in a refrigerator or freezer, must meet the standards described by the U-M Controlled Substances in Research Monitoring Program. Contact the Controlled Substance Monitors at CS-monitors@med.umich.edu for further details.
  • Appendix A: Pharmaceutical Calculations for Diluting and Combining Drugs

  • References

    1. Blood DC, Studdert VP. 1999. Saunders comprehensive veterinary dictionary. London ; New York: WB Saunders.
    2. Lake T. 2003. Dosage calculations for veterinary nurses and technicians. Edinburgh ; New York: Butterworth-Heinemann.
    3. 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.
    4. Plumb DC. 2005. Plumb's veterinary drug handbook. Stockholm, Wis. Ames, Iowa: PharmaVet ; Distributed by Blackwell Pub.
    5. Office for Animal Care and Use, NIH. Updated February 19, 2009. (http://oacu.od.nih.gov/)