Use and Expiration of Medical Materials (IACUC)
Purpose
Boston University (BU) is committed to observing Federal policies and regulations and the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International standards for the humane care and use of animals. The intent of this policy is to describe the process for reviewing reported concerns or non-compliance related to the care and use of live vertebrate animals at BU.
Covered Parties
This policy is applicable to all persons responsible for conducting research, teaching, training, breeding, and related activities, hereinafter referred to collectively as “activities”, involving live vertebrate animals conducted at or under the auspices of Boston University.
University Policy
Most medical materials (e.g., drugs, fluids, disinfectant solutions, catheters, sutures, etc.) are imprinted with an expiration date. Beyond this date, the manufacturer does not guarantee the sterility, safety, or stability of the item. The use of expired materials in live animals without justification constitutes inadequate veterinary care. If scientific justification is provided, expired drugs (other than anesthetic, analgesic, and emergency drugs, which must be used before expiration per The Guide) may be used for non-survival procedures. Pain-relieving drugs may lose potency after the expiration date, resulting in unpredictable effects that can jeopardize humane animal use even in a non-survival setting.
Expired Materials
Drugs and medical materials administered to live vertebrate animals during survival procedures must be used within their expiration date (see applicable regulations below and note that Boston University policy covers all live vertebrate animals). This includes fluids (such as saline and Heparin) and materials (such as sutures). Therefore, please adhere to the following policy:
- Expired anesthetic, analgesic, or emergency drugs cannot be used in live animals under any circumstances.
- Other expired drugs or medical supplies cannot be used for any survival procedures, but can be used for non-survival procedures in cases where their use would not compromise the experiment. Scientific justification for their use must be approved by the IACUC.
- All drugs and sterile medical supplies must be marked with an expiration date in accordance with the following guidelines for expiration dating of medical materials.
Take the time to examine your inventory and discard any outdated items. Please be aware that the animal facility staff has been instructed to dispose of any and all materials housed within the animal facility that are beyond their expiration date.
Practical Guidelines
In cases where you reconstitute or aliquot drugs so that they are no longer in bottles marked with a manufacturers’ expiration date, please make sure to write the expiration date on each new bottle aliquoted from stock. Please check for manufacturers’ instructions regarding expiration after reconstitution or first puncture.
Expired drugs kept for in vitro use must be kept together in an area physically separate from all other medical materials and drugs that are used in live animals and must be marked with the expiration date.
When ordering drugs or materials that you don’t use up quickly, it is wise to inquire at the time of ordering about the expiration date of the lot that the company plans to send you, and make sure they don’t send old items that will be expiring soon. Alternatively, order in smaller amounts. Many drugs and solutions have a shelf life of at least two years, but there are exceptions.
Dating of Materials
All drugs and sterile medical devices intended for use in live animals must be marked with an expiration date.
Segregation of Expired Drugs and Medical Materials
All expired materials that are to be kept in inventory and used for non-survival procedures must be clearly and individually labeled as “expired materials–for non-survival use only” and be kept together in an area physically separate from all other medical materials and drugs.
Conditional Use of Expired Drugs and Medical Materials
Expired drugs (other than anesthetic, analgesic, and emergency drugs) and medical materials may be used for non-survival procedures in cases where their use would not compromise the experiment. Scientific justification for their use must be approved by the IACUC.
Inventory
In order to assure that expired items are identified in a timely fashion so that they can either be discarded or appropriately labeled for conditional use, each research group must inspect their animal drug and material storage areas on a regular basis (i.e., every 30 to 60 days).
Manufactured Drugs
Follow the manufacturer’s recommendations as printed on the bottle or package insert for expiration date and storage temperature. If drugs are placed into a container other than that supplied by the manufacturer or altered by diluting or mixing, the new container must be labeled with the name of the substance, the concentration, and an expiration date. All drugs for parenteral administration must be sterile and must not be aliquoted into nonsterile containers. Drugs for oral administration need not be sterile or prepared aseptically.
Drugs that are altered from their original form (e.g., diluted, reconstituted, or mixed with other drugs) or aliquoted into a new container do not necessarily keep their original expiration dates. Generally, drugs that are diluted or mixed may be kept up to 30 days. Where published, peer-reviewed evidence is available for longer stability and efficacy of drug dilutions or mixtures, that evidence may be provided in the IACUC protocol as justification to keep those solutions beyond 30 days. For example, some common dilutions for rodents (meloxicam, buprenorphine, carprofen) have been tested beyond 30 days.
1,2,5 - Meloxicam can stay sterile and stable for 365 days.2
- Buprenorphine may be diluted in glass up to 180 days but not stored in plastic syringes.1
- Carprofen dilution retains strength and sterility for 60 days at room temperature and for 180 days under refrigeration.5
Dilution, mixing, or transfer to a new container may cause the drugs to lose potency or degrade due to a change in pH, buffering, atmosphere (some drugs are packed under special gases), or precipitation. In addition, drugs that are not kept in a sealed, sterile container may become contaminated and subject to bacterial degradation. Many drugs are incompatible with other agents and cannot be mixed.
Sterile Medical Devices and Supplies
Prepackaged sterile medical devices (e.g., sutures, sterile gloves, catheters, etc.) are distributed with an expiration date or with a statement to indicate that the contents are “sterile if the packaging is undamaged.” Medical devices marked with an expiration date cannot be used for survival procedures after that date, and should usually be discarded or, if applicable, re-sterilized. If retained past the expiration date, these materials must be stored in a separate location and labeled “expired materials–for non-survival procedures only.”
Sterile Surgical Packs
Instruments or supplies sterilized by the investigator must be marked with an expiration date based on the date of sterilization. They must be marked with an external “process indicator” (e.g., autoclave or ethylene oxide tape) and must contain a sterilization indicator (usually a chemical indicator strip that indicates exposure to sufficient heat or ethylene oxide to sterilize). Cloth-wrapped, paper-wrapped, or Dennison®-wrapped sterilized equipment has a shelf life of six months. Plastic-wrapped sterilized items (e.g., peel-packs) have a shelf life of six months.
Drug Mixtures and Non-Manufactured Drugs
All drug mixtures for parenteral administration must be sterile and prepared aseptically; if aliquoted into secondary containers, sterile containers must be used. Drug mixtures for oral administration need not be sterile. Frozen aliquots can usually be kept indefinitely (at –80°C), but then have a 24-hour shelf life once thawed.
Generally, IV fluids (e.g., normal saline) are considered to expire in 24 hours after opening if kept unrefrigerated, or may be kept up to a week if refrigerated. However, there is published evidence that Lactated Ringers’ Solution (LRS) bags may be maintained as a sterile multi-use container for up to 30 days.3 Punctured or open fluid bags should always be marked with the first date of puncture.
If a drug is aliquoted unchanged into a sealed, sterile container (e.g., a red-top vacutainer, an empty sterile vial, a saline or sterile water bottle completely emptied of contents), it should keep its original expiration date (except if the drug is packaged in a special atmosphere such as argon or nitrogen). Material of the aliquot container should match the original container (e.g. glass or plastic). Drugs that come in dark containers should be covered in foil or an alternative light blocking material and stored in a dark place to avoid faster degradation.
Generally, if a drug is diluted or mixed with another compatible drug and put into a sealed, sterile container, it expires in thirty days (or at the earliest expiration date of the component drugs, whichever comes first). If there is peer-reviewed evidence available that a specific drug or cocktail is sterile and efficacious beyond 30 days, that may be used as justification to keep mixtures longer.
A rodent anesthetic cocktail, when stored in a sterile sealed container, may be kept up to one month. However, there is published evidence that ketamine-acepromazine-xylazine (KAX) dilution is safe and efficacious for 180 days.4 This also applies to ketamine-xylazine (KX). This solution does not need to be refrigerated. For dilutions or cocktails beyond those listed in this policy, references should be included in the IACUC protocol if they are to be kept beyond 30 days.
Other: Contact the IACUC office or veterinary staff for guidance on materials not specifically addressed above.
Responsible Parties
Principal Investigators are responsible for: preparing and submitting applications; making modifications in applications in order secure IACUC approval; ensuring adherence to approved protocols; ensuring that all personnel have completed required training; and reporting any adverse events to the IACUC.
The Animal Welfare Program and the Institutional Animal Care and Use Committee are responsible for overseeing implementation of and ensuring compliance with this policy.
The Attending Veterinarian has been delegated authority to implement BU’s veterinary care program, and to oversee the adequacy of all other aspects of animal care and use.
Animal Welfare Act
Guide for the Care and Use of Laboratory Animals, Eighth Edition
- DenHerder, J. M., Reed, R. L., Sargent, J. L., Bobe, G., Stevens, J. F., & Diggs, H. E. (2017). Effects of time and storage conditions on the chemical and microbiologic stability of diluted buprenorphine for injection. Journal of the American Association for Laboratory Animal Science: JAALAS, 56(4), 457-461.
- Kawano, H. K., Simonek, G. D., Moffitt, A. D., Tahara, J. M., & Brignolo, L. L. (2019). Sterility and stability of diluted meloxicam in compounded multi-dose vial after 365 Days. Journal of the American Association for Laboratory Animal Science: JAALAS, 58(5), 594-596.
- Matthews, K. A., & Taylor, D. K. (2011). Assessment of sterility in fluid bags maintained for chronic use. Journal of the American Association for Laboratory Animal Science: JAALAS, 50(5), 708–712.
- Taylor, B. J., Orr, S. A., Chapman, J. L., & Fisher, D. E. (2009). Beyond-use dating of extemporaneously compounded ketamine, acepromazine, and xylazine: safety, stability, and efficacy over time. Journal of the American Association for Laboratory Animal Science: JAALAS, 48(6), 718-726.
- Xu, J. J., Renner, D. M., & Lester, P. A. (2021). Strength and sterility of stock and diluted carprofen over time. Journal of the American Association Laboratory Animal Science: JAALAS, 60(4), 470-474.
History
Effective Date: 01/04/2022
Next Review Date: 01/03/2025
First Approved: 10/XX/2008 as “Conditional Use of Expired Medical Materials”
Revised: 01/08/2019, 01/28/2014