Refrigeration of medications is often required to maintain medication stability and increase a drug's shelf life. Any break in cold-chain storage can potentially affect the safety and efficacy of a medication that requires special temperature requirements.
With the increased availability of therapeutic protein products, such as biologic agents and vaccines, the need for cold storage has increased. It is essential that pharmacists and pharmacy technicians are knowledgeable about these requirements.
A study was conducted examining Lexicomp and Micromedex databases for information on all new molecular entities and new therapeutic biologic products approved by the FDA between January 1, 2000, and June 30, 2021. The intent of this project was to determine the completeness of information on the maximum duration at which refrigerated medications can tolerate room temperature (RT) excursions while maintaining stability and potency. RT was defined as 20 to 25 degrees Celsius (68-77 degrees Fahrenheit) based on the United States Pharmacopoeia's definition of "controlled RT." Refrigeration was defined as 2 to 8 degrees Celsius (36-46 degrees Fahrenheit).
If RT storage was adequate for the medications studied, no further action was taken. However, if either Lexicomp or Micromedex indicated that refrigeration (or a temperature colder than RT) was required for storage, the investigators checked the most recent version of the product's prescribing information. Information was gathered on the allowable excursions of the intact, unaltered product from RT and for allowable temperature excursions for the drug during various stages of preparation for administration (e.g., following reconstitution and/or dilution). If this information was not available in the FDA prescribing information, the investigators contacted the pharmaceutical manufacturer via telephone or email. Information on drugs withdrawn from the market were excluded from further analysis (n = 8).
The investigators found that of the 705 products or formulations approved during this 20-year period, 35% (n = 246) required cold storage. Acceptable periods of excursion to temperatures at RT or higher were identified for 214 products. These products included SC, IV, IM, intravitreal, oral, intraocular implant, ophthalmic, topical, intralesional, vaginal, inhalation, and intrathecal preparations, as well as hyaluronidase injectable.
The data related to allowable RT excursions were completely unavailable for 32 products (or 13% of those approved) since 2000. Of these agents, 10 were IV (bevacizumab, brentuximab vedotin, copanilisib, dinutuximab, enfortumab vedotin-ejfv, fam-trastuzumab deruxetecan-nxki, idursulfase, lisocabtagene maraleucel, posaconazole, and sacituzumab govitecan-hzly); nine were SC (abatacept, afamelanotide, burosumab-twza, canakinumab, mecasermin, ofatumumab, parathyroid hormone, pegcetacoplan, and risankizumab-rzaa); six were IM (abobotulinumtoxinA, elapegademaase-lvlr, fulvestrant, influenza A H5N1 vaccine, meningococcal groups A, C, Y, W vaccine, and prabotulinumtoxinA-xvfs); three were oral (larotrectinib, macimorelin acetate, and peanut allergen powder-dnfp); and one each were intraventricular (cerliponase alfa), otic (finafloxacin), intravitreal (pegaptanib), and topical (sinecatechins) preparations.
This lack of readily available information on the safety of temperature excursions can lead to unexpected adverse patient effects, reduced therapeutic efficacy, and unnecessary drug waste and expenditures.
Pharmacists and pharmacy technicians should be aware of this list of drugs for which temperature excursion information is unavailable so that they can use extra caution when handling these products in order to avoid safety, efficacy, and cost issues.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
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