Michelle Then, PharmD, MBA

The pharmaceutical industry continually develops novel therapeutics, many of which require refrigeration and are associated with high costs. In the event of such temperature excursions as a breach in the cold chain protocol, pharmacists are looked upon as experts who can deter- mine whether medications are still viable. Besides resulting in a quantifiable loss, temperature excursions can expose medications to temperature insults that lead to chemical (eg, potency, antigenic) and physical (eg, dissolution, particulates)

 changes in the properties of the drug product. The clinical implications of excursions include a subpotent product, packaging contamination, patient harm, and therapeutic failure.

For medication stability inquiries during temperature excursions above 8oC, many resources are available, including medication package inserts that typically indicate recommended storage environments (Table5-24). Peer-reviewed articles, such as “Room-Temperature Storage of Medications Labeled for Refrigeration” by Cohen et al

from 2007, are also an asset when determining the viability of high-cost refrigerated medications. An abundance of guidance for storage conditions above manufacturers’ recommendations was noted in our research. However, it was challenging to find published information on temperature excursions below recommended refrigeration temperatures.

In the event of a break in the cold chain process used to maintain high-cost medications, a privileged pool of data, beyond what is required for package labeling, typically exists for reference. Federal regulations mandate that manufacturers ensure product'quality, essentially until'patient treatment.

 Because'of the immense aggregate'cost of a medication passed'through full drug development and supply chain'processes, manufacturers'of high-cost medications'routinely conduct additional distribution stability studies to ascertain a'product’s temperature limitations with respect to product integrity and quality.

 This information is generally reserved for “in-house” use during distribution and transport to ensure drug products endure temperature excursions during shipping and handling, as well as meet meticulous distribution protocols. If used, this unpublished data could help your pharmacy recoup over $200,000 in pharmaceutical products, including medications for which there is a national shortage.

Recent breaches in the cold chain process of select high-cost medications led to their exposure to freezing temperatures for more than 4 hours, which prompted preemptive action to ensure patient safety and product quality. After taking inventory, a clinical specialist from each manufacturer of a product affected by the breach was contacted with an inquiry into “temperature excursions.” Specifics (ie, lot number, expiration date, exposure temperature, duration of exposure, return time to refrigerator temperature) were provided at the request of the manufacturer. With each conversation, the manufacturer was asked to send a letter stating its temperature excursion data for the medication in question. This written confirmation of stability should not be over- looked. Once all manufacturer conversations had been properly documented, the medications deemed unaffected by the breach were specially marked in case they might need to be re-pulled from hospital supply. This process is an example of how health systems can use resources just behind the curtain. All it takes is a few good ideas, a few good people, and a few good hours.

				Based on information provided, product use supported by manufacturer

				Manufacturer gave verbal in-house temperature excursion data to support use of product after site-specific breach

				Prior to 2012, Botox was approved for storage in the freezer; product use supported by manufacturer

				Based on site-specific breach details, product use supported by manufacturer

				Product found to be stable after a freeze-thaw cycle

				Unreconstituted vials remain stable if exposed to —10°C to +2°C during 1 continuous excursion of ≤12 hr

				Unreconstituted vials remain stable if exposed to —25°C to +25°C during 1 continuous excursion of ≤7 days

				Specific breach conditions will have 

Articles

The pharmaceutical industry continually develops novel therapeutics, many of which require refrigeration and are associated with high costs. In the event of such temperature excursions as a breach in the cold chain protocol, pharmacists are looked upon as experts who can deter- mine whether medications are still viable.