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Developing a Stability Rationale for Shipment of Thermally Sensitive Drugs & Combination Product

Stability Rationale for Shipment of Thermally Sensitive Drugs

Combination products are a growing product area and there is an increasing need for packaging to provide product temperature protection resulting from the large molecule/protein structures of drug-devices, biologics-devices, and the growth of regenerative medicines. I will provide some useful references for the packaging engineer to use to build their thermal packaging systems requirements and processes.

As a starting point, a very good reference primer on temperature sensitive packaging can be found in an article written by Mr. Kevin O’Donnell, Exelsius Cold Chain Management, published in “Healthcare Packaging” magazine. Kevin walks you through 10 steps to develop a validated time or temperature sensitive package.

Regarding external compliance and guidance, I would like to highlight two documents which are used for regulatory guidance on storage and shipment of regulated drugs and devices. USP, US Pharmacopeia, USP 29, Chapter 1079, “Good Storage and Shipping Practices” and PDA, parenteral drug association, Technical Report 53: Guidance for Industry, Stability Testing to support distribution of new drug products. These are two documents that I highly recommend obtaining if you need to understand the temperature storage and shipping guidance around any drug products or combination products containing drugs and devices.

USP 29, Chapter 1079, “Good Storage and Shipping Practices” provides general guidance concerning storing, distributing and shipping of pharmacopeial preparations. If you are involved in a drug-device product, this USP chapter is a basic reference document for procedures necessary to maintain proper storage environments to ensure integrity and efficacy to the end user.

The Parenteral Drug Association, PDA, has developed Technical Report 53 to address the stability studies that a manufacturer has performed in order to support the distribution conditions of that product. A concept from Technical Report 53 that I highlight here is the concept of a stability budget. A stability budget considers the results of long term, accelerated, freeze-thaw and temperature cycling studies to determine the amount of time out of storage that a drug substance may experience without any significant risk to quality. The temperature cycling studies can include extreme temperature studies to include accidental thermal exposures or temperature excursions to the product.

An important concern of stability testing is the impact of a significant temperature stress early in the shelf life of the drug product. Even if the results of the testing would indicate no significant effect on the quality of the drug product on an immediate basis, what is the potential long term impact? PDA Technical Report 53 suggests that if no significant trend is observed over six months under accelerated conditions, then concerns above for more extreme temperature excursions for much shorter times may be deemed negligible.

My recommended take away—work with your product development team to design your drug product stability testing to include at least one study with temperature extremes (based on your supply chain data) together with freeze-thaw cycling and then followed by accelerated aging to front load your product stability test with anticipated temperature excursions and freezing and thawing. In this way, you will have data to support longer term effects of temperature extremes on your product performance. This will allow for the most cost effective thermal packaging system for your product. Real time aging is always required to back up your accelerated aging studies.


Karen K. Greene, CPP is Vice President, Client Solutions Western Region, Network Packaging Partners and President, Life Pack Labs. You can contact her at or visit her contributor page.

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