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Singh-finalBiotherapeutic drug substances are very often stored under frozen conditions to maximize their use period and decouple this use period from drug product shelf life. Almost all biotherapeutic drug products are labeled to be stored under refrigeration, although at early stages in development, these may also use frozen state storage. Biopharmaceutical operations are increasingly being conducted on a global scale in different regions and countries, requiring materials to be shipped at various stages in the processing and distribution of the product. For example, a biotherapeutic drug substance may be produced in the United States, converted to drug product in the European Union and then distributed worldwide for clinical trials or for sale. The monetary value of the material being shipped is often very high, and the consequences of loss of control of the shipping/storage conditions can be significant both from an economic and from a supply perspective.


As a consequence, frozen-state storage and cold-chain transport have become key operations in the development and commercialization of biopharmaceuticals. The science and technology of these operations has advanced significantly over the last few years, moving from empiricism to fundamental understanding. New cold-chain technology has been developed for storage and for shipping, including phase change materials and electromechanical systems (e.g., Envirotainer , Cold Chain Technologies , Cryopak , Thermosafe). Likewise, monitoring and reporting technologies are being improved (e.g., Dyzle). Regulatory requirements have also been formalized, and a number of guidelines have been published on good distribution practices. Development studies are conducted to assess the impact of possible temperature excursions and provide data on viability of material that has undergone excursions. Qualification guidance for active temperature controlled systems has also been published by the Parenteral Drug Association.

The minisymposium session Storage and Shipping of Biopharmaceuticals has been organized for the 2015 AAPS National Biotechnology Conference to look at current developments in this field. Topics to be covered include the cold chain aspects in the new United States Pharmacopeia chapter Good Distribution Practices, a case study on the development of frozen state container/closure systems, and the concept of “stability budget.”

Satish Singh, Ph.D., is a research fellow at Pfizer in the Biotherapeutics Pharmaceutical Sciences group. He has expertise in formulation, product and process development activities for biologics and therapeutic vaccines, and is involved with regulatory aspects of biologics development.