The first step is selection of the primary package system components (vial, stopper, seal). As discussed in the previous blog posting, Storage of Cell Therapies Advantages of Cyclic Olefin Polymer Vials, systems based on Daikyo Crystal Zenith^® cyclic olefin polymer vials offer outstanding performance. The next step is ensuring proper assembly, in particular, determining the elastomer stopper compression level that will provide container closure integrity (CCI). This should be done experimentally; through its Integrated Solutions platform, West has the expertise and facility to both determine proper compression level and verify CCI. Finally, once the drug product is introduced and system is sealed, cooling to storage temperature is performed – ultra-low (-80^oC) for genes, cryogenic (-180^oC, vapor of liquid nitrogen) for cells. Best practice for this begins with controlled cooling (approximately 1^oC/minute) to -80^oC, followed by placement in the ultra-low or cryogenic freezer. Because contents can expand on freezing, safe fill volumes have been established:

For storage at these temperatures, achieving CCI is even more important. Loss of CCI not only causes loss of drug product, but over-pressurization of the package system (as high as approximately 50 lbs/in2). Note that cryogenic storage by immersion in liquid nitrogen is never permissible; on loss of CCI, over-pressurization can be as high as 10,000 lbs/in2. This is discussed in detail in a recent Technical Service Bulletin. For more on how West can help, contact an Account Manager or Technical Customer Support representative.