Bulk storage, freezing, and transfer are important steps which ensure that the final product is safely and promptly delivered to fill–finish sites and patients. Current bulk freeze-thaw practices use predominantly stainless steel systems. Unfortunately, stainless steel bulk freeze-thaw systems have their share of disadvantages. This article addresses Genentech's evaluation of single-use technologies for bulk freeze-thaw, storage, and transportation, including operational and functional testing, the mechanical properties of film, controlled freezing, and the risks involved in bulk shipping.
Storage Hold Process and Transporting Bulk
As it becomes compulsory to lengthen the lifetime of a protein product to reach patients worldwide, considerable effort and thought must go into the storage hold process. One option for bulk protein storage is holding the product in a liquid-state, either in a stainless steel tank or a disposable container. Although a viable option, the use of liquid-state storage has its own drawbacks. First, proteins may aggregate, resulting in product loss. Second, oxidation may cause some spontaneous reactions that would be detrimental to the bulk. Regardless of these concerns, there has been data that proves that this option may be suitable under certain conditions.1
One example of a stainless steel freeze-thaw system would be Sartorius-Stedim Biotech's CryoFin. CryoFin cryopreservation technology consists of several separate components that include CryoVessels, thermal control units, and mixers. The freeze-thaw is controlled by active and passive heat transfer surfaces and is specifically designed for large-scale freezing of biotherapeutics. Although this system is novel and offers valuable flexibility to both the manufacturers and clients, it has some drawbacks. For example, because of its need to be tested and validated before use for sterile hold and other sampling and validation qualifications (which could take months or even years), by the time a stainless steel system is commissioned, the particular campaign in which the system might have been useful may have already been completed. Furthermore, the amount of capital necessary to invest in such a system is significant compared to equivalent disposable systems.