Practice of Cryopreservation of Cellular Starting Materials from the Asia-Pacific Region: An Industrial Perspective.

Chimeric antigen receptor T-cell (CAR-T) therapy uses autologous T cells from patients to eliminate malignant targets. Cryopreservation of cellular starting materials, particularly fresh leukocytes, is an important step before production. While this promising specialized immune therapy is advancing, regulations have evolved, as specified in the US (21CFR1271) and Europe (EU Annex 1, 1394/2007). Cryopreservation is considered by this as minimal manipulation or is not considered as substantial manipulation unless there is alteration of relevant biological cell characteristics or cellular engineering. Similar consideration has been made by health authorities in Australia and South Korea. Conversely, the health authority in Japan determines if the starting material is applicable to Good Gene, Cellular, and Tissue-based Products Manufacturing Practice based on scientific data regarding the impact on product quality and safety. Whereas regulations have evolved in the US and EU, this is the first article to systemically review, from a manufacturer's perspective, the specific regulatory positions taken towards cryopreservation in Asia-Pacific (APAC) countries, i.e. Japan, Australia and South Korea. These positions generally consider that formulation and cryopreservation should be performed in a closed system, thus protecting cellular starting materials from contaminant exposure with a low-risk approach. Local and centralized cryopreservation logistics are discussed along with optimal implementation practices. The impact of geographic access on cryopreservation logistics, as well as the importance of careful evaluation of logistical and cost aspects for successful supply of CAR-T therapies in APAC, are also discussed.