Variation in the manufacturing reproducibility of autologous cell-based products depending on raw material shipment conditions

Manabu Mizutani; Hiroshi Terunuma; Hazuki Samejima; Keisuke Ashiba; Masahiro Kino-Oka

doi:10.1016/j.reth.2019.04.005

Variation in the manufacturing reproducibility of autologous cell-based products depending on raw material shipment conditions

Regen Ther. 2019 Apr 27:12:102-107. doi: 10.1016/j.reth.2019.04.005. eCollection 2019 Dec 15.

Authors

Manabu Mizutani¹, Hiroshi Terunuma², Hazuki Samejima², Keisuke Ashiba², Masahiro Kino-Oka¹

Affiliations

¹ Division of Science and Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
² Biotherapy Institute of Japan, 2-4-8 Edagawa, Koto-ku, Tokyo 135-0051, Japan.

Abstract

To prepare an autologous cell-based product in a cell processing facility, the raw material, which is collected from a patient, must first be shipped from a medical institution to the facility. The quality of this raw material varies depending on the patient, and variations due to transport methods also occur. Because the quality must be uniform and manufacturing processes need to be adjusted to account for these variations, determining the effect of shipment conditions on raw materials is very important for estimating cell manufacturability in the process design. In this study, a group of medical institutions located in different areas requested similar cell-based products processed by the same manufacturing method to a company that is licensed under the Act on the Safety of Regenerative Medicine in Japan. Manufacturing reproducibility was analyzed based on 456 cell batches received from two clinics that were processed used the same manufacturing method. The specific growth rates that were observed in the early growth phase supposed that the proliferative potential of the primary cells in the raw material was influenced by transit time. Simultaneously, the variation of the specific growth rates in the late phase were supposed to be hardly occurred. Thus, this study evaluated shipping conditions of the raw materials for an autologous cell-based product, and a strategy for verifying the influence of transportation on quality in manufacturing was suggested.

Keywords: Autologous cells; Individual difference; Manufacturing reproducibility; Specific growth rate; Standard deviation; Transit time.