바이오의약품 생산용 세포배양배지의 오염관리 방안 연구

Contamination Control Strategy of Cell Culture Media Used for Manufacture of Biopharmaceutical Products

The revision and enforcement of EU GMP Guideline Annex 1 in 2023 makes it mandatory to establish a contamination control strategy to ensure the safety of sterile pharmaceutical products. For biopharmaceutical manufacturers, the safety assurance begins with critical raw materials such as cell culture media. Therefore, these regulations may now apply to cell culture media manufacturers. However, cell culture media are not classified as pharmaceutical products, and there is currently a lack of a scientific and systematic approach to ensure safety. Given this lack, the purpose of this study was to apply the principles of EU GMP Guideline Annex 1 for sterile pharmaceuticals to cell culture media used in the manufacture of biopharmaceutical products. This study systematically identified potential sources of contamination in a cell culture media manufacturing environment and proposed a contamination control strategy using two quality risk management tools, Hazard Analysis and Critical Control Points (HACCP) and Failure Mode and Effects Analysis (FMEA), according to ICH Guideline Q9. Using HACCP, the major sources of contamination in the manufacturing environment were identified as Critical Control Points which were subsequently evaluated quantitatively using FMEA. In line with the contamination control strategy requirements of EU GMP Annex 1, a strategy to reduce contamination risks was proposed providing an effective response framework. In conclusion, this study provides foundational data to support advancement of quality systems in biopharmaceutical manufacturing by presenting an empirical model for a scientific and systematic approach to contamination control in the manufacture of cell culture media for biopharmaceutical products.