Implementing high-temperature short-time media treatment in commercial-scale cell culture manufacturing processes

• Published in: Applied microbiology and biotechnology Vol. 98; no. 7; pp. 2965 - 2971
• Main Authors: Pohlscheidt, Michael, Charaniya, Salim, Kulenovic, Fikret, Corrales, Mahalia, Shiratori, Masaru, Bourret, Justin, Meier, Steven, Fallon, Eric, Kiss, Robert
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2014; Springer Berlin Heidelberg; Springer; Springer Nature B.V
• Subjects: Amino acids; Analysis; Antibodies; Bacteria; Biomedical and Life Sciences; biopharmaceuticals; Biosynthesis; Biotechnological Products and Process Engineering; Biotechnology; Cell culture; Cell Culture Techniques; Cell research; Cellular biology; Culture media; Culture media (Biology); Culture Media - radiation effects; Dihydrofolate reductase; Disinfection - methods; equipment design; filtration; fungi; Heat; High temperature; Hot Temperature; Inactivation; inactivation temperature; Life Sciences; mammals; Manufacturing; Manufacturing industry; Media; Methods; Microbial Genetics and Genomics; Microbiology; Mycoplasma; Process controls; Production methods; Protein expression; Proteins; Raw materials; Reagents; risk; Safety barriers; Studies; supply chain; Supply chains; Technology transfer; Testing; Time Factors; Viruses; Adventitious agents; Cell culture; Large-scale manufacturing; High-temperature short-time
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-013-5451-3

The production of therapeutic proteins by mammalian cell culture is complex and sets high requirements for process, facility, and equipment design, as well as rigorous regulatory and quality standards. One particular point of concern and significant risk to supply chain is the susceptibility to contamination such as bacteria, fungi, mycoplasma, and viruses. Several technologies have been developed to create barriers for these agents to enter the process, e.g. filtration, UV inactivation, and temperature inactivation. However, if not implemented during development of the manufacturing process, these types of process changes can have significant impact on process performance if not managed appropriately. This article describes the implementation of the high-temperature short-time (HTST) treatment of cell culture media as an additional safety barrier against adventitious agents during the transfer of a large-scale commercial cell culture manufacturing process. The necessary steps and experiments, as well as subsequent results during qualification runs and routine manufacturing, are shown.