2.68 - Aseptic Operations

https://doi.org/10.1016/B978-0-08-088504-9.00148-3Get rights and content

Abstract

Controlling microbial contamination during bioprocess operations is reviewed using laboratory and pilot scale facility experience in combination with literature examples. The primary focus is biologics oriented, for the production of recombinant proteins or monoclonal antibodies, using microbial fermentation or cell culture. Recommendations are described for equipment design, process operation procedures, managing maintenance, validation, and sterility analysis. These are discussed across a bioprocess from fermentation, purification, formulation, and fill of the drug product. The implementation of disposables to reduce the number of sterile manipulations and to increase sterility assurance is discussed. Finally, a summary of the relevant contamination testing methods is presented in conjunction with a strategy for contamination investigation. This provides a framework for sustaining low contamination rates for microbial and cell culture processes.

References (0)

Cited by (1)

David Pollard is an associate director of biologics process development at the Merck Research Labs. He has over 15 years of experience in leading cross-functional teams for the process development of anti-infectives, bioconversions, vaccines, and therapeuticc proteins, using a range of expression systems. This experiences include working interactions of lead optimization with basic research, relationship building with CMOs and tech transfers to manufacturing. Since completing his PhD in Biochemical Engineering at University College London, Pollard has written over 20 first author manuscripts including a similar number of second author papers, patents, and oral presentations. These cover a diverse range of activities from the first industrial example of fermentation monitoring using in situ mid-IR to fermentation scale-up strategy and bioconversion process development. His current interests include biologics process development efficiency by the introduction of effective scale-down automation technology. Recently, David has managed an upstream process development group of 22 scientists for the production of protein therapeutics and monoclonal antibodies. His current Merck assignment is leading project groups for single-use technology and automation as part of a team to implement biologics new and enabling technologies.

View full text