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Advancing Our Cell Culture Platform: Incorporating Lessons Learned and New Technologies

  • Carole Heath
Chapter
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume XI)

Abstract

Based on experience with multiple molecules, Amgen developed a cell culture platform for process development of monoclonal antibodies and Fc fusion proteins to increase the speed to market and to minimize resource commitment during early phase development. While most parameters are pre-specified, a small subset does require some optimization because of performance differences across molecules and their cell lines. As measured by cell culture performance (titer and scalability) and business metrics, use of the platform has been very successful. A couple of Amgen’s earlier projects, however, did not perform as well as others under the platform conditions. The atypical molecules have required more time and/or resources to meet performance goals and, even then, they did not necessarily achieve the targeted levels. Despite the difficulties, the experience of working with these molecules did provide some information for improving overall platform success at both bench and pilot scales. Periodic updates of the platform by a peer-review process that incorporates “lessons learned” and advances from in-house technology development have resulted in higher titers, greater consistency in performance across Amgen sites, and improved operations in our pilot-scale and clinical manufacturing environments. While intended as an approach for early phase molecules, experience gained over multiple projects has resulted in evolution of the platform that is moving us closer to a single phase of upstream process development.

Keywords

Clone Selection Host Cell Protein High Mannose Culture Duration Cell Culture Process 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

CE-SDS

Capillary electrophoresis sodium dodecyl sulfate

CHO

Chinese hamster ovary

cIEF

Capillary isoelectric focusing

DHFR

Dihydrofolate reductase

DOE

Design of experiments

GMP

Good manufacturing practice

HMW

High molecular weight

HTS

High throughput screening

IND

Investigational new drug

LMW

Low molecular weight

MAb

Monoclonal antibody

P&AS

Process and Analytical Sciences

QbD

Quality by design

SEC

Size exclusion chromatography

SE-HPLC

Size exclusion high performance liquid chromatography

Notes

Acknowledgments.

The author thanks Thomas Seewoester, Victor Fung, Brian Hubbard, and the Cell Science & Technology Groups in Seattle, WA and Thousand Oaks, CA for contributions to this article.

Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  1. 1.Process DevelopmentAmgen Inc.SeattleUSA

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