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A Different Perspective: How Much Innovation Is Really Needed for Monoclonal Antibody Production Using Mammalian Cell Technology?

  • Brian Kelley
  • Robert Kiss
  • Michael Laird
Chapter
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 165)

Abstract

As biopharmaceutical companies have optimized cell line and production culture process development, titers of recombinant antibodies have risen steadily to 3–8 g/L for fed-batch mammalian cultures at production scales of 10 kL or larger. Most new antibody products are produced from Chinese Hamster Ovary (CHO) cell lines, and there are relatively few alternative production hosts under active evaluation. Many companies have adopted a strategy of using the same production cell line for early clinical phases as well as commercial production, which reduces the risk of product comparability issues during the development lifecycle. Product quality and consistency expectations rest on the platform knowledge of the CHO host cell line and processes used for the production of many licensed antibodies. The lack of impact of low-level product variants common to this platform on product safety and efficacy also builds on the established commercial history of recombinant antibodies, which dates back to 1997.

Efforts to increase titers further will likely yield diminishing returns. Very few products would benefit significantly from a titer greater than 8 g/L; in many cases, a downstream processing bottleneck would preclude full recovery from production-scale bioreactors for high titer processes. The benefits of a process platform based on standard fed-batch production culture include predictable scale-up, process transfer, and production within a company’s manufacturing network or at a contract manufacturing organization. Furthermore, the confidence in an established platform provides key support towards regulatory flexibility (e.g., design space) for license applications following a quality-by-design strategy.

These factors suggest that novel technologies for antibody production may not provide a substantial return on investment. What, then, should be the focus of future process development efforts for companies that choose to launch antibody products using their current platform? This review proposes key focus areas in an effort to continually improve process consistency, assure acceptable product quality, and establish appropriate process parameter limits to enable flexible manufacturing options.

Keywords

Cell culture production CHO platform CHO technology Continuous processing Innovation Mabs Mammalian cell technology Monoclonal antibodies, Perfusion 

Notes

Acknowledgements

Numerous technical staff at Genentech and Roche have contributed over the years to the collective platform process and the understanding of its capabilities, its historical challenges, and the opportunities for future improvements briefly summarized in this chapter. In addition, further acknowledgement is warranted to the many individuals and companies within the biotechnology industry that have driven the advances responsible for making the mammalian cell culture processes for antibody production the highly productive systems they are today.

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Vir Biotechnology, Inc.San FranciscoUSA
  2. 2.Sutro Biopharma, Inc.San FranciscoUSA
  3. 3.Genentech (A Member of the Roche Group)San FranciscoUSA

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