Summary and Outlook
As demand and titers continue to increase for MAbs, the DSP costs will become an increasingly dominant proportion of the COG/g
with the DSP handling capacity representing a potential bottleneck that could reduce productivity. These factors have encouraged
a shift in development efforts toward new DSP solutions that improve the process economics and alleviate bottlenecks. Consequently,
the industry is taking advantage of improvements that affect the critical process economic drivers by looking to: improve
the overall DSP yield and reduce the batch duration using platform processes based on two chromatography operations without
intermediate buffer exchange steps; increase DSP capacity by taking advantage of improvements in chromatography resins that
allow increased throughput over shorter times; and lower buffer demands and validation costs using new technologies such as
membrane chromatography.
These improvements will be important for facilities that already have large bioreactor capacities installed, and also for
newer facilities that will probably be built with smaller capacities with flexibility in mind to allow rapid turnaround between
campaigns for multiple products. Furthermore, if cheaper and faster expression technologies, such as glycoengineered Pichia pastoris, become more widespread, there will be an even greater spotlight on DSP costs. Although new DSP approaches may present complex
and challenging problems to tackle, it is anticipated that this line of enquiry will dominate studies in the near future so
that more cost-effective MAb platform technologies can evolve. However, with each of these new approaches there are trade-offs
and potential risks that need to be evaluated to assess the impact on process economics. The capacity to cost such alternatives
provides a common basis for such decision-making and will prove a vital tool for bioprocess designs in the future. Process
economics can also be dramatically improved if the potency of MAbs is increased; recent efforts in this area are an encouraging
sign for the future.
This is an excerpt from the chapter entitled "Process Economic Drivers in Industrial Monoclonal Antibody Manufacture" in the
2009 John Wiley and Sons book Process Scale Purification of Antibodies edited by Uwe Gottschalk.
SUZANNE S. FARID, PhD, is a senior lecturer (associate professor) at the Advanced Centre for Biochemical Engineering, Department of Biochemical
Engineering, University College London, London, UK, +44 20 7679 4415, s.farid@ucl.ac.uk
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