Facing the Challenges in Vaccine Upstream Bioprocessing - 17

Facing the Challenges in Vaccine Upstream Bioprocessing * Integrated Continuous Manufacturing of Biologics: Trends in the Field

Dr. Najera: Any product with an expensive
chromatography resin is a suitable candidate for
continuous chromatography, especially for earlyphase clinical products, where resin cost can be
cost prohibitive. Continuous capture is also attractive for high-titer processes, since several small
volumes can be used instead of a single large
column. In fact, facility fit limitations are common
for high-titer processes (>5 g/L), and continuous
chromatography can help manufacturers avoid
the capital costs associated with procurement of
large stainless-steel columns (>80 cm diameter)
and associated equipment. Finally, the concept of
integrated continuous manufacture, (i.e., a fully
continuous process), would be best suited for a
well-established late-phase process with a stable
market demand where cost-savings are realized
through basic efficiencies related to batch versus
continuous processing.
Dr. Zydney: This is a difficult question to
answer-it very much depends upon one's
perspective. In some ways, the 'best' candidates

17

| GENengnews.com

Integrated Continuous
Manufacturing of Biologics
Karl Rix, Ph.D.,
Head of Business Unit Bioprocess, Eppendorf
GEN: What types of biologic medications are the best/
most feasible candidates for integrated continuous
manufacture?
Dr. Rix: Besides for the production of less stable proteins
which in a perfusion process are constantly harvested
from the culture, perfusion processes could be especially
advantagous to respond to fluctuations in the market.
Scale can be varied by modulating the process time or by
changing the number of parallel production lines. This can
be easier than traditional scale-up of a fed-batch process.
GEN: The manufacturers of Prezista (Janssen), a
small-molecule drug, got FDA approval to change its
processes to a continuous method. To your knowledge,
are any biologics manufacturers looking into a similar
manufacturing change? Do you think manufacturers are
more likely to address the end-to-end manufacture of a
totally new product, rather than for an existing product?

Dr. Rix: Though there have been examples, it is still quite
unlikely that a manufacturer would change an approved
batch or fed-batch manufacturing process to continous
operation. Usually, the decision for a process mode
will be made in product development. In that phase,
influencing variables, including product titer, costs for
media, labor, and equipment, and product quality, can be
systematically assessed.
GEN: To date, why do you think so few biologic
manufacturers have explored the use of an end-to-end
continuous line?
Dr. Rix: In my view, one issue ist that process
development as well as process monitoring strategies
for continuous processes are less well established
than for traditional fed-batch processes. This includes
among others cell line and media development, online
monitoring technologies, and scale-down model
development. This might increase process development
time and risks. And in my opinion, regulatory
uncertainties are still an issue.
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Facing the Challenges in Vaccine Upstream Bioprocessing

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