Facing the Challenges in Vaccine Upstream Bioprocessing - 20

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

the process are exchanged to become fully
continuous, and those which would benefit from
intrinsic step process improvements. A conventional fed-batch process can be nicely coupled to
continuous downstream purification with one of
several steps performing continuous batch (flipflop) or countercurrent processes (capture and
polish). If combined with membranes and singleuse concepts, we expect a significant productivity
increase having an implication on both CAPEX
and OPEX. We estimate that besides the improvement in product quality, both CAPEX and OPEX
could be lowered by 50%.
Mr. Zijlstra: Continuous and single production
plants will be able to lower costs several fold and
produce the same amount of product as current
standard stainless-steel facilities. This facilitates
greenfield investment decisions and reduces
investment risks considerably.
Dr. Lacki: A standard argument is that equipment for a continuous line will be smaller. At the
same time, truly continuous operations run 24/7,
which means that even the downstream opera20

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tion might need to be run in shifts, increasing
labor cost. Undoubtedly, continuous operation
will be more control-heavy. Cost of controllers,
equipment maintenance, contingency plans-all
of it needs to be considered when evaluating
continuous processes. That said, advances in
detection technologies and modularization of
standard processing technologies (e.g., prepacked
columns, flow paths, and even introduction of
humanoid robots) will bring us closer toward
continuous processing.
GEN: To date, why do you think so few biologic
manufacturers have explored the use of an endto-end continuous line?
Dr. Morbidelli: We think there are actually quite a
few [therapies] in the exploration phase for either
perfusion culture or continuous downstream or
both. We know that manufacturers are currently
exploring continuous systems at the pilot scale
[that] would move into clinical trial manufacturing in 2018. FDA has consistently supported
and guided continuous manufacturing and we
believe that the regulatory risk for a new product

development is low. As with any new technology,
continuous manufacturing for biologics will
need some evaluation time to be taken into the
commercial setting, as the technology has to
show that it is robust and provides the expected
benefits. There might be a level of confusion as
to the quality of available technology platforms
with different claims on performance/productivity. We believe that a strict scientific approach
in evaluating the benefits of each technology may
drive the choice to platforms that are simple and
robust, reducing the validation effort and likeliness of hardware failure in continuous operation.
Dr. Lacki: The short answer could be, a lack of
real need. The industry is still young, and fairly
profitable. The focus from the beginning was
more on drug safety than on reducing the cost
of goods. But as in the case of all industries, with
technology maturation comes challenges related
to implementation of technological solutions
that will be able to address the market pressure,
without sacrificing the safety profile of a product.
The pressure is both related to the pure amount
that needs to be produced (number of medicines

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Facing the Challenges in Vaccine Upstream Bioprocessing

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