CHANGING SITUATION
The biopharmaceutical manufacturing industry has accepted disposable components in manufacturing in the same way that food
services and other industries have; disposables are seen as effective and useful tools to be adopted within each manufacturer's
system. The regulated nature of biopharmaceutical manufacturing, however, and the associated risk of using new technologies
on multimillion dollar batches of pharmaceutical ingredients, differentiates it from other industries.
Though some early visionaries had projected rapid conversions to fully disposable manufacturing facilities, these components
have been integrated into production facilities ad hoc rather than using a whole-systems approach, and disposables usage has
grown only moderately. This stepwise integration, which started more than a decade ago with basic filtration components, tubing,
and connectors, has progressed to include media and buffer bags, and is now moving on to disposable bioreactors, mixing devices,
sampling devices, and disposable probes. The regulatory and operational fears associated with the use of disposables early
on have rarely materialized.
As current technologies develop, decisions to use disposables are being based on factors such as whether they are compatible
within a given system or if they make sense economically. Typical issues of single-source vendors are emerging. For example,
companies may be more reluctant to use disposable bioreactors until there is sufficient competition. In comparison, similar
concerns are not seen with filters, since competition is greater and these components are well established.
Today, most disposables are used for process development and clinical-scale manufacturing. There might not be any substantial
growth in the use of disposables until they break into the production of licensed products at commercial scale. For this to
occur, regulatory strategies will be required for changeover from hard-piped systems to disposables. Because legacy systems
are unlikely to shift to a disposable approach, expansion in the use of disposables will happen only for current pipeline
products, not the existing ones. A major exception may be vaccines, where pressure for new technology drives greater use of
single-use components.
Leachables and extractables, a current regulatory concern in the industry, is an issue vendors heard over 15 years ago regarding
filters. At that time, as today, disposable components, including filters, required extensive testing to ensure compatibility.
Changing conditions required product-and system-specific analysis. Such product compatibility testing will likely always be
required for most disposable products. Still to be decided is whether vendors should take responsibility for leachables testing,
whether industry should improve methods of analysis, or whether should vendors evaluate ways to improve the products themselves.
In the future, increased levels of partnering among vendors and users regarding leachables and extractables will be needed.
Vendors will be expected to identify types of extractables in their products and simplify the process for manufacturers to
identify sources and types of leachables.
THE ROAD AHEAD
Most participants at the IVT meeting tended to agree with industry analysts, and do not expect disposables to radically change
the way biopharmaceuticals are made in the near future. There will continue to be reliance on stainless, fixed common-use
assets and equipment trains. Areas of potential use for disposables include upstream and downstream systems, filtration, tubing
and components, fill–finish, cell therapy, and other applications. Some applications in disposables, however, have the potential
for radically altering production strategies. The meeting participants also discussed potential opportunities for disposables
to improve future biopharmaceutical manufacturing.
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