The principles of PAT can be applied to biopharmaceutical products, not just small-molecule drugs. Biopharmaceutical processes,
particularly the cultivation process step, are intrinsically more complex than processes used to make chemical drugs. By applying
a sound scientific approach for development of process understanding and by using the appropriate sensors and monitoring techniques,
a biopharmaceutical process can become as stable and capable as any world-class manufacturing process.
The ultimate benefits of PAT application are mitigation of risks (failures) during manufacturing, flexibility in process optimization,
and safer and more pure products. The effort to understand the process will be rewarded when scale-up, process changes, or
even medium optimizations are more easily implemented throughout the product's manufacturing lifetime. Furthermore, on-line
monitoring of product quality and subsequent adjustment to the optimal trajectory will lead to fewer failed runs and a more
consistent product of high quality. Real-time quality assurance will lead to shorter cycle times and fewer stockpiles. This
case study shows that monitoring cell cultivation, combined with process understanding condensed in chemometrical models,
allows the optimal harvest point to be determined, and thereby allows the monitoring of product quality throughout the batch,
opening the possibility for real-time product release. This increased process understanding leads to shorter production times
and faster detection of batch failures, reduces cost and increases productivity.
These benefits have encouraged FDA to make PAT application the mandatory backbone of future pharmaceutical process development
and manufacturing. This case study demonstrates that it can even be applied to a complex and undefined product such as a whole-cell
vaccine, which means it should also be feasible for any pharmaceutical or biopharmaceutical product currently on the market.
The PAT initiative can therefore help to increase the safety and efficacy of medicines while reducing the time-to-market for
new products and the operational costs of manufacturing. This situation is good news for regulatory inspectors, manufacturers,
Kjell François, PhD,* is senior PAT consultant for Siemens NV, Curie Square 30, 1070 Brussels, Belgium, Kjell.Francois@siemens.com
. Mathieu Streefland, PhD, is project leader of the PaRel project at The Netherlands Vaccine Institute (NVI). Rebecca Vangenechten is a consultant for business and project development life sciences USA, and Leo Hammendorp is director of business and project development for global life sciences, both at Siemens NV.
*To whom all correspondence should be addressed.
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