Biomedical Engineering Reference
In-Depth Information
flexibility is predicated on the level of relevant scientific knowledge provided [1].”
Design space and regulatory flexibility should not be confused with relaxed process
control or increased process variability. Regardless of how wide the design space is,
process consistency is still the goal for commercial manufacturing. Therefore, the
manufacturing process would be performed in a reasonably narrow operating space
based on equipment capability and for maintaining process consistency. Excursions
outside the operating space would indicate unexpected process drift and initiate
appropriate investigations into the cause of the deviation and subsequent corrective
action. As long as operating parameters remain within the design space, however,
product release should not be in jeopardy. As manufacturing experience grows and
opportunities for process improvement are identified, the operating space could be
revised within the design space without the need for postapproval submission. In
addition, process understanding gained from process monitoring can also be used for
future changes to the design space. Such changes should be evaluated against the need for
further characterization and/or revalidation and subsequent filing.
ACKNOWLEDGMENT
The authors would like to thank Duncan Low (Amgen), Yuan Xu (Novartis), Tony Mire
Sluis (Amgen), for their critical reading of the manuscript and helpful suggestions.
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