Monday, July 27, 2009 - 3:00 PM
S38
Utilizing QbD principles to shorten timelines to large-scale performance qualification lots
Susan Abu-Absi, LiYing Yang, Patrick Thompson, Bernhard Schilling, and Abhinav Schukla. Manufacturing Sciences, Bristol-Myers Squibb Co., P.O. Box 4755, Syracuse, NY 13221
The timelines for development, scale-up and validation of processes for biological products are increasingly compressed. Quality by Design (QbD), as described in ICH Q8, begins during development to establish robust processes and continues through process characterization. QbD principles of process characterization are applied to efficiently and systematically examine the impact of process inputs and their interactions via a risk-based approach. This knowledge is then used to define controls at select process steps to ensure high product quality. Rapid progression to manufacturing-scale performance qualification lots can be achieved by leveraging small-scale characterization data to define the in-process control (IPC) strategy.
This presentation will highlight the successful establishment of an IPC strategy for a fed-batch cell culture process prior to manufacturing-scale experience. The IPC was developed to ensure process robustness and an additional requirement of analytical comparability to an earlier process version. DOE studies were conducted to classify key process parameters, establish ranges of operability and gain a quantitative understanding of the impact of critical process parameters on critical quality attributes. Moreover, a linkage between upstream and downstream unit operations was established to define harvest criteria.