Using enhanced development tools offered by analytical Quality by Design to support switching of a quality control method

• Published in: Biotechnology and bioengineering Vol. 120; no. 11; pp. 3299 - 3310
• Main Authors: Simeoni, Philippe, Deissler, Michael, Bienert, Roland, Gritsch, Manuela, Nerkamp, Jörg, Kirsch, Stephan, Roesli, Christoph, Pohl, Thomas, Anderka, Oliver, Gellermann, Gerald
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2023
• Subjects: Capillary electrophoresis; Commercialization; Control methods; Data acquisition; Design; Design analysis; Design of experiments; Electrophoresis; Mathematical analysis; Monoclonal antibodies; Parameters; Pharmaceutical industry; Polyacrylamide; Principles; Quality control; Quality management; Risk assessment; Sodium dodecyl sulfate; Sodium lauryl sulfate; Stability tests; analytical quality by design; method development; analytical target profile; CE-SDS reduced; design of experiments
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.28517

Quality by Design (QbD) principles play an increasingly important role in the pharmaceutical industry. Here, we used an analytical QbD (AQbD) approach to develop a capillary electrophoresis sodium dodecyl sulfate under reducing conditions (rCE-SDS), with the aim of replacing SDS-polyacrylamide gel electrophoresis (SDS-PAGE) as release and stability test method for a commercialized monoclonal antibody product. Method development started with defining analytical method performance requirements as part of an analytical target profile, followed by a systematic risk assessment of method input parameters and their relation to defined method outputs. Based on this, design of experiments studies were performed to identify a method operable design region (MODR). The MODR could be leveraged to improve method robustness. In a bridging study, it was demonstrated that the rCE-SDS method is more sensitive than the legacy SDS-PAGE method, and a conversion factor could be established to compensate for an off-set due to the higher sensitivity, without losing the correlation to the historical data acquired with the former method. Overall, systematic application of analytical Quality by Design principles for designing and developing a new analytical method helped to elucidate the complex dependency of method outputs on its input parameters. The link of the method to product quality attributes and the definition of method performance requirements were found to be most relevant for derisking the analytical method switch, regarding impact on the control strategy.