Simeoni, Philippe, Deissler, Michael, Bienert, Roland, Gritsch, Manuela, Nerkamp, Joerg, Kirsch, Stephan, Pohl, Thomas, Anderka, Oliver and Christoph, Roesli (2023) Using enhanced development tools offered by analytical Quality by Design to support switching of an analytical quality control method. Using enhanced development tools offered by analytical Quality by Design to support switching of a quality control method. pp. 1-12. ISSN doi.org/10.1002/bit.28517

Abstract

Quality by Design (QbD) principles play an increasingly important role in pharmaceutical industry. Here, we used an analytical QbD (AQbD) approach to develop a capillary electrophoresis method under reducing conditions (rCE-SDS), with the aim of replacing 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 (ATP), followed by a systematic risk assessment of method input parameters and their relation to defined method outputs. Based on this, design of experiments (DoE) 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 correlation 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 AQbD 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 critical quality attributes and the definition of method performance requirements were found to be most relevant for de-risking the analytical method switch, regarding impact on the control strategy.

Item Type:	Article
Keywords:	Analytical quality by design; analytical target profile, method development; design of experiments; CE-SDS reduced
Date Deposited:	20 Oct 2023 00:46
Last Modified:	20 Oct 2023 00:46
URI:	https://oak.novartis.com/id/eprint/48058