Implementation of USP antibody standard for system suitability in capillary electrophoresis sodium dodecyl sulfate (CE-SDS) for release and stability methods.

Capillary electrophoresis sodium dodecyl sulfate (CE-SDS) is widely used for purity analysis of monoclonal antibody therapeutics for release and stability to demonstrate product consistency and shelf life during the manufacturing and life cycle of the product. CE-SDS method development is focused on exploring the method capability to provide the information about the product purity and product related degradants (fragmentation, aggregation etc.). In order to establish the functionality of the instrumentation, software, and sample preparation; system suitability criteria need to be defined for analytical methods using a well characterized reference standard run under the same protocol and analysis as the test articles. Typically the reference standard is produced using a manufacturing process representative of the clinical material. The qualification, control, and maintenance of in-house reference standards are established through rigorous quality and regulatory guidelines. The U.S. Pharmacopeia (USP) has developed a monoclonal IgG System Suitability Reference Standard to be utilized for assessment of system suitability in CE-SDS methods. In this communication, we evaluate the system suitability acceptance criteria performance of the USP IgG standard using two methods, the recommended USP protocol provided in monograph <129> and a molecule specific Bristol-Myers Squibb (BMS) CE-SDS method. The results from USP IgG standard were compared with two in-house monoclonal antibody reference standards. The data suggest that the USP CE-SDS method may not be suitable for CE-SDS analysis for release and stability of monoclonal antibody therapeutics due to the high level of method induced partial reduction observed for all molecules tested. This high level of fragmentation observed utilizing the USP method will result in reporting lower purity levels, which will impact the overall quality assessment of the molecule. The system suitability criteria recommended by the USP method can be achieved by using the USP reference standard during the development and pre-validation stages. Furthermore, the USP reference standard does not offer significant advantages to existing SST criteria in the BMS method during release and stability testing, and therefore we propose use of the USP standard only during the optimization and pre-validation stages of method development.