14/15 December 2023
In the publications in the 'USP Proposals PF 49_5 there is also a draft of a chapter <1060> "Mass Spectrometry-Based Multi-Attribute Method for Therapeutic Proteins".
This chapter describes the importance of characterizing product quality attributes (PQAs) in therapeutic protein development and the use of multi-attribute methods (MAMs) to monitor multiple PQAs simultaneously. Conventional assays such as chromatography and electrophoresis often provide only indirect information about PQAs, whereas MAM, based on LC-MS and automated data analysis, allows direct quantification of many PQAs in one method.
It is emphasized that the application of MAM can serve in the context of Quality by Design (QbD) and as a tool for Process Analytical Technologies (PAT) in product and process development. MAM enables site-specific identification, quantification, and monitoring of PQAs, leading to better understanding of products and processes, shorter development times, and improved control strategies.
It is also explained how MAM is applied in the biopharmaceutical industry, particularly through peptide mapping-based approaches in which therapeutic proteins are digested under denaturing conditions and analyzed by mass spectrometry. It is further demonstrated how MAM can help to understand and monitor changes in the charge or size distribution of proteins. In addition, methods for sample preparation, system preparation, and data analysis associated with MAM are explained. The importance of identifying and quantifying critical quality attributes (CQAs) that are critical to the safety and efficacy of therapeutic proteins are also addressed.
Finally, it describes how MAM is applied in practice, both in product development and quality control, and how it helps to improve product quality and process control. The text also explains the difference between targeted and non-targeted analysis as it relates to MAM, and points out that MAM has certain limitations and may require additional analytical methods to capture specific PQAs.
More details can be found on the USP website by prior registration.