Presented at CASSS-AT Europe 2019, Dublin, Ireland
Biopharmaceutical firms adopt complex and costly process monitoring strategies and quality systems to ensure final product quality. This is achieved by monitoring critical quality attributes (CQAs) using an array of analytical techniques. Although routinely used as release tests, these techniques generally do not measure attributes at the molecular level. Consequently, many manufacturers of biopharmaceuticals are exploring innovative analytical approaches based on mass spectrometry (MS) that enable direct measurement of CQAs at the molecular level. MS-based methodologies also offer the benefit of measuring numerous quality attributes on a given biotherapeutic with a single test. Therefore, the multi-attribute method (MAM) has the potential to reduce development and manufacturing costs and at the same time increase product quality.
In our approach, dedicated workflows perform system suitability tests (SSTs) to verify that the performance of the analytical instrumentation is adequate for the intended analysis. If these tests are passed, data sets obtained from tryptic digests of samples are analyzed using highly configurable data processing workflows that measure the CQAs of a given biomolecule, test for impurities, and search for new features. The basis of all MS-data processing and analysis is Genedata Expressionist (Genedata AG, Basel, Switzerland).
This approach can be fully automated and employed as part of a bioprocess control strategy. We present an example of real-time monitoring of quality attributes of the materials produced in a bioreactor. The enterprise nature of the software facilitated the creation of a database from which knowledge generated in upstream processes could be leveraged to automate downstream routine peptide mapping. A compliance module including GxP functionalities such as audit trails, electronic signatures, and data security allows the deployment of this MAM implementation in regulated environments.