An Automatic Online Multiple Attribute Method Workflow for Real Time Product Quality Attributes Monitoring during the Monoclonal Antibody Biomanufacturing Process

Description:
Since the first licensing for clinical use three decades ago, the pharmaceutical industry has observed unprecedented proliferation of innovations with the emergence of over a dozen novel biologic modalities, such as monoclonal antibodies (mAbs), CAR-T therapies, oncolytic viruses, etc. The global value of this market is estimated to be more than $20 billion per year. Due to the complexity of macromolecules and cellular biosynthetic processes, biologic active pharmaceutical ingredients (API) have a high degree of natural variability which makes them more challenging to fully characterize and control with precision. Hence, there is a demand for sensitive and precise quality attribute (QAs) characterization and monitoring during macromolecule development and manufacturing. In this study, we demonstrate a fully automatic online workflow connected to bioreactors that include aseptic sampling, sample preparation, UHPLC separation, and high-resolution mass spectrometry for the simultaneous in-process monitoring of more than 20 product quality attributes in real-time. Through the 17-day 3L bioreactors process, this workflow demonstrated consistent quality profiles compared to offline analysis. This online HPLC/MS-based workflow is being adapted to support other processing steps such as downstream purification with minimal software re-configuration, eliminating a key barrier to implement the high resolution, high sensitivity technique to practically support QbD bioprocess development. This automated workflow could provide real-time monitoring and feedback control, improving the process yield, robustness as well as product quality, and is applicable at many stages of bioprocess development and manufacturing.

Speaker: Chi Zhang - GSK