A systems approach to characterization, validation and monitoring of commercial processes

BIOT 192

Abhinav A Shukla, abhinav.shukla@bms.com, Bioprocess Engineering, Bristol-Myers Squibb, 6000 Thompson Road, East Syracuse, NY 13057 and Steven Lee, Technical Operations, Bristol-Myers Squibb, 6000 Thompson Road, East Syracuse, NY 13057.
Systems biology views an organism through an integrated and interacting network of complex biochemical pathways. This provides a framework for combining detailed micro-level understanding of individual pathways to create a better understanding of the entire organism. Analogous to biological systems, commercial manufacturing processes for biologics are complex combinations of unit operations that interact and integrate with each other and ultimately produce a complex product with significant microheterogenity. This presentation highlights the relevance of taking a systems approach towards understanding the relevant details of each unit operation and how they combine together to create a well controlled process that operates at multiple commercial manufacturing sites to produce consistent and high quality drug substance.

Characterizing the operational design space for each unit operation is an important first step. Even more important is understanding the interplay between various process steps and how they combine together to influence key product attributes. Several case studies of process characterization and validation study designs to highlight this interplay will be presented for both upstream and downstream processes.