(424f) A High Throughput, Parallel, Microscale, Fully Automated Approach to Biologics Formulation Development and Stress Test Studies

Developing robust formulations for biological materials (proteins, antibodies, vaccines, etc.) requires the screening and analysis of a comprehensive matrix of formulation compositions and stress conditions. This talk will focus on the development and use of a fully-automated workflow for stressing these types of formulations in their final container closure systems; such a system is intended to fit into a Quality by Design(QbD) program in which scientists seek "a full understanding of how product attributes and process relate to product performance based on scientific,risk-based, holistic and proactive approaches to product development." Guzman, R. "A Regulatory Approach to Contract Manufacturing", Pharmaceutical Outsourcing, March/April 2010, p 16-20. The system comprises automated environmental chambers (-20, 4, 25, and 40 deg C), several stationary sample preparation and measurement robots (Freeslate Core Module with pH probes, dispensing and mixing tools, balance and camera) and a multitude of analytical instruments (HPLCs, osmometer, electrophoresis-on-chip, UV-Vis/fluorescence and dynamic light scattering plate readers) and it enables automated post-stress analytical sample workup and measurement. The system is integrated through an informatics system using Freeslates's Laboratory Execution and Analysis software to create an informatics platform that allows scientists to view, aggregate and make conclusions on large analytical datasets collected by the system. In addition, these instruments are physically integrated with a 6-axix robotic arm on a linear track, with changeable end-effectors, that moves sample plates, reagents and consumables to the various workstations. Data generated using the system for two case studies will be presented. The first study examines the effect of surfactant composition and concentration on protein stability. The second study examines the temperature stability of an antibody formulation as a function of pH and composition.