Identification And Risk Mitigation Of A Critical Process Parameter During Antibody Process Scale-Up

By Christa Short, Midge Bonzon, Jonathan Mitschelen, Upstream Process Development, R&D Services

This poster is a version of slides presented at PEGS Summit in Boston, MA, in the session of "Scaling Up and Down Strategies for Protein Production."

The case study presented involved the production of a Phase 1 clinical trial material at a100 L scale with limited process development prior to cGMP production and productivity of <1 g/L, below industry standard. A scale-up to 1,000 L was planned for a Phase 2 clinical supply, with an initial 1,000 L batch being successful with similar yield to 100 L batches. The second 1,000 L batch failed to reach normal cell density, and yield was much lower than normal. Risk mitigation for a third batch included rigorous data review and the implementation of a process control strategy.

Topics include:

• Impact on Manufacturing
• Company Strategies
• Regulatory Considerations
• mAb Process Flowchart
• mAb Production Process
• Process Performance History
• Glutamate Issues & Process Range
• Process Change Options
• Final Change and Justification
• Results
• Conclusions