Change in production facility for a Monoclonal Antibody.

Details: Need to develop a regulatory strategy for the US FDA that will be successful in meeting their requirements and expectations. You should consider the following information and develop a detailed proposal to move production from one facility to the other
• Exercise Information:
– Standard 12,000 liter CHO cell culture batch process
– Standard recovery process centered on Protein A Chromatography, ion exchange, UF/DF formulation
– Standard Certificate of Analysis methodology and specifications for a Monoclonal Antibody
– Monoclonal Antibody aggregation levels increase over time. The increased aggregation in coorlated with aggitation and mixing speed, also with formulation time
– The facilities are not identical
– Cell culture tanks at 2000L and 12,000L are different design. New tanks: Air sparge speed has 2X greater range and diffusor manifold is 3X larger.
– UF/DF equipment is different. New unit: 1.5X greater surface area for filtration
– Freezing tanks for drug substance are larger volume. Freeze time is 1.5X longer
Important things need to be answered:
• What is the process and facility comparability strategy?
• What is the reporting mechanism to the FDA?
• Will you request a meeting with FDA? Why? What type? (need to add 30 days if you request a meeting with FDA)
• What type of change approval are you requesting and why? What is a summary of your analytical, process, facility studies and acceptance criteria?
• You have 15 months of product inventory remaining from facility #1 for the US market. You want at least 5 months reserve inventory. When and where does the team recommend the next campaign be produced? (tell operation person to make another X month inventories)