FDA regulatory experience with drug manufacturing process models in approved applications

Area of Science:

• Pharmaceutical Manufacturing
• Regulatory Science
• Process Modeling

Background:

• Process models are integral to drug manufacturing, supporting development and control.
• The U.S. Food and Drug Administration (FDA) has observed a rise in their regulatory application.

Purpose of the Study:

• To analyze the application and impact of drug manufacturing process models in FDA regulatory submissions.
• To highlight the types of models used and their role in various manufacturing stages.

Main Methods:

• Review of FDA-approved applications (2012-2025) utilizing process models.
• Categorization of models (mechanistic, empirical, hybrid) and their risk levels.
• Analysis of model impact on submission review timelines.

Main Results:

• Over 15 FDA-approved applications from 8 companies between 2012-2025 utilized process models.
• Eleven applications involved continuous manufacturing, requiring residence time distribution (RTD) models.
• Models supported various applications, including design space establishment and real-time process control across different risk levels.
• Drug submissions using process models were approved an average of 20.3 days ahead of schedule.

Conclusions:

• Process models are successfully integrated into drug manufacturing regulatory submissions.
• Their use, particularly in continuous manufacturing, accelerates approvals and enhances process understanding.
• Sharing FDA's experience promotes transparency, innovation, and policy development in pharmaceutical manufacturing.