(594a) Advanced Control Strategy Approaches for Continuous Pharmaceutical Manufacturing: The Regulatory Landscape

The FDA believes that strategic efforts to encourage and sustain improvements in pharmaceutical manufacturing quality are critical to the FDA mission of making safe, effective and high-quality drug products consistently available to the patients who need them. Over the past decade since the publication of the PAT guidance, there has been significant progress in modernizing the pharmaceutical manufacturing sector. There has been a general move away from fixed uni-variate parameter specifications towards a multivariate design space approach and the adoption of in-process measurement systems to aid process development. At the same time industry and regulators are being confronted with and increasing complex challenges including unprecedented drug recalls and shortages. The implementation of advanced control strategies can help address these challenges by increasing the efficiency, flexibility, and robustness of manufacturing processes. In FDA’s experience to date, continuous pharmaceutical manufacturing is serving as a driving force for modernizing control strategy approaches including model based control, multivariate monitoring, analysis of large of data sets, and Real Time Release Testing (RTRT). Process models that can capture the dynamic relationships between process parameters, raw materials, and product attributes in a quantitative and predictive manner support the development and implementation of these advanced control strategy approaches. While there are no regulatory barriers for adopting advanced control strategy approaches, there still may be hurdles encountered when fitting these approaches into the existing regulatory framework. In this presentation, scientific and regulatory considerations for advanced control approaches designed to mitigate identified risk areas are discussed including performance criteria and lifecycle considerations. Continuous drug product and drug substance manufacturing case studies are utilized to highlight these considerations.