February 28, 2019 | FDA’s New Continuous Manufacturing Guidance Carries Process Validation Implications

In a new 27-page Guidance, ‘Quality Considerations for Continuous Manufacturing’, released February 27, 2019, the FDA and CDER (Center for Drug Evaluation and Research) describe key quality considerations [for continuous manufacturing]…and recommendations for how applicants should address these considerations in new drug applications (NDA’s).’

In addition to these considerations, the FDA emphasized the importance of ‘the ability to evaluate real time data to maintain operations within established criteria to produce drug products with a high degree of assurance’ as well as outlining measures to better understand inter-  and intra- batch variability.

C.Process Validation

The guidance for industry Process Validation: General Principles and Practices and ICH Q8, 481 Q9, and Q10, is applicable to continuous manufacturing processes. For these types of manufacturing processes, the ability to evaluate real time data to maintain operations within established criteria to produce drug products with a high degree of assurance of meeting all the attributes they are intended to possess is an integral element of process validation. Manufacturers using continuous manufacturing processes may find that some process validation stages are more  concurrent and interrelated (e.g., process design and equipment qualification) than they are with batch manufacturing processes. This is, in part, because the development of a continuous manufacturing process generally uses commercial scale equipment. This offers significant advantages in that equipment size scale-up issues commonly encountered in the development of batch manufacturing processes will likely be minimized. Consequently, there may be activities described below in stages 2 and 3 that may be more appropriate to perform during stage 1. For example, it may be more appropriate to perform some equipment qualification activities prior to some stage 1 validation studies as those studies may also be used to demonstrate inter- and intra-batch variability at commercial scale (i.e., during process performance qualification (PPQ)). That is, it is important to ensure that the equipment operates properly prior to generating data that satisfies some of the expectations for PPQ. Furthermore, to better understand inter- and intra batch variability, the design of the process monitoring strategy during development should consider monitoring needs for commercial scale continued process verification throughout the life cycle of the product (stage 3).

– Quality Considerations for Continuous Manufacturing| February 28, 2019