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By Carly Evans and Kelly Swinney

As an industry, we are uncovering ways to treat more complex targets, develop precision medicines, and advance transformative therapies. This evolving drug development landscape has resulted in the rapid advancement of molecules from development to the commercial stage. Accordingly, timelines for developing deep process understanding and performing essential activities prior to commercialization, such as process validation, have shortened.

The implementation of continuous manufacturing (CM) has been shown to streamline development timelines and enable the rapid advancement of these therapies. Due to the relatively small scale nature of CM equipment, processes can be developed on commercial scale equipment, reducing the need for and risks associated with scale-up and enabling relevant commercial manufacturing experience to be gained early in development. Additionally, advanced control strategies based on continuous monitoring, high levels of automation, and additional levels of control are typically employed for routine CM. These advanced control strategies, coupled with the use of commercial equipment for process development and clinical manufacture, result in high assurance that the proposed commercial process and control strategy will consistently manufacture high quality products.

Now that continuous manufacturing in the pharmaceutical industry has become a reality, what does process validation mean for a continuous process? Traditionally, three commercial scale batches have been manufactured for process validation with additional sampling/testing performed. If the proposed CM commercial control strategy includes routine increased sampling and monitoring of parameters throughout the time domain of every batch, should the process validation approach be different? For example, can and should the validation approach be different if in one single CM batch more data points are collected than in ten batches manufactured by a traditional batch process? How is process validation impacted if the control strategy is capable of segregating non-conforming material or process disturbances without disrupting or stopping manufacture?

With commercial equipment being used for process development and clinical manufacture, validation activities can start earlier in development.  Is Continuous process verification, an alternative approach to process validation where manufacturing process performance is continuously monitored and evaluated, more appropriate? If the purpose of validation is to confirm the suitability of the control strategy for routinely producing high quality product consistently, is the traditional three batch minimum really relevant to CM?

Now it is time for the industry to re-think process validation for a CM process. For more on this topic, read our previous post, “Continuous Manufacturing and Accelerating Drug Development.”

Carly Evans is a Director in Global Regulatory Affairs at Vertex Pharmacetuicals Inc.  She has a Masters in Chemical Oceanography from Old Dominion University and has focused on Orphan Disease Drug Development throughout her career in Industry.
Kelly Swinney is currently the Head of Analytical Development at Vertex Pharmaceuticals. She has a Ph.D. in Chemistry from Texas Tech University.  Kelly has held many leadership positions in the pharmaceutical industry, including Drug Product Continuous Manufacturing Lead and implementation of all process analytical technologies at Vertex.