Process Analytical Technology (PAT); the infamous paradigm shift

Anoop Naik is a seasoned leader with over 12 years of dedicated experience in the pharmaceutical industry. Over the past 8 years, he has demonstrated leadership in critical areas, including Quality Management System, Analytical Quality Assurance, Validation, and IT compliance. Anoop holds a MTech degree in Pharmaceutical Operations and Management from BITS Pilani and has done MBA from Goa Institute of Management. Currently with Indoco Remedies., he has also contributed to Encube Ethicals, Abbott, and Cipla. He engaged in a conversation with the India Pharma Outlook magazine to share information about Process Analytical Technology (PAT) in healthcare.

It was at the start of the 21st century, that the concept of continuous manufacturing was gathering momentum in the pharmaceutical industry. The traditional batch manufacturing was very well established but had many lacunas that needed to be addressed. Time Management was one of the biggest concerns among them. The increasing setup and changeover times with average production efficiency triggered the need for innovation in that area. The complexity in production planning and high wastage had to be also dealt with. Continuous manufacturing philosophy was the ideal surrogate for it and there was also a need for continuous analytical testing.  Traditional analytical technology was amusingly slower and often carried sampling bias. To overcome this, the concepts of Process Analytical Technology were ushered. Process Analytical Technology uses information management systems to integrate various analytical techniques, tools, and sensors into the manufacturing process. Process Analytical Technology includes widespread application at various stages of pharmaceutical manufacturing such as Quality control and testing, in-process monitoring, etc. Throughout the lifecycle, PAT aids in continuous improvement and optimization by providing insights into process variations and opportunities for enhancement. Looking at the benefits of ‘Process Analytical Technology’; it was considered a revolutionary step and was often referred to as a paradigm shift in the functioning of pharmaceutical manufacturing. In the year 2004, the FDA (US) released ‘PAT guidance’ which acted as a concurrence by the regulatory bodies for the pharmaceutical industry to necessitate the implementation of Process Analytical Technology.

Process Analytical Technology embodies a charter for designing, analyzing, and controlling pharmaceutical manufacturing procedures through timely measurements of critical quality and performance attributes. This approach enables real-time monitoring, fostering continuous improvement and thereby reducing the risks associated with substandard product quality. As per FDA guidance, ‘the goal of PAT is to enhance understanding and control the manufacturing process, which is consistent with our current drug quality system: quality cannot be tested into products; it should be built-in or should be by design’. Thus, PAT aligns with regulatory agencies' emphasis on quality by design and supports compliance with stringent quality standards. PAT also improves the quality through online control which results in consistent product quality thereby reducing the risk of defective or substandard medications reaching consumers. The efficiency can also be increased as PAT enables quicker process development, shorter production cycles, and reduced resource consumption, leading to cost savings and improved productivity. Since there is vigilant monitoring, the deviations are promptly identified, minimizing the need for rework and/or disposal of batches. The result is, that it reduces wastage and overhead costs. The adoption of Process Analytical Technology has several benefits and also triggers innovation in the pharmaceutical manufacturing process. This has also led to many novel technologies surfacing and has the potential to disrupt traditional concepts in our understanding of safety and quality in drug products. This includes integration with artificial intelligence, portable analytical devices, advanced sensor technology, etc.

Despite the numerous advantages, Process Analytical Technology has to offer, it is still not prevalent in the pharmaceutical manufacturing framework. It is very hard to reckon the crawling pace at which the adoption of this technology has happened. Unlike other technology, this had the unanimity of the FDA but still, there were unseen hurdles that were sighted only when they moved forward. The most obvious one would be the upfront cost. This includes acquiring analytical instruments, sensors, data management systems, etc. This investment did not have a tangible return of investment which led to many industrialists not taking the undue risk. Another problem faced was the integration with the existing system. The brave decision of complete overhaul was not practically feasible but ensuring compatibility and seamless integration with legacy systems without disrupting ongoing operations required careful planning and execution. Also, PAT required specialized expertise and companies faced challenges in finding or training personnel who are proficient in its methodologies.PAT implementation lodges scalability for different production scales and elasticity to acclimatize variations in raw materials and manufacturing processes. The ability to predict the diverse manufacturing requirements was challenging which led to the designing of PAT systems that were not versatile enough to handle complexities. The need for extensive validation to avoid potential disruptions because of the looming uncertainties might have deterred the companies from embracing PAT. What was once considered a revolutionary change, is now just tapered down to an option that will be leveraged only when the benefits of PAT will become more evident.