Process Analytical Technology (PAT) in Pharmaceuticals

Process Analytical Technology is a system for designing, analyzing and controlling manufacturing processes through timely measurement during processing. With the goal of ensuring final product quality, it analyzes raw and in-process materials. The PAT is now being deployed in the pharmaceutical industry, where it is seen as a technology that can help companies to improve their conformity with manufacturing regulations. The emphasis in PAT is in the manufacturing process to increase the basic premise of the current drug quality system because quality can’t be tested into products, it should be built-in or should be by design.

The Food and Drug Administration (FDA) launched PAT in 2001 to reduce the risk of making a poor product. With the help of PAT, pharmaceutical companies are now better equipped to increase process efficiencies and design quality product. PAT is a methodology consistent with the FDA's belief that quality is not a question of testing but one of designing. Quality is designed into products, not tested them.

In 2003 the FDA promulgated its Process Analytical Technology (PAT) initiative to "encourage the voluntary development and implementation of innovative pharmaceutical manufacturing and quality assurance." This initiative was designed to improve process efficiencies, both manufacturing and regulatory, and has four components: data analysis, process analytical tools, process monitoring, and continuous feedback. The quality by design (QbD) aspect of PAT will reduce cycle time thus reducing the wastes of waiting and inventory identified by lean manufacturing.

Early on, efforts with PAT were focused chiefly on the single aspect of developing and applying analytical tools for timely in-process measurements. But to fully realize PAT's goal of complete understanding and control of the manufacturing process, a bigger toolkit must be used. 

The tools recommended by the FDA are multivariate tools (to handle design, information gathering, and analysis), tools for process analysis, tools for process control, and tools for continuous improvement. Then, with these tools, pharmaceutical manufacturers can move toward goals shared by both PAT and lean manufacturing: reduced cycle times, fewer rejects, increased automation, and continuous improvement in the process.

Related: Concept of GAMP 5 in Pharmaceuticals

PAT is not a product or service. It is a concept of manufacturing analytics, a working principle or a framework for operating, depending on you to implement it. The PAT market is developing and evolving rapidly as pharmaceutical companies strive to implement the framework set in place by regulators. You can purchase the tools and technologies that make up the framework and can buy the services and capabilities that you need to implement for qualitative analysis.

Benefits of implementing PAT -

1. Reduces processing cost

2. Improves quality

3. Provides product uniformity

4. Reduces product change-over time

5. Meets all kinds of regulatory requirements.

6. Increases automation to improve operator safety and reduce human errors.

7. Prevents rejects and re-processing.

The objective of the PAT framework is to design and develop well-understood processes that will consistently ensure a predefined quality at the end of the manufacturing process. When all critical sources are identified and explained properly, then a process is generally called well understood. Still, the pharmaceutical industry has been slow to take to the PAT initiative and to lean manufacturing quality assurance solutions and for largely the same reasons. 

The main reason, and probably the hardest to overcome, is one having to do with cultural issues and mindset. In this industry, a decades-long attitude of risk aversion has produced a narrow focus on avoiding mistakes rather than improving processes. So error-free documentation (and that largely paper-based) becomes more important than radical knowledge of the process. The problem here is that PAT calls for a risk-based approach and process understanding.

Related: Quality Management System (QMS)

The pharmaceutical industry has been similarly slow in fully adopting lean manufacturing mainly because of, again, culture and mindsets. The industry is highly compartmentalized, and so the manufacturing process is composed of many discrete parts rather than being a continuous, integrated flow. It's difficult to improve a process that isn't quite a process yet.

Also, there's a reluctance to make necessary changes when changing a batch size means the extra burden of extensive documentation and testing. As with PAT, the very things that need improvement prevent companies from taking the necessary steps toward that improvement.

Related: Concept of GxP in Pharmaceuticals

When it comes to process and quality control, the pharmaceutical industry has historically taken a reactive approach. When something broke, then it was fixed that is, when a product-quality issue arose, only then was it addressed. Now, however, that's changing, and the industry is moving away from post-product quality testing and toward a quality-by-design approach. And this approach meshes well with the twin objectives of lean manufacturing waste reduction and continuous improvement.