The U.S. Food and Drug Administration (FDA) defines process analysis technology(PAT) as a process analysis technique that is used to design and control drug manufacturing processes by measuring critical process parametersthat affect the critical quality attributes (CQA) of (CPP). critical process parameters{(CPP) affecting critical quality attributes (CQA) to design, analyze, and control pharmaceutical manufacturing processes.

The concept aims to understand the process by defining the Critical Process Route (CPP) and accordingly monitor it in a timely manner (preferably in-line or on-line), leading to more efficient testing while reducing over-processing, enhancing consistency, and minimizing scrap.

FDA has developed a regulatory framework for PAT implementation. According to Hinz, the FDA is trying to incentivize the pharmaceutical industry to improve manufacturing processes through this framework. Because of the stringent regulatory requirements and the long development time for new drugs, manufacturing technology "freezes" during Phase 2 clinical trials.

Overall, the FDA's PAT program is just one theme in a broader program called "21st Century Pharmaceutical cGMP - A Risk-Based Approach".

The Basics

PAT is a term that is used to describe the broader changes in the pharmaceutical industry from static batch production to more dynamic methods. It involves defining the Critical Process Parameters (CPPs) of the equipment used to manufacture a product that affects the Critical Quality Attributes (CQAs) of the product, and then controlling those CPPs within defined limits. This enables manufacturers to produce products of consistent quality and also helps reduce waste and overall costs.

This mechanism for producing consistent product quality and reducing waste provides a great example of utilizing continuous manufacturing techniques. When you understand upstream and downstream impacts, control of the steady state process becomes easier because common causes of variation are easier to define and monitor.

Variables

It is acceptable that the attributes of the raw materials used to manufacture the drug product (e.g., moisture content, crystal structure, etc.) may vary. It is also accepted that the manufacturing equipment does not always operate in exactly the same way due to the inherent tolerances of the equipment and its components. Therefore, it is reasonable to say that variations in raw materials combined with static batch processing, together with inherent variations in the process equipment, will result in different products. This is based on the fact that static batches produce products according to fixed recipes and fixed set points.

Taking this into account, the PAT driver will have a dynamic manufacturing process that compensates for variations in raw materials and equipment to produce a consistent product.

PAT Implementation

To date, the challenge pharma manufacturers have faced with PAT is knowing where to start. A common problem is choosing a complex process and then getting bogged down in the challenges of collecting and analyzing the data.

The following criteria are the basic framework for a successful PAT implementation: (from "Getting Started with PAT")

• Choose a simple process. (Think Water For Injection (WFI) or Building Monitoring System (BMS)
• All the details and nuances of that process are well understood and explained.
• Determine what information can be easily collected and accessed with the current instrumentation.
• Understand the appropriate intervals for collecting data.
• Evaluate tools that can be used to read and synchronize data.