It's the right time for PAT

By Alex Habib

The Food and Drug Administration's Process Analytical Technology (PAT) initiative is an idea whose time has come.

Instead of depending on validation protocols, reports, and other documentation that still leave us with processes we do not understand and can't control, in a PAT framework, the manufacturing processes will be monitored and controlled using on-line process instrumentation and control systems.

This will lead the industry into continuous improvements in quality and productivity.

Most food and pharmaceutical manufacturing facilities have an established general quality system, product-specific standard operating procedures, and equipment qualification and validation procedures to insure a product's quality before it ships to customers.  

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The FDA now recognizes PAT has the added advantage of being a real-time monitoring and controlling tool and can facilitate continuous improvement of the process and hit the best quality target.

PAT has four recognized tools:

1. Process and endpoint monitoring and control systems
2. Multivariate data acquisition and analysis tools
3. Modern process analyzers and process analytical chemistry tools
4.Continuous improvement and knowledge management tools

A clear and concrete example of how on-line process mentoring and control works is a fermentation process, and one can visualize the control and quality validation in process. 

Monitoring the fermentation process starts from the seed stage with mostly off line measurements.

As the fermentation moves to the production stage, online measurements begin with the fundamentals such as temperature, pressure, oxygen flow and then the more complex analyzers that deal with gases and liquid chromatography.

Distributed control systems (DCS) and programmable logic controllers (PLC) play an important role in creating the optimum fermentation conditions by automating the oxygen addition and controlling the temperature, pH, dissolved oxygen, and others.

These PLCs and DCSs coupled with batch-sequence-control software further insure the product consistency and quality from batch to batch.

One of the most important aspects of optimizing the fermentation process is determining the end point. This is possible using multivariate statistical process-control software tools that take several signals from the process and create a fingerprint of the ideal batch. 

By ending the fermentation process at the perfect time, optimal and maximum product is possible. Of course, off-spec product is at a minimum. Additional benefits to the fermentation process are possible by using modern alarm-management software tools to predict sensor failure. 

For example, the pH and dissolved oxygen sensors are subject to several heating and cooling conditions as the fermenter goes through the sterilization cycles. 

By predicting a sensor's failure accurately, a valuable batch of product won't be become waste product.

ABOUT THE AUTHOR

Alex Habib (alex-habib@msn.com) is chair of ISA ISA-5.6 Control Software Documentation Standard. He is an automation and validation consultant with over 17 years experience working with process control systems for pharmaceutical facilities. For a detailed explanation of PAT, please visit www.isa.org/PAT/Interplex.