TOC analyzers can play a key role in PAT initiatives such as real-time release or on-line cleaning validation.

Process Analytical Technology (PAT)

Process Analytical Technology (PAT)/Quality by Design (QbD) is a initiative from the Food and Drug Administration (FDA) that promotes using advanced manufacturing processes to achieve more cost-effective and higher quality pharmaceuticals. PAT/QbD is a system for designing, analyzing, and controlling manufacturing through timely measurements, process understanding, and process control. PAT/QbD directly reduces the risk of implementing new, advanced technologies by eliminating regulatory uncertainty. Changes and improvements to a successfully implemented PAT/QbD process receive regulatory relief.

PAT/QbD Guidelines

For a process control system to qualify as a PAT/QbD process it must incorporate an appropriate combination of some, or all, of the following basic PAT/QbD tools as listed in the PAT Guidance for Industry (A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance):

For more details the official PAT Guidance document can be found on the FDA web site. On-line TOC analyzers can play a key role in a PAT/QbD plan by providing real-time, continuous analysis and real-time release of Process Water (PW) or Water for Injection (WFI) for use in manufacturing. The use of TOC analyzers to control the end point of equipment rinse down after cleaning is also a viable PAT process. The FDA encourages the use of on-line TOC instruments in cleaning validation processes and automated TOC systems to help eliminate manual manufacturing errors.

Using TOC Endpoint Detection within a PAT Framework

Real-time TOC Water Release

Most pharmaceutical companies today release water for PW and WFI using manual sampling and laboratory TOC testing. However, there are many advantages to using on-line TOC water testing over laboratory TOC analysis. Since on-line analyzers automatically collect samples directly from the water system, they eliminate the possibility of manual errors and sample contamination. In addition, the use of on-line TOC Analyzers demonstrates significant cost savings over traditional grab/laboratory analysis. Payback for a laboratory to on-line conversion is usually less than a year.

Cleaning Validation Using TOC Endpoint Detection

This method of dynamically controlling the rinse end point is superior to simple time and flow based rinsing processes. Using TOC to control the rinse down end point insures the equipment is clean even in the event of an unexpected situation. This system will be much more robust compared to a simple rinse system that is controlling flow and time. For more information about Cleaning Validation click here.

PAT Advantages

Although most companies implement these systems using non-PAT filings, there are advantages to filing under a PAT framework. Because the science behind the control process and an on-line TOC release system are well understood, PAT filings are simpler and are open to future process improvements and changes without additional filings.

PAT Solutions from GE Analytical Instruments

The Sievers 900 Series (Laboratory, On-Line and Portable) and 500 RL On-Line TOC Analyzers are ideally suited for process control applications. We provide a complete suite of TOC support services and products, including on-site calibration, system suitability and validation testing, on-site service, and the highest quality TOC standards manufactured in a cleanroom under ideal conditions to insure maximum quality and reliability. These support services and products insure reliable, worry-free, and optimum performance in critical process applications.

Resources

To read more about On-Line TOC Release and PAT, visit our library and select the "Applications" and "Document/Media Type" dropdown menus.