OPS Process Analytical Technology - (PAT) Initiative
- Guidance for Industry PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance [PDF]
- Educational Activities
- Other Resources
The goal of PAT is to understand 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.
Process Analytical Technology is:
- a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.
It is important to note that the term analytical in PAT is viewed broadly to include chemical, physical, microbiological, mathematical, and risk analysis conducted in an integrated manner.
Process Analytical Technology tools:
There are many current and new tools available that enable scientific, risk-managed pharmaceutical development, manufacture, and quality assurance. These tools, when used within a system can provide effective and efficient means for acquiring information to facilitate process understanding, develop risk-mitigation strategies, achieve continuous improvement, and share information and knowledge. In the PAT framework, these tools can be categorized as:
- Multivariate data acquisition and analysis tools
- Modern process analyzers or process analytical chemistry tools
- Process and endpoint monitoring and control tools
- Continuous improvement and knowledge management tools
An appropriate combination of some, or all, of these tools may be applicable to a single-unit operation, or to an entire manufacturing process and its quality assurance.
A desired goal of the PAT framework is to design and develop processes that can consistently ensure a predefined quality at the end of the manufacturing process. Such procedures would be consistent with the basic tenet of quality by design and could reduce risks to quality and regulatory concerns while improving efficiency. Gains in quality, safety and/or efficiency will vary depending on the product and are likely to come from:
- Reducing production cycle times by using on-, in-, and/or at-line measurements and controls.
- Preventing rejects, scrap, and re-processing.
- Considering the possibility of real time release.
- Increasing automation to improve operator safety and reduce human error.
- Facilitating continuous processing to improve efficiency and manage variability
- Using small-scale equipment (to eliminate certain scale-up issues) and dedicated manufacturing facilities.
- Improving energy and material use and increasing capacity.
To support Process Analytical Technology activities, FDA created:
- A PAT subcommittee composed of senior pharmaceutical and generic manufacturers; government officials; and private and academic consultants to the pharmaceutical industry. This subcommittee reported to FDA's Advisory Committee for Pharmaceutical Science and provided recommendations on issues to be addressed in the proposed FDA guidance for adoption of PAT by regulated industry.
- A Steering Committee comprised of senior managers in FDA, which oversees PAT activities for the Agency.
- A PAT Team to approach to CMC review and CGMP inspection. This team of reviewers, compliance officers and investigators is being jointly trained and certified on PAT issues and new technology to manage the review and inspection process.
- A PAT Research Team in the Office of Testing and Research, which conducts research to provide a scientifically based policy development process and support for the PAT Team.
- An Office of Pharmaceutical Science PAT Policy Development Team which will support and advise the PAT Team.
- "Sunrise School." A sunrise school was established for continuing education to foster in-depth discussions and understanding of various multivariate data analysis techniques.
- Journal Club. The Journal Club discusses articles and research relating to the implementation and development of systems and methods for PAT applications.
- Training Program. A training program was established for the PAT Team members who will manage the review/inspection process. This program was developed in coordination with several academic centers of excellence and includes didactic sessions, as well as advanced on-site practicums.
- Off-The-Shelf Software Use in Medical Devices. Center for Devices and Radiological Health. Guidance for Industry, FDA Reviewers and Compliance. September 9, 1999.
- General Principles of Software Validation; Final Guidance for Industry and FDA Staff. Center for Devices and Radiological Health. January 11, 2002. This guidance describes how certain provisions of the medical device Quality System regulation apply to software and the agency’s current approach to evaluating a software validation system.
- Part 11, Electronic Records; Electronic Signatures — Scope and Application [PDF]