Office of Pharmaceutical Science (OPS)
Process Analytical Technology
(PAT) Initiative

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• Introduction
• FDA PAT Team Members (ORA, CDER, CVM) 
• Steering Committee Members (12/14/2005)
• Guidance for Industry PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance [HTML] or  [PDF]
• Presentations
  • Presentations and Meeting Information for the Process Analytical Technology Subcommittee of the Advisory Committee for Pharmaceutical Science
  • Advisory Committee for Pharmaceutical Science
  • FDA Science Board
  • Other Presentations 
• Educational Activities,
• Additional Information on Process Analytical Technology
• Other Resources
• Contact Us

Introduction

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.

The FDA is actively involving its stakeholders in this process. The PAT initiative has received support from the FDA Science Board  and the Advisory Committee for Pharmaceutical Science.  

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.

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FDA PAT Team Members (ORA, CDER, CVM)

PAT Review - Inspection Team

Investigators	Center
Bob Coleman	Office of Regulatory Affairs/ATL-DO
Erin McCaffrey	Office of Regulatory Affairs/NWJ-DO
George Pyramides	Office of Regulatory Affairs/PHI-DO
Rebecca Rodriguez	Office of Regulatory Affairs/SJN-DO
Dennis Guilfoyle	NELD
Compliance Officers	Center
Albinus D’Sa	CDER
Mike Gavini	CDER
William Bargo	CVM
Brenda Uratani	CDER
Reviewers	Center
Rosario D’Costa	CDER
Raafat Fahmy	CVM
Bryan Riley	CDER
Lorenzo Rocca	CDER
Norman Schmuff	CDER
Vibhakar Shah	CDER
PAT Policy Development Team	Center
Chris Watts	CDER/Office of Pharmaceutical Science
Ali Afnan	CDER/Office of Pharmaceutical Science
Huiquan Wu	CDER/Office of Pharmaceutical Science
PAT Training Coordinators	Center
John Simmons	CDER
Karen Bernard	CDER
See Lam	CDER

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Steering Committee Members (updated 12/14/2005)

Chair	Helen Winkle	Center for Drug Evaluation and Research
Members	Patricia Alcock	Office of Regulatory Affairs
	Dennis Bensley	Center for Veterinary Medicine
	Douglas Ellsworth	Office of Regulatory Affairs
	Joseph Famulare	Center for Drug Evaluation and Research
	Frank Holcomb	Center for Drug Evaluation and Research
	Chris Joneckis,	Center for Biologics Evaluation and Research
	Steven Kozlowski	Center for Drug Evaluation and Research
	Moheb Nasr	Center for Drug Evaluation and Research
	Keith Webber	Center for Drug Evaluation and Research

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Presentations

Process Analytical Technology Subcommittee of the Advisory Committee for Pharmaceutical Science, meeting information and presentations, Rockville, MD.

• October 23, 2002 
  • Presentations
• June 12-13, 2002
  • Presentations
• February 25-26, 2002
  • Presentations

Advisory Committee for Pharmaceutical Science Presentations, Rockville, MD.

• October 21, 2002
  • Process Analytical Technologies Subcommittee Report. Tom Layloff, FDA. [PPT]
• May 8, 2002
  • Summary: The Subcommittee on Process Analytical Technologies.  Ajaz Hussain, Deputy Director, Office of Pharmaceutical Science, FDA.[PDF]   [PPT]   
• November 28, 2001
  •  The Advisory Committee for Pharmaceutical Science Process Analytical Technologies Subcommittee. Ajaz Hussain, Deputy Director, Office of Pharmaceutical Science, FDA. [PPT]  [HTML]

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Science Board to the Food and Drug Administration Presentations, Rockville, MD.

• April 4, 2002
  • Quality by Design: A Challange to the Pharma Industry. Raymond H. Scherzer, Senior Vice-President for Engineering Global Manufacturing and Supply GSK. [HTML]
  • FDA Regulation of Drug Quality: New Challenges. Janet Woodcock, Director, Center for Drug Evaluation and Research, FDA. [HTML]
  • The Process Analytical Technology (PAT) Initiative: Progress Report and Next Steps.  Ajaz Hussain, Deputy Director, Office of Pharmaceutical Science, FDA. [HTML]
    
    
• November 16, 2001
  • FDA Regulation of Drug Quality: New Challenges. Janet Woodcock, MD, Director, Center for Drug Evaluation and Research, FDA. [PPT]  [HTML]
  • Productivity and the Economics of Regulatory Compliance in Pharmaceutical Production.  Doug Dean and Frances Bruttin, PWC Consulting.  [PPT]  [HTML]
  •  Pharmaceutical Manufacturing: New Technology Opportunities. G.K. Raju, PhD, MIT Program on the Pharmaceutical Industry, Massachusetts Institute of Technology. (PHARMI).  [PPT]  [HTML]
  •  An Industry Perspective on the Potential for Emerging Process Analytical Technologies. Norman Winskill and Steve Hammond, Pfizer Global Manufacturing Services. [PPT] 
  • Pharmaceutical production -- Batch Processes.  Nouna Kettaneh-Wold, Umetrics. [PPT]  [HTML]
  • TQMS, Statistically Based In-Process control with Real Time Quality Assurance, The AstraZeneca Total Quality Management Strategy. R. S. Chisholm, International Technology Manager, AstraZenica . [PPT]  [HTML]
  • Emerging Science Issues in Pharmaceutical Manufacturing: Process Analytical Technologies. Ajaz S.Hussain, Deputy Directory, Office of Pharmaceutical Science, FDA.  [HTML]
    

Other Presentations

• A Shared Vision for Pharmaceutical Development and Manufacturing in the 21st Century: Contributions of the PAT Initiative, [PDF] Ajaz S. Hussain, B. Pharm., Ph.D., FDA, September, 2005
• PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, [PDF] D. Christopher Watts, Ph.D., FDA, March, 2005
• PAT Guidance Workshop at the Royal Pharmaceutical Society, December, 2004, London, U.K.
  • PAT Regulatory Process: Review and Inspection , Vibhakar Shah, Ph.D, FDA
  • PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance , D. Christopher Watts, Ph.D., FDA
  • PAT Guidance: Going from the Current Negative Vocabulary to a Manufacturing Science Enabling Vocabulary , Ajaz S. Hussain, B. Pharm., Ph.D., FDA
  • The European Regulatory View , Dr Keith Pugh, MHRA
  • Implementing PAT – Industry Example , David Radspinner, Ph.D., Aventis
  • PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance , Ali Afnan, Ph.D., FDA
     
• Engineering a Proactive Decision System for Pharmaceutical Quality: Integrating Science of Design, Process Analytical Technology and Quality System , Ajaz S. Hussain, Ph.D., FDA, IFPAC, January 2005, Crystal City, VA
• Pharmaceutical Quality by Design: Improving Emphasis on Manufacturing Science in the 21st Century, [PDF] Ajaz S. Hussain, Ph.D., Deputy Director, Office of Pharmaceutical Science,  CDER, FDA, FDA Pharmaceutical Inspectorate, August 5, 2004.  (8/16/2004)
• Process Analytical Technology (PAT): What’s in a name?, D. Christopher Watts, Ph.D, Office of Pharmaceutical Science, CDER, FDA. [HTML] or [PowerPoint] (Posted 5/14/2004)
• The Process Analytical Technology Initiative: PAT and the Pharmacopeias, Ajaz S. Hussain, Ph.D., Deputy Director,  Office of Pharmaceutical Science,  CDER, FDA [HTML] or [PowerPoint]  (Posted 5/5/2004)
• Rapid Microbiology Methods: A Regulatory Viewpoint. Bryan S. Riley, Ph.D. FDA, 6/23/2003. [HTML] or [PowerPoint]
• Utilizing PAT to Monitor and Control Bulk Biotech Processes. Rick E. Cooley; Eli Lilly and Co. University of Michigan Pharmaceutical Engineering Seminars, March 4, 2003. (Posted 4/23/2003)

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Educational Activities

• FDA/ISPE Forum on New PAT Guidance, November 16, 2004, Arlington, VA (international locations also available) Meeting Information  (10/18/2004)
• "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.

Additional Information on Process Analytical Technology

• CDER aims to improve drug manufacturing: Center to build consensus, science base for latest technology CDER News Along the Pike, July 24, 2002. 
• OPS forms advisory group for process analytical technologies CDER News Along the Pike, July 24, 2002. 

Other Resources

FDA Guidance

• Draft Guidance Document: PAT — A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance [HTML]  [PDF] 
• 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 [HTML] [PDF]

Useful Standards

• ASTM Standards
  • D 3764 - 01: Standard Practice for Validation of Process Stream Analyzer Systems.
  • D 6624-01: Standard Practice for Determining a Flow-Proportioned Average Property Value (FPAPV) for a Collected batch of Process Stream Material Using Stream Analyzer Data.
  • D 4855 - 97: Standard Practice for Comparing Test Methods.
  • D 6299 - 02: Standard Practice for Applying Statistical Quality Assurance Techniques to Evaluate Analytical Measurement System Performance.
  • E 178 - 02: Standard Practice for Dealing with Outlying Observations.
  • E 1655 - 00: Standard Practices for Infrared Multivariate Quantitative Analysis.
  • E 1866 - 97: Standard Guide for Establishing Spectrophotometer Performance Tests.
  • E 131-00a: Standard Terminology Relating to Molecular Spectroscopy.
  • E 456-02: Standard Terminology Relating to Quality and Statistics.

• International Society of Pharmaceutical Engineers
  • GAMP Guide for Validation of Automated Systems, issued on December 2003.
• Parenteral Drug Association
  • PDA. May/June 2000. Technical Report No. 33: Evaluation, Validation and Implementation of New Microbiological Testing Methods. PDA Journal of Pharmaceutical Science and Technology 54(3) Supplement TR33.
    
    
• Literature References

Contact Us

Please send questions or comments regarding the PAT initiative to pat@cder.fda.gov, or

FDA Process Analytical Technology Team
Office of Pharmaceutical Science, HFD-003
Center for Drug Evaluation and Research
5600 Fishers Lane, Rockville, MD 20857