1. One Quality Place Edison, NJ 08820 732-906-6155 e-mail: smarash@thesamgroup.comsmarash@thesamgroup.com Visit: www.statamatrix.com/fda The Interrelationship between PAT and Six Sigma Presented by Dr. Stanley A. Marash, P.E. Chairman and CEO STAT-A-MATRIX/The SAM Group Food and Drug Administration - PAT Pharmaceutical Science Advisory Committee Meeting October 21-23, 2002

2. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 2 Motivation  Significant potential and need exists for improving the efficiencies of pharmaceutical manufacturing and associated regulatory processes (Dr. Ajaz S. Hussain - May 8, 2002)

3. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 3 PAT  Technological opportunities (e.g. PAT) available for realizing this potential–but industry reluctant due to regulatory uncertainties (Dr. Hussain)

4. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 4 Six Sigma  Many aspects of the industry have adopted Six Sigma. Both PAT and 6  are process oriented approaches to achieving efficiencies, reduced cycle time and improved quality

5. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 5 Why PAT?  PAT provides an opportunity to move from the current “testing to document quality” paradigm to a “continuous quality assurance” paradigm that can improve our ability to ensure quality was “built-in” or was “by design” – ultimate realization of the true spirit of cGMP. (Dr. Hussain)

6. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 6 Why Six Sigma? DefineMeasureAnalyzeDesignVerify DefineMeasureAnalyzeImproveControl  Six Sigma embraces both continuous improvement and breakthrough performance. The process includes models for manufacturing, design and administrative services Design For Six Sigma (DFSS) Manufacturing & Administrative

7. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 7 Goals and Objectives  Using PAT as a model technological opportunity, develop a regulatory framework to facilitate introduction of new manufacturing technologies that enhance process efficiencies and understanding Identify and eliminate perceived/real regulatory hurdles Develop a dynamic, team based, scientific approach for regulatory assessment…of new technologies (Dr. Hussain)

8. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 8 PAT  Can PAT win the industry’s confidence or are the perceived/real “regulatory hurdles” too difficult to overcome?

9. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 9 Six Sigma  Does Six Sigma have the advantage of: No (or less) regulatory constraints Perception of an industry program not an agency program

10. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 10 Fusion Management TM  A tool for fusing PAT and Six Sigma to overcome the existing constraints

11. © 2002 STAT-A-MATRIX, All Rights Reserved #5147 FMOQ Rev. 1 11 For More Information Visit Our Web Site At: www.statamatrix.com/fda