1. 20 Oct 2004www.Torbeck.Org1 Impact of PAT on the Use of Statistics Lynn Torbeck Lynn@Torbeck.Org

2. 20 Oct 2004www.Torbeck.Org2 FDA Position  Clearly promoting the use of statistics:  “…new strategy is to alleviate the fear.”  Avoid regulatory impasse.  “best principles of quality management.”  “manage variability”  “an opportunity to use more rigorous statistical principles for a quality decision”

3. 20 Oct 2004www.Torbeck.Org3 FDA Training in Statistics  PAT Certification Program for FDA Investigators and Reviewers –Data handling and basic statistics –Regression and correlation –Statistical Process Control, SPC/SQC –Statistical sampling –Design of Experiments, DOE –Process capability

4. 20 Oct 2004www.Torbeck.Org4 Application Areas as in PAT  New Product and Process Development  Manufacturing / Production  Quality Assurance and Control –Using current data collection: Jeff Davis of Genentech Robert Chisholm of AstraZeneca Richard Poska of Abbott Labs

5. 20 Oct 2004www.Torbeck.Org5 Major Areas of Statistics  Basic Statistics: –Descriptive Statistics, Avg, S, graphs –Inferential Statistics, t-tests. C.I. –SPC/SQC tools and techniques  Design of Experiments  Regression and Model Building  Multivariate Analysis

6. 20 Oct 2004www.Torbeck.Org6 Statistical Terms Used in PAT  Basic Statistics: –Manage variability –Reference distributions –Randomization –Confidence intervals –Correlation –Capability of process control –Statistical and risk analysis

7. 20 Oct 2004www.Torbeck.Org7 Statistical Terms Used in PAT  Design of Experiments: –Factorial design of experiments –Multi-factor relationships and systems –Orthogonality –Interactions defined –Response surface methodologies

8. 20 Oct 2004www.Torbeck.Org8 Statistical Terms Used in PAT  Multivariate Statistical Tools: –Multivariate mathematical approaches –Multivariate statistical process control –Pattern recognition tools –Model predictions –Regression analysis

9. 20 Oct 2004www.Torbeck.Org9 Chemometrics  “…the art of extracting chemically relevant information from data provided in chemical experiments.” S. Wold  “…the science of relating measurements made on a chemical system to the state of the system via application of mathematical or statistical methods.” B. Wise

10. 20 Oct 2004www.Torbeck.Org10 Chemometrics Tools  Design of Experiments  Time Series Analysis  Multivariate correlation  Multivariate regression  Partial Least Squares  Principle Component Analysis  Mathematical Pattern Recognition

11. 20 Oct 2004www.Torbeck.Org11 Areas of Strength  ASQ/FD&C Division  USP Statistics Expert Committee  PhRMA Statistics Committee  Leading Companies –Abbott –Genentech –Lilly

12. 20 Oct 2004www.Torbeck.Org12 Further Reading  “Impact of PAT Implementation on Product and Process Specifications.” –Jean-Marie Geoffroy –Abbott Labs –American Pharmaceutical Review

13. 20 Oct 2004www.Torbeck.Org13 Further Reading  “Risk/Science-Based Approach to Validation: A Win-win-win for Patients, Regulators, and Industry.” –Karen A. Welch –Conrad A. Fung –Stephen R. Schmidt –PDA Journal, Vol. 58, No. 1, Jan/Feb 04

14. 20 Oct 2004www.Torbeck.Org14 Further Reading  “Process Analytical Technology and Multivariate Statistical Process Control.” –By Theodora Kourti –McMaster University, Ontario –The Journal for Process Analytical Technology –Vol. 1, Issue 1, Sept/Oct 2004

15. 20 Oct 2004www.Torbeck.Org15 Further Reading  “Process Analytical Technology: Concepts and Principles.” –Mark L. Balboni –Pharmaceutical Technology –October 2003, p 54

16. 20 Oct 2004www.Torbeck.Org16 The Impact of PAT  Few presentations at meetings  Few journal articles  Early adopters are all ready on board  Too soon to tell for the majority?  A need for real case studies  Publish your successes!