1. Rapid Microbiology Methods A Regulatory Viewpoint Bryan S. Riley, Ph.D. U.S. Food and Drug Administration Center for Drug Evaluation and Research Office of Pharmaceutical Science PDA Sterile Manufacturing Practices in the Third Millennium: A Regulatory and Industry Perspective Milan, Italy 23 - 25 June 2003

2. Bryan S. Riley, Ph.D.2 FDA Experience Release Tests –Microbial Limits –Sterility Other –Water –Bioburden –Environmental Monitoring

3. 23 - 25 June 2003Bryan S. Riley, Ph.D.3 Micro Methods Overview Traditional Methods (plate counts, mpn) –simple –inexpensive –accepted Rapid Methods –fast –sensitive

4. 23 - 25 June 2003Bryan S. Riley, Ph.D.4 FDA Concerns Increased Sensitivity of Rapid Methods –changing (raising?) microbial limits acceptance criteria Sterility Test “False Positives” –clear criteria for invalidation of test result

5. 23 - 25 June 2003Bryan S. Riley, Ph.D.5 Validation Test Organisms –Compendial Organisms –Environmental Isolates Sample Specific Issues –Inhibition/Interference –Parallel Testing

6. 23 - 25 June 2003Bryan S. Riley, Ph.D.6 Validation Equivalent or Better? Guidance –PDA Technical Report 33 - Evaluation, Validation and Implementation of New Microbiological Testing Methods –USP Draft Chapter - Validation of Alternative Microbiological Methods

7. 23 - 25 June 2003Bryan S. Riley, Ph.D.7 FDA Initiatives Process Analytical Technology (PAT) –Includes rapid micro Microbiology Subcommittee for ACPS GMP’s for the 21 st Century –Product specialists for inspections –Dispute resolution process at Center level

8. 23 - 25 June 2003Bryan S. Riley, Ph.D.8 Summary Rapid Methods vs. Traditional Methods –Is there a comparison? Apprehension by Industry –Why?

9. 23 - 25 June 2003Bryan S. Riley, Ph.D.9 What Next? Meet with CDER Microbiologists –Validation issues –Filing requirements Submit applications containing rapid microbiology methods