Rapid Microbiology Methods Rapid Microbiology Methods A Regulatory ViewpointA 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, Italy23 - 25 June 2003

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FDA ExperienceFDA Experience

• Release Tests– Microbial Limits– Sterility

• Other– Water– Bioburden– Environmental Monitoring

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Micro Methods OverviewMicro Methods Overview

• Traditional Methods (plate counts, mpn)– simple– inexpensive– accepted

• Rapid Methods– fast– sensitive

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FDA ConcernsFDA Concerns

• Increased Sensitivity of Rapid Methods– changing (raising?) microbial limits acceptance

criteria

• Sterility Test “False Positives”– clear criteria for invalidation of test result

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ValidationValidation

• Test Organisms– Compendial Organisms– Environmental Isolates

• Sample Specific Issues– Inhibition/Interference– Parallel Testing

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ValidationValidation

• Equivalent or Better?

• Guidance– PDA Technical Report 33 - Evaluation,

Validation and Implementation of New Microbiological Testing Methods

– USP Draft Chapter <1223> - Validation of Alternative Microbiological Methods

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FDA InitiativesFDA Initiatives

• Process Analytical Technology (PAT)– Includes rapid micro

• Microbiology Subcommittee for ACPS

• GMP’s for the 21st Century– Product specialists for inspections– Dispute resolution process at Center level

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SummarySummary• Rapid Methods vs. Traditional Methods

– Is there a comparison?

• Apprehension by Industry– Why?

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What Next?What Next?

• Meet with CDER Microbiologists– Validation issues– Filing requirements

• Submit applications containing rapid microbiology methods