FDA's Revision of the Aseptic Processing Guidance

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FDA's Revision of the Aseptic Processing Guidance

• Joseph C. Famulare
• Director, Division of Manufacturing Product
  Quality

10/22/02 OPS Advisory Committee/ Aseptic
Processing
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Status of Guidance Revision Process

• Joint CDER, CBER, and ORA document has been
  completed
• Concept Paper provided today to solicit feedback
• Publication of Draft Guidance is next step

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Scope of Concept Paper

• Format Improved
• More user friendly
• Table of Contents, Headings
• Easier to read and follow
• New Definitions Added
• air lock, components, colony forming unit,
  dynamic, endotoxin, gowning qualification,
  barrier, isolator, etc.
• Old Sections
• updated
• New Sections
• e.g., personnel, isolators, early processing

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Why Improve Guidance?

• Current Manufacturing Guidance
• Has been requested by Industry
• Promotes better CGMP understanding
• Facilitates compliance
• Proactive communication of expectations for firms
  building or modifying facilities saves money
• Clarifies issues for which questions persist

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Why Improve Guidance?

• Updated Manufacturing Guidance
• Reflects evolution of knowledge
• Removes obsolete information
• Addresses newer technologies
• Fills major voids illuminated over time
• Reflects current standards
• Incorporates latest scientific principles

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Why Improve Guidance?

• Reflects uniformity between
• Drug and Biologics Centers (CBER and CDER)
• Field co-sponsoring this document
• Move forward beyond perennially debated issues,
  and work together on new matters of importance

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Why Improve Guidance?

• Original 1987 Guidance Document
• Written circa 1980 in lieu of regulations
• Guidance route provided latitude
• Current Vacuum of updated CGMP guidance on high
  risk area of sterile drugs

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Quality of Sterile Drugs

• State of the industry
• Some persistent problems that need to be resolved
  and averted
• Need to maintain a steady supply to the American
  public
• Important therapies
• National security concerns
• Time consuming regulatory problems for FDA and
  the Industry
• Better adherence to CGMP through
• Improved Guidance
• Inspectional Focus
• Better understanding of scientific principles

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Lack of Sterility Assurance
recalls
Fiscal Year (Source CDER Recall Staff)
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Aseptic Processing Many Variables

• Aseptic Processing requires daily vigilance and
  attention to many details
• A true test of CGMP conformance
• Adherence to procedures and details is
  fundamental to sterility assurance
• Process Consistency is of utmost importance for
  aseptic processing
• Overriding objective is that each unit produced
  in a batch is free of microorganisms

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Sterile Drugs Risk-Based Approach

• Hazards to the Product
• Are also hazards to a patient
• Unacceptable risk to patients posed by
  contaminated drug

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Sterile Drugs Risk-Based Approach

• Failure to adhere to CGMPs can impact on product
  safety and efficacy
• Top priority of our risk-based program

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Sterile Drugs Risk-Based Approach

• Causes of Contamination
• Where are the potential routes of contamination
  in a firms process?
• Focus on issues of most concern
• Critical Control Points

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Good Science

• Focus on issues of most concern
• Scientific Basis
• Science-based approach to CGMP emphasized in
  Concept Paper
• Key Sources
• Journals
• Technical Documents
• Textbooks
• Vectors illuminated by Facility Contamination
  Findings
• CGMP Case Reviews

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CGMP in the 21st Century

• Our New Initiatives Objective
• To outline risk-based approaches that will better
  focus FDAs and Industrys resources
• Make even a very goodsystem better
• Focus on critical process parameters
• critical control points
• Encourage Innovation

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CGMP in the 21st Century

• The Diverse Nature of the Industry
• New guidance will address this essential
  practicality while also providing meaningful
  insight into our expectations
• Encourages Innovation by acknowledging new
  technologies and liberalizing some old standards
• This will be a guidance, not a regulation!

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Todays Broad Questions

• What additional considerations needed to ensure
  that the proposed guidance
• contributes to the improvement of aseptic
  manufacturing processes across the industry
• improves consistency in FDA inspection process
• encourages innovation in the aseptic
  manufacturing arena

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Todays Broad Questions

• Is FDAs Current Thinking on these topics as
  outlined in the concept paper, well grounded in
  science and sufficiently detailed to provide
  industry with clarity on FDA expectations with
  respect to assuring appropriate quality of
  sterile drugs produced by aseptic processing

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SUMMARY

• We see compelling need for a revision
• Concept paper represents our current thinking
• We value your feedback
• Feedback on the level of specificity is
  important
• We will listen carefully and do comprehensive
  review of all advisory comments
• Modifications to be made prior to publishing
  draft for public comment