Environmental Control and Developing a Science-based Monitoring Program

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Environmental Control and Developing a
Science-based Monitoring Program

• Richard L. Friedman, M.S.
• FDA/CDER

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Aseptic Processing Line D/M
Process -personnel flow -material
flow -layout
Facility Room D/M
Personnel

Daily Sterility Assurance
QA/QC
HVAC/ Utilities
Media Fills
Response to Deviations Environmental
Control Trends
Disinfection Procedures Practices

• D Design
• M Maintenance

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Risk-Based EmphasisConcept Paper

• Sample timing, frequency, and location should be
  carefully selected based upon its relationship to
  the operation performed. Samples should be taken
  throughout the aseptic processing facility (e.g.,
  aseptic corridors gowning rooms) using
  appropriate, scientifically sound sampling
  procedures, standards, and test limits.
• Locations posing the most microbiological risk
  to the product are a critical part of the
  program. It is especially important to monitor
  the microbiological quality of the aseptic
  processing clean zone to determine whether or not
  aseptic conditions are maintained during
  filling/closing activities.

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• 1987 Guideline
• Numbers No numerical surface limits
• Critical Surfaces Equipment surfaces which
  contact sterilized drug product or sterilized
  container/closure surfaces should, of course, be
  sterile.
• Establishing Action Limits States air monitoring
  action levels without qualification.
• ID Routine identification of the recovered
  microorganisms. Not every every isolate needs
  to be identified to genus and species keep a
  valid database.

• 2002 Concept Paper
• Numbers No numerical surface limits
• Critical Surfaces Critical surfaces which
  contact sterile product should be sterile.
• Establishing Action Limits Provides new latitude
  for different limits to be established where
  justified by nature of the operation.
• ID Essentially the same. Stresses ID in aseptic
  processing room (as highest product risks are
  generally present there).

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Other Environmental Monitoring Issues

• Trending
• Adequate systems to detect emerging or existing
  problem
• When meaningful adverse trend is illuminated by
  EM data, problem needs to be promptly addressed
  to prevent product contamination (211.42 and
  211.113).  
• Interpretation
• No statement indicating that a critical zone
  positive is a surrogate sterility test.
• CGMP expectation is for a holistic batch
  assessment, with explanation of significance and
  impact of environmental, or other, deviations.

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Summary of Risk-Based Program

• Emphasis on product risk areas
• Not just a grid approach
• The nature of the operation determines its
  criticality.
• Strategic collection of meaningful samples, based
  on understanding of personnel and material flow
  through the facility
• Detection of adverse environmental trends
• Systems allow detection before there is a product
  contamination consequence
• Responsive to identified problems
• Corrective action implemented where appropriate