FDA PROCESS ANALYTICAL TECHNOLOGY SUB COMMITTEE

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FDA PROCESS ANALYTICAL TECHNOLOGY SUB COMMITTEE
MEETING 25TH FEBRUARY 2002
PERSPECTIVE ON PROCESS AND ANALYTICAL VALIDATION
Robert S Chisholm
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• THE TRADITIONAL APPROACH
• Processes Validated at Life cycle commencement
• Operated/Controlled by Standard Operating
  Procedures (SOPs)
• Quality Assurance based on off-line testing of a
  sample of product at the end of each batch
• THE PAT BASED APPROACH
• On or at line Analysis for real time quality
  control of each unit operation process control
  throughout the batch
• Real time statistically based quality assurance
  throughout the batch
• Increased statistically based testing regimes
  provide the potential for release of product
  without further off-line testing

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QUOTATION 1
THE NEED FOR STATISTICS
Statistical thinking will one day be as
necessary for efficient citizenship as the
ability to read and write
H G WELLS 1925
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Implementation of the TQM Strategy

• In-Process Control Monitoring
• Key Process Operations
• Identification / specification of all incoming
  raw materials in the dispensaries ( the
  warehouse)
• Fluid Bed Drier end point control
• Continuous in-line monitoring of blending end
  point control
• In-line monitoring of Tablet Quality parameters
  against registered specifications
• 21CFR11 compliant data management system
• Real-time continuous quality assurance
• The platform for parametric release

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Solid Dosage Facility
FB Drier
Dispensary
Wet granulation
Direct Compression
Milling
Press
Blender
Sieve
Figure 1
Coater
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GENERALISED MODEL OF A PAT SYSTEM

• THE MODULES (Functionalities)
• Spectral (or other) data/model storage
• Analytical (or other) data storage
• Modelling
• Reporting (Batch and Validation Records and
  Storage)
• Statistical Process control (SPC) and Historic
  Trending
• THE MODES OF OPERATION
• Modelling
• Validation
• Manufacturing

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GENERALISED MODEL OF A PAT SYSTEM
Figure 2
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CONSIDERATIONS FOR THE VALIDATION WG

• Regulatory status of Model source Data (Spectral
  analytical etc.) traceability and long term
  storage
• Traceability of spectral data, related,
  analytical data and model predictions for the
  model validation phase and its long term storage
• In manufacturing what form will the PAT batch
  record and release data take,How can it be used
  by QA to release product and how would a
  regulatorybody inspector find an audit path from
  it for verification
• The MES/SPC Activities provide process
  understanding and knowledge What regulatory
  status if any is associated with them

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FURTHER AREAS FOR DISCUSSION

• Registered processes (traditional) and
  statistically quality controlled processes
• Fundamental science and validation
• 21CFR11 and Computer validation complexity Open
  and closed systems

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QUOTATION FOR THE DAY
THE IMPACT OF INNOVATION

• There is nothing More difficult to plan
• More doubtful of success
• More dangerous to manage
• Than the creation of a new system
• For the initiator has
• The enmity of all who profit by preservation of
  the old institutions
• AND
• Merely lukewarm defenders in those who should
  gain by the new ones
• Machiavelli (1527)