CBER Manufacturing Changes

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CBER Manufacturing Changes

• Rebecca A. Devine, Ph.D.
• FDA/PDA Joint Conference
• Breakout

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CHANGES TO AN APPROVED APPLICATION

• Proposed Rule, Federal Register, Vol. 61, No. 19,
  2739, Monday January 29, 1996
  
• Final Rule, Federal Register, Vol. 62, No. 142,
  39890, Thursday July 24, 1997

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CHANGES TO AN APPROVED APPLICATION - 21 CFR 601.12

• Supplement - Prior Approval (PAS)
• 30 Day Supplement - Changes Being Effected (CBE)
• CBE (30 days waived)
• Annual Report

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VALIDATION/LACK OF ADVERSE EFFECT

• Appropriate validation and/or
• Clinical and/or
• Non-clinical laboratory studies

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PRIOR APPROVAL SUPPLEMENTMAJOR CHANGES

• Change requiring human study of equivalence
• New master cell bank or seed
• Affect product sterility assurance
• Changes in
• Qualitative or quantitative formulation/specs
• Virus/adventitious agent removal/inactivation
• Source material or cell line

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CHANGES BEING EFFECTED IN 30 DAYS

• Products may be distributed 30 days after FDA
  receives the supplement
• 30 days to ensure proper categorization and
  completeness
• Waiver of 30 days possible

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SUPPLEMENT CHANGES BEING EFFECTED IN 30 DAYS

• Change in site of testing
• Increase/decrease in scale during finishing steps
  w/ new or different equipment
• Replacement of equipment if similar in design and
  operating principle (no change in methodology)

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WAIVER OF 30 DAYS FOR CBE

• Waiver of 30 days possible under 601.12(c)(5)
• Based on experience with the change it is usually
  complete
• Similarity to a change which is a CBE
• Guidance document
• Comparability protocol

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SUPPLEMENTS (PAS and CBE) CONTENTS

• Detailed description
• Products involved
• Manufacturing sites or areas
• Methods used and studies performed
• Data from the studies
• Validation protocols and data
• List of relevant SOPs

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ANNUAL REPORTMINOR CHANGES

• Change to comply with official compendium
  (consistent w/ FDA requirements)
• Deletion of an ingredient which only affects
  color
• Extension of expiration date based on full data
  from approved protocol
• Addition/deletion of an alternate analytical
  method

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ANNUAL REPORT - CONTENTS

• A list of all products involved
• Full description of manufacturing and controls
  changes including
• Date
• Cross reference to relevant SOPS and validation
  protocols
• Manufacturing sites
• Data

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COMPARABILITY PROTOCOL21 CFR 601.12 (e)

• An applicant may submit one or more protocols
  describing the specific tests and validation
  studies and acceptable limits to be achievedfor
  specified types of manufacturing changes...