Comparability Protocols

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Comparability Protocols

• Lore Fields MT(ASCP)SBB
• Consumer Safety Officer
• DBA/OBRR/CBER
• September 16, 2009

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Agenda

• Define Comparability Protocol (CP)
• When can a CP be used?
• CP Submissions
• Content of CP submissions
• Content of subsequent submissions
• Summary

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Comparability Protocol (CP)

• What is a CP?
• Described in 601.12(e)
• An applicant may submit one or more protocols
  describing the specific tests and validation
  studies and acceptable limits to be achieved to
  demonstrate the lack of adverse effect for
  specified types of manufacturing changes on the
  identity, strength, quality, purity, or potency
  of the product as they may relate to the safety
  or effectiveness of the product. Any such
  protocols, or change to a protocol, shall be
  submitted as a supplement requiring approval from
  FDA prior to distribution of the product which,
  if approved, may justify a reduced reporting
  category for the particular change because the
  use of the protocol for that type of change
  reduces the potential risk of an adverse effect.

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Comparability Protocol (CP)

• What is a CP? (cont)
• Submission option
• Highly specific, well-defined plan for
  implementing a change in manufacturing
• Demonstrate that change does not affect safety,
  identity, purity or potency

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Comparability Protocol (CP)

• What is a CP? (cont)
• Specific for the change and for the applicant
• FDA will approve CP if change does not adversely
  affect product
• Approval of CP may allow a reduced reporting
  category for future implementation of the
  specific change in the CP
• Expedite interstate distribution of products
• Not appropriate for all changes

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Comparability Protocol (CP)

• When can a CP used?
• Product manufactured using the change will meet
  approved product standards
• Manufacturing process has been validated and all
  equipment has been qualified
• Appropriate validated assays are available to
  detect effect of the change on the product
• Implementation of single change in multiple
  locations operating under the same license using
  SOPs, forms, labels, etc. approved in CP

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Comparability Protocol (CP)

• When should a CP not be used?
• Broad plan covering any conceivable change
• Change has potential to adversely effect product
• Pre-specified acceptance criteria are not
  available to determine effect on product
• Change results in newly defined product that is
  not licensed
• Use of new manufacturing facility needing
  pre-license inspection
• Change in process, equipment or facility that may
  need pre-approval inspection

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Comparability Protocol (CP)

• CP Submissions
• Submit as a PAS under 601.12(b)
• May be combined with product manufacturing
  supplement
• Once approved, CP must be implemented exactly as
  described in CP
• If implementation deviates from CP, all future
  submissions for same change must be reported as
  PAS

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Comparability Protocol (CP)

• CP Submissions
• Future supplements reporting implementation of
  same change described in CP may be reported in
  reduced category specified in approval letter
  (eg, PAS to CBE30)
• Supplements reporting implementation of CP should
  include information committed to in approved CP
• Submit a new CP or a change to an existing
  approved CP as a PAS

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Routine SubmissionExample

• Applicant wants to implement Platelet Pheresis
  collection at 4 centers using instrument X
• Implements at center 1
• Develops SOPs performs testing, validation,
  training, etc.
• Submits supplement for center 1 as PAS
• FDA approves implementation at center 1
• Center 1 distributes product interstate after
  approval
• Submits implementation at centers 2 - 4 as PAS
• Distribute product interstate after approval

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Comparability Protocol (CP)Example

• Applicant wants to implement Platelet Pheresis
  collection at 4 centers using instrument X
• Implements at center 1
• Develops CP and SOPs performs testing,
  validation, training, etc.
• Submits CP and supplement for center 1 as PAS

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Comparability Protocol (CP)Example

• FDA approves CP and implementation at center 1
• Approval letter states future implementation of
  CP may be reported as CBE30 and expected content
• Center 1 distributes product interstate after
  approval
• Submits implementation for centers 2 - 4 using
  approved CP as CBE30
• Implementation must follow CP implementation plan
• Distribute product interstate 30 days after FDA
  receives supplement

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Comparability Protocol (CP)

• Contents of CP Submission
• FDA form 356h
• Cover letter
• SOPs
• Records and Forms
• Product Quality Control Logs
• Labeling
• May reference previously approved SOPs, forms and
  labeling (include reference number)

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Comparability Protocol (CP)

• Contents of CP Submission (cont)
• Description of the change
• Implementation plan, including description of
  training
• Specific tests and validation protocols
• Product acceptance criteria
• Supportive data obtained from testing and
  validation
• summary of validation and
• 2 months QC

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Comparability Protocol (CP)

• Contents of CP Submission (cont)
• QC testing procedures, including sampling plan
• Description of actions if acceptable results not
  achieved
• QA program oversight
• Request a CBE-30 downgrade for subsequent
  facilities

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Comparability Protocol (CP)

• Subsequent Submissions Content
• Cover Letter
• Summary of Validation
• 2 Months QC

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Summary

• Comparability Protocol is a submission option
• Specific change for manufacturing product
• Requires full evaluation of potential impact of
  change on product
• May allow future implementation of CP in a
  reduced reporting category expedite interstate
  distribution

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Summary

• CP must be implemented exactly as approved
• Report any changes in approved CP
• CP not appropriate for all types of submissions