Comparability Protocols

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Comparability Protocols
Nancy Sager Associate Director,
QIS-Chemistry FDA/CDER/OPS
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Overview

• What is a comparability protocol?
• Why has FDA issued a guidance on comparability
  protocols?
• What are the benefits of using comparability
  protocols?
• Why are we making the ACPS aware of this
  guidance?
• What are the principles of comparability
  protocols? (Stephen Moore)

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Comparability Protocols

• A well-defined, detailed written plan for
  assessing the effect of specific postapproval
  chemistry, manufacturing, and controls (CMC)
  changes on the identity, strength, quality,
  purity, and potency of a specific drug product
• A plan for anticipated future CMC changes
• The protocol can be submitted in an original
  application or a prior approval supplement
  (postapproval)

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Why Develop a Guidance

• Concept for comparability protocols first
  introduced for biotechnology products (1997)
• Industry requests to extend concept to all drugs
  and for additional guidance

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Why Develop a Guidance

• Provide recommendations to applicants on
  developing a protocol to assess the effect of
  postapproval changes based on specific knowledge
  of a product and process (e.g., development data,
  manufacturing experience)

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Why Develop a Guidance

• Consistent and complimentary to FDA initiatives
  on risk management
• A well-planned protocol provides sufficient
  information for FDA to determine whether the
  potential for an adverse effect on the product
  can be adequately evaluated and can lower the
  risk for implementing the change without FDAs
  prior approval
• Augments the Scale-up and Postapproval Changes
  (SUPAC) and Changes to an Approved NDA or ANDA
  guidances

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Why Develop a Guidance

• Consistent and complimentary to FDA initiatives
  on pharmaceutical cGMPs for the 21st century
• Promote continual process and product improvement
  and innovation by facilitating CMC changes

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Benefits

• FDA can designate, where appropriate, a reduced
  reporting category for future reporting of CMC
  changes covered by the approved protocol
• Prior approval supplement
• Changes-being-effected in 30 Days supplement
  (CBE-30)
• Changes-being-effected supplement (CBE-0)
• Annual report

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Benefits

• An FDA request for additional information to
  support a change is less likely when the change
  is covered under an approved protocol
• Could allow an applicant to implement CMC changes
  and place product in distribution sooner than
  without the use of a comparability protocol

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Benefits

• Allows companies to design their own SUPAC
  based on their knowledge of and experience with a
  product
• Provides an opportunity for a reduced reporting
  category for CMC changes when the dosage form is
  not covered by a SUPAC type document

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ACPSs Role

• At this time, CDER has little experience with
  comparability protocols. The ACPS may be asked
  to provide advice on
• Issues raised by public comments on the
  guidance
• Specific proposals for comparability protocols

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Guidance

• Available at http//www.fda.gov/cder/guidance/542
  7dft.pdf
• Draft guidance published February 25, 2003
• Comment period closes June 25, 2003