ACPS November 15, 2000

1
ACPSNovember 15, 2000

• 314.70 Update
• Nancy B. Sager, Associate Director
• Office of Pharmaceutical Science
• Center for Drug Evaluation Research
• Food and Drug Administration

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Regulatory Approach

• CDERs regulatory approach to post approval CMC
  changes is evolving
• 21 CFR 314.70 (1985 rewrite)
• SU/PACs (early 90s to present)
• FDAMA (1997)
• Implementation of FDAMA 116 (now)
• Next ?

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21 CFR 314.70Supplements and Other Changes to
an Approved Application (1985 rewrite)

• The applicant shall notify FDA about each change
  in each condition established in an approved
  application beyond variations provided for in the
  application
• Provides a general listing of changes with
  reporting mechanisms

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Scale Up/Post Approval Change - Guidance Documents

• Minor change
• Moderate change
• Major change
• Application / Compendial Tests
• In Vitro Dissolution / Release
• In Vivo
• Annual Report
• Changes Being Effected Supplement
• Prior Approval Supplement

Level of Changes

Tests
Filing
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FDA Modernization ActSection 116 (November 1997)

• Recognized the importance of the SU/PAC approach
• Amended the Food, Drug, and Cosmetic Act by
  adding Section 506A
• Required revision of 314.70
• Guidance was developed to document FDAs current
  thinking on how to apply Section 506A

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FDAMA Section 116

• Reporting categories are based on the potential
  for the change to adversely affect the identity,
  strength, quality, purity, or potency of a
  product as they may relate to the safety or
  effectiveness of the drug product.

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FDAMA Section 116Reporting Categories

• Substantial potential
• Prior approval supplements
• Moderate potential
• Supplement changes being effected in 30 days
  (CBE-30)
• Supplement changes being effected (CBE-0)
• Minimal potential
• Annual reports

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FDAMA 116 Implementation Status

• Draft guidance published for public comment on
  June 28, 1999 comment period closed on Aug. 27,
  1999 final guidance published Nov. 1999
• (30 comment letters, 1200 individual comments)
• Proposed regulation published for public comment
  on June 28, 1999 comment period closed on Sept.
  13, 1999
• (30 comment letters, 300 individual comments)

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Changes to an Approved NDA or ANDA (Nov. 1999
guidance)

• Modeled on SU/PACs
• Recommends reporting categories only
• Covers all dosage forms
• No recommendations on specific information that
  should be developed by the applicant to assess
  the effect of the change

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FDAMA 116 Implementation Status

• The November 1999 guidance on Changes to an
  Approved NDA or ANDA represents FDAs current
  thinking on how it will apply the requirements of
  section 506A of the Act for NDA and ANDA
  products.

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FDAMA 116 Implementation Status (contd)

• Until the final regulation for 314.70
  publishes, section 506A is the sole basis for
  FDAs regulation of postapproval manufacturing
  changes for products approved in NDAs or ANDAs

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FDAMA 116 Implementation Status (contd)

• The final rule for 314.70 has been drafted and
  is in the beginning stages of the clearance
  process (ETA winter/spring)
• The guidance on Changes to an Approved NDA or
  ANDA is being revised to conform to 314.70 and
  will publish at the same time as the final rule.