HIGHLIGHTS ON GUIDELINES FOR VARIATION

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HIGHLIGHTS ON GUIDELINES FOR VARIATION
Stakeholders meeting 16 May 2008, Land Mark
Hotel, Dar Es Salaam David Matle
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Presentation outline

• About the guidelines
• Definition
• Applicability of the guidelines
• Types of Changes
• Requirements for Submission
• Questions

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About the Guidelines

• Made under the Guideline (Fourth Edition)
• Consultations made Guidance Document on
  Variations to a PQ Product Dossier
• First edition
• Defines a more systematic and easy way of
  handling variations to registered products

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DEFINITION

• Variation
• Means a change to any aspect of a pharmaceutical
  product, including but not limited to a change to
  formulation, method and site of manufacture,
  specifications for the finished product and
  ingredients, container and container labelling
  and product information.

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Applicability of the guidelines

• Applicable only to APIs and chemically
  synthesized or semi-synthesized excipients
• FPPs containing such APIs and excipients.
• Minor changes denoted by a letter N are
• considered as Notifications (Do not need TFDA
  approval)
• All other changes must get TFDA approval
• Fee - Fees and Charges Regulations in force

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Types of Changes

• Four Annexes define various types of changes
• Annex I Lists minor changes
• Annex II Lists examples of major changes.
• Annex III Lists types of changes which make
  a new application necessary.
• Annex IV Lists stability requirements for
  variations and changes to registered FPPs

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DOSSIER REQUIREMENTS FOR MINOR CHANGES Annex I

• The guide clarifies what documentation should be
  submitted with each type of minor change
• Dossier all parts affected by a variation are
  to be resubmitted
• Present a summary in a tabulated format

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DOSSIER REQUIREMENTS FOR MINOR CHANGES Annex I

• Justification for the change should be provided.
• Redundant or irrelevant information does not
  facilitate rapid procedures
• Deficient documentation - Non-validation/rejection
  of the change.

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Example of a Minor change

• Conditions
• 1. The site is appropriately authorized by the
  NDRA.
• 2. Method transfer from the old to the new site
  or new test laboratory has been successfully
  completed.
• Documentation
• 1. The corresponding letter should clearly
  outline the registered and proposed quality
  control sites.
• 2. Documented evidence that the site is
  appropriately authorized by the NDRA.
• 3. Documented evidence that the Method transfer
  from the old to the new site or new test
  laboratory has been successfully completed.

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MAJOR CHANGES Annex II

• Exceed the scope of minor changes
• i.e. they exceed/do not comply with the
  conditions to be fulfilled along with the change,
  but still do not cover the changes listed in
  Annex III.
• Most likely consist of
• Change in the manufacturing process of the API
• Change in the composition of the finished product
• Change of immediate packaging of the product
• Applicant to provide relevant documentantion
  Prove quality of the product

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CHANGES THAT MAKE A NEW APPLICATION Annex III

• Changes to the API
• Change of the API to a different API.
• Inclusion of an additional API to a
  multi-component product.
• Removal of one API from a multi-component
  product.
• Change in the dose of one or more APIs.

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Cont..

• Changes to the pharmaceutical
• form/dosage form
• Change from an immediate-release product to a
  slow- or delayed-release dosage form and vice
  versa.
• Change from a liquid to a powder for
  reconstitution, or vice versa.
• Changes in the route of administration

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STABILITY REQUIREMENTS Annex IV

• In all cases of variations and changes
  Investigate Quality of API and Stability
• Stability data required - Test conditions - refer
  to the Guideline (Fourth Edition)
• Variations - generation of stability data on the
  FPP Studies should be continued up to the
  approved shelf-life
• Problems during storage?? Inform TFDA

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Thank you
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• Questions?
• Discussions
• Comments