The GCC guidelines for variation requirements (Version 3.0)
This article is summary of GCC guidelines for variation requirements in API. In introduction, the guideline
mentions that it is adapted from the EMEA guideline on the details of the
various categories of variations, Regulation (EC) No. 1234/2008 article
4(1)(a), Doc Ref: EMEA/122634/2009[1].
This document has been developed to assist applicants
in the preparation and submission of drug applications for variations to exist
products to the SFDA [1].
What is definition of variation?
Variation means a post approval 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
pharmaceutical product, ingredients, container and container labelling, and
product information. [2]
Scope [1]:
This document applies to change(s) made on drug
product that have already received a marketing authorization from the SFDA.
General notes [1]:
GCC has provided
some general notes which the applicant should follow when submitting any
variation application. They are as follows:
- - All
variations requests should be sent through applications for variation to
marketing authorizations which is available on SFDA website [1].
- - Whatever
the changes are being presented, they should be presented in a comparative
tabular format [1]. This will help the reviewer to get clear idea of
the intended change.
Example:
Summary of change:
(Summarize
the intended changes)
Before change
|
After change
|
- - A
justification should be provided for reason of introducing the change/
variation [1].
- - Some documents such as certificate of analysis (COA), specification sheet, approval letters from the country of origin etc. should be submitted when relevant [1].
- - SFDA
can request any additional information and data which is not specifically
described in the guideline, in order to assess quality, safety and efficacy of
the drug product [1].
- - “Days”
mentioned in the guideline are working days (subjected to change). [1]
- - Deficient
documents may lead to rejection of the application whereas redundant or
irrelevant information may hamper approval procedures [1]
Types of variation [1]
The variation or post marketing changes are classified
into two categories:
A (Minor changes) and B (Major
changes)
Minor change is further categorized into two types, Type 1A and Type 1B
 |
| types of variation |
A (Minor changes):
Type IA:
- - These are minor variations and do not require prior approval before implementation.
- - These are “Do and Tell” procedure, meaning first these changes can be implemented and then notified to agency. However, this notification needs to be submitted by the marketing authorization holder (MAH) within 60 working days after implementation.
- - When one or more conditions established in this guideline for minor change of Type IA are not met, the concerned change may be submitted as Type IB variation unless the change is specifically classified as a major change variation of type II.
- -Type IA variation will be rejected when not all of the conditions for the Type IA variation are met, the MAH shall immediately cease to apply the rejected changes.
Type IB:
- -Such
minor variations must be notified to the SFDA by the Marketing Authorization
Holder (MAH) before implementation, but do not require a formal approval.
- -However,
the MAH must wait a period of 120 working days to ensure that the application
is deemed acceptable by the SFDA before implementing the change.
- - These
are “Tell, Wait and Do” procedure.
B. (Major variation):
Type II:
- - These
are major variations which may have a significant impact on the Quality, Safety
or Efficacy of a medicinal product and require prior approval before
implementation.
-
This guideline mentions detailed requirements of types
of changes, conditions to be fulfilled and documents to be supplied for
respective change.
The guideline further mentions 3 appendices [1].
Appendix 1 is list of some major changes and most minor changes which
are classified by the type of change and the conditions which frame the type of
change. When the conditions are not met, the change may either classified as a
major change or may make a new application necessary.
Appendix
2
lists examples for major changes.
Appendix
3
lists the types of changes that make a new application (New DMF) is necessary.
After going through
guideline, following points are observed:
- v All administrative changes come under Minor Change/
Type I A variation.
- v Changes related to manufacturing section, control of
drug substance, container closure system and stability section come under Major
change/ Type I B and Major change/ Type II variation.
- v Tightening of specification or any limits will come
under Minor Change/ Type I A variation.
Some examples are tabulated as below:
 |
| example of changes |
References:
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