Article 5 recommendation: classification request under the Variations Regulation
An Article 5 recommendation is a formal classification ruling from the CMDh or EMA on a change that the variation classification guideline does not cover.
Article 5 of Commission Regulation (EC) No 1234/2008 gives holders and authorities a route to settle how an unlisted change should be classified before it is filed. A holder, or a Member State's competent authority, asks the CMDh for a recommendation where the product is nationally authorised, including through the mutual recognition and decentralised procedures, or asks EMA where the product is centrally authorised. The request describes the change and explains why the existing classification guideline and the default Type IB category do not give a clear answer.
The CMDh or EMA considers the request and issues a recommendation on whether the change is a Type IA, Type IB or Type II variation, or an extension. Recommendations are published, so other holders can rely on them for the same kind of change, and the Commission takes them into account when it next updates the classification guideline. In practice the published lists of Article 5 recommendations have become a second reference alongside the guideline, especially for changes to novel manufacturing processes, device components and digital elements that the guideline did not anticipate.
What goes wrong: filing a change as Type IB by default when a published recommendation already classes it as Type II, which the authority will pick up at validation; asking for a recommendation for a change that the guideline does list, which is refused; and treating a recommendation as authority-specific when it applies across the procedure type. Companies also lose time by asking for a recommendation late, after the regulatory and manufacturing timelines have been fixed around an assumed category, and by submitting a request so thin that the group cannot judge the impact of the change.
Where a change is borderline, a recommendation gives certainty on the category, the timetable and the fee before resources are committed. For a change that affects both centrally and nationally authorised products, the holder may need to approach both EMA and the CMDh, which usually coordinate their answers.
Under the new pharma package (not yet in force), variation categories and procedures will be set by Commission delegated acts, which will determine how classification questions are handled; see variations changes.
Timing
Under Article 5(2) of the Regulation the CMDh or EMA delivers its recommendation within 45 days of receiving a valid request. The period can be extended by 25 days where consultation with EMA or the CMDh is needed because the change affects products in the other procedure. The recommendation is then published and the holder files the variation in the recommended category.
Used in
Before filing, search published Article 5 recommendations and the classification guideline for a change in Workbench, with every answer cited.
Related terms
- Classification guideline: Commission guideline on variation categoriesThe classification guideline is the Commission's list of variation changes, with the conditions and documents that make each one Type IA, IB or II.
- Type IB variation: minor change notified before implementationA Type IB variation is a minor change that is neither Type IA nor Type II and must be notified to the authority before it is implemented.
- Type II variation: major change requiring prior approvalA Type II variation is a major change that may significantly affect a medicine's quality, safety or efficacy and needs approval before implementation.
- CMDh: Co-ordination Group for Mutual Recognition and Decentralised ProceduresThe CMDh is the group of national authority representatives that resolves disagreements in MRP and DCP and coordinates nationally authorised medicines.
- Line extension: extension application to an existing authorisationA line extension (in EU terms, an extension application) adds a new strength, pharmaceutical form or route of administration to an authorised product.
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