Criteria For Creating MRP Grouped VariationsAccording to Article 7 of the variation Regulation, Commission (EU) No 1234/2008, there are particular cases in which several variations can be grouped and submitted simultaneously under 1 application. The three cases are listed below: 1) The same holder applying for several identical variations of type 1A or IAIN to the terms of one or several marketing authorisations to the same authority eg. One variation to several MAs, Several identical variations to several MAs, several Variations to one MA. 2) The same holder applies for several identical variations of type IA to the terms of one or several marketing authorisations to the same authority 3) Annex III of the regulation lists examples of where it is possible to group several variation types as referred to in Article 7(2)(b) and 13d(2)(b) of the regulation. These variations include grouping Type IA, IAIN, IB and II or extension applications to the terms of the same marketing authorisation at the same time into one application. In the case where several variations are not listed in Annex III, under Art 7(2)(c), the RMS in consultation with the CMS may agree to group these single variations to one procedure.
The Variation TypesThe Variation type and the timetable of the grouped application is dependent on the highest type of single variation included in the group ie. if there is at least one type IB variation (Article 9) included with other minor or Type IA variations then the variation is classified as a type IB and will have the type IB timetable assigned. In the case where a grouped variations highest type is an extension application it will be handled according to the timelines of a new application procedure. The grouped variation is submitted as one single application with one variation procedure number and only one CTS record. The exception to this is in the case of national MAs where the variation procedure number has to be allocated according to the national rules of the relevant CA and there will be no CTS record created. MRP Grouped variations are submitted simultaneously to the RMS and CMS and should contain the elements detailed in Annex IV of the Regulation, presented in eCTD format. In the case where the applicant is submitting a grouped variation of Type IA and IAIN for a group of products with different RMSs, a lead RMS must be appointed, the lead RMS will then issue the variation procedure number and commence communication with the other member states. For consequential variations the relationship between the variations should be clearly explained in the eAF to ensure it is clear to the authorities why the variations have been grouped. With regards to the associated fees for a grouped variation, each variation applied for is declared as a separate variation and therefore each variation incurs a separate fee.
- To prevent a delay in approval of a grouped variation, it is possible for the MAH to withdraw single variations from the group if the particular variation is causing issues with validation or if it appears that it may not be approved.
- On approval of the grouped variation the RMS will circulate the approval letter to the MAH and the CMS will be notified via CTS.
- In the case where a variation is not approved or withdrawn the RMS will issue a combined letter stating the reasons, the letter is sent to the MAH and also shared with the CMS on CTS.
- In the case where a CMS cannot approve the application on the basis of a potential serious risk to public health, the RMS will refer the procedure to the CMDh, following receipt of a statement from the CMS detailing the reasons for not approving the application.
- CMDh/173/2010 lists Examples for acceptable and not acceptable groupings for MRP and DCP products.
General Points to Note on Variations
- Any variations that are grouped should be consequential or the reason for grouping should be obvious to the agency.
- Although grouping is encouraged It is not recommended to group for reasons of ‘convenience’. The MAH must ensure, particularly in the case of product information updates, that the recommended or expected approval times are adhered to.
- It is not recommended to group Quality, non-clinical and clinical changes.
- Quality changes to the active substance should not be grouped with quality changes to the finished product unless justified.
- Type IA and IAIN variations for the implementation of safety-relevant changes should not be grouped with type IB or type II variations as this can cause a delay in the implementation of the safety-relevant information.
- All of the changes in one variation application must apply to all of the products that are listed in the eAF. It is not permitted that single changes in the application apply to one or some of the products listed.
- The eAF should be completed with sufficient detail in relation to the classification of each individual variation. If there are two variations with the same classification included in the grouping these must be listed individually on the form. The scope must clearly detail all of the changes individually and all relevant justifications should be included. The present and proposed section should contain concise details for each change.
Further Reading from Acorn Regulatorymore than 5600 orphan designated drugs in the biopharmaceutical pipeline. As the sector continues to grow there has been a tendency for facts about orphan drugs to get lost in the midst of issues concerning specific patients’ needs, pricing and availability. We look at some facts about orphan designation that companies considering entering the sector should be aware of. Read more about orphan drugs here. Title V of Directive 2001/83/EC on the ‘Community code relating to medicinal products for human use’ (as amended). Read more about medicinal product labelling here.
- Companies that maintain control of electronic publishing at the corporate and head office level
- Others that have retained the day-to-day eCTD maintenance and lifecycle at a local level
- Companies that have outsourced eCTD entirely