Variations

Variations

In accordance with Regulation (EEC) No. 2309/93 and Directives 2001/82/EC and 2001/83/EC, a common approach to the procedures for variations to the terms of a marketing authorisation have been identified. These procedures facilitate the task of both industry and authorities and also guarantee that changes to the medicinal product do not give rise to public health concerns.

Note: An invoice on the application fee will be sent upon receipt of the application, so no payment should be made in advance. For further information regarding fees, see “Fees” in the left margin.

Variation Regulation (EC) No 1234/2008 and LVFS 2006:11

The variation regulation (EC) No 1234/2008 applies from 1 January 2010 for medicinal products approved via the mutual recognition procedure (MRP), decentralised procedure (DCP) and the centralised procedure. The new variation regulation replaces the former regulations: (EC) No 1084/2003 (MRP/DCP) and (EC) No 1085/2003 (centralised marketing authorisations).

Also for nationally approved medicinal products the MPA accepts, from January 1, 2010, variation applications submitted according to the regulation (EC) 1234/2008, but with different timelines, see information about timetables below. As of October 1, 2010 variation applications submitted according to the old regulation will not be accepted. Note that worksharing does not apply to nationally approved medicinal products until regulation (EC) 1234/2008 has been updated with information regarding nationally approved medicinal products. See press release from CMDh;

 Report from the CMDh meeting, December.

For information regarding variations for centralised marketing authorisations, see “European Medicines Agency (EMA)” in the right margin.

Current legislation

Medicinal products approved via MRP/DCP and the centralised procedure:
Commission regulation (EC) No 1234/2008. See “Current legislation” in the right margin.

Nationally approved medicinal products:
MPA’s Codes of statutes LVFS 2006:11, which includes a reference to regulation (EC) No 1234/2008. See “Current legislation” in the right margin.

Application form, procedure number and guidelines

Application form is available under “Application form and Regulatory Guidance” in the right margin, where you also find links to guidelines from the Commission and the CMD. Relevant part of the Commission classification guideline should be attached to the application form for type I variations and the relevant boxes for conditions and documentations need to be ticked.
Allocation of variation procedure number for human medicinal products are handled by the applicant according to Chapter 1 of the CMD(h) Best Practice Guides for the Submission and Processing of Variations in the Mutual Recognition Procedure. With the new variation Regulation (EC) No 1234/2008 arises, however, two exceptions:

– Grouping > IMA (IA variations only)
– Worksharing

In these cases, the variation procedure number needs to be obtained from the Reference Member State or Reference Authority (worksharing). For veterinary medicinal products, the RMS/Reference Authority allocate variation procedure number, as in the past. Requests for variation procedure numbers should be sent to email address: sok.central@mpa.se.

Electronic submissions

The MPA accepts electronic only applications (NeeS or eCTD) but the switch from paper to e-only has to be applied per product. For further information on electronic submissions and the switch from paper to e-only, see "Electronic submissions "in the left margin.

If the application is submitted in paper format, an electronic copy of the background documents is still recommended.

Information from the MPA in connection with variation applications

For nationally authorised medicinal products, a confirmation letter/approval letter is sent to the applicant when the case is closed. For applications in the mutual recognition procedure, the RMS/Reference Authority always notifies the end of the procedure. In order to facilitate communication between agencies and the applicant, it is essential that an e-mail address is provided in the application form. In cases where the product information is affected, updated Swedish texts and confirmation letter/approval letter will be sent separately from the MPA.

Timetables (days)¹

Prior to start of variation procedures, there is a mandatory auto validation period (7 calendar days for type IB, and 14 calendar days for type II). Note that a clock stop in the mutual recognition procedure includes both the applicant's reply limit and the authorities’ time to assess the response. In the national procedure, the procedure is re-started upon receipt of the response.

Recommendations

In order to make it possible for us to process the applications within the narrow timeframes given, it is essential that all supporting documents are submitted with the application. Preferably, separate cover letters should be used for type IA, IB and type II variations, respectively. Note that the MPA recommends that quality variations and clinical variations are submitted as separate applications.
For IA and IB variations that affects the product information, only changes resulting from the variation applied for, i.e. the name of the product, the name or address of the MAH etc, will be considered. If the MAH wants to make other changes in the texts, they are to be submitted separately. For these IA and IB variations, revised product information should be submitted with the application in which the changes appear as tracked changes and for products approved in the mutual recognition procedure, both in Swedish and in English.

The product information in the context of variations

When contacting the MPA regarding the product information please use the latest approved version of the current product information (published on the MPA website). All proposed changes should be presented using the Word feature "track changes". It should be clearly stated in the cover letter, what changes have already been implemented in the product information and the date it occurred. The cover letter should also indicate a reference to the variation procedure number, as appropriate, and a brief description of the variation.

Approval letter and updated Swedish product information (SmPC, PIL or labelling) will be sent to the applicant (MAH or the local representative) for all types of changes that affect the product information. If the applicant feel it necessary to implement IA and IAIN variations in the product infomration before the MPA has sent out approval letters, applicants can enter a new date of approval in the product information. If so, the text in the package leaflet is changed as follows:  "This leaflet was last approved ..." to "This leaflet was last updated ...". Section 10 of the SmPC is however left unchanged. When the updated product information is then sent from the MPA, it will have a new approval date. MAH should then at the next printing update their package leaflet with this date and also change back to the original wording: "This leaflet was last approved ..." in accordance with the approved version published on the MPA website. In all other cases, we ask the applicant to await the approval letter with updated product information prior to the amendment in question is implemented in the product information.

National type II variations regarding update of the SmPC: Submission information

When applying for a national type II variation for a SmPC change the requirements for documentation is the same as in the mutual recognition procedure. The following documents are needed:

• Cover letter and Variation application form
• A summary report justifying the proposed change with cross-references to the scientific papers, case reports and/or study reports referred to in the application
• Original scientific papers and study reports referred to (if not earlier submitted as an eCTD sequence)
  Please note that review articles, core data sheets and extracts from texts books are not considered detailed enough for the scientific assessment
• SmPC in electronic (word) format as tracked changes version. When affecting PL and labelling, these should also be submitted in this format (Please, use the “tracked change function” in word).
• It is recommended that the background documents are submitted also in an electronic format to allow an expedite process.

Update of the dossier prior to MRP with Sweden as RMS (including repeat-use)

For further information see “Update of the dossier prior to MRP with Sweden as RMS (including repeat-use)” under heading “New applications” in the left margin.