Variations

The variation regulation (EC) No 1234/2008 regulates variations to a marketing authorisation for medicinal products approved via the national procedure, the mutual recognition procedure (MRP), decentralised procedure (DCP) and the centralised procedure.

For changes not covered by the variation regulation, please see links in the left margin leading to pages for Article 61(3) notifications, MAH transfer, changes to the local representative or change in legal status (OTC).

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

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.

Application form, procedure number and guidelines

Under "Application form and Regulatory Guidance" in the right margin you will find links to the application form and guidelines from the Commission and the CMD. The electronic application form is mandatory in all procedures as of 1 January 2016. The MPA strongly recommends submission in one of the electronic formats accepted in EU, eCTD, NeeS or VNeeS, for all application types. For further information on electronic submissions see "Electronic submissions "in the left margin.

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. However, with the variation Regulation (EC) No 1234/2008 arises two exceptions:

  • For Grouping including more than one MA in the mutual recognition procedure (type IA only) the variation procedure number needs to be obtained from the Reference Authority.
  • For Worksharing the pre-submission information should be submitted to the preferred reference authority. For more information see Chapter 7 of the CMD(h) Best Practice Guides for the Submission and Processing of Variations in the Mutual Recognition Procedure.

For veterinary medicinal products, the RMS can still allocate variation procedure number upon request.

Requests for variation procedure numbers should be sent to email address: RIC@mpa.se.

The list of dispatch dates when Sweden is RMS for MR/DC products should be sent to email address RIC@mpa.se.

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. When Sweden is CMS, a national approval is only sent when the Swedish product information is affected.

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

Variation type 

National procedure 

Mutual recognition procedure

Type IA 

30

30

Type IB

30 (60)

30 (60)

Type II reduced (e.g. following USR)

60 (90) 

22 (30)

Type II standard 

60 (90)

60 (90)

Type II extended (e.g. change in therapeutic indication or addition of non-food producing target species)

90 (150)

90 (120)

1 Primary round. Total evaluation time excluding clock stop is given within the parenthesis.

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.

For type IA variations that affect the product information, only changes resulting from the variation applied for will be considered. If the MAH wish to make minor editorial corrections in the texts in connection with a variation type IB or II under chapter C in the classification guideline and that affects the product information, the corrections should be clearly outlined in the application form under scope and present/proposed, and marked as tracked changes in the product information.

Regarding grouping of variations, the MPA supports the CMDh recommendations for acceptable groupings for purely nationally authorised products also (see ”Examples for acceptable and not acceptable groupings for MRP/DCP products” on CMDh webpage linked in the right margin).

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, which 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 and/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 finds it necessary to implement IA and IAIN variations in the product information before the MPA has sent out approval letters, applicants can enter a new date of revision in the product information. When the updated product information is sent from the MPA, it will have a new approval date. The MAH should then at the next printing update their package leaflet with this date 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 Word format with changes marked using the function "track changes". When PL and labelling are affected, these should also be submitted in the same format.
  • It is recommended that the background documents are submitted also in an electronic format to allow an expedite process.

 

 
 
 

Swedish Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, SWEDEN | +46 18 17 46 00 | registrator@lakemedelsverket.se | Contact information