After the granting of a Marketing Authorisation for a medicinal product, the Marketing Authorisation Holder (MAH) is responsible for any amendment to any part of the dossier and to the product information - Summary of Product Characteristics (SmPC), Package Leaflet (PL), Labelling.
Variations to medicinal products can be classified in different categories, depending on the level of risk to public health and the impact on the quality, safety and efficacy of the medicinal product concerned. Variation Regulation (EC) No 1234/2008 describes four different types of changes:
Variation Regulation (EC) No 1234/2008 has introduced several new concepts, such as the possibility of a 'tell and do' procedure, where certain types of variations can be implemented immediately upon notification. Other new possibilities include that of grouping of variations belonging to one marketing authorisation holder, worksharing and new timelines. Regulation (EU) No 712/2012 amends this regulation introducing the possibility of worksharing over different types of procedures, timelines and to take into account the new pharmacovigilance regulations.
"Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures", can be accessed through this link; these guidelines apply for all types of variations - National and European.
This guideline is kept updated by the European Commission. Also refer to the Q&A documents and various other guidelines related to variations which can be found on the CMDh website.
Directive 2009/53/EC is applicable for variations submitted for products authorised through the national procedure.
According to this Directive, the requirements for national applications are similar to those for European procedures and work sharing and grouping of variations is possible.
National variation applications for products with a marketing authorisation and those authorised through the PMA-MA process and their line extensions, should be submitted using the variations application form found at EudraLex - Volume 2 - Pharmaceutical Legislation Notice to applicants and regulatory guidelines medicinal products for human use.
No paper applications should be submitted. Electronic submissions and the use of the electronic application form are outlined in the section on Submission Requirements.
It is important that application forms for variations are filled in correctly and that all the documents that should be appended to the application form are submitted in accordance with the categorisation guidelines. Applications should be sent electronically preferably through the Common European Submission Portal (CESP). No additional paper cover letters or application forms should be sent. Requirements for electronic submissions are available on the CMDh website.
The following is a list of mandatory documents to be submitted to the Medicines Authority for a variation to a nationally authorised product:
Important:
Variation Regulation (EC) No 1234/2008 applies for products authorised through the Centralised Procedure and those authorised through the Decentralised Procedure (DCP) and Mutual Recognition Procedure (MRP).
The European Commission categorisation guidelines and the application form for variations submitted in accordance with Regulation EC 1234/2008, are applicable. Detailed information on the submission and processing of variations through the MRP, together with other relevant guidelines, can be found in the Variations Section on the CMDh website.
Implementation of variations approved by the Reference Member State where Malta is Concerned Member State can be carried out immediately following official notification by the RMS that the variation is approvable. No further approval by the Medicines Authority is required for implementation.
The Medicines Authority follows the following system for issuing of approvals for variations, notifications and renewals.
This process will apply to national applications (PMA-MA) and their line extensions:
If any of the details on the Marketing Authorisation (MA) document change following the approval of a variation or renewal, the licence will not be reissued. A letter will be issued instead outlining the scope and outcome of the variation or renewal. This letter will become part of the MA package and must be retained with the formal documents relating to the licence. Product information that has changed will be uploaded on the Medicines Authority website.
For European variation procedures, no further approval letter will be issued by the Medicines Authority and variations can be considered approved in Malta following approval confirmation by the Reference Member State (without prejudice to any other national legislation in place e.g. indication for medical abortion). When the variations have an impact on the product information (SmPC and/or PL and/or labelling), these documents must be sent, quoting the EU reference number immediately following approval by the RMS, to the mailbox mrp-dcp.adm@gov.mt or via CESP. The updated product information, where applicable, will then be published on the Medicines Authority website.
The front page of the Marketing Authorisation document will be revised and sent to the Marketing Authorisation Holder should the details included change as a result of a variation.
For notifications of changes to Parallel Import licences and authorisations in line with Article 126(a) of Directive 2001/83/EC, please refer to the respective sections of the website.
To ensure continued availability of a medicinal product on the market in Malta, batch specific requests can be submitted. Such applications may be required when the product in full compliance with the details of the marketing authorisation cannot be sourced for a short, defined period of time (maximum of 6 months). The request to bring the batch into compliance with the marketing authorisation can be submitted using the appropriate application form. Marketing authorisation holders are strongly discouraged from applying for a BSR when a batch does not comply with the registered finished product specifications. However, in exceptional cases non-critical deviations may be considered on a case-by-case basis.
Where the applicant is someone other than the marketing authorisation holder, a specific letter of consent from the holder is required for the request.
Where changes to the outer pack, immediate pack and package leaflet are being proposed, mock-ups with all the differences highlighted should be submitted. Over-labelling or re-packaging must be carried out in line with the General guidelines on the repackaging of medicinal products for human use.
A batch specific variation can be submitted when an extension to the implementation time for an approved variation is required. In such instances where the variation has been approved and the Marketing Authorisation Holder cannot meet the required timeline for implementation of the change an extension may be sought via submission of a batch specific variation.
The application form and cover letter should be sent to the Licensing Directorate in accordance with the submission requirements (which can be accsssed through this link), through the CESP.
For batch exemptions from the requirement of the Falsified Medicines Directive, where there is substantiated evidence that no alternative supply for CPSU is available, and the consequences of non availability may be of detriment to patient health, the specific form for these exemptions should be used for consideration by the Licensing Authority. This form is in two parts which need to be completed in full by both CPSU and the marketing authorisation holder. Only one completed application form is to be submitted to the email address licensing.medicinesauthority@gov.mt. Applications sent through other routes/to personal email addresses or in two separate parts will not be considered.
National Variations to change the legal status of a product from "subject to medical prescription" to "not subject to a medical prescription"
The National guideline is for use by marketing authorisation holders applying for a national change in the legal classification for supply of a medicinal product from "subject to a medical prescription" to "not subject to a medical prescription". This guideline applies to National and European approved products in Malta only. These include products authorised via the Decentralised/Mutual Recognition Procedures and National Marketing Authorisation Procedures including Parallel Import products and products authorised via Article 126(a) of Directive 2001/83/EC.
A presentation to guide applicants can be found here.
Updated on: 27 September 2022