Fimea's Instructions to the National Implementation of the Directive 2010/84/EU
The regulations concerning the pharmacovigilance of medicinal products for human use have been revised due to the Directive 2010/84/EU ("the pharmacovigilance directive"). The main source for information on the new regulations is the website of the European Medicines Agency at 2010 Pharmacovigilance Legislation. This page contains clarifications concerning the national implementation of the regulations. The clarifications have been created as a result of questions presented to Fimea. The page will be updated as needed.
The regulation No 1235/2010 by the European Parliament and Council is legally binding in its entirety and has been applied as is in all member states since 2 July 2012.
The European Commission has issued an Implementing Regulation (EU) No 520/2012 on the implementation of pharmacovigilance operations laid down in the Regulation (EC) No 726/2004 of the European Parliament and Council and in the Directive 2001/83/EC of the European Parliament and Council. This regulation is legally binding in its entirety and has been applied in as is in all member states since 10 July 2012.
The Finnish national legislation has been updated to conform to the Pharmacovigilance Directive 2010/84/EU by the amendment 330/2013 to the Medicines Act. The Act entered force on 1 June 2013. Pursuant to the Act, Fimea has issued revised regulations on pharmacovigilance as well as labelling and package leaflets for medicinal products.
The European Medicines Agency and the Member States have jointly prepared Good Pharmacovigilance Practices (GVP) that consists of independently published and revised modules grouped by subject. The GVP is based on Article 108a of the Directive 2001/83/EU, covers the pharmacovigilance processes in the European Union and applies to holders of marketing authorisation and registration, the European Medicines Agency and competent authorities of the Member States. The GVP modules are published on the website of the European Medicines Agency. The published GVP modules replace the corresponding parts of the guidelines "Rules governing medicinal products in the European Union,
Volume 9A – Pharmacovigilance".
Periodic Safety Update Reports
A continually updated list containing the European Union reference dates (EURD) and the requirements for submitting the periodic safety update reports (PSUR) was published for the first time at the European Medicines Agency website on 1 October 2012.
The list became legally binding 6 months after it had been approved, i.e. 1 April 2013. The EURD list is updated each month, and the updates become valid 6 months after they have been published. Holders of marketing authorisations are obliged to follow these updates for their respective products.
If a product is not included in the EURD list and does not have a confirmed European Union reference date, the PSUR cycle and the PSUR submitting date must be agreed separately with Fimea's Medicinal Products, Pharmacovigilance unit. In addition to these principles, an authority can request a PSUR at any time for the evaluation of pharmacovigilance data, in which case the PSUR must be submitted immediately at the authority's request.
For products whose DLP date is between 1 April 2013 – 31 August 2014 in the EURD list published in October 2013, and which have been temporarily removed from the updated list, the instructions applied in the intermediate period shall be the ”Assessment of Periodic Safety Update Reports for Nationally Authorised Products in 2013/2014 - Cover note” published on the CMD(h) website, and the list ”List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised” published in the work sharing project.
Holders of marketing authorisation must monitor and follow the PSUR assessment reports and recommendations published on the CMD(h) website.
A PSUR is not submitted for a generic product that has been granted a marketing authorisation pursuant to Article 10(1) or Article 10a (Directive 2001/83/EC) and the marketing authorisation does not contain a condition concerning the submitting of a PSUR, or the PSUR submission schedule does not differ from the reference product. If these conditions are not met, the frequency of PSUR submission shall be normal until the European Union reference dates have been confirmed.
If you have questions on the obligation to submit a PSUR, please send email to PSUR@Fimea.fi. Please include the following information in the enquiry: name of the medicinal product, active ingredient, ATC code, type of application (an original product or a generic product), information in the EURD list (DLP, PSUR cycle, whether a PSUR must be submitted for generic products and whether the active ingredient is not in the list) and the reporting period of the PSUR last submitted to Fimea.
The PSUR is created according to the instruction in the GVP module VII.
Fimea does not require a variation application for a change to the PSUR cycle, if the active ingredient is listed in the EURD list.
Renewal of Marketing Authorisation
1. Renewal applications must be submitted 9 months before the expiration date of the marketing authorisation.
If a marketing authorisation has a harmonised renewal date, the renewal application shall still be submitted according to the agreed and harmonised renewal schedule.
2. A PSUR, PSUR addendum or SBR shall not be submitted with the renewal application. Instead, the applicant shall attach an Addendum to the Clinical Overview that contains the required information to evaluate the risk-benefit balance of the medicinal product. The submission of renewal applications and PSURs have their own schedules, and the applicant must collect information in such a way that the renewal application contains relevant and up-to-date information for the evaluation of the risk-benefits balance.
3. If a Risk Management Plan (RMP) has not been part of the marketing authorisation of a product, an RMP shall not be submitted along with the renewal application. For such products, an RMP shall only be submitted at the request of an authority, or if the marketing authorisation holder considers it necessary due to new information obtained on the safety on of the product. In the latter case, the submission of an RMP must also be negotiated in advance with the Medicinal Products, Pharmacovigilance unit.
4. EMA and CMD(h) have published on their websites updated instructions concerning renewal applications.
Reporting Adverse Reactions
During the intermediate period, Fimea will only receive reports on suspected serious adverse reactions that have occurred in Finland. The marketing authorisation holder must report these using an expedited electronic process and must submit all related information on the adverse reaction to Fimea (Act on the Amendment of the Medicines Act 330/2013, Section 30 e and Section 30 f).
Risk Management Plan
All new marketing authorisation applications must contain a Risk Management Plan (RMP). The applicant shall enclose for assessment an RMP document in the marketing authorisation application of a medicinal product. The scope of the RMP document depends on the characteristics of the product (for instructions, see GVP module V, e.g. figure V.3). Instructions for updating the RMP document are in the GVP module V. The RMP shall be created according to the revised RMP-template "Guidance on format of the risk management plan (RMP) in the EU", published on the European Medicines Agency website.
A part of the RMP document is a summary of the risk management plan (Part VI, Summary of activities in the risk management plan by product). The section VI.2 Elements for a Public Summary belonging to the summary shall be submitted to Fimea both in Finnish and in Swedish. The translations shall be submitted within 60 days from the granting of the marketing authorisation. If the RMP document is presented using a variation application, or if the variation application affects the summary of the RMP document, the translations shall be submitted within 60 days from the approval of the variation.
European Medicines Agency publishes summaries of RMPs for centrally authorised medicines. For these products, translations of RMP summaries in Finnish and Swedish are recommended to be submitted only from RMP summaries published by the European Medicines Agency.
European Medicines Agency publishes RMP summaries for newly authorised medicines and updates of RMP summaries when major changes are made. Changes will be considered to be major if they relate to the following: new indications, restriction of indication, updated contraindications, new important risks or important changes to a known risk or any additional risk minimization measure which is added or removed.
The translation shall be submitted by email to email@example.com.