Marketing authorisation renewal and the sunset clause in the EU

Article 24(1) of Directive 2001/83/EC makes a marketing authorisation valid for five years. Article 24(2) allows it to be renewed after those five years on the basis of a re-evaluation of the risk-benefit balance by the competent authority. For that re-evaluation the holder provides a consolidated version of the file in respect of quality, safety and efficacy, including an evaluation of the data in suspected adverse reaction reports and periodic safety update reports, and a list of all variations introduced since the authorisation was granted, at least nine months before the authorisation ceases to be valid. Article 24(3) then makes the renewed authorisation valid for an unlimited period, unless the authority decides, on justified grounds relating to pharmacovigilance, including exposure of an insufficient number of patients, to require one additional five-year renewal.

Article 14(1) to (3) of Regulation (EC) No 726/2004 contains the same rule for centrally authorised products, with the five years counted from the date of notification of the Commission decision and the renewal application made to the European Medicines Agency (EMA). The nine-month deadline was set by the 2010 pharmacovigilance legislation, Directive 2010/84/EU and Regulation (EU) No 1235/2010, which lengthened it from six months. If no renewal application is made, the authorisation lapses on its last day of validity. A suspended authorisation still has to be renewed.

Two special regimes sit outside the five-year cycle. A conditional marketing authorisation under Article 14-a of the regulation is valid for one year and renewed annually, with the application due at least six months before expiry under Article 6 of Regulation (EC) No 507/2006. An authorisation granted under exceptional circumstances (Article 22 of the directive and Article 14(8) of the regulation) is reassessed every year against its specific obligations; EMA treats that annual reassessment as a separate procedure from the five-year renewal.

The legal text speaks of a consolidated file, but the current practice is lighter than that suggests, because the holder is already obliged to keep the dossier up to date through variations. For products authorised through the mutual recognition and decentralised procedures, the CMDh best practice guide on renewals (February 2023) sets the standard application at a renewal cover letter and the renewal electronic application form, submitted simultaneously to the RMS and all CMS. No consolidated dossier is expected. Member States may request full documentation during validation, for national reasons or because of a benefit-risk concern, and the guide's Annex 3 lists what that means: the consolidated version of the quality, safety and efficacy file, a quality expert statement, a clinical overview addendum with a clear statement that the product can be renewed for an unlimited period, a non-clinical expert statement where new data exist, each signed and with a CV, the chronological list of variations, and the current product information.

For centrally authorised products EMA's procedural guidance asks for an eCTD submission with a signed cover letter and the renewal application form, a list of presentations and Member State marketing data, a chronological list of post-authorisation submissions, the status of any conditions and specific obligations, GMP and qualified person declarations, the clean and highlighted product information, a risk management plan where an update is proposed, and Module 2 addenda, in particular a clinical overview that discusses the benefit-risk balance on the basis of the periodic safety update reports, and a clinical expert statement. EMA charges no fee for the five-year renewal. Specimens are sent separately.

Whichever route, the assessment is a benefit-risk re-evaluation, not a re-registration. The authorities check that the holder has kept the authorisation current through the appropriate variations, that the product information reflects the dossier, and that conditions imposed at grant have been met; conditions can be modified or added at renewal, and the product is not renewed if serious public health issues remain. The grounds for non-renewal are those in Article 116 of the directive: harm under normal conditions of use, lack of therapeutic efficacy, a negative benefit-risk balance, or a composition that is not as declared.

The renewal application is due at least nine months before the authorisation ceases to be valid. EMA does not accept applications more than two months early, so the submission window for a centralised product opens eleven months before expiry. In the mutual recognition and decentralised procedures the RMS sets a common renewal date, usually five years after the end of the initial procedure; the application is submitted no later than nine months before that date, and in any event nine months before the authorisation expires in any of the Member States concerned, because the national expiry dates can differ. Where some Member States have already granted unlimited validity, the application goes only to the RMS and the Member States that still require a renewal.

For planning, the nine-month deadline is the hard date and everything else counts back from it: the data lock point for the clinical overview, the check that every variation has been filed and the product information is current, and the internal sign-off of the expert statements. Teams that run renewals alongside variations and PSURs keep the common renewal date per product and market in one plan; the regulatory lifecycle planning workflow is built around that calendar.

Article 24(4) and (5) of the directive, mirrored in Article 14(4) and (5) of the regulation, add a use-it-or-lose-it rule. An authorisation that is not followed within three years of grant by the actual placing of the product on the market of the authorising Member State ceases to be valid. An authorisation for a product that was placed on the market but is then no longer actually present on that market for three consecutive years also ceases to be valid. For nationally authorised products the test is per Member State, so a product can lapse in one country while remaining valid in the others; for a centrally authorised product EMA applies the clause to the authorisation as a whole, and the three years run from the Commission decision, or, for generics and similar products, may run from the end of the reference product's protection period.

The clause depends on the marketing status data the holder itself reports. Under Article 23a of the directive the holder informs the competent authority of the date of actual marketing in each Member State and notifies any temporary or permanent cessation at least two months in advance, unless exceptional circumstances make that impossible. For centralised products the same duties flow from Article 13(4) of the regulation, and EMA collects the data through its IRIS platform: placing on the market within 30 days, cessation at least 60 days ahead, per presentation and per Member State. EMA uses those records to monitor the sunset clause and, once three years without marketing have elapsed, informs the Commission that the authorisation has lapsed. The glossary entry on the sunset clause summarises the mechanics.

Monitoring it in a portfolio means three things: a reliable record of the first placing on the market per presentation and per country, an alert when a presentation leaves a market, and a review of dormant authorisations well before the third anniversary, so that a planned launch, a transfer or an exemption request can be arranged in time. Regunaut Atlas tracks marketing status and lapse dates on one licence timeline for this purpose, and Alerts catches authority notices that affect those products.

Article 24(6) of the directive and Article 14(6) of the regulation allow the competent authority, or the Commission for centralised products, to grant an exemption in exceptional circumstances and on public health grounds, and the exemption must be duly justified. EMA's guidance gives examples: medicines for public health emergencies recognised by the World Health Organization or the EU, and certain antimicrobials or immunologicals held against bio-terror agents. Requests for a centralised product go to the Commission's Directorate-General for Health and Food Safety with copies to EMA. Commercial reasons alone do not qualify; the argument has to be that the public needs the authorisation to remain available.

Two further points often decide a dormant licence's fate. A temporary cessation stops the product being present on the market, so the three years run from the last release into the distribution chain, not from the formal notification; reintroduction resets the clock. And a transfer of the authorisation to another holder does not by itself count as placing on the market, so a buyer of a dormant licence inherits the remaining time. The glossary entry on MAH transfers covers the transfer procedure.

The routine renewal disappears for new authorisations, and the agreed text provides for authorisations that expire after the new rules apply to follow the new procedures (Article 221(7) of the Council text). What does not disappear is the oversight the renewal used to force. Authorities can ask at any time for data showing that the benefit-risk balance remains favourable (Article 92(4)), periodic safety update reports remain the structured review point, variations remain mandatory, and authorities keep the power to vary, suspend or revoke an authorisation. The Council text as adopted contains no sunset clause; marketing status notifications and the new supply and shortage obligations take over the role of showing whether a product is actually on the market. Our page on MA validity under the agreed package tracks the provisions and the transition.

Until the directive is published and applies, the current rules stand: renewals due in the next few years are filed under Article 24, and dormant licences still lapse after three years. The legislative timeline lists the steps that remain, and the glossary entry on PSURs explains the reporting cycle that becomes the main periodic checkpoint once renewals go.