Renewal: five-year re-evaluation of a marketing authorisation

Article 24 of Directive 2001/83/EC and Article 14 of Regulation (EC) No 726/2004 make a marketing authorisation valid for five years. It may be renewed after that period on the basis of a re-evaluation of the benefit-risk balance, for which the holder provides a consolidated version of the file on quality, safety and efficacy, including an evaluation of the data in suspected adverse reaction reports and periodic safety update reports, and all variations introduced since grant. Once renewed, the authorisation is valid for an unlimited period, unless the authority decides on justified pharmacovigilance grounds, including exposure of an insufficient number of patients, to require one further five-year renewal.

The renewal application is a lifecycle document rather than a new dossier. For centrally authorised products EMA's post-authorisation guidance describes the content: an updated clinical overview and summaries, a list of the variations approved, the current product information and a benefit-risk evaluation, with the quality part limited to a declaration unless changes are pending. For national, MRP and DCP products the CMDh best practice guide on renewals applies, with the RMS leading the assessment and the concerned member states agreeing the outcome. National authorities charge a renewal fee.

Renewal is also the moment when the authorities check that the product information is up to date and that commitments made at grant have been met. Where the product has not been marketed, the sunset clause can bite independently of the renewal, and the holder has to show that the authorisation is still needed. Conditional marketing authorisations are renewed every year instead, on the basis of the specific obligations.

What goes wrong: the application filed later than nine months before expiry, which can leave the authorisation lapsing while the assessment is still running; a renewal dossier that ignores PSUSA outcomes or referrals that changed the product information; commitments from the original approval that nobody has tracked; and translations of the renewed product information that are not ready for the national phase. Portfolio companies with hundreds of authorisations also struggle simply to list which products are due when.

Under the new pharma package (not yet in force), marketing authorisations become valid for an unlimited period from grant by default, with five years only where the authority limits validity on safety grounds or the authorisation is granted in exceptional circumstances; renewals of authorisations expiring after the rules apply follow the new procedures; see MA validity changes.