EC issues notice on the handling of duplicate MAAs of pharmaceutical products under Article 82(1) of Regulation (EC) No 726/2004

The European Commission (EC) has issued a notice on the handling of duplicate marketing authorisation applications (MAAs) of pharmaceutical products under Article 82(1) of Regulation (EC) No 726/2004. Basically, this means duplicate MAAs for products authorised via the centralised procedure.

What does Article 82(1) of Regulation (EC) No 726/2004 state?

Only one authorisation may be granted to an applicant for a specific medicinal product.

However, the Commission shall authorise the same applicant to submit more than one application to the Agency for that medicinal product when there are objective verifiable reasons relating to public health regarding the availability of medicinal products to health-care professionals and/or patients, or for co-marketing reasons.

What is the aim of the notice issued by the European Commission?

The detailed 10 page notice aims to provide guidance to those who wish to submit a request for an application for a duplicate marketing authorisation.

While guidance documents are not legally binding, this Notice is based on the Commission’s interpretation of Article 82(1) of Regulation (EC) No 726/2004. In case of doubt, reference should be made to the appropriate EU directives and regulations. In addition, only the European Court of Justice can give an authentic interpretation of the EU law.

Marketing Authorisation Applications that fall under the scope of Article 82(1)

Applications that fall under the scope of Article 82(1) include the following:

The active substance is a different salt, ester, ether, isomer, mixture of isomers, complex or derivative that does not differ significantly in properties regarding safety or efficacy.
The medicinal product contains different excipients that do not result in significant differences in safety or efficacy.
Different manufacturer or manufacturing site, unless this leads to significant differences in safety or efficacy.
Differences in the data submitted in connection with the marketing authorisation application for a medicinal product with the same composition in active substance(s) and pharmaceutical form (e.g. data to show bioequivalence), provided that the product does not significantly differ in terms of safety or efficacy.

In addition, the fact that one marketing authorisation application is submitted in accordance with Article 8(3) of Directive 2001/83/EC and the other marketing authorisation application is submitted under an abridged procedure (e. g. generic, biosimilar or hybrid application, informed consent is irrelevant provided that both applications relate to a medicinal product with the same qualitative and quantitative composition in active substances and the same pharmaceutical form.

Marketing Authorisation Applications that fall outside outside the scope of Article 82(1)

Applications that fall outside the scope of Article 82(1) include the following:

The active substance(s) is not the same.
The active substance is a different salt, ester, ether, isomer, mixture of isomers, complex or derivative that differs significantly in properties regarding safety or efficacy.
The medicinal product contains different excipients that result in significant differences in safety or efficacy.
The manufacturer or manufacturing site is different and may, as a result of the characteristics of the product (notably in the case of biological products), lead to significant differences in safety or efficacy.
Applications submitted under Article 7(3) of Regulation (EC) No 141/2000: that provision provides that an orphan and non-orphan indication cannot be covered by the same marketing authorisation.
Applications submitted under Article 30 of Regulation (EC) No 1901/2006 or applications for marketing authorisations for other indications where the initial marketing authorisation has been submitted under Article 30 of Regulation (EC) No 1901/2006. Article 30 provides for a new, self-standing type of marketing authorisation called the Paediatric Use Marketing Authorisation.

Under what circumstances can the Commission grant a duplicate marketing authorisation under Article 82(1) of Regulation (EC) No 726/2004?

Under Article 82(1) of Regulation (EC) No 726/2004, the Commission can grant a duplicate marketing authorisation:

if there are objective, verifiable reasons relating to public health that show an increased availability of medicinal products to healthcare professionals and/or patients
for co-marketing reasons when the marketing authorisation holder can prove that he will stipulate a co-marketing agreement with one or more companies for the product for which the duplicate is requested. A co-marketing arrangement is generally understood as an agreement between two parties to commercialise a specific medical product under different trademarks.

Greater detail is provided in Annex I of the notice.

Can a duplicate application contain fewer indications or pharmaceuticals forms than the original application/marketing authorisation?

A duplicate application may contain fewer indications or pharmaceutical forms than the original application/marketing authorisation when this is necessary to market the product in Member States where a specific indication or pharmaceutical form is protected by patent law.

However, in order to maintain the harmonisation of the Summary of Product Characteristics (SmPCs), the applicant should provide a commitment letter undertaking to extend the indication(s)/pharmaceutical form(s) of the duplicate marketing authorisation when the patent restrictions no longer exist.
Alternatively, the applicant may also commit to withdrawing the marketing authorisation with restricted indications/pharmaceutical forms after the relevant patents are no longer in force.
Given that the harmonisation of SmPCs across the EU is one of the basic pillars of the centralised procedure, applicants of duplicate marketing authorisations should not market the two products with different indications/ strengths/ pharmaceutical forms in the same country. The commitment letter should accompany the marketing authorisation application dossier.