Earlier this month, the European Commission published an updated version of the 2011 Note on the handling of duplicate marketing authorisation applications for medicinal products (the 2011 Note). Following a long period of consultation and exchange with stakeholders and representatives from the EU Member States, the European Commission has sought to clarify the conditions under which applications for duplicate marketing authorisations will be assessed. In this blog post, we discuss the relevant changes, as well as the implications for the industry.
Under Article 82.1 of Regulation (EC) No 726/2004, only one authorisation may be granted to an applicant through the centralised procedure for a specific medicinal product. However, there are limited exceptions to this, firstly when the second authorisation is required for co-marketing with an independent company, and secondly when there are objective verifiable reasons relating to public health regarding the availability of medicinal products to healthcare professionals and/or patients.
The 2011 Note described how the Commission handled duplicate marketing authorisation applications. In general, approval of duplicates for co-marketing has not given rise to major issues and the updated guidance does not make material changes to the procedure. However, the 2011 Note interpreted the second exception as allowing the original marketing authorisation holder for a product to obtain a duplicate in order to launch a “first generic” of that product, because the first introduction of a generic product can improve the availability of a medicinal product and thereby make it easier for patients to access the product.
However, there has been some controversy surrounding the guidance, and in particular, on the impact of duplicate authorisations of biological medicinal products. Companies marketing biosimilars had voiced concerns that where the first “copy” of the originator’s biological product was marketed by the originator, this did not improve availability of the product, but rather made the marketing of biosimilars less attractive.
In 2018, the European Commission launched a public consultation proposing changes to the 2011 Note (see our previous blog here). The consultation sought stakeholders’ views on the impact of duplicate authorisations of biological medicinal products. The consultation stated that “the first introduction of a generic product by the holder of a biological medicinal product may not improve availability” and that “requests for duplicate marketing authorisation applications need to be properly substantiated and based on sound evidence”.
On 7 November 2019, during the discussions with representatives of the EU Member States at the Pharmaceutical Committee meeting, the European Commission clarified that the proposed revisions to the 2011 Note would apply to both biological and chemical medicinal products (more in our previous blog here).
Almost three years later, the European Commission has finally published an updated Note, which largely reflects the proposed revisions in the public consultation and discussed at the Pharmaceutical Committee meeting.
The updated Note reflects the European Commission’s current interpretation of the legislation that duplicate marketing authorisations must be granted on an exceptional basis. Section 1 of the Annex to the updated Note has been revised to clarify how the European Commission expects applicants to demonstrate that a duplicate marketing authorisation will increase availability and patient access under the public health ground. In particular, we note the following updates:
- There is no automatic link between grant of a duplicate marketing authorisation to the holder of the original medicinal product and increased availability. In order to identify such a link, a case-by-case analysis will be conducted, where the European Commission will assess in detail “objective and verifiable evidence” submitted by the applicant. This applies to applications for both chemical and biological products. Such evidence should include:
– the Member States where the original medicinal product is marketed;
– the Member States where the duplicate medicinal product is intended to be marketed;
– the Member States in which the duplicate is not to be placed on the market: the applicant should explain the reasons for not marketing the product in these countries.
- When a separate marketing authorisation application is required by law, it is not necessary to submit a request for a duplicate marketing authorisation to the Commission. This is relevant to orphan medicinal products, for example, where it is necessary that orphan and non-orphan indications are on separate marketing authorisations. It is also stated that applications for Paediatric Use Marketing Authorisations do not need to request a duplicate authorisation.
- A template is provided for companies to made such requests. The template should be used for all applications submitted from 1 April 2021 onwards.
Implication of the updated guidance
The updated Note means that the first entry of a generic on the market will no longer be automatically considered to increase the availability of the medicinal product. These changes will have a particular effect on applications for duplicates of chemical medicinal products, which have previously been accepted without detailed analysis of the reasons why this will increase availability to patients. While the industry has been made aware of the Commission’s concerns about biological products, the changes in the updated Note apply to all products.
Further, it is questionable whether it will be possible to generate “objective and verifiable evidence” on increased availability, as by definition the duplicate product is not yet on the market when the application is made. The guidance in the updated Note is limited and does not address the practical implications or provide concrete examples of what is needed that would help applicants to provide such evidence. It is unclear what level of evidence the Commission expects to be provided other than the details of the Member States in which the product will be marketed, as set out above.