In this blog, John McIntyre looks at one of the most crucial choices Marketing Authorisation Holders must make when submitting a marketing authorisation application (MAA) – the choice of legal basis.
In the European Union (EU), the legal basis of a MAA is laid down in Directive 2001/83/EC as amended. The choice of legal basis in turn will determine the dossier content, paediatric requirements and data exclusivity. Legal basis is therefore of critical importance from a regulatory perspective.
Under Directive 2001/83/EC, the available legal basis are as follows:
|Article 8||Full application|
|Article 10 (1)||Generic|
|Article 10 (3)||Hybrid (Generic + additional data)|
|Article 10 (4)||Biosimilar|
|Article 10a||Well established use|
|Article 10b||Fixed combination|
|Article 10c||Informed consent|
Article 10a – Well Established Use
Here we look specifically at article 10a –the guidance available to MAHs, and what stance regulators have taken over the years in relation to this legal basis.
According to Article 10a of Directive 2001/83/EC it is possible to replace results of the pre-clinical and clinical trials by detailed references to published scientific literature if it can be demonstrated that the active substances of a medicinal product in the claimed therapeutic indication have been in well-established medicinal use within the Union for at least ten years, with recognised efficacy and an acceptable level of safety. In this regard, the provisions of Annex I of Directive 2001/83/EC shall apply.
Well-established use refers to the use for a specific therapeutic use. If well-known substances are used for entirely new therapeutic indications and it is not possible to solely refer to a well-established use, then additional data on the new therapeutic indication together with appropriate pre-clinical and human safety and/or efficacy data should be provided. In such a case, another legal basis should be used for the marketing authorisation application. Unfortunately, the concept of ‘specific therapeutic use’ is not defined under community legislation, although ‘Notice to Applicants’ volume 2 ‘A Guideline to Summary of Product Characteristics’ does provide guidance. From our own experience, the definition of ‘therapeutic indication’ differs radically among member states. Hence for some ‘border-line’ products, certain member states may accept a specific product under this legal basis, while others will suggest the MAH to choose another legal basis.
Our Experience of Well Established Use
Well established use MAAs continue to be subject to arbitration procedures of the Committee for Medicinal Products for Human Use (CHMP) due to differences in interpretation of guidance by member states. From our experience, MAHs should not choose this legal basis when their product will be used to treat new indications or populations, or if the product is a new pharmaceutical form. The latter in particular may throw up problems when the bibliographic data used in the application is not aligned with the sought formulation.
We would be delighted to speak to you about issues relating to article 10a – well established use. You can call us at any time on 00353 52 61 76706 or simply complete the webform below and we will get back to you.