The European Court of Justice (ECJ) has ruled on the discretion of a Concerned Member State under the mutual recognition procedure to refuse an application for a marketing authorisation for a medicinal product that has been granted by the Reference Member State.
Directive 2001/83 (the "Directive") sets out the community code relating to medicinal products for human use. The Directive requires that "no medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued…in accordance with the Directive".
Article 10(1) of the Directive sets out the procedure for making an abridged application for a marketing application. Where an application is made under Article 10(1), full toxicological and pharmacological tests and/or trial data are not required if "…the medicinal product is essentially similar to a medicinal product which has been authorised within the Community…for not less than six years and is marketed in the Member State for which the application is made…".
Synthon applied to the Danish Medicines Agency (DMA) as the Reference Member State for a marketing authorisation in respect of its Varox product. Synthon applied in accordance with the abridged procedure, using Seroxat (a SmithKline Beecham product) as the reference product on the basis that Seroxat and Varox contained the same active moiety (paroxetine) although they were different salts. The DMA agreed that the two products were essentially similar and granted the marketing authorisation.
Using the Danish marketing authorisation, Synthon applied (twice) to the UK licensing authority (acting as a Concerned Member State) for mutual recognition under Article 28 of the Directive.
Under Article 28 of the Directive, each Concerned Member State has to recognise the marketing authorisation granted by the Reference Member State unless it has grounds for supposing that it may present a risk to public health. In such a case, the matter then enters arbitration under Article 29.
The UK licensing authority had a general policy in place that different salts of the same active moiety would not be deemed essentially similar. On that basis, it refused to validate Synthon's application (in other words, it would not start the assessment process as it said that the documents submitted were not compatible with the legal basis upon which the application was submitted). The UK licensing authority did not come to the conclusion that Varox presented a risk to public health or initiate the arbitration process.
Synthon sought a review of the decision in the High Court of Justice of England and Wales (QBD, Administrative Court) requesting annulment of the decision.
Some time after this decision, the UK licensing authority changed its policy so that products containing different salts would, going forwards, be considered essentially similar. Moreover, in a preliminary ruling in a related case, the ECJ considered and approved the DMA's original decision to grant the original marketing authorisation in respect of Varox. As a result, Synthon re-applied to the UK licensing authority and was granted a marketing authorisation.
Notwithstanding the grant of the UK marketing authorisation, Synthon continued with its action and questions were referred to the ECJ. In summary the questions asked were:
- whether a Concerned Member State can refuse to accept and review an application on the basis that the product is not essentially similar to the reference product despite the opposite conclusion being reached by the Reference Member State? or
- are the only two options available to a Concerned Member State (a) to recognise the marketing authorisation granted by the Reference Member State or (b) to refer the matter to arbitration on the grounds that the product may present a risk to public health; and
- whether the failure to grant a marketing authorisation either:
- on the basis that the relevant licensing authority does not agree that the product in question is essentially similar to the reference product, or
- because of a general policy which prevents different salts from being considered essentially similar;
is a breach significant enough to give rise to a claim for damages from the Concerned Member State?
The ECJ said that where a marketing authorisation is applied for under the mutual recognition procedure, having been approved by the Reference Member State on the grounds that it was "essentially similar" to the reference product, a Concerned Member State is not entitled to refuse to validate the application on the grounds that the medicinal product is not "essentially similar". The only two options available to a Concerned Member State are (a) to recognise the marketing authorisation granted by the Reference Member State or (b) to refer the matter to arbitration on the grounds that the product may present a risk to public health.
The rationale for such a view was that i) it is not possible to abolish barriers to free movement of medicinal products unless marketing authorisations granted by a Reference Member State are recognised in other Member States; and ii) the Directive sets out in Article 29 the only ground (a risk to public health) upon which a Concerned Member State is entitled to object to recognition of a marketing authorisation granted by the Reference Member State.
Further, the ECJ said that where a Concerned Member State fails to recognise a marketing authorisation applied for under Article 28, which was granted by the Reference Member State either on the grounds that they consider it is not "essentially similar" to the reference product or because that Concerned Member State has a general policy which means that it does not allow it to be considered "essentially similar", this represents a "sufficiently serious breach of Community law, capable of rendering that Concerned Member State liable in damages".
The guidance of the ECJ is that there is only one ground (the risk to public health) that a Concerned Member State can rely on to refuse to recognise a marketing authorisation granted by the Reference Member State. The ECJ also confirmed that, to invoke this ground, the procedure set out in Article 29 must be used. Therefore, the scope for the licensing authorities acting in their Concerned Member State role to refuse, in particular, generic applications will be limited. This also means that there will be fewer opportunities for innovator companies to challenge the authorisation of generic marketing authorisations by the Medicines and Healthcare Regulation Authority (MHRA) through judicial review, where the MHRA is acting as the Concerned Member State.