The division of competences between Member States in mutual recognition procedures is still evolving. The extent to which a Concerned Member State has discretion to evaluate a medicinal product which has already been assessed by the Reference Member State is an issue that still needs clarification. In the case of C-452/06, Synthon BV v The Licensing Authority of the Department of Health,¹ the Queen’s Bench Division (Administrative Court) of the High Court of Justice of England and Wales was confronted with such a question of competence.

Synthon BV filed an application for mutual recognition in, amongst others, the United Kingdom for the medicinal product Varox® (paroxetine mesylate). It had already obtained a marketing authorisation for this medicinal product in Denmark under the abridged procedure – Article 10(1)(a)(iii) of Directive 2001/83/EC, which frees the applicant from providing relevant data on pharmacological and toxicological tests and clinical trials for his application, if he can demonstrate that the medicinal product is ‘essentially similar’ to a medicinal product already authorised and marketed in that Member State.

In its decision to provide a marketing authorisation for Varox®, the Danish Medicines Agency qualified the substances paroxetine mesylate and paroxetine hydrochloride hemihydrate (Seroxat®) as ‘essentially similar’. This decision had been challenged before European Court of Justice (the Court). The essential similarity of the two substances was accepted by the Court because Varox® ‘contained the same therapeutic moiety as the reference product, even though combined with another salt.’² In parallel to these proceedings the British Medicines Control Agency (MHRA) representing the UK as a Concerned Member State denied the application twice by arguing that Varox is not ‘essentially similar’ to the reference medicinal product Seroxat® (paroxetine hydrochloride hemihydrate).

Synthon BV challenged the second denial of the application before the national courts claiming that the denial did not comply with Article 29 of Directive 2001/83/EC. According to this Article the MHRA had to recognise the marketing authorisation issued by the Danish Medicines Agency within 90 days unless it considered that there was a risk to public health. The MHRA did not mention the presence of such risk. The High Court of Justice posed preliminary questions to the Court relating to the discretion of the MHRA in its role as medicines agency of a Concerned Member State. Was it allowed to examine the essential similarity of a medicinal product and subsequently deny a marketing authorisation in an application for mutual recognition, where the marketing authorisation was issued by the Reference Member State under the abridged procedure?

The decision of the Court is scheduled for the 16 October. Nevertheless, in his Opinion on this case, Advocate General Bot gives some ideas along which the Court may reason in its decision. Preliminarily, he signals that the current national administrative practice at the MHRA has already moved away from the approach depicted here, to a more favourable approach for Synthon BV. According to the Advocate General: “[t]he authority now allows applications claiming essential similarity between products containing different salt forms of the same active moiety.”³ This resulted in the authorisation of Varox® based on the Danish authorisation in the UK on 6 February 2006.⁴

The Advocate General concluded that:

1. A Member State, receiving an application for mutual recognition of a marketing authorisation issued by another Member State under the abridged procedure

    a. is bound to recognise that authorisation, unless it invokes the exception set out in Article 29(1) of Directive 2001/83, based on the existence of a potential risk to public health;

    b. may not investigate afresh the essential similarity of the two medicinal products and to reject the application in question on the ground that the two products are not ‘essentially similar’.

2. In circumstances such as those in the case at hand, the interpretation of the meaning and scope of the Mutual Recognition Procedure adopted by the MHRA is capable of constituting a serious breach of Community law.

Without giving a too extensive an interpretation of these conclusions in combination with the changed practice in the UK, there seems to be a good chance that the Court will decide along similar lines. If this is the case, this would mean that the discretion of Concerned Member States in Mutual Recognition Procedures of marketing authorisations issued by the Reference Member State under the abridged procedure has relatively clear-cut limitations. Only in case of a potential risk to public health may such authorisation not be recognised. Moreover, investigating the essential similarity of two medicinal products once more is out of the question.

Although it is of no direct concern in this case, the Advocate General gives his opinion on the discretion that Member States generally have where they act as Reference Member States – so not only under the abridged procedure:

‘80. (…) a Member State receiving an application for mutual recognition of a marketing authorisation pursuant to Article 28 of Directive 2001/83 has only very limited discretion. It cannot but be observed that that provision does not give the Member State concerned the option of making the recognition of an authorisation subject to conditions other than that referred to in Article 29(1) of the Directive.

81. In my view, that interpretation of Article 28 of the Directive is valid, whether the marketing authorisation was issued by the reference Member State under the normal procedure referred to in Article 8 of Directive 2001/83 or under the abridged procedure laid down in Article 10(1) of the Directive.’⁵

Finally, a few words on the concept of ‘risk to public health’: According to Bot, a Member State needs to show serious grounds that there are risks connected with the quality, safety, and efficacy of the product. Also on this point the Advocate General has a clear opinion:

‘76. The Member State concerned may thus challenge the findings made by the reference Member State in assessing the product if there are scientific facts showing that it does not fulfil the required conditions of safety, efficacy or quality. It is only in this context that, in my view, a Member State which receives an application for mutual recognition may challenge the assessment made by the reference Member State, based on the precautionary principle. Pursuant to Article 29(1) of Directive 2001/83, the Member State concerned must therefore give reasons for its point of view in a detailed manner and, I believe, produce the scientific data on the basis of which it considers that the marketing of the product might entail a risk to public health.

77. Where the Member State concerned has doubts as to the efficacy, quality or safety of the product, the Community legislature has not made provision for it to reject an application for mutual recognition on its own initiative. On the contrary, it has laid down, in Article 29 of Directive 2001/83, a procedure for consultation between the Member States concerned and for Community arbitration.’⁶

This universal reasoning would also apply to homeopathic and anthroposophic medicinal products produced in accordance with a homeopathic manufacturing procedure, with the exception of the possibility to use arbitration. This part has been explicitly excluded for these products in Article 39 of Directive 2001/83/EC. Therefore, if consultation fails, arbitration is not an option. The legislation remains silent on what should happen if consultation fails. There is no certainty as to what would happen since this situation has not yet occurred, but there is a good chance that in such a case the decision would in the end be given back to the individual Member States. This would however be counter-productive to the general idea of Mutual Recognition as Bot has described it:

‘That procedure [consultation and, if necessary, arbitration] must enable the Member States to adopt a common approach with regard to marketing authorisations. It is, therefore, only under that procedure that the scientific evaluation of the area of disagreement is undertaken and the action to be taken in response to the application for mutual recognition is decided.’⁷

We will have to wait and see how the system will evolve. The Court will take its next step on the 16 October. Probably, it will be less extensive in its decision than Advocate General Bot, and restrict itself to the specific facts of the case. To be continued!

Johan Hulshof
Van Benthem & Keulen Advocaten