Issue No. 2008/02
This EU Pharma & Life Sciences e-bulletin contains summaries of recent developments in European law.
European Court of Justice
On 10 July 2008, Advocate General (AG) Bot rendered his opinion in this case and concluded that a Concerned Member State (CMS) acting in the context of MRP of a generic product has only limited power to challenge the approval granted by a Reference Member State (RMS). He also considered that the refusal by the UK Licensing Authority, as CMS, to recognise the RMS approval on the grounds that essential similarity between the generic and the reference products was not established might be a serious breach of EU law which could render the UK authority liable for damage.
On 23 October 2000, SYNTHON obtained a marketing authorisation with Denmark as RMS for a generic product containing paroxetine mesylate. It was considered by the Danish Medicines Agency as essentially similar to SKB’s product Seroxat (paroxetine hydrochloride hemihydrate). SKB challenged the validity of the authorisation and the matter was referred to the ECJ (case C-74/03). In its ruling of 20 January 2005, the ECJ did not exclude the use of the abridged procedure and essential similarity in a situation where both products contain the same active moiety combined with different salts.
In parallel, SYNTHON applied to the UK Licensing Authority of the Department of Health for a marketing authorisation under the MRP in the UK (CMS). The Licensing Authority rejected the application on 19 January 2001 on the grounds that different salts of the same active moiety have a different qualitative and quantitative composition and therefore cannot be regarded as essentially similar. The rejection was not based on risk to public health (Article 29 of Directive 2001/83).
Following proceedings brought by SYNTHON before the High Court, the matter was referred to the ECJ, which was asked to determine the margin of discretion enjoyed by a CMS when it receives an MRP application under the abridged procedure.
Synthesis of the opinion
The AG insists on the unequivocal wording and the binding character of the MRP mechanism to ensure the unity of the law and on mutual confidence between the Member States. He considers that a CMS which receives an application for mutual recognition of a marketing authorisation granted under an abridged procedure, has to recognise it within the time-limit set down by the Directive (90 days). It may not reject that application on the ground that the generic product is not essentially similar to the reference product and no distinction should be made between the complete and the abridged procedure.
Therefore, the margin of discretion of the CMS is limited to the strictly legal aspects of the application and it cannot investigate afresh the essential similarity of the two medicinal products. The CMS may only challenge the assessment made by the RMS by relying on the exception in Article 29(1) of Directive 2001/83 to not recognise the marketing authorisation issued by the RMS i.e. "there are grounds for supposing that the marketing authorisation of the medicinal product concerned may present a risk to public health" and to start the consultation and arbitration procedure.
In such a case, the AG also considers that the CMS must not only explain its point of view in a detailed manner but must also provide the scientific data on the basis of which it considers that the marketing of the product might entail a risk to public health.
SYNTHON also asked for damages from the UK authority on the basis of an alleged serious breach of Community law. The AG considers that Article 28 of Directive 2001/83 leaves to the competent national authority a particularly narrow margin discretion and the wording of Article 28(4) of the Directive is very clear and precise. It requires the CMS to recognise the RMS approval unless it can rely on the exception related to the public health risk included in Article 29(1). Article 29 of Directive 2001/83 also describes with all necessary clarity the procedure which a Member State is to initiate when it has any doubt as to the quality, safety or efficacy of a medicinal product.
Therefore the AG concluded that the United Kingdom by its interpretation renders meaningless the principle of mutual recognition as well as the consultation and arbitration procedures established in Articles 28 and 29 of Directive 2001/83. This interpretation which results in a re-examination of the application, in a rejection of the application on grounds other than those expressly set out in Directive 2001/83, and in a failure to initiate the procedure for consultation and mutual assistance, is capable of constituting a serious breach of Community law.
This judgement, which was rendered on 21 February 2008, was seen as an opportunity for the ECJ to clarify or even amend the peculiar decision in the Kohlpharma case related to medicinal products for human use (C-112/02).
The Kohlpharma judgement concerned the parallel import into Germany of a product (Jumex from Chiesi) approved in Italy but not in Germany. The parallel importer referred to another product with the same active ingredient (Movergan) sold in Germany by an unconnected company (Orion). The ECJ basically ruled that in a case where the safety and efficacy assessment of Movergan can be used without any risk to public health for the imported product the PIL request cannot be rejected on the sole grounds that the two products do not have a common origin. This ruling was peculiar and did not tackle important related issues such as pharmacovigilance, differences in SmPCs, TM, liability issues, etc.
The present case relates to plant protection products. The marketing of plant protection products is specifically regulated by the Council Directive 91/414/EEC of 15 July 1991 which establishes uniform rules on the conditions and procedures for authorisation to place such products on the market and for their review and withdrawal. It harmonises the applicable rules in the context of free movement of goods but also aims at ensuring a high level of protection of human/animal health and also of the environment.
For parallel import of plant protection products, the French Law requires that both the product imported in parallel and the reference product authorised in France have a common origin. The Commission considered that this French requirement constitutes a restriction on free movement of goods which was contrary to Article 28 EC. The Commission also explicitly referred to the Kohlpharma judgement.
In this judgement, the ECJ underlines the differences between the legislation applicable to medicinal products and to plant protection products respectively and concluded that regarding the latter the requirement of common origin cannot be considered as contrary to Article 28 EC.
The ECJ also states that “contrary to what the Commission submits, Kohlpharma does not call that assessment into question. In that case, the Court took as a basis the premise that, for the purposes of assessing their safety and efficacy, the imported medicinal product and the reference medicinal product did not differ significantly although they had been manufactured by two separate undertakings. After pointing out that the principle of proportionality requires that the legislation in question be applied within the limit of what is necessary in order to achieve its primary objective of protecting public health, the Court stated that the circumstances of that case were characterised by the fact that the active ingredient had been sold to two different manufacturers of medicinal products established in two Member States, with the result that the applicant for the parallel import authorisation could, for the purpose of assessing its safety and efficacy, demonstrate by means of available or accessible information that the medicinal product to be imported did not differ significantly from the medicinal product which had already been authorised ... In such circumstances, the assessment of safety and efficacy carried out for the medicinal product which had already been authorised could be used in the application for a marketing authorisation for the second medicinal product without any risk to public health …”.
Specific GCP Guidelines applicable to advanced therapy medicinal products are required by Article 4 of Regulation (EC) n° 1394/2007. As this Regulation will apply from 30 December 2008, the Commission issued, on 4 July 2008, preliminary draft guidelines for public consultation.
The draft addresses several issues such as traceability requirements and responsibilities, safety reporting and long term follow-up, issues related to the Protocol, the Investigator Brochure and Essential documents. Comments can be addressed to the Commission before 15 October 2008.
The Commission has also started a public consultation on the Revised Clinical Trial Application Form as regards advanced therapy investigational medicinal products and has published the outcome of the Public Consultation on amendments to Annex I to Directive 2001/83/EC as regards advanced therapy medicinal products.
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