Article 10a of EU Directive 2001/83/EC, as amended, provides a route by which an applicant seeking marketing authorisation for a medicinal product can secure such an authorisation without the need to submit pre-clinical data and clinical trial data as to safety and efficacy, or to cross reference (after expiry of the period of regulatory data protection) an existing marketing authorisation for the same active substance based on such data. Article 10a requires that the applicant:
"demonstrate that the active substances of the medicinal product have been in well-established medicinal use within the [EU] for at least 10 years, with recognised efficacy and an acceptable level of safety in terms of the conditions set out in Annex I".
It goes on to provide that "[in] that event, the test and trial results are to be replaced by appropriate scientific literature".
Laboratoires CTRS had sought a centralised marketing authorisation under the Article 10a route for its medicinal product Orphacol (cholic acid), used to treat two rare, but serious liver disorders. Cholic acid had not previously received a marketing authorisation in the European Union. Despite a recommendation from the relevant standing committee of the European Medicines Agency that a marketing authorisation be granted in respect of Orphacol, after seeking unsuccessfully to pressure the standing committee into changing its opinion, the European Commission eventually adopted an implementing decision refusing a marketing authorisation, as it took the view that there was no legal basis for granting such an authorisation in this case.
On July 4 2013 the General Court upheld an appeal by Laboratoires CTRS seeking to annul the European Commission's decision. In so doing, the court rejected all three reasons advanced by the European Commission in reaching its decision.
First, the European Commission asserted that the well-established medicinal use of cholic acid had not been proved, arguing that its use as a hospital preparation between 1993 and 2007 was insufficiently systematic and well documented to prove well-established medicinal use over a period exceeding 10 years. In support of this, it argued that 'hospital preparations' are not covered by Directive 2001/83/EC. However, the court held that these are covered by Article 5(1), which subsequently relieves certain medicinal products from the provisions of the directive, such as the need to secure a marketing authorisation, where these are:
"supplied in response to a bona fide unsolicited order, formulated in accordance with the specification of an authorised health care professional and for use by an individual patient under his direct personal responsibility".
The European Commission's second argument was that it was inconsistent with the well-established medicinal use route for Laboratoires CTRS to have been able to rely on 'exceptional circumstances' as a reason for not providing comprehensive data on safety and efficacy, as is allowed by Article 22 of Directive 2001/83/EC where the applicant can show that it is unable to do so for "objective, verifiable reasons". The court also rejected this argument, noting that nothing in the legislation precludes the simultaneous application of the concepts of 'well-established medicinal use' and 'exceptional circumstances'; the court observed that Laboratoires CTRS had "objective, verifiable reasons" in the rareness of the disorders in question and in ethical considerations. Indeed, the conditions that Orphacol was used to treat were sufficiently rare for it to have secured designation as an orphan medical product.
Finally, the European Commission argued that the grant of such a marketing authorisation would undermine the objectives of the EU Paediatric Regulation (1901/2206) and the protection of innovation. As to the second point, the court held that this had not been presented in the European Commission's decision as a free-standing ground for refusing to grant the marketing authorisation, but merely as a remark. As to the first point, the court noted that Article 9 of the Paediatric Regulation specifically excludes applications under the well-established medicinal use route from the relevant requirements of the regulation. Thus, the court also rejected this third line of argument.
This decision represents a setback for the European Commission in its attempts to limit the scope of the well-established medicinal use route for securing marketing authorisation for a medicinal product. The European Commission has in the past uccessfully sought to limit reliance on the well-established medicinal use route in cases where it has been used in an attempt to circumvent the regulatory data protection afforded to new active substances which have already received marketing authorisation. An example of this is the Plavix case in Germany, as a result of which the European Commission threatened proceedings against Germany for allowing such circumvention to take place; however, the European Commission did not then proceed, presumably because it received satisfactory assurances from the German authorities that their practice had changed. However, the Orphacol case is different and concerns an active substance that had not previously received a marketing authorisation in the European Union. It is clear that by extending its hostility to the well-established medicinal use route to this different situation, the European Commission has overreached itself.
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