Data exclusivity for innovators - a bridge too far?

September 2016

In R (on the application of Napp Pharmaceuticals Ltd) v Secretary of State for Health acting as the Licensing Authority [2016] EWHC 1982 (Admin), which concerned the interpretation of Article 10(3) of Directive 2001/83/EC (the "Directive"), the High Court has ruled that a generic applicant for marking authorisation ("MA") can rely on bridging data submitted by a different applicant to support an earlier application under Article 10(3). The Court found that it did not matter who had generated such data, if the later product was materially identical to the earlier one.

Facts

Napp sought judicial review of a decision by the MHRA to grant MAs to Sandoz, the interested party, in relation to Sandoz's product Reletrans.

Reletrans is a transdermal patch containing the opioid analgesic buprenorphine and is a generic version of BuTrans, Napp's transdermal buprenorphine patch. Napp's own MA application was first made and granted in Denmark in 2003 and then subsequently recognised by other Member States, including the UK in 2005, under the Mutual Recognition Procedure. Napp's application to the Danish regulatory authority was made under Article 10(3) of the Directive, citing Temgesic (from Schering-Plough), a sub-lingual buprenorphine tablet, as reference medicinal product ("RMP") for the purpose of its application. Article 10(3) was the legal basis of Napp's application because in BuTrans the active substance was delivered by a different route of administration (i.e. via a patch) compared to the RMP. As part of the application, Napp provided bridging data to demonstrate equivalence to the RMP.

In 2013, Sandoz applied to the German regulatory authority, BfArM, for an MA for its transdermal patch Reletrans under the decentralised procedure ("DCP"). The application was made under Article 10(3) and cited Temgesic as the RMP. Sandoz also sought to rely on the bridging data submitted by Napp in support of Napp's BuTrans MA application, and the only new data Sandoz submitted was bioequivalence data showing that its product was bioequivalent to BuTrans.

Summary of Napp's Arguments

In Napp's view, the MHRA was wrong to have allowed Sandoz to rely on the bridging data provided by Napp in support of its application for an MA for BuTrans.

Napp contended that the Directive did not permit a generic applicant such as Sandoz to rely on the bridging data provided at an earlier date by another applicant to support an authorisation under Article 10(3) for a different product and then simply provide bioequivalence data to show that its product was the bioequivalent of another generic product. Sandoz, it alleges, were required to provide data to support the safety of Reletrans relative to Temgesic, the RMP in Sandoz's application, and not to BuTrans.

In Napp's view, it would be contrary to the objective of the Directive to extend the principles of Article 10 to a "generic of a generic". Furthermore, such an extension would render Napp's bridging data entirely unprotected, which Napp claimed would be a disincentive to innovation.

Judgment

The judge dismissed the application for judicial review of the MHRA's decision to grant an MA for Reletrans and concluded that Sandoz could rely on the bridging data previously submitted by Napp.

The judge held that unlike the data exclusivity period afforded to the innovator, the Directive does not specify any particular protection for bridging data supplied under Article 10(3). This conclusion was supported by case law, in particular in Novartis v MHRA, where it was held that bridging data could not be afforded any additional period of protection over and above that already afforded to the original product.

The wording of the Directive does not specify that a generic applicant must submit its own bridging data. The use of the word "appropriate" in Article 10(3), in relation to pre-clinical tests or clinical trials, was not specific about who must commission those tests or trials. If the intention had been to require a specific person or entity to produce that data, words to that effect could and should have been included. Guidance in the relevant edition of the European Commission's Notice to Applicants also supported the view that bridging data submitted in support of an application under Article 10(3) can be referred to in an application for authorisation of a subsequent version of a generic drug.

Medicine

When considering the meaning of the relevant provisions, the judge also stated that the wording in Article 10(3) that the authorisation could only be granted if "appropriate pre-clinical tests or clinical trials" were provided, plainly gave some latitude to the competent authorities of the Member State to decide what, in any given case, was "appropriate". It is the competent authority who is best placed to decide, in each case, what data is "appropriate" to demonstrate that a new medicine is equivalent to an already authorised product.

Comment

The judge's decision in this case that bridging data submitted by others can be referred to in order to obtain an MA under the hybrid abridged procedure described in Article 10(3), appears to be consistent both with the wording and the purpose of the Directive.

Requiring a generic applicant to submit their own bridging data to the reference product, when such data already existed as the basis for approval of another generic medicine, would be contrary to the stated purpose of the Directive, leading to unnecessary repeat testing on animals and would also be a disincentive to the development of generic medicines, which are in the public interest.

The Global Marketing Authorisation ("GMA") concept was mentioned in the judgment and was accepted by all parties to apply where the innovator had filed the bridging data. The judge's conclusion that the identity of the developer of the first generic product was not important to the analysis suggests that the GMA concept applies regardless of the identity of the company filing the bridging data. It is unclear whether this decision will be appealed.

If you have any questions on this article or would like to propose a subject to be addressed by Synapse please contact us.