The Bolar exemption – protection of API suppliers

18 May 2014

The CJEU has recently been asked by the German courts to consider whether the Bolar exemption extends to a third party manufacturer which supplies a patent-protected substance to a generic drug company for use in trials for the purpose of generating data to be used to support  an abridged marketing authorisation application.

The Bolar Exemption

Directive 2004/27/EC (which amended Directive 2001/83/EC on Medicinal Products for Human Use) obliged member states to introduce into national law an exemption from patent infringement in circumstances where the patented drug was used in trials which were necessary in order to obtain an abridged marketing authorisation.  Its purpose was to address uncertainty about the application of the experimental use exemption to the bioequivalence trials which are required for submission of an abridged marketing authorisation application.

Astellas v Polpharma

Polpharma S.A. Pharmaceutical Works is the biggest manufacturer of generic medicines and Active Pharmaceutical Ingredients (APIs) in Poland. A dispute with Astellas Pharma Inc., a Japanese pharmaceutical company, arose after Polpharma advertised on its website and in industry magazines a list of APIs which it offered for sale. This list included solifenacin succinate, which was covered by Astellas' Polish patent PL182344 for quinuclidine derivatives and pharmaceutical preparations containing these (being the national designation of EP 0 801 067). The advert included a disclaimer stating that products were not offered or supplied for commercial purposes in countries where this would constitute patent infringement and, in particular, that in Poland solifenacin succinate was offered solely for experimental purposes or for use falling within the confines of the Bolar exemption. Polpharma had an EU Drug Master File (detailing pharmaceutical production and quality assurance) for solifenacin succinate as would be required by the regulatory authorities if its customers were to apply for a marketing authorisation for a drug containing this API.  A German generic drug manufacturer, Hexel AG, purchased and took delivery of a large amount of the patented API from Polpharma.

- Polish litigation

Astellas brought an action against Polpharma for patent infringement in Poland, which concluded with the Polish Supreme Court finding in Astellas' favour. Polpharma had argued that its customers (who were clearly covered by the Bolar exemption) were going to use the API it supplied solely for performing the studies and testing required for registration or marketing authorisation and that to deny it the protection of the Bolar provision would deny generic companies which are unable to manufacture API themselves the opportunity to launch immediately on expiry of the patent. On the other hand, Astellas argued that only those conducting the studies and trials are entitled to rely on the Bolar exemption. Upholding the judgments of the lower courts, the Polish Supreme Court held that marketing of a patented API, irrespective of its purpose, is not covered by the Bolar exemption and therefore constitutes patent infringement. The Court disregarded the fact that the purchaser intended to use the API exclusively for acts related to obtaining a marketing authorisation, emphasising that Polpharma had no control over how its customers used the patented product. Polpharma had requested that preliminary questions be submitted to the CJEU, however, the Court deemed such a reference unnecessary.

- German litigation

The same dispute is also being litigated in Germany. Having heard similar arguments, the Düsseldorf district court held that a third party API supplier such as Polpharma will only be protected by the Bolar exemption when it is a co-organiser of the studies carried out by its customer. However, the Düsseldorf Court of Appeal interpreted the exemption more widely, holding that the third party API supplier will be protected if the supply is aimed at a purpose falling within the Bolar exemption. The Court of Appeal court also agreed to Polpharma's request to refer preliminary questions to the CJEU, which took the following form:

1. Must Art. 10 para. 6 of Directive 2001/83/EC be interpreted as meaning that those acts of delivery are also excluded from patent protection by which a third party offers or delivers a patented active substance to a manufacturer of generic products for purely commercial reasons, which the manufacturer of generics intends to use for studies or trials in order to obtain a marketing authorisation or approval within the meaning of Art. 10 para. 6 of Directive 2001/83/EC?

2. If this first question is to be answered in the affirmative:

(a) Does the privileged status of the third party depend on whether the manufacturer of generics supplied indeed uses the provided active substance in privileged studies or trials within the meaning of Art. 10 para. 6 of Directive 2001/83/EC? In such a case, does the exclusion from patent protection also apply if the third party is unaware of its customer's intended privileged use and has not ascertained whether this is the case? Or does the privileged status of the third party merely depend on whether, at the time of the act of delivery, the third party can rightly assume that, judging all of the circumstances (i.e. profile of the supplied company, small amount of the provided active substance, imminent expiration of the patent protection of the relevant active substance, experience gained concerning the customer's reliability), the supplied manufacturer of generics will use the provided active substance for privileged trials and studies in the context of a marketing approval only?

(b) In the context of its act of delivery, is the third party obliged to take separate precautions to ensure that its customer will indeed use the active substance for privileged trials and studies only or do the precautionary measures of the third party differ, depending on whether the patented active substance is merely offered or actually delivered?

Comment

The CJEU's preliminary ruling in response to the above questions is of considerable importance.  The main purpose of the Bolar exemption is to facilitate market entry of generics immediately on patent expiry; a restrictive interpretation of this exemption so as to exclude supplies of API by third party API manufacturers could undermine this purpose.

The ability of generic drug companies who do not manufacture API themselves to launch their products immediately on expiry of the relevant patent or SPC would be severely hampered if they were unable to source API from third party API manufacturers.

On the other hand, the CJEU may interpret the exemption so as not to exclude such third party supplies of API even if the activities of Polpharma in this particular case are deemed to fall outside the scope of the exemption.

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