Marketing authorisation holders of generic medicinal products sometimes remove information from the summary of product characteristics (SmPC) and the patient information leaflet to prevent the potential infringement of a use patent.
A generic medicinal product is described in Directive 2001/83/EC (as amended by Directive 2004/27/EC) as “a medicinal product that has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product (the originator product), and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies”. As the generic medicinal product is equivalent to the reference medicinal product, the product information such as the SmPC and the patient information leaflet of a generic medicinal product need to correspond with those of the reference medicinal product.
Use patent claims are so-called second medical use claims, which generally serve to protect the use of a known active ingredient for the treatment of a new medical indication. An issue of patent infringement may arise if a generic manufacturer starts marketing a medicinal product under a marketing authorisation which contains multiple medical indications, one or more of which fall within the scope of the claims of a use patent. Patent protection of the active ingredient (and of the first medical indication) may have expired, but if there is still relevant protection under the use patent, the patentee might argue that trade in the medicinal product under the marketing authorisation nevertheless constitutes infringement of the use patent. To prevent such patent infringement disputes, the generic marketing authorisation holder may remove from its SmPC and patient information leaflet those indications that are still covered by such a use patent.
Article 11 of Directive 2001/83/EC as amended, allows marketing authorisation holders to exclude those parts of the SmPC referring to indications or dosage forms which are still covered by patent protection. In an explanation of this legislation by the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (‘CMDh’), it is stated that exclusion of parts of the SmPC and patient information leaflet in a mutual recognition procedure (‘MRP’), or decentralised procedure (‘DCP’), may take place during the final national approval of the MRP or DCP. No information due to a use patent will be deleted in the final SmPC recognised by all concerned Member States at the end of a MRP or DCP. The applicant of a marketing authorisation will need to propose a revised SmPC and patient information leaflet to the national authority concerned. This revision is made at a national level as the use patent may not be valid in all the concerned countries. In addition the Member States may decide nationally whether to include a clause explaining why an indication is not included in the patient information leaflet.
For those generic products which have been registered through the Central European Procedure, patented indications are not included in the approved SmPC or in the patient information leaflet and there is also no clause explaining the lack of an indication in the patient information leaflet.
Article 11 of Directive 2001/83/EC as amended has been implemented in The Netherlands by the Dutch Medicines Act and in the Regulation Medicines Act. The Dutch MEB is, however, of the opinion that as a result of the deletion of certain indications in a patient information leaflet, patients are incompletely and insufficiently informed on certain applications of generic medicinal products. To ensure that pharmacists, doctors and patients have access to fully approved product information, the Dutch MEB has, as of 1 December 2009, amended its policy in respect of use patents. Prior to this date the MEB would approve, after a request from a marketing authorisation holder of a generic medicinal product, the amendment of the SmPC and patient information leaflet in the medicines database of the MEB where a use patent was applicable. Under the new policy, the SmPC and patient information leaflet can no longer be amended in the medicines database. The medicines database must now contain the complete SmPC and patient information leaflet including all indications approved upon registration of the medicinal product, whether patented or not. A marketing authorisation holder of a generic medicinal product may now however, on its own initiative, delete the patented indications from the printed version of the SmPC and patient information leaflet when certain requirements are met:
- only the information in § 4.1, 4.2 and 5.1 of the SmPC and the corresponding sections of the patient information leaflet may be removed;
- no information may be removed which relates to the safety associated with the indications;
- a standard clause mentioning that not all indications are included in the patient information leaflet should be included; and
- the SmPC and patient information leaflet must include a reference that detailed information about the medicinal product is available in the medicines database on the website of the MEB.
The removal of the patented indications and the inclusion of the standard clause in the printed versions of the SmPC and patient information leaflet is the responsibility of the marketing authorisation holder. The text of the printed SmPC and patient information leaflet with the removed indications should be sent to the Dutch MEB with a declaration that these documents comply with the above requirements. Also, the expiration of the patent must be notified to the MEB.
This new policy of the MEB results in two different versions of a SmPC and patient information leaflet of a generic medicinal product:
- the complete SmPC and leaflet in the medicines database of the MEB, which is accessible to everyone; and
- the printed version of the marketing authorisation holder in which the patented indications are removed.
It remains to be seen what effect the new policy of the MEB will have on potential patent infringement by generic manufactures as result of the online availability of SmPCs and patient information leaflets with patented indications. To date, we are not aware of any formal objection to this policy.