Biosimilars and the issue of duplicates

‘Biosimilars’ refer to products which are similar to a biological product that has already been authorised for use. As the name suggests, the complexities of manufacturing these products means that whilst they may be closely similar to the original “innovator” product, they are not identical.

The European Medicines Agency has only authorised a few biosimilars since the first such authorisation in 2006, and has been at the forefront of developing a specific procedure for the authorisation of such products through the centralised procedure. Despite this innovation, the use of the centralised procedure has posed challenges, especially where the patent for the original biosimilar compound has expired, but there is patent protection for a second medical use of that compound. Under the centralised procedure there is no mechanism to remove the patented indication from the Summary of Product Characteristics (the “SmPC”) or Patient Information Leaflets (“PIL”) for those countries where that use is protected. This leaves the manufacturer at risk of allegations of patent infringement. Therefore, where the manufacturer of a biosimilar wishes to launch in those countries where the second medical use is patent protected, it must submit a duplicate application with the necessary carve out on the SmPC/PIL.

Under article 82(1) of Regulation 726/2004:

“the Commission shall authorise the same applicant to submit more than one application to the Agency for that medicinal product when there are objective verifiable reasons relating to public health regarding the availability of medicinal products to health-care professionals and/or patients, or for co-marketing reasons.”

A common reason to allow duplicates is where an indication in the original application is protected by a patent in a Member State. Although this may overcome the issue of the carve out, it in turn creates further issues. Although it is clear that the original application and the duplicate are the same product, under EU regulations each application requires a separate name for the medicinal product to be submitted. This has an impact on patient care, for the same product will have a different name in different countries. This may result in patients being prevented from accessing their prescribed medicine in different countries, but it may also create confusion for both patients and healthcare professionals alike. Once the second use patents have expired, doctors would need to switch the name of the prescribed medicine to that used in the original application to ensure harmonisation. Indeed the applicant must provide a commitment letter upon application undertaking to ensure that once the patent expires, the shortened label is extended to include the indication that was patent protected. In that respect, it is essential that both labels bear the same name. Otherwise, a company will have to re-market the product under the new (and harmonised) name once the patent expires, which has financial implications for manufacturers.

Overcoming these issues would require a reinterpretation of EU regulations. Either the indications that are patent protected by the second medical use are removed before marketing the product in those Member States that afford that protection, or duplicates that are solely applied for due to such patents are allowed to bear the same name. The former approach could be justified under article 11 of Directive 2001/83, and would mean that the centralised procedure is brought into line with the decentralised procedure. The latter approach would require a new interpretation of article 6 of Regulation 726/2004, which states that each application for authorisation “shall include the use of a single name for the medicinal product”. However, as the original and duplicate applications are for the same product, this interpretation should not be problematic.

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