Europe’s draft Directive on biosimilars is due to be finalised in the first quarter of 2006, but there are still several deficiencies in the document that need to be addressed, according to Thomas Bols, director of government affairs, Europe, at biotechnology major Amgen.

He told a press conference at the Cordia convention in London, UK, yesterday that there is still a lot of work to be done on some key issues, such as the generic names of biosimilar drugs, pharmacist substitution of a biosimilar for an innovator product, confidentiality of innovator dossiers and the balance between pre- and post-marketing studies in supplying safety and efficacy data.

The EU recognises that copies of off-patent biologic drugs cannot be treated in the same way as conventional generics, because it is not possible to make a biologic by one production process that is completely identical to another using a different process [[10/10/02e]].

As a result, faced with patent expiries on a number of big-selling biologic drugs and political pressure to provide access to cheaper biologics, the European Medicines Agency (EMEA) has developed a route to market based on the principle of a “comparability exercise,” which allows biosimilars to be approved without a full application package, providing studies showing that they have the same basic safety and efficacy profile as the pioneer drug. Applications for interferon alfa and human growth hormone biosimilars are already under review at the agency [[14/09/05f]].

On the issue of generic names, Bols said it will be important to differentiate biosimilars from the innovator drug, and indeed from each other, in order to allow accurate post-marketing surveillance and trace any product-related problems back to the source. At present this is not covered in the draft guidance, he noted.

The issue of pharmacist substitution is also not covered in the guidance, but must be addressed, said Bols, as some EU countries such as Germany and Sweden allow pharmacists to dispense a generic, even if a doctor has specified the brandname drug. As biosimilars are not considered identical to the innovator, this should not occur without consultation with the prescriber, suggested Bols.

Meanwhile, there are still some other fundamental issues that need to be tackled before the guidance is finalised. One big question is how guidance to biosimilar firms can be provided without reference to innovator data, which may be confidential? he asked.

And, of course, the safety problems that can emerge with small changes in the production process of a biologic mean there must be thoughtful and transparent discussions about the level of clinical safety data that must be provided before marketing and how much safety monitoring will occur after a biosimilar reaches the market.

The most notable example of the potential safety concerns is the serious, autoimmune-like haematological disorder that occurred after a change in the process used to make Johnson & Johnson’s erythropoietin product Eprex in the late 1990s.

The comment period on the draft guidance expires at the end of this month.