Biosimilars have been available in Europe since the 2006-approval of Omnitrope, Sandoz's version of Pfizer's growth-hormone product Genotropin (somatropin). Several versions of two other biologics, erythropoietin and filgrastim, are also now available from various companies. While none are yet approved in the United States, a legal framework towards biosimilar approval is now in place, and it is only a matter of time before the innovator companies face competition in this market.
The European Union (EU) authorities implemented their guidelines for biosimilars in 2004 as part of an amendment to the community code relating to medicinal products for human use. In Europe, however, the term "biosimilar" is not explicitly defined, and whether a product would be acceptable via the "similar biological medicinal product" approach is dependent on analytical procedures, the manufacturing processes used, and clinical and regulatory experience. The European Medicines Agency (EMA) also demands comparability studies to substantiate the similar nature of the two products in terms of quality, safety, and efficacy.The clinical trials for biosimilars that have been demanded by the EMA ahead of approval have somewhat varied. Products have been approved despite differences in the glycosylation patterns and impurity profiles between the biosimilar and the innovator product. So far, all the biosimilars approved in Europe have been versions of naturally occurring hormones or cytokines, and draft guidelines for monoclonal-antibody products were published in 2011 (1).
FDA established the US framework in March 2010, and there are a number of key differences from the guidelines delineated in Europe. The US guidelines state that the clinically active ingredients in a biosimilar must be highly similar to the reference biologic, with no clinically meaningful differences in terms of safety, purity or potency. It must have the same mechanism of action, be administered in the same way via the same dosage form and have the same strength as the reference product.
With no biosimilars approved in the US to date, the guidelines have yet to be tested in practice for a marketed product. However, the experience gained in Europe during the past seven years may provide pointers. So what does the European experience tell us?