Regulation of Biosimilars

Biosimilar Regulations

In the last blog post, I discussed the differences between biosimilar drugs and small molecule drugs. In this post, I will discuss the guidelines that the World Health Organization and the European Medicines Association have laid down in terms of marketing approval for biosimilar drugs.

First, why are new regulatory guidelines required? As explained in the last blog post, it is currently not possible to conclusively demonstrate that one therapeutic protein is identical to another – even if both are produced by the same gene – if different cell lines or manufacturing processes are used. Because of these potential differences, regulatory agencies cannot simply approve a biosimilar drug based on the safety and efficacy data that was used for approval of the innovator drug. However, in many cases the two drugs will be similar enough that a complete data portfolio supporting the safety and efficacy of the biosimilar is unneccasary.

The question, then, is in determining just what is required to assure the safety and efficacy of biosimilars without wasting the resources of drug companies and regulatory agencies alike. The standard that has been adopted by the European Medicines Association (EMA), and which the Food and Drug Administration (FDA) seems likely to adopt, is that of “comparability”. What this means is that if a biosimilar manufacturer is able to demonstrate, using state of the art analytics and lab-based functionality tests, that a the biosimilar product is in fact highly similar to an already licensed product, then the biosimilar product may be eligible for an abbreviated approval pathway in terms of preclinical and clinical testing.

The EMA approved its first biosimilar drug, Omnitrope, in 2006. Omnitrope is a biosimilar version of human growth hormone. Since that time, thirteen additional biosimilars have been approved in the EU – although all fourteen of the EU-approved biosimilars fall under just three different drug categories: human growth hormones, granulocyte-colony stimulating factors, and erythropoietins. These types of proteins are all relatively simple in terms of their structure – making it easier to demonstrate comparability. In May of 2011, the EMA released guidelines for the approval of biosimilar monoclonal antibodies, illustrating the need for a different approach to demonstrating comparability for these more complex molecules.

The FDA has not yet begun to approve biosimilars; however last month the FDA published a paper suggesting that their guidelines, promised to be released sometime this year, will be similar to the EMA guidelines , with demonstration of comparability as a minimum requirement for the reduction of preclinical and clinical trials data.