The European Medicines Agency (EMA) has published its revised overarching guideline on biosimilars. The main change brought by this new guidance is the possibility for medicines developers to use a comparator authorized outside the European Economic Area (EEA) during the clinical investigation of a biosimilar. This new concept is expected to facilitate the global development of biosimilars and to avoid unnecessary repetition of clinical trials. The revised guideline will come into force as of April 20, 2015; however, applicants can apply some or all provisions of this guideline currently, according to the EMA.
A biosimilar is a biological medicine that is similar to a reference biological medicine that has already been authorized in the EEA. A biosimilar is granted a marketing authorization only if the developer has demonstrated in studies that it is as safe and effective as the reference medicine. EMA established a regulatory framework for the development of biosimilars in 2005 with the publication of the first overarching guideline defining key principles to be applied for these medicines. This document, together with a series of complementary guidelines that were subsequently developed by the EMA, have led to the approval of 19 biosimilars in the European Union to date, including the first two monoclonal-antibody biosimilars.
As part of the development of a biosimilar, an applicant has to conduct studies that show the similar nature, in terms of quality, safety, and efficacy, of the biosimilar and the chosen reference medicine authorized in the EEA. The revised guideline introduces the possibility of comparing a biosimilar in certain clinical studies and in vivo non-clinical studies with a non-EEA-authorized comparator. This comparator will need to be authorized by a regulatory authority with similar scientific and regulatory standards to those of the EMA. It will then be the applicant's responsibility to establish that the comparator is representative of the reference medicine authorized in the EEA.
In addition to this new concept, the revised guideline also clarifies key principles in light of the experience gained since its first release in September 2005, including: the terminology for biosimilars; the principles of biosimilarity, including safety and efficacy aspects; the requirements regarding the posology, route of administration, and formulation of biosimilars.
This guideline is one of three EMA overarching biosimilar guidelines. The other two are: a guideline addressing the quality issues related to biosimilar development: a revision of this guideline was published in June 2014 and will come into effect in December 2014; and a guideline on the clinical and non-clinical aspects related to biosimilar development; following a public consultation that took place in 2013, a revised guideline is expected to be published by the end of 2014.
The overarching guidelines are complemented by product-specific guidelines, which give more detailed guidance to applicants in relation to the respective class of products. EMA’s procedural advice on biosimilars has been updated to reflect these changes.