On 22 May 2014, the European Medicines Agency (“EMA”) published a finalised version of its Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (hereafter “EMA Guideline”). The revised EMA Guideline is expected to come into force in December 2014 and will replace the current guideline which came into effect in June 2006.

Since the adoption of the current guideline in June 2006, the European Commission has authorised 14 new biosimilar medicinal products. Moreover, there has been a substantial increase in the number of requests for scientific advice received by the Committee for Medicinal Products for Human Use (CHMP) concerning the development of biosimilar medicinal products.

It is for this reason that the EMA adopted this revised EMA Guideline. The EMA Guideline outlines the general principles concerning the quality aspects of biosimilars containing recombinant proteins and derivatives as active substance(s).

Furthermore, the revised EMA Guideline provides guidance concerning the quality requirements that are to be assessed as part of an application for marketing authorisation of a biosimilar which claims to be similar to an authorised biological product in the European Union (“EU”).

The EMA Guideline outlines the quality requirements for biosimilars in the following areas:

  • manufacturing processes;
  • the biosimilar comparability exercise for quality;
  • the choice of reference medicinal product;
  • analytical methods;
  • physicochemical characterisation;
  • biological activity; and
  • purity and quality attributes for relevant specifications of the similar biological medicinal product.

According to the EMA Guideline, an extensive comparability exercise between the reference medicinal product and the biosimilar will be required to demonstrate that the biosimilar has a similar profile in terms of quality, safety and efficacy to the reference medicinal product. This should include a comprehensive analysis of the proposed biosimilar and the reference medicinal product using sensitive and orthogonal methods to determine any similarities or potential differences in quality attributes.

This analysis should include comparative studies unless otherwise justified. Any detected differences in the quality attributes must be appropriately justified with regard to their potential impact on safety and efficacy.

Furthermore, the EMA Guideline requires extensive state-of-the-art characterisation studies to be performed in parallel on both the reference medicinal product and the biosimilar. These studies will demonstrate that the quality of the biosimilar is comparable to the reference medicinal product.