Revised Guideline Draft on Biosimilar Medicinal Products published

A biosimilar medicinal product is a product which is similar to a biological medicinal product (so-called "reference medicinal product" which has already been granted a marketing authorisation) with regard to APIs, efficacy and therapeutic indication. (A "biological medicinal product" is manufactured with an API made by or derived from a living organism like a bacterium or yeast). Many extensive studies must be performed to prove the comparability between biosimilar and biological reference medicinal products to compare the quality and consistency of both the API and the finished product as well as of the whole manufacturing process.

On 31 May 2012, the EMA published the draft of a guideline entitled "Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1)" for comment. This draft guideline is basically an update of the biosimilar guideline from 1st June 2006 which is currently still in force. Each single chapter has been revised in-depth and rigorously and contains many more detailed requirements - compared to the existing guideline. The chapter about comparative studies - referred to as "comparability exercise" in the guideline - describes in details how to perform such investigations which must be submitted for the marketing authorisation of a biosimilar medicinal product. The further chapters provide details about the analytical procedure, physicochemical properties, biological activity, purity and impurities. An additional chapter about immunochemical properties in comparative studies has been added. We have listed here some examples of requirements on the comparative analysis of physicochemical properties:

  • Proof of the primary (and/ or higher order structures) structure of the API
  • Evidence of the amino acid sequences and their identity with the sequence of the reference API
  • Identification of the N- and C-terminal amino acid sequences as well as free SH groups and disulfide bridges
  • Quantification of modifications or truncations of the protein chain
  • Determination of the glycosylation pattern

Unusual glycosylation structures which differ from the reference pattern must be described and require appropriate justification.

These requirements and the instructions made in the further paragraphs are definitely much more extensive and precisely show how complex the performance of comparative studies will be when the guideline will come into effect.

Please see the draft of the "Guideline on similar biological medicinal products 5 containing biotechnology-derived proteins as active 6 substance: quality issues (revision 1)" for further information.

On the EMA website, you can also find a document "Questions and Answers on biosimilar medicines", providing basic information on biosimilar medicinal products.

The EMA has also developed an interesting brochure "Biosimilar medicinal products" about the different types of biosimilars and their respective responsible working groups.

Dr Gerhard Becker
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

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