CRED ERP 25

3. Similar biological medicinal product “biosimilar” (Article 10.4)

A “biosimilar” is a new biological medicinal product that is “similar” but not the same as a licensed reference biological medicinal product (a biosimilar, by nature of the fact that it is a biologically produced product, will never be truly “identical” to the originator; hence “similar” ). • Biological medicinal products are medicinal products containing biotechnology-derived proteins as active substance, e.g., vaccines, blood-derived products, monoclonal antibodies, recombinant proteins etc. The legal basis for similar biological applications can be found in Article 6 of Regulation (EC) No 726/2004 and Article 10(4) of Directive 2001/83/EC, as amended and defines a biosimilar as follows: • “ Where a biological medicinal product which is similar to a reference biological product does not meet the conditions in the definition of generic medicinal products, owing to, in particular, differences relating to raw materials or differences in manufacturing processes of the biological medicinal product and the reference biological medicinal product, the results of appropriate pre- clinical tests or clinical trials relating to these conditions must be provided. The type and quantity of supplementary data to be provided must comply with the relevant criteria stated in Annex I and the related detailed guidelines. The results of other tests and trials from the reference medicinal product's dossier shall not be provided. ” Further information on biosimilars: biosimilars are not generics Generics are chemically identical to their reference products whereas biosimilars are never identical to their reference products. The quality profile of biologics is defined by the manufacturing process; process differences are inevitable between manufacturers; the manufacturing process will unlikely ever be identical as to that of the originator. As a result, small physicochemical differences can lead to marked changes in clinical profiles. Therefore, there are a number of principles that need to be applied when attempting to establish bio-similarity including: • Comprehensive physicochemical and biological characterisation • Determination of the extent of non-clinical in vivo studies and clinical studies required • Comparability exercise should be performed in order to identify and assess any relevant differences between the biosimilar and the reference medicinal product • Information to be supplied not to be limited to Modules 1, 2 and 3 (pharmaceutical, chemical and biological data), but supplemented with bioequivalence and bio-availability data • A full Module 3 is required in line with the revised Annex I to the Directive 2001/83, Ph Eur and CHMP and ICH guidelines and requirements • The type and amount of additional data (i.e., toxicological and other non-clinical and appropriate clinical data) determined on a case-by-case basis in accordance with relevant scientific guidelines • Due consideration should be given to immunogenicity issues • If the reference medicinal product has more than one indication, the efficacy and safety of themedicinal product claimed to be similar must be justified or, if necessary, demonstrated separately for each of the claimed indications • Comparability is more likely to be possible for highly purified products which can be highlycharacterised including those produced by biotechnical processes • If no product class specific guideline exists then seeking scientific advice is highly recommended The dossier requirements for similar biological medicinal products are found in Part II, Section 4 of Annex I of Directive 2001/83/EC, as amended.