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Focus


Focus on glatiramoids and follow on compounds


Here, we give insights into the glatiramoid class of NBCDs and issues arising in the development and introduction of generic forms


Jana Lizrova Preiningerova MD Department of Neurology and Centre of Clinical Neuroscience Charles University in Prague First School of Medicine and General University Hospital, Prague,


Glatiramoids are a family of synthetic copolymer mixtures comprising the four amino acids, L-glutamic acid, L-alanine, L-lysine and L-tyrosine, in a defined molar ratio. Glatiramoids are specific in that due to the complexity and heterogeneity of the mixture of polypeptides, it is not possible to identify the active epitopes (that is, amino acid sequences responsible for the clinical effect). Although the individual glatiramoids are similar, no two can be identical. Individual glatiramoids can be distinguished, for example, on the basis of the average molecular weight, peptide mapping, certain non-random and reproducible patterns of amino acid sequence, secondary and tertiary structures, or the specific ratio between the molecules with C-terminal carboxyl groups and C-terminal diethylamide groups.1


Even slight changes in molecular weight distribution, in folding of antigenic polypeptide sequences, or any other characteristics mentioned above, which are primarily dependent on the manufacturing process, will significantly affect the efficacy, safety and immunogenicity of glatiramoids. This means that any glatiramoid synthesised by another manufacturer


14 www.hospitalpharmacyeurope.com


should be regarded as a new member of the family, with a specific profile of efficacy, safety and immunogenicity. The first and most widely studied glatiramoid is glatiramer acetate (GA, Copaxone), approved for the treatment of relapsing remitting multiple sclerosis. A more recent glatiramoid, protiramer, was developed as a follow on product to GA. In addition there are several generic forms of GA. Composition, quality and drug effects are highly dependent upon the manufacturing process and its control.2 It follows that the same non-biological complex drugs (NBCDs) from different manufacturers, or an original drug and


its copy (generic), cannot be considered identical from the chemical point of view nor with regards to clinical efficacy and safety.


What are the requirements for a ‘generic’ NBCD?


When approving generic forms of conventional medicines, that is, chemicals with a small, precisely defined molecule, the manufacturer must demonstrate chemical equivalence (the contents of the same active ingredient) and pharmaceutical equivalence and bi0equivalence. Furthermore, it must submit the results of these bioequivalence studies intended


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