Physicochemical and Biological Examination of Two Glatiramer Acetate Products
AbstractHerein we compared 40 mg/mL lots of the active ingredient, glatiramer acetate, manufactured by Mylan/Natco to the active ingredient, glatiramer acetate in Copaxone (Teva Pharmaceuticals, Ltd., Netanya Israel) using physicochemical (PCC) methods and biological assays. No differences were seen between the Mylan/Natco and Teva lots with some low resolution release PCC assays (amino acid analysis, molecular weight distribution, interaction with Coomassie Brilliant Blue G-250). Changes in polydispersity between Mylan/Natco and Copaxone lots were found using size exclusion chromatography and the high resolution PCC method, known as Viscotek, and suggestive of a disparity in the homogeneity of mixture, with a shift towards high molecular weight polypeptides. Using RPLC-2D MALLS, 5 out of 8 Mylan/Natco lots fell outside the Copaxone range, containing a high molecular weight and high hydrophobicity subpopulation of polypeptides not found in Copaxone lots. Cation exchange chromatography showed differences in the surface charge distribution between the Copaxone and Mylan/Natco lots. The Mylan/Natco lots were found to be within Copaxone specifications for the EAE model, monoclonal and polyclonal binding assays and the in vitro cytotoxicity assay, however higher IL-2 secretion was shown for three Mylan/Natco lots in a potency assay. These observations provide data to inform the ongoing scientific discussion about the comparability of glatiramer acetate in Copaxone and follow-on products. View Full-Text
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Komlosh, A.; Weinstein, V.; Loupe, P.; Hasson, T.; Timan, B.; Konya, A.; Alexander, J.; Melamed-Gal, S.; Nock, S. Physicochemical and Biological Examination of Two Glatiramer Acetate Products. Biomedicines 2019, 7, 49.
Komlosh A, Weinstein V, Loupe P, Hasson T, Timan B, Konya A, Alexander J, Melamed-Gal S, Nock S. Physicochemical and Biological Examination of Two Glatiramer Acetate Products. Biomedicines. 2019; 7(3):49.Chicago/Turabian Style
Komlosh, Arthur; Weinstein, Vera; Loupe, Pippa; Hasson, Tal; Timan, Bracha; Konya, Attila; Alexander, Jessica; Melamed-Gal, Sigal; Nock, Steffen. 2019. "Physicochemical and Biological Examination of Two Glatiramer Acetate Products." Biomedicines 7, no. 3: 49.
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