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Open AccessArticle

Physicochemical and Biological Examination of Two Glatiramer Acetate Products

Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel
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Biomedicines 2019, 7(3), 49; https://doi.org/10.3390/biomedicines7030049
Received: 5 June 2019 / Revised: 25 June 2019 / Accepted: 26 June 2019 / Published: 3 July 2019
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Abstract

Herein 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
Keywords: glatiramer acetate; multiple sclerosis; physicochemical assays; non-biological complex drugs; Copaxone glatiramer acetate; multiple sclerosis; physicochemical assays; non-biological complex drugs; Copaxone
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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.

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