Physicochemical and Biological Examination of Two Glatiramer Acetate Products.

Autor:	Komlosh A; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel., Weinstein V; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel., Loupe P; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel. Pippa.Loupe@tevapharm.com., Hasson T; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel., Timan B; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel., Konya A; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel., Alexander J; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel., Melamed-Gal S; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel., Nock S; Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, Israel.
Jazyk:	angličtina
Zdroj:	Biomedicines [Biomedicines] 2019 Jul 03; Vol. 7 (3). Date of Electronic Publication: 2019 Jul 03.
DOI:	10.3390/biomedicines7030049
Abstrakt:	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. Competing Interests: All authors are employees of Specialty Research and Development Teva Pharmaceutical Industries.
Databáze:	MEDLINE
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