Physicochemical and Biological Examination of Two Glatiramer Acetate Products
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...
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MDPI AG
2019-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/7/3/49 |
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| author | Arthur Komlosh Vera Weinstein Pippa Loupe Tal Hasson Bracha Timan Attila Konya Jessica Alexander Sigal Melamed-Gal Steffen Nock |
| author_facet | Arthur Komlosh Vera Weinstein Pippa Loupe Tal Hasson Bracha Timan Attila Konya Jessica Alexander Sigal Melamed-Gal Steffen Nock |
| author_sort | Arthur Komlosh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T02:19:45Z |
| format | Article |
| id | doaj.art-dbf7312f505e49ae846734aeae737e85 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-13T02:19:45Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-dbf7312f505e49ae846734aeae737e852022-12-22T03:07:02ZengMDPI AGBiomedicines2227-90592019-07-01734910.3390/biomedicines7030049biomedicines7030049Physicochemical and Biological Examination of Two Glatiramer Acetate ProductsArthur Komlosh0Vera Weinstein1Pippa Loupe2Tal Hasson3Bracha Timan4Attila Konya5Jessica Alexander6Sigal Melamed-Gal7Steffen Nock8Specialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelSpecialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelSpecialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelSpecialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelSpecialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelSpecialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelSpecialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelSpecialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelSpecialty Research and Development, Teva Pharmaceutical Industries Ltd, Netanya 4250419, IsraelHerein 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.https://www.mdpi.com/2227-9059/7/3/49glatiramer acetatemultiple sclerosisphysicochemical assaysnon-biological complex drugsCopaxone |
| spellingShingle | Arthur Komlosh Vera Weinstein Pippa Loupe Tal Hasson Bracha Timan Attila Konya Jessica Alexander Sigal Melamed-Gal Steffen Nock Physicochemical and Biological Examination of Two Glatiramer Acetate Products Biomedicines glatiramer acetate multiple sclerosis physicochemical assays non-biological complex drugs Copaxone |
| title | Physicochemical and Biological Examination of Two Glatiramer Acetate Products |
| title_full | Physicochemical and Biological Examination of Two Glatiramer Acetate Products |
| title_fullStr | Physicochemical and Biological Examination of Two Glatiramer Acetate Products |
| title_full_unstemmed | Physicochemical and Biological Examination of Two Glatiramer Acetate Products |
| title_short | Physicochemical and Biological Examination of Two Glatiramer Acetate Products |
| title_sort | physicochemical and biological examination of two glatiramer acetate products |
| topic | glatiramer acetate multiple sclerosis physicochemical assays non-biological complex drugs Copaxone |
| url | https://www.mdpi.com/2227-9059/7/3/49 |
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