Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur<sup>®</sup>) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency
Recombinant human follicle stimulating hormone (r-hFSH) is widely used for infertility treatment and is subject to the development of biosimilars. There are different purification strategies that can yield r-hFSH of pharmaceutical quality from Chinese hamster ovary cell culture broth. We developed a...
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MDPI AG
2022-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/1/96 |
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| author | Maria Sinegubova Ivan Vorobiev Anatoly Klishin Dmitry Eremin Nadezhda Orlova Natalya Orlova Mikhail Polzikov |
| author_facet | Maria Sinegubova Ivan Vorobiev Anatoly Klishin Dmitry Eremin Nadezhda Orlova Natalya Orlova Mikhail Polzikov |
| author_sort | Maria Sinegubova |
| collection | DOAJ |
| description | Recombinant human follicle stimulating hormone (r-hFSH) is widely used for infertility treatment and is subject to the development of biosimilars. There are different purification strategies that can yield r-hFSH of pharmaceutical quality from Chinese hamster ovary cell culture broth. We developed a purification process for r-hFSH centered on immunoaffinity chromatography with single-domain recombinant camelid antibodies. The resulting downstream process is simple and devoid of ultrafiltration operations. Studies on chromatography resin resource and ligand leakage showed that the immunoaffinity matrix employed was suitable for industrial use and stable for at least 40 full chromatography cycles, and the leaked single-domain antibody ligand was completely removed by subsequent purification steps. All chromatography resins employed withstood the same 40 cycles of use without significant changes in separation efficiency and product binding capacity. The resulting industrial purification process yielded batches of r-hFSH with consistent levels of purity and bioactivity. |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T00:43:32Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj.art-c8b83b31245144bd89126b82ec3e88ff2023-11-23T15:03:47ZengMDPI AGPharmaceutics1999-49232022-01-011419610.3390/pharmaceutics14010096Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur<sup>®</sup>) to Yield a Pharmaceutical Product with High Batch-to-Batch ConsistencyMaria Sinegubova0Ivan Vorobiev1Anatoly Klishin2Dmitry Eremin3Nadezhda Orlova4Natalya Orlova5Mikhail Polzikov6Laboratory of Mammalian Cell Bioengineering, Institute of Bioengineering, Federal State Institution «Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences», Leninsky Prospect, 33, Build. 2, 119071 Moscow, RussiaLaboratory of Mammalian Cell Bioengineering, Institute of Bioengineering, Federal State Institution «Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences», Leninsky Prospect, 33, Build. 2, 119071 Moscow, RussiaState Research Institute of Genetics and Selection of Industrial Microorganisms of National Research Center «Kurchatov Institute», Dorozhniy Proezd, 1, 117545 Moscow, RussiaIVFarma LLC, Nauchnyi Proezd, 20, Build. 2, 117246 Moscow, RussiaLaboratory of Mammalian Cell Bioengineering, Institute of Bioengineering, Federal State Institution «Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences», Leninsky Prospect, 33, Build. 2, 119071 Moscow, RussiaState Research Institute of Genetics and Selection of Industrial Microorganisms of National Research Center «Kurchatov Institute», Dorozhniy Proezd, 1, 117545 Moscow, RussiaIVFarma LLC, Nauchnyi Proezd, 20, Build. 2, 117246 Moscow, RussiaRecombinant human follicle stimulating hormone (r-hFSH) is widely used for infertility treatment and is subject to the development of biosimilars. There are different purification strategies that can yield r-hFSH of pharmaceutical quality from Chinese hamster ovary cell culture broth. We developed a purification process for r-hFSH centered on immunoaffinity chromatography with single-domain recombinant camelid antibodies. The resulting downstream process is simple and devoid of ultrafiltration operations. Studies on chromatography resin resource and ligand leakage showed that the immunoaffinity matrix employed was suitable for industrial use and stable for at least 40 full chromatography cycles, and the leaked single-domain antibody ligand was completely removed by subsequent purification steps. All chromatography resins employed withstood the same 40 cycles of use without significant changes in separation efficiency and product binding capacity. The resulting industrial purification process yielded batches of r-hFSH with consistent levels of purity and bioactivity.https://www.mdpi.com/1999-4923/14/1/96biopharmaceuticalsbiosimilarsrecombinant human follicle stimulating hormone (r-hFSH)follitropin alphadownstreamimmunoaffinity chromatography |
| spellingShingle | Maria Sinegubova Ivan Vorobiev Anatoly Klishin Dmitry Eremin Nadezhda Orlova Natalya Orlova Mikhail Polzikov Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur<sup>®</sup>) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency Pharmaceutics biopharmaceuticals biosimilars recombinant human follicle stimulating hormone (r-hFSH) follitropin alpha downstream immunoaffinity chromatography |
| title | Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur<sup>®</sup>) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency |
| title_full | Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur<sup>®</sup>) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency |
| title_fullStr | Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur<sup>®</sup>) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency |
| title_full_unstemmed | Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur<sup>®</sup>) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency |
| title_short | Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur<sup>®</sup>) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency |
| title_sort | purification process of a recombinant human follicle stimulating hormone biosimilar primapur sup r sup to yield a pharmaceutical product with high batch to batch consistency |
| topic | biopharmaceuticals biosimilars recombinant human follicle stimulating hormone (r-hFSH) follitropin alpha downstream immunoaffinity chromatography |
| url | https://www.mdpi.com/1999-4923/14/1/96 |
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