Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur(R)) 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 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.

Automated summary

A purification process for r-hFSH centered on immunoaffinity chromatography with single-domain recombinant camelid antibodies was developed, allowing for pharmaceutical quality r-hFSH to be obtained from Chinese hamster ovary cell culture broth. The use of immunoaffinity matrix was suitable for industrial use and stable for at least 40 full chromatography cycles, with leaked single-domain antibody ligand completely removed by subsequent purification steps. The industrial purification process yielded consistent batches of r-hFSH with high purity and bioactivity levels.