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Evaluation of Process Efficiency and Bioequivalence of Biosimilar Recombinant Human Chorionic Gonadotropin (rhCG)

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Abstract

Background

Human chorionic gonadotropin (hCG) is a therapeutic protein used for ovulation induction in women with infertility. Dong-A Pharm. Co. has developed recombinant hCG (rhCG) [product code DA-3803] produced in Chinese hamster ovary cells and evaluated its biologic properties, such as biologic potency, efficacy, and pharmacokinetic profile, compared with a reference product, Ovidrel®.

Objective

The purpose of this study was to evaluate the efficiency of the purification process of Dong-A rhCG (DA-3803) and its bioequivalence from a biosimilar perspective.

Methods

The efficiency of the purification process was estimated through scale-down clearance studies for viruses, endotoxins, host cell DNAs (HCDs) and host cell proteins (HCPs). To confirm bioequivalence, the in vivo/in vitro biologic potency, ovulation induction rate, and pharmacokinetic profile of DA-3803 were compared with those of Ovidrel®.

Results

In the clearance studies, the lowest log reduction value (LRV) for model viruses was 8.43. LRVs for endotoxins, HCDs, and HCPs were greater than 5.27, 16.36, and 3.37, respectively. DA-3803 showed equivalent potency with Ovidrel®, and similarity between DA-3803 and Ovidrel® was observed in an efficacy evaluation that measured ovulation induction. The bioequivalence was also confirmed in a rat pharmacokinetic study, which compared pharmacokinetic parameters such as maximum serum concentration, area under the concentration-time curve, time to reach maximum serum concentration, and half-life. In a comparison of different isoform groups of DA-3803, it was shown that the potency and pharmacokinetic profile depend on the sialic acid content.

Conclusion

The purification process of DA-3803 was effective in removing the major process impurities, and DA-3803 showed similar biologic properties to the reference drug, Ovidrel®.

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Acknowledgments

No sources of funding were used to assist in the preparation of this original research article. The authors have no conflict of interest directly relevant to the content of this study.

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Authors and Affiliations

  1. Biopharmaceutical Research Laboratory, Dong-A Pharmaceutical Co., Ltd, Yongin, Kyunggi, Korea

    Kwang Seok Seo, Jin Wook Yoon, Kyu Heum Na, Eun Jeong Bae, Jung Gyu Woo, Sung Hee Lee & Soo Hyoung Kang

  2. Department of Life Science, Sogang University, Mapo-gu, Shinsu-dong 1, Seoul, Korea

    Kwang Seok Seo &  Jai Myung Yang PhD

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  1. Kwang Seok Seo
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Correspondence to Jai Myung Yang PhD.

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Seo, K.S., Yoon, J.W., Na, K.H. et al. Evaluation of Process Efficiency and Bioequivalence of Biosimilar Recombinant Human Chorionic Gonadotropin (rhCG). BioDrugs 25, 115–127 (2011). https://doi.org/10.2165/11589430-000000000-00000

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