title: Evaluation of process efficiency and bioequivalence of biosimilar recombinant human chorionic gonadotropin (rhCG).
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.
  
  
  CONCLUSIONS
  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®.
authors: Biopharmaceutical Research Laboratory, Dong-A Pharmaceutical Co., Ltd, Yongin, Kyunggi, Korea.
authors: Kwang Seok
authors: KS
authors: Seo
authors: Jin Wook
authors: JW
authors: Yoon
authors: Kyu Heum
authors: KH
authors: Na
authors: Eun Jeong
authors: EJ
authors: Bae
authors: Jung Gyu
authors: JG
authors: Woo
authors: Sung Hee
authors: SH
authors: Lee
authors: Soo Hyoung
authors: SH
authors: Kang
authors: Jai Myung
authors: JM
authors: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000302:isolation & purification* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019158:N-Acetylneuraminic Acid / Q000032:analysis / Q000737:chemistry; D010053:Ovary / Q000187:drug effects; D010062:Ovulation Induction; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000302:isolation & purification* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013810:Therapeutic Equivalency
chemical_list: D006063:Chorionic Gonadotropin; D011994:Recombinant Proteins; D019158:N-Acetylneuraminic Acid