Abstract
BackgroundThe current study was designed to determine if follitropin alfa (recombinant human follicle-stimulating hormone; r-hFSH) and lutropin alfa (recombinant human luteinizing hormone; r-hLH) biopotencies were unchanged by reconstituting in sterile water for injection and mixing prior to injection.MethodsThe biopotencies of r-hFSH and r-hLH were determined following injection of female Sprague-Dawley rats with a mixture of follitropin alfa revised formulation female (RFF) and lutropin alfa (1:1, r-hFSH:r-hLH). Biopotencies of follitropin alfa RFF and lutropin alfa were measured using ovarian weight and ascorbic acid depletion assays, respectively, and compared with a reference standard. Stock mixtures of follitropin alfa RFF and lutropin alfa (1:1) were prepared within 1 h prior to each respective assay's injection and stored at 6 +/- 2°C. Separate low dose (follitropin alfa RFF 1.5 IU/rat, lutropin alfa 2 IU/rat) and high dose (follitropin alfa RFF 3 IU/rat, lutropin alfa 8 IU/rat) treatments were prepared from stock mixtures or individual solutions by diluting with 0.22% bovine serum albumin saline solution and injected within 1 h of preparation. The main outcome measures were ovarian weight and ovarian ascorbic acid depletion.ResultsFSH bioactivities were similar (p > 0.10) between the individual follitropin alfa RFF test solution (84.2 IU) and follitropin alfa RFF/lutropin alfa (87.6 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2°C. LH bioactivities were similar (p > 0.10) between lutropin alfa (94.7 IU) test solution and lutropin alfa/follitropin alfa RFF (85.3 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2°C for not more than 1 h prior to injection.ConclusionMixing follitropin alfa RFF and lutropin alfa did not alter the bioactivity of either FSH or LH.
Highlights
The current study was designed to determine if follitropin alfa and lutropin alfa biopotencies were unchanged by reconstituting in sterile water for injection and mixing prior to injection
In 1988, human follicle-stimulating hormone was successfully expressed using Chinese hamster ovary cells, representing the initial steps for commercial development of gonadotropin products originating from recombinant deoxyribonucleic acid (r-DNA) technology [1]
Statistical analysis According to the United States Pharmacopeia (USP), FSH or LH potency is adequate if it falls within a range of 80–125% of the labeled potency and if the confidence interval is not >1.8 [19]
Summary
The current study was designed to determine if follitropin alfa (recombinant human follicle-stimulating hormone; r-hFSH) and lutropin alfa (recombinant human luteinizing hormone; rhLH) biopotencies were unchanged by reconstituting in sterile water for injection and mixing prior to injection. In 1988, human follicle-stimulating hormone (hFSH) was successfully expressed using Chinese hamster ovary cells, representing the initial steps for commercial development of gonadotropin products originating from recombinant deoxyribonucleic acid (r-DNA) technology [1]. By the turn of the century, recombinant human luteinizing hormone (rhLH, lutropin alfa for injection, Luveris®) and recombinant human chorionic gonadotropin (r-hCG, choriogonadotropin alfa injection, Ovidrel®) were commercially produced, marking the availability of all three human recombinant gonadotropins for infertility treatment. While the urine-derived products have long represented the mainstay of infertility therapy, the recombinant products alone provide the distinct advantage of solo administration. Numerous recent clinical investigations have focused on controlled ovarian stimulation (COS) protocols that incorporate LH activity at various doses and phases in the treatment cycle [5,6,7,8]
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