SPL Set ID: b52dfa36-f90b-4e19-9b5e-26db9d04df2b

Thyrotropin alfa, a recombinant human thyroid stimulating hormone, is a heterodimeric glycoprotein comprised of two non-covalently linked subunits, an alpha subunit of 92 amino acid residues containing two N-linked glycosylation sites and a beta subunit of 118 residues containing one N-linked glycosylation site. The amino acid sequence of thyrotropin alfa is identical to that of human pituitary TSH. Thyrotropin alfa is synthesized in a genetically modified Chinese hamster ovary cell line. Both thyrotropin alfa and naturally occurring human pituitary TSH are synthesized as a mixture of glycosylation variants. Unlike pituitary TSH, which is secreted as a mixture of sialylated and sulfated forms, thyrotropin alfa is sialylated but not sulfated. The biological activity of thyrotropin alfa is determined by a cell-based bioassay. In this assay, cells expressing a functional TSH receptor and a cAMP-responsive element coupled to a heterologous reporter gene, luciferase, enable the measurement of thyrotropin alfa activity by measuring the luciferase response. The specific activity of thyrotropin alfa is determined relative to an internal Genzyme reference standard that was calibrated against the World Health Organization (WHO) human TSH reference standard. THYROGEN (thyrotropin alfa) for injection is a sterile, white to off-white lyophilized powder in a single-dose vial for intramuscular use after reconstitution . Each single-dose vial provides 0.9 mg of thyrotropin alfa, and contains mannitol (36 mg); sodium chloride (2.4 mg);sodium phosphate dibasic, heptahydrate (3.7 mg); and sodium phosphate monobasic, monohydrate (1.4 mg). After reconstitution with 1.2 mL of Sterile Water for Injection, USP, the concentration is 0.9 mg/mL with a deliverable volume of 1 mL (0.9 mg) and a pH of approximately 6.5 to 7.5.