Thyrogen

DRUG DESCRIPTION

Thyrogen® (thyrotropin alfa for injection) contains a highly purified recombinant
form of human thyroid stimulating hormone (TSH), a glycoprotein which is produced
by recombinant DNA technology. Thyrotropin alfa is synthesized in a genetically
modified Chinese hamster ovary cell line.

Thyrotropin alfa 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 thyroid stimulating hormone.

Both thyrotropin alfa and naturally occurring human pituitary thyroid stimulating
hormone 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 rhTSH activity by measuring
the luciferase response. The specific activity of thyrotropin alfa is 4-12 IU/mg
using this cell-based bioassay. The specific activity of thyrotropin alfa is
determined relative to an internal Genzyme reference material that was calibrated
against the World Health Organization (WHO) human pituitary derived TSH reference
standard NIBSC 84/703 using an in vitro bioassay that measures the amount
of cAMP produced by a bovine thyroid microsome preparation in response to rhTSH.

Thyrogen (thyrotropin alfa for injection) is supplied as a sterile, non-pyrogenic, white to off-white lyophilized
product, intended for intramuscular (IM) administration after reconstitution
with Sterile Water for Injection, USP. Each vial of Thyrogen contains 1.1 mg
thyrotropin alfa (4-12 IU/mg), 36 mg Mannitol, 5.1 mg Sodium Phosphate, and
2.4 mg Sodium Chloride.

After reconstitution with 1.2 mL of Sterile Water for Injection, USP, the thyrotropin
alfa concentration is 0.9 mg/mL. The pH of the reconstituted solution is approximately
7.0.