CeredaseÒ
(alglucerase injection)
Rx only
DESCRIPTION
CeredaseÒ (alglucerase injection) is a modified form of the enzyme, b -glucocerebrosidase (b -Dglucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45). Alglucerase is a monomeric glycoprotein of 497 amino acids with carbohydrates making up approximately 6% of the molecule (Mr = 59,300 as determined by SDS-PAGE). The unmodified enzyme (b -glucocerebrosidase) also contains 497 amino acids and contains approximately 12% carbohydrate (Mr = 67,000). The carbohydrates on the unmodified enzyme consist of N-linked carbohydrate chains of the complex and high mannose type. Glucocerebrosidase and alglucerase catalyze the hydrolysis of the glycolipid, glucocerebroside, within the lysosomes of the reticuloendothelial system.
Alglucerase is prepared by modification of the oligosaccharide chains of human b -glucocerebrosidase. The modification alters the sugar residues at the non-reducing ends of the oligosaccharide chains of the glycoprotein so that they are predominantly terminated with mannose residues which are specifically recognized by carbohydrate receptors on macrophage cells.
CeredaseÒ is supplied as a clear sterile non-pyrogenic solution of alglucerase in a citrate buffered solution (53 mM citrate, 143 mM sodium) containing 1% albumin human USP. The enzyme is supplied in one concentration, 400 units per bottle (80 units/mL) with a fill volume of 5 mL per bottle. An enzyme unit (U) is defined as the amount of enzyme required to hydrolyze in one minute one micromole of the synthetic substrate, p-nitrophenyl-b -D-glucopyranoside.
CeredaseÒ is purified from a large pool of human placental tissue collected from selected donors. Steps have been introduced into the manufacturing process to reduce further the risk of viral contamination. However, no procedure has been shown to be totally effective in removing viral infectivity. (See PRECAUTIONS). Each lot of product has been tested and found negative for hepatitis B surface antigen (HBsAg) and for human immunodeficiency virus antigen (HIV-1) and antibody (HIV-1/2).
Human chorionic gonadotropin (hCG) is a naturally occurring hormone in human placenta. It is likely the hCG is partially deglycosylated. In vitro studies have previously demonstrated biological activity of approximately 3 units of hCG activity per unit CeredaseÒ , as determined by an in vitro cell based assay. New process steps have since been introduced into the manufacturing process that significantly reduce the amount of hCG present in the CeredaseÒ product. Initial manufacturing data indicate that the resulting level of hCG in the product is less than 1 µg hCG per mg CeredaseÒ protein, as determined by the ELISA assay. These data indicate that the level of hCG in the product has been reduced about 15 fold as a result of the new process steps.
