BioMarin Aldurazyme Recombinant human  -L-Iduronidase

Milestones Application Received: July 29, 2002 First Action Due Date: January 28, 2003

Aldurazyme Drug Substance Recombinant human α-L-iduronidase Single peptide with a molecular weight of 83 kDa Produced in a continuous Chinese Hamster Ovary cell line transfected with cDNA encoding α-L-iduronidase Sequence is identical to a natural polymorphism of the endogenous protein (1 Glutamine to Histidine substitution) Six N-linked complex oligosaccharide sites One disulfide bond Well characterized and highly purified molecule

Aldurazyme Drug Product Sterile solution intended for intravenous administration Each vial of Drug Product contains: 2.90 mg α-L-iduronidase 43.9 mg sodium chloride USP/EP 63.5 mg sodium phosphate, monobasic monohydrate USP/EP 10.7 mg sodium phosphate, dibasic heptahydrate USP/EP 0.05 mg polysorbate 80 NF/EP 5 ml water for injection USP/EP pH Storage: 2-8  C Expected dating period: 24 months No outstanding Drug Product issues

FDA Reviewers Product Clinical Pharm Melanie Hartsough, Ph.D. Martin Green, Ph.D Blair Fraser, Ph.D. Howard Anderson, Ph.D. Biostatistics Clara Chu, Ph.D Clinical Ilan Irony, M.D. Facility Deborah Trout Pharm/Tox Cynthia Kelley, M.S. Richard Mcfarland, M.D., Ph.D. Calvin Koerner Marlene Swider Reg. Coordinator Katherine Needleman, M.S.Biomonitoring Bradley Glasscock, Pharm D.Debra Bower, MT (ASCP)