® TSE Advisory Committee The TSE-Safety of Serologicals Products: Use in Global Healthcare Presentation by Serologicals Corporation Wayne E. Vaz Bethesda, MD, July 2003

® Goals of Presentation Raise level of awareness re. pervasive use of bovine products in the production of life-saving drugs, essential diagnostic assays, other global healthcare products Present facts supporting the high safety and quality of Serologicals’ bovine-based products Work with TSE AC and regulators to further develop industry guidelines to assure the continued availability of bovine products

® Business Description Serologicals enables the development of Life Science Products Serologicals is a global provider of biological products and enabling technologies which are essential for the research, development, and manufacturing of biologically-based life science products. Products: antibodies, cell culture supplements, products for diagnostics & research.

® Serologicals Bovine-Based Products Bovine Serum Albumin (BSA) 3 manufacturing formats, >25 products EX-CYTE® (Lipoprotein Fraction) Transferrin (Apo & Holo) Aprotinin Prepared Leptospira Media (PLM-5) Gamma Globulin (IgG) Plasma Diagnostic Base (PDB) DNase Manufacturing Facilities: Toronto, Canada Kankakee, IL Lawrence, KS (under construction)

® Use of Bovine Products in Global Healthcare Serologicals bovine-based products are used in the development & production of life-saving FDA-approved drugs, FDA-licensed diagnostics, medical devices and animal vaccines Healthcare SegmentIndication/Use BiologicsCancer, Rheumatoid Arthritis, Crohn’s Disease, Psoriasis, Blood Clotting Disorders, Ankylosing Spondylitis, RSV treatment, orphan disease Diagnostic AssaysHBSAg, HCV & HIV screening in U.S blood supply, cancer markers, serological tests Medical DeviceSurgery involving tissue repair Animal VaccineTreatment of Leptospirosis worldwide Life Science ResearchReagents/laboratory tests – electrophoresis, chromatography, protein assays etc.

® Industry Guidance April 19, 2000 FDA update to manufacturers of biological products (Kathryn C. Zoon): FDA letters (May 3, 1991, Dec. 17, 1993, May 9, 1996) and guidance document (Sept. 1997): Avoid using ruminant- origin materials derived from BSE-affected countries, in the production of FDA-regulated products intended for humans Identify all ruminant materials used in production of regulated products, document the country of origin and maintain traceability records/each lot

® Consequences for Drug Manufacturers & Patients Regulatory uncertainty re. products under development made with bovine ingredients Risk of current production of approved drugs which use bovine ingredients Possible interruption to supply if BSE/U.S Bovine-based products provide unparallelled performance; few attempts to replace these products result in lower productivity, higher costs

® Serologicals: Prion Infectivity Clearance Studies Hamster-adapted strain of Scrapie, 263K Spike known titers of infectivity prior to key process steps – titrate infectivity downstream In-vivo infectivity assay – Golden Syrian Hamsters Clinical signs – gait abnormality, tremors, ataxia Histopathology to confirm clinical diagnosis Protease resistance of transformed prions ProductNo. Process StepsTotal Clearance Bovine Serum Albumin (HS)416.2 Log10 Bovine Aprotinin417.3 Log10 EX-CYTE®13.7 Log10 Conclusion:

® Serologicals Products – High Safety, Quality Bovine blood – low risk of TSE-infectivity according to WHO & EC; Serologicals uses plasma or serum for added safety Bovines <30 months old and typically <20 months: No BSE reported in cattle <20 months and uncommon under 30 months (DEFRA) USDA-approved RMs, USDA-licensed est. Manufactured within ISO9002 Registered GMP environment Prion & viral clearance studies Similar clearance studies completed by drug producer EDQM CoS Proven track record of safety in global healthcare

® Virus Clearance Studies: BSA Product Line VirusFamilySize (nm)TypeEnvelope BVDTogaviridae40-70RNA (single)Yes IBRHerpesvridae DNA (double)Yes BTVReoviridae70RNA (double)No PPVParvoviridae18-26DNA (single)No Conclusion: ≥6 Log10 clearance bovine viruses, ≥3.5 Log10 clearance PPV (porcine parvovirus)

® Summary Bovine-based products are critical to the production of life- saving healthcare products Manufacturers of FDA regulated products cannot replace bovine ingredients quickly, easily or economically High safety and quality of Serologicals’ products supported by low TSE-risk RMs, controlled manufacturing, research studies demonstrating robust viral & prion clearance, track record of safety/success Serologicals is pleased to work with the TSE AC to further develop TSE-risk guidelines covering these important products to permit their continued use

® Considerations In addition to using low TSE-risk RMs, recognize the value of prion clearance studies, establish min. acceptance criteria Require suppliers perform clearance studies to demonstrate product safety Consider prohibiting sourcing from countries with a high incidence of BSE rather than one or two cases Request that the FDA (and USDA) carefully weigh damages to: end consumers (patients) producers of biomedical products (our customers) supply chain producers (like Serologicals)

® Serologicals Contacts Wayne E. Vaz, Director, Corporate Business Development Sue Sutton-Jones, VP Global Regulatory Affairs, Quality Assurance, Compliance, and Medical Affairs