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TSE Advisory Committee

The TSE-Safety of Serologicals Products: Use in Global

Healthcare

Presentation by Serologicals Corporation

Wayne E. Vaz

Bethesda, MD, July 2003

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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

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Business DescriptionSerologicals 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.

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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)• DNaseManufacturing Facilities:• Toronto, Canada• Kankakee, IL• Lawrence, KS (under

construction)

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Use of Bovine Products in Global HealthcareSerologicals bovine-based products are used in the development & production of life-saving FDA-approved drugs, FDA-licensed diagnostics, medical devices and animal vaccines

Healthcare Segment Indication/Use

Biologics Cancer, Rheumatoid Arthritis, Crohn’s Disease, Psoriasis, Blood Clotting Disorders, Ankylosing Spondylitis, RSV treatment, orphan disease

Diagnostic Assays HBSAg, HCV & HIV screening in U.S blood supply, cancer markers, serological tests

Medical Device Surgery involving tissue repair

Animal Vaccine Treatment of Leptospirosis worldwide

Life Science Research

Reagents/laboratory tests – electrophoresis, chromatography, protein assays etc.

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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

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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

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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

Product No. Process Steps

Total Clearance

Bovine Serum Albumin (HS)

4 16.2 Log10

Bovine Aprotinin 4 17.3 Log10

EX-CYTE® 1 3.7 Log10

Conclusion:

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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

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Virus Clearance Studies: BSA Product Line

Virus Family Size (nm)

Type Envelope

BVD Togaviridae 40-70 RNA (single) Yes

IBR Herpesvridae

120-250 DNA (double)

Yes

BTV Reoviridae 70 RNA (double)

No

PPV Parvoviridae

18-26 DNA (single)

No

Conclusion: ≥6 Log10 clearance bovine viruses, ≥3.5 Log10 clearance PPV (porcine parvovirus)

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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

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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)

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Serologicals Contacts

Wayne E. Vaz,Director, Corporate Business Development wvaz@serologicals.com

Sue Sutton-Jones,VP Global Regulatory Affairs, Quality Assurance, Compliance, and Medical Affairsssjones@serologicals.com