Table of Contents

PREFACE ix

CONTRIBUTORS xi

SECTION 1 INTRODUCTION TO PLASMA FRACTIONATION

1 The History and Development of the Plasma Protein Fractionation Industry 3
John Curling, Neil Goss, and Joseph Bertolini

SECTION 2 PLASMA PROTEINS FOR THERAPEUTIC USE

2 Production and Clinical Profile of Human Plasma Coagulation Factor VIII 31
Sami Chtourou

3 Production and Clinical Profile of Human Plasma-Derived Von Willebrand Factor 41
Sami Chtourou and Michel Poulle

4 Factor Eight Inhibitor Bypassing Activity 49
Peter Turecek and Hans Peter Schwarz

5 Prothrombin Complex 65
Jürgen Römisch and Katharina Pock

6 Factor IX 81
Salvador Grancha, Steven Herring, Antonio Pa'ez, Pere Ristol, and Juan Ignacio Jorquera

7 Factor XI 93
Sami Chtourou and Michel Poulle

8 Factor XIII and Factor X 101
Peter Feldman

9 Fibrinogen: Science and Biotechnology 117
Gerard Marx

10 Fibrin Glues and Bandages 137
Hans Christian Hedrich and Heinz Gulle

11 Production and Clinical Use of Plasma Antithrombin III 147
Andrea Morelli

12 Human Serum Albumin: A Multifunctional Plasma Protein 159
John More and Mark Bulmer

13 IntravenousImmunoglobulinGfromHumanPlasma?Purification Concepts and Important QualityCriteria 185
Andrea Buchacher and Waltraud Kaar

14 Hyperimmune Immunoglobulin G 207
Hugh Price, Maurice Genereux, and Christopher Sinclair

15 Rh (D) Immunoglobulin 217
Maurice Genereux, Jodi Smith, William Bees, and Christopher Sinclair

16 Alpha1-Proteinase Inhibitor: The Disease, the Protein, and Commercial Production 227
Wytold Lebing

17 C1-Inhibitor 241
Jan Over, Christine Kramer, Anky Koenderman, Diana Wouters, and Sacha Zeerleder

18 Acid-Stabilized Plasmin as a Novel Direct-Acting Thrombolytic 259
Valery Novokhatny, James Rebbeor, Philip Scuderi, and Stephen Petteway Jr.

19 Reconstituted, Plasma-Derived High-Density Lipoprotein 273
Peter Lerch

20 Plant-Derived Manufacturing of Apolipoprotein AIMilano: Purification and Functional Characterization 283
Cory Nykiforuk, Yin Shen, Elizabeth Murray, Joseph Boothe, and Maurice Moloney

21 Transferrin 301
Leni von Bonsdorff, Hennie ter Hart, Ingrid Prins-de Nijs, Anky Koenderman, Jan Over, and Jaakko Parkkinen

22 Plasminogen: Its Role in the Therapy of Ligneous Conjunctivitis 311
Claudia Nardini

23 Haptoglobin 321
Joan Dalton and Azubuike Okemefuna

24 Ceruloplasmin: Biology, Manufacture, and Clinical Use 337
Aron Berkovsky and Vladimir Vaschenko

25 Solvent/Detergent Plasma 345
Tor-Einar Svae, Andrea Heger, Lothar Biesert, Andrea Neisser-Svae, and Wolfgang Frenzel

SECTION 3 PATHOGEN SAFETY OF PLASMA PRODUCTS

26 Ensuring Virus Safety of Plasma Products 361
Herbert Dichtelmu¨ller

27 Transmissible Spongiform Encephalopathies and Plasma Products 369
Luisa Gregori, David Asher, and Dorothy Scott

SECTION 4 THE PHARMACEUTICAL ENVIRONMENT APPLIED TO PLASMA FRACTIONATION

28 Quality Assurance Requirements in Plasma Product Manufacture 383
Jens Jesse

29 Regulatory Activities Associated with Production and Commercialization of Plasma Protein Therapeutics 403
Nancy Kirschbaum and Timothy Lee

30 The Emerging Role of Global Medical Affairs in the Twenty-First Century 413
Hartmut Ehrlich, David Perry, David Gelmont, and Ramin Farhood

31 Plasma for Fractionation 423
Joseph Bertolini and Timothy Hayes

32 The Pharmaceutical Manufacturing Environment 437
Ernst Hetzl

SECTION 5 THE MARKET FOR PLASMA PRODUCTS AND THE ECONOMICS OF FRACTIONATION

33 The Economics of Plasma Fractionation 451
Neil Goss and John Curling

34 Future Trends in the Plasma Products Market 461
Paolo Marcucci

INDEX 471

About the Author

JOSEPH BERTOLINI, BSc (HONS.), MSc, PhD, is R&DManager at CSL Bioplasma where he has been closely involved in thetechnical development and improvement of immunoglobulin and albuminproducts. He is active in national and international conferencesand industry organizations and is a strong advocate for theadvancement of bioprocessing. NEIL GOSS, BSc (HONS.), PhD, is Executive Director atFurther Options Pty Ltd., a consulting company specializing inbiotechnology and the plasma fractionation industry. He waspreviously Director of R&D, CSL Bioplasma and is the foundingorganizer for both the Plasma Product Biotechnology Meeting seriesand the BioProcessing Network. JOHN CURLING, BSc, is a consultant in bioseparations andprotein purification whose clients have included numerousbiopharmaceutical, biotechnology, and vendor companies. Hepioneered the development of chromatographic methods of plasmafractionation and was the President of the Process SeparationDivision of Pharmacia. He has acted as an advisor to the WorldHealth Organization.