Protein Drugs: Global Markets and Manufacturing Technologies

Protein Drugs: Global Markets and Manufacturing Technologies

STUDY GOALS AND OBJECTIVES

Protein drugs have received enormous attention from pharmaceutical companies due to a combination of their bioreactivity, specificity, safety and overall success rate. Yet there are still improvements to be made, especially with respect to their formulation and delivery method. Advances in protein drug delivery are certain to increase patient compliance and expand many drug markets.

REASONS FOR DOING THE STUDY

Although the drug development industry still focuses primarily on small molecules, in recent years protein and peptide therapeutics comprise a significant percent of the product line and pipeline for most major pharmaceutical companies. Peptide and protein therapeutics, especially antibody drugs, are attractive due to their high specificity and potency and low incidence of toxicity. Developments in manufacturing, including transgenic, recombinant and synthetic methods, have been key as protein drugs have moved into the mainstream. A previous report by BCC, Protein Drugs in 2003, discussed the early days of these manufacturing improvements and focused on emerging recombinant methods of protein production.

Recombinant protein technologies are now standard and the current focus has shifted from the method of bulk production to post-production techniques that promise to enhance stability and delivery. In the effort to produce orally available therapeutics, formulation issues have become critical. 
 

CHAPTER ONE: INTRODUCTION

STUDY GOALS AND OBJECTIVES

REASONS FOR DOING THE STUDY

SCOPE OF REPORT

INTENDED AUDIENCE

INFORMATION SOURCES

ANALYST CREDENTIALS

RELATED REPORTS

BCC ONLINE SERVICES

DISCLAIMER

CHAPTER TWO: SUMMARY

SUMMARY TABLE GLOBAL MARKET FOR PROTEIN THERAPEUTICS, THROUGH 2013 ($ MILLIONS)

SUMMARY TABLE (CONTINUED)

SUMMARY FIGURE GLOBAL MARKET FOR PROTEIN THERAPEUTICS, 2007-2013 ($ MILLIONS)

CHAPTER THREE: OVERVIEW

DEFINING THE TERMS: PROTEINS AND PEPTIDES

PROTEIN DRUGS: THEN AND NOW

TABLE 1 NEW DRUGS ENTERING CLINICAL TRIALS, BY TYPE, 2007

DRUG ADMINISTRATION: MILESTONES AND CHALLENGES

PEGYLATION

PEPTIDE-MEDIATED RECEPTOR TARGETING

PATIENT COMPLIANCE

Patient Compliance (Continued)

CHAPTER FOUR: MARKETS BY PRODUCTS

TABLE 2 GLOBAL SIZE OF PROTEIN DRUGS MARKET BY PRODUCTS, THROUGH 2013 ($ MILLIONS)

FIGURE 1 GLOBAL SIZE OF PROTEIN DRUGS MARKET BY PRODUCTS, 2008 AND 2013 ($ MILLIONS)

FIGURE 2 GLOBAL SHARE OF PROTEIN DRUGS MARKET BY PRODUCT, 2008 (%)

FIGURE 2 (CONTINUED)

FIGURE 3 GLOBAL SHARE OF PROTEIN DRUGS MARKET BY PRODUCT, 2013 (%)

ANTIBODY DRUGS

PRODUCTION OF ANTIBODIES FOR THERAPY

Murine Monoclonal Antibodies

Chimeric and Humanized Monoclonal Antibodies

Human Monoclonal Antibodies

Antibody-directed Enzyme Prodrug Therapy (ADEPT)

HOW ANTIBODY DRUGS WORK

How Antibody Drugs Work (Continued)

TABLE 3 FDA-APPROVED MONOCLONAL ANTIBODIES, 2008

THE ANTIBODY DRUG MARKET

TABLE 4 GLOBAL MARKET FORECAST FOR ANTIBODY DRUG PRODUCTS, THROUGH 2013 ($ MILLIONS)

FIGURE 4 GLOBAL MARKET FOR ANTIBODY DRUGS, 2008 (%)

FIGURE 4 (CONTINUED)

FIGURE 5 GLOBAL MARKET FOR ANTIBODY DRUGS, 2013 (%)

FIGURE 5 (CONTINUED)

CHANGES IN A DYNAMIC MARKET

Possible new indications for Campath

EGF-R Antibodies: Still Investigational Therapies

Side Effects Could Affect Tysabri’s Future

TABLE 5 FDA-APPROVED MONOCLONAL ANTIBODIES FOR CANCER TREATMENT, 2008

CYTOKINES

THE CYTOKINE MARKET

Granulocyte-colony Stimulating Factors

Interferon â

Interferon á

Interferon ã

Interleukins

TABLE 6 GLOBAL MARKET FORECAST FOR CYTOKINE PRODUCTS, THROUGH 2013 ($ MILLIONS)

FIGURE 6 GLOBAL MARKET FOR CYTOKINE DRUGS, 2008 (%)

FIGURE 7 FORECAST GLOBAL MARKET FOR CYTOKINE DRUGS, 2013 (%)

PEPTIDE HORMONES

TABLE 7 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, THROUGH 2013 ($ MILLIONS)

FIGURE 8 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, 2008 AND 2013 ($ MILLIONS)

FIGURE 9 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, 2008 (%)

VACCINES

KINDS OF VACCINES

Killed Whole Organisms

Attenuated Organisms

Toxoids

Surface Proteins

Inactivated Virus

Attenuated Virus

TABLE 8 VACCINE PREPARATIONS, BY DISEASE

TABLE 9 VACCINE-PREVENTABLE DISEASE IN THE U.S., PRE- AND POST- VACCINATION PROGRAMS

THE GLOBAL PROTEIN VACCINE MARKET

TABLE 10 GLOBAL MARKET FORECAST FOR VACCINES, THROUGH 2013 ($ MILLIONS)

FIGURE 10 GLOBAL MARKET FORECAST FOR VACCINES, 2008 AND 2013 ($ MILLIONS)

TABLE 11 NEW AND EMERGING VACCINE PRODUCTS

BLOOD PRODUCTS

WHAT DRIVES DEMAND FOR BLOOD PRODUCTS

THE GLOBAL MARKET FOR BLOOD PRODUCTS

TABLE 12 GLOBAL MARKET FORECAST FOR BLOOD PRODUCTS, THROUGH 2013 ($ MILLIONS)

FIGURE 11 GLOBAL MARKET FORECAST FOR BLOOD PRODUCTS, 2008 AND 2013 ($ MILLIONS)

FIGURE 12 GLOBAL MARKET FOR BLOOD PRODUCTS, 2008 (%)

Recombinant Albumin

Factor VIII

TABLE 13 COMPANIES INVOLVED IN FACTOR VIII DEVELOPMENT

Factor IX

Hemoglobin

Second Generation Hemoglobins in Development

TABLE 14 COMPANIES INVOLVED IN RECOMBINANT HEMOGLOBIN MANUFACTURE

Protein C

PEPTIDE ANTIBIOTICS

TYPES OF PEPTIDE ANTIBIOTICS

TABLE 15 GLOBAL MARKET FORECAST FOR PEPTIDE ANTIBIOTICS, THROUGH 2013

THE RESISTANCE PROBLEM

THERAPEUTIC ENZYMES

Glucocerebrosidase

Tissue Plasminogen Activator

Pancreatin

Thrombin

TABLE 16 GLOBAL MARKET FORECAST FOR THERAPEUTIC ENZYMES, THROUGH 2013

CHAPTER FIVE: MANUFACTURING TECHNOLOGY

NATURAL SOURCING AND EXTRACTION

HUMAN SOURCING

SPECIAL FEATURES OF HUMAN-SOURCING MANUFACTURE

TABLE 17 PROTEIN DRUGS MADE BY HUMAN-SOURCE EXTRACTION

SPECIAL FEATURES OF ANIMAL SOURCING MANUFACTURE

TABLE 18 PROTEIN DRUGS MADE BY NATURAL ANIMAL-SOURCE EXTRACTION

TABLE 19 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

FIGURE 13 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, 2008 AND 2013 ($ MILLIONS)

FIGURE 14 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT 2008 (%)

FIGURE 15 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, 2013 (%)

MICROBIAL FERMENTATION

TABLE 20 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

FIGURE 16 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2008 AND 2013 ($ MILLIONS)

FIGURE 17 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2008 (%)

FIGURE 18 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2013 (%)

MAMMALIAN CELL CULTURE

BIOREACTORS

TABLE 21 TYPES OF BIOREACTORS

Bioreactors (Continued)

OTHER CELL CULTURE SYSTEMS: INSECT CELLS

TABLE 22 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

FIGURE 19 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, BY PRODUCT, 2008 AND 2013 ($ MILLIONS)

FIGURE 20 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, 2008 (%)

FIGURE 21 PROJECTED PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, 2013 (%)

TRANSGENICS: PLANTS AND ANIMALS

TRANSGENIC PLANTS PHARMING

TABLE 23 TRANSGENIC PLANT PHARMACEUTICALS UNDER DEVELOPMENT

TRANSGENIC ANIMALS

Founder Animal Production

History in the Making: the First Transgenic Drugs

TABLE 24 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

FIGURE 22 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, THROUGH 2013

FIGURE 23 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, 2013 (%)

TABLE 25 PROTEIN DRUGS DERIVED FROM TRANSGENIC ANIMALS, 2008

On the Horizon: Gene Therapy with Transgenics?

CHEMICAL SYNTHESIS

HOW IT WORKS

COST AND SCALING- UP

TABLE 26 PEPTIDE PHARMACEUTICALS MANUFACTURED BY CHEMICAL SYNTHESIS

TABLE 27 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

FIGURE 24 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

FIGURE 25 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, 2008

FIGURE 26 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, 2013

CHAPTER SIX: TECHNOLOGY

MANUFACTURING, PROCESSING AND FORMULATION

FIGURE 27 MANUFACTURING PROCESS FLOW CHART

PROCESSING AND DOWNSTREAM

PROTEIN AGGREGATION HAS CLINICAL RAMIFICATIONS

FOCUS ON FORMULATION

FREEZE-THAW

Challenges in the Freezing Process

Thawing

Freeze-Thaw Technologies

FORMULATION STEP

Formulation Step (Continued)

FILTRATION

DRUG PRODUCT FILLING

LYOPHILIZATION

Lyophilization (Continued)

Lyophilization (Continued)

INSPECTION AND PACKAGING

DRUG STORAGE, TRANSPORT AND DELIVERY

Protein-Silicone Oil Interactions

Leachables and Extractables

TRANSPORTATION

PHOTOSTABILITY

CHAPTER SEVEN: PATENT ANALYSIS

PATENTS BY PRODUCT TYPE

TABLE 28 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008

FIGURE 28 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY PRODUCT, AUGUST 2005 TO AUGUST 2008

PATENTS BY REGION

TABLE 29 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY REGION, AUGUST 2005 TO AUGUST 2008

TABLE 29 (CONTINUED)

TABLE 30 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008

FIGURE 29 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008 (%)

IMPORTANT PATENT ISSUES FOR FOLLOW-ON BIOLOGICS

PATENTS OF INTEREST IN THE PROTEIN DRUGS FIELD

TREATMENTS USING TRANSGENIC GOAT PRODUCED ANTITHROMBIN III

HIGHLY PHOSPHORYLATED AND SULFATED RECOMBINANT FACTOR IX

HEPATITIS C RECEPTOR PROTEIN CD81

PURIFICATION OF POLYPEPTIDES

Purification of Polypeptides (Continued)

CHAPTER EIGHT: INTERNATIONAL ASPECTS

TABLE 31 GLOBAL PROTEIN THERAPEUTIC MARKET PRODUCTION BY REGION, 2008 ($ MILLIONS)

UNITED STATES

WESTERN EUROPE

JAPAN

CHINA

CHAPTER NINE: MARKET SHARE

TABLE 32 MARKET SHARE OF COMPANIES INVOLVED IN ANTIBODY DRUGS, 2008 (UNIT, %)

TABLE 33 MARKET SHARE OF COMPANIES INVOLVED IN CYTOKINES, 2008 (UNIT, %)

TABLE 34 MARKET SHARE OF COMPANIES INVOLVED IN PEPTIDE HORMONES, 2008 (UNIT, %)

TABLE 35 MARKET SHARE OF COMPANIES INVOLVED IN VACCINES, 2008 (UNIT, %)

TABLE 36 MARKET SHARE OF COMPANIES INVOLVED IN BLOOD PRODUCTS, 2008 (UNIT, %)

TABLE 37 MARKET SHARE OF COMPANIES INVOLVED PEPTIDE ANTIBIOTICS, 2008 (UNIT, %)

TABLE 38 MARKET SHARE OF COMPANIES INVOLVED ENZYMES, 2008 (UNIT, %)

CHAPTER TEN: COMPANY PROFILES

ABBOTT LABORATORIES

TABLE 39 ABBOTT LABS PROTEIN DRUGS

AEGIS THERAPEUTICS

ALEXION PHARMACEUTICALS

AMGEN

TABLE 40 AMGEN’S PROTEIN DRUGS

BAYER DIAGNOSTICS

BIOGEN IDEC, INC

TABLE 41 BIOGEN IDEC’S PROTEIN DRUGS

CENTOCOR

ELI LILLY & CO

TABLE 42 LILLY’S PROTEIN DRUGS

GENENTECH, INC.

TABLE 43 GENENTECH’S PROTEIN DRUGS

GENZYME CORP.

TABLE 44 GENZYME CORPORATION PROTEIN DRUGS

TABLE 44 (CONTINUED)

JOHNSON & JOHNSON INC.

MEDIMMUNE, INC.

MEDAREX

TABLE 45 MEDAREX’S PIPELINE PROTEIN DRUGS

MERCK & CO., INC.

TABLE 46 MERCK’S PROTEIN DRUGS

MERCK SERONO

TABLE 47 MERCK-SERONO’S PROTEIN DRUGS

NOVARTIS PHARMA AG

TABLE 48 NOVARTIS’ PROTEIN DRUGS

NOVO NORDISK A/S

NOVO NORDISK A/S (CONTINUED)

ROCHE HOLDINGS, LTD.

TABLE 49 ROCHE’S PROTEIN DRUGS

SANGART

SANOFI-AVENTIS

UNIGENE LABORATORIES, INC

UNIGENE LABORATORIES, INC. (CONTINUED)

VACCINOGEN INC

WYETH

WYETH (CONTINUED)

TABLE 50 WYETH’ PROTEIN DRUGS

APPENDIX: WEB RESOURCES FOR PROTEIN DRUG DESIGN

THE NATIONAL CANCER INSTITUTE 3D STRUCTURE DATABASE

KIBANK

COMBINATORIAL CHEMISTRY REVIEW

GDB: STRUCTURES

LIST OF TABLES

SUMMARY TABLE GLOBAL MARKET FOR PROTEIN THERAPEUTICS, THROUGH 2013 ($ MILLIONS)

TABLE 1 NEW DRUGS ENTERING CLINICAL TRIALS, BY TYPE, 2007

TABLE 2 GLOBAL SIZE OF PROTEIN DRUGS MARKET BY PRODUCTS, THROUGH 2013 ($ MILLIONS)

TABLE 3 FDA-APPROVED MONOCLONAL ANTIBODIES, 2008

TABLE 4 GLOBAL MARKET FORECAST FOR ANTIBODY DRUG PRODUCTS, THROUGH 2013 ($ MILLIONS)

TABLE 5 FDA-APPROVED MONOCLONAL ANTIBODIES FOR CANCER TREATMENT, 2008

TABLE 6 GLOBAL MARKET FORECAST FOR CYTOKINE PRODUCTS, THROUGH 2013 ($ MILLIONS)

TABLE 7 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, THROUGH 2013 ($ MILLIONS)

TABLE 8 VACCINE PREPARATIONS, BY DISEASE

TABLE 9 VACCINE-PREVENTABLE DISEASE IN THE U.S., PRE- AND POST- VACCINATION PROGRAMS

TABLE 10 GLOBAL MARKET FORECAST FOR VACCINES, THROUGH 2013 ($ MILLIONS)

TABLE 11 NEW AND EMERGING VACCINE PRODUCTS

TABLE 12 GLOBAL MARKET FORECAST FOR BLOOD PRODUCTS, THROUGH 2013 ($ MILLIONS)

TABLE 13 COMPANIES INVOLVED IN FACTOR VIII DEVELOPMENT

TABLE 14 COMPANIES INVOLVED IN RECOMBINANT HEMOGLOBIN MANUFACTURE

TABLE 15 GLOBAL MARKET FORECAST FOR PEPTIDE ANTIBIOTICS, THROUGH 2013

TABLE 16 GLOBAL MARKET FORECAST FOR THERAPEUTIC ENZYMES, THROUGH 2013

TABLE 17 PROTEIN DRUGS MADE BY HUMAN-SOURCE EXTRACTION

TABLE 18 PROTEIN DRUGS MADE BY NATURAL ANIMAL-SOURCE EXTRACTION

TABLE 19 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

TABLE 20 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

TABLE 21 TYPES OF BIOREACTORS

TABLE 22 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

TABLE 23 TRANSGENIC PLANT PHARMACEUTICALS UNDER DEVELOPMENT

TABLE 24 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

TABLE 25 PROTEIN DRUGS DERIVED FROM TRANSGENIC ANIMALS, 2008

TABLE 26 PEPTIDE PHARMACEUTICALS MANUFACTURED BY CHEMICAL SYNTHESIS

TABLE 27 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 28 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008

TABLE 29 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY REGION, AUGUST 2005 TO AUGUST 2008

TABLE 30 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008

TABLE 31 GLOBAL PROTEIN THERAPEUTIC MARKET PRODUCTION BY REGION, 2008 ($ MILLIONS)

TABLE 32 MARKET SHARE OF COMPANIES INVOLVED IN ANTIBODY DRUGS, 2008 (UNIT, %)

TABLE 33 MARKET SHARE OF COMPANIES INVOLVED IN CYTOKINES, 2008 (UNIT, %)

TABLE 34 MARKET SHARE OF COMPANIES INVOLVED IN PEPTIDE HORMONES, 2008 (UNIT, %)

TABLE 35 MARKET SHARE OF COMPANIES INVOLVED IN VACCINES, 2008 (UNIT, %)

TABLE 36 MARKET SHARE OF COMPANIES INVOLVED IN BLOOD PRODUCTS, 2008 (UNIT, %)

TABLE 37 MARKET SHARE OF COMPANIES INVOLVED PEPTIDE ANTIBIOTICS, 2008 (UNIT, %)

TABLE 38 MARKET SHARE OF COMPANIES INVOLVED ENZYMES, 2008 (UNIT, %)

TABLE 39 ABBOTT LABS PROTEIN DRUGS

TABLE 40 AMGEN’S PROTEIN DRUGS

TABLE 41 BIOGEN IDEC’S PROTEIN DRUGS

TABLE 42 LILLY’S PROTEIN DRUGS

TABLE 43 GENENTECH’S PROTEIN DRUGS

TABLE 44 GENZYME CORPORATION PROTEIN DRUGS

TABLE 45 MEDAREX’S PIPELINE PROTEIN DRUGS

TABLE 46 MERCK’S PROTEIN DRUGS

TABLE 47 MERCK-SERONO’S PROTEIN DRUGS

TABLE 48 NOVARTIS’ PROTEIN DRUGS

TABLE 49 ROCHE’S PROTEIN DRUGS

TABLE 50 WYETH’ PROTEIN DRUGS

LIST OF FIGURES

SUMMARY FIGURE GLOBAL MARKET FOR PROTEIN THERAPEUTICS, 2007-2013 ($ MILLIONS)

FIGURE 1 GLOBAL SIZE OF PROTEIN DRUGS MARKET BY PRODUCTS, 2008 AND 2013 ($ MILLIONS)

FIGURE 2 GLOBAL SHARE OF PROTEIN DRUGS MARKET BY PRODUCT, 2008 (%)

FIGURE 3 GLOBAL SHARE OF PROTEIN DRUGS MARKET BY PRODUCT, 2013 (%)

FIGURE 4 GLOBAL MARKET FOR ANTIBODY DRUGS, 2008 (%)

FIGURE 5 GLOBAL MARKET FOR ANTIBODY DRUGS, 2013 (%)

FIGURE 6 GLOBAL MARKET FOR CYTOKINE DRUGS, 2008 (%)

FIGURE 7 FORECAST GLOBAL MARKET FOR CYTOKINE DRUGS, 2013 (%)

FIGURE 8 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, 2008 AND 2013 ($ MILLIONS)

FIGURE 9 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, 2008 (%)

FIGURE 10 GLOBAL MARKET FORECAST FOR VACCINES, 2008 AND 2013 ($ MILLIONS)

FIGURE 11 GLOBAL MARKET FORECAST FOR BLOOD PRODUCTS, 2008 AND 2013 ($ MILLIONS)

FIGURE 12 GLOBAL MARKET FOR BLOOD PRODUCTS, 2008 (%)

FIGURE 13 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, 2008 AND 2013 ($ MILLIONS)

FIGURE 14 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT 2008 (%)

FIGURE 15 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, 2013 (%)

FIGURE 16 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2008 AND 2013 ($ MILLIONS)

FIGURE 17 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2008 (%)

FIGURE 18 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2013 (%)

FIGURE 19 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, BY PRODUCT, 2008 AND 2013 ($ MILLIONS)

FIGURE 20 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, 2008 (%)

FIGURE 21 PROJECTED PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, 2013 (%)

FIGURE 22 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, THROUGH 2013

FIGURE 23 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, 2013 (%)

FIGURE 24 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

FIGURE 25 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, 2008

FIGURE 26 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, 2013

FIGURE 27 MANUFACTURING PROCESS FLOW CHART

FIGURE 28 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY PRODUCT, AUGUST 2005 TO AUGUST 2008

FIGURE 29 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008 (%)