A Guide to Biosimilars, Biogenerics and Follow-On Biologics

Table of Contents

• 1.1 The advent of biosimilars
• 1.2 The role of patents in the drug industry
• 1.3 Protein-based biopharmaceuticals
  • 1.3.1 Background
  • 1.3.2 Manufacturing processes
  • 1.3.3 Protein characterisation
  • 1.3.4 The global market
• 1.4 Biosimilars
  • 1.4.1 Market drivers and inhibitors
  • 1.4.2 The INN nomenclature system
• 1.5 Biosimilars regulation
  • 1.5.1 The EU position
  • 1.5.2 US pathways
    • 1.5.2.1 Government initiatives

• 2.1 Introduction
  • 2.1.1 Approved follow-on proteins/biosimilars
• 2.2 Characteristics of high-selling peptides and proteins
  • 2.2.1 Products with expired patents
  • 2.2.2 Challenging originator' s patents
• 2.3 Target products for FOB/biosimilar development
• 2.4 Peptides (NDA Pathway)
  • 2.4.1 Octreotide
  • 2.4.2 Desmopressin
  • 2.4.3 Cyclosporine
  • 2.4.4 Calcitonin
  • 2.4.5 Eptifibatide
  • 2.4.6 LHRH
  • 2.4.7 Bivalirudin
  • 2.4.8 Enfuvirtide
  • 2.4.9 Glucagon
  • 2.4.10 Nesiritide
  • 2.4.11 Teriparatide
• 2.5 Recombinant non-glycosylated proteins (NDA Pathway)
  • 2.5.1 Insulin
  • 2.5.2 Somatropin
  • 2.5.3 Lepirudin
• 2.6 Recombinant non-glycosylated proteins (BLA pathway)
  • 2.6.1 Interleukin-2
  • 2.6.2 Interferons
    • 2.6.2.1 Interferon-alfa
    • 2.6.2.2 Interferon-beta
    • 2.6.2.3 Interferon-gamma
  • 2.6.3 Granulocyte-CSF
  • 2.6.4 Interleukin-11
  • 2.6.5 Anakinra
  • 2.6.6 Other proteins
• 2.7 Recombinant glycosylated proteins (NDA pathway)
  • 2.7.1 Follitropin
  • 2.7.2 Thyrotropin
  • 2.7.3 Urokinase
  • 2.7.4 Glucocerebrosidase
  • 2.7.5 Other products
• 2.8 Recombinant glycosylated proteins (BLA pathway)
  • 2.8.1 Becaplermin
  • 2.8.2 Granulocyte-macrophage-CSF
  • 2.8.3 Erythropoietin
  • 2.8.4 DNase
  • 2.8.5 Factor VIIa
  • 2.8.6 Factor IX
  • 2.8.7 Factor VIII
  • 2.8.8 Activated protein C
  • 2.8.9 Tissue plasminogen activator
  • 2.8.10 Monoclonal antibodies
    • 2.8.10.1 Chimaeric mAbs
    • 2.8.10.2 Humanised mAbs
    • 2.8.10.3 Human mAbs and fusion proteins
  • 2.8.11 Other proteins
• 2.9 Strategies of originator companies
  • 2.9.1 Increasing product patent protection
  • 2.9.2 Next-generation branded products
  • 2.9.3 Development of authorised generics
  • 2.9.4 Price reduction of the branded product

• 3.1 Introduction
• 3.2 Problems in characterising biologics
  • 3.2.1 Definitions
  • 3.2.2 Types of biologic
    • 3.2.2.1 Peptides
    • 3.2.2.2 Non-glycosylated proteins
    • 3.2.2.3 Glycosylated proteins
    • 3.2.2.4 Monoclonal antibodies
  • 3.2.3 Equivalence issues
  • 3.2.4 Post-translational modifications
  • 3.2.5 Effect of microheterogeneity
  • 3.2.6 Pharmacokinetics
  • 3.2.7 Pharmacodynamics
  • 3.2.8 Clinical efficacy
  • 3.2.9 Immunogenicity
• 3.3 Analytical methods
  • 3.3.1 Introduction
  • 3.3.2 Chromatography
  • 3.3.3 Protein sequencing
  • 3.3.4 Mass spectrometry
  • 3.3.5 Nuclear magnetic resonance
  • 3.3.6 Electrophoresis
  • 3.3.7 Western blotting
  • 3.3.8 Bioassays
  • 3.3.9 Other procedures
• 3.4 Case studies
  • 3.4.1 Introduction
  • 3.4.2 Erythropoietin
    • 3.4.2.1 European position
    • 3.4.2.2 US position
    • 3.4.2.3 Immunogenicity: pure red cell aplasia
    • 3.4.2.4 Immunogenicity: product consistency issues
  • 3.4.3 Somatotropin
    • 3.4.3.1 European position
    • 3.4.3.2 US position
    • 3.4.3.3 Immunogenicity issues
  • 3.4.4 Alpha interferon
    • 3.4.4.1 European position
    • 3.4.4.2 US position

• 4.1 Preface
• 4.2 India-based companies
  • 4.2.1 Biocon
    • 4.2.1.1 Company overview
    • 4.2.1.2 Biosimilar strategy
    • 4.2.1.3 Biosimilar pipeline
    • 4.2.1.4 Biosimilar collaborations
  • 4.2.2 Dr Reddy' s
    • 4.2.2.1 Company overview
    • 4.2.2.2 Biosimilar strategy
    • 4.2.2.3 Biosimilar pipeline
  • 4.2.3 Reliance Life Sciences/Genemedix
    • 4.2.3.1 Company overview
    • 4.2.3.2 Biosimilar strategy
    • 4.2.3.3 Biosimilar pipeline
    • 4.2.3.4 Biosimilar collaborations
  • 4.2.4 Ranbaxy Laboratories
    • 4.2.4.1 Company overview
    • 4.2.4.2 Biosimilar strategy
    • 4.2.4.3 Biosimilar pipeline
    • 4.2.4.4 Biosimilar collaborations
• 4.3 Germany-based companies
  • 4.3.1 Ratiopharm/Biogenerix
    • 4.3.1.1 Overview
    • 4.3.1.2 Biosimilar strategy
    • 4.3.1.3 Biosimilar pipeline
    • 4.3.1.4 Biosimilar collaborations
  • 4.3.2 Sandoz International (Novartis)
    • 4.3.2.1 Company overview
    • 4.3.2.2 Biosimilar strategy
    • 4.3.2.3 Biosimilar pipeline
    • 4.3.2.4 Biosimilar collaborations
  • 4.3.3 Stada Arzneimittel/Bioceuticals Arzneimittel
    • 4.3.3.1 Company overview
    • 4.3.3.2 Biosimilar strategy
    • 4.3.3.3 Biosimilar pipeline
    • 4.3.3.4 Biosimilar collaborations
• 4.4 Other EU-based companies
  • 4.4.1 Bioton/Biopartners
    • 4.4.1.1 Company overview
    • 4.4.1.2 Biosimilar strategy
    • 4.4.1.3 Biosimilar pipeline
    • 4.4.1.4 Biosimilar collaborations
  • 4.4.2 DSM (DSM Biologicals)
    • 4.4.2.1 Company overview
    • 4.4.2.2 Biosimilar strategy
    • 4.4.2.3 Biosimilar pipeline
    • 4.4.2.4 Biosimilar collaborations
• 4.5 US-based companies
  • 4.5.1 Barr Pharmaceuticals/Pliva
    • 4.5.1.1 Company overview
    • 4.5.1.2 Biosimilar strategy
    • 4.5.1.3 Biosimilar pipeline
    • 4.5.1.4 Biosimilar collaborations
  • 4.5.2 Hospira/Mayne Pharma
    • 4.5.2.1 Company overview
    • 4.5.2.2 Biosimilar strategy
    • 4.5.2.3 Biosimilar pipeline
    • 4.5.2.4 Biosimilar collaborations
  • 4.5.3 Dynavax Technologies/Rhein Biotech
    • 4.5.3.1 Company overview
    • 4.5.3.2 Biosimilar strategy
    • 4.5.3.3 Biosimilar pipeline
    • 4.5.3.4 Biosimilar collaborations
• 4.6 Canada-based companies
  • 4.6.1 Cangene
    • 4.6.1.1 Company overview
    • 4.6.1.2 Biosimilar strategy
    • 4.6.1.3 Biosimilar pipeline
  • 4.6.2 Microbix
    • 4.6.2.1 Company overview
    • 4.6.2.2 Biosimilar strategy
    • 4.6.2.3 Biosimilar pipeline
    • 4.6.2.4 Biosimilar collaborations
• 4.7 Other companies
  • 4.7.1 Teva Pharmaceutical Industries/Sicor
    • 4.7.1.1 Company overview
    • 4.7.1.2 Biosimilar strategy
    • 4.7.1.3 Biosimilar pipeline
    • 4.7.1.4 Biosimilar collaborations

• 5.1 Introduction
• 5.2 Leading drug classes
• 5.3 Major players
• 5.4 Market outlook
• 5.5 Pricing of biosimilars
• 5.6 Profitability of biosimilars
• 5.7 Substitutability and interchangeability
• 5.8 World pharmaceutical market overview
• 5.9 World market for protein biopharmaceuticals
• 5.10 Approved biosimilar products
  • 5.10.1 US
  • 5.10.2 Europe
• 5.11 Forecasts by product
  • 5.11.1 Erythropoietin
  • 5.11.2 Insulin
  • 5.11.3 Interferons
  • 5.11.4 Granulocyte colony stimulating factor
  • 5.11.5 Somatotropins
  • 5.11.6 Other proteins and peptides
• 5.12 Forecasts by Region

• 6.1 Biosimilars market gaining momentum
• 6.2 Competing through superior delivery
• 6.3 Diversifying biosimilar pipelines
• 6.4 Tackling immunogenicity
• 6.5 Expanding the range of cell production systems
• 6.6 Exploring transgenic production systems
• 6.7 Developing cell-free protein synthesis

• Table 1.1 Leading protein products in 2006
• Table 1.2 Leading monoclonal antibody products in 2006
• Table 2.1 Peptides (NDA pathway)
• Table 2.2 Recombinant non-glycosylated proteins (NDA pathway)
• Table 2.3 Recombinant non-glycosylated proteins (BLA pathway)
• Table 2.4 Recombinant glycosylated proteins (NDA pathway)
• Table 2.5 Recombinant glycosylated proteins (BLA pathway)
• Table 2.6 Patents - peptides (NDA pathway)
• Table 2.7 Patents - recombinant non-glycosylated proteins (NDA pathway)
• Table 2.8 Patents - recombinant non-glycosylated proteins (BLA pathway)
• Table 2.9 Patents - recombinant glycosylated proteins (NDA pathway)
• Table 2.10 Patents - recombinant glycosylated proteins (BLA pathway)
• Table 2.11 Commercialisation of candidate biosimilars
• Table 2.12 Candidate biosimilars by gene target
• Table 2.13 Launched peptides and proteins by primary pharmacology description
• Table 2.14 Candidate biosimilars (interferon alpha)
• Table 2.15 Candidate biosimilars (insulin)
• Table 2.16 Candidate biosimilars (erythropoietin)
• Table 2.17 Candidate biosimilars (factor VIII)
• Table 2.18 Candidate biosimilars (cyclosporin)
• Table 2.19 Candidate biosimilars (granulocyte stimulating factor)
• Table 2.20 Candidate biosimilars (interferon beta)
• Table 2.21 Candidate biosimilars (calcitonin)
• Table 2.22 Candidate biosimilars (LHRH)
• Table 2.23 Candidate biosimilars (interleukin 2)
• Table 2.24 Candidate biosimilars (factor IX)
• Table 2.25 Candidate biosimilars (tissue plasminogen activator)
• Table 2.26 Candidate biosimilars (urokinase plasminogen activator)
• Table 2.27 Candidate biosimilars (follitropin)
• Table 2.28 Candidate biosimilars (somatotropin)
• Table 2.29 Candidate biosimilars (granulocyte macrophage colony stimulating factor)
• Table 2.30 Candidate biosimilars (interferon gamma)
• Table 2.31 Candidate biosimilars (octreotide)
• Table 2.32 Candidate biosimilars (desmopressin)
• Table 2.33 Candidate biosimilars (factor VIIa)
• Table 2.34 Candidate biosimilars (protein C)
• Table 2.35 Candidate biosimilars (teriparatide)
• Table 2.36 Candidate biosimilars (glucocerebrosidase)
• Table 2.37 Candidate biosimilars (hirudin)
• Table 2.38 Candidate biosimilars (bevacizumab)
• Table 2.39 Candidate biosimilars (enfuvirtide)
• Table 2.40 Candidate biosimilars (glucagon)
• Table 2.41 Candidate biosimilars (interleukin 11)
• Table 2.42 Candidate biosimilars (thyrotropin)
• Table 2.43 Candidate biosimilars (abciximab)
• Table 2.44 Candidate biosimilars (adalimumab)
• Table 2.45 Candidate biosimilars (alemtuzumab)
• Table 2.46 Candidate biosimilars (anakinra)
• Table 2.47 Candidate biosimilars (aprotinin)
• Table 2.48 Candidate biosimilars (becaplermin)
• Table 2.49 Candidate biosimilars (cetuximab)
• Table 2.50 Candidate biosimilars (DNase)
• Table 2.51 Candidate biosimilars (efalizumab)
• Table 2.52 Candidate biosimilars (eptifibatide)
• Table 2.53 Candidate biosimilars (etanercept)
• Table 2.54 Candidate biosimilars (gemtuzumab)
• Table 2.55 Candidate biosimilars (infliximab)
• Table 2.56 Candidate biosimilars (natalizumab)
• Table 2.57 Candidate biosimilars (nesiritide)
• Table 2.58 Candidate biosimilars (omalizumab)
• Table 2.59 Candidate biosimilars (palivizumab)
• Table 2.60 Candidate biosimilars (rituximab)
• Table 2.61 Candidate biosimilars (trastuzumab)
• Table 3.1 Examples of post-translational modifications
• Table 3.2 Analytical procedures useful for assessing the equivalence of biotechnological products
• Table 5.1 Leading protein drug classes in 2006
• Table 5.2 World pharma market by therapeutic category, 2006-2011
• Table 5.3 World pharma market by region, 2006-2011
• Table 5.4 Biopharmaceuticals market by application in 2006 and 2011
• Table 5.5 Biopharmaceuticals market by company in 2006 and 2011
• Table 5.6 Biopharmaceuticals market by protein in 2006 and 2011
• Table 5.7 Biosimilars market by protein in 2006 and 2011
• Table 5.8 Biopharmaceuticals market by region in 2006 and 2011
• Table 5.9 Biosimilars market by region in 2006 and 2011
• Table 6.1 Recently published cell-free protein synthesis patents and applications