Table of Contents

Cover

Related Titles

Title Page

List of Contributors

Foreword

Chapter 1: Introduction to the Book

Reference

Chapter 2: Global Epidemiological Developments

2.1 Introduction
2.2 Model of Epidemiological Transition
2.3 Global Burden of Diseases
2.4 Infectious Diseases
2.5 Noncommunicable Diseases
2.6 Antimicrobial Resistance
2.7 Dynamics
References

Chapter 3: The Value of Pharmaceutical Innovation: Concepts and Assessment

3.1 Introduction
3.2 Concepts and Definitions of Value
3.3 Stakeholder's Perspectives on Value
3.4 Recent Developments Influencing the Definition and Assessment of Value
3.5 Recommendations: Implications for R&D
3.6 Discussion
3.7 Conclusion
References

Chapter 4: A Review of the Pharmaceutical R&D Efficiency: Costs, Timelines, and Probabilities

4.1 Introduction
4.2 The Historical Perspective
4.3 The R&D Phase Model
4.4 The Low R&D Success Rates
4.5 The Long R&D Time Intervals
4.6 The High Cost of Pharmaceutical R&D
4.7 The Reduced R&D Efficiency
4.8 Can an Increase in R&D Value Compensate the Reduced R&D Efficiency?
References

Chapter 5: Financing Pharmaceutical Innovation

5.1 Introduction
5.2 Measuring Innovation: Categories of New Drugs
5.3 Productivity of Pharmaceutical Industry throughout Time
5.4 Measuring the Cost of Developing New Medicines
5.5 Funding Drug Development: a Global Endeavor
5.6 Public and Private Funds: Complementary Finance for Drug Development
5.7 How Commercial Drug Development Projects Are Financed Today: Big Firms, Small Firms, and Their Cooperation
5.8 Public Health Economics and Financing Pharmaceutical Innovation
5.9 Conclusion
Acknowledgment
References

Chapter 6: Challenges and Options for Drug Discovery

6.1 Introduction
6.2 Paradigm Shifts of R&D Organizations
6.3 Productivity of Drug Discovery
6.4 Is There an Innovation Gap in Biomedical Research?
6.5 Why Did Drug Candidates Fail?
6.6 Implications from the “Lessons Learnt” for Future Drug Discovery Research
Acknowledgment
References

Chapter 7: Translational Medicine: Enabling the Proof of Concepts

7.1 Introduction
7.2 Translational Medicine and Its Role/Value in Early Development
7.3 Knowledge Generation
7.4 Types of Data, Experiments, and Tools Needed to Move from Basic Research to Early Clinical Development
7.5 FIM (Dose Escalation and MTD)
7.6 Proof of Concept (PoC)
7.7 Summary
References

Chapter 8: Preclinical Safety and Risk Assessment

8.1 Introduction
8.2 Test Systems
8.3 Case Study: hERG Assay
8.4 The Preclinical “Package” during the Development of an NME
8.5 Factors Influencing the Preclinical Data Set
8.6 Translation into Humans: The “Therapeutic Window”
8.7 Influence of Intended Therapeutic Use on the Risk Assessment (RA)
8.8 Deep Dive Case Study: Safety Assessment of Biological Drug Formats
8.9 NBE Case Study 1
8.10 NBE Case Study 2
8.11 Carcinogenicity Risk Assessment for Marketed Drugs
8.12 Treatment Duration
8.13 Conclusion – the “Art” of Preclinical Safety: Summarizing the Concept of Hazard Identification and Description, Risk Assessment, and Risk Management
Acknowledgment
Disclosures
References

Chapter 9: Developing Commercial Solutions for Therapeutic Proteins

9.1 Introduction
9.2 Developing Commercial Solutions for Therapeutic Proteins
9.3 Quality by Design
9.4 Examples for Innovations in Manufacture of Sterile Pharmaceutical Products
9.5 Summary
List of FDA/ICH Guidances Referenced
Disclaimer
References

Chapter 10: The Evolution of Clinical Development: From Technical Success to Clinical Value Creation

10.1 Introduction
10.2 CD: Changes and Challenges
10.3 Technical Success and Clinical Value Creation in CD in the Future
Disclaimer
References

Chapter 11: Translational Development

11.1 Introduction
11.2 Translational Development
11.3 Dose Optimization
11.4 Pharmacogenomics
11.5 Biomarker Development
11.6 Systems Pharmacology
11.7 Rational Drug Development
11.8 Concluding Remarks
References

Chapter 12: Forty Years of Innovation in Biopharmaceuticals – Will the Next 40 Years Be as Revolutionary?

12.1 Introduction
12.2 The Evolution of Biologics Manufacturing
12.3 The Evolution of Alternative Scaffolds
12.4 Antibody-Drug Conjugates
12.5 The Next Wave of Biologics
Disclaimer
References

Chapter 13: Vaccines: Where Inertia, Innovation, and Revolution Create Value, Simultaneously and Quietly

13.1 Introduction
13.2 The World of Vaccines
13.3 The Vaccine Market: Substantial, Fast Growing, with Intense and Concentrated Competition
13.4 The Vaccine Industry: Domination of the Heavyweights, for Now…
13.5 New Vaccine Developments: Strategic Trends and Why Innovation Is Needed All along the Value Chain
13.6 Where Will Innovation Come from? Strategy and Players
References

Chapter 14: The Patient-Centric Pharma Company: Evolution, Reboot, or Revolution?

14.1 Introduction
14.2 Health, Always…
14.3 The Mission of the Healthcare Industry
14.4 Megatrends Affecting the Strategic Scorecard of the Healthcare Industry
14.5 Focus on the Societal Trends and Their Consequences for the Management of Healthcare Innovation
14.6 The DNA of the Healthcare Industry: R&D and the Management of Innovation
14.7 Societal Expectations for Personalized Medicine
14.8 New Players Contributing to Information Management to Substantiate Value Propositions for Novel Therapies
14.9 The Role of the Key Stakeholders in Shaping a New Regulatory Framework
14.10 The Consequences for the Healthcare Industry in Terms of Governance and Capabilities
14.11 The Sustainable Path Forward for the Healthcare Industry
References

Chapter 15: The Pharmaceutical Industry is Opening Its R&D Boundaries

15.1 Introduction
15.2 Open Innovation versus Closed Innovation
15.3 Business Models in an Open Innovation Framework
15.4 Open Innovation Processes
15.5 Capabilities and Attitudes Enabling Open Innovation
15.6 Open Innovation in the Pharmaceutical Industry
15.7 New Business Models in View of the Potential of Open Innovation
15.8 Outlook
References

Chapter 16: Out-Licensing in Pharmaceutical Research and Development1

16.1 Introduction
16.2 Performance-Based R&D Collaborations on the Rise
16.3 The Impact of Collaborations on the Value Chain
16.4 Generating Value from Pipeline Assets by Out-Licensing
16.5 Pharmaceutical Companies' Resistance toward Out-Licensing
16.6 Managing Out-Licensing at Novartis: A Case Study
16.7 Future Directions and Trends
References

Chapter 17: Trends and Innovations in Pharmaceutical R&D Outsourcing

17.1 Introduction
17.2 Drivers to the Use of Outsourcing
17.3 Genesis of Outsourcing in the Twentieth Century: From Commodity to Contribution
17.4 Current and Future Trends in Outsourcing: From Contribution to Innovation
17.5 Discussion and Conclusion
References

Chapter 18: New Innovation Models in Pharmaceutical R&D

18.1 Introduction
18.2 Some Attempts That Were Recommended in the Past
18.3 The Increasing Pipeline Size
18.4 The Reduction of R&D Investments
18.5 The Opening of the R&D Processes
18.6 The Challenge with the Return on Investment
18.7 Changing the R&D Processes Is Not Enough
18.8 What Is the Best R&D Model?
References

Chapter 19: The Influence of Leadership Paradigms and Styles on Pharmaceutical Innovation

19.1 Introduction
19.2 What Is Your Concept or Model of Good Leadership?
19.3 Approaches to Leadership Modeling and Profiling
19.4 The Developmental Approach to Leadership Paradigms and Styles
19.5 Inner and Outer Leadership
19.6 Dynamics of How Leadership Paradigms Evolve
19.7 Leadership at Different Levels within Pharma
19.8 Optimizing Innovation in Different Organizational Models and Cultures
19.9 How Do We Support the Development of Evolutionary Leaders?
19.10 What Does It Mean to Operate from the Evolutionary Paradigm?
19.11 Leadership and Personal Mastery
19.12 Building an Evolutionary Bridge to Release Innovation
19.13 Conclusions
References

Chapter 20: The Role of Modern Portfolio Management in Pharma Innovation

20.1 Introduction
20.2 Challenges in R&D and the Origin of Pharmaceutical Portfolio Management
20.3 Goals and Metrics of Portfolio Management
20.4 Portfolio Management as Enabler of Innovation
20.5 Modern Portfolio Management Integrates In-House R&D, Business Development, and M&A
References

Chapter 21: Patent Management Throughout the Innovation Life Cycle1

21.1 Introduction
21.2 The Changing Role of Patents: From Legal to Strategic
21.3 The Patent Life Cycle Management Model
21.4 Example: Managing IP Rights at Bayer
21.5 Concluding Remarks
References

Index

End User License Agreement

List of Illustrations

Chapter 1: Introduction to the Book

Figure 1.1 The pharmaceutical innovation hemisphere.
Figure 1.2 The traditional R&D phase model; IND (Investigational New Drug), NDA (New Drug Application), FDA (Food and Drug Administration), PTRS (probability of technical and regulatory success), WIP (work in progress), USD (U.S. Dollar), data derived from Paul S. et al. (2010)

Chapter 2: Global Epidemiological Developments

Figure 2.1 Composition of global DALYs in 1990 and 2010 (Murray et al., 2012).
Figure 2.2 2010 Composition of DALYs for different economic and geographic regions (Institute for Health Metrics and Evaluation (IHME), 2013c).
Figure 2.3 Composition of causes of death in 2015 and 2030 in three different regions.

Chapter 4: A Review of the Pharmaceutical R&D Efficiency: Costs, Timelines, and Probabilities

Figure 4.1 The traditional R&D phase model; IND (Investigational New Drug), NDA (New Drug Application), FDA (Food and Drug Administration), PTRS (probability of technical and regulatory success), WIP (work in progress), USD (U.S. dollar).
Figure 4.2 Proportion of total R&D expenditures based on CMR 2014 data of 11 research-based pharmaceutical companies.

Chapter 5: Financing Pharmaceutical Innovation

Figure 5.1 Annual NME approval rates by decade. Source: U.S. Food and Drug Administration (2013).
Figure 5.2 Breakdown of out-of-pocket (before accounting for the cost of capital) costs by drug development stage. The milestone “first toxicity dose” is reached when the first dose is given in the first animal toxicity study required to support administration to a human. The “first patient dose” milestone is reached when the active substance for the relevant project is administered to patients for a specific indication with the intention of treating for that indication. The date for the “first pivotal dose” is the date when the first dose is given to the first patient in the first pivotal safety and efficacy trial – the large-scale clinical study necessary to support registration in one of the core markets. Source: Mestre-Ferrandiz et al. (2012) and Adams and Brantner (2010).
Figure 5.3 Global public and private biomedical R&D expenditure.
Figure 5.4 Size of the public and private biomedical R&D expenditures relative to the domestic GDP.
Figure 5.5 Private sector expenditures in biomedical R&D during 1987–2013 for selected countries. The time series for the United States uses a secondary scale axis on the right hand side.
Figure 5.6 Geographic origins of novel drugs.
Figure 5.7 Efficiencies of domestic pharmaceutical industries.
Figure 5.8 Public funding of health R&D in 1998–2005, selected countries.

Chapter 7: Translational Medicine: Enabling the Proof of Concepts

Figure 7.1 The exposure at the site of action that is responsible to trigger a pharmacological action and humanization of the animal PK/PD models.

Chapter 8: Preclinical Safety and Risk Assessment

Figure 8.1 Schematic screening cascade for selection of compounds through application of “in silico” (left), “in vitro” (center), and “in vivo” methods (right).
Figure 8.2 Exemplary electrocardiogram with induction torsades de pointes (TdP). The arrows represent falling T-wave which is initiating the induction of the TdP.
Figure 8.3 The development of a compound and the preclinical data set.
Figure 8.4 Schematic Figure describing the therapeutic window (or range, or index).
Figure 8.5 Exemplary decision tree for carcinogenicity risk assessment.
Figure 8.6 The concept of hazard identification and risk assessment.

Chapter 9: Developing Commercial Solutions for Therapeutic Proteins

Figure 9.1 Key parameters to be investigated and well selected during product/target product profile for an injectable peptide/protein product.
Figure 9.2 Schematic high-level overview on development steps for a commercial solution.

Chapter 10: The Evolution of Clinical Development: From Technical Success to Clinical Value Creation

Figure 10.1 Chain of evidence in clinical development.

Chapter 11: Translational Development

Figure 11.1 Translating research into clinical utility and commercial success.
Figure 11.2 Relationship PKPD and systems pharmacology as parallel approaches to build confidence around proof of concept.

Chapter 12: Forty Years of Innovation in Biopharmaceuticals – Will the Next 40 Years Be as Revolutionary?

Figure 12.1 Comparison of Biologics with small molecules. (a) Three-dimensional ribbon structure of an Immunoglobulin G IgG molecule. (b) Comparison of general properties of biopharmaceuticals compared with small-molecule therapeutics. COGs, cost of goods sold.
Figure 12.2 (a) Probability of success rates of Biologics (black bars) and small molecules (gray bars) and average development costs (b) in various phases of development. SMOL, small-molecule therapeutic.
Figure 12.3 Typical annual sales rate progression in the life cycle of a Biologic.
Figure 12.4 Biologics sales from 2007 to 2013 and market growth rate for Biologics versus overall pharma market growth (gray bars).
Figure 12.5 Number of FDA drug approvals 1998–2014 split by drug modality.
Figure 12.6 Antibody scaffolds and bispecific antibodies. While antibodies, single-domain antibodies and single-chain Fv fragments are monospecific, all other derivatives can be engineered to recognize more than one antigen.
Figure 12.7 Essential elements of an antibody-drug conjugate (ADC).
Figure 12.8 Mechanism of action of an ADC: Upon binding of a tumor antigen, the ADC can be internalized via various mechanisms. Trafficking to the lysosome results in mAb degradation and payload release into the cytoplasma. Depending on the mechanism of action of the payload, the target cell undergoes programmed cell death in a cell cycle dependent or independent manner.

Chapter 13: Vaccines: Where Inertia, Innovation, and Revolution Create Value, Simultaneously and Quietly

Figure 13.1 Top 10 therapy sales in 2013, market share and sales growth (2012–2013).
Figure 13.2 Top 10 therapy areas in 2020, market share and sales growth.
Figure 13.3 Worldwide sales, market share, and sales growth (2013–2020). Note: Bubble = WW sales in 2020.

Chapter 15: The Pharmaceutical Industry is Opening Its R&D Boundaries

Figure 15.1 The logic of closed innovation.
Figure 15.2 R&D funnel in the logic of closed innovation.
Figure 15.3 Open innovation paradigm for managing R&D.
Figure 15.4 The three open innovation processes.
Figure 15.5 Reported in-licensing in clinical development phases in 2002 and 2010.

Chapter 16: Out-Licensing in Pharmaceutical Research and Development1

Figure 16.1 Distribution of pharmaceutical deals.
Figure 16.2 Restructuring of pharmaceutical R&D departments and resulting interaction with external partners (Gassmann and Reepmeyer, 2005).
Figure 16.3 Classification of partnerships in pharmaceutical R&D activities (Reepmeyer, 2005).
Figure 16.4 Different types of collaboration in pharmaceutical R&D (perspective: pharmaceutical company) (Reepmeyer, 2005).
Figure 16.5 Out-licensing: The neglected strategy to gain complementary assets for the utilization of a company's own technology (compare Megantz, 2002).
Figure 16.6 Out-licensing as a way to open new markets (Reepmeyer, 2005).
Figure 16.7 Out-licensing process at Novartis (Reepmeyer, 2005).
Figure 16.8 Out-licensing collaboration between Novartis and Speedel (Reepmeyer, 2005).

Chapter 17: Trends and Innovations in Pharmaceutical R&D Outsourcing

Figure 17.1 Degree of outsourcing as a function of pipeline volume and internal resource and capabilities.

Chapter 18: New Innovation Models in Pharmaceutical R&D

Figure 18.1 Total R&D expenditures of PhRMA members in the years of 1995–2012. Data derived from PhRMA (PhRMA, 2013) Pharmaceutical Industry 2013 Profile, http://www.phrma.org/sites/default/files/pdf/PhRMA%20Profile%202013.pdf.

Chapter 19: The Influence of Leadership Paradigms and Styles on Pharmaceutical Innovation

Figure 19.1 Spectrum of leadership team options.
Figure 19.2 Innovation at the edge of chaos.

Chapter 20: The Role of Modern Portfolio Management in Pharma Innovation

Figure 20.1 Projects of a portfolio can be plotted in ascending order by their “productivities,” that is, the ratio of risk-adjusted (RA) NPV and RA investment. Productivity is represented as the slope of the curve, and the steeper the slope, the higher the value contribution of a project relative to the investment required. If, for example, the budget limit equals $250 million, all projects to the right of the budget limit may be licensed out or, in the event the slope is negative (negative NPV), abandoned.
Figure 20.2 Future project values can be calculated and plotted as a function of development phase. Innovative projects may add significant more value at later stages than less innovative projects. The information of how much value will likely be added once a particular milestone will be reached should contribute to decision making. For example, management may want to support and fund project “B” because of its value gain in later stages, although its NPV at the time of decision is negative.
Figure 20.3 Plot of a value distribution of a portfolio consisting of nine preclinical, three phase I, two phase II, and one phase III projects. The portfolio value mean is used as a single descriptor of the portfolio's value, the standard deviation (SD) being a measure of portfolio risk. The portfolio can be said to be reasonably diversified as the probability of portfolio failure (negative NPV) is in the order of 1%. Of interest is the “value-to-risk” ratio that can be obtained by dividing portfolio value by its SD. The more projects are added to a portfolio, the larger the ratio becomes, that is, more value is created per “unit of risk.” Therefore, large portfolios have a much higher probability to provide a return on investment than small ones, and the return becomes bigger relative to the risk assumed.
Figure 20.4 Modern portfolio management spans internal R&D, business development, and M&A functions. This structure allows a company to take a bird's-eye view onto potential portfolios, whose individual project members are recruited for the entire world.

Chapter 21: Patent Management Throughout the Innovation Life Cycle1

Figure 21.1 The “innovation scissors” in the pharmaceutical sector.
Figure 21.2 Value effect of monopolizing patents in the pharmaceutical sector.
Figure 21.3 The patent life cycle management model.
Figure 21.4 External exploitation of intellectual property at Bayer.

List of Tables

Chapter 2: Global Epidemiological Developments

Table 2.1 2010 DALY rate, change of rate since 1990, and three leading causes in geographic and socioeconomic regions (Institute for Health Metrics and Evaluation (IHME), 2013b; Institute for Health Metrics and Evaluation (IHME), 2013a)
Table 2.2 Classification of infectious diseases (Nelson, Masters, and Graham, 2001)
Table 2.3 Impact of major infectious diseases, as share of global DALYs and global deaths (Institute for Health Metrics and Evaluation (IHME), 2013b; Anonymous, 2015)
Table 2.4 Selection of some NTDs (not comprehensive) (Hotez et al., 2014; Institute for Health Metrics and Evaluation (IHME), 2013b)
Table 2.5 Major NCDs based on DALYs, deaths, and change of DALYs per 100 000 since 1990 (Institute for Health Metrics and Evaluation (IHME), 2013b; Murray et al., 2012)
Table 2.6 Selection of pathogen antibiotic resistances in WHO regions (World Health Organization, 2014a)

Chapter 3: The Value of Pharmaceutical Innovation: Concepts and Assessment

Table 3.1 Strategies for early assessment of value during the drug research and development process

Chapter 4: A Review of the Pharmaceutical R&D Efficiency: Costs, Timelines, and Probabilities

Table 4.1 Success rates per phase of pharmaceutical R&D
Table 4.2 Average timelines of pharmaceutical R&D phases
Table 4.3 Costs of pharmaceutical R&D and costs per phase of R&D.
Table 4.4 R&D efficiencies (2001–2012) of multinational pharmaceutical companies.

Chapter 5: Financing Pharmaceutical Innovation

Table 5.1 Estimates of drug development costs

Chapter 7: Translational Medicine: Enabling the Proof of Concepts

Table 7.1 Types of studies conducted and their outcome to mitigate the risk for first-in-human trials for the investigational medicinal product

Chapter 8: Preclinical Safety and Risk Assessment

Table 8.1 Affinity (K_D, dissociation constant) of an IL-6 mAb against various preclinical species epitopes
Table 8.2 Comparison of various cross-species properties of biologics and their influence on the design of the safety package

Chapter 9: Developing Commercial Solutions for Therapeutic Proteins

Table 9.1 Moving from a minimal approach to quality by design
Table 9.2 WHO: Maximum permitted airborne particle concentration (World Health Organization, 2011)
Table 9.3 WHO: Recommended limits for microbial contamination^a (World Health Organization, 2011)

Chapter 10: The Evolution of Clinical Development: From Technical Success to Clinical Value Creation

Table 10.1 Changes and their impact on the clinical development area
Table 10.2 Factors driving technical success and value creation in the clinical development area

Chapter 11: Translational Development

Table 11.1 Target occupancy requirements for clinical efficacy
Table 11.2 Examples of known alleles influence the outcomes of specific drug therapy mentioned within product labels
Table 11.3 Examples of genetic variants that are used to enable optimum selection of specific oncology therapy

Chapter 12: Forty Years of Innovation in Biopharmaceuticals – Will the Next 40 Years Be as Revolutionary?

Table 12.1 Annual sales in US$ of the 10 best-selling drugs in 2013
Table 12.2 A typical downstream recovery process for a monoclonal antibody
Table 12.3 Select ADCs in clinical development

Chapter 13: Vaccines: Where Inertia, Innovation, and Revolution Create Value, Simultaneously and Quietly

Table 13.1 Worldwide ranking of healthcare companies according to 2020 projected prescription sales
Table 13.2 Top 10 companies and total worldwide vaccine sales 2013–2020
Table 13.3 Top 5 vaccine products worldwide in 2020
Table 13.4 Top 20 most valuable R&D projects (ranked by net present value)

Chapter 15: The Pharmaceutical Industry is Opening Its R&D Boundaries

Table 15.1 Contrasting principles of closed and open innovation
Table 15.2 Key R&D pipeline figures of multinational pharmaceutical companies
Table 15.3 Outsourced R&D expenditures by type in the years 1997, 2001, 2005, and 2009 (Hu, 2007)

Chapter 17: Trends and Innovations in Pharmaceutical R&D Outsourcing

Table 17.1 Key objectives to utilize outsourcing in the early days
Table 17.2 Basic requirements and enablers for innovation in the pharmaceutical outsourcing process

Chapter 18: New Innovation Models in Pharmaceutical R&D

Table 18.1
Table 18.2 Externally acquired R&D pipeline of research-based pharmaceutical companies

Chapter 19: The Influence of Leadership Paradigms and Styles on Pharmaceutical Innovation

Table 19.1 Leadership paradigms and styles summary (Howard, 2015)
Table 19.2 Leadership style descriptions (Howard, 2015)
Table 19.3 Leadership style and organizational culture, innovation, and situationality
Table 19.4 Definitions of the six critical organizational capabilities

Chapter 20: The Role of Modern Portfolio Management in Pharma Innovation

Table 20.1 Values, standard deviations (SDs), and value-to-risk ratios of value distributions representing portfolios that become increasingly rich (more projects) and mature (late-stage projects)

Chapter 21: Patent Management Throughout the Innovation Life Cycle1

Table 21.1 Overview of the investigated firms

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List of Contributors

Martin A. Bader
BGW AG
Management Advisory Group
Varnbüelstrasse 13
9000 St. Gallen
Switzerland
and
Technische Hochschule Ingolstadt
THI Business School
Esplanade 10
85049 Ingolstadt
Germany

Ulrich A. K. Betz
Merck KGaA
Frankfurter Str. 250
64293 Darmstadt
Germany

Michael Buckley
Independent Principal Consultant
Livermore
CA

Rob Caldwell
Abbvie Inc. R466
AP13A-3, 1 North waukegan Road
North Chicago
IL 6000064
USA

John Darbyshire
Mooshagweg 10
CH 4123 Allschwil
Switzerland

Oliver Gassmann
University of St. Gallen
Institute of Technology Management
Dufourstrasse 40a
9000 St. Gallen
Switzerland

Paul Germann
AbbVie Deutschland GmbH & Co KG
Knollstraβe 50
67061
Ludwigshafen am Rhein
Germany

Joachim M. Greuel
Bioscience Valuation BSV GmbH
Am Zigeunerbergl 3
82491 Grainau
Germany

Antal K. Hajos
Procelsis Holding UG
Am Farnberg 3
79289 Horben
Germany

Galina Hesse
Sanofi-Aventis Deutschland GmbH
Industriepark Hoechst
65926 Frankfurt am Main
Germany

Markus Hinder
Novartis Pharma AG
Novartis Institutes for Biomedical
Research
Postfach, Forum 1
4002 Basel
Switzerland

Aubyn Howard
Château Chavagnac
07610 Lemps
Ardèche
France
and
Psychosynthesis Coaching Limited
London
United Kingdom

Paul Kamudoni
Institute of Medicines Development
Duffryn House
CF 23 6NP
Cardiff
UK

Werner Kramer
Biomedical & Scientific Consulting
55130
Mainz- Germany

Carol A. Krech
AG Management Advisory Group
Varnbüelstrasse 13
9000 St. Gallen
Switzerland
Technische Hochschule Ingolstadt
THI Business School
Esplanade 10
85049 Ingolstadt
Germany

Gezim Lahu
Takeda Pharmaceuticals International
Thurgauerstrasse 130
CH 8152 Glattpark-Opfikon (Zürich)
Switzerland

Qiang Liu
Takeda California, Inc.
10410 Science Center Drive
San Diego
CA 92121
USA

Stephan Luther
IHPH – Institute for Hygiene and Public Health
WHO Collaborating Centre for Health Promoting Water
Management and Risk Communication
Medical Geography & Public Health Workgroup
University of Bonn
Sigmund-Freud-Straβe 25
D-53105 Bonn
Germany

Nigel McCracken
Debiopharm Group
Forum ℌaprès-demain”
Chemin Messidor 5-7
Case postale 5911
1002 Lausanne
Switzerland

Pierre A. Morgon
AJ Biologics
Level 4, Menara Atlan
161B Jalan Ampang
50450 Kuala Lumpur
Malaysia
and
Mérieux Développement
17 rue Bourgelat
69002 Lyon
France
and
Theradiag SA
14 rue Ambroise Croizat
77183 Croissy Beaubourg
France
and
Eurocine Vaccines AB
Fogdevreten 2
17165 Solna
Sweden
and
MRGN Advisors
Rue du Mont-Blanc 4
Case postale 2067
1211 Genève 1
Switzerland

Hannah Nawi
AJ Biologics
Level 4, Menara Atlan
161B Jalan Ampang
50450 Kuala Lumpur
Malaysia

Sanjay Patel
Takeda California, Inc.
10410 Science Center Drive
San Diego
CA 92121
USA

Gerrit Reepmeyer
Ockham Razor Ventures
33717 Woodward Avenue #143
Birmingham
MI 48009
USA

Sam Salek
University of Hartfordshire
School of Life and Medical Sciences
Department of Pharmacy
Pharmacology and Postgraduate Medicine
College Lane
Hartfield
Herts
AL10 9AB
UK
and
Institute of Medicines Development
Duffryn House
CF 23 6NP
Cardiff
UK

Mathias Schmidt
Takeda California, Inc.
10410 Science Center Drive
San Diego
CA 92121
USA

Peter Schmitz
IHPH – Institute for Hygiene and Public Health,
WHO Collaborating Centre for Health Promoting Water
Management and Risk Communication,
Medical Geography & Public Health Workgroup,
University of Bonn
Sigmund-Freud-Straβe 25
D-53105 Bonn, Germany

Alexander Schuhmacher
Reutlingen University
School of Applied Chemistry
Alteburgstrasse 150
72762 Reutlingen
Germany

Sviataslau Sivagrakau
Goethe University Frankfurt
Theodor-W.-Adorno-Platz 1
60323 Frankfurt
Germany

Petter Veiby
Takeda Pharmaceuticals International
40 Landsdowne Street
Cambridge
MA 02139

Axel Wiest
Merck Serono
Frankfurter Straβe 250
64293 Darmstadt
Germany

Foreword

The main driver for sustainable profitable growth in the pharmaceutical industry is innovation.

Research and development (R&D) is the primary source for product innovation; it is the lifeblood of our industry. Product innovation is the result of long-term investments, which at the same time takes place in a challenging and dynamic environment, as pharmaceutical companies are highly pressurized by long development times, shorter commercialization of the intellectual property (IP) rights, and cost pressure by the public healthcare sector. R&D requires commitment, flexibility and perseverance: We need to invest and believe, learn from setbacks, scrutinize, and execute.

With the objective to provide new and differentiated therapies to patients and society, our biopharmaceutical company, AbbVie, is devoted to having a remarkable impact on patients' lives, especially in areas with a high unmet medical need AbbVie's approach to innovation builds on track record of developing breakthrough science. For example, our work in immunology has benefited over 850,000 patients with rheumatoid arthritis, psoriasis, Crohn's disease and other chronic autoimmune conditions. And, at the beginning of 2015, we received the approval for our oral, interferon-free treatment option for patients with chronic hepatitis C, which provides a very high probability of cure. Decades of research, extensive investment, and collaboration across functions and countries have made this kind of innovation possible.

With this book, Alexander Schuhmacher, Markus Hinder, and Oliver Gassmann provide a unique overview of the success-critical components necessary to deliver pharmaceutical innovation. The authors have compiled an overview of today's state-of-the-art pharmaceutical R&D processes and the challenges the industry is facing. All authors are thought leaders in the industry and academia and offer a wide range of experience. They give the reader comprehensive insights into research-, development-, and business-related subjects of the pharmaceutical industry. In addition, each author provides his or her personal view of how the industry might evolve in the future and how current issues and challenges can be addressed to increase overall productivity.

Starting with two epidemiological and pharmacoeconomic analyses, this book provides first-class strategic and operational insights into drug discovery, translational and clinical development up to more managerial aspects such as portfolio or IP management. As the industry is increasing its integration and as some companies need to adopt a more effective approach to their R&D organizations, the chapters on open innovation and new innovation models give a brilliant summary of some key drivers in pharmaceutical R&D today and tomorrow.

This book is a exclusive compilation of challenges and state-of-the-art solutions within the pharmaceutical R&D process. In its wider significance, the book deals with the critical path towards value creation in the pharmaceutical industry. Thus, the book is targeted at R&D managers, business managers, researchers, drug developers, marketing leaders, and sales managers – in a nutshell to all innovators in the pharmaceutical sector. In addition, it should be a valuable platform for academics, educational organizations, and university students who are interested in today's world of pharmaceutical innovation.

Ludwigshafen, September 2015

Dr Friedrich Richter
Vice President
Global Drug Product Development

Related Titles

Value Creation in the Pharmaceutical Industry

The Critical Path to Innovation

List of Contributors

Foreword