Changing Innovation in the Pharmaceutical Industry. Globalization and New Ways of Drug Development

Transcription

1 Changing Innovation in the Pharmaceutical Industry Globalization and New Ways of Drug Development

2 Springer-Verlag Berlin Heidelberg GmbH

3 Andre Jungmittag Guido Reger Thomas Reiss (Eds.) Changing Innovation in the Pharmaceutical Industry Globalization and New Ways of Drug Development With 46 Figures and 28 Tables 'Springer

4 Dr. Andre Jungrpittag University of Potsdam Economic Policy/International Economic Relations August-Bebel-StraSe Potsdam Germany Prof. Dr. Guido Reger Fachhochschule Brandenburg University of Applied Science Magdeburger StraSe Brandenburg an der Havel Germany Dr. Thomas Reiss Fraunhofer Institute for Systems and Innovation Research (lsi) Breslauer StraSe Karlsruhe Germany ISBN Library of Congress Cataloging-in-Publication Data Die Deutsche Bibliothek - CIP-Einheitsaufnahme Changing Innovation in the Pharmaceutical Industry: Globalization and New Ways of Drug Development; with 28 tables I Andre Jungmittag... (ed.). ISBN ISBN (ebook) DOI / This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1%5, in its current version, and permission for use must always be obtained from Springer-Verlag Berlin Heidelberg GmbH. Violations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg 2000 Originally published by Springer-Verlag Berlin Heidelberg New York in 2000 Softcover reprint of the hardcover 1st edition 2000 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Hardcover-Design: Erich Kirchner, Heidelberg SPIN / I 0 - Printed on acid-free paper

5 Preface The internationalization of research and technology is one key component of the globalization of trade and business, with potentially major impacts on patterns of economic development and public policies worldwide. Although certain aspects of this internationalization trend are well documented, and some effects can be quantified, the overall processes are extremely complex and the outcomes are highly uncertain. The existence of the phenomenon is generally accepted, but its importance and the trends are currently the topic of a lively debate. This study on "New Ways in Drug Development in Pharmaceuticals" is part of a three year project which aims at investigating how new concepts of industrial knowledge creation are implemented in the different environments of the innovation systems of the United States and Germany. The main focus of the overall project is a series of case studies of innovation practice in different national and sectoral contexts. The following sectors and technological fields are investigated: pharmaceuticals and new ways in drug development by the Fraunhofer Institute for Systems and Innovation Research (ISI), advanced materials by the University Hohenheim, Institute of International Management and Innovation (Alexander Gerybadze), financial services and home banking by the Massachusetts Institute of Technology (MIT), Center for Industrial Performance (Richard Lester) and the Sloan School of Management (Edward Roberts). Financially the project was supported by the German-American Academic Council, the German Federal Minstry of Education, Science Research and Technology and the Fraunhofer Society. The project is linked to research in Japan (University of Tokyo and NISTEP, Ryo Hirasawa) and Australia (Australian National University, Canberra, Mark Dodgson), where case studies with overlapping questions are being conducted. This case study impressively shows the far-reaching consequences of new ways in drug development on the research system as well as the industrial system and market structures. A new emerging modular interactive framework for innovation challenges R&D-performing actors and government policy. Karlsruhe, February 2000 Frieder Meyer-Krahmer Director, Fraunhofer Institute for Systems and Innovation Research

6 Contents 1 Introduction 1 Andre Jungmittag, Guido Reger, Thomas Reiss 1.1 New Ways in Drug Development: Changes of the Locus of Innovation Research Approach The National System of Innovation in the United States and Germany 7 Andre Jungmittag 2.1 The Concept of the "Systems of Innovation" Approach Systems of Innovation in the German and US Pharmaceutical Sector Some General Characteristics of the National Innovation Systems of Germany and the US Innovation Systems in the Narrow Sense of the Pharmaceutical Sectors in the US and Germany Regulations Concerning the Pharmaceutical Industry 21 3 Dynamics of the Markets and Market Structure 27 Andre Jungmittag, Guido Reger 3.1 Introduction: Market Categories and Structure Production, Consumption and Employment Foreign Trade and Foreign Direct Investment Conclusions for the International Competitiveness of Selected Countries Innovation Process and Techno-scientific Dynamics 53 Thomas Reiss, Sybille Hinze 4.1 Innovation Process in Pharmaceuticals Characteristics of the Innovation Process in Pharmaceuticals The Importance of R&D for the Generation of Innovation Techno-Scientific Changes Introduction New Ways of Drug Discovery and Development Implications for the Industry

7 viii Contents 5 Generation, Transfer and Exploitation of New Knowledge 71 Angela Hullmann 5.1 Changes in the Division of Labor. 5.2 Alliances of Pharmaceutical Firms Theoretical Background Research Approach Results of the Empirical Analyses Aggregated Analyses Analyses of the Alliances of the Top Twenty Pharmaceutical Companies Country Analyses 5.4 Conclusions Internationalization of Research and Development in Pharmaceuticals 97 Guido Reger 6.1 Introduction R&D and Technological Specialization on Country Level Trends in R&D Expenditure for Selected OECD Countries R&D Output and Technological Specialization of Selected Countries Internationalization Strategies of Selected Pharmaceutical Companies Enterprises Investigated Global Distribution of Patents for Selected Firms Increasing R&D Internationalization in the 1980s and Partly Re-centralization in the 1990s The Formation of Centers of Excellence in Selected Enterprises Factors Affecting the Selection of Locations for R&D The Formation of Regional Innovation Clusters in the US Attractiveness of Germany and the US as Locations for Research and Technology Conclusions Case Study on New Therapies for Selected Autoimmune Diseases Sybille Hinze, Thomas Reiss 7.1 Introduction Statistical Analysis Methodology Results

8 Major Players.... Core Success Factors for Companies in this Field Internationalization and Cooperation New Distribution of Roles in the R&D Process Conclusions Contents IX Summary and Conclusions Andre Jungmittag, Guido Reger, Thomas Reiss Changes in the Innovation Process and Conclusions for R&D-performing Actors Conclusions for Research and Technology Policy 183 References 187 A Top Twenty Pharmaceutical Companies with Subsidiaries 197 B R&D Agreements in the Autoimmune Diseases Area 201 C From the Call for Tender for the NIH Program "Autoimmunity Centers of Excellence" Released in May 1998 (NIH 1998) 215

9 List of Tables 2.1 Financing of the healthcare system Ranking of exports and imports Examples of HTS robotic systems companies 4.2 Examples of combinatorial chemistry companies. 4.3 Examples of genomics companies Top-twenty pharmaceutical companies in Groups of alliances Number of alliances of top-twenty pharmaceutical companies Locations of subsidiaries of top-twenty companies Pharmaceutical enterprises investigated Proportion of patents originating abroad for selected pharmaceutical companies Shares of patents in the US in the fields of biotechnology for selected companies Determinants of the internationalization of technological competences in pharmaceuticals Selection of autoimmune diseases Top 30 patent applicants for autoimmune diseases in the US between 1984 and Top 30 patent applicants for autoimmune diseases in the US between 1992 and Top 20 patent applicants for autoimmune diseases in Germany between 1984 and Top 30 patent applicants for autoimmune diseases in Germany between 1992 and Top 20 patent applicants for autoimmune diseases in Japan between 1984 and Top 30 patent applicants for autoimmune diseases in Japan between 1992 and Top 20 patent applicants for autoimmune diseases in Great Britain between 1984 and Top 30 patent applicants for autoimmune diseases in Great Britain between 1992 and

10 xii List of Tables 7.10 Top 16 patent applicants for autoimmune diseases in France between 1984 and Top 30 patent applicants for autoimmune diseases in France between 1992 and Top 5 patent applicants for autoimmune diseases in Switzerland between 1984 and Top 18 patent applicants for autoimmune diseases in Switzerland between 1992 and Collaboration in autoimmune disease research. Based on SCI data for NIH research programs on autoimmune diseases in the 90s. 172

11 List of Figures 2.1 Systemic structure of innovation systems Shares of pharmaceutical markets Pharmaceutical production in billions PPP-$ Percentage share of the pharmaceutical industry in the manufacturing industry as a whole (1980 to 1994) Consumption-to-production ratios for pharmaceutical products Development of employment in the pharmaceutical industry Development of employment in the pharmaceutical sector as a proportion of employment in the manufacturing industry as a whole Absolute growth in employment in the pharmaceutical industry and in the manufacturing industry as a whole (in %), compared with the relative share of the pharmaceutical industry in overall employment, Exports in pharmaceutical products (billions of US $), Imports in pharmaceutical products (billions of US $), Development of shares in world trade Foreign trade balances (billions of US $), Indices of the development of intra-industrial trade, Shares of intermediate products in foreign trade Stocks of foreign direct investment in 1988 (millions of US $) Market shares of foreign-controlled firms in Levels and annual average growth rates of production of pharmaceuticals in selected countries Levels and annual average growth rates of exports of pharmaceuticals in selected countries Levels and annual average growth rates of employment in the pharmaceutical industries of selected countries Levels and annual average growth rates of labor productivity in the pharmaceutical industries of selected countries Clusters of pharmaceutical industries in selected countries The innovation process in the pharmaceutical industry New ways of drug discovery and development

12 xiv List of Figures Shares of the groups of alliances. Profiles of alliances... Number of different types of alliances in a time scale ( ).... Number of alliances with pharmaceutical and biotechnological companies and others Profiles of alliances of the top twenty pharmaceutical companies Profiles of alliances (continuation) Number of alliances of US, European and German pharmaceutical companies in a time scale. Number of different types of alliances of US, European and German pharmaceutical companies R&D expenditure in billion US$ PPP R&D intensity (in percent), R&D expenditure within the pharmaceutical industry as a proportion of R&D expenditure in the manufacturing industry.. R&D expenditure in the pharmaceutical industry as a proportion of R&D expenditure in industry as a whole. Annual growth of R&D expenditure in pharmaceuticals and in the manufacturing industry of the OECD countries, Patent applications to the European Patent Office in the technological subfields of pharmaceuticals, Specialization (by countries of origin) in the technological field pharmaceuticals in patent applications to the EPO Specialization in subsectors of pharmaceuticals in patent applications to the European Patent Office, and Global distribution of patents for 16 selected enterprises in pharmaceuticals. Internationalization of R&D increases with high foreign turnover and limited domestic market Comparison of the two indicators "percentage of patents abroad" and "R&D expenditure abroad"... Patent share abroad and growth rate of patents between and Competencies in research centers of selected pharmaceutical enterprises, by therapeutic areas "Stylized facts" : organization of research and development in a highly internationalized pharmaceutical enterprise

13 List of Figures xv 7.1 Distribution of insulin-dependent diabetes mellitus cases by region Scientific publications on autoimmune diseases in the Triad as covered by the database MEDLINE Scientific publications on autoimmune diseases in European countries (MEDLINE) Patent applications at the EPO Patent applications at the EPO (European Countries only) 7.6 Relative patent specialization in the field of autoimmune diseases Alliances in autoimmune diseases by partners involved Types of agreements between pharmaceutical companies only (N=20) 7.9 Types of agreements between pharmaceutical companies and biotech firms (N=138) Types of agreements between biotech companies only (N=46) Types of agreements between research institutions and biotech companies (N=79)