医療分野でのイノベーションの実現に向けて Toward the realization of innovation in the healthcare sector 経済産業省大臣官房審議官（産業技術担当）徳増有治 Yuji Tokumasu Deputy Director-General for Industrial Science and Technology Policy, Ministry of Economy, Trade and Industry 自律的イノベーションを阻害している市場の構造的要因 Structural factors inhibiting the self-sustaining innovation in the market １．国の財政支出を安定化させるために、投資意欲のある市場そのものの発展を阻害 Inhibition of the spontaneous growth to an attractive market for Investors, for the purpose of stabilization of government spending ２．行政的対応による公的管理のため科学技術の進歩、社会環境変化等への対応の遅れ Slow response to the progress in scientific technology and changes in the social environment, due to bureaucratic responses in public management ３．公定価格、情報開示の遅れのため、コストの削減意欲、質の向上意欲の阻害 Reduced motivation to cost reduction and quality improvement, due to official prices and the delay in information disclosure 医療費の推移 3 自律的イノベーションを阻害している市場の構造的要因 Structural factors inhibiting the self-sustaining innovation in the market １．国の財政支出を安定化させるために、投資意欲のある市場そのものの発展を阻害 Inhibition of the spontaneous growth to an attractive market for Investors, for the purpose of stabilization of government spending ２．行政的対応による公的管理のため科学技術の進歩、社会環境変化等への対応の遅れ Slow response to the progress in scientific technology and changes in the social environment, due to bureaucratic responses in public management ３．公定価格、情報開示の遅れのため、コストの削減意欲、質の向上意欲の阻害 Reduced motivation to cost reduction and quality improvement, due to official prices and the delay in information disclosure ４．均質が優先されることによる競争的環境の阻害 Inhibition of competition, due to a preference for homogeneity ５．旧来的技術、手法、考え方に対する旧来的安全規制のため、 Conventional safety regulations for conventional technologies, methods and thinking, resulting in: ○ 科学技術の急速な進展や社会情勢変化に対応した効用とリスクのバランスの欠如 Lack of a balance between risks and benefits that responds to the rapid progress of scientific technology and changes in the social situation ○ ベンチャー企業や、市場のない新規技術（再生医療等）に対する経営実態や社会的（国民的）意義に対する配慮の欠如 Lack of consideration for the business status and the social (national) meanings of venture companies and new technologies without markets (such as regenerative medicine) The Trend of Bio-venture • • • • 日本のバイオベンチャーは５００社を超える規模にまで拡大。 Japanese bio-venture will expand to more than 500 corporations. バイオ関連分野に対する新規投資先社数は増加傾向。 The number of corporations associated with bio related sector to be newly invested has an increased trend. 図４バイオベンチャー企業数の海外比較図３バイオベンチャーの企業数推移 Chart 4 Comparison of Numbers of Bio-venture Corporations in the World Chart 3 Transition of the Numbers of Bio-venture Corporations Number of Corporation 600 531 464 500 387 400 304 300 333 Source: “The Bioindustry Infrastructure Project Report for the year 2002” 図５ＩＴ、バイオ関連新規投資先推移（社数比率） 254 Chart 5 Transition of IT and Bio Related New Investment (Comparison of Numbers of Corporations) 212 200 102 116 132 150 167 60% 50% 100 0 ＩＴ関連バイオ／医療／ヘルスケア 40% 年度 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 Source: “The Bio Venture Statistical Survey 2005”, the Japan Biondustry Association 30% 20% 10% 0% 98年 99年 00年 01年 02年 03年 04年 05年 Source: “Investment Trend Survey including Venture Capital”, VEC 6 創薬分野におけるベンチャーへの期待 Expectations for Venture in the Drug Discovery Sector • In the USA, on contrary to the number of new drugs placed onto the market by major pharmaceutical corporations, the number of approval of new drugs produced by bio-venture corporations has continued to be increased, and its number of releases exceeded that of major corporations. The role of venture corporations has been enhanced in the innovative seeds development where there are high risks, which major pharmaceutical corporations have difficulty in being involved, as drug discovery becomes more advanced and complicated. • Chart 7 Big Pharma’s and Biotech’s R&D Budget and Number of Chart 6 Number of Corporations and Its Structure Releases in the USA in relation to the Origin of New Medical Product Ｒ＆Ｄ費用ＦＤＡ新規化合物認可数（件）（ｂｉlｌ＄） R&D 費用（Big pharma) R&D 費用（Biotech) Component Development 70 米国 33 フランス 5 23 60 0 日本 7 その他スペイン 3 スイス 3 オランダ 2 英国 20 40 0 15 0 0 3 30 製薬企業ベンチャー企業 1 ベンチャーは増加 20 4 4 イタリア 25 2 5 韓国大手製薬は減少 50 0 8 30 認可件数（Biotech) 0 22 ドイツ認可件数（Big pharma) 10 1 5 10 0 10 20 30 40 50 60 Source: Report by the Office of Pharmaceutical Industry Research 0 1998 1999 2000 2001 2002 2003 2004 0 2005 年（Source ：Ernst & Young Beyond Borders Global Biotechnology Report 2006） 7 バイオベンチャーを巡る厳しい状況（投資環境） Difficult Conditions Surrounding Bio-venture (Investment Climate) • In comparison to Europe and the USA, Japanese venture capital investment climate is extremely weak. 図６ベンチャーキャピタル投資額の対ＧＤＰ比率の国際比較（２０００～２００３年） Chart 6 International Comparison of Venture Capital Investment in comparison to GDP Ratios 図７日米欧のベンチャーキャピタルの投資残高の推移 Chart 7 Transition of Remaining Venture Capital Investment Value in Europe, the USA, and Japan (％) Note 1: Investment in the early stage and expansion stage Note 2: Japan and Korea take the values from 1998 to 2001, and Iceland takes the values from 2000 to 2002. Source ：OECD「OECD Science, Technology and Industry Scoreboard 2005」 Note 1: 107 yen/dollar conversions for the USA. Note 2: 139 yen/euro conversions for Europe. Source: “Investment Trend Survey including Venture Capital (the year 2005)” 8 バイオベンチャーを巡る厳しい状況（アライアンス） Difficult Conditions Surrounding Bio-venture (Alliance) • • In comparison to Europe and the USA, the alliances of major pharmaceutical corporations and bio-venture corporations in Japan are weak. The expenditure on research funds from Japan to overseas institutions is especially large in the pharmaceutical industry. Chart 11 Transition of Number of Alliances by Major Pharmaceutical Corporations in Europe, the USA, and Japan Chart 12 Percentage of Development Funds to Overseas, Outside the Company プラスチック製品工業 0.7% 電子部品・デバイス工業 1.1% 情報通信業 1.3% 機械工業 2.5% サービス業 2.8% その他の工業 3.3% 化学工業 3.3% 食品工業 0.7% 非鉄金属工業 0.7% 電気・ガス・熱供給・水道業 0.7% その他 4.3% 医薬品工業 36.4% 電気機械器具工業 3.6% 精密機械工業 6.5% 輸送用機械工業 15.1% 情報通信機械器具工業 16.9% Source: Created by the Ministry of Economy, Trade and Industry from “The Scientific Technology Development Study Report (annual)”, the Ministry of Internal Affairs and Communications 9 • In order to stimulate Japanese economy, creating technological innovation by strengthening industrial technologies and utilizing seeds of technology for actual application and commercialization in the market through research and development is a pressing issue. The issue is that advanced scientific technology and its achievements are not applied into business. (Presence of “Valley of Death”) On “Valley of Death” ~ From the materials presented by NIST* at a OECD Workshop” The Wall of Nonsense Why is it so tall? Why is it so stiff? To begin with, why is a wall necessary here? → Unfortunately, no one can understand! ←Easy 資金調達の容易さ • ﾍﾞﾝﾁｬｰｷﾔﾋﾟﾀﾙエンジェル Difficult→ The Valley of Death Because it is difficult to determine whether a specific technology can be commercialized or not in the development and scale-up phase between “basic study phase” and “release”, funding is not easy. The gap between the research phase and release is recognized to be an issue as “The Valley of Death” in the USA as well. “死の谷” Basic Study Development, Scale-up Release * NIST: National Institute of Standards and Technology １ 10 The Flow to Realize Institutional Reforms in Medical Care and Health Industries Life Science Summit (April 2006) Indicate the importance of clinical trial reformation and promotion of health industries based on the collaboration of industry, government, and academia. Life Science Federation of LDP Diet Members declares their initiative in clinical trial reformation. Economic Growth Strategy Outline (July 2006) As well as promoting research and development of medical products and equipment, the infrastructure to deliver them promptly to citizens is necessary, and communication between public and private sectors will be carried out proactively in order to actualize these objectives. Life Science Federation of LDP Diet Members Chairman Omi, Acting Chairman Tanigaki, and Secretary-general Hosoda August 2006, establishment of a special committee on clinical trial reformation December, a resolution on activation of clinical trial and clinical researches, acceleration of approval examinations, and establishment of communication between public and private sectors is adopted. Group on Regeneration Medicine of Diet Members December 2006, proposes a legislation by members on the conversion of one’s own cells Japan Association of Bioindustries Executives (JABEX)/JBA Release an interim report on proposals for the enhancement of the clinical trial system and acceleration of approval examinations in December 2006 Policy Speech by Prime Minister Abe (September 2006) ○ Submit “Innovation 25”, a long-term strategic guideline on medicine, etc., which will contribute to growth. Execution. Council for Science and Technology Policy, Cabinet Office (December 2006) Provide an opinion on the activation of clinical trial and clinical researches and acceleration of approval examinations (promotion of regeneration medicine) to the government as an institutional reform that leads to application of research and development. Examination starts at Council on Fiscal and Economic Policy Elimination of complete regulations, transition to the growth strategy Establishment of “Communication for Innovative Drug Discovery between Public and Private Sectors” (January 2007) Hold the Second Communication between Public and Private Sectors (April 2007) Formulate the Five-year Strategy for Innovative Drug Discovery Formulate government policies Promote institutional reforms Ensure policy effectiveness ○Transfer the policy focus on medical and nursing care to prevention and promote “New Health Frontier Strategy” to increase healthy life expectancy. Measures and Policies presented by Prime Minister Abe (January 2007) ○Support for development of medical products that have drastic effects and reformation of regulations in the medical industry are necessary. ○Formulation of “New Health Frontier Strategy”. Japan Science and Technology Agency December 2006, proposes the reformation of clinical trial system Examination of Innovation 25 starts (November 2006) Doubled number of PMDA judges (January 2007) Revision of the Pharmaceutical Act in regard to regeneration medicine (March 2007) Establishment of “New Health Frontier Strategy Council” (November 2006) Overview of Five-year Strategy to Create Innovative Medical Products and Equipment Provide the world’s most advanced medical products and equipment to citizens Have the pharmaceutical and medical equipment industries be a driving force of Japan’s growth April 2007 MEXT ◎MHLW METI Measures and Policies aiming for Japan-lead Development and Simultaneous Worldwide Development including Japan ①Concentrated Input of Research Funds • Prioritize and expand budgets related to medical products and equipment • Establish an industry-governmentacademia organization to coordinate research sectors to be emphasized • Examine the expansion and enhancement of a research and development tax system ②Development of Venture Corporations and so on • Expand research funds • Share institutions and equipment and so on • Establish a support system for corporatization, utilize experienced personnel, improve consultation services, etc. • Examine a possibility of support for examination charges • Examine measures to promote the provision of medical equipment ⑦Communication between Public and Private Sectors ③ Improvement of Clinical Research and Clinical Trial Conditions ⑤ Acceleration of Examination Processes and Improvement of Examination Quality • Promote international joint clinical trials • • Establish “Medical Care Cluster” which precedes clinical researches by close collaborations of industries, government and academia, lead by national advanced specialized medical institutions, in regard to diseases that greatly impact citizens Shorten the period by the release of a new drug by 2.5 years (eliminate the drug lag) • Double the number of judges and improve their quality (increased by 236 people over 3 years) • Clarify the approval examination procedure and standards and improve the operation of GCP • Establish a bridge-building research center, a regeneration medicine center, and a clinical research system • Create guidance for international joint clinical trials and carry out consultations of preferential clinical trials • Have a center of clinical trials, establish network and utilize IT for clinical trials, involving medical care clusters • Discuss about the introduction of joint clinical trial consultations among examining authorities in Europe, the USA, and Japan • Train and recruit personnel who support medical doctors and clinical researches • • Take measures to improve the evaluation of clinical performance of medical doctors and so on Promote streamlining and simplification of examinations of clinical trials and approval while maintaining safety of medical equipment • Improve and train judges for medical equipment • Promote the appropriate regulation for clinical researches • Improve the operation of medical equipment GCP ④Collaboration in Asia • Promote joint researches on important diseases • Joint researches on application methods of data collected in East Asia Strengthen the collaboration among related Ministries, research institutions, and industries. ⑥Appropriate Evaluation of Innovation Examine more appropriate evaluations of innovative products in the NHI drug price scheme and so on Have periodical communication between public and private sectors 12 Great achievements in basic studies are not applied to medical care researches and actual scenes. ○Many research papers are published in relation to the basic study sector, but the number of research papers published is extremely small in the clinical sector. The Number of Judges in Examining Authorities USA: 2200 France: 900 UK: 690 Japan (New): About 430 Japan: 190 Acquisition of Regulatory Science Quality and Quantity of Science Germany: 1100 Safety Level 世界初の上市から、各国での上市までのイメージ Illustration of the Process from the First Release in the World to Releases in Each Country Large Amount of Time European Countries and the USA Japan Disadvantages to citizens and inhibition of their selections Increased burden on citizens and increased medical service fees ↓ Loss of economic efficiency and increased non-released products Scientific Safety to be Ensured 4 years Cost Required for Examination 1.5 years Cost Required for Examination Cost Required for Examination The First Release (Approval) in the World Time Required for Examination Safety Level 世界初の上市から、各国での上市までのイメージ Illustration of the Process from the First Release in the World to Releases in Each Country Number and quality of judges (Medical doctor, statistic, engineering, etc.) Quality and quantity of science at examinations are the parameters Approval Scientific Safety to be Ensured Ｘ In particular, regeneration medicine and advanced medical equipment/device 1.5 years 4 years Relinquish ment Time Required for Examination Basic Concept of Technology Development to Promote Bridging between Basic Studies and Clinical Researches Basic Study Basic Study Basic Study Basic Study R&D Phase Bridge-building Study Portfolios for Promoting Bridge-building Studies Research for Practical Application ③ Demonstration Study for Regulatory Science Support Study for Scientific Regulation & Examination Basic Study ② Initiative Study Large-scale Clinical Research (Drug discovery, Diagnosis, Regeneration, Treatment) ① Bridge-building Study PJ Establishment of Regulatory Science Development of Innovative Medical Technology