Academician and Distinguished Research Fellow Academia Cinica Perspective of Biomedical Industry in Taiwan: Challenges and Opportunities Chien-Jen Chen, Sc.D. Academician and Distinguished Research Fellow Academia Cinica

IMD World Competitiveness Yearbook Taiwan Rank in 2005-2009 Item 2005 2006 2007 2008 2009 Overall performance 11 17 18 13 23 infrastructure 16 21 Technological 5 4 15 Scientific 8 6 Source：The World Competitiveness Yearbook 2005-2009, International Institute for Management Development (IMD). 57 economies were ranked.

IMD World Competitiveness Yearbook, 2009 Items USA HK Singapore Switzerland Sweden Japan China Taiwan Korea India Overall performance 1 2 3 4 6 17 20 23 27 30 1. Economic performance 8 13 24 45 12 2. Governmental efficiency 10 40 15 18 36 35 3. Industrial efficiency 16 37 22 29 11 4. Infrastructure 19 5 32 57 (1) Fundamental 7 (2) Technology 9 21 14 (3) Science (4) Health and environment 53 39 (5) Education 26 49 Source：International Institute for Management Development (IMD) World Competitiveness Yearbook, 2009 57 economies ranked

WEF Global Competitiveness Report, 2009-2010 Indices Switzerland USA Singapore Sweden Denmark German Japan Hong Kong Taiwan Korea China Overall performance 1 2 3 4 5 7 8 11 12 19 29 Infrastructure 28 27 6 18 23 36 Efficiency 14 17 20 32 Innovation 10 16 Source：WEF (World Economic Forum) Global Competitiveness Report, 2009-2010 133 economies included in 2009 report

WB Knowledge-based Economic Development, 2009 Rank Denmark Sweden Finland USA Taiwan Singapore Japan Hong Kong Israel Korea World 1 2 3 9 18 19 20 23 26 29 Asia - 4 5 6 Source：World Bank, Knowledge-based Economic Development 2009 146 economies are ranked

R&D Budget and Manpower in OECD Countries, 2007 綜合上述資料，同時比較世界主要國家投入研發的人和錢，我國的大致位於這張圖的中間位置，表示我國具有良好的研究人力素質，並且積極投入研發所需的經費。 Source：Main Science and Technology Indicators, 2007/1, OECD. 註：圓圈的面積表示研發經費的多寡，研發經費係以購買力平價折算

Number and Rank of Research Papers in Taiwan, 2004-2008 Indices 2004 2005 2006 2007 2008 SCI papers 13,621 16,721 17,846 18,571 22,509 　Rank 18 17 16 Citations＊ 144,466 174,910 203,941 234,766 280,357 24 23 22 Average citations＊ 2.45 2.65 2.81 2.94 3.14 EI papers 10,980 11,661 13,076 16,657 17,124 11 9 10 SSCI papers 785 1,030 1,226 1,548 2,236 20 15  world average of citation per SCI paper in 2004~2008 was 4.70。 7

Number of U.S. Utility Patents Country 2003 2004 2005 2006 2007 2008 NUP Rank USA 87,893 1 84, 271 74,637 89,823 79,526 77,051 Japan 35,515 2 35,348 30,341 36,807 33,354 33,682 Germany 11,444 3 10,779 9,011 10,005 9,051 8,915 Taiwan 5,298 4 5,938 5,118 6,360 6,128 5 6,339 Korea 3,944 4,428 4,352 5,908 6,295 7,519 Nether-lands 1,325 11 1,273 12 993 1,323 1,250 1,329 10 China 297 22 404 20 402 18 661 16 772 1225 Source：U.S. Patent and Trademark Office NUP, Number of Utility Patent

Leading Industry/Products in Taiwan, 2008 世界排名第一 (10項) 世界排名第二 (12項) 世界排名第三 (7項) 晶圓代工 IC design 印刷電路板 Mask Rom DRAM PU合成皮 IC封裝 WLAN PTA IC測試 OLED面板 聚酯絲 TN/STN LCD面板 大型TFT-LCD面板(>10”) 耐隆纖維 PND 中小尺寸TFT-LCD 面板 筆記型電腦 電解銅箔 LED --胡蘿蔔素 光碟片 玻纖布 電動代步車與電動輪椅(失能人士用機動車) IC載板 TPE 綠藻 ABS 主機板 資料來源：經濟部技術處ITIS計畫。不含海外生產 9

Knowledge-based Economy Globalization and Value-addition Biotech Information and communication Electrical/ mechanical engineering Agriculture BC6000 1769 1947 2000 Time and Technology Source：The Coming Biotech Age, Richard W. Oliver

Biotechnology R&D in Taiwan: A Brief History Since 1995, the biotech industry has been recognized as one of the most important industries in Taiwan. It was regarded as one of the “rising star” industries in the 6-year “Two Trillions, Two stars” national development plan in 2002. Recently, the healthcare industry has been identified as a major target of the “Economic Development Vision for 2015.” Biotechnology has become an important sector for scientific research, technology innovation, and industrial development in Taiwan, as is the case elsewhere in the world. Its aim is for Taiwan to become a global partner in biotech innovation and commercialization, and to be the Asian hub for biotechnology.

Biotech Industry in the World, 2006 USA EU Canada Asia Pacific Companies 4,275 1,452 1,621 465 737 Revenue (Billion US$) 735 555 115 32 33 R&D budget (Billion US$) 28 23 4 1 0.4 Ernst & Young Global Biotechnology Report 2007

Biotech Industry in Taiwan, 2006 World Taiwan Emerging biotech (billion US$) 160 1.3 (0.8%) Medical devices (billion US$) 170 2.0 (1.2%) US Biotech patents - Rank: 15th Preclinical trials 907 17 (1.9%) Phase I trials 580 2 (0.3%) Phase II trials 615 1 (0.2%) Phase III trials 260 2 (0.8%) Taiwan DCB ITIS Report 2007

Current Status of Biotech Industry in Taiwan, 2006 Emerging biotech Pharma-ceuticals Medical devices Total Revenue* 1.29 1.94 2.06 5.29 Export* 0.51 (40%) 0.39 (20%) 0.88 (42%) 1.78 (34%) Import* 0.56 1.77 1.34 3.67 Domestic market demand* 1.33 3.34 2.53 7.20 *Billion US$ Biotechnology and Pharmaceuticals Industry Program Office, MOEA, 2007

SWOT Analysis of Biomedical Industry in Taiwan: Strength . High-priority industry supported by government . Well-implemented National health insurance system . Excellent clinical research activities in 17 medical centers and regional hospitals . Strong electronic and ICT industries . Excellent scientists and technologists in biomedical R&D organizations and industries

SWOT Analysis of Biomedical Industry in Taiwan: Weakness . Lack of integration of basic research and technological development . Lack of integration of governmental agencies . Lack of foreign or local capital investment . Lack of successful story . Lack of senior managerial experts . IPR protection and biosafety regulation needs improvement . Small local market and lack of experiences in international marketing

SWOT Analysis of Biomedical Industry in Taiwan: Opportunity . Huge market in Asia-Pacific Region . Trend of individualized medicine . Global collaboration of high value-added industries . Rapid development of biomedical R&D service industries . Biomedical industry for unique Chinese diseases . Increasing need in health care of aging population

SWOT Analysis of Biomedical Industry in Taiwan: Threat . Competition with neighboring Asian countries . Competition with high-tech products from developed countries . Competition with low-cost products from developing countries . Competition for Chinese talents and international investments

Biotechnology R&D in Taiwan Type of Research Governmental Funding Agencies in R&D Universities & Governmental Research Inst. Non-profit Research Institutes Industries Fundamental Research Applied Research Implementation NSC, MOE, DOH Universities, Academia Sinica, etc. MOEA, MOTC, MOD, COA, DOH, EPA, etc. ITRI, NHRI, NARL, NSRRC, etc. Nuclear Energy Research Institute, ChungShan Institute of S&T, etc. Public/ Private Enterprise Research Laboratory Technology Development

Biomedical Technology Research Programs National Science and Technology Program Biotechnology and Pharmaceuticals Genomic Medicine Nanoscience and Nanotechnolog Industrial-Academic Cooperative Researches Integrated Program Projects Individual Research Projects

NTPS for Biotechnology and Pharmaceuticals

Drug Discovery Preclinical Trial Clinical Trial Commercialization National Science and Technology Programs for Biotechnology and Pharmaceuticals Drug Discovery Preclinical Trial Clinical Trial Commercialization National Science Council (NSC) Ministry of Economic Affairs (MOEA) Department of Health (DOH) Enterprises Biotechnology Chemical Synthesis Natural Products Formulation Investigational New Drug (IND) I Phase II III Pharma-cology New Drug Application (NDA) NCE Toxicology Drug Marketing Phase IV ADME MDS Pan Lab Center for Drug Evaluation R&D Institutes (DCB, BMEC, PDC ATIT, INER) Medical Center Bio/pharm Companies Bio/pharm Companies Universities Research Institutes

NTPS for Genomic Medicine To capitalize on the knowledge embodied in the human genome sequence in order to Develop Taiwan's visibility and international competitive edge in bio-medical research Act as an initiator for the local bio-medical industry

National Research Program for Genomic Medicine CANCER LIVER LUNG ELSI INFECTIOUS DISEASES HIGHLY HERITABLE DISEASES INNOVATIVE RESEARCH Bio-medical Industry

NTPS for Nanoscience & Nanotechnology Through the establishment of common core facilities and education programs to achieve academic excellence in basic research, to create innovative industrial applications, and to speed up the commercialization of nanotechnology. Education programs Industrialization Nanotechnology Academic Excellence Establishment of Core Facilities

Manufacturer investment Unit:USD Budget (2004~2008) Year　 2004 2005 2006 2007 2008 Budget 122.4 M 115.0 M 119.7 M 89.7 M 91.1 M Output & Outcome (2004~2007) Publication Talent training Patent Technology transfer Manufacturer investment 4,983 5,763 226 5.3 M 46.9 M

R&D and Industrialization

2005-2006 Pharmaceutical Industry in Taiwan millions US$ Category Turnover Export Import Demand in Taiwan 2005 2006 Bulk# 471 1,187 207 174 465 1,358 729 2,371 Chemical Drugs 1,387 761 155 229 1,394 681 2,626 1,213 Chinese Herbal Medicine* 181 10 39 3 213 148 355 Total 2,013 2,129 372 442 1,862 2,252 3,503 3,939 # Bulk of 2006 including human and animal usages. * Chinese Herbal Medicine of 2006 including herbal medicine preparations and medicinal herbs. Data from PITDC and Biotechnology Industry in Taiwan, 2006 & 2007

Biomedical Engineering Research Laboratories , ITRI (BEL)

ITRI Biomedical Engineering R&D Biomedical Engineering laboratory Medical Electronics and device Technology Center Medical Device Research Molecular Diagnostic Research

Biomedical Engineering Research Laboratories , ITRI (BEL)

Mission　 The Center's mission is to offer guidance and advice on relevant technology to the domestic pharmaceutical industry; strive to develop key technology for new products; realize the industrial development of high quality products; and open up the international market. The Center is highly committed to the development of new Chinese and Western medicines and becoming an international R&D center.

DCB R&D Programs and Facilities Environmental Biotechnology Program Pharmaceutical Program Herbal Medicine Program Biopharmaceutical Program GPCR Drug Discovery Facility Center of Toxicology and Preclinical Sciences Biopharmaceutical Pilot Plant Facility

National Health Research Institutes Division of Biotechnology and Pharmaceutical Research Division of Medical Engineering Research Vaccine Research and Development Center

Supervision and Regulation of Biotechnology Industry

Regulation of Drugs and Medical Devices in Taiwan ■ Regulatory Agencies Taiwan Food and Drug Administration (TFDA) Bureau of Pharmaceutical Affairs (BPA) Center for Drug Evaluation (CDE) Committee on Chinese Medicine and Pharmacy (CCMP)

Bureau of Pharmaceutical Affairs

Center for Drug Evaluation (CDE)

http://www.ccmp.gov.tw/en/index.asp Committee on Chinese Medicine and Pharmacy (CCMP) Department of Health, Executive Yuan

National Centers of Excellence for Clinical Trial and Clinical Research National Taiwan University Hospital National Cheng-Kung University Hospital Tri-Service General Hospital Taipei Municipal Wan-Fang Hospital

Number of New Clinical trials in Taiwan 2005 2006 Phase I 14 12 Phase II 33 32 Phase III 69 86 Phase IV 4 3 Total 120 133 Taiwan ranks third in “Country Rankings in Clinical Medicine” in the Asia Pacific, just after Japan and Australia.

Chinese Medicine Clinical Trial (I) 22 cases of IND analysis (2001-2005) : Inherent prescription: 2 cases New compound: 12 cases Foreign compound: 3 cases Patrimonial recipe: 2 cases New officinal plant: 1 case Partial purified articles in Traditional Chinese herbal medicine: 2 cases

Chinese Medicine Clinical Trial (II) 22 cases of IND analysis (2001-2005) : Phase I : 1 case Phase II : 12 cases Phase III : 7 cases Pilot study : 2 cases The first new Chinese medicine license has been issued under the authorization of the DOH.

Laws for Biotechnology Development The Basic Law for Science and Technology provides intellectual property management-related measures to encourage patent application and technology transfer. Incentives are also offered to researchers and their institutions for their engagement in academic-industrial collaborative R&D. A new Act for Development of New Drug Industry, which aims to facilitate the establishment of new companies specializing in pharmaceutical R&D, has recently been passed by the Legislative Yuan (Congress). Incentives given include tax reduction, participation of government employees in the biotech industry, etc.

Science Parks: Biotech Company Clusters Lungtan Base (107h) Hsinchu Biomedical Science Park (38h) Hsinchu Science-based Industrial Park (625h) Ilan Base (101h) Chunan Base (141h) Tungluo Base (350h) Houli Base (255) Central Science-based Industrial Park Taichung Base (413h) Huwei Base (97h) Total area: 3,743 hectares Hsinchu Science-based Industrial Park: 1,362 hectares (semiconductor and IT industries) Central Science-based Industrial Park: 765 hectares (nano-based optoelectronics, aerospace and precision machinery industries) Southern Science-based Industrial Park: 1,616 hectares (optoelectronics industry) Southern Science-based Industrial Park (1,038h) Kaohsiung Base (570h) Kaohsiung Biotechnology Industrial Park

Investment in Biotechnology R&D National Development Fund provides investment and financing to underpin private sector investment in the biotech industry. Incentives are given to the investment of venture capitals in biotechnology.

Conclusion Through the above-mentioned integrated efforts to promote scientific research, technology innovation and industry development in biotechnology, Taiwan will be on its way to becoming a biomedical technology island and will play an important role in international biotechnology industry.

Thank You!

政府在生物醫藥研發扮演的角色 創造適合生物醫藥產業發展的有利環境 發展完善的生物醫藥研發基礎建設 培育及延攬各級生物醫藥研發人才 支持生物醫藥研發的國際合作研究 鼓勵生物醫藥研發成果管理、技術轉移及產 業應用

台灣生物醫藥產業發展策略: 強化轉譯研究 加強臨床前動物實驗及臨床一、二期試驗相關之轉譯研究與組織架構。 台灣生物醫藥產業發展策略: 強化轉譯研究 加強臨床前動物實驗及臨床一、二期試驗相關之轉譯研究與組織架構。 建立符合GMP之蛋白質及生物製劑量產設施，以作為臨床實驗及商業製造之用。 鼓勵現有製造學名藥、原料藥或小分子化合物中間產物之GMP設施升級，以製造可供臨床實驗之創新產品。

臺灣生物醫藥科技研發體系 執 行 機 關 推動機關 政府機構 學校及研究機構 財團法人 企 業 界 負責 單位 研究 層次 基礎研究 執 行 機 關 負責 單位 推動機關 研究 層次 政府機構 學校及研究機構 財團法人 企 業 界 中央研究院 教 育 部 國 科 會 中央研究 院各所 各大學系所 基礎研究 工 研 院 食 品 所 資 策 會 生 技 中 心 國 研 院 同步輻射中心 國 衛 院 等 應用研究 中 科 院 核 能 所 勞 安 所 政府所設 之各類研 究所 經 濟 部 國 防 部 交 通 部 農 委 會 原 能 會 衛 生 署 環 保 署 公民營 企 業 技術發展

台灣生物醫藥產業發展策略: 改組生技中心 改組生技中心成為「生技醫藥臨床前研發中心」。 改善組織與薪資結構，禮聘有經驗之執行長及專業人才。 台灣生物醫藥產業發展策略: 改組生技中心 改組生技中心成為「生技醫藥臨床前研發中心」。 改善組織與薪資結構，禮聘有經驗之執行長及專業人才。 足夠資金、能力與誘因以主動尋找並承接國內早期創新研發成果，協助開發至可供臨床試驗階段，再技轉業界。 提供業界臨床前動物試驗，及臨床試驗用藥品之量產服務，並由服務及技轉取得現金與股票等回饋。

台灣生物醫藥產業發展策略: 成立生技創投基金 台灣生物醫藥產業發展策略: 成立生技創投基金 提升「行政院開發基金」投資於生技製藥的專業能力，或成立專屬生技製藥之創投基金。 延攬具有國際創投經驗之專家，善用基金，積極主動尋找、分析早期創新研究成果，或已接近上市之後期產品之可行性及獲利性，將初期研發成果落實在產業發展，且與金融資本市場接軌，形成生技產業聚落。

台灣生物醫藥產業發展策略: 整體布局 利用技轉或合作模式取得高階醫療器材及在初期臨床實驗之新藥的智慧財產權及相關製造、行銷權益，並建立生產設施。 工研院加強協助研究機構及業界開發高階醫療器材及精密生醫儀器。 結合中研院、研究型大學、生技中心、國衛院、卓越臨床實驗中心及業界，共同完成臨床前及臨床試驗，開發有智慧財產保護的小分子及生技藥品。

台灣生物醫藥產業發展策略: 法規鬆綁 落實「科學技術基本法」，加強人才延攬與技轉，並鼓勵創業。 調整公教人員及產業專家人員之薪資結構 台灣生物醫藥產業發展策略: 法規鬆綁 落實「科學技術基本法」，加強人才延攬與技轉，並鼓勵創業。 調整公教人員及產業專家人員之薪資結構 提升藥品及醫材審查之品及效率。 修訂「生技新藥產業發展條例」施行細則，使從事新劑型及新用途之藥品及醫療器材，且須進行臨床試驗者得以適用。

台灣生物醫藥產業發展策略: 建立生醫科技園區 台灣生物醫藥產業發展策略: 建立生醫科技園區 園區名稱 園區設施特色 園區經營方向 新竹生物醫學園區 ‧分醫學研究中心區及產業專用區兩大區塊(醫學、育成、研究中心 ) ‧以臨床醫學為主 ‧轉譯醫學研究與相關產品開發 ‧癌症與腦心血管疾病之主題以及生醫電子影像領域研究 竹南園區生技聚落 ‧園區內包括：國家衛生研究院、台灣動物科技研究所 ‧ 30單位生物科技標準廠房 ‧以生物晶片及醫療器材為發展重點 ‧可配合國衛院及動科所的腫瘤治療與胚胎研究 高雄園區醫療器材專區 ‧人工植入物及手術工具 ‧醫療儀器 ‧醫療用機器人及輔具 ‧與「金屬工業研究中心」合作 ‧結合南部地區既有金屬產業聚落如金屬製造﹑加工﹑鑄造﹑模具等，設置14公頃專區，發展生技醫療器材產業

台灣生技醫藥產業發展的願景 全球生技醫藥產業研發及商業化不可或缺之重要環節 具特色之亞太生技醫藥產業發展樞紐： 亞洲多發性疾病研發及臨床中心 生技及藥物重要量產基地 醫療工程應用及產製中心 亞洲生技醫藥創業投資重鎮 未來五年生技產業營業額年平均成長25%，帶動1,500億元投資 十年內成立500家生技公司，促成成功投資案例

敬請指教！

藥物法規發展趨勢:生技學名藥 1990-2005年，美國核准新藥(NME)總數達449個，其中27個是生技藥品(NBE)；EMEA核准127個新藥中有44個是生技藥品。近10年生技藥品快速成長。 2005年全球生技藥品的銷售額達530億美元。 2005～2010年多項生技藥品專利到期，將創造近200億美元的市場。 生技學名藥未來市場快速擴大，歐盟與亞太區域國家正研擬相關法規，國內目前尚未有相關規範可供產業依循。

亞洲新興生技產業的共同現況 以製造或低成本為政策思維 政府扮演主導推動的角色 許多新興的小型公司，技術及基礎建構尚發展中 缺乏具有商業化潛力的技術成果 智財保護與法規國際化是最大的挑戰

亞洲新興生技產業的發展利基 委託研究與生產(CRO、CMO) 專利過期的藥物 跨領域生醫工程 傳統草藥 成本、專業品質 學名藥(Generics)=>廣大人口市場、價格/成本 生技學名藥(Biosimilar) =>高技術層次(智財權保護)、高資本投資(cGMP plant)、法規障礙 跨領域生醫工程 醫療器材、生物材料、生技檢測儀器、生物資訊等 傳統草藥 科學化醫藥研究 功能性保健品、植物性新藥

台灣新興生技產業已漸成型 200家至少30年歷史的GMP學名藥藥廠，主要競爭台灣40%藥品市場。 國際藥廠及代理商在台約40家，競爭台灣另60%藥品市場。 300家的新興生技公司，與製藥相關約佔30%，大多成立5-6年尚在研發階段。 2005年國內研發新藥pipelines共55項；有29項在國內外執行臨床試驗，其中生技藥品1項、中藥新藥20項。 資料來源：生技中心ITIS計畫調查整理

台灣的醫療市場與品質仍不容忽視 我國雖內需市場小，但市場成長率高，且醫療消費能力強，藥品之購買能力高於中國、印度等其他亞洲國家 項目 新加坡 南韓 印度 中國大陸 日本 基本資料 人口（百萬） 4.4 22.9 48.6 1,080.3 1,306.3 127.4 GDP/人（美元） 26,546 15,118 16,027 705 1,458 35,316 競爭指標 製藥市場（百萬美元） 515 3,900 8,063 8,800 19,158 66,200 醫療支出/人 (美元) 117.0 170.3 165.9 8.1 14.7 519.6 製藥市場成長率（%） 4% 7.0% 7.5% 7.2% 8.5% 0.5% 資料來源：Frost & Sullivan;生技中心ITIS計畫整理