Introduction of Chunghwa Chemical Synthesis & Biotech Co., - PowerPoint PPT Presentation

Introduction of Chunghwa Chemical Synthesis & Biotech Co., Ltd. Chunghwa Chemical Synthesis & Biotech Co., Ltd.

Brief History of CCSB Profile  Founded in 1964  First registered and one of the largest bulk pharmaceutical chemical manufacturers in Taiwan  First Taiwan FDA approved plant (1984)  Turning Points in 1997  Formed the New Management Team in 1997  Invested US$ 20 million to construct • 4 cGMP Plants for Synthetic Products • 2 cGMP Plants for Biotechnology Products  Established US Sales Office-Pharmaports in 2000  Products  Developing both synthetic & biotech products  Participate new drug development and contract manufacturing  Global Market Oriented with Emphasis on U.S.A., Europe, Japan   Initial public offering on December 20, 2010 2

Sales from 2004 to 2016 USD Thousands 45,000 Export Domestic 40,000 35,000 30,000 25,000 20,000 15,000 10,000 5,000 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 3

Sales from 1998 to 2016 USD Thousands Synthetic Products Biotech Products Contract Manufacturing 35,000 30,000 25,000 20,000 15,000 10,000 5,000 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 4

Sales Area in 2016 Europe Europe Americas Americas 7.9% 7.9% Asia Asia 53.03% 53.03% 30.79% 30.79% Domestic Domestic ROW ROW 8.22% 8.22% 0.06% 0.06% 5

Management Team  President – Dr. Chih-Ping Yang – Ph.D., Organic Chemistry, Univ. Texas at Austin, USA – General Manager, Chugai Pharma Taiwan 2005-2015 – Founder, President & CEO, CytoPharm, Inc., Taiwan 2003-2004 – President & CEO, GeneTrol Biotherapeutics, Inc., Oakland, California, USA 2002-2004  VP of Administration Management - Mr. Denry Huang – Deputy Plant Manager – Marketing & Sales Manager – General Manager, Shaoguan City Fermentec Co., China 6

Management Team  VP of Sales Management - Mr. Chuan Wen Chen – Marketing Director, Chugai Pharma Taiwan 2009 - 2016 – Business Development & Pharmaceutical Consultant, A-strong Co., Ltd. 2008 - 2009 – General Manager/Pharmaceuticals, Abbott Pharmaceutical Division, Taiwan 2001 - 2008 – Marketing Director, Serono Taiwan 1997 – 2001  Plant Manager – Mr. K. H. Tseng – B.E. in Chemical Engineering – Pharmaceutical Manufacturing since 1976 7

Management Team (cont.)  Biotech R&D Lab Director – Dr. Alex Mai – Ph.D. Chemistry, National Taiwan University – API R&D since 1994  Synthesis R&D Lab Director – Dr. Kevin Lee – Ph.D. Chemistry, National Tsing Hua University – API R&D since 1994  Analytical R&D Lab Deputy Director – Dr. Ping-Shu Chen – Ph.D. Chemistry, National Sun Yat-sen University – API R&D since 1997 8

Management Team (cont.)  Regulatory & QA Manager – Dr. W. P. Wang – Ph.D. Ch.E., University of Massachusetts – Experienced in API R&D, Production and QA/QC since 1995  Chief Operation Officer, Pharmaports – Mr. Joseph Chen – Master, National Yang-Ming University, Taipei, Taiwan – Manager, Global business 2006 – 2016 – Sales Specialist, Merck Display Tech. Ltd., Taiwan 2005 – 2006 – Account Manager and Marketing Specialist, Everlight Chemical Indl. Corp., Taipei 2002 - 2005 9

Management Team (cont.)  Production Technology Lab Deputy Director – Dr. Yen-Shih Tung – Ph.D. Chemistry, National Tsing Hua University – API R&D since 2007-2015 – Production Technology since 2016  Projects Management Office Deputy Manger – Dr. Ting-Huei Lee – Ph.D. Chemistry, University of Sussex, UK – API R& D since 2005 10

CCSB Organization Chart The Board Chairman Mr. Derek Wang The Auditor Mr. Jacky Hong President Dr. Chih-Ping Yang President Office Pharmaports R&D Div. Administration Div. Engineering Div. Production Div. Business Div. Mr. Joseph Dr. Alex Mai Mr. Denry Huang Mr. G. F. Tsai Mr. Chuan Wen Chen Chen (Acting) 11

Research and Development 12

R & D Manpower Synthesis Biotech Analytical Total % Ph.D. 6 5 2 13 25.49% Master 10 8 8 26 50.98% Bachelor 4 2 3 9 17.64% Others 1 2 0 3 5.88% Total 21 17 13 51 13

Biotech Capabilities  Strain Improvement Obtain high producer strain through screening and mutation  Fermentation Process Development & Commercialization Pravastatin Sodium; Rapamycin (Sirolimus); Mycophenolate Mofetil; Tacrolimus(FK506); Caspofungin; Temsirolimus; Everolimus; Biolimus; Zotarolimus 14

Contract Research & Development  Antiarrhythmia Drug – Collaborated with National Science Council & National Taiwan University in Taiwan  Blood Substitute, Antioxidant Drugs – Collaborated with SynZyme in U.S. funded by DOD & NIH  Antiradiation Drugs – Collaborated with SynZyme in U.S.  Macrolide – Collaborated with a U.S. Biotech company  COX II Inhibitor – Collaborated with a German company 15

Official cGMP Inspections Year Authorities Nation Product 2002 FDA US Methocarbamol 2005 FDA US Pravastatin 2007 KFDA Korea Methocarbamol 2008 TFDA Taiwan Trandolapril 2009 Koln Germany Pravastatin 2009 TFDA Taiwan GMP Systems 2011 FDA US Dexb; MMF; Tacrolimus 2012 Koln Germany Pravastatin 2013 TFDA Taiwan OLO; RAPA 2013 PMDA Japan Tacrolimus 2013 KFDA Korea Tacrolimus 2014 FDA US Full Products 2015 Koln Germany Pravastatin Sodium; Tacrolimus 2015 TFDA Taiwan Full Products 2015 Cofepris Mexico Caspofungin 16

Active US DMF List  DMF 18985  DMF 26271  DMF 13080 Tacrolimus Ethyl lcosapentate Methocarbamol  DMF 22430  DMF 26819  DMF 14234 Olopatadine HCl Everolimus Pre-Mix Guaifenesin  DMF 14235  DMF 23213  DMF 27216 Tacrolimus SD20 Everolimus Pravastatin Sodium  DMF 23434  DMF 17399  DMF 27585 Rapamycin Metaxalone Caspofungin Acetate  DMF 23435  DMF 17573  DMF 30103 Mycophenolate Trandolapril Omega-3-Varboxylic Acids  DMF 31189  DMF 18494 Sodium  DMF 24372 Mycophenolate Rapamycin (Sirolimus)  DMF 31276 Mycophenolate Mofetil Mofetil HCl Carfilzomib 17

Equipment for Synthesis Glass-lined Reactors: Total Volume 24,000 L Reactors Stainless Steel Reactors: Total Volume 140,000 L Hot-Air Tray Dryers Synthesis Centrifuges Dryers Vacuum Tray Dryers Double-cone Dryers Hastelloy Centrifuges Stainless Steel Centrifuges Hammer Mill Mills Fitz Mill Jet Mill 18

Equipment for Biotech 1,250 L – 30,000 L Fermentors Fermentation Total 137,000 L Fermentation Volume Biotech Filter Press Disk Centrifuge Lyophilization Purification Columns Ultra-filtration Preparative HPLC Lyophilizer 19

Equipment for Analytical X-ray Powder LC/MS Diffraction Analytical UPLC GC HPLC GC/MS 20

Instrumentation 2 inch and 3 inch HPLC column 6 inch MPLC system 21

Instrumentation (cont.) Waters preparative HPLC system 2 inch DAC column 22

Instrumentation (cont.) HPLC Powder X-Ray Diffraction GC 23

Instrumentation (cont.) GC/MS UPLC LC Mass 24

Instrumentation (cont.) GE AKTA Purifier UPC 100 KvickLab Cross Flow System BioTek Synergy H1 Hybrid Reader 25

Instrumentation (cont.) Pyros Kinetix Flex Automatic GEA Niro High Pressure Homogenizer Endotoxin Detection System 26

Instrumentation (cont.) Mbraun Glove box Type: UNILAB-B Bio Rad ChemiDoc XRS+ Imaging System 27

Location & Buildings  Located in Shu-Lin, New Taipei City  20 km South West of Taipei  34,000 m 2 Taoyuan Int’l Airport  273 Employees Taipei Songshan Airport As of December 2017 CCSB 28

CCSB Campus Layout 29

Chunghwa Chemical Synthesis & Biotech 30

cGMP Commercial Plants cGMP Plants 31

Synthetic Pilot Plant 50 L Glass Lined Reactor 75 L Stainless Steel Reactor 50 L Cone Dryer & 25” Centrifuge 32

Synthetic Pilot Plant (cont.) Freeze Dryers 33

Synthetic Commercial Plants 3,000 L Glass Lined Reactors 34

Synthetic Commercial Plants (cont.) Cone Dryer in Controlled Room Stainless Steel Reactors 35

Biotech Pilot Plant 5 L Fermentor 22 L Fermentor 600 L Fermentor 36

Biotech Commercial Plant ABEC 250LBioreactors ABEC 75L, 250L & 1250 L Bioreactors 37

Biotech Commercial Plant (cont.) Incubator & Shock Box Autoclave Biosafety Cabinet 38

Biotech Commercial Plant (cont.) 20,000 L & 30,000 L Fermentors 39

Biotech Commercial Plant (cont.) 5,000 L Glass-lined and Stainless Steel Reactors for Purification Process 40

Biotech Commercial Plant (cont.) Recovery & Purification Equipment Ultra Filtration 41

Whole Drug Life Cycle Support Pre-clinical Phase I/II Phase III/Launch Drug Life Time grams kilograms tons/multi-tons 42

Summary of CCSB  Over 50 years of API manufacturing experience  FDA and Health Authorities approved c GMP facilities for synthesis & biotech APIs  Fully cGMP trained and experienced personnel  Strong R&D support  Proven records for cost effective and on-time delivery of contract manufacturing from lab to commercial scales  Good communication skills & prompt response 43