Chunghwa Chemical Synthesis & Biotech Co., Ltd.

Introductionof 

Chunghwa Chemical Synthesis& Biotech Co., Ltd.

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 Obtain the necessary land for plant expansion in 2012

2

Brief History of CCSB

3

Sales from 1998 to 2013

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

USD Thousands

Domestic Export

4

Sales from 1998 to 2013

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

USD Thousands

Synthetic Products Biotech Products Contract Manufacturing

5

Sales Area in 2013

Asia35.0%

US53.9%

Europe6.8%

ROW0.3%

Domestic4.0%

6

Management Team

President – Dr. Steve Chang– D.Sc. Chemistry, Univ. Texas at Arlington– Abbott Laboratories, Abbott Parks, IL, 1989‐1998– QA/QC Manager, CCSB 1999‐2002– VP of Operation 2002‐2004– President since 2004

Chief Operation Officer, Pharmaports – Dr. Jack Yen– Ph.D., Chemistry,  Drexel University – Johnson & Johnson Pharmaceutical R&D 1996‐2007– Glaxo SmithKline Pharmaceutical R&D 1988‐1996– Wyeth Laboratories Pharmaceutical R&D 1986‐1988

7

Management Team (cont.)

VP of Business Management ‐Mr. Denry Huang– Deputy Plant Manager

– Marketing & Sales Manager

– General Manager, Shaoguan City Fermentec Co., China

Plant Manager – Mr. K. H. Tseng– B.E. in Chemical Engineering

– Pharmaceutical Manufacturing since 1976

8

Management Team (cont.)

Synthesis R&D Director – Dr. Kevin Lee– Ph.D. Chemistry, National Tsing Hua University 

– API R&D since 1994

Biotech R&D Director – Dr. Alex Mai– Ph.D. Chemistry, National Taiwan University 

– API R&D since 1994

9

Analytical R&D Director – Dr. H. Y. Cheng– Ph.D., Analytical Chemistry, Ohio State University, Columbus, Ohio

– Lead Researcher, Industrial Technology Research Institute, Taiwan, 2009‐2011

– Applications Lab Manager, Eksigent Technologies, Dublin, CA, 2005‐2008

– Various Research and Management Positions in Drug Discovery and Pre‐Clinical Development, GSK Pharmaceuticals, King of Prussia, PA, 1984 ‐ 2004

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

Management Team (cont.)

10

CCSB Organization Chart

11

Research and Development

12

R & D Manpower

Synthesis Biotech Analytical Total %

Ph.D. 4 3 1 8 19.5%

Master 8 9 4 21 51.2%

Bachelor 5 3 2 10 24.4

Others 0 2 0 2 4.9%

Total 17 17 7 41

13

Biotech Capabilities

Strain ImprovementObtain high producer strain through screening and mutation

Fermentation Process Development & CommercializationPravastatin Sodium; Rapamycin (Sirolimus); Mycophenolate Mofetil; Tacrolimus(FK506);Caspofungin; Micafungin; Anidulafungin;Temisirolimus; 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 Product2002 FDA US Methocarbamol

2005 FDA US Pravastatin

2006 TFDA Taiwan Perindopril

2007 KFDA Korea Methocarbamol

2008 NIP Hungary Perindopril

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

16

Active US DMF List

DMF 23435Mycophenolate Sodium

DMF 24372Mycophenolate Mofetil HCl

DMF 26271Ethyl lcosapentate

DMF 26819Everolimus Pre‐Mix 

DMF 27216Everolimus

DMF 27585Caspofungin Acetate  

DMF 8625Dexbrompheniramine Maleate

DMF 13080Methocarbamol

DMF 14234Guaifenesin

DMF 14235Pravastatin Sodium

DMF 17399Rapamycin

DMF 17400Carisoprodol

DMF 17573Trandolapril

DMF 18494MycophenolateMofetil

DMF 18985Tacrolimus

DMF 22430Olopatadine

DMF 23213Tacrolimus SD20

DMF 23434Metaxalone

17

Equipment for Synthesis

Glass‐lined Reactors: Total    Volume 24,000 LStainless Steel Reactors:   Total 

Volume 140,000 L

Hot‐Air Tray DryersVacuum Tray DryersDouble‐cone Dryers

Hammer MillFitz MillJet Mill

Hastelloy CentrifugesStainless Steel Centrifuges

Dryers

Reactors

SynthesisCentrifuges

Mills

18

Equipment for Biotech

1,250 L – 30,000 L FermentorsTotal 137,000 L Fermentation Volume

Filter Press Disk CentrifugeColumnsUltra‐filtrationPreparative HPLCLyophilizer

Lyophilization

Biotech

Fermentation

Purification

19

Equipment for Analytical

Analytical

GC/MS

LC/MS

UPLC

X-ray Powder

Diffraction

GC

HPLC

206 inch MPLC system

2 inch and 3 inch HPLC column

Instrumentation

21

Waters preparative HPLC system 2 inch DAC column

Instrumentation (cont.)

22

Instrumentation (cont.)

Powder XRD

HPLC

GC

LC Mass

UPLC

23

Instrumentation (cont.)

GC/MS

24

Instrumentation (cont.)

GE AKTA Purifier UPC 100

BioTek Synergy H1 Hybrid Reader

KvickLab Cross Flow System

25

Instrumentation (cont.)

Pyros Kinetix Flex Automatic Endotoxin Detection System

GEA Niro High Pressure Homogenizer

26

Instrumentation (cont.)

Mbraun Glove box

Type: UNILAB-BBio Rad ChemiDoc XRS+ Imaging System

27

Location & Buildings

CCSB

Taoyuan Int’l Airport

Located in Shu‐Lin,New Taipei City

20 km South West of Taipei

34,000 m2

244 EmployeesTaipei Songshan Airport

28

CCSB Campus Layout

29

Chunghwa Chemical Synthesis & Biotech

30

cGMP Commercial Plants

cGMP Plants

31

Synthetic Pilot Plant

75 L Stainless Steel Reactor

50 L Glass Lined Reactor

50 L Cone Dryer & 25” Centrifuge

32Freeze Dryers

Synthetic Pilot Plant (cont.)

33

Synthetic Commercial Plants

3,000 L Glass Lined Reactors

34

Synthetic Commercial Plants (cont.)

Stainless Steel Reactors

Cone Dryer in Controlled Room

35

Biotech Pilot Plant

5 L Fermentor

600 L Fermentor

22 L Fermentor

36

Biotech Commercial Plant

ABEC 75L, 250L & 1250 L Bioreactors

ABEC 250LBioreactors

37

Biotech Commercial Plant (cont.)

6,000 L Fermentor

Feed Tanks of Fermentor

38

Biotech Commercial Plant (cont.)

20,000 L & 30,000 L Fermentors

39

Biotech Commercial Plant (cont.)

5,000 L Glass-lined and Stainless SteelReactors 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 45 years of API manufacturing experience  FDA and Health Authorities approved cGMP 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