introduction of ccsb 2020 nov.pdfnational taiwan university api r&d since 1994 jacky hong avp,...

Chunghwa Chemical Synthesis & Biotech Co., Ltd.

Introduction

of

Chunghwa Chemical Synthesis

& Biotech Co., Ltd.Nov. 2020

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

Brief History of CCSB

3

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000

Domestic Export

Sales from 1998 to 2019

USD Thousands

4

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

Synthetic Products

Biotech Products

Contract Manufacturing

Sales from 1998 to 2019

USD Thousands

Americas47.3%

Domestic13.3%

Europe18.4%

Asia21.0%

Sales Area in 2019

5

6

Audit Office

The board Chairman

Admin. Center

Finance

Human Resources

Procurement

General Admin.

Information Technology

Sales Div.

Sales

Business

Development

Production

Div.

API production

EHS Dept.R&D Div.

Biotechnology

Research Lab

Synthesis

Research Lab

Analytical

R&D Lab

Production Technology

Project Management

Regulatory and QA Dept.

Pharmaports

President

President Office

CCSB Organization Chart

Management Team

Name Title Education Experience

Denry Huang President Bachelor, Chemical Engineering,Chung Yuan Christian University

API industry since 1977

K. H. TsengVP,Production Division

B.E. in Chemical EngineeringNational Cheng Kung University

Pharmaceutical Manufacturing since 1976

Patrick Wei

VP,Research & Development Division

Ph.D., Chemistry,National Tsing Hua University

VP of Research & Development Formosa Laboratories, Inc.

Joseph ChenVP, Sales Division

Master, Microbiology & Immunology,National Yang-Ming University

Chief Operating Officer, Pharmaports LLC2016-2019 Manager, Global business,CCSB 2006 – 2016

7

Management Team (cont.)

Name Title Education Experience

W. P. WangAVP,Regulatory and QualityAffairs Dept.

Ph.D. Ch.E.,University of Massachusetts

API R&D, Production and QA/QC since 1995

Alex MaiAVP,Biotechnology Research Lab.

Ph.D. Chemistry,National Taiwan University

API R&D since 1994

Jacky HongAVP, Audit Office

MBA,Chung Yuan Christian University

Audit Manager since 2003IT Manager, Albatron Technology Co., Ltd.

Y. L. HsuDirector,Synthesis Research Lab.

Bachelor, Chemical Engineering,Chung Yuan Christian University

API R&D since 1986

Eason Wang Director,Finance Dept.

MA in Accounting, Chinese Culture University

MAX ZIPPER CO.,LTD.Finance Manager

Ching-MingTien

Plant Manager,Production Division

Bachelor, Food science and Biotechnology,Da-Yeh University

Pharmaceutical Manufacturing since 1995

P. S. ChenDeputy Director,Analytical R&D Lab.

Ph.D.,National Sun Yat-Sen University

API R&D since 1997

8

Manpower

9

Regulatory Sales R&D Production Adminstration

Production (52 %)

Regulatory (12 %)

R&D(23 %)

Administration(9 %)

Sales (4 %)

Effective Apr. 30, 2020

27%

35%

32%

2%

15%

6%

1%

Effective Apr. 30, 2020

5%

10

CCSB R&D team

Doctoral degree

Master’s degree

Bachelor’s degree

Others (Inc. associate’s degree,

college)

Education attainment

Research & Development

Synthesis

Process Research

Process Improvement

Biotechnology

Strain Improvement

Fermentation Process Development

Purification Process Development

Purification Process Development

Analytical

Method Development

Analytical Method Validation

Specification Set Up

Project Mgmt

Peptide & Protein Process Development

Standard Preparation

Stability Study

ProductionTechnology Lab

Peptide & Protein Process DevelopmentPeptide & Protein Process Development

Pilot ( Scale- up ) Pilot ( Scale- up )

Trouble shooting

Pilot ( Scale- up )

Research and Development

12

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

13

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

14

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

2017 USFDA USA EPAE

2017 TFDA Taiwan CDMO Products

2017 PMDA Japan Rapamycin

2018 USFDA Taiwan Full Products

2019 ANSM France Methocarbamol

Official cGMP Inspections

15

Active US DMF List

DMF 26271Ethyl lcosapentate

DMF 26819Everolimus Pre-Mix

DMF 27216Everolimus

DMF 27585Caspofungin Acetate

DMF 30103Omega-3-Varboxylic Acids

DMF 31189Rapamycin (Sirolimus)

DMF 31276Carfilzomib

DMF 13080Methocarbamol

DMF 14234Guaifenesin

DMF 14235Pravastatin Sodium

DMF 17399Rapamycin

DMF 17573Trandolapril

DMF 18494Mycophenolate Mofetil

DMF 18985Tacrolimus

DMF 22430Olopatadine HCl

DMF 23213Tacrolimus SD20

DMF 23434Metaxalone

DMF 23435Mycophenolate Sodium

DMF 24372Mycophenolate Mofetil HCl

16

Equipment for Synthesis

Glass-lined Reactors: Total Volume 24,000 L

Stainless Steel Reactors: Total Volume 140,000 L

Hot-Air Tray Dryers

Vacuum Tray Dryers

Double-cone Dryers

Hammer Mill

Fitz Mill

Jet Mill

Hastelloy Centrifuges

Stainless Steel Centrifuges

Dryers

Reactors

SynthesisCentrifuges

Mills

17

Equipment for Biotech

1,250 L – 30,000 L Fermentors

Total 137,000 L Fermentation Volume

Filter Press

Disk Centrifuge

Columns

Ultra-filtration

Preparative HPLCLyophilizer

Lyophilization

Biotech

Fermentation

Purification

18

Equipment for Analytical

Analytical

GC/MS

LC/MS

UPLC

X-ray

Powder

Diffraction

GC

HPLC

196 inch MPLC system

2 inch and 3 inch HPLC column

Instrumentation

20

Waters preparative HPLC system 2 inch DAC column

Instrumentation (cont.)

21

Instrumentation (cont.)

HPLC GC

LC Mass

UPLC

22

Instrumentation (cont.)

GC/MS

23

Instrumentation (cont.)

GE AKTA Purifier UPC 100

BioTek Synergy H1 Hybrid Reader

KvickLab Cross

Flow System

24

Instrumentation (cont.)

Pyros Kinetix Flex Automatic

Endotoxin Detection SystemGEA Niro High Pressure Homogenizer

25

Instrumentation (cont.)

Mbraun Glove box

Type: UNILAB-BBio Rad ChemiDoc XRS+ Imaging System

26

Location & Buildings

CCSB

Taoyuan Int’l Airport

Located in Shu-Lin,

New Taipei City

20 km South West of Taipei

34,000 m2

261 Employees

Taipei Songshan Airport

27

Chunghwa Chemical Synthesis & Biotech

28

CCSB Campus Layout

29

cGMP Commercial Plants

cGMP Plants

30

Synthetic Pilot Plant

75 L Stainless Steel Reactor

50 L Glass Lined Reactor

50 L Cone Dryer & 25” Centrifuge

31

Freeze Dryers

Synthetic Pilot Plant (cont.)

32

Synthetic Commercial Plants

3,000 L Glass Lined Reactors

33

Synthetic Commercial Plants (cont.)

Stainless Steel Reactors

Cone Dryer in Controlled Room

34

Biotech Pilot Plant

5 L Fermentor

600 L Fermentor

22 L Fermentor

35

Biotech Commercial Plant

ABEC 75L, 250L & 1250 L Bioreactors

ABEC 250LBioreactors

36

Biotech Commercial Plant (cont.)

Autoclave

Incubator & Shock

Box

Biosafety Cabinet

37

Biotech Commercial Plant (cont.)

20,000 L & 30,000 L Fermentors

38

Biotech Commercial Plant (cont.)

5,000 L Glass-lined and Stainless Steel

Reactors for Purification Process

39

Biotech Commercial Plant (cont.)

Recovery & Purification Equipment Ultra Filtration

40

grams

kilograms

ton/ multi-tons

Pre-clinical

Phase I/II

Phase III/Launch

Whole Drug Life Cycle Support

41

Summary of CCSB

Over 55 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