General description of Qiming Bio-Tech, plants, development, chemistry

1. Zhejiang Qiming Biotech Co., Ltd.
Generic API Manufacturer
G i API M f t
Custom Process Development
Contract Manufacturing

2. History
• Qiming Biotech was formed in 2010 from the merger of
Eastbound Synopharma and the API division of Qiming
Pharma
• Eastbound was a company established in 2002 in
Shanghai and well known for custom process
development of key pharmaceutical intermediates
• Qiming Pharma is a long term manufacturer of both APIs
and intermediates for the pharmaceutical industry with
di t di t f th h ti l i d t ith
more than 17 years of experience.

3. Organizations
Qiming Biotech
Eastbound Synopharma
Qiming Pharma
(HK) Holdings Ltd
Financial Non‐cGMP Manufacturing
Shangyu Process
Process
Shangyu
Development
Manufacturing
Institute
cGMP Manufacturing
g Process Development
p
Quality Assurance
Technology Transfer

4. Management Team
Management Team
Dr. Leo Lin
VP Quality and
Regulatory Affairs
Chris Vance
Michael Zhang VP Sales, Marketing and
President & CEO Business Development
Dr. Yuan Li
VP Process Development
VP Process Development
Operations
Dr. Young Lo
Research Fellow
R h F ll
Linzhong Zhou
Over 100 years of Western
Over 100 years of Western Finance Director
Finance Director
Pharmaceutical Business Experience

5. Our Advantages
• cGMP and non‐cGMP manufacturing of APIs and
GMP d GMP f t i f API d
intermediates for pharmaceutical and veterinary industry
• Sophisticated development and manufacturing capability
p p g p y
offers custom solutions to complex problems
• Frequent communication with clients; no surprises
• Broad technology platform with niche capabilities on
commercial scale
• Experienced team of managers with western
Experienced team of managers with western
pharmaceutical experience

6. Business Focus
B i F
cGMP and Non‐GMP Manufacturing
APIs and Intermediates
Custom Solutions to Complex Problems

7. Qiming Biotech Manufacturing
Qiming Biotech Manufacturing
• Shangyu site is 43,000 m2
(10+ acres) located in
Hangzhouwan Industrial
Industrial
Park in Shangyu, Zhejiang
• Plant 1 certified by China’s
SFDA for APIs and inspected
by major pharma
by major pharma companies
• Plant 2 installation
underway. Designed for ICH
Q7A level cGMP compliance

8. APIs List
APIs List
No. API CAS # Pharmaceutical Status
US DMF filed. Inspected by US customer and waiting
non‐steroidal anti‐inflammatory
for FDA inspection at 2Q 2012. ANDA approval is driving FDA
1 Mefenamic acid 61‐68‐7
61 68 7 drug (NSAID).
drug (NSAID)
schedule. Commercial production presently for non‐
Tradename: PONSTEL
regulatory market
Anitinflammatory,
mucoregulator. No SFDA file, but in commercial production for non‐
2 Talniflumate 66898‐62‐2
Tradename TALMAIN (Korea), regulatory market
LOMUCIN
non‐steroidal anti‐inflammatory
drug (NSAID). Tradename: No SFDA file, but in commercial production for non‐
3 Tolfenamic acid 13710‐19‐5
CLOTAM regulatory market
Calcium
4 51828 93 4
51828‐93‐4
Phenylpyruvate
5 α‐Ketovaline Calcium 51828‐94‐5 Combination of amino acids for
6 α‐Ketoleucine Calcium 51828‐95‐6 use in managing protein Product licenses approved by SFDA. Final documentation
D,L‐α‐Ketoisoleucine metabolism during renal underway. SFDA inspection expected in 3Q 2012 with
7 66872‐75‐1
Calcium insufficiency. Tradename: approval thereafter.
y y
2‐Hydroxy‐4‐ Ketosteril
8 (methylthio)butyric 4857‐44‐7
acid calcium salt
Antihistamine, In commercial production for non‐regulatory market.
9 Fexofenadine HCl 15439‐40‐8
Tradename: Allegra US DMF will be filed in Q3, 2012
Antidepressant
10 Venlafaxine 93413‐69‐5 In commercial production for non‐regulatory market.
Tradename: Effexor
Tradename: Effexor
Stroke recovery Process development completed, documents will be filed
11 Edaravone 89‐25‐8
Traded by Mitsubishi with SFDA in Q4 2012
Respiratory stimulant. Process development completed and US DMF will be filed
12 Doxapram 7081‐53‐0
Tradename: Dopram with FDA in Q4 2012

9. Q
Qiming Biotech Manufacturing
g otec a u actu g
• cGMP Production in two multi‐purpose manufacturing units.
– I l t d
Isolated areas for finishing final API steps including drying, milling, blending
f fi i hi fi l API t i l di d i illi bl di
– Wide range of vessels, glass and SS, to permit flexible process arrangements
– Solid procedures and training programs to assure cGMP quality adherence
• Experienced QC and QA team to review and audit manufacturing
Experienced QC and QA team to review and audit manufacturing
procedures
– On site analytical laboratories assure timely data for manufacturing and validated
procedures for regulatory filing.
• Western pharma audited facilities
– Major pharma inspections
– PAI inspection by US FDA completed. Facility approved with no 483
• Non‐GMP Production partnerships with Qiming Pharma and Dafeng
Eastbound
– Large scale facilities permit easy scale‐up and supply of critical intermediates
– Wide range of chemistry practiced
•
•

10. Key Technologies
Key Technologies
• Oxidation with various oxidants
O id ti ith i id t
• Halogenation including Br, I and Cl
• Heterocyclic chemistry: indoles, pyridines, piperidines, etc.
Heterocyclic chemistry: indoles pyridines piperidines etc
• Grignard reactions
• Sandmeyer Reactions
y
• Nitration using nitric acid
• Hydride reactions
• Other chemical reactions such as acylation, esterification,
condensation, cyclization, sulfonation, polymerization etc.

11. Plant 1: cGMP
Plant 1: cGMP Plant
• B ilt i 2005 t
Built in 2005 to produce API and
d API d
late stage intermediates
• Certified by SFDA in 2006
• Five additional APIs developed for
Five additional APIs developed for
SFDA and western regulatory
approval
Vessels 11.0 m3 Glass lined Stainless
• US DMF submitted for mefenamic
US DMF submitted for mefenamic 2000 liter
2000 lit 2 2
acid; awaiting FDA inspection and 500 liter 4 2
certification
Centrifuge flatbed 2 stainless
Dryer Tray dryer 1
500 liter Double cone vacuum 1
1000 liter Double cone vacuum 1
Purified Water System
Mill
HVAC class 100,000 rated
FDA rating: D
15 Pa
±1°C, ±10% RH

12. Vessels 16.6 m3 Glass lined Stainless
3000 liter 1
Plant 2: cGMP Plant 2000 liter
1000 liter
500 liter
1
3
3
1
1
1
300 liter 3
200 liter 1
100 liter 1
Centrifuge 2 Halar coated 2 Stainless
Dryer Tray dryer
d 4
2nd Floor
Double cone vacu 1
GMP section
500 liter Glass lined
Filter dryer
Mill
Blender 200 liter
HVAC class 100,000 rated
FDA rating: D
15 Pa
±1°C, ±10% RH
1st Floor
Controlled access and HVAC

13. Vessels 16.6 m3 Glass lined Stainless
3000 liter 1
Plant 2: cGMP Plant 2000 liter
1000 liter
500 liter
1
3
3
1
1
1
300 liter 3
200 liter 1
100 liter 1
Centrifuge 2 Halar coated 2 Stainless
Dryer Tray dryer
d 4
2nd Floor
Double cone vacu 1
GMP section
500 liter Glass lined
Filter dryer
Mill
Blender 200 liter
HVAC class 100,000 rated
FDA rating: D
15 Pa
±1°C, ±10% RH
1st Floor

14. Vessels 16.6 m3 Glass lined Stainless
3000 liter 1
Plant 2: cGMP Plant 2000 liter
1000 liter
500 liter
1
3
3
1
1
1
300 liter 3
200 liter 1
100 liter 1
Centrifuge 2 Halar coated 2 Stainless
Dryer Tray dryer
d 4
2nd Floor
Double cone vacu 1
GMP section
500 liter Glass lined
Filter dryer
Mill
Blender 200 liter
HVAC class 100,000 rated
FDA rating: D
15 Pa
±1°C, ±10% RH
1st Floor

15. Facilities and Utilities
Facilities and Utilities
• Total area: 43,000 m2
• Total reactor volume: Plant 1: 11 m3
Plant 2: 17 m3
• Reactors: Glass, Stainless
Glass Stainless
• Total employees: 70
• Reaction Temperature Range: ‐30 to 150 °C
Utilities:
• Po er
Power: Total capacity 800 kw
Total capacit 800 k
• Steam: 10 bar max
• Refrigeration:
g 120,000 kCal
,

16. Shangyu Process Development Institute
• More than 300 projects completed in the past 7 years;
• Over 15% of developed projects moved into pilot or
p p j p
commercial scale;
• Professional R&D team with western pharma working
experience;
• Long term business relationship with big pharmas and
western CMO companies.

17. Shangyu Process Development Institute
Process Development Institute

18. Shangyu P
Sh Process Development Institute
D l t I tit t
Process Development, Analytical Method
p , y
Development and Production Support
• 20 Chemists & Engineers including Dr
Young Lo and Dr Yuan Li
• 1400 m2 modern development and
analytical laboratory
• 24 fume hoods for bench development
• 3 walk‐in hoods for cGMP kilo lab
• State of the art analytical capability
– HPLC, GC, UV, FT‐IR, etc
– Easy access to AA, LC‐MS, TGA, DSC,
NMR, EA, X‐ray, etc
• Onsite access to chemical research
Onsite access to chemical research
resources
– SciFinder, Reaxys

19. Development Laboratory
& Kilo Lab
Development Laboratory
Bench Labs
Bench Labs 7 350 m2
350 m
Fume hoods 24
Each lab air controlled independently
Kilo Lab
Vessels Glass 50‐200 liters
Capacity 1‐5 kg
p y g
cGMP finishing section
tray dryer
filter press
HVAC class 100,000
Kilo lab
Analytical Lab
Analytical Lab 7 700 m2
700 m
HPLC
GC
IR
Microbiology
Stability
y

20. Development Laboratory
& Kilo Lab
Development Laboratory
Bench Labs
Bench Labs 7 350 m2
350 m
Fume hoods 24
Each lab air controlled independently
Kilo Lab
Vessels Glass 50‐200 liters
Capacity 1‐5 kg
p y g
cGMP finishing section
tray dryer
filter press
HVAC class 100,000
Analytical Lab
Analytical Lab 7 700 m2
700 m
HPLC
GC
IR
Microbiology
Stability
y

21. No Surprises
N S i
Reply to inquiry
Project evaluation within 3 days
Detailed proposal
Project preparation presented within 10 days
Frequent progress reports;
Project execution
j no surprises
no surprises
Project completion Campaign reports and
Campaign reports and
analytical documentation

22. Thank You
Visit us in
Shangyu, Zhejiang
Dr. Yuan Li Chris Vance
VP Process Development Operations VP Sales, Marketing Business Dev
Sales Marketing,
yuan.li@qimingbiotech.com chris.vance@eastboundpharma.com
+86 (575) 8272 6990-8011 +1 (804) 601-2760