presentation of qiming biotech august 2012

Zhejiang Qiming Biotech Co., Ltd.

G i API M f tGeneric API Manufacturer

Custom Process Development

Contract Manufacturing

History

Qiming Biotech was formed in 2010 from the merger of • 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 intermediatesdevelopment of key pharmaceutical intermediates

• Qiming Pharma is a long term manufacturer of both APIs d i t di t f th h ti l i d t ith and intermediates for the pharmaceutical industry with

more than 17 years of experience.

OrganizationsOrganizations

Qiming Biotech

Eastbound Synopharma(HK) Holdings Ltd

Qiming Pharma

Financial Non‐cGMP Manufacturing

Shangyu ProcessShangyu

Manufacturing

Shangyu Process Development 

InstitutecGMP Manufacturing Process Developmentg p

Quality AssuranceTechnology Transfer

Management TeamManagement TeamDr. Leo Lin

VP Quality and 

Michael ZhangChris Vance

VP Sales, Marketing and 

Regulatory Affairs

President & CEO

Dr. Yuan Li

VP Process Development

Business Development

VP Process Development Operations

Dr. Young Lo

R h F llResearch Fellow

Linzhong Zhou           

Finance DirectorOver 100 years of Western Finance DirectorOver 100 years of Western Pharmaceutical Business Experience

Our Advantages

GMP d GMP f t i f API d• cGMP and non‐cGMP manufacturing of APIs and intermediates for pharmaceutical and veterinary industry

• Sophisticated development and manufacturing capability p p g p yoffers 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 

B i FBusiness Focus

cGMP and Non‐GMP ManufacturingAPIs and Intermediates

Custom Solutions to Complex Problems

Qiming Biotech ManufacturingQiming Biotech Manufacturing

• Shangyu site is 43,000 m2

(10+ acres) located in Hangzhouwan IndustrialHangzhouwan Industrial Park in Shangyu, Zhejiang

• Plant 1 certified by China’s SFDA for APIs and inspected by major pharma companiesby major pharma companies

• Plant 2 installation underway.  Designed for ICH Q7A level cGMP compliance

APIs ListAPIs ListNo. API CAS # Pharmaceutical Status

1 Mefenamic acid 61 68 7non‐steroidal anti‐inflammatory drug (NSAID)

US DMF filed. Inspected by US customer and waiting for FDA inspection at 2Q 2012. ANDA approval is driving FDA 

1 Mefenamic acid 61‐68‐7 drug (NSAID).  Tradename:  PONSTEL

schedule.  Commercial production presently for non‐regulatory market

2 Talniflumate 66898‐62‐2

Anitinflammatory, mucoregulator. Tradename TALMAIN (Korea), LOMUCIN

No SFDA file, but in commercial production for non‐regulatory market

LOMUCIN

3 Tolfenamic acid 13710‐19‐5

non‐steroidal anti‐inflammatory drug (NSAID).  Tradename:  CLOTAM

No SFDA file, but in commercial production for non‐regulatory market

4Calcium 

51828‐93‐44Phenylpyruvate

51828 93 4

Combination of amino acids for use in managing protein metabolism during renal insufficiency.  Tradename: Ketosteril

Product licenses approved by SFDA. Final documentation underway. SFDA inspection expected in 3Q 2012 with approval thereafter. 

5 α‐Ketovaline Calcium 51828‐94‐56 α‐Ketoleucine Calcium 51828‐95‐6

7D,L‐α‐Ketoisoleucine Calcium

66872‐75‐1

2‐Hydroxy‐4‐8

y y(methylthio)butyric acid calcium salt

4857‐44‐7

9 Fexofenadine HCl 15439‐40‐8Antihistamine,Tradename:  Allegra

In commercial production for non‐regulatory market.US DMF will be filed in Q3, 2012

10 Venlafaxine 93413‐69‐5AntidepressantTradename: Effexor

In commercial production for non‐regulatory market.Tradename:  Effexor

11 Edaravone 89‐25‐8Stroke recoveryTraded by Mitsubishi

Process development completed, documents will be filed with SFDA in Q4 2012

12 Doxapram 7081‐53‐0Respiratory stimulant.  Tradename:  Dopram

Process development completed and US DMF will be filed with FDA in Q4 2012

Qiming Biotech Manufacturing

• cGMP Production in two multi‐purpose manufacturing units.  I l t d f fi i hi fi l API t i l di d i illi bl di

Q g otec a u actu g

– Isolated areas for finishing final API steps including drying, milling, blending

– 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 DafengEastbound

– Large scale facilities permit easy scale‐up and supply of critical intermediates

– Wide range of chemistry practiced

••

Key TechnologiesKey Technologies

O id ti ith i id t• Oxidation with various oxidants

• Halogenation including Br, I and Cl

• Heterocyclic chemistry: indoles pyridines piperidines etc• Heterocyclic chemistry: indoles, pyridines, piperidines, etc.

• Grignard reactions

• Sandmeyer Reactionsy

• Nitration using nitric acid

• Hydride reactions

• Other chemical reactions such as acylation, esterification, condensation, cyclization, sulfonation, polymerization etc.

Plant 1: cGMP PlantPlant 1:  cGMP Plant

B ilt i 2005 t d API d• Built in 2005 to produce API and late stage intermediates

• Certified by SFDA in 2006• Five additional APIs developed for• Five additional APIs developed for 

SFDA and western regulatory approval

• US DMF submitted for mefenamic Vessels 11.0 m3 Glass lined Stainless2000 lit 2 2US DMF submitted for mefenamic

acid; awaiting FDA inspection and certification

2000 liter 2 2500 liter 4 2

Centrifuge flatbed 2 stainlessDryer Tray dryer 1

500 liter Double cone vacuum 11000 liter Double cone vacuum 1Purified Water SystemMillHVAC class 100,000 rated

FDA rating: D15 Pa±1°C, ±10% RH

Vessels 16.6 m3Glass lined Stainless

3000 liter 12000 liter 1 11000 liter 3 1Plant 2: cGMP Plant 1000 liter 3 1500 liter 3 1300 liter 3200 liter 1100 liter 1

Centrifuge 2 Halar coated 2 Stainlessd

Plant 2: cGMP Plant

Dryer Tray dryer 4Double cone vacu 1

GMP section500 liter Glass linedFilter dryerMill2n

dFl

oor

Blender 200 literHVAC class 100,000 rated

FDA rating: D15 Pa±1°C, ±10% RH

1stFl

oor

Controlled access and HVAC

Vessels 16.6 m3Glass lined Stainless

3000 liter 12000 liter 1 11000 liter 3 1Plant 2: cGMP Plant 1000 liter 3 1500 liter 3 1300 liter 3200 liter 1100 liter 1

Centrifuge 2 Halar coated 2 Stainlessd

Plant 2: cGMP Plant

Dryer Tray dryer 4Double cone vacu 1

GMP section500 liter Glass linedFilter dryerMill2n

dFl

oor

Blender 200 literHVAC class 100,000 rated

FDA rating: D15 Pa±1°C, ±10% RH

1stFl

oor

Vessels 16.6 m3Glass lined Stainless

3000 liter 12000 liter 1 11000 liter 3 1Plant 2: cGMP Plant 1000 liter 3 1500 liter 3 1300 liter 3200 liter 1100 liter 1

Centrifuge 2 Halar coated 2 Stainlessd

Plant 2: cGMP Plant

Dryer Tray dryer 4Double cone vacu 1

GMP section500 liter Glass linedFilter dryerMill2n

dFl

oor

Blender 200 literHVAC class 100,000 rated

FDA rating: D15 Pa±1°C, ±10% RH

1stFl

oor

Facilities and UtilitiesFacilities and Utilities

• Total area:  43,000 m2

• Total reactor volume: Plant 1:  11 m3

Plant 2:  17 m3

• Reactors: Glass Stainless• Reactors: Glass, Stainless• Total employees: 70• Reaction Temperature Range:   ‐30 to 150 °C

Utilities:• Po er Total capacit 800 k• Power: Total capacity 800 kw• Steam: 10 bar max• Refrigeration: 120,000 kCalg ,

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;experience;• Long term business relationship with big pharmas and 

western CMO companies. 

Shangyu Process Development InstituteShangyu Process Development Institute

Sh P D l t I tit tShangyu Process Development Institute

Process Development, Analytical Method p , yDevelopment 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 researchOnsite access to chemical research resources

– SciFinder, Reaxys

Development Laboratory & Kilo LabDevelopment Laboratory

Bench Labs 7 350 m2Bench Labs 7 350 mFume hoods 24Each lab air controlled independently

Kilo LabVessels Glass 50‐200 litersCapacity 1‐5 kgp y g

cGMP finishing sectiontray dryerfilter press

HVAC class 100,000

Analytical Lab 7 700 m2Kilo lab

Analytical Lab 7 700 mHPLCGCIRMicrobiologyStabilityy

Development Laboratory & Kilo LabDevelopment Laboratory

Bench Labs 7 350 m2Bench Labs 7 350 mFume hoods 24Each lab air controlled independently

Kilo LabVessels Glass 50‐200 litersCapacity 1‐5 kgp y g

cGMP finishing sectiontray dryerfilter press

HVAC class 100,000

Analytical Lab 7 700 m2Analytical Lab 7 700 mHPLCGCIRMicrobiologyStabilityy

N S iNo Surprises

Project evaluationReply to inquiry within 3 days

Project preparationDetailed proposal 

presented within 10 days

Project executionFrequent progress reports; 

no surprisesj no surprises

Campaign reports andProject completion Campaign reports and analytical documentation

Thank YouVisit us in 

Shangyu, Zhejiang

Chris VanceVP Sales Marketing Business Dev

Dr. Yuan LiVP Process Development Operations VP Sales, Marketing, Business Dev

chris.vance@eastboundpharma.com+1 (804) 601-2760

VP Process Development Operationsyuan.li@qimingbiotech.com+86 (575) 8272 6990-8011