UQUIFA COMPANY PROFILE

HISTORY

Uquifa is founded

Uquifa is the first manufacturer of penicillin in Spain

Uquifa is purchased by the UK group HCH

Uquifa acquires the Sant Celoni Site (Spain)

Uquifa acquires the Cuernavaca site in Mexico to SKB

Uquifa is transferred to the UK group Yule Catto

We celebrate the 75th anniversary

1936 1948 1990 1991 1997 1998 2011

Uquifa is purchased by the Vivimed Group, India

2012

FIGURES

• Manufacturing sites in three continents

• 1000 employees

• Turnover 160m€

• More than 50 generic in our portfolio

• More than 75 years of experience in the pharmaceutical industry

Guangzhou, China Sales and Purchasing office

Spain Uquifa and QSynth

USA Mahwah (NJ) North American sales

Cuernavaca, Mexico Manufacturing, pilot and R&D

WHERE WE ARE

India Vivimed Labs India

Lliçà de Vall

Sant Celoni Barcelona

Mallapur (Hyd) A.P.

Chennai, A.P.

Bidar, Karnataka Bonthapally (Hyd) A.P.

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QSYNTH: THE UQUIFA’S CMO

• QSynth is the CMO business division of Uquifa SA. • Headquartered in Barcelona, Spain, it is a major player in the Custom manufacturing business

• Uquifa manages all aspects of research, development and manufacture of intermediates and API’s for QSynth • Created to be a preferred partner for your CMO Business

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QSYNTH: THE UQUIFA’S CMO

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QSYNTH: THE UQUIFA’S CMO • The primary focus of QSynth is to be a key partner for the Custom Manufacturing business to the Pharmaceutical Industry • Development and Industrial production of APIs and Intermediates:

From small scale supplies up to large Industrial production

Scale-up from Laboratory to Pilot Plant

Scale-up from Pilot Plant to commercial

• Novel synthetics routes and optimization of processes:

Reduce isolation steps

Improve yields and efficiency

Improve safety and environmental impact: eliminate the use of toxic and/or

dangerous reagents.

• Transfer of commercial scale processes.

QSYNTH: THE UQUIFA’S CMO

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Disease

discovery

Basic

research

Drug

discovery

Drug

development

Drug

trials Production Packaging

Marketing

Sales

Distribution

R&D 90 Scientist

Kilo-Lab SS, enamelled and

glass vessels up

to 50L

Pilot Plants Glass lined, SS and

Hastelloy, from 200

to 1000L

Large scale 1000 m3

· Speed: for clinical supplies

· Efficiency: for scale up and process development

· Experience: for a successfull commercial launch

· Competitiveness: for long term industrial supplies

LABORATORY AND PP DEVELOPMENT

R&D labs opened in Sant Celoni in 2005

2 M Euros investment

20 fume hoods (3 walk-in) HPLC-MS

UHPLC GC-MS

Preparatory HPLC RC-1 calorimeter

RESEARCH & DEVELOPMENT

RESEARCH & DEVELOPMENT

R&D labs opened in Mallapur, India

40 Scientists

HPLC-MS UHPLC GC-MS

RESEARCH & DEVELOPMENT • Process development and Process improvement

• New processes • Capable of producing from 1g to 1 kg • Small-scale up to 10L glass reactors • Focus on scale up efficiency, safety and environmentally

friendly processes:

• Reduce isolation steps • Improve yields • Minimize batch cycle time • Limited use of toxic and/or dangerous reagents

• Dedicated Analytical Development group

• UHPLC, HPLC, GC-MS, IR, UV, TGA, DSC, PSD (Malvern Mastersizer and Air-Jet)

• Total personnel in R&D: 90 (>10 PhD’s) in Spain, Mexico and India

R&D PROJECT MANAGEMENT

From Lab. to PP

From PP to Large Scale Plant

Laboratory stage: Team project: Team leader + Organic Chemist + Analytical Development chemist

Pilot plant stage: Team project: Team leader + PP Development chemist

Manufacturing stage: Team project: Team leader + PP Development chemist + Manufacturing Transfer chemist

TEAM LEADER: R&D PhD. Technical contact with the customer

· Research report · Thermo chemistry report · Analytical Methods (Validation methods report if needed) · Technical batch (100g scale) · COA

· Batch records · Development Report · Pilot plant batches · CoA’s

· Batch records · Technical Transfer report · Manufacturing batches · CoA’s · Validation report if process validation is needed

Deliveries Deliveries Deliveries

MULTIPURPOSE PILOT PLANTS

• Scale-up and small scale production • 1kg to 50kg for clinical trials and for small scale commercial

production • Variety of vessel sizes and materials of construction

• Installations are flexible for various combinations of reactors, filters and dryers • Cryogenic capability • Ozonolysis, hydrogenation and nitration

• Qualified technicians run the plants under cGMP • Identical quality control systems in the PP as applied for commercial

production

MANUFACTURING SITES

Cuernavaca, Mexico

Barcelona, Spain

Lliça de Vall, Spain

Sant Celoni, Spain

API SITES

• Headquarter

• Total capacity 140 m3

• High tech site with R+D centre for APIs and CRAMs

• Total capacity of 150m3

• FDA last inspection in 2012

• R&D centre for APIs and CRAMs

• Low cost manufacturing base

• Total capacity of 180m3

• FDA last inspection in 2011

• FDA last inspection 2012

VIVIMED SITES

Bidar, India

• Total capacity of 350 m3

Mallapur, India

• Mallapur is a R+D centre for APIs and KSMs

• Final Dose Form Factory

Chennai, India

Bonthapally, India

• Total capacity of 300m3

• Specialty chemical focus

• Site for pharma KSMs • Solid dosages, tablets and capsules

• FDA last inspection in Sept 2013

Lliçà Sant Celoni Mexico Chennai

Capacity 140,000 120,000 150,000 1,2 billion SKU’S

Last FDA Inspection

July 2012 July 2012 August 2011 Sept 2013

Holder of ANDA’s

c-GMP Yes Yes Yes Yes

Korean FDA June 2011 June 2011 June 2011 No

Japanese Certification

Yes Yes Yes No

ANVISA (Brazil) - Yes Yes No

COMPLIANCE

• Experience in all major geographies

• 21 Certificates of Suitability granted

• Many years of successful Regulatory

Over 42 Type II DMF’s filed with the FDA More than 150 active DMF’s worldwide

COMPLIANCE

• 3 ANDA’s from Chennai formulation facility for the USA

CONTRACT FORMULATION

• Focus on product development efforts for multiple regulated (USA, Canada, EU, South Korea, etc) and non-regulated markets

• Oral solid formulations

WHY WITH QSYNTH

• We protect your Intellectual Property

• Strong quality system approved by leading National Health Authorities and blue chip pharmaceutical companies

• Technical expertise in the manufacture of API’s to benefit your CMO products

• Back integration ensures cost efficient operations

JOIN OUR PARTNERS

CONTACT US

• For Corporate enquires contact Mark Ian Robbins – Uquifa CEO

(mrobbins@uquifa.com)

• For API’s enquires contact Alistair Swanson – Sales Director (aswanson@uquifa.com)

• For regulatory dossiers contact Gustavo Porras – BD Manager (gporras@uquifa.com)

• For Custom Synthesis projects contact Cristóbal Rodríguez or Bob Titus– CMO QSynth (crodriguez@uquifa.com or btitus@qsynth.com)

• To get the updated list of API’s products and Dossiers, visit our web page www.uquifa.com

• A detailed description of our facilities can be found in our CMO web page www.qsynth.com

THANK YOU!

CASE STUDIES

CASE STUDIES

• CASE 1 CS project Process transferred from small Scandinavian biotech company Uquifa developed the RoS, scaled it up and currently manufactures the commercial amounts

• CASE 2 API project Uquifa found a new patentable RoS Uquifa entered in the market with it

• CASE 3 Outsourcing Process transferred from a American blue chip company complete transfer from large scale to commercial, including process validation, in 8 months

CASE 1

• API-1 and API-2 Projects

– Both APIs were developed by a Scandinavian company in the late 90’s

– When the product was in Phase III, the manufacturing process was transferred to Uquifa (2003)

Cl

O

R1

O

n

+ NH

O

OH

O O

N

O

O

R1

O

n

NH

O

O

OH

O

n

OH

O

NH2

O

OH

O

n

NH2

O

R2

O

n

CASE 1

• API-1 and API-2 Projects (Timeline)

– Process transferred in 2003

– Process validated in 2004 (1st MA)

– Large scale process scaled up in 2005

– FDA audited the Sant Celoni site in 2007 for this product

– API-1 licensed out to another European Company in 2008

– Currently we are the only manufacturer for the commercial amounts of both products

CASE 2

• Quetiapine hemifumarate Project

– Quetiapine (Seroquel®) is an antipsychotic approved for the treatment of schizophrenia, bipolar disorders and major depressive disorders

– The manufacturing process of the originator involves hazardous reagents (POCl3) and three manufacturing steps

– In 2004 Uquifa decides to develop a new RoS which avoided these problem

– In 2005 Uquifa issues a process patent covering the new RoS discovered

CASE 2

N

S

Cl

NH

S

O

N

S

N

N O

OHNH

NH

OPCl3

NH

N O

OH

Ti(iPro)4

New Uquifa's process

Original process

N

S

N

NH

OOHCl

CASE 2

• Quetiapine hemifumarate Project

– The same year Uquifa scaled up the process to get commercial amounts (250kg batch size)

– Uquifa had to invest EUR250K to set up new capabilities (reaction temperature >160ºC)

– Currently Uquifa is one of the major producers of Quetiapine in the world using a safer and environmentally friendly process.

CASE 3

• Antiretroviral

– Uquifa received a transfer of an antiretroviral API from a Blue Chip American Pharmaceutical company

– Uquifa started the lab transfer in Feb’12

– In May’12 Uquifa scaled up the five steps process in our Pilot Plant

– Engineering and validation batches in the large scale plant (>300kg/batch) finished in Nov’12

– In December12 Uquifa manufactured the first commercial batches

CASE 3

• Antiretroviral

– Uquifa invested 1m€ to set up new equipment

– A new shift was introduced to keep open the manufacturing plant 24/7 days

– Uquifa will manufacture >20 Tn in 2013 and will double its capacity in 2014