1. CARBOGEN AMCIS
Company Overview

2. …Innovative Chemistry Solutions
Who we are
CARBOGEN AMCIS is a Swiss leading provider of drug development and commercialization services, offering Custom Development & Manufacture of APIs.
Our Mission is to help pharmaceutical industries:
Bring new generation medicines to market
Reduce time and risk associated with the drug development
Take chemistry off the critical path by providing…
…Innovative Chemistry Solutions

3. Locations Dishman facilities & offices CARBOGEN AMCIS Local sales
Dishman CRAMS
Manchester
United Kingdom
Early / Late Phase
Neuland
Switzerland
Early / Commercial Phase
Bubendorf
Switzerland
Late Phase / Commercial
Bavla
India
Late Phase / Commercial
Shanghai
China
Late Phase / Commercial
Riom
France
Early Phase
Aarau
Switzerland
Early /Commercial Phase
Bavla
India
Late Phase/ Commercial

4. Company History
2012
Acquisition of CARBOGEN AMCIS SAS in Riom, France
2007
Creation of CARBOGEN AMCIS Ltd in
Manchester, UK
2005
Investment in High Potency Facility in Bubendorf
1990
Foundation CarboGen Spin-off of the University of Zurich focused on research services and early-phase API supply
2006
Creation of CARBOGEN AMCIS AG
2008
New High Potency Facility in Ahmedabad, India
2006
Acquisition of CARBOGEN AMCIS AG by Dishman Pharmaceuticals and Chemicals Ltd
2000
Acquisition of CarboGen and AMCIS by Solutia
1982
Foundation AMCIS joint an pharma company focused venture with on PR&D and cGMP manufacturing

5. Business Units & Company Structure
Dishman Group
Dishman Pharma Services
Dishman Marketable Molecule
Dishman
Specialty
Chemicals
Dishman
Vitamins &
Chemicals
Dishman
Disinfectants
CARBOGEN AMCIS
Dishman CRAMS
Manchester
United Kingdom
Early/Late Phase
Neuland
Switzerland
Early/Commercial
Phase
Bubendorf
Switzerland
Late Phase/
Commercial
Bavla
India
Late Phase/
Commercial
Shanghai
China
Late Phase/
Commercial
Riom
France
Early Phase
Aarau
Switzerland
Early/Commercial
Phase
Bavla
India
Late Phase/
Commercial

6. Dishman Group Key Facts
Established in 1983
Public company quoted on BSE
US $300 M turnover company
Year on year growth approx. 30% since 2004
More than 1000 technical staff
Global presence – manufacturing sites
Europe (5),
India (2),
China
ISO 9001:2000, ISO :2004, OHSAS :2007
Successful audit history
FDA inspected May 2006 (Bavla), Feb 2010 (Naroda), March (Bavla, Ahmedabad)
EDQM/TGA inspected June (Bavla), TGA:  Sept 2011 (Bavla)
DCGI / WHO:   July 2006, Feb 2010, May 2012
Korean FDA  Feb 2013 ( Naroda )
Accreditation as foreign manufacturer for Japan

7. CARBOGEN AMCIS Key Facts
Over 20 years experience
6 sites (3 in Switzerland, 1 in the United Kingdom, 1 in France and 1 in India)
Over 200 chemists, with >40% Ph.D.
Well over 500 projects per annum
75% of projects are return customers
Over 100 projects involving production, 30% HiPo
15 Commercial products
Successful audit history
Since 2006 part of the Dishman Group
FDA, Swiss Medic, French Health Agency (ANSM), Korean FDA
Accreditation as foreign manufacturer for Japan

8. Our Added Value Technology
We continuously invest in new technologies to stay at the forefront of chemical service providers.
Service
Our customers benefit from the most efficient, flexible, collaborative and seamless experience possible.
Partnership
Our long-term business success is our customer’s long- term success.

9. Business Focus: Client Satisfaction
Sole focus on the pharmaceutical sector
Highest quality standards
Exclusive custom synthesis
No proprietary products
All compound IP belongs to the customer
Flexible and tailored solutions
Impressive in-house technologies to support different types of chemistry
Product lifecycle management through the Dishman Group
Ongoing review/implementation of new technology
Chromatography (SMB, SFC)
Drug Product Services
High Potency
ADC

10. Our Services Early Phase Late Phase Commercial Phase
Process Research and Rapid
Supply of APIs prepared
according to non cGMP
Late Phase
Process Development
and cGMP
Manufacture
Commercial Phase
Process Optimisation
FDA audited
Manchester (UK)
500 Kg I non GMP
Research
Preclinical
Phase I
Phase II
Phase III
Market
Drug Substances (DS) / API
Aarau (CH)
50 Kg I GMP
Research
Preclinical
Phase I
Phase II
Phase III
Neuland (CH)
50 Kg I GMP
Research
Preclinical
Phase I
Phase II
Phase III
Bubendorf (CH)
200 Kg I GMP
Preclinical
Phase I
Phase II
Phase III
Market

11. Our High Potency Services
Early Phase
Process Research and Rapid
Supply of APIs prepared
according to non cGMP
Late Phase
Process Development
and cGMP
Manufacture
Commercial Phase
Process Optimisation
FDA audited
Riom (FR)
4000 vials I GMP
Preclinical
Phase I
Phase II
Phase III
Drug Products (DP)
Bubendorf (CH)
75 Kg I GMP
Preclinical
Phase I
Phase II
Phase III
Market
Drug Substances (DS) / HAPI
Bavla (India)
200 Kg I GMP
Phase I
Phase II
Phase III
Market
Shanghai (China)
350 Kg I GMP
Phase I
Phase II
Phase III
Market

12. Drug Substances (API) & Drug Products
Process Research
Route scouting
Route development
Process Optimization
Scale-up
cGMP Manufacturing
cGMP chromatography from g to 100s Kg scale
Lifecycle Management
Drug Products
Pre-Formulation Services
Formulation Services
Development and optimization of lyophilization cycles
Aseptic filling
Process Validation (Media Fill Testing)
Liquid forms, semi-solids and injectables

13. October 2010 - confidential
PR&D Laboratory
October confidential 13

14. Regulatory Consultancy
Support and guide customers through successive phases
High quality documentation for successful due diligence
Maintain experience and avoid handovers
Support for the success of a projects for future license, sale or funding
Common & best practices
What is necessary at which stage of development
What adds additional value

15. Commercial Supply Manufacture started in 1996, no product recalls
15 Commercial products
3 Oncology commercial products (parenteral application)
Multiple products undergoing validation (including lifecycle), including several HiPo
1-2 NDA filings annually
Commercial supply into the major markets (US, EU, Japan, Korea, Australia, Brazil)
Regulatory Support
CMC support for IND, IMPD, NDA and MAA
Multiple DMFs (US, EU, Japan)
CTD (Common Technical Document) format
Post-Approval Change Documentation
Type II Drug Master Files (DMFs)
European Drug Master Files (EDMFs)
Commercial Products as of end 2013 (confidential information):
9 APIs – brinzolamide, brimonidine tartrate, lodoxamide tromethamine, nepafenac, tropicamide, apraclonidine HCl, azacitidine (hipo), pomalidomide (hipo), bendamustine (hipo).
2 RegisteredIntermediates – for eribulin mesylate (Eisai), for Iloprost (Bayer).
1 Regulatory Starting Material - for bortezomib (J&J)
3 Ingredients / Excipients – Polyquad, RLM-100, myristinamide

16. Track Record of Quality
SwissMedic
March 2012 – Aarau, Neuland
March 2012 – Bubendorf
No major findings
FDA
September 2011 – Bubendorf
No 483’s noted on this or any previous FDA audit
ANSM (French Health Agency)
May 2012 – Riom
2013 – Korean FDA 
Japan
Accreditation as foreign manufacturer for Japan since 2009
Customers
>25 different customer audits annually
At least 4 different (Top 10 Pharma) customer ESH audits annually

17. Lifecycle Management
Track record of successful technology transfer of processes to Dishman Group
>15 processes transferred to date including RSM, intermediates and launched APIs
Continuous monitoring of process performance
Continuous evaluation and implementation of process improvements (Lean and 6-sigma techniques)
In depth experience of managing the post-approval change processes of all main regulatory bodies
Continuous monitoring of the changing requirements
Transition management to generic supply
Experience of filing CEPs at the EDQM

18. Quality Assurance Strategy
“Fit for Purpose” supply chain
Strategy agreed up front
Classical & Lifecycle validation approach according to FDA guideline
Expedite filing through registration batch approach
Quality by Design approach
Fully compliant with ICH-Q8,9, 10 & 11
PAR studies
Optimisation by statistical DoE as required
Product quality risk assessment

19. Analytical Services Overview
Characterization
Control
Stability
• Structure Elucidation
• Absolute Configuration
• Solubility Profile
• Salt Screening
• Polymorphism
• Particle Sizing
• Compatibility
• Impurity Profiling
Solid State Characterization
Drug Product
Characterization
• Method Development
• Inpurity Tracking
• Method Verification
• Specification Development
• Specification Justification
• Method Validation • Raw Material
• IPC • API
• Release Analysis
• Method Transfer
Reference Standards
ICH Stability
• Stress Stability
• Drug Substance Stability
• Drug Product Stability
• Degradation Profiling

20. Equipment for Drug Products
GMP Production
5 Isolators
Laminar Flow Hoods
1 GMP Freeze Dryer Terruzzi m² CIP+SIP
1 Autoclave
1 Dry Heat Oven
Dedicated Formulation and Pre-formulation Labs
Solid Forms (oral drugs)
Liquid Forms (injectables)
Stability Chambers
Safe location in Switzerland
Fully GMP validated and mapped
Operational at ICH conditions
Stringent IQ, OQ, and PQ
Routing calibration
Continuous monitored (24/7)
Monitoring systems FDA compliant (21CFR Part 11)
Real-time access to data via LIMS-System

21. Equipment for API Manufacturing
70 general-purpose reactors (from 6 L to 4500 L)
5 cryogenic reactors (40 L to 3000 L)
High temp reactor (200 L)
High pressure autoclaves (range of scales)
Hastelloy filter dryers (from 0.25 to 1 m2)
Temp range: -100°C to +160°C
Pressure range: 1 mbar to 25 bar
Milling / Micronization

22. Pilot / Manufactutring
Milling Equipment
Site
Type
Scale
Sieve Size (mm)
GMP
Category
Lab NE
IKA MF 10 basic
5 – 500 g
0.25 – 3
0 - II AA
Jetpharma MC-one
0.5 – 500 g
N/A
Pilot / Manufactutring
Frewitt TC-150
1 – 12 Kg
0.5 / 1 / 5 a
0 - I BU
Frewitt
100 Kg 1
Quadro Comil U10
0.279 / 0.6 / 1 / 4.7
Jetpharma MC-50
0.5 – 2 Kg

23. Loop Milling Volume (L) Transfer Milling Volume (L)
Wet Milling Equipment
Site
Type
Loop Milling Volume (L)
Transfer Milling Volume (L)
Feed (L/hr)
d90 (µm)
GMP
Category
Lab
Mobile*
IKA Magic Lab
≤ 120
20 – 50 a
0 - IV
Pilot / Manufacturing
IKA Process Pilot /4
IKA Process Pilot /4 Atex
IKA DR 2000/5
~ 2500
* Aarau, AA (CH): up to Category II, Neuland, NE (CH): up to category II, Bubendorf, BU(CH): up to category IV; Bavla (IN): up to category IV

24. Freeze and Spray Drying
Site
Type
Productivity Range
Ice Capacity
Condenser T (°C)
# Trays
GMP
Category
Lab
BU (mobile)
Lyo Zirbus 2x3x3/5
max 300 g/run *
max 4 Kg/run
- 80°C
3 (2 L) a
0 - IV
Riom
Telstar Lyobeta 20 (1)
7.2 L/run (bulk)
max 12 Kg/run
4 + 1 NE
Büchi Mini Spray Dryer B- 290
up to 100 g/h*
n.a.
-10°C
0 - II
Pilot / Manufacturing AA
Telstar Lyobeta 20 (2)
max 1 Kg/run*
max 30 Kg/run
Terruzzi (3)
14.4 L /run (bulk)
* (Solutions: 10% w/w)
Max 2'480 vials (2R) - Automatic stoppering possible
Automatic stoppering possible
Max 3'952 vials (2R) - Automatic stoppering possible

25. Chromatography Services g to Kg
g/d
SMB Licosep
10-50
Binary
Separations
racemates
1-5 kg/d
Flash
Chromatography
Biotage 400 L
System
Multi-component
separations
g/d
2x Preparative
HPLC
Knauer +
Dan-process
10 cm ID
Columns
Multi-component
separations
g/d
Preparative HPLC
Novasep
20 cm ID column
5 and 15 cm ID
columns for HiPo
Multi-component
separations
kg/d
Preparative
HPLC
Novasep
30cm and 45cm
ID column
Multi-component
separations
g/d
Preparative
MPLC
Verdot/Armen
Large-scale
Normal phase
Dedicated department
8 people specialized in Chromatographic solutions
Central service supporting all sites
Extensive set of technologies
From feasibility study through to commercial production
August confidential 25 25

26. High Potency Capabilities
Highly Potent APIs for (pre)clinical trials and commercial use
Riom
France
Bubendorf
Switzerland
Bavla
India
Shanghai
China
Aseptic
Filling
Up to 4000 vials
Laboratories
Up to 10 L
Kilo-Scale
Manufacturing
Facility
Up to 250 L
Pilot Plant
Manufacturing
Facility
Up to 1600 L
Large-Scale
Manufacturing
Facility
Up to 1600 L
Large-Scale
Manufacturing
Facility
Up to 8000 L
OEL<1g/m3
OEL<0.1g/m3
OEL<0.1g/m3
OEL<10g/m3
OEL<0.1g/m3
OEL1-100g/m3
Up to Category IV
Up to Category IV
Up to Category IV
Up to Category III
Up to Category IV
Up to Category III

27. HiPo Manufacturing – Cat III

28. HiPo Analytical Capabilities
October confidential 28

29. Categorisation HiPo Criteria Category 0 Category I Category II
Category III
Category IV
Potency (1)
> 500
> 100
100 – 10
10 – 0.1
< 0.1
OEL range (2)
5000 – 1000
1000 – 100
10 – 1
1 – 0.05 *
Toxicity oral LD50 (3)
> 1000
1000 – 300
300 – 50
50 – 5
< 5
NOAEL (4)
100 – 10
10 – 1
1 – 0.1
Acute adverse effects
None
Slight
Moderate; reversible
Moderate – severe; reversible
Severe; irreversible
Chronic adverse effects
Slight – moderate
Moderate; irreversible
Severe; irreversible – lethal
Genotoxicity
None – (+) Ames Test
(+) in a battery of studies
(1) Dose [mg/d] (2) g/m3as 8h – TWA (3) mg/kg, rat (4) 28d, mg/Kg, oral rat
* Standard value based on industrial hygiene data. Lower equipment or process specific values possible, depending on additional measures

30. Project Management Communication
Customer
CARBOGEN AMCIS
Management
Steering Committee
Management
Purchasing
Ad hoc communication
Sales
Project Leader
Weekly Report
Project Leader
Regular Phone Conference Technical Visits
Chemists
Chemists 30

31. Flexible Approach Open Business Model One-off Project
Framework Agreement
FTE Agreement
Manufacturing
• Deliverables • Project budgets
• Payment terms
• Termination
• Overall budget • Payment terms
• Termination
• FTE Rates
• Resource level
• Payment terms
• Renewal • Termination
• Budget ($/Kg)
• Payment terms
• Forecasting
• Termination
Project
Project
Project
Project
Project
Project
Project
Project
Project 31

32. CARBOGEN AMCIS Advantages
Long track record in handling complex and long synthetic processes
500+ projects in 2011
100+ projects involving production (30% of which are HiPo)
126 standalone analytical projects
50+ R&D projects
40+ Stability Studies
20+ Chromatography projects
Phase appropriate development
Robust, reproducible & industry- scalable process
Experience from a broad customer base
Comprehensive package
Within available budget & timelines
Tailored based on customer preferences
One-stop-shop to limit the number of suppliers to be managed for drug products and substances
Commercial track records
Lifecycle management
High quality infrastructure (nonGMP, cGMP)
Flawless audit history

33. What‘s New ? – Bubendorf, Switzerland
~ 4 Mio USD invested
cGMP clean room for antibody drug conjugates (ADCs)
Sterile room (grade D/ C)
OEL <1 µg/m3 8h-TWA
Pressure Cascade (+30 Pa, +15 Pa, 0 Pa, -15 Pa)
Equipment Available:
Isolators, Barrier Systems and Walk-in fume hoods
Bio-safety cabinets (grade C)
Dry oven sterilizer and autoclave for sterilization
~ 1 Mio USD invested
cGMP suite for High Potency Chromatography
Equipment Available:
3 Walk-in-Barrier Hoods HPLC 10 and 15 cm ID column
g/day
1000 ml/min at 70 bar

34. What‘s New ? – Riom, France
Investment: ~ $950,000 USD
Implementation of a new VHP (Vaporized Hydrogen Peroxide) disinfection system
Acquisition of 2 new aseptic filling isolators
New Bag-In/Bag-Out system for HEPA filters exchange
Increased level of sterility assurance in terms of disinfection, air-tightness and air flow
Grade A (ISO 4.8) compliant throughout the entire process

35. What‘s New ? – Bavla, India
New High Potency Kilo-lab (~ 110 m2 floor space)
Class
Separate material and personnel airlocks
Negative Pressure Cascade among corridor/airlocks/operational areas(+15 Pa, 0 Pa, -15 Pa)
HEPA Filters for air in and out (AHU single pass)
[8hr TWA]: 50 ng/m³ > OEL < 1 μg/m³
3 reactors (glass lined and SS) equipped with charging isolators
1 Agitated Nutsche Filter Drier (ANFD) equipped with discharging isolator

36. Thank you! Name Surname, Ph.D. Title Tel: xx-xxx-xxx-xxx
CARBOGEN AMCIS
Hauptstrasse 171
CH-4416 Bubendorf
Switzerland