carbogen amcis company overview. 2 who we are carbogen amcis is a swiss leading provider of drug...
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CARBOGEN AMCISCompany Overview
2
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
Locations
Dishman facilities & officesCARBOGEN AMCISLocal sales
Dishman CRAMS
AarauSwitzerlandEarly /Commercial Phase
NeulandSwitzerlandEarly / Commercial Phase
ManchesterUnited KingdomEarly / Late Phase
BubendorfSwitzerlandLate Phase / Commercial
BavlaIndiaLate Phase / Commercial
RiomFranceEarly Phase
ShanghaiChinaLate Phase / Commercial
BavlaIndiaLate Phase/ Commercial
CARBOGEN AMCIS
Company History
2006Acquisition of CARBOGEN AMCIS AG by Dishman Pharmaceuticals and Chemicals Ltd
2000Acquisition of CarboGen and AMCIS by Solutia
1990Foundation CarboGen Spin-off of the University of Zurich focused on research services and early-phase API supply
2005Investment in High Potency Facility in Bubendorf
2006Creation of CARBOGEN AMCIS AG
2007
Creation of CARBOGEN AMCIS Ltd in
Manchester, UK
2008New High Potency Facility in Ahmedabad, India
1982Foundation AMCIS joint an pharma company focused venture with on PR&D and cGMP manufacturing
2012Acquisition of CARBOGEN AMCIS SAS in Riom, France
Business Units & Company Structure
DishmanSpecialty Chemicals
Dishman Pharma Services
DishmanVitamins & Chemicals
DishmanDisinfectants
CARBOGEN AMCIS Dishman CRAMS
AarauSwitzerlandEarly/CommercialPhase
NeulandSwitzerlandEarly/Commercial Phase
ManchesterUnited KingdomEarly/Late Phase
BubendorfSwitzerlandLate Phase/Commercial
BavlaIndiaLate Phase/Commercial
RiomFranceEarly Phase
ShanghaiChinaLate Phase/Commercial
Dishman Marketable Molecule
BavlaIndiaLate Phase/Commercial
Dishman Group
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 14001:2004, OHSAS-18001:2007
Successful audit history– FDA inspected May 2006 (Bavla),
Feb 2010 (Naroda), March 2012 (Bavla, Ahmedabad)
– EDQM/TGA inspected June 2009 (Bavla), TGA: Sept 2011 (Bavla)
– DCGI / WHO: July 2006, Feb 2010, May 2012
– Korean FDA Feb 2013 ( Naroda )– Accreditation as foreign
manufacturer for Japan
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
Our Added Value
TechnologyWe continuously invest in new technologies to stay at the forefront of chemical service providers.
ServiceOur customers benefit from the most efficient, flexible, collaborative and seamless experience possible.
PartnershipOur long-term business success is our customer’s long-term success.
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
Our Services
Early PhaseProcess Research and Rapid
Supply of APIs preparedaccording to non cGMP
Late PhaseProcess Development
and cGMPManufacture
Commercial PhaseProcess Optimisation
FDA audited
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
Manchester (UK)500 Kg I non GMP Research Preclinical Phase I Phase II Phase III Market
Drug Substances (DS) / API
Our High Potency Services
Early PhaseProcess Research and Rapid
Supply of APIs preparedaccording to non cGMP
Late PhaseProcess Development
and cGMPManufacture
Commercial PhaseProcess Optimisation
FDA audited
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
Bubendorf (CH)75 Kg I GMP
Preclinical Phase I Phase II Phase III Market
Drug Substances (DS) / HAPI
Riom (FR)4000 vials I GMP Preclinical Phase I Phase II Phase III
Drug Products (DP)
Drug Substances (API) & Drug Products
Drug Substances / API
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
13October 2010 - confidential
PR&D Laboratory
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
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)
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 No major findings 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
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
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
Analytical Services Overview
• 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
Control StabilityCharacterization
Equipment for Drug Products
GMP Production
5 Isolators
Laminar Flow Hoods
1 GMP Freeze Dryer Terruzzi 1.2 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
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
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 0 - II
Pilot / Manufactutring
AA Frewitt TC-150 1 – 12 Kg 0.5 / 1 / 5 0 - I
BU Frewitt 100 Kg 1 0 - I
NE Quadro Comil U10 1 – 12 Kg 0.279 / 0.6 / 1 / 4.7 0 - I
AA Jetpharma MC-50 0.5 – 2 Kg N/A 0 - I
Wet Milling Equipment
* 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
Site TypeLoop
Milling Volume (L)
Transfer Milling
Volume (L)
Feed (L/hr)
d90 (µm) GMP Category
Lab
Mobile* IKA Magic Lab 0.5 - 5 0.5 - 5 ≤ 120 20 – 50 0 - IV
Mobile* IKA Magic Lab 0.5 - 5 0.5 - 5 ≤ 120 20 – 50 0 - IV
Pilot / Manufacturing
Mobile*IKA Process Pilot 2000/4
10 - 100 100 - 1000 120 -500 20 – 50 0 - IV
Mobile*IKA Process Pilot 2000/4 Atex
10 - 100 100 - 1000 120 -500 20 – 50 0 - IV
Mobile* IKA DR 2000/5 100 - 400 400 - 5000 ~ 2500 20 – 50 0 - IV
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) 0 - IV
Riom Telstar Lyobeta 20 (1)
7.2 L/run (bulk)
max 12 Kg/run - 80°C 4 + 1 0 - IV
NEBüchi Mini Spray Dryer B-290
up to 100 g/h*
n.a. -10°C n.a. 0 - II
Pilot / Manufacturing
AA Telstar Lyobeta 20 (2)
max 1 Kg/run*
max 30 Kg/run - 80°C 4 + 1 0 - II
Riom Terruzzi (3) 14.4 L /run (bulk)
max 30 Kg/run - 80°C 4 + 1 0 - IV
* (Solutions: 10% w/w)(1) Max 2'480 vials (2R) - Automatic stoppering possible(2) Automatic stoppering possible(3) Max 3'952 vials (2R) - Automatic stoppering possible
25
Chromatography Services g to Kg
200-2000 g/d
SMB Licosep10-50Binary
Separationsracemates
1-5 kg/d
Flash Chromatography
Biotage 400 LSystem
Multi-componentseparations
20-350 g/d
2x PreparativeHPLC
Knauer + Dan-process
10 cm IDColumns
Multi-componentseparations
500-10000 g/d
Preparative MPLC
Verdot/ArmenLarge-scale
Normal phase
100-1500 g/d
Preparative HPLCNovasep
20 cm ID column5 and 15 cm ID columns for HiPoMulti-component
separations
0.4-30 kg/d
Preparative HPLC
Novasep30cm and 45cm
ID columnMulti-component
separations
August 2013 - confidential
High Potency Capabilities
Highly Potent APIs for (pre)clinical trials and commercial use
Pilot PlantManufacturing
Facility
Up to 1600 L
Laboratories
Up to 10 L
OEL<0.1g/m3
Up to Category IV
Kilo-Scale Manufacturing
Facility
Up to 250 L
Large-ScaleManufacturing
Facility
Up to 1600 L
Large-ScaleManufacturing
Facility
Up to 8000 L
BubendorfSwitzerland
BavlaIndia
ShanghaiChina
OEL<0.1g/m3
Up to Category IV Up to Category III
OEL<0.1g/m3
Up to Category IV Up to Category III
OEL<10g/m3
RiomFrance
Aseptic Filling
Up to 4000 vials
OEL<1g/m3
Up to Category IV
OEL1-100g/m3
HiPo Manufacturing – Cat III
28October 2010 - confidential
HiPo Analytical Capabilities
Categorisation
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 – 100 100 – 10 10 – 1 1 – 0.05 *
Toxicity oral LD50
(3)
> 1000 1000 – 300 300 – 50 50 – 5 < 5
NOAEL (4) > 100 100 – 10 10 – 1 1 – 0.1 < 0.1
Acute adverse
effects
None Slight Moderate;
reversible
Moderate – severe;
reversible
Severe; irreversible
Chronic adverse
effects
None None Slight – moderate Moderate;
irreversible
Severe; irreversible
– lethal
Genotoxicity None None None – (+) Ames
Test
(+) in a battery of
studies
(+) 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
HiPo
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Project Management Communication
Steering Committee
Weekly Report
Regular Phone Conference Technical Visits
Management
Customer
Project Leader
Chemists
Purchasing Ad hoc communication
Management
CARBOGEN AMCIS
Project Leader
Chemists
Sales
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Flexible Approach
Open Business Model
One-off ProjectFrameworkAgreement
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
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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
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
50 - 500 g/day
1000 ml/min at 70 bar
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
What‘s New ? – Bavla, India
New High Potency Kilo-lab (~ 110 m2 floor space)
Class 100.000
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
Thank you!
Name Surname, Ph.D.TitleTel: xx-xxx-xxx-xxxCARBOGEN AMCIS Hauptstrasse 171CH-4416 BubendorfSwitzerland