dishman corporate presentation 26may09 for pdf trial and error · may 2009 mission statement...

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About Dishman

Business units

Chemistry capabilities

High potency services

Analytical capabilities

Customer service

Why Dishman

About Dishman ¦ Chemistry capabilities ¦ Analytical capabilities ¦ Customer service ¦High potency ¦ Why DishmanBusiness units ¦

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About Dishman

Mission statement

Key facts

Locations


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Mission statement

Dishman group continually invests in the global pharmaceutical industry, ensuring Dishman’s business can provide pharmaceutical customers with high-value, high-quality products and services today and in the future.

Our focus is to add value to the global pharmaceutical industry by serving as a reliable partner.

Our business is successful only when our customers are successful


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Dishman group key facts

• Established in 1983

• Public company quoted on BSE

• US $200 M turnover company

• Year on year growth more than 30% since 2004

• More than 1,000 technical staff

• Global presence – manufacturing sites in Europe (5), India (2), China, Saudi Arabia

• Successful audit history

• ISO 9001:2000, ISO 14001:2004, OHSAS-18001:2007

• FDA inspected, May 2006


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Locations


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Jay R. Vyas, Managing Director

“I saw the need for a company that could provide high

quality, high value products and services and be a good,

reliable partner to pharmaceutical companies

worldwide”

“Having a competitive cost base and efficient operations

is important, but what’s really key is the quality of our

people, the service they provide, and the value they

offer to our pharmaceutical customers.”


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Business units


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Business units

Dishman Group

DishmanDisinfectants

DishmanVitamins & Chemicals

DishmanContract Research and Manufacturing Services (CRAMS)

Carbogen Amcis

DishmanSpecialty

Chemicals

Dishman Pharma Services


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Dishman specialty chemicals

• Manufacture and supply of quaternary compounds (Quats)

• Extensive product range including ammonium and phosphonium high purity solid Quats, phosphoranes and wittig reagents

• Applications as phase transfer catalysts, personal care ingredients, fine chemicals, pharma intermediates and disinfectants

• Dedicated facilities – Naroda, India

• A number of products made under GMP manufacturing

• Maintain local product stocks

• Significant expertise in custom manufacturing of Quats and fine chemicals


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Dishman specialty chemicals

• Manufacture of quality active pharmaceutical ingredients (APIs) and intermediates

• Expertise in process optimization and large scale cGMP production

• An offering of over 25 APIs

• Substantial regulatory expertise and support

• Development of DMFs, CTDs for advanced intermediates and final APIs

• Strong technology offering to both the generic and ethical pharmaceutical industry


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• Established 1948

• Acquired by Dishman in 2007

• Cholesterol and vitamin D products

• Based in Veenendaal (Netherlands)

• cGMP production

• Continuous saponification facility

• Large scale chromatography

Sometimes nature needs a helping hand

Dishman vitamins and chemicals


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Dishman vitamins and chemicals

Cosmetics

• Cholesterol NF and HP (emulsifier)

• Dusoran MD (hair care)

• Dusogel (gelifier for cosmetics)

Technical uses

• Cholesterol NF (liquid crystals)

• Lanolin Alcohol

• Lanolin Fatty Acids

Custom work

• On request

Pharmaceuticals

• Ergocalciferol (vitamin D2)

• Cholecalciferol (vitamin D3)

• Dohyfral (vitamin D3 in oil)

• DHT2

• Calcitriol

• Calcifediol

• Alfacalcidol

• Cholesterol HP

Food/feed

• Cholecalciferol

• Dohyfral

• Cholesterol SF and XG

About Dishman ¦ Chemistry Capabilities ¦ Analytical Capabilities ¦ Customer Service ¦ High Potency ¦ Why DishmanBusiness Units ¦

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Dishman disinfectants

• Antiseptics & disinfectants

• Standardized & stabilized for physical, chemical & microbial properties

• Documented as per regulatory requirements

• Innovative user friendly packs

• Superior over leading brands for MIC

Labsept®HTD (Hexetidine) Labsept®BTC (Benzethonium)

Labsept®OCT (Octenidine) Labsept®CHG (Chlorhexidine)


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CARBOGEN AMCIS

Research Preclinical Phase I Phase II Phase III Market

Niche scale commercial manufacture

API Supply to support clinical requirements

Process research and development

Highly potent API supply

EARLY STAGEProcess research & rapid

supply of APIs

LATE STAGEProcess development& cGMP manufacture

NICHE COMMERCIALProcess optimisation

FDA audited


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Aarau, SwitzerlandEarly stage

PR & D

cGMP API supply

Neuland, SwitzerlandEarly stage

PR & D

cGMP API supply

CARBOGEN AMCIS

Facilities

Manchester,UK

Early / late stage

PR & D

Intermediates

Bubendorf, SwitzerlandLate stage / commercial

Process development

cGMP API manufacture

Highly potent API

Bavla, India

Late stage / commercial

Highly potent API

Commercial supply


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Contract research and manufacturing services (CRAMS)

Large scale and commercial manufacture

Process optimisation

Process development & scale-up

EARLY STAGEProcess research and API supply to support early phase clinical trials

LATE STAGEProcess development and

cGMP manufacture

COMMERCIAL SUPPLYSecure, value-for-money

supply

About Dishman ¦ Chemistry Capabilities ¦ Analytical Capabilities ¦ Customer Service ¦ High Potency ¦ Why DishmanBusiness Units ¦

Process R&D

API supply to support clinical requirements


Preclinical Phase I Phase II Phase III Market


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AM

CIS

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Aarau Neuland Manchester Bubendorf Naroda Bavla Shanghai

Contract research and manufacturing services

Process research and development

API supply to support early clinical trial requirements

Process optimisation


Large scale and commercial manufacture of APIs and intermediates



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Process R&D

• Problem solving and safe, efficient scale-up

• Delivery of robust, economic, optimised processes

• 200 R&D staff, 70% higher degree

• 250 fume hoods

• Continuous 3 shifts, 6 day, R&D operations (Bavla)

• Strict IP protection policies

We protect our customers interests as if they were our own


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R&D lab at Bavla, India


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Kilo, Pilot Scale

• Extensive range of segregated, purpose-built, kilo and pilot scale facilities, for cGMP production of API

• Integral part of R&D centres to facilitate maximum interaction and ensure seamless process transfer from laboratory to plant

• Reactions ranging from 50L to 3000L

• Production from kg to several hundred kg scale


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cGMP pilot plant, Bavla


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Full scale and commercial supply

• 12 manufacturing plants

• US FDA inspected facilities

• > 1150 m3 cGMP reactor capacity

• Skills and capabilities encompassing all routine chemistries and a wide range of sophisticated modern technologies

• Multi-site, multi-country locations

• Over $40M invested in the last 3 years


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A cGMP manufacturing plant, Bavla

Dishman offer an unparalleled range of both dedicated and multipurpose facilities for the production of APIs and intermediates


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Dishman China

• Shanghai chemical industrial park• $18M investment

• Production facility operational mid 2009

• 4 segregated suites with capability to interlink• 10 reactors from 2500L to 8000L• Class 100,000 product separation, drying, solids handling• Fully segregated RM and finished API warehousing

• QC capabilities for API product release and sourced RM release

Multiple site risk management for pharmaceutical customers


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Chemical industrial park, Shanghai, China


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Chemistry capabilities


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Chemistry equipment

Standard equipment

• More than 250 hoods available for PR&D

• 250 general purpose reactors (50L-16,000L)

• Temp-range: -80oC to +220oC

• Pressure range: 1mbar to 20bar

• Cryogenic reactors to 2,500L

Special equipment

• High pressure autoclaves up to 9,000L

• Dedicated hydrogenation to 5,000L at 20 bar

• Dedicated ozonolysis to 3,000L, 20kg/hr ozone

• Jet milling / micronisation

About Dishman ¦ Chemistry capabilities ¦ Analytical capabilities ¦ Customer service ¦High potency ¦ Why DishmanBusiness nits ¦

All facilities follow internationally recognised equipment qualification and change control

procedures

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Chemistry equipment

Chemical laboratory Kilo scale set-up


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Pilot plant, R&D centre at Bavla, India


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Chemistry equipment

Manufacturing, commercial scale equipment


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Chemistry equipment

Filters & filter dryers

• Agitated Nutch & pressure Nutch filters / filter dryers from 0.5-7.5m3

Centrifuge

• 50 centrifuges from 480mm –1440mm diameter (35-350kg capacity)

Rotary dryers

• 30 RVD from 150-5,000L glass -Hastealloy

Jet milling

• 150-200kg / hour

Mechanical mills

• Up to 300kg / hour

Spray drying

• 50 kg / hour feed rate


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High potency services


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• Offered under the CARBOGEN AMCIS business

• Containment facilities for PR&D, clinical trial and commercial material

• Dedicated analytical labs

• 4 R&D labs

• Kilo plant

• Large scale manufacturing facilities (2009, Bavla)

• Successful FDA PAI of HiPo product February 2008


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HiPo laboratories

• 4 category 4 (<1 µg/m3 OEL) laboratories

• Class 10,000 clean room

• Barrier benches

• Pressurized airlocks

• Dedicated clean-down areas

• Fume hoods with HEPA filters

• Solids handling isolator with drying oven

• Laminar-Flow for analytical samples preparation


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HiPo kilo plant

• Category 4 ( <1 µg/m3 OEL)

• Facility operates over 3 floors

• 160 L GL reactor

• 250 L GL reactor

• 250 L Hast reactor

• 100 L Hast reactor

• Temp -100°C to +160°C, Press.12 bar

• 0.125 m2 Hast. filter dryer in glove box

• Barrier isolator technology for solids handling

(dispensing, loading, unloading)


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HiPo manufacturing

• Category 3 (1-10 µg/m3 OEL)

• 250 L Gl reactor

• 250 L SS reactor

• 630 L Hast. reactor

• Temp -100°C to +160°C, Pres. to 25 bar

• 0.25 m2 Hast. filter dryer

• Pressurized airlocks on all floors

• La Calhène transfer ports for solids charging

in reactors

• Ventilation segregated


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HiPo analytical capabilities

• Laminar flow hoods and glove boxes for sample preparation

• NMR

• HPLC (SEC-UV, GPC-MALLS, HPLC-MS)

• Hydrolysis method available to capture polymer-bound impurities for conjugates

• GC (FID, Headspace)

• Titrations

• pH-Measurements

• UV/VIS

• IR (KBr pellet)

• KF-determination

• DSC (only closed pan)

• Heavy metals

• Residue on ignition

• Optical rotation

• RC1


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HiPo facility in Bavla

• Internal fit out of building underway

• Fully cGMP compliant

• Complimentary to existing Bubendorf facility

• Completion H2 2009

• Up to 1,600 L scale


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Building concept

• Dedicated stand alone facility with dedicated utilities

• Category 3(OEL<10µg/m3) and 4(OEL<1µg/m3)

• 4’300 m2 of operational floor space

• Designed to hold 4 segregated High potency handling cells each with 3 reactors and filter/drying plus larger ‘custom’ cell

• Initially 2 cells will be fitted out each having 1 x 630 L, 1 x 1000 L and 1 x 1600 L and 1.0m2 pressure filter dryer

• Further cells are designed for reactors up to 2500L

• The ‘custom’ cell can take reactors up to 6300 L


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Capability

• Category 3(OEL<10µg/m3) and 4(OEL<1µg/m3)

• Barrier Isolation technology

• Fully cGMP compliant

• Able to handle cytotoxic and cytostatic compounds

• Particle size reduction capability

• 2 x Development Labs

• 1 x QC/Analytical Lab


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Analytical capabilities


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Stability

• ICH stability studies

• Stressing studies

• Photostability studies

• Drug substance

stability

• Drug product

stability

• Degradation profiling

• Method development

• Method validation

• Raw material

• IPC

• API

• Method transfer

• Specification

development

• Release analysis

Control

Analytical services overview

• Structure elucidation

• Physical

characterisation

• Polymorphism

investigation

• DSC, XPRD, FTIR

studies

• Particle sizing

• Impurity profiling

• Impurity identification

• Formulation studies• Solubility profile• Salt screening• Compatibility studies

Characterization


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Analytical equipment

• HPLC (DAD, UV, RI) • Ion chromatography• HPLC-MS • GC (FID, NPD)• GC (Head space) • GC-MS • TLC with scanner

• NMR 400 MHz• FTIR • ICP• CHN• XRD• UV-Spectrophotometers• Polarimetry

• Malvern particle sizer• Microscopy• DSC• Auto titrators• Nephelometer• Refractometer• Wet chemical techniques

Chromatography Spectroscopy Physical


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Customer service

Project management

Technology transfer

Quality, regulatory, SHE


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Project management

Management

Purchasing

Project leader

Chemists

Management

Sales

Project leader

Chemists

Steering committee

Ad hoc communication

Routine reporting, tracking

Routine phone conferencing, technical visits

Open, responsive customer service and project management

Customer Dishman

Direct communication e-mail/phone


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Project management

Raw Material Price + Delivery

• Dedicated project manager assigned

• Customer interactive process

• Clarity of requirements

• Comprehensive, detailed, transparent

• Define detailed outputs, deliverables

• Rigorous, proactive tracking

• Provision of data, documentation as appropriate, formal project review

Enquiry Package

Evaluation

Customer Review

Quotation

Project Initiation

Routine Reporting

Completion + Review

Open, responsive customer service and project management


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Technology transfer

• People• Dedicated teams

• Process• Robust well defined processes• Tech transfer package and master plan• Trialling, piloting and change review• All party sign-off

• Expertise• Proven track record• Substantial, multiple project experience


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Technology transfer – example 1

• European customer requiring contract manufacture of a late lifecycle API

• Tech transfer and process optimisation at Bavla site

• Pilot scale validation batches then 10mt commercial production within 9 months

• Agreed regulatory programme completed and client provided with full technical dossier to enable regulatory filings

• Successful project resulted in client transfer of a further 3 projects into the Dishman group

Main advantages are security of supply and cost competitive commercial manufacture


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• US customer, 3 stage process, very high purity

• CARBOGEN AMCIS (Manchester) produced 600 kg

• Bavla scaled the entire process to 1500 kg production

• Now going through final QA hurdles prior to acceptance.

Likely volumes 8 t/pa

• Product launched in Japan, soon to be launched in US & EU

Seamless scale-up within the Dishman group affording,

cost competitive commercial supply


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• Multinational pharmaceutical company required significant cost of goods reduction to deliver market leading drug product

• Dishman optimised process and built dedicated facility for API production

• Dishman further reduced costs by developing its own routes for the 3 key starting materials

• Overall costs reduced by more than 50%. Routine commercial manufacture ongoing at Bavla Site

Significant cost advantage to customer, simplified and

secure supply chain



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Quality and regulatory overview

• Batch release procedure

• Record retention

• Sample retention

• Documentation maintenance

• Internal audits

• Change control

• Annual product reviews

• Manufacturing investigations

• API sampling

• Audit preparation & hosting

• Validation related activities

• Batch release testing

• Chromatographic techniques

• Wet chemical techniques

• Microbiological techniques

• Impurity tracking

• Method validation

• Method transfer

• Result trending

• Specification development

• US Type II DMF

• ASMF

• CEP

• Regulatory responses

• Dossier maintenance

• Annual updates

• eCTD capabilities

QC RAQA


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SHE overview

• OHSAS 18001 certified

• Safety training programme

• Permit to work system

• Fire prevention &

protection plan

• Emergency and accident

management programme

• Risk assessment & Hazop

studies

• Safety audits

• Occupational health &

hygiene programme

• Work place/ personnel

monitoring

• Doctor, health centre

• Periodical health check

• ISO 14001 certified

• Environment and social

audits

• Waste management

programme

• Environmental laboratory

Health EnvironmentSafety


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Why is Dishman the partner for you?


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People

Our biggest asset is our people:

• Well educated and experienced staff

• Depth and breadth of chemistry and industry experience

• Expert resources not hired hands

Dr Himani Dhotre

V.P. SCIENTIFIC PROJECT COORDINATION

DIRECTOR TECHNOLOGY TRANSFER

Dr Henk Pluim

Dr Denish ShahGENERAL MANAGER

R&DPRESIDENT

QA/QC/RA/ADL

Alan Barnes


Dr Ravi RavalGENERAL MANAGER

PILOT PLANT

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Why Dishman?

Partnership

• A dynamic, global partner offering a continuum of services

• Open to new ideas, new solutions, new ways of doing business

Customer Service• A relationship driven business model • Transparency

Adding Value• Commitment to deliver cost competitive, technical excellence• Our business is successful only when our customers are successful


Reliability • Technical and manufacturing excellence in multiple-country locations • Unparalleled range of physical assets, high quality infrastructure

Quality • People• Recognised best practice in systems, procedures and processes

Customer Service• A relationship driven business model • Transparency

Adding Value• Commitment to deliver cost competitive, technical excellence• Our business is successful only when our customers are successful

Reliability • Technical and manufacturing excellence in multiple-country locations • Unparalleled range of physical assets, high quality infrastructure

Quality • People• Recognised best practice in systems, procedures and processes

dishman corporate presentation 26may09 for pdf trial and error · may 2009 mission statement...

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