About Dishman Business units Chemistry capabilities High potency Analytical capabilities Customer service. Why Dishman. Business units.

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2 About Dishman Business units Chemistry capabilities High potency services Analytical capabilities Customer service

3 About Dishman Mission statement Key facts Locations

4 Mission statement Dishman group continually invests in the global pharmaceutical industry, ensuring Dishman s business can provide pharmaceutical customers with high-value, highquality 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

5 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

6 Locations

7 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.

8 Business units

9 Business units Dishman Group Dishman Pharma Services Dishman Specialty Chemicals Carbogen Amcis Dishman Contract Research and Manufacturing Services (CRAMS) Dishman Vitamins & Chemicals Dishman Disinfectants

10 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

11 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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13 Dishman vitamins and chemicals 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

14 Dishman vitamins and chemicals 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 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 About Dishman Business Units Chemistry Capabilities Analytical Capabilities Customer Service High Potency

15 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 OCT (Octenidine) Labsept CHG (Chlorhexidine) Labsept HTD (Hexetidine) Labsept BTC (Benzethonium)

16 CARBOGEN AMCIS EARLY STAGE Process research & rapid supply of APIs LATE STAGE Process development & cgmp manufacture NICHE COMMERCIAL Process optimisation FDA audited Process research and development API Supply to support clinical requirements Niche scale commercial manufacture Highly potent API supply Research Preclinical Phase I Phase II Phase III Market

17 CARBOGEN AMCIS Facilities Aarau, Switzerland Early stage Neuland, Switzerland Early stage Manchester, UK Early / late stage Bubendorf, Switzerland Late stage / commercial Bavla, India Late stage / commercial PR & D cgmp API supply PR & D cgmp API supply PR & D Intermediates Process development cgmp API manufacture Highly potent API Commercial supply Highly potent API

18 Contract research and manufacturing services (CRAMS) EARLY STAGE Process research and API supply to support early phase clinical trials LATE STAGE Process development and cgmp manufacture COMMERCIAL SUPPLY Secure, value-for-money supply CARBOGEN AMCIS Process R&D API supply to support clinical requirements Niche scale commercial manufacture Highly potent API supply Preclinical Phase I Phase II Phase III Market Dishman Process development & scale-up Process optimisation Large scale and commercial manufacture About Dishman Business Units Chemistry Capabilities Analytical Capabilities Customer Service High Potency

19 Contract research and manufacturing services Aarau Neuland Manchester Bubendorf Naroda Bavla Shanghai Process research and development API supply to support early clinical trial requirements Process optimisation Niche scale commercial manufacture Large scale and commercial manufacture of APIs and intermediates Highly potent API supply

20 Contract research and manufacturing services 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

21 R&D lab at Bavla, India

22 Contract research and manufacturing services 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

23 cgmp pilot plant, Bavla

24 Contract research and manufacturing services Full scale and commercial supply 12 manufacturing plants US FDA inspected facilities > 1150 m 3 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

25 A cgmp manufacturing plant, Bavla Dishman offer an unparalleled range of both dedicated and multipurpose facilities for the production of APIs and intermediates

26 Dishman China Shanghai chemical industrial park $18M investment Production facility operational mid 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

27 Chemical industrial park, Shanghai, China

28 Chemistry capabilities

29 Chemistry equipment Standard equipment More than 250 hoods available for PR&D 250 general purpose reactors (50L- 16,000L) Temp-range: -80 o C to +220 o C 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 All facilities follow internationally recognised equipment qualification and change control procedures About Dishman Business nits Chemistry capabilities High potency Analytical capabilities Customer service

30 Chemistry equipment Chemical laboratory Kilo scale set-up

31 Pilot plant, R&D centre at Bavla, India

32 Chemistry equipment Manufacturing, commercial scale equipment

33 Chemistry equipment Filters & filter dryers Agitated Nutch & pressure Nutch filters / filter dryers from m 3 Centrifuge 50 centrifuges from 480mm 1440mm diameter (35-350kg capacity) Rotary dryers 30 RVD from 150-5,000L glass - Hastealloy Jet milling kg / hour Mechanical mills Up to 300kg / hour Spray drying 50 kg / hour feed rate

34 High potency services

35 Highly potent API supply 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

36 Highly potent API supply

37 HiPo laboratories 4 category 4 (<1 µg/m 3 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

38 HiPo kilo plant Category 4 ( <1 µg/m 3 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 m 2 Hast. filter dryer in glove box Barrier isolator technology for solids handling (dispensing, loading, unloading)

39 HiPo manufacturing Category 3 (1-10 µg/m 3 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 m 2 Hast. filter dryer Pressurized airlocks on all floors La Calhène transfer ports for solids charging in reactors Ventilation segregated

40 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

41 HiPo facility in Bavla Internal fit out of building underway Fully cgmp compliant Complimentary to existing Bubendorf facility Completion H Up to 1,600 L scale

42 Building concept Dedicated stand alone facility with dedicated utilities Category 3(OEL<10µg/m 3 ) and 4(OEL<1µg/m 3 ) m 2 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 1.0m 2 pressure filter dryer Further cells are designed for reactors up to 2500L The custom cell can take reactors up to 6300 L

43 Capability Category 3(OEL<10µg/m 3 ) and 4(OEL<1µg/m 3 ) 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

44 Analytical capabilities

45 Analytical services overview Characterization Structure elucidation Physical characterisation Polymorphism investigation DSC, XPRD, FTIR studies Particle sizing Impurity profiling Impurity identification Formulation studies Solubility profile Salt screening Compatibility studies Control Method development Method validation Raw material IPC API Method transfer Specification development Release analysis Stability ICH stability studies Stressing studies Photostability studies Drug substance stability Drug product stability Degradation profiling

46 Analytical equipment Chromatography Spectroscopy Physical 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

47 Customer service Project management Technology transfer Quality, regulatory, SHE

48 Project management Customer Management Steering committee Dishman Management Purchasing Ad hoc communication Sales Project leader Routine reporting, tracking Project leader Chemists Routine phone conferencing, technical visits Chemists Direct communication /phone Open, responsive customer service and project management

49 Project management Raw Material Price + Delivery Enquiry Package Evaluation Customer Review Dedicated project manager assigned Customer interactive process Clarity of requirements Quotation Comprehensive, detailed, transparent Project Initiation Define detailed outputs, deliverables Routine Reporting Completion + Review Rigorous, proactive tracking Provision of data, documentation as appropriate, formal project review Open, responsive customer service and project management

50 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

51 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

52 Technology transfer example 2 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

53 Technology transfer example 3 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

54 Quality and regulatory overview QA QC RA 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

55 SHE overview Safety Health Environment OHSAS 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 certified Environment and social audits Waste management programme Environmental laboratory

56 Why is Dishman the partner for you?

57 People Alan Barnes PRESIDENT QA/QC/RA/ADL Dr Himani Dhotre V.P. SCIENTIFIC PROJECT COORDINATION Dr Denish Shah GENERAL MANAGER R&D Dr Ravi Raval GENERAL MANAGER PILOT PLANT 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 Henk Pluim DIRECTOR TECHNOLOGY TRANSFER

58 ? Customer Service A relationship driven business model Transparency 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 Adding Value Commitment to deliver cost competitive, technical excellence Our business is successful only when our customers are successful Partnership A dynamic, global partner offering a continuum of services Open to new ideas, new solutions, new ways of doing business