1. NORSC Presentation

2. What is iPRD?  Founded in 2008 at the University of Leeds  Established to support chemical companies of all sizes by providing solutions for product and process development.  Research focus driven entirely by challenges in chemical manufacturing  Developing technologies to improve products and product manufacture:  Working with a diverse range of industries: RobustnessProcess Efficiency (throughput, waste, energy) Quality ControlEnvironmental & worker safety issues Product CostSustainability (raw materials, supply chain) ConstructionAgrochemicalWaste RecoveryDyes & Pigments (textiles) Personal CareElectronicsMineral ProductsEnergy & Renewables PharmaceuticalSecurity PrintingAutomotiveFine & Speciality Chemicals

3. John Blacker Chris Rayner Professor of Organic Chemistry >20 years experience of working with a wide range of industries (pharma, cosmetics & power generators!) Director of 3 chemistry-based SMEs (pigmentation, carbon capture) Frans Muller Prof. of Chem. Process Engineering 17 year’s experience in industrial product development (AZ, Syngenta) Focused on the interaction between process and equipment Expert in Scale up, mixing, modelling and computer simulation. Management Team Steve Marsden Professor of Organic Chemistry >30 industrial research collaborations Secondment in the speciality chemicals industry examining the challenges in technology transfer between Universities & industry. Professor of Process Chemistry 19 year’s experience in the fine chemicals industry (ICI) Technical Director at Piramal Healthcare. Research interests include catalysis Inventor on 25 patents Kevin Roberts Brotherton Professor of Chemical Engineering World expert in the formation and processing of crystalline solids Application in Process R&D (PAT) Industrial Fellowship at AstraZeneca Philip Kocienski FRS Professor of Organic Chemistry New methodology for the synthesis of biologically active targets >30 years consulting experience with pharmaceutical and agrochemical industries

4. Integration of Expertise at iPRD  Expertise at Leeds throughout the product development process  Industrial R&D uses integrated teams of chemists and chemical engineers to solve problems in a holistic manner  iPRD working model reflects the industrial approach Route design Process design Isolation design Formulation design Product Concept/ candidate Synthetic chemistry Catalysis Separation sci/eng Crystallisation Particle Science Physical organic chem. Reaction engineering

5. Expertise Chemistry and Process Catalysis Crystallisation/ Particle Science Process Engineering Formulation

6. Process Laboratory  Industry-standard development and scale-up facilities and procedures  £4.8m investment by Yorkshire Forward/EU (ERDF)  650m 2 refurbished laboratory space  Unique facility in academia worldwide −non-aqueous solvent handling capabilities  Projects executed by industrially-experienced scientists  Dedicated laboratory manager and technician  On-site mechanical and electrical workshops  Safety training for all staff and students  Access to all University analytical facilities  Specialist services provided by professional partners:  iPOS (Agilent Centre of Excellence): http://www-old.hud.ac.uk/ipos/http://www-old.hud.ac.uk/ipos/  ParticlesCIC (Particle Characterisation): http://particlescic.org/http://particlescic.org/

7. Batch Manufacture  Remotely-controlled 20 and 50 L reactors with: −5 L addition vessel −20 L distillate receiver −1 m 2 condenser −variable speed agitator motor −pitched bladed agitator  ATEX rated (temperature, gas apparatus)  Operational temperature range: -20 to 160 o C  Integrated PAT: −Temperature sensors (Tr, Tj, condenser, BOV) −Coolant flow meters for vessel jackets and condensers −Rotation sensors on agitator to monitor agitation rate −Reaction monitoring via IR, pH and conductivity probes −FBRM (LasenTech) probe for crystallisation monitoring

8. Flow Manufacture Flow Reactors  Syrris-Afrika Microreactor  2*800ml high pressure cascade CSTR  Variable residence time static mixer 40-200ml/min  Oscillating baffled reactor  High pressure fixed-bed catalyst flow reactor  Semi-continuous microwave  Mercury-lamp photoreactor Flow Work-up and isolation  Continuous liq-liq extraction  Lab-scale thin film evaporator  Short-path continuous distillation  Rotary drum filter

9. Process Development Technologies Specialist equipment available to aid all aspects of process development: Small-scale parallel reactors (solubility/reaction screening) Continuous reaction and work-up assessment High pressure reaction vessels Calorimetry and Process Safety Crystallisation and Isolation Development 100  m

10. Current Projects TSB Immobilised Catalyst Project for purer, lower cost products in more intensive process iPRD, AstraZeneca, Pfizer, Reaxa, Cambridge Uni TSB Mild, selective extraction of chemicals from seaweed iPRD, Böd Ayre Products, Critical Processes, The Body Shop, Independent Cosmetic Advice, Higgins Consultancy IMI/EUGreen Chemistry for the 21 st Century 20 academic and industry collaborators across Europe including Durham, York, Manchester, Leeds TSB Control of crystal growth for integrated primary and secondary manufacturing iPRD, AstraZeneca, Pfizer, Syngenta, Avantium TSB Mild, selective extraction of chemicals from fruit iPRD, Critical Processes, Higgins Consultancy EPSRC Phosgene-free synthesis of isocyanates for fine chemicals iPRD, Pfizer

11. Avoiding going through the mill  Pharmaceuticals/agrochemicals are typically isolated as large crystals of variable size (primary manufacture)  Processing to the appropriate size for formulation by milling, granulation, or micronisation (secondary manufacture) is energy intensive & wasteful  Leeds technology facilitates real-time measurement of crystal growth  TSB High Value Manufacturing award - £1.6m project (£590k @ Leeds) with Syngenta, Pfizer, AstraZeneca, Avantium to investigate effects of crystal growth modifiers on control of crystal size  Aim: avoid secondary manufacture (safer, cheaper, more active products) 100  m

12.  Strategic process and manufacture related R&D using Leeds and other expertise, public-private funding via individual or collaboratively funded projects  Contract work in process development, testing and small scale manufacture  Students trained in process R&D  Professional development courses  Industrial Club  Consultancy and advisory service Industry Offering

13. Process Design Process Understanding Process Measurement Technology Design Process Optimisation Bulk ManufactureData Analysis Physical & Chemical Analysis Renewable Feedstocks Product Isolation Continuous Processing Materials Safety Analysis Catalysis Green Chemistry Scale-Up Risk Assessment Understanding Impurities Process Modelling Waste Stream Reduction & Recycling PAT Process Understanding Reaction Screening Improving Energy Efficiency Understanding Bulk Properties Our Research and Consultancy Services include:

14.  iPRD has an excellent track record of delivering high quality contract research and consultancy projects  All services tailored to meet client’s commercial needs  Contracts managed by University KT professionals (confidentiality, IP)  Our experts have a diverse skill set but a common focus: application of research expertise to commercial business situations Contract & Consultancy Services

15. iPRD Industrial Club  iPRD hosts two meetings per year  Brainstorm cross-industry challenges  Identify potential areas for collaboration  Showcase iPRD projects and activities  Annual Research Symposium  Symposium topics:  Green Chemistry  Crystallisation  Intensive Processing  Process Optimisation  Process Modelling (March 2012) Current Members:BakhuPfizerYPTChiralQuest AstraZenecaEscubedSyngentaLonzaDyeCat BromChemGSKScientific UpdateDr ReddysDeDietrich

16.  Joint Chemistry/Chemical Engineering activity  High quality students recruited from both disciplines  Unique courses to Leeds University  Student bursaries from EPSRC and Industry (£3.5k) Get Involved in Training Scientists for Process Industries Course Material:  Industry-led lectures and workshops  Industry-sponsored laboratory projects for student training  Use of large scale laboratories where appropriate (25 and 50 L reactors) TitleDuration MSc in Chemical Process Research and DevelopmentOne year Integrated MSc and PhD (Centre for Doctoral Training) in Chemical Process Research and Development Four Years  MSc in Pharmaceutical Process Engineering also available

17. Summary: Acknowledgements: Prof. John Blacker, Prof. Steve Marsden, Prof. Kevin Roberts, Prof. Xue Wang, Prof. Jonathan Williams, ERDF, Yorkshire Forward, EPSRC, TSB  What is iPRD?  Research Facilities and Infrastructure  Working with the Chemical and Chemical-Using Industries  Strategic Process and Manufacturing-Related R&D  Research Collaborations  iPRD Industrial Club  Student Training and Professional Development  Knowledge Transfer Partnerships  Contract Research and Consultancy Services