Innovative Chemical Solutions from iPRD at University of Leeds

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:

3. Management Team • 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. John Blacker • 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 • 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.  • 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 • 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) • 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 Concept/ candidate Route design Process design Isolation design Formulation design Product Synthetic chemistry Catalysis Separation sci/eng Crystallisation Physical organic chem. Reaction engineering Particle Science

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

6. Process Laboratory • Industry-standard development and scale-up facilities and procedures • £4.8m investment by Yorkshire Forward/EU (ERDF) • 650m2 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/ • ParticlesCIC (Particle Characterisation): http://particlescic.org/

7. Batch Manufacture • Remotely-controlled 20 and 50 L reactors with: • 5 L addition vessel • 20 L distillate receiver • 1 m2 condenser • variable speed agitator motor • pitched bladed agitator • ATEX rated (temperature, gas apparatus) • Operational temperature range: -20 to 160 oC • 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-AfrikaMicroreactor • 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. 100m • 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

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, BödAyre Products, Critical Processes, The Body Shop, Independent Cosmetic Advice, Higgins Consultancy • IMI/EU Green Chemistry for the 21st 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. 100m 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)

12. Industry Offering • 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

13. Our Research and Consultancy Services include:

14. Contract & Consultancy Services • 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

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)

16. Get Involved in Training Scientists for Process Industries • 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) • 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) • MSc in Pharmaceutical Process Engineering also available

17. Summary: • 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 Acknowledgements: Prof. John Blacker, Prof. Steve Marsden, Prof. Kevin Roberts, Prof. Xue Wang, Prof. Jonathan Williams, ERDF, Yorkshire Forward, EPSRC, TSB