09:00 - 09:10 Chairperson’s Opening Address

09.10 - 09:55 Integration of Computational Approaches for Solid Form Design to Ensure Investment into the Candidates with the Most Potential for Success.

• Realise the possibility of solid form design using structural tools and computational methods
• Discussion of the integration of these technologies and how this remains an opportunity in pharmaceutical companies
• Examples demonstrating the challenges and opportunities with implementation of these tools

Dr Bob Docherty
Director, Materials Science
Pfizer

09.55 - 10:40 How the Computed Crystal Energy Landscape Can Complement Experimental Polymorph Screening to Better Identify the Application of Early Predictions

Although we do not yet understand all the factors which determine the outcome of crystallisation processes, current methods of searching for the thermodynamically feasible structures can already provide a useful complement to polymorph screening, providing insight into the possible complexities of the solid state. This talk will provide:

• Case studies where genuine predictions of the crystal structure have been made, and later verified
• Case studies where the energy landscape rationalises polymorphism, co-crystal and solvate formation
• Case studies of the rationalisation of disorder and problems of crystal growth
• An overview of how the crystal energy landscape can provide insight into the factors that control polymorphism or generate problems in controlling the crystallisation process

Professor Sally Price
Professor of Chemistry
UCL

11.10 - 11:55 Computational Insights into Solvates: Predicting their Formation and Stability to Minimise Risk in Future Development

Computational methods for the prediction of crystal structures have developed to a point of being useful for understanding and anticipating polymorphism of organic molecules. These methods are now starting to be applied to more complex systems that involve more than one type of molecule. The session will discuss how computational studies can be used to predict the formation and stability of solvate crystals produced from organic molecules. The presentation will include:

• Review of crystal structure prediction by global lattice energy minimisation
• Insight into how lattice energy calculations can rationalise the inclusion of solvate molecules in the crystal lattice
• Insights from computation studies into the lattice energy stabilisation provided by solvent inclusion
• Case studies illustrating the prediction of solvate inclusion in crystal structures, and the first principles prediction of the crystal structure of solvates

Dr Graeme Day
Professor
University of Cambridge

11.55 - 12:40 Roundtable Session: Implementing Crystal Structure Computational Tools in the Pharmaceutical Industry to Aid Efficient Drug Development

• Using crystal and polymorph predicted structures tools to choose the optimal form
• Employing prediction to tailor the implementation of analytical and processing tools
• Benefits and limitations of the predictive tools: Benchmark against other companies to understand which are the most appropriate tools to implement in your company strategy

This will be your chance to network with your peers on some of the hot topics pertinent to Predictive Crystallisation now! Come armed with questions you would like to discuss. Materials to support this session will be provided on the day.

Facilitated by focus day speakers

14.00 - 14:45 Predicting Properties of Crystalline Materials Produced via Batch Crystallisation Process A significant part of high added value materials are produced by batch precipitation or crystallization. The properties of such materials are largely determined by the way the batch process is conducted.

• What it takes to successfully manufacture crystalline materials at a larger scale
• How to run the batch crystallization process in order to predictively and consistently obtain crystalline material of desired properties
• Is seeding going to help?
• How to control polymorphism and hydration level for hydrates
• Are automation, robotics, and parallel reactors employed in the laboratory stage going to help?
• Is it worthwhile to deploy in-line technology (PAT) to monitor process performance at various scales?

Dr Peter Karpinski
Senior Principle Fellow
Novartis Pharmaceuticals

14.45 - 15:30 Predictive Model Based Control of Crystal Size and Shape Using a Population Balance Modelling Framework to Effectively Use Technology for Process Optimisation during Drug Production and Development

• One and two dimensional population balance models (PBM) for prediction of crystal size and shape
• Model based optimisation of crystallisation processes for designing crystal habit and shape of CSD
• Seed recipe design for crystal size distribution control
• Modelling of combined cooling and antisolvent crystallisation processes
• Quality-by-design of crystallisation processes using batchto- batch iterative learning control

Dr Zoltan Nagy
Chemical Engineering Department
University of Loughborough

15.30 Chairperson’s Closing Remarks

16.00 - 18:30 Workshop: Crystal Structure Prediction: A Valuable New Tool to Reduce Risk in Pharmaceutical Development

The workshop on Crystal Structure Prediction will address the following topics in lectures and a discussion forum:

• CSP using dispersion-corrected density functional theory and tailor-made forcefields
• A detailed overview of the technology behind crystal structure prediction
• Case studies – A practical view on all the current possibilities
• Applications of the technology in addition to crystal structure prediction
• Risk reduction in pharmaceutical development: when does the technology add most value?
• The next big step: How to make structures predicted by CSP?

Workshop leaders

Evening refreshments will be provided