09:00 Chairperson’s Welcome and Opening Address

A Detailed Analysis of Process Development and Control and Future Prospects for Crystallisation Development in Industry

09:10 Case Studies: Continuous Crystallisation Process Development

Batch-based manufacturing system currently employed by the pharmaceutical industry is costly and inefficient. A drug’s active ingredients are synthesized in a chemical manufacturing plant and then shipped to a separate facility where they are converted into large batches of pills, liquids, or creams. With multiple interruptions, including transport to separate locations, the production of just one batch of drugs can take weeks. What’s more, the manufacturing design and scale-up required to produce a new drug can be financially unsustainable and exceedingly time-consuming. Continuous Processes/Manufacturing offers a paradigm shift that will enable the industry to produce quality products more efficiently. This presentation will…

• Highlight the current approaches to continuous crystallisation
• Assess the advantages of a continuous crystallisation process
• Analyse the key challenges and draw on real life case studies to present the key points

James Evans
Associate Director
Novartis-MIT Centre for Continuous Manufacturing

09:50 Modeling, Measurements and Close Loop Control of the Shape Distribution of Crystals Growing From Solution

The presentation will present advances in:

• Applying on-line 2D and 3D imaging and image analysis technique for real-time monitoring of crystallisation processes
• Novel population balance (PB) modelling technique, the so-called morphological PB model, for simulating and optimizing crystallisation processes for the purpose of not only size control but also shape distribution control
• Achieving closed-loop optimization and automatic control of crystal shape distribution in experiments and simulation
• The presentation will also present results on a platform for studying the impact of crystal growth modifiers (impurity) on crystal growth

Professor Xue Wang
School Director of Research and Chair of Intelligent Measurement and Control
University of Leeds

11:00 Advanced Batch and Continuous Process Development

Presentation details to follow

Mark Barrett
Senior Research and Development Engineer
Solid State Pharmaceutical Cluster/ UCD Ireland

11:40 Get a Better Grip on Your Crystallisation Process With Fewer Experiments Using gCRYSTAL’s Model-based Decision Support Techniques

A real life case study is used to show how PSE’s gCRYSTAL is applied to

• develop a model of an API crystallisation process
• estimate kinetic parameters and validate the model based on one or more experiments
• connect the validated model to CFD using the gCRYSTAL Hybrid Multizonal interface to predict, for example, local primary and secondary nucleation, growth (and dissolution) and agglomeration rates

This presentation will show that a model-based approach to process development in the pharmaceutical industry can reduce the number of experiments required to understand and predict crystallisation behaviour. Further, the approach used here enables the prediction of critical process parameters at the same scale but different operating conditions as well as at different scales. This approach allows scale up of crystallisation processes with a reduced and, more importantly, known level of risk.

Sean Bermingham
VP Solids
Process Systems Enterprise Ltd

13:20 Assessing the Advances Towards a Robust Continuous Crystallisation Processes

• What is the best platform for a continuous crystalliser
• Potential advantages of continuous crystallisation over traditional batch processes
• The application of PAT and Quality by Design for robust control and scale-up of continuous crystallisations

Chris Rielly
Head of Department of Chemical Engineering
University of Loughborough

14:00 Case Study: PAT Based Automated Design Control and Scale Up of Crystallisation Processes Using a Crystallisation Process Informatics System

• Overview of process analytical technologies for monitoring crystallisation processes
• Concentration feedback control based direct design for rapid scale up of crystallisation processes
• Application of direct nucleation control for robust crystallisation property control at laboratory and industrial scales
• Case studies with the application of super saturation and direct nucleation control of size distribution, polymorphic form, reduction of solvent inclusion and in oiling out crystallisation

Zoltan Nagy
Professor of Process Systems Engineering
University of Loughborough

15:10 Exquisite Control of Crystallisation Processes By Pre-Conditioning Seeds

• Why do apparently visually identical crystals can behave differently in the same crystallisation process?
• What kind of corrective measures can be put in place to deliver product of desired quality?

Mei Lee
Investigator
GlaxoSmithKline

15.50 Case Study: Gaining Insight Into API Crystallization Processes Through the Use of Process Analytical Tools

The presentation will cover various case studies on how Process Analytical Tools provided insight into crystallization processes:

• How PVM (Particle Vision Microscope) and Raman tools resolved an undesired polymorph assay in a pilot plant batch
• The use of FBRM (Focused Beam Reflectance Measurement) and PVM to find unexpected phases of an active pharmaceutical ingredient, and how these tools aided in the construction of a phase diagram
• The use of FTIR (Fourier Transfer Infrared Spectroscopy) and FBRM in understanding the impact of stream purity on de-super saturation kinetics.
• The use of FBRM and PVM in understanding the mechanism behind rotor-stator wet milling and annealing of an active pharmaceutical ingredient

Eric Sirota
Project Chemical Engineer
Merck

16:30 Chairperson’s Closing Remarks and End of Day One