ChromWorks - the software that create a unique usefulness in preparative and continuous chromatography

1. CHROMWORKS in Pharma
“Create a unique usefulness in continuous chromatography”
Copyright © 2011 ChromWorks, Inc.
www.chromworks.com

2. CONTENTS
 Introduction
 Challenges in Continuous Chromatography Process
 ChromWorks for “Useful” Toolbox in Modeling and Simulation
 The Software Features and Capabilities
 Live Demonstration
 YouTube Movies and Contact Information
www.chromworks.com

3. Introduction
ChromWorks is a computer modeling software for simulation,
design, analysis and optimization of continuous and preparative
chromatography processes:
• Simulated Moving Bed (SMB)
• VARICOL
• Intermittent SMB
• Bio-chromatography†
• Refining SMB (Parex, Eluxyl)†
• Batch elution/gradient chromatography
www.chromworks.com

4. ChromWorks has sub-systems based on industry domain and
the specific type of chromatography application.
• Pharmaceuticals (Small molecules, e.g. Enantiomers)
• Bio-Pharmaceuticals (Large molecules, e.g. Proteins)†
• Petrochemicals (Bulk hydrocarbons, e.g. Xylenes)†
www.chromworks.com

5. ChromWorks in Pharma is a dedicated modeling system for
manufacturing chromatography processes in Pharmaceuticals. It
covers following use-cases based on demands:
• Process design (Triangle Theory)
• Design parameter acquisition (ECP and Dynamic estimation)
• Equilibrium
• Mass transfer
• Dispersion
• Process simulation (SMB,VARICOL, Intermittent SMB)
• Quality by Design analysis (Temperature/Solvent Gradients)
www.chromworks.com

6. CONTENTS
 Introduction
 Challenges in Continuous Chromatography Process
 ChromWorks for “Useful” Toolbox in Modeling and Simulation
 The Software Features and Capabilities
 Live Demonstration
 YouTube Movies and Contact Information
www.chromworks.com

7. Challenges in the Laboratory
 Separation feasibility
 Stationary phase evaluation and solvent screening
 Data acquisition and analysis
Anti-Langmuir behavior
 Adsorption equilibrium
 Sorption kinetics
 Separation factors
 Model-based parameter estimation
 Equilibrium constants
 Heat and mass transfer coefficients
 Batch column tests
 Pulse injection experiments
 Frontal analysis
www.chromworks.com

8. Challenges in the Conceptual Design
 Process design
 Number of columns
 Zone configuration
 Valve switching method
 Equipment rating and model validation
 Column size, packing and pressure drop constraint
 Feed and product port arrangement
 Plumbing (piping/tubing) and dead volumes
 Process performance and productivity
 Product purity and recovery
 Solvent consumption
www.chromworks.com

9. Challenges in the Operation
 Quality by Design (QbD)
 Extra column dead volume
 Non-homogeneous column set
 Operation temperature
 Solvent composition
 Plant data tuning and regression
 Property degradation in stationary phase
 Impurity in feed and solvent
 Operational safety
 Process revamp
 Design capacity adjustment
 Column re-conditioning
 Process start-up and shut-down operation
Photo courtesy of AMPAC Fine Chemicals
www.chromworks.com Source: www.ampacfinechemicals.com

10. CONTENTS
 Introduction
 Challenges in Continuous Chromatography Process
 ChromWorks for “Useful” Toolbox in Modeling and Simulation
 The Software Features and Capabilities
 Live Demonstration
 YouTube Movies and Contact Information
www.chromworks.com

11. Differentiation! Differentiation! Differentiation!
 Easiest-to-use interface among peer-class simulators
 Software designed based upon extensive mentors provided by chromatography
experts and process chemists (not by software engineers!)
 No need to develop a simulation flow sheet  Fast simulation study
 Software learning curve is very short (1-2 hours will be sufficient to get started)
 Use highly robust solver based on Adaptive Moving Mesh
to solve the first principle mathematical models
 Wide range of equilibrium isotherm models
 Interoperability with Microsoft Excel to allow various
methodologies in automation and optimization
www.chromworks.com

12. { Adaptive Mesh Refinement as PDE method }
 The ChromWorks solver uses the adaptive mesh refinement
algorithm for spatial discretization in column model, and presents
highly robust and accurate simulation. Adaptive mesh refinement is
one of major differentiating features in ChromWorks
Moving PDE Mesh Adaptive Mesh in 2-D
In Chromatography
www.chromworks.com

13. { Equilibrium Models Supported in Version 1.0 }
 Langmuir
 Linear
 Modified Langmuir
 Generalized Langmuir
 Bi-Langmuir
 Ideal Adsorbed Solution Theory (IAST)
 IAST + Langmuir
 IAST + Modified Langmuir
 IAST + Bi-Langmuir
 IAST + Polynomial
All isotherm model can be temperature dependent for QbD study
www.chromworks.com

14. CONTENTS
 Introduction
 Challenges in Continuous Chromatography Process
 ChromWorks for “Useful” Toolbox in Modeling and Simulation
 The Software Features and Capabilities
 Live Demonstration
 YouTube Movies and Contact Information
www.chromworks.com

15. { SMB and VARICOL Process Models }
 These are top-level assumptions used in the mathematical
models of SMB and VARICOL process
 Maximum 32 columns setup
 Support conventional 4 zone SMB (synchronous stepping)
 Support VARICOL process (asynchronous stepping)
 “As is” modeling for non-homogeneous column set
 “As is” modeling for extra column dead volumes, such as connecting
tubing parts and column top/bottom voids
 Possible extension to more complex operational configuration (e.g.
Intermittent SMB, PowerFeed, ModiCon, so on)
www.chromworks.com

16. { Dead Volume Modeling }
 ChromWorks uses "As is" approach to address the system dead
volume in SMB and VARICOL process. The user can model extra-
column dead volumes existing in the apparatus, and simulate it all
together. Using this approach, the user could understand and quantify
the impact of presence of dead volume and the location. The user will
then be able to adjust operating condition to meet the design
constraint and process performance.
www.chromworks.com

17. { Non-homogeneous Column Set }
 ChromWorks uses "As is" approach to address a non-homogeneous
column set on SMB and VARICOL process performance. The user can
model the packing characteristics differently for each column. Using
this approach, for example, the user could understand and quantify
reductions in the purity of the product streams caused by the column-
to-column fluctuations of the retention times of the mixtures arising
from porosity differences.
www.chromworks.com

18. { Triangle Theory }
 ChromWorks’s Triangle Theory provides explicit criteria for the
choice of the operating conditions of SMB units to achieve the
prescribed separation of a mixture characterized by various
equilibrium isotherm models.
www.chromworks.com

19. { ECP Isotherm Estimation }
 In industry, the ECP (Elution by Characteristic Points) method is used
extensively to obtain competitive equilibrium isotherm for
enantiomers.
www.chromworks.com

20. { Dynamic Estimation }
 Using the user interface that is designed for dynamic estimation, one
can utilize real process model to extract design data (such as
isotherm, mass transfer, and dispersion coefficients) from your
experimental or plant measured data.
Before Estimation
After Estimation
www.chromworks.com

21. { Gradient Operations (QbD) }
 ChromWorks has special functions to study the effects of
temperature and solvent composition on the SMB process
performance. The objective of the simulation capability of gradient
operation is to investigate a possibility of improvement of separation
resolution and also to execute a QbD (Quality by Design) analysis by
simulate adsorption behavior at various operating conditions.
“Good” Gradient Sample “Bad” Gradient Sample
www.chromworks.com

22. { Excel Interoperability }
 You could use Microsoft Excel (2003, 2007 and 2010) to run
ChromWorks SMB and Varicol models. It can be utilized for
automation and process optimization.
www.chromworks.com

23. { Model Tuning to Fit Data }
 ChromWorks provides a unique interface that allows the user to fit
the model with the measured data.
www.chromworks.com

24. { Chemicals Properties Library }
 Chemical Properties Library presents various thermodynamic properties for
over 1500 pure components.
 Temperature dependent properties
 Liquid Mass Density
 Liquid Molar Density
 Liquid Viscosity
 Thermal Conductivity of the Liquid
 Heat Capacity of Liquid
 Saturated Vapor Pressure
 Heat of Vaporization
 Surface Tension
 Rackett Liquid Molar Volume
 Scalar properties
 Molecular weight, Normal boiling point, Acentric factor, Liquid molar volume at 298.15 K, Critical
temperature, Critical pressure, Critical volume, Critical compressibility, Dipole moment, van der Waals
reduced volume, van der Waals area, Refractive index, Auto ignition temperature
www.chromworks.com

25. CONTENTS
 Introduction
 Challenges in Continuous Chromatography Process
 ChromWorks for “Useful” Toolbox in Modeling and Simulation
 The Software Features and Capabilities
 Live Demonstration
 YouTube Movies and Contact Information
www.chromworks.com

26. CONTENTS
 Introduction
 Challenges in Continuous Chromatography Process
 ChromWorks for “Useful” Toolbox in Modeling and Simulation
 The Software Features and Capabilities
 Live Demonstration
 YouTube Movies and Contact Information
www.chromworks.com

27. { 2-2-2-2 SMB Simulation }
www.chromworks.com

28. { 1-1.5-2-0.5 VARICOL Simulation }
www.chromworks.com

29. { ChromWorks Simulation on Excel }
www.chromworks.com

30. { Non-Langmuirian Chromatogram }
www.chromworks.com

31. ChromWorks Movies in YouTube
 SMB Simulation (GUI Demo)
http://youtu.be/HGovvG4RPbM
 VARICOL Simulation (GUI Demo)
http://youtu.be/DkfzQ_PHZ8E?hd=1
 Run Simulation on Excel
http://youtu.be/9jbYI60ZNjg?hd=1
 Non-Langmuirian (Case M1) Batch Chromatography
http://youtu.be/aowo1JSWpZ4?hd=1
 Non-Langmuirian (Case M2) Batch Chromatography
http://youtu.be/VDeJw76f8Cw?hd=1
 Adaptive Mesh Refinement – Batch Chromatography
http://youtu.be/lCOUzCxxI10
www.chromworks.com

32. Contact Information
 ChromWorks Website: www.chromworks.com
 Support email: support@chromworks.com
 YouTube Channel: www.youtube.com/user/chromworks
Feel free to contact us if you need a trial version
or more information on the software
CHROMWORKS in Pharma
“Create a unique usefulness in continuous chromatography”
 Copyright © 2011 ChromWorks, Inc.
 www.chromworks.com
www.chromworks.com