CHROMWORKSCreate a unique usefulness in continuous chromatography

Copyright © 2011 ChromWorks, Inc.

www.chromworks.com

in Pharma

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

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

† Under development

Introduction

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)†

† Under development

Introduction

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)

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

Challenges in the Laboratory Separation feasibility

Stationary phase evaluation and solvent screening

Data acquisition and analysis

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

Anti-Langmuir behavior

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

Challenges in the Operation Quality by Design (QbD)

Extra column dead volume

Non-homogeneous column set

Operation temperature

Solvent composition

Plant data tuning and alignment

Possible degradation in stationary phase

Impurity in feed and solvent

Operational safety

Revamp analysis

Design capacity adjustment

Column re-conditioning

Process start-up and shut-down operationSource: www.ampacfinechemicals.com

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

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

{ 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. In ChromWorks,

the adaptive mesh refinement is one of major differentiating

featuresAdaptive Mesh in 2-DMoving PDE Mesh

In Chromatography

{ 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

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

{ 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)

{ 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.

{ 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.

{ 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.

{ ECP Isotherm Estimation } In industry, the ECP (Elution by Characteristic Points) method is

used extensively to obtain competitive equilibrium isotherm for

enantiomers.

{ 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.

After Estimation

Before Estimation

{ 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

{ Excel Interoperability } You could use Microsoft Excel (2003, 2007 and 2010) to run

ChromWorks SMB and Varicol models. It is possible by

accessing the COM object of ChromWorks from Excel VBA.

{ Model Tuning to Fit Data } ChromWorks provides a unique software interface that allows

the user to fit the model with the measured data.

{ 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

Constant 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

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

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

{ 2-2-2-2 SMB Simulation }

{ 2-2-2-2, 2-3-2-1 VARICOL Simulation

}

{ ChromWorks Simulation on Excel }

{ Non-Langmuirian Chromatogram }

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

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

CHROMWORKSin PharmaCreate a unique usefulness in continuous chromatography

Copyright © 2011 ChromWorks, Inc.

www.chromworks.com