ChromWorks Introduction

CHROMWORKS “Create a unique usefulness in continuous chromatography”

Copyright © 2011 ChromWorks, Inc.

in Pharma

www.chromworks.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

www.chromworks.com

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

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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)†

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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

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

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

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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

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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

Source: www.ampacfinechemicals.com www.chromworks.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

www.chromworks.com

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

{ 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

Adaptive Mesh in 2-D Moving PDE Mesh

In Chromatography

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{ 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

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

{ 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

{ 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.

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{ 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.

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{ 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.

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{ ECP Isotherm Estimation }

In industry, the ECP (Elution by Characteristic Points) method is used

extensively to obtain competitive equilibrium isotherm for

enantiomers.

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{ 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

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{ 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

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{ 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

{ 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

{ 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

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

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

{ 2-2-2-2 SMB Simulation }

www.chromworks.com

{ 1-1.5-2-0.5 VARICOL Simulation }

www.chromworks.com

{ ChromWorks Simulation on Excel }

www.chromworks.com

{ Non-Langmuirian Chromatogram }

www.chromworks.com

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

Contact Information

ChromWorks Website: www.chromworks.com

Support email: [email protected]

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