A new dimension in purification

Contichrom®

Preparative Liquid Chromatography

Do you want to combine flexibility with excellent process economics in purification?

Contichrom®

lab equipment

Lag

una

Des

ign

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Having more… choices in process development

Contichrom® lab is a preparative liquid chroma-tography system designed for discovery, process development and scale-up, offering great flexi-bility in process choices. With Contichrom® lab, all process modes (batch, SMB, MCSGP, multi- column) can be performed with a single equip-ment and control software. The Contichrom® control software has been developed to enable the conversion of batch to multicolumn pro-cesses using a method wizard and to allow the fast development of scalable processes, omitting extensive screening steps.

The Contichrom® lab adds another dimension to process chromatography, as it allows develop-ment of processes based on the MCSGP (Multi-column Countercurrent Solvent Gradient Purifica-tion) principle which is much more efficient than a batch process.

All standard media (Ion exchange, mixed-mode, HIC, RP, SEC, Affinity) can be used as well as all standard organic solvents and aqueous buffers.

Introducing the flexible Contichrom® lab (all-in-one) process capability.

•Contichrom® allows development of all downstream pro-cessmodes (batch, SMB, multicolumn, MCSGP) with one single piece of equipment and easy process conversion

Flexibility

Process Economics

Scalability•Contichrom® allows retention of the developed product- profile, yield and purity specifications upon upscaling

•TheMCSGPprocessincreasesbothpurityandyieldby 50% compared to the corresponding batch process

•Contichrom® allows rapid automated process- development

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Processchallenge

Ternaryseparation

Very dif�cultseparation

MCSGP

Dif�cultseparation

MCSGP

Baselineseparated

Batch

Binary separation

Dif�cultseparation

SMB

Baselineseparated

Batch

Having more…choices in process development

Flexibility in process development means that based on the purification challenge the best process is chosen with respect to ease, development time and costs.

For simple separations, batch processes are the best option as product (red) and impurity (grey) are well separated. However for difficult ternary separations of overlapping impurities, the MCSGP process is superior. The isolation of product-re-lated impurities for pre-clinical and toxicological assessments, normally a tedious task, is easy using the MCSGP process (far left). With Contichrom® lab equipment all processes as shown above can be performed.

Contichrom® lab equipment allows development of a simple batch process first and then automatic switching to an MCSGP process, providing superior process economics.

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Having more… product extracted from a downstream run

The MCSGP process operates with twin columns instead of one column, whereby the impure side fractions containing product are recycled inter-nally, extracting all product and thereby increa-sing both yield and purity. The MCSGP process mode is typically operated with the same transit time as a batch chromatography step.

A batch derived from a MCSGP process has the same «batch definition» as one from a normal single column batch process. It is a specific quan-tity of material or API processed in one process or series of processes so that it could be expected to be homogenous.

Application Areas

•Discovery:isolationofleads•Processdevelopment:purificationofproteins,syntheticpeptides•Purificationofoligonucleotides• Isolationofproduct-relatedimpurities•PurificationofconjugatesandPEGylatedproteins•Purificationofsmallmoleculesandnaturalproducts

Conventional batchchromatography

Chromacon‘s novelinternal recycling chromatography

(MCSGP)

time

more and purer product

Reprocess impureproduct

time

pure product

impureproductto waste

Cut narrow= obtain

purer product

Conventional batchchromatography

Chromacon‘s novelinternal recycling chromatography

(MCSGP)

time

more and purer product

Reprocess impureproduct

time

pure product

impureproductto waste

Cut narrow= obtain

purer product

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Having more… choices in compound isolation

Applications in Discovery and in the isolation of product-related impurities:

The Problem:

•Discovery:Inshotgunproteomics(bottom-up),due to the complexity of the samples, extensive front-end separation is essential to alleviate the problem of peptide undersampling, to maximi-ze protein identifications and to tackle the vast dynamic range.

• Related impurities: Isolation of product-relatedimpurities is normally a tedious task requiring several hundred injections to isolate sufficientmaterial for pre-clinical and toxicological studies.

The Solution:

•TheMCSGPprocessallowsselectiveenrichmentof a defined region of the chromatogram (red)

•Theenrichedfractioncanbeisolatedforfunc-tional characterization or analyzed directly on-line using mass spectrometry analysis

Selectively enriched fractions

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Developing a fast and robust process with more yield and higher purity:

Having better…process economics in purification

The process development goal is to develop a robust and scalable process with optimal pro-cess economics. Reduced cost of goods and development time are part of the process econo-mics. Contichrom® lab equipment employing the MCSGP process allows achieving superior process economics compared to batch processes. As the MCSGP process adds another, continuous dimen-sion to the batch process, both yield and purity can be optimized and typically increased by 50 %.

In addition, throughput is typically increased 10-fold while buffer consumption is reduced by 70 %, an important consideration in large volume processing applications. Fast and robust process development for an MCSGP process is achieved despite omitting batch processing efforts. Instead, a basic batch process is automatically switched to an MCSGP process using the Contichrom® soft-ware wizard providing superior process perfor-mance and economics.

process &productquality

requiredthresholdquality

processdevelopment time

threshold quality = scalable process+ purity+ controlled impurities+ economic yield

shorter time of PD for MCSGP process

processswitch

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Having automation assistance…in process development

Contichrom® lab equipment and software have been designed to be very user-friendly. The control software helps the user to easily navigate and ma-nage process setup, execution, and reporting.

Mainwindow

Batchwizard

Batch toMCSGPwizard

Methodeditor

Evaluation& reportcenter

Systemonline

monitoring

Flowsheetand active�owpath

• Wizards with graphical user interface for easy method programming• Automated conversion from batch to MCSGP process• Extensive library of pre-defined methods for all standard operations

Fast and automated process developmentFast and automated process development

• Intuitive software for operation of batch and MCSGP• Active flow path highlighted in flowsheet• Pause/continue functionality, even for continuous chromatographic operations

Easy to operateEasy to operate

• Detailed evaluation capabilities with standardized PDF reports• Data export functions

Integrated evaluation and reportingIntegrated evaluation and reporting

• Full audit trail and change control• User management hierarchy provides high operational and data security• FDA 21 CFR Part 11 compliant

Full data security and traceabilityFull data security and traceability

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Having automation assistance…in process development

The Contichrom® wizard allows switching a batch process to a superior MCSGP process in just three steps:

Step 1: Firstly, a non-optimized batch process is developed, the product peak is identified and the batch chromatogram is stored in the database. For conversion of a batch to an MCSGP process, the respective batch chromatogram is retrieved.

Step 2: Using the Contichrom® software wizard, the borders of the product peak (red) are defined by simply dragging bars to define the boundaries. The narrower the boundaries are defined, the purer the isolated product. Then the boundaries of the recycling fractions (blue) are set by dragging another set of bars and the start and end points are defined.

Step 3: Pressing the software wizard button will automatically convert batch process into an MCSGP process.

Step 1:retrievechromatogram ofbatch run fromdatabase

Step 2: interactive de�nitionof product range (red) andrecycling fractions (blue): drag bars to de�neboundaries (dotted lines)

Step 3:press button to convert batch toMCSGP process

Contichrom® MCSGP-Wizard

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Multi-functionality with a small footprint

Application fields:

• Processdevelopment:facilitatedthroughflexibilityinchoosingtherightprocess for a given process challenge

• Isolationofproduct-relatedimpurities:thetedioustaskofisolatingpro-duct-related impurities for pre-clinical/toxicological characterization is considerably facilitated using Contichrom® with MCSGP mode

• Preparativeproductpurification:TheContichrom® lab is available in two versions with two different pumps:

• Contichrom® lab-10: 0.01–10 mL/min for up to 20 g product /day

• Contichrom® prep-100: 1–100 mL/min for up to 200 g product /day

Sample pump with high precision

Two UV-detectors with low hold-up volume

Six reliable multi-posi- tion valves

Two precise gradient pumps with integrated seal wash

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Multi-functionality with a small footprint

• Contichrom® is a preparative liquid chromatography system intended for process screening and develop-ment.

• Insteadoftime-consumingDesignofExperiments(DoE)for establishing optimized starting conditions, Conti-chrom® offers a software wizard tool to easily convert a basic batch process to a superior MCSGP process, thus reducing development time for robust and economic processes considerably.

• TheContichrom® operating software provides pre-de-fined methods for standard batch operations and for an intuitive user-friendly operation and data security, being compliant to 21 CFR part 11 requirements.

• TheContichrom® lab has a modular design where parts can be easily accessed and replaced. It has an interac-tive instrument display and many functionalities, such as a pause/continue functionality. A large buffer storage area on top of the instrument provides sufficient space for continuous process modes.

• Thesystemandsamplepumpsarebasedonhighqual-ity KNAUER Blue Shadow pump technology, ensuring reproducible flow rates at both low and high pressures.

• Thesystemissuitableforlow,mediumandhighpres-sure and is solvent resistant and biocompatible, offer-ing functionality for small molecule and macromolecule preparative purifications.

• TheContichrom® system is scalable to pilot and process scale. At up-scaling, the product profile is retained.

• TheContichrom® system is particularly suitable for PAT in line with QbD.

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Contichrom®

Technical specifications

Main system components:•MCSGPconfigurationwithtwin-columnsetup•3xgradientpumps,2xUVdetectors•4x6-way7-portvalves,2x2-way6-portvalves•1xdegasser,1xpH/conductivitysensor•1xcomputer/monitor/keyboard/mouse•1xContichrom® operating software•1xethernetswitch

Maximum system pressure: 100 bar

Pump description: •doublepistonpumpwithelectronicresidual

pulsation absorption•biocompatible,titaniuminlays•activepistonsealwash•flowrate: • Contichrom®lab-10:0.01–10mL/min • Contichrom®prep-100:1–100mL/min•maximumdeliverypressure:100bar•gradientcapability

UV detector description: •spectrophotometerforroutineHPLCandother

flow-through detection tasks•wavelengthrange190–750nm• lightsource:deuteriumlamp

Degasser description (lab-10): •4-channeldegassermodule•degassingbygaspermeationthroughTeflon®

AF amorphous fluoropolymer membrane

Valve description: •electricalvalvedrive•LEDdisplay•PEEKbody,TEFZELseal

pH/conductivity sensor description:•Conductivity0–500mS/cm•pHmeasurements0–14•temperaturesensor

Materials: •allbiocompatible•tubing:PEEK • Contichrom®lab-10:0.5mmi.d.

• Contichrom®prep-100:1.0mmi.d.

Fraction collector (optional):•FractioncollectorFOXYR1ISCOwithintegrat-

ed diverter valve •Fractioncapacityfrom36–144tubes, 0.2mL–50mLperfraction

•biocompatibleandcanbeusedincoldrooms

Purified product output capacity:•Contichrom®lab-10:upto20g/day•Contichrom®prep-100:upto200g/day

Operation:•roomtemperature•coldroom(4°C)compatible

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Contichrom® Operatingsoftwarefeatures

Software description:

•Contichrom® operating software (in English) in-cluding manual.

• Integrated,intuitivesoftwareforoperationandevaluation of batch and continuous chromatog-raphy.

•Wizard allows easy programming of methodsincluding MCSGP.

•Run logstoresall information foreachexperi-ment.

•Easy-to-usegraphicaluserinterfaceformethodprogramming. Advanced users can access pro-gram detailed settings.

•Unique pause/continue functionality, even forcontinuous chromatographic operations.

•Usermanagement gives high operational anddata security.

•FDA21CFRPart11andAnnex11compliant.

• Administrators• R&D-, production-users

Pre-defined user groups

• Each group has defined rights as set by the administrator• User accounts are password protected

Rights management

• All user/hardware activities are logged with time stamp and user name

Logging

• A checksum of the log & measurement file is computed and saved together with the files in order to create an electronic signature

Electronic signature

• Administrators• R&D-, production-users

Pre-defined user groups

• Each group has defined rights as set by the administrator• User accounts are password protected

Rights management

• All user/hardware activities are logged with time stamp and user name

Logging

• A checksum of the log & measurement file is computed and saved together with the files in order to create an electronic signature

Electronic signature

• Administrators• R&D-, production-users

Pre-defined user groups

• Each group has defined rights as set by the administrator• User accounts are password protected

Rights management

• All user/hardware activities are logged with time stamp and user name

Logging

• A checksum of the log & measurement file is computed and saved together with the files in order to create an electronic signature

Electronic signature

• Administrators• R&D-, production-users

Pre-defined user groups

• Each group has defined rights as set by the administrator• User accounts are password protected

Rights management

• All user/hardware activities are logged with time stamp and user name

Logging

• A checksum of the log & measurement file is computed and saved together with the files in order to create an electronic signature

Electronic signature

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Operatingsoftware:mainwindow:status&flowsheettab

Main-Flowsheet Tab

•activeconnectionsarehighlighted

•displayofstatus/measurementof • valve position • pump parameters • UV-signals / settings • conductivity • pH / temperature • tank levels

•runtimeinformaion • method in operation • duration of time step

To obtain an offer, please contact:

ChromaCon AGTechnoparkstrasse 18005ZuerichSwitzerland

Phone:+41444452010 Phone:+41789733449

www.chromacon.chsales@chromacon.ch

To obtain technical information and support, after-sales service, shipping information, please contact:

Dr. Ing. Herbert Knauer GmbHHegauer Weg 3814163BerlinGermany

Phone:+49308097270

www.knauer.netcontichrom@knauer.net

A new dimension in purification

ChromaConandContichromareregisteredtrademarksofChromaConAG|AllgoodsandservicesaresoldsubjecttotermsandconditionsofsaleofKnauerandChromaCon.|Acopyoftheseareavailableuponrequest.|©2012–14ChromaConAG–allrightsreserved.FirstpublishedApril2012|ChromaConAG,Technoparkstrasse1,8005Zuerich