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
To obtain technical information and support, after-sales service, shipping information, please contact:
Dr. Ing. Herbert Knauer GmbHHegauer Weg 3814163BerlinGermany
Phone:+49308097270
A new dimension in purification
ChromaConandContichromareregisteredtrademarksofChromaConAG|AllgoodsandservicesaresoldsubjecttotermsandconditionsofsaleofKnauerandChromaCon.|Acopyoftheseareavailableuponrequest.|©2012–14ChromaConAG–allrightsreserved.FirstpublishedApril2012|ChromaConAG,Technoparkstrasse1,8005Zuerich
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