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ChromaCon Applications


The Contichrom® equipment, through its twin-column setup and its ChromIQ® operating software allows using our novel cyclic and continuous process principles. When applying these process principles for capture and polish applications, large savings in CAPEX and OPEX can be realized. As the processes can be run continuous, large volume processing applications using chromatography as a high resolution separation principle becomes reality.  

 CaptureSMB® is most useful in capture applications where either fast processing and/or optimization of capture capacity is required. The twin-column setup captures product breakthrough from the first column into the second column. Typical applications are the capture of monoclonal antibodies on Protein A. Applications of CaptureSMB® in Contichrom®equipment is made easy by using the ChromIQ® software wizard that automates the process.

Continuous capture processes: Capture SMB (2C PCC) :

During production of monoclonal antibodies, the Protein A capture step is the first important purification step. A fast capture step is critical to retaining product integrity and processing of large feed volumes in reasonable times. Novel periodic counter-current (PCC) processes are superior to batch processes and offer a significant economic benefit. ChromaCon’s two-column PCC process (CaptureSMB) is the least complex and most effective PCC process allowing two-fold faster processing. It saves up to 60% of expensive Protein A resin and buffer. The Contichrom CUBE and CUBE Combined  systems are process development FPLC systems employing CaptureSMB on the lab scale. The CaptureSMB process can seamlessly be scaled up to pilot- and process-scale with the EcoPrime Twin systems from LEWA.

How does CaptureSMB work?

In general, the CaptureSMB process is used for optimizing capture steps with affinity resins (protein A, Ni-NTA). In batch chromatography, the column cannot be fully loaded due to the product breakthrough. Breakthrough curves of single-column batch processes show that only 50-60% of the resin material is used. The CaptureSMB process operates by fully loading one column and capturing the product breakthrough on second column (see animation below). The product is eluted from the first column and the roles of the columns are reversed. Thus, all possible product is captured and all of the available affinity resin, for example Protein A, is efficiently used.

The CaptureSMB technology is patented by ChromaCon and can be run on both the Contichrom CUBE and the Contichrom CUBE Combined. CaptureSMB processes can be created and optimized towards throughput or resin cost savings using the software wizard.

How does CaptureSMB compare to 3 or more column processes?

ETH Zurich

A recent study by scientists at ETH Zurich investigated the efficiency of multi column processes for capture processes. Multicolumn processes were found to reduce resin costs by 40-60%, decrease buffer consumption and increase product concentration, compared to batch chromatography.

Furthermore, CaptureSMB (2C PCC) outperformed 3C PCC and 4C PCC in terms of productivity, while operating at similar capacity utilization and buffer consumption. CaptureSMB (2C PCC) requires least complex hardware of all multi-column process, positively impacting equipment costs and risks of failure.

MCSGP is most useful for polish applications, where high resolution, purity and throughput have to be combined. Applications include the removal of aggregates from monoclonal antibodies and refolded proteins, the separation of bi-specific antibodies, the separation of conjugates such as antibody-drug conjugates (ADCs) and PEGylated proteins. Starting with a simple batch process, the automation software ChromIQ® wizard converts the batch process into an MCSGP process within minutes.

Continuous Polishing Processes: MCSGP :

For high resolution separations in traditional single column batch chromatography gradients can be used. However, if there still are overlapping impurities, there is a trade-off between yield and purity. The MCSGP (Multi-column Counter-current Solvent Gradient Purification) process resolves this issue.

MCSGP automatically recycles impure product fractions, while in batch chromatography impure fractions have to be discarded.

In batch chromatography, impure side fractions (R1 & R2 in the figure above)  often have to be discarded to reach a certain purity level for the product (P). With MCSGP, impure product-containing side fractions are automatically recycled in a periodic closed loop process (see animation below on the left). Thereby, the yield of pure product is maximized. This allows for a significant improvement in process economics. MCSGP gives higher yield and purity than batch chromatography (see Figure above).



MCSGP increases productivity by maximizing both yield and purity at the same time.

MCSGP is for example used for:

  • blood plasma products
  • recombinant proteins from microbial production
  • small molecules from fermentation or natural product extractions (Stevia, Flavonoides, fish oil)
  • synthetic peptides
  • complex organic synthesis products

The MCSGP technology is patented by ChromaCon. The Contichrom CUBE Combined is capable of executing MCSGP processes. A dedicated software wizard in the accompanying ChromIQ software allows for easy batch-to-continuous process transfer and optimization.

N-Rich® is most useful for isolation of product-related impurities or other minor constituents from complex mixtures. The process is automated and runs over two steps: the product of interest is selectively enriched and the contaminants depleted simultaneously in a first step, before the product of interest is isolated by step or gradient elution.

 As these process principles are general they can be used in many different industries, addressing difficult or cost-sensitive separation challenges.

Continuous polishing processes: N-Rich :

The isolation of minor components of complex mixtures with major components is a very difficult purification task. It typically requires significant time and resources.

The N-Rich process provides large quantities of a desired high-purity compound in an automated process. The two-step enrichment and separation step yields sufficient material in high purity for structure elucidation or subsequent biochemical, cell- and even animal-based assays. It is an invaluable tool for any research and development laboratory.

N-Rich is applied for:

  • isolation of product-related impurities for active pharmaceutical ingredients
  • biosimilar CMC characterization
  • characterization of antibody-drug conjugate isoforms
  • identification of biomarkers and compounds in proteomics and metabolomics research
  • purification of ultra-pure compounds as reference materials
  • purification of proteins for protein crystallography
  • isolation of impurities after stability and formulation studies

The N-Rich process employs a cyclic step where the desired molecule is selectively enrichment and interfering substances are depleted (see animation below). After enrichment of several hundred to thousand-fold, the enriched fraction is separated automatically, using a shallow gradient.

The Contichrom CUBE Combined and the Contichrom HPLC are capable of executing N-Rich processes.


In Life Science applications, in particular biologics purification, the Contichrom® all-in-one process equipment is very useful, as it provides a tool that can be used in different product development steps offering significant flexibility in choosing the best process for any given application.

  • Discovery: selective enrichment of leads in the presence of a large excess of background. Combined with mass spectrometry, it is a very useful tool for top-down and bottom-up proteomics
  • Development: significant shortening of development time using Contichrom’s® automation software. Instead of extensive screening for batch process optimization, a simple batch is converted to an MCSGP process with superior performance.
  • Impurity isolation: the isolation of product-related impurities is a tedious task. Often preparative chromatography does not provide sufficient resolution and therefore it needs repetitive analytical runs in order to isolate sufficient material for pre-clinical and toxicological studies. Using the MCSGP process allows to selectively enrich any impurity, saving significant development time and retaining the integrity of the isolated impurity.
  • Production: The MCSGP process offers significant increase in process economics as it allows increasing both purity and yield by typically 50% compared to a batch process at a 10-fold processivity increase. It is particularly useful for QbD approaches as it allows monitoring the process using PAT, therefore providing additional compliance.
  • All-in-one process: Contichrom® can be operated with all processes: For MAb purification, Protein A capture using the twin columns can be optimized using the CaptureSMB® process principle that allows optimal use of Protein A resins, thereby reducing Protein A resin cost up to 50% or running the process step at a up to 3-fold higher throughput. For polish, either batch or consecutive multicolumn flow-through or MCSGP processes can be used.


For industrial chemical applications, the setting of specifications and the characterization of impurities is becoming increasingly important, as chemicals are becoming more complex and often are derived from a combination of fermentation and synthetic processes. As an example, Antibiotics have been recently regulated through new requirements for related impurity characterization (EMA/CHMP/CVMP/QWP/199250/2009) by the European Medicines Agency (EMA). Chemicals have typically been purified after synthesis using crystallization, as the only available large volume purification method. Often, wastestreams from crystallization contain valuable product albeit contaminated with difficult to separate impurities. Thus, maximizing yield and polymorph control can only be achieved with a high resolution process. With the MCSGP process principle, continuous chromatography for large volume ternary separations offers a real alternative to crystallization, particularly for complex chemical processes where related impurities arise that cannot be separated sufficiently through crystallization. The Contichrom® equipment has been used for discovery, development and production of complex chemical products.

The Contichrom® equipment helps to

  • discover and isolate leads in sufficient quantities for further characterization
  • isolate product-related impurities for further characterization as required by regulatory guidelines
  • develop fast robust chemical purification processes retaining product and impurity profile at up-scaling
  • optimize API yield and retain polymorph control
  • switch inefficient chemical purification processes with low selectivity and yield based on crystallization to highly selective and productive chromatography processes retaining the product impurity profile at scales of larger than 100 tons. (Contichrom Platform_API_impurities)


ChromaCon has extensive experience in natural product purification. Application examples include omega-3 fatty acids such as DHA and EPA, flavonoids from citrus and other natural extracts.

Contichrom® equipment is designed to be operated in both aqueous buffers and organic solvents with low, medium or high pressure. The unique selectivity offered by the MCSGP process can be combined with low particle-size (5-15 µm) high resolution resins to provide unparalleled resolution from lab to production scale.

  • For production of gram to multi-kg scale the Contichrom® labscale system is suitable
  • For production of up to several hundred kg/year, the Contichrom® pilot-scale unit is suitable
  • For production at multi-ton scale, typically bulk 15 µm particles have been used to efficiently separate compounds obtaining a more than 10-fold higher productivity at greatly reduced (>80%) solvent consumption
  • For some cases, such as for omega-3 fatty acids, the MCSGP process has been shown to be the best available process for high purity, high volume natural products
  • As the Contichrom® process is much more efficient than batch process, the equipment and utility dimensions are significant smaller. Typically, for the same performance, an up to 50% lower CAPEX and OPEX is needed when employing the MCSGP process compared to batch processes


For non-pharma applications such as for example the purification of industrial biotech products, food ingredients, natural products, chemical intermediates, rare earth metals, sugars, remediation waste, please contact us for details.