Packing Sephacryl® S200 HR in the Verdot Ips² InPlace™ column

The Sephacryl® S200*, a size exclusion chromatography media from Cytiva, requires a special packing method for obtaining the best performance (Theoretical plates number and assymetry) in large scale columns. Merck Aubonne and VERDOT Ips² drove together a packing study of Sephacryl® S200 HR in VERDOT Ips² D45cm Column using axial compression, with great results. 

Please refer to the tech note for more details.
*Sephacryl is a registered brand from Cytiva, formerly GE healthcare.


FlexiPro™ by VERDOT, The Single-Use Chromatography Solution for AAV, Lentiviral and plasmid DNA Purification Challenges

The purification of gene therapies based on viral vectors and/or plasmid DNA present unique equipment requirements.  Systems must be fully GMP-compliant, prevent potential for cross-contamination between batches, be operator-friendly, and provide capability to isolate fractions based on nucleic acid and protein concentration.  These requirements, and more, must be met in systems capable of running purification columns with milliliters of media.
VERDOT’s FlexiPro™ Single-Use Chromatography System is ideal for AAV, Lentivirus, and plasmid DNA purification processes:

- Two sizes of Flow kits especially designed for these applications: 
         * UltraLowFlowKit: pump flow range 4-117mL/min compatible with columns size as small as 8mL,
         * VeryLowFlowKit: pump flow range 17-500mL/min compatible with columns size 40mL and larger.
- Disposable Flow Paths are pre-assembled and mount in twenty minutes.
- Four bar operating pressure capability.
- The dual-pump system enables precise and reproducible in-line dilution and gradient elution steps.
- Simultaneous dual-wavelength UV detection allows real-time monitoring of nucleic acid and protein concentrations and optimal fraction collection.
- The user interface provides self-explanatory  real-time process monitoring, controlled user access, and an easy-to-use workflow for method development/review/release for manufacturing.
- Full GMP-compliant documentation comes with every system and flow kit, at no extra charge.
- Complete batch record, alarm history and process data collection, exportable and accessible by third-party plant-wide data systems.

For more information, click here to contact us about FlexiPro™ 



Quality Assurance Manager for the company VERDOT Ips² for 17 years, I have built our QMS on the model of a major American group while taking into account the specificities of an SMB.
Some of our customers are surprised to see that a company of 40 people, with 4 dedicated resources (a system QA manager, a welding coordinator, a quality controller / EHS coordinator and a documentation technician), can have such an organization and so many applicable and applied procedures!
My answer is that our management system encourages all staff members, at all levels, from operator to director, to be quality collaborators with daily tasks related to the quality commitments described in each process.
At VERDOT Ips², everyone is aware of the importance of traceability and finish of the products manufactured with regard to their use by our customers. Self-checking and cross-checks between all members are habits. Each employee can freely report a deviation or dysfunction observed internally, it is not just a matter of QA or QC. Moreover, as a QAM, I hardly write any non-conformity reports since they are communicated to me by the operational staff. I then focus on monitoring the corrective and preventive actions that allow VERDOT Ips² to progress.
I also built our QMS so that the customer, the end user, is at the heart of our concerns, in all processes. Most of our procedures describe flow charts that allow us to adapt to the variability of customer requirements while maintaining, at a minimum, a very high level of quality (total traceability of parts in product contact and subjected to pressure, very low roughness ≤ 0.4 µm, qualifications of all welders).
In conclusion, our QMS is stable and mature. Our ISO 9001 certification exists since 2006 and has been issued successively by 3 different notified bodies with only 2 minor non-conformities noted in 13 years. The quality audits of our customers allow us to give VERDOT Ips² the status of approved supplier each time. 
Stéphanie, QAM for VERDOT Ips² (2019)


InPlace D160cm Column Packing with NanoMicro Uni Resin S-60M

In order to facilitate the start-up of our chromatography columns, the VERDOT process experts offer their service all over the world, especially for the column packing. In this context, VERDOT recently intervened at a customer site in China, to adjust the packing and unpacking method of the InPlace D160cm column with a resin Uni S-60M from NanoMicro. The package performance test  (HETP, Asymetry)  showed a very good performance, given the size of the column, with a number of trays greater than 4500pl / m and an asymmetry of 1.05. The experiment has also shown an excellent ability of the InPlace column to re-suspend the resin in place and extract it completely from the column with a minimum of buffer.


Collaboration between TOSOH Bioscience and VERDOT Ips²

VERDOT Ips² SAS and Tosoh Bioscience have entered into a Memorandum of Understanding whereby the two companies plan on engaging in joint-marketing activities in the Americas and Europe. Combining best-in-class chromatography resins from Tosoh Bioscience and leading-edge column hardware and purification skids from VERDOT® will provide an unmatched technology platform for efficient purification of biomolecules in downstream bioprocessing.

“We are very excited to enter into this agreement with a partner who shares the same core corporate values: professional integrity, dedication to advancing scientific boundaries, and commitment to enhancing customer experience”, said Eric Merlot, Deputy Managing Director at VERDOT Ips². He added, “Both VERDOT Ips² and Tosoh Bioscience have a long history of excellence in the field of process chromatography, recognized by our peers and customers, and together we are able to offer cutting-edge chromatography platform solutions with an unparalleled technical support.”
The chromatography specialists from Tosoh Bioscience and VERDOT Ips² will work together to combine their expertise to tackle the biopharmaceutical industry’s challenges related to production-scale chromatography operation and performance. Dr. Romain Dabre, Product Manager for Process Resins at Tosoh Bioscience GmbH, explained: “Our best-in-class resins together with VERDOT®’s chromatography hardware will enable our customers to develop cost-effective, safe, and efficient methods for the purification of most common biotherapeutics, such as antibody constructs, recombinant proteins, and oligonucleotides.”
According to Sébastien Lefebvre, Customer Applications Expert at VERDOT Ips², this collaboration will allow the two companies to share their experience and knowledge in order to better serve their customers. “Users will thus be able to benefit from advice and good practices to obtain an excellent and reproducible package performance thanks to the unique packing techniques that VERDOT Ips² has offered to the market since the 1990s. Moreover, using the unique functions of the VERDOT® InPlace™ column will minimize the time and the buffer consumption required for packing and unpacking operations, helping to improve the environmental footprint of our customers’ processes”.

Ali Soleymannezhad, Director of Sales and Marketing at Tosoh Bioscience LLC, emphasized the significance of this relationship regarding Tosoh Bioscience’s newly launched hydroxyapatite resin, Ca++Pure-HA®: “For years, VERDOT®’s InPlaceTM chromatography columns have offered an ideal solution for packing, unpacking, and cleaning in place of incompressible ceramic resins. With its unique low-shear slurry valves, InPlaceTM is the perfect hardware solution for effortless and reproducible packing of Ca++Pure-HA®. I’m sure our Ca++Pure-HA® users will be excited to hear about our collaboration with VERDOT® and to have a direct access to a reliable large-scale column packing solution for hydroxyapatite resins.”


Obtain high performance packing with Sephacryl® S200 in large scale columns using VERDOT InPlace™ technology

While commonly used for purification at laboratory scale, size exclusion chromatography is also unavoidable in some applications at process scale for fine separation of molecules. Such separation is very demanding in terms of packing performance (HETP, As) as it directly influences the quality of the purification (yield and purity).   Uniform and reproducible packing of the preparative column are thus essential.

Special operating methods are required when packing this media in large scale columns. However, the unique features of the InPlace columns combined with a process chromatography system make the packing easy and reproducible.

In collaboration with Merck, Aubonne (Switzerland), a packing study was performed with Sephacryl® S-200 High Resolution*from GE Healthcare, in a VERDOT InPlace ™ column, ID446mm with a bed height of 330mm. The packing study validated the packing method to consistently obtain a high number of theoretical plates (HETP) and good asymmetry.
The InPlace column was packed in downflow and the performance was assessed in upflow for ensuring the stability of the performance in both directions.
Under the stated conditions, our packing method delivered an average of 10000 plates/meter, a reduced HETP** of 2.0, and asymmetry values of 0.8 – 1.7 in a campaign of three packings.
Contact your VERDOT representative for more information.
(*) Sephacryl is a registered trademark of GE Healthcare
(**) reduced HETP: rHETP = HETP/mean particle size. Refer to our tech note HETP Test


VERDOT InPlace™ column, the best technology for packing & unpacking of Ceramic Hydroxyapatite (CHT)

Ceramic Hydroxyapatite requires special consideration during process scale chromatography packing. This is primarily due to the high specific gravity and rapid settling rate of CHT, moreover for the CHT 80µm that has a free-settling velocity of 125-275 cm/hr.  Additionally, as the CHT media is sensitive to mechanical shear, it can lead to fracturing of particles and creation of fines.
VERDOT InPlace columns offer a unique solution for media such as CHT with smooth slurry transfer, packing in axial compression and unpacking with minimal amount of buffer.

Please refer to the technical note CHT in VERDOT InPlace to know more about it. This technical note gives information on the best practices of using CHT in VERDOT InPlace columns.


VERDOT expands its range of FlexiPro with two « very low flowrate » disposable fluidic paths

The VERDOT Chromatography skid is now available in its «  very low flowrate » version for  small scale purification processes

FlexiPro ™ chromatography equipment is a compact system with disposable fluid path capable of handling small and medium scale GMP biopharmaceutical molecule purification processes. It has been specifically designed for single-use processes as well as for multi-product production units.

So far the initial range has been offering two fluidic path scales:
  • the “low flow kit” (LFK) that runs from 5 to 150 L / h and
  • the “high flow kit” (HFK) that runs from 20 to 600 L / h.
To meet the growing demand of very small volumes applications (like in the case of orphan diseases, clinical trials, …), VERDOT has developed two new fluid paths compatible with the same flexipro system allowing to work from 0.6 to 7LPH, with Ultra Low Flow kit “(ULFK) and 1 to 30 LPH with the” Very Low Flow Kit “(VLFK).
An adaptation device has been installed enabling the FlexiPro to adapt to the size of each fluid path. As a result the same FlexiPro system can cover wide scale ranges to provide purification of therapeutic molecules ranging from a few grams to several kilograms.

Time to changing the adaptation set and the fluidic path is less than half an hour.

All of the FlexiPro fluidic paths meet the following specifications:
  • 4 sizes of fluidic paths:
    • ULFK: 0.6 – 7LPH (10-116mL / min)
    • VLFK: 1 – 30LPH (17-500mL / min)
    • LFK: 5-120LPH (83-2000mL / min)
    • HFK: 20-600LPH
  • 7 process inputs, spread over 2 pumps
  • Automated inline gradient and dilution possibility
  • High precision disposable instrumentation
  • Possibility of up to 4 bar of operating pressure
  • Flow kits assembled in ISO 7 clean room and delivered in double packaging
  • Documentation and records respecting all regulatory requirements


Close collaboration maximizes value of engineered solutions and saves time in start-up

This article has been issued in La Vague Magazine N#53, April 2017 – pages 27 to 29.

The case study of BioMarin Fast-Track project with VERDOT Ips²

This paper reports a very fruitful collaboration between a Biopharmaceutical company, BioMarin International Ltd and a manufacturer of purification equipment, VERDOT Ips², which contributed to a fast start-up of an installation for manufacturing a recombinant human tripeptidyl peptidase 1 (rhTPP1), for the treatment of neuronal ceroid lipofuscinosis Type 2 (CLN2) disease, also known as Batten Disease.

The successful start-up of every manufacturing process depends on:

  • Design and building of equipment, engineered for purpose and qualified to deliver the quality and efficacy attributes of the product;
  • Validated procedures for operating, cleaning, and maintaining operations, which must be optimized according to the installation;
  • Trained and competent engineering and technical staff for operating, maintaining, and supporting the operation;
  • Continued support by supplier-partners who maintain understanding of the equipment, application, and project history through the qualification and start-up phases and hand-off to operations.

VERDOT Ips² InPlace™ Chromatography Column

Since 1987, VERDOT Ips² is a worldwide supplier of purification solutions, especially in Low Pressure Liquid Chromatography, for applications in Biopharmaceutical and Nutraceutical manufacturing.

BioMarin ( is a world leader in developing and commercializing innovative biopharmaceuticals for rare diseases driven by genetic causes. In that respect, Children with CLN2 disease typically begin to present symptoms between the ages of two and four, with the majority of affected children losing their ability to walk and talk by approximately six years of age. During the later stages of the disease, feeding and tending to everyday needs become very difficult, and death often occurs between 8 and 12 years of age. Saving months on the market release of such therapy can save years of life expectancy for the young patients. Thus, after positive results obtained during clinical phase, BioMarin accepted to launch an early access program to provide experimental drug prior to marketing phase.

The collaboration between BioMarin Shanbally Ireland and VERDOT Ips² in this project started in September 2015. The goal was to start up a large scale process chromatography installation within eight months to respect the timing of the early access program.

In addition to the stringent planning, the project also involved difficult space constraints, as the new installation had to fit in existing production suite dimensioned for smaller scale.  Smart chromatography column design, capable to reduce volume of consumables for its preparation (packing/unpacking/cleaning) was thus considered as a strong advantage for minimizing the impact on utilities, such as the WFI installation.

Excellent team work and communications were critical to respond to the challenge. The engineering teams of BioMarin and VERDOT Ips² worked closely together to address the space & utilities constraints with consideration of operational requirements and work ergonomics. The project managers of both companies met weekly through the project completion to satisfy the milestones of the planning, and respond to challenges in coordinating the supply chain of equipment and fabrication.

Standard Operating Procedures (SOPs) are the most important documents available to operators, engineers and maintenance technicians. They describe very precisely the implementation of the design intention with the installation, and ensure the consistency of quality and efficacy in batch, whatever the operator. Very often this document is drafted by a process expert alone, who writes it based on his own experience and following template procedures close to the ongoing application. The specificities of the installation and the current application can thus not be fully considered. This approach does not allow us to integrate new know-how from external experts, such as suppliers of consumables (chromatography resins, filtration membranes) or equipment suppliers. Useful tips can be found in the instruction manuals of each one, but these being generic are rarely applicable as described.

Based on successful experience between the two partners, BioMarin and VERDOT Ips² implemented an intensive collaborative approach to speed up the preparation for installation and commissioning of the equipment.  This approach was based on the co-writing and co-validation of the SOPs.   Following BioMarin’s standard format and based on the existing installation and quality attributes defined for the new product, BioMarin and VERDOT Ips² very openly shared their experience to write the detailed procedures for equipment preparation: packing, unpacking and pre- and post -packing cleaning. The new procedures were pilot tested in generic and non-GMP conditions, just after the Site Acceptance Test.  This early procedure walk-through allowed optimization of parameters settings and sequence of operations. The revised procedures were tested again in cGMP conditions with the set of buffers and stationery media defined for each purification step. The static phases, i.e.: chromatographic media, were supplied from various international suppliers. One also provided his assistance during the packing.

BioMarin and Verdot Ips2 also know from experience that important design features can often be left behind in the hand-off of equipment from supplier to customer engineering to operations.  Without critical communication, awareness, and training, operational practices quickly default to familiar techniques developed on obsolete equipment.  The opportunity provided by a new manufacturing process with purpose-engineered equipment and an aggressive timeline means everyone involved can be hyper-focused on the details of change.

Results and Discussion

Column cleaning

The column was sanitized with 1N NaOH (Sodium Hydroxide), injected via suction using the motorized adapter as a large syringe.  The adapter equipped with an inflatable seal was fully soaked in Sodium hydroxide with seal deflated. After 2 hours of soaking, an alternated circulation of NaOH between down flow and up flow performed a full sanitization of the distributors and bed support. The design of the adapter ensured that the mobile phase was distributed everywhere, enclosing the border of the dynamic seal to avoid risk of bioburden.

Column packing

The InPlace™ column of VERDOT Ips² being equipped with slurry valves, the media was transferred in “close” conditions minimizing the risk of contamination. The media transfer performed via suction with a controlled stroke allowed transferring a precise amount of media, for ensuring packing reproducibility. The column degassing was instantaneously obtained by actuating the embedded column tilter while deflating the dynamic seal. The media was simply packed in axial compression by lowering the adapter at controlled speed and automatic height monitoring for precise compression control.

This ensured a high performance packing. For instance, an agarose based media bed gave a reduced HETP (Height equivalent to theoretical plate divided by mean particle size) of 2.16, with 4400 plates/m and an asymmetry of 0.96, all within BioMarin acceptance criteria.

Column unpacking

The packed bed was re-slurried in place by injecting one column volume of water alternatively in up flow and down flow, followed with a 20 minutes air-sparging by simply injecting low pressure air through the bottom process connection. For emptying the column, the column was tilted and the slurry valve located at the lowest point of the tilted column was opened to the slurry tank.  Air sparging was maintained during the slurry transfer to keep the media suspended, maintain slight pressurization and help the media flow toward the slurry valve. Only small traces of media were left in the column, easily removed with a few liters of water. As result, less than 2.5 columns volume were required to reslurry the bed transfer the slurry back into the tank (maintaining a 50/50 slurry) and completely rinse the column, leaving no trace media.

After validation by VERDOT Ips² and BioMarin process experts, BioMarin Operating teams took over and repeated the procedures without assistance to ensure documentation was sufficiently detailed and precise to ensure reproducible results with the different teams working around the clock.


This experience has confirmed that the equipment intrinsic performance is only one success factor of a successful new process implementation. A thorough collaboration between the Users and the equipment supplier all along the project, and especially at the project start-up is also paramount for the success. The very open discussion and confident share of information between the different parties, under non-disclosure agreement, has finally made the collaboration efficient. As result, it contributed to the timely manufacture of the first lots of rhTPP1 under the early access program and smooth step-up to the forth-coming manufacturing phase. 


The new VERDOT Chromatography Column 2S for food, cosmetic and nutraceutical purification

Food, cosmetic and nutraceutical applications often require separation of molecules or families of molecules with high purity, usually from vegetal or milk sources. Process chromatography is a good means for this purification when co-products and target molecules are close to the same size, especially using reverse phase or ion exchange techniques.

Very often, these applications involve food grade media, with large particles that are often subject to swelling and require high Height/Diameter ratio.
Current columns available on the market, with tank-based designs and large distribution chambers, are adequate for product treatment (demineralization, decoloration, debittering,…), but less suitable for molecule purification due to the large dilution induced by their distributors.

The VERDOT Chromatography Column 2S, has been designed from the wheels up for molecule separation applications .

The features of the Verdot Column 2S include:
  • High performance distributors with low void volume for maximum purified product concentration
  • High H/D, customizable for specific applications
  • Various solutions for media replacement, depending on frequency
  • Complete documentation for regulatory submissions
  • Optional configurations with higher solvent resistance
  • Robust design compatible with frequent wash downs in production environments


A versatile system for Continuous Chromatography Purification

Continuous purification processes are emerging as tools to deliver greater productivity and manufacturing efficiency than batch process.  For pilot and production scale continuous purification methods, VERDOT Ips² is pleased to propose its new Multi-Purpose Continuous Purification Platform, the Verdot P3C system.
The Verdot P3C system offers a wide range of capabilities:
  • Simultaneous use of up to 5 chromatography columns with diameters of 1.5 cm to 10.0 cm.
  • Flow ranges of 5 ml/min. to 280 ml/min, with tubing diameters of 0.75 mm to 2.5 mm ID.
  • Operating pressure up to 3.8 bar.
  • Six pumps heads, two flow meters, and in-line continuous pH, Conductivity and UV absorbance sensors.
  • Open design for quick re-configuration of flow pattern.
Customized solutions are available to meet unique requirements.

The features of the control system for the Verdot P3C include:
  • Real-time monitoring of the separation process by continuous flow rate, UV absorbance, Conductivity, and pH measurements.
  • Process run history including all events, alarms, set points and operating sequences.
  • Opportunity for integration with plant-wide information systems through the Open Platform Communication (OPC) server of the P3C system.
  • Straight-forward programming of process sequences using functional blocks.
This platform makes it possible to operate a sequential chromatography scheme in Bind & Elute mode with multiple columns, and to use columns in series with different ligands for performing two purification steps at one time. The isocratic mode, like Simulated Moving Bed, and other continuous purification technique are also possible.

Several applications for the purification of proteins and heterosides have been successfully developed on this platform, and scaled to our larger production systems.


Verdot Ips2 ‘s AgiChrom, a simple solution when LPLC chromatography with packed bed is difficult (Diatomaceous earth, silica, etc.)

Some chromatography supports based on diatomaceous earth, silica, and alumina are rarely used in packed bed chromatography for LPLC applications.    These supports can be difficult to clean, pack consistently, and run at low back pressures. The column packing is tricky due to the physical properties of the particles:  brittle tensile strength limits compressibility and small and variable particle sizes lead to dense packing and high back pressure.
The VERDOT Ips² AgiChrom agitated column circumvents these limitations and allows the user to perform several unit operations in one piece of equipment:
  • Dry Chromatography media can be loaded through the open top. Slurried media can be poured in from the top or pumped through the slurry valves mounted in the bottom flange.
  • The impeller, with motorized height adjustment, allows progressive slurrying of the media in a mobile phase, minimizing the shear stress on chromatography media.
  • The level of liquid in the column can be automatically controlled, by introduction of liquid through the ports on the cover and draining through the bottom filter.
  • The chromatography media can therefore be cleaned in place one or more times. The  mobile phase burdened with particles can be siphoned through a dip tube.
    Then the chromatography media can be mixed with the raw product and the various mobile phases for the mass transfer.
  • At last, the chromatography media can be removed from the column through the slurry valve(s), with automatic column tilting.
The mass transfer in agitated mode allows using of the full media binding capacity, while being relieved from the flow resistance due to chromatography media and product viscosity.
For the same reasons, the AgiChrom column is also very adapted for applications using very soft media unstable in settled bed mode (dextran matrix,…)


MiniPro system as pilot scale LPLC process chromatography system

VERDOT Ips² MiniPro system is now also proposed as pilot scale LPLC process chromatography system.

The VERDOT Ips² MiniPro system, the most compact LPLC process chromatography system in the market, is now also proposed with a low flow configuration (1-60L/h), for serving as pilot chromatography system.

This system can thus be supplied with pilot flow kit (1-60L/h) and process flow kit (5-120L/h) for allowing scale-up with minimal investment. As standard, it is proposed with dual pumps for precise in-line dilution and gradient and it encloses all the instrumentation for fully automated LPLC purification, with safety controls and trends records. One hour presentation suffice for a new User to run the system and program simple or complex purification method.


Packing & unpacking of Sepharose(™)Fast Flow(GE) in InPlace(™) column

Testing was performed in order to evaluate the packing and unpacking capabilities of the Verdot Ips² InPlace column, using Sepharose(™)(1) media.  A 14cm bed of GE Zinc Imac Sepharose(™) Fast Flow media was packed in an 80 cm diameter Verdot Ips² InPlace column, using a compression factor of 1.15.

(1)Sepharose is a Trade mark of GE HEALTHCARE BIO-SCIENCES
Two packings were performed. The initial packing was performed with an empty column, the second following the performance of re-slurrying within the column.  Both packings were evaluated using HETP and Asymmetry tests and provided great results and reproducibility.

Prior to removal, air sparging and the InPlace columns tilting feature were used to re-suspended the media within the column in less than 20 minutes.  Through the column slurry valves, all media was transferred into the slurry tank in less than 5 minutes.