June 15, 2015 (Vol. 35, No. 12)

David M. Johnson Global Product Manager, Chromatography Hardware Pall Life Sciences

Automation as a Route to Reducing the Risks Associated with Large-Scale Chromatography Column Operations

To mitigate the risks associated with column packing, the biopharma industry is moving toward a more science-based approach from the traditional stance of regarding column packing as artistry. The key is fully automating the operations involved in preparing a column for production. Existing semiautomated packing technology typically only automates portions of the process, leaving considerable potential for operator error.

The essence of column packing is to achieve an efficient and stable packed bed. Process-scale bioseparations often involve a high turnover in packing activity which increases the potential for a packing failure to occur. In the case of global manufacturing, column performance should be consistent across multiple plants and geographies.

As an illustration of the benefits of full automation, a multinational vaccine company that previously used manual methods noted that creep in standard operating procedure (SOP) execution and operator error was significantly affecting productivity. By moving to a fully automated packing platform, the company forecast a packing success rate increase from 62% to 99%.

The use of automation is on track to reduce labor costs by 35% on average. The adoption of a single-use slurry-handling system also simplifies operation and reduces cleaning time. The new columns also have a smaller cleanroom footprint which translates into more space in tight cleanrooms.

Another limitation of some existing technologies is that the piston movement is controlled with one centrally placed actuator, creating the potential for uncontrolled skew that can, in extreme cases, damage the column. The latest generation of packing technology addresses these challenges by fully automating the packing, unpacking, and clean-in-place processes and offering active  monitoring and control of the piston to prevent or detect skew conditions.


Figure 1. Columns equipped with the latest automated packing systems

Skilled Operators

Traditional manual and semiautomated packing methods depend heavily on the capabilities and attention levels of a few skilled operators. At any time, these operators may leave the company or otherwise become unavailable, and they may be succeeded by personnel who fail to achieve the required levels of performance. When processes are transferred to new sites, the SOPs are transferred, but the new operators often have to learn how to make the packing procedures work. These operators may develop their own ways of doing things even after training. Consistent and adequate performance may not happen soon, if ever.

Manual and semiautomated packing methods can waste substantial amounts of media, the costs of which can run as high as $15,000 per liter; typically 5% to 10% of the total column volume of media is left in the slurry tank after packing. Expiry issues with blending this excess into the next pack often mean that the excess media is thrown out.

The use of manual or semiautomated packing relies heavily on the skill of the operator; valve adjustment, pump flow rates, and piston movement must be manually controlled by the operators and recorded in a batch record. These are lengthy, complex, and error-prone processes.


Figure 2. Typical hardware to enable fully automated packing

New Automated Systems

A new generation of columns provides a fully automated approach to packing, unpacking, and cleaning that elevates packing from an art to a science. The packing system is fully integrated with the actuation system of the column, making a separate packing skid or pump unnecessary for all operations (Figure 1). To achieve full automation, the column is supplied with mobile phase and bypass valve blocks. An additional valve block to control liquid flow from the buffer and slurry tanks is included (Figure 2).

Valves dedicated to air entry are provided to both the slurry tank inlet and bottom mobile phase valve blocks, assisting buffer-efficient resuspension of settled slurry and packed media beds.

The automated packing system has full control of this valving, as well as adjuster movement and nozzle operation. The system additionally has a liquid sensor that allows it to monitor the column liquid levels and thus offer greater process and personnel safety.

The software that controls the fully automated operation uses industry-standard PLC control and touchscreen interfaces. The software also permits manual control of the column for legacy operations, while the on-screen schematic provides a real-time indication of the system status during all operations. For typical fully automated operation, the operator is only required to push the start button to begin the relevant process (Figure 3).

From this point, the automated packing system controls the entire sequence until packing is complete, and no further operator attention is required. A selection of packing methods is provided, each fully configurable to match the target application.

The column is self-priming, first by filling the column interior and then priming the rest of the system by sequential opening of the column pipework. Next, the system starts the slurry suction step. Tank agitation is stopped, and slurry is drawn from the tank into the column.

An exact amount of slurry can be drawn into the column through the packing nozzle. The column is sized so that enough slurry (and therefore media) can be drawn into the column to meet the desired compression factor at the target bed height. The system can also empty the slurry tank during the suction phase, eliminating the waste that occurs with some conventional manual and semiautomated packing systems. The packing sequence then continues seamlessly into the consolidation and packing phase.

The piston descends using the chosen packing profile to form an optimally packed bed. Dependent on the equipment, a bed detection algorithm can be used to detect an optimally compressed bed. At the end of the sequence, the operator is informed that the packing is complete; the column is now ready for testing and production.

The column can also automatically unpack and clean itself at the push of a button. As with the automated packing sequences, these operations do not require any extra equipment to complete. This reduces the cost burden of maintenance and cleaning of additional capital equipment.

Unpacking is made more efficient by the use of air to resuspend the media bed inside the column, often only consuming the same buffer as when the operation is controlled by an experienced operator. The equipment can also resuspend and repack a column without removing the slurry from the column, providing further savings in buffer consumption, equipment cleaning, and turnaround time. This methodology is useful in cases where the packing has failed before the media has reached the end of its life.

At all times during piston movement, the software monitors the position of the piston moving and actively controls the levelness of the piston in response to a deviation from the set point. With a single actuator control system, it is generally not possible to control or even monitor piston levelness, resulting in an increased risk of column damage from a skew event.

The equipment has a built-in maintenance function that provides easy operator access for safe change out of consumables from ground level without compromising the cleanroom footprint. Other solutions to providing hoist-free maintenance include functions that move assemblies out horizontally, which means that extra floor space must be provided. The new generation provides a vertical form factor that eliminates the need for additional floor space.

All in all, the move to full automation enables biopharmaceutical manufacturers to produce more efficiently at a lower cost and risk.


Figure 3. Fully automated packing sequence




























David Johnson (david_m._johnson@europe.pall.com) is global product manager, chromatography hardware, Pall Life Sciences.

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