Process Development Scale Continuous Purification System

Virus inactivation steps are a critical component of biopharmaceutical purification processes. Continuous virus inactivation in the PAK system is achieved with inline pH adjustment or inline addition based on a volumetric ratio for detergent. Flow through a residence chamber provides the specified hold time to achieve the required virus log reduction values (LRV).

Additional highlights of the systems capabilities include:

• Continuous monitoring of pH and residence time to ensure out-of-spec material is not directed to the downstream purification stage.
• Inline pH, conductivity, or volumetric ratio buffer addition at the outlet of the virus inactivation step to meet target ranges for the subsequent stage.

Please contact us if you have questions or would like to ask us about our preferred inline virus inactivation method.

Flow-through filtration steps include a 0.2 µm filter, depth filter, virus filter, or anion exchange membrane, among others. For these steps, the PAK System monitors the totalized process throughput, notifies the user when the membrane is nearing maximum capacity, and pauses the process if capacity is reached. Filters are often specified for once or twice daily replacement to not exceed capacities. The PAK system allows for inline buffer adjustments at the inlet and outlet of the step based on pH, conductivity or volumetric ratios. Back pressure control can also be performed with variable position pinch valves.

A dual column chromatography step enables bind and elute chromatography to be performed in a semi-continuous manner. Two stages of the system can be configured to perform a dual column chromatography step. The first product pump of the two stages continuously feeds product intermediate from the upstream step onto one of the two columns where it binds to the resin. A sequence of buffers is flushed through the other column to remove impurities or elute product intermediate. After the buffer cycle is completed and the column in the load step has reached capacity, the two columns switch positions.

The system provides gradient capabilities as well as inline dilution to reduce buffer tank volumes. Two UV wavelengths can be monitored simultaneously, with a single wavelength and/or column volume set points used for elution collection criteria. The elution collection vessel is sized for at least five elution volumes and mixed to ensure material supplied to the next stage is consistent and does not result in a spike in product concentration, pH or conductivity during an elution step.

Concentration steps are performed with single pass tangential flow filtration (SPTFF).

With The PAK System, you can:

• Achieve your target concentration factor with a variable pinch valve for back pressure control.
• Calculate concentration factor based on flow rate ratios or monitor density with the single-use mass flow meter.

A series of concentration and dilution steps, typically two or more, are performed in series to perform diafiltration or buffer exchange. A single PAK System can perform three concentration and dilution steps in series, followed by a final concentration step, to achieve the concentration and diafiltration targets of a traditional batch ultrafiltration/diafiltration (UFDF) process with greater than 99.75% buffer exchange.

New to continuous UFDF methods?  Reach out to us if you would like assistance converting your traditional UFDF process to an inline concentration and diafiltration step.

Dimensions   43” W  x  31” D  x  33” H (67.5” height with optional cart)

Flow Rate Range  0.01 µl/min to 10 mL/min

Tubing Diameters Accepted  1/32”

Pressure Limit  4 bar (58 psi)

Equipment 4 buffer pumps, 4 product pumps, 4 rotary buffer valves, 8 rotary product valves

PurSync™ Automation Control Package

Synchronous operation of four sequential purification stages per system, and up to four systems in series.

• Control schemes for low pH viral inactivation, TFF for single pass concentration and diafiltration, viral and other filtration, and chromatography.
• Inline buffer adjustment based on pH, conductivity, or volumetric ratio on inlet and outlet of purification stages. Pressure control for each purification stage.
• Automated startup and shutdown, including priming, sanitization, equilibration, and storage.

21 CFR Part 11 Compliant Automation

Pressure  4.1 bar (60 psi) maximum (qty. 8)

UV  Any two specified wavelengths from 185nm to 2600nm (qty. 4)

pH Sensors  0 to 14 (qty. 8 max)

Conductivity 0.01 mS/cm to 100 mS/cm (qty. 8)

Scales Bench scales with 12kg capacity (qty. 2)

Electrical Requirements   120 VAC, 20A

PLC   Rockwell CompactLogix™ 5380