The PAK System Continuous Manufacturing Equipment

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.

The mass flow control scheme controls the last product pump in the series to a flow rate set point, which sets the overall mass flow rate of the entire process. This flow rate set point adjusts based on the monitored flow rate of a critical unit operation.

The flow kit vessel level control scheme continuously controls all upstream product and buffer pumps to ensure constant levels in the small break vessels between each process stage.

The dual column vessel level control scheme periodically adjusts the product and buffer flow rates of the chromatography step to ensure the outlet vessel level of this stage remains within an acceptable range.  Since the fill of this vessel is periodic rather than constant (when an elution step occurs), the dual column vessel level control and associated buffer and product pump flow rate adjustments occur only one time at the start of each load cycle.

Vessel high-low level control stops the pumps from running when vessels reach their minimum or maximum levels, in extreme circumstances.

Dimensions   53” W  x  31” D  x  33” H (65” height with cart)

Flow Rate Range
Option 1: 0.3 ml/min to 240 ml/min (low flow pump)
Option 2: 1.3 ml/min to 1.7 L/min (high flow pump)

Tubing Diameters Accepted  1/16”, 1/8”, 3/16”, 1/4”

Pressure Limit  4 bar (58 psi)

Equipment 4 buffer pumps, 4 product pumps, 20 pinch valves, and 20 buffer inlet 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.

Materials of Construction
Flow Kit: Nylon 12 with fused silica windows    |  Product contact materials meet USP Class VI and/or ISO 10993.

Pressure 60 psi max (qty. 8)

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

pH range 0 to 14 (qty. 8 max)

Conductivity Range and Accuracy  0.02 mS/cm to 500 mS/cm (qty. 8 max)

Mass Flow Meter  20 g/min to 1500 g/min with density reading (qty. 2)

Scales  Floor scales with 450kg capacity (qty. 0-2), bench scales with 10kg capacity (qty. 4-6)

Electrical Requirements   120 VAC, 20A

Required Air Supply   90 psi

PLC   Rockwell CompactLogix™ 5480

21 CFR Part 11 Compliant Automation