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Because the pressure differential remained unchanged, we attributed the increase in pressure readings from both filters during the filling of each individual bag to increased fouling of the 0.2-µm filter. The pressure differential remained constant at ~5 psi for the first 120 minutes of processing, at which point 600 L of cell culture harvest were filtered. At the end, the pressure differential reached 8 psi. Regardless of that minor increase, the pressure differential did not approach the maximum allowable value for this depth filter (20 psi).
A spike in pressure at ~85 minutes was due to a piece of kinked tubing. The PressureMAT monitor's audible alarm, which can be triggered by a predetermined high or low pressure value, alerted the operator to the flow-path obstruction. Without that alarm, it could have gone unnoticed. The alarm set point can also trigger an internal relay that can be easily wired to automate process control by shutting off a pump or opening a valve.
Comparing Figures 3 and 5, it's clear that the combined PendoTECH pressure sensor and PressureMAT system are superior to the analog stainless steel pressure gauges alone. This new approach offers frequent, accurate, and automatic pressure readings that provide a complete picture of depth filter performance. The information assists in process monitoring, process improvement, and trouble-shooting. In addition, the automated pressure monitoring and recording function can free up operators for other tasks, reducing the labor demand of these operations.
PendoTECH single-use pressure sensors are available in a wide range of sizes. They are easily adaptable to filter screening experiments with small disc filters or scale-up to high flow rates with sensors for 1-inch tubing size. Each sensor is tested during manufacturing to be in calibration, but there is no ability to directly calibrate the sensors or PressureMAT monitor. If a demand for verifying proper functioning of the monitor and the output of a sensor exists, particularly for a GMP process, it is feasible to test the sensors and the system without interfering with the flow path. Each pressure sensor has a test port on its connector cable that can be used to access the atmospheric reference side of the pressure-sensing chip. The test port is a female Luer port, and by applying a calibrated vacuum source to this port, it will give a pressure reading with the same absolute value on the monitor.
For demands on validating the pressure readings, PendoTECH has developed the National Institute of Standards and Technologies (NIST) traceable PressureChecker device to perform this operation (Figure 5). It has an internal cylinder with an external adjustment knob that can create vacuum and pressure to the sensor test port. This testing can be done without flow-path interferance and serves to verify proper functioning of a newly installed sensor. It has a pressure sensing chip simulator embedded that references the internal cylinder. In addition, the PressureMAT monitor cable can be connected to the simulator port and the PressureMAT can be tested to verify it is functioning properly.
Advantage: Process ControlAt Centocor, we found PendoTECH single-use pressure sensors and the PressureMAT monitoring system to provide many advantages. Disposables eliminate the demand for cleaning verification or validation, saving time and cost. Set-up is easy, and the configuration does not create deadlegs in process streams. This system could also provide for automation and feedback control functions.
The PressureMAT system offers 4–20 mA outputs that can be interfaced with a distributed control system (DCS).
This feature would allow end users to connect it with other instruments (e.g., pumps and scales) that might not be directly connected to the system, but that would offer additional control over a particular process. Analog inputs configured in DCS can also be sent to data historian programs for data collection purposes.
These pressure sensors provide accurate and reliable data that can be automatically recorded into data historians and control systems, allowing operators to focus on other tasks. This is ideal for pilot plants and multiproduct facilities, where product turnover and equipment changeover are frequent. This new technology is being tested and evaluated in development operations, and its application in routine manufacturing operations will be further evaluated later. The system also can be used on other applications in which pressure monitoring is needed, such as for filter capacity testing, determining chromatography column pressure flow curves, and controlling tangential flow filtration operations.
