Single-use technology has major benefits for the biopharmaceutical manufacturing industry. It enables rapid turnaround times between batches and allows facilities to be multi-product while driving down the cost of goods.
This, in turn, enables more people to access life-saving medicines.
But the use of single-use technology can be greatly enhanced by automating single-use processes, with data acquisition, process monitoring and control, and batch record generation all possible. This allows more complex unit operations to be run in cGMP compliant production environments.
For operators that remember the early days of single-use technology, turning down a pump speed when a line started to balloon due to pressure build-up may have been a very familiar exercise. Manual interventions in single-use platforms handling NFF were common.
Then came the first step in automating single-use processes. a pressure sensor linked to a display, which enabled the pressure to be read from a monitor. Although this still required attention to be paid to the system, it did free up operators from being "pump watchers".
The next step was linking this to an alarm to alert the operator — further freeing up the operator but requiring them to be local — and the next level of automation applied would monitor the dP and then switch off the pump once a trigger point had been reached, again freeing up the operator but not adding real value to the process.
Through Parker's SciLog® technology, we can apply the R/P stat method, which brings the full benefits of automation to NFF.
R/P Stat is an automated method for controlling NFF that can also improve filter capacity by up to 30 percent.
It works by controlling the pump speed based on the measurement of the pressure across the membrane (dP). The process starts running at a set speed and pressure in monitored.
As the pressure builds up over time, instead of reaching a trigger point for pressure and switching the pump off, the pump speed is reduced to prevent the dP building to a point that would trigger a process stop.
By running in this fashion, the process can run for longer.
Firstly, a smaller filter can potentially be used as the safety margin on the surface area need not be as great.
Secondly, the R/P Stat method makes it easier to handle unpredictable feed streams, for example, harvesting cell cultures in process development laboratories where the cell density, cell viability and productivity can vary widely from batch to batch.
In a more complex operation like TFF, a number of inputs need to be monitored and controlled and there are a range of outputs that could trigger the endpoint.
The volume of mass related process endpoints is relatively easy to control, based on measurements from a load cell. Through monitoring a change in the volume by measuring weight, process decisions can be made.
Obtaining a particular mass in the retentate tank during a concentration step would indicate that a certain concentration factor has been reached.
Alternatively, during a diafiltration step, reaching a set point on the permeate side would indicate that the required number of diavolumes have been processed.
Process decisions involving pressure are more complex as pressure is a function of the pump speed and pressure control valves. However, through automation, this balance can be achieved, for example, to maintain a set dP or TMP in the process.
The system will open and close valves and increase or decrease pump speed based on the programming logic to maintain the required set points, usually pressure, but also maintain the required process conditions, such as cross flow rates in a TFF filtration device.
It would be impossible to manually take a reading from three pressure sensors, two pumps and a couple of balances ever second over a four-hour period while at the same time calculating dP and/or TMP then adjusting the system to maintain a set point. Automation, however, makes this level of data capture and process control possible.
In addition, another advantage of an automated process is the generation of a data set that captures all the outputs from sensors, pumps and balances which is unambiguous, has the capacity to be copied without error, can be stored in multiple places, has an audit trail of changes, and can be downloaded easily for analysis without error. All of these are essential for bioproduction.
Read the full white paper - Automation in Single-Use: Unlocking the True Potential of Single-Use Technology
This post was contributed by Guy Matthews, division marketing manager at Parker Bioscience Filtration, United Kingdom.
Parker Bioscience Filtration specializes in automating and controlling single-use bioprocesses. By integrating sensory and automation technology into a process, a manufacturer can control the fluid more effectively, ensuring the quality of the final product.