I spend roughly 90% of my time working with iCELLis™ 500+ bioreactor systems. These are intricate and complex pieces of equipment that play a crucial role in helping biomanufacturers all over the world develop and distribute drugs.
In my view, one of the most important aspects of servicing bioreactors is the preventive maintenance. This annual procedure ensures that the system is in optimum condition, reducing downtime and allowing users to maximize the use of the equipment. Because preventive maintenance is so important, especially for sophisticated systems, I thought I would share some highlights about how I approach this procedure.
When I first arrive at a site for the annual preventive maintenance, I conduct a visual inspection for damage to external components so that I can get a sense of what I’m working with. Then it is power on and setting up the bioreactor and maintenance tools for a deep dive into the unit.
Key component maintenance
Firstly, I take a look at the Mass Flow Controller, which is the part of the component that supplies gas into the vessels for cell growth. This part of the instrument needs to be calibrated to ensure that there is the appropriate flow quality to the vessels so that cells grow efficiently. With calibrations, precise measurements are taken on a component and then adjusted as needed to be within a specific range. With calibration of the Mass Flow Controller, the gas flow needs to be within 1% tolerance. On average, the calibration takes around 2.5 hours. If it’s within tolerance from the start, the process may take slightly less time, but individual components still need to be reviewed to ensure everything is functioning as expected.
Within the Mass Flow Controller, I replace the Agitation Motor Gearbox that controls the agitation of the media (without agitation cells won’t grow). Significant wear to the gearbox gaskets can occur over time which is typical of any gearbox when subjected to repetitious actions, such as the loading and unloading of units.
My second step is to maintain the Media Pre-Heater and Filter Heater. The media pre-heater needs to be at the right temperature to keep the cells alive, so it’s critical to check that the temperature settings are accurate. The filter heater is important because it heats up the gas as it exits from the unit and ensures that it’s not entering the atmosphere as a potential hazard.
Next, I check the speeds of the pumps and verify that they are spinning correctly. For this step, I use a calibrated tachometer to set the speeds at a certain point. If they are outside the specified range, it is indicative of a problem with the motor or head and is further investigated, either by stripping down the pump or replacing individual components.
Maintenance of critical monitoring components
Careful monitoring and optimizing of sensitive cell growth is achieved through knowledge of key parameters of the fluid such as pH and dissolved oxygen (DO). These are monitored using digital probes and during this stage of the preventive maintenance, I use a buffer to verify that the pH and DO readings are at the right level so that the living cells inside the vessel won’t die. During this stage, I also check the operation of the temperature probe going into the vessel. To do this, I investigate the physical conditions of the probes, as well as measure the temperature of the media inside the vessel to ensure that it’s not too hot or too cold. End-users also need to ensure the unit is operating at the right amount of pressure for optimal cell growth, so my next action will be to check and calibrate the pressure transmitter for the bioreactor and pressure double jacket. Having too much pressure or a vacuum in the unit can also lead to negative implications, worst case being explosion of the vessel!
After that, I check and calibrate the load cells for bed support. I perform tests and maintenance procedures so that the vessel has the correct weight on the scale. Doing so ensures that the correct quantity of media is in the vessel. If the scale isn’t functioning as expected, there’s a risk that there might be too much or too little media.
My final step to wrap up the preventive maintenance is to verify the operation of the temperature control unit. I perform a variety of checks to confirm that it heats up and cools down so that the media can stay at a consistent temperature while it is circulating in the vessel.
This is typically what an iCELLis™ 500+ bioreactor preventive maintenance visit looks like. The reality is that many maintenance issues are not overtly evident until an engineer starts looking deeper into the instrument and the performance of individual components. Producing and harvesting cells is clearly a process that is very sensitive to the smallest changes which can drastically effect yield size and cell quality. For me, this is what makes preventive maintenance so important. The iCELLis™ 500+ bioreactor is a complex, powerful piece of equipment and is used in drug development for many of the world’s leading biotech companies. Bioreactor preventive maintenance is just one piece of the bigger picture that aims to minimize batch loss and provide modern biotherapeutics, developed for everyday people, to combat gene-based disease.