Pumps have played a crucial role throughout the COVID-19 pandemic helping to keep essential services running, and food and products available to people, but another important area where pumps will have a major impact is in the biopharmaceutical industry which is hard at work manufacturing a vaccine so society can return to normal. Here, we look at four commonly used pumps that are found in biopharmaceutical applications.
Pumps are used in biopharmaceutical processes to move fluids – such as buffer, media and water for injection – through tubing to the process equipment.
Due to the need to maintain hygiene and sanitary standards, they must be able to prevent contamination and be able to be validated.
To achieve this, they may use single-use components or be designed to be cleaned easily.
There are several types of positive displacement pumps commonly used in the biopharmaceutical industry including peristaltic, diaphragm, rotary lobe and piston pumps.
The term “peristaltic pumps” refers to hose or tube pumps, and are commonly used in biopharmaceutics for applications such as reagent and product dosing, and blood transfer.
Although there are specific differences between hoses and tubing, these terms are generally used interchangeably.
Peristaltic pumps are self-priming rotary positive displacement pumps, and have a hose that is located in the tubing bed between the rotor and housing.
The rotor has a number of “rollers” or “shoes” attached to the external circumference.
During operation, the liquid is trapped between these shoes or rollers, and as these move across the hose, the hose is occluded, pushing the liquid along. The hose behind the shoe or roller recovers its shape, creating a vacuum and drawing more fluid in.
As the fluid is completely contained within the tube or hose and connectors, process validation is simplified.
For biopharmaceutical processes, while the hose or tubing can be treated as multi-use, where it is cleaned and sterilised between batches, it is typically treated as single-use and disposed of after each process to prevent cross-contamination with following batches.
As maintaining fluid path sterility is key in these processes, the hose or tube is manufactured from biocompatible materials that meet purity requirements.
The flow rate is determined by multiplying speed (rpm) by the volume of trapped liquid. The volume moved is consistent, even under a wide range of viscosities or densities. The flow rate is therefore directly proportional to the gearbox speed.
The size of the hose or tube is determined by fluid viscosity and the deliverable flow, with higher viscosity products requiring a large bore size tube, but a low running speed.
In downstream processing – including tangential flow filtration and high performance liquid chromatography – flow linearity with only trace pulsation and a wide pressure range is desired.
The key advantage of peristaltic pumps is the sealless design with no moving parts in the pumped fluid. Discharge pulsations are low, self-priming is good, the pump can handle high viscosities, and capacity accuracy is maintained for good process control. The pumps can also be run dry.
As they are low shear – unlike centrifugal, gear or other types of rotating pumps – cell suspensions will not be damaged when they are circulated or pumped, making them ideal for biopharmaceutics where product being pumped can be damaged by high fluid velocities or contact with mechanical parts.
While hosing or tubing occlusion can still cause cell death, this can be mitigated by reducing pump speed and increasing hosing or tubing diameter.
The amount of shear allowed is dependent on the sensitivity to shear forces due to flow of the product being pumped. For example, peptides and small proteins are relatively insensitive, while mammalian cells and vaccines can be very sensitive.
Selecting the right sized pump is one way to ensure shear is kept to a minimum to maintain product integrity. Low shear is further achieved by lowering the pump’s speed and increasing the tubing bore size to reduce fluid velocity.
Hose or tubing life and material are critical for maintaining performance as a failure can cause the loss of an entire campaign, but these are also the biggest concerns for peristaltic pumps in biopharmaceutical applications as the main wearing part of the pump is the hose or tube.
If properly and conservatively selected, the hose, and therefore the pump, will give long operating life between overhauls. Preventative maintenance is also key. But if care is not taken, hose life can be short.
Diaphragm pumps are a type of reciprocating positive displacement pumps and fall under the category of metering pumps.
They are used for biopharmaceutical applications such as chromatography, buffer inline dilution, homogenisation, injection of fluids into extruders, coating operations, filling, caustic dilution, and aseptic transfer of proteins, cells, and other materials.
There are various types of diaphragm pump, including air-operated-double-diaphragm, mechanically actuated, hydraulically actuated, electromagnetic (solenoid), and electronic.
- Air-operated-double-diaphragm (AODD): These pumps are used in biopharmaceutics for transferring fluids from one place to another and for ultrafiltration or diafiltration. They consist of two pumping chambers that are alternately filled and discharged by the movement of flexible diaphragms. Compressed air is alternately fed to, and vented from, air chambers on the opposite sides of the diaphragms to create the pumping action. They are also self-priming, sealless and can be run dry. However, they do not have volumetric control
- Mechanically actuated: In these pumps, a reciprocating connecting rod or cam, located within an oil bath lubricated gearbox, displaces a diaphragm over a given length within the pumping chamber. Via the hydraulic opening and closing of the internal inlet and outlet check valve, this accurately displaces a continuous injection of the liquid to the process, the amount of which can be adjusted either manually or automatically. Typically, these pumps are driven by AC motors. These pumps are sealless, which can be very important when pumping hazardous or expensive fluids, and are capable of running dry
- Hydraulically actuated: This type of pump combines the benefits of the sealless construction of the mechanical diaphragm pump with higher pressure capabilities. The diaphragm is hydraulically coupled to the plunger so that the plunger displaces oil within a cavity, which in turn displaces the diaphragm. This design requires a positive flooded suction and normally features an inbuilt pressure release valve for pump protection
- Electromagnetic (solenoid): In this pump design, the diaphragm is displaced by energising/de-energising the restricted movement of a plunger within a solenoid coil. The plunger is mechanically linked to a diaphragm that displaces the liquid volume on a noncontinuous (on/off) principle. Capacity adjustment is achieved manually or by a range of direct automatic input signals
- Electronic: Based on the same principles as the mechanically actuated diaphragm pump, this design incorporates both manual and electronic control features similar to the electromagnetic diaphragm pump by varying the “off period” of time of a single phase AC motor
Furthermore, diaphragm pumps can be multi-use or single-use. Multi-use pumps are still commonly used in the industry, and have housings made from stainless steel that can be reused after cleaning in place.
Single-use pumps are ideal if there are frequent or fast product changeovers required.
They have chambers made from plastic and are designed to be used for a single process or batch before being replaced.
The benefit of this is that they save time and money as cleaning and cleaning validation are not needed, and there is no risk of cross-contamination between batches.
Rotary lobe pumps
Rotary lobe pumps are common in the biopharmaceutical industry due to their high sanitary qualities, high efficiency, reliability, and good clean-in-place (CIP) or sterilise-in-place (SIP) characteristics. They have large pumping chambers, and if wetted, they are self-priming.
Furthermore, like peristaltic pumps, they are low shear, making them ideal for sensitive products. When operating rotary lobe pumps, the fluid flows around the interior of the casing.
The benefit of these pumps is that the lobes don’t make contact due to external timing gears being located in the gearbox, and since the bearings are out of the pumped liquid, pressure is limited by bearing location and shaft deflection.
A shaft seal is required for each shaft which are usually special short designs to minimise shaft length and overhang. Rotary lobe pumps are manufactured with a variety of lobe operations including single, bi-wing, tri-lobe and multi-lobe.
Rotary lobe pumps designed for sanitary uses can be broken down depending on the service and specific sanitary requirements, including 3-A, EHEDG and USDA.
These pumps offer reversible flows and can operate dry for long periods of time. Flow is relatively independent of changes in process pressure so output is constant and continuous.
Since the lobes don’t make contact and clearances are not as close as in other positive displacement pumps, internal leakage is increased and volumetric efficiency decreased when pumping low viscosity liquids.
High-viscosity liquids require considerably reduced speeds to achieve satisfactory performance. Reductions of 25 per cent of rated speed and lower are common with high-viscosity liquids.
Piston pumps work by cycling through a suction phase and a pressure phase to move fluid. They are well-established and popular in all areas of biopharmaceutical processes, in particular liquid filling, due to their reliability and accuracy.
However, compared to other pump types, there is greater concern of cross-contamination as they require regular maintenance and disassembly for cleaning and sterilising.
Therefore, multiple piston sets need to be managed: one for each injectable drug being filled. Due to these drawbacks, there has been a shift towards peristaltic pumps for these applications.