Goodwin Biotechnology Inc. (GBI) is a US-based, GMP contract development and manufacturing organization (CDMO) that offers cell line development, process development, cGMP contract manufacturing, and aseptic fill/finish of mammalian cell-culture derived monoclonal antibodies, recombinant proteins, vaccines, and antibody drug conjugates (ADCs) for early- and late-stage clinical trials.
Seeking to speed up completion of a purification platform for one of its customers, they found that their existing pump technology could not handle the high pressures on the ultrafiltration membranes for the large volumes required. After opting for Watson-Marlow’s Quantum peristaltic pump technology, they were able to concentrate 1500 liters of a product to 100 liters in about seven hours.
Higher Pump Pressure Needed
GBI was working on a platform for a two-step concentration process involving viral filtration (VF) and ultrafiltration/diafiltration (UF/DF). As a CDMO, GBI has completed more than 400 projects, mostly for Phase I through Phase III clinical trials. They have developed and optimized bioreactor and purification processes for such industrially relevant cell lines as CHO, NS/0, BHK, 293, and murine hybridomas. Global Health & Pharma News recently named GBI Biologics cGMP Manufacturer of the Year 2018.
GBI typically purifies harvested antibody from a 500 liter fed-batch bioreactor process platform, with concentration normally at levels of five milligrams per milliliter (mg/mL) or less. For the perfusion bioreactor process platform, antibody is purified from a more than 10,000 liter (L) harvest, where the intermediary process pressures were also expected to be high. Their existing pumps for fed-batch processes had insufficient pressure to drive the large-scale UF/DF system or VF filters for the perfusion process. At the same time, controlling flow was also an issue.
“We are accustomed to working on small volumes with fed-batch, and we needed a more powerful pump technology,” said Garth Cole, GBI’s manager of downstream manufacturing operations. “Processing 60 liters for the UF process using a maximum of 3 meters square (m2) of UF was taking four to five hours to do the concentration because the power was not there. We did the calculations and realized our existing pumps would not give us the pressures we need with the consistent flow required to meet our goal of completing a six unit purification process in one to two weeks.”
During an exhaustive search of the industry options that would satisfy their processing requirements, they reviewed the Quantum pump capabilities, which seemed to be the best fit. The decision considerations included a consistent flow with low pulsation, ability to handle high pressure, and not breaking the bank with associated operational costs.
GBI learned about this new high-pressure, single-use (SU) peristaltic pump technology, which is suited for downstream filtration applications requiring virtually pulse-free linear flow. The Quantum pump, developed by Watson-Marlow Fluid Technology Group, delivers higher accuracy with flow linearity independent of back-pressure, which was ideal for this requirement.
The Quantum pump has a very high turn-down ratio (4000:1) and a powerful motor that responds rapidly to changes in downstream pressure, providing linear speed control across a wide range of pressures, (0 to 43.5 pounds per square inch (psi)/(3 bar)). At the same time, the unique single-use cartridge with four parallel fluid paths acts to deliver extremely low pulsation (only 1.74 psi (0.12 bar)) at full speed, which is a key requirement for reliable operation of many filtration schemes.
At the heart of the Quantum pump is the patented ReNu SU Technology cartridge, which is simple to install, positioning the aseptic fluid paths quickly and accurately for ready to use. The ReNu SU Technology cartridge slides effortlessly into position, allowing for a change of fluid path in seconds and eliminating any scope for alignment errors.
Other pump technologies, like quaternary diaphragm pumps, have greater pulsation and more complex fluid paths that generate double the shear forces, which can damage delicate biological fluids. Quantum also offers advantages over other single-use pump technologies such as centrifugal pumps, which have poor (non-linear) flow control response and are sensitive to changes in inlet pressure. This lack of control makes it difficult to reproduce the process and therefore validate it.
Reduced Processing Time
GBI uses the pump for both VF and UF/DF. According to GBI, the Quantum pump exceeded their expectations during VF, where they were filtering 200 liters of an antibody across a 1-m2 virus removal filter. “With the Quantum, we were able to maintain 40 psi on the filter, which we were not able to achieve on other pumps.” They also had excellent flow rates. Cole noted that whenever the flux increased, the pump speed feed flow rate was increased to maintain the 40 psi pressure–and the pump was able to maintain the pressure and flow. “Our processing time was reduced dramatically as a result.”
They also used the Quantum for UF/DF, where they reduced an antibody solution from 400 L to 26 L by concentration with 6-m2 50 kDa membrane, using a 10x diafiltration process. The permeate flow in each instance was 3.5 L/min at a TMP (trans-membrane pressure) of 14 psi for concentration and 11 psi for diafiltration. What would normally be a 12-hour day operation was reduced to three hours processing time with the Quantum pump.
Ideal for Viral Filtration and Concentration
According to GBI, the Quantum pump technology offers flow accuracy, sustained high pressure, improved processing time, and a small footprint for the power it can supply. Also, an intuitive user interface makes it extremely easy for workers to use. New employees have been able to begin using the pump properly within two minutes of starting it up. Starting and stopping, and gradually stepping up the pump speed, are accomplished with the push of a button. The display makes it easy to increase in gradual increments and get feedback on status.
Filed Under: Product design