Biotech Firm Accelerates Concentration Process With Quantum Pump

The Quantum Pump is used to accelerate the concentration process deployed on a customer purification platform. The Quantum 600 pump was selected after the company’s existing pump could not handle the high pressures on the ultrafiltration membranes for the large volumes required. Using Quantum meant the company could concentrate 1500 litres of product to 100 litres in just 7 hours.

Goodwin Biotechnology Inc (GBI) offers cell line development, process development and cGMP contract manufacturing services. The company also provides aseptic fill/finish of mammalian cell-culture derived monoclonal antibodies, recombinant proteins, vaccines and antibody drug conjugates for early and late-stage clinical trials.

Insufficient pressure
GBI was working on a platform for a two-stage concentration process involving viral filtration (VF) and ultrafiltration/diafiltration (UF/DF). Here, the company typically purifies harvested antibody from a 500 litre fed-batch bioreactor process platform, with concentration normally at levels of 5 mg/ml or less. However, for the new perfusion bioreactor process platform, antibody is purified from a more than 10,000 litre harvest, where the intermediary process pressures were also expected to be high. GBI’s existing pumps for fed-batch processes did not have sufficient pressure to drive the large scale UF/DF system or VF filters for the perfusion process. At the same time, effective flow control was proving to be an issue.

“We are accustomed to working on small volumes with fed-batch and we needed more powerful pump technology,” explains Garth Cole, GBI’s manager of downstream manufacturing operations. “Processing 60 litres using a maximum of 3 m2 of UF was taking 4 to 5 hours to achieve the concentration because the power was not there. We did the calculations and realised our existing pumps would not provide the pressures and consistent flow required to meet our goal of completing a six-unit purification process in one to two weeks.”

Quantum tops shortlist
GBI duly reviewed the market for a pump that offered consistent flow with low pulsation, the ability to handle high pressure, and low operational costs, opting for the Quantum 600 from WMFTG.

Quantum high-pressure, single-use pump technology is ideally suited to downstream filtration applications requiring virtually pulse-free linear flow. The pumps deliver higher accuracy with flow linearity independent of back pressure, which was a perfect match for the GBI application.

With a very high turn-down ratio (4000:1) and a powerful motor that responds rapidly to changes in downstream pressure, Quantum pumps provide linear speed control across a wide range of pressures (0 to 3 bar). At the same time, the unique single-use cartridge with four parallel fluid paths acts to deliver extremely low pulsation (only 0.12 bar) at full speed, which is a key requirement for the reliable operation of many filtration schemes.

Other pump technologies, like diaphragm pumps, have greater pulsation and more complex fluid paths that can double the shear forces and damage delicate biological fluids. Quantum also offers advantages over 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 and validate processes.

Exceeding expectations
According to the company, the Quantum pump exceeded expectations during VF, where 200 litres of an antibody were filtered across a 1 m2 virus removal filter.

“With the Quantum, we were able to maintain 2.75 bar on the filter, which we could not achieve using our previous pump,” says Mr Cole. “Furthermore, whenever the flux increased, the pump speed feed flow rate was increased to maintain the 2.75 bar pressure – and the pump was able to maintain the pressure and flow. Our processing time was reduced dramatically as a result.”

GBI also used the Quantum for UF/DF, where an antibody solution was concentrated from 400 to 26 litres with a 6 m2 50 kDa membrane (using a 10 x DF process). The permeate flow in each instance was 3.5 l/min at a TMP (trans-membrane pressure) of 1 bar for concentration and 0.75 bar for DF. What would normally be a 12-hour operation was reduced to 3 hours.

According to GBI, 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 operate. New employees have been able to begin using the pump properly within two minutes of start-up.

“The Quantum 600 is a powerful pump that we have found to be very good for UF/DF and VF processes,” concludes Cole. “I even loaned the pump to another group in the company which was under time pressure and they were also very happy with its performance.”