By Gareth Macdonald
A novel continuous monoclonal antibody (mAb) production process could help drug firms reach quality goals and cope with changing capacity needs, according to CDMO Fujifilm Diosynth Biotechnologies.
The process in question—full details of which will be unveiled at the annual bioProcess UK Conference later this month—is designed to be both cost- and time- efficient, says Charles Heise, PhD, who is the CDMO’s associate director of process development.
“The process involves a perfusion bioreactor connected to an ATF cell retention device that continuously feeds 600 L per day into downstream. Subsequent steps include low pH viral inactivation, cation and anion chromatography, viral filtration, and formulation using recirculating TFF.
“The downstream process is based on a standard mAb purification process; however, because we use a single column high cycling strategy, the perfusate is conditioned and concentrated to reduce the volume of the Pro A load,” he says.
And reducing Protein A usage represents a potentially significant saving for biopharmaceutical manufacturers as, according to one recent study, the resin can cost between $11,000 and $18,000 per liter.
Another difference from traditional mAb manufacturing methods is the way the technologies are combined in the new process, according to Fujifilm Diosynth.
The firm’s CHO DG44-based cell line—ApolloX—is used for protein expression, while its SymphonX liquid handling system is employed for the control and management of all downstream operations, everything from chromatography and filtration through point-of-use buffer dilution.
And linking these processes is effective from a product quality standpoint, according to Leon Plybus, PhD, a Fujifilm Diosynth Biotechnologies associate director, MCC process development.
“The connected process produced a similar yield to a batch process of the same size with similar or better product quality attributes,” he points out.
The process’ continuous operation also minimizes handling, according to Plybus, who says “Intensification allowed more efficient resin utilization, realized through smaller columns and the automation reduced operator interventions and sampling requirements.”
Fujifilm Diosynth Biotechnologies operates 24-7 manufacturing processes at plants in Asia, the U.S., and Europe, including in Billingham in Teesside in the U.K., which it describes as a “proof-of-concept facility for continuous biomanufacturing.”
And knowledge gained from the new process will help shape manufacturing operations at the Billingham site and other facilities, predicts Plybus.
“The main [main takeaway from the process] has been to gain a better understanding of the process and environmental control strategy approaches and how we can transfer processes from fed-batch to perfusion processes through the use of the ApolloX cell line and SymphonX purification systems.
“This learning has informed the design of our latest facility builds,” he adds.