Process development teams have relied for decades on benchtop bioreactors to perform mammalian-cell–culture experiments; however, doing so requires significant resources and staffing. During a 24 February 2021 presentation, Deborah Pascoe, PhD, vice president of operations at Culture Biosciences (Culture), explained how to leverage her company’s high-throughput, cloud-connected bioreactors to execute Chinese hamster ovary (CHO) cell cultures with high reproducibility and scalability.
Pascoe described her company as an extension of a customer’s laboratory. After technology transfer, Culture and a client enter into an ongoing guaranteed-capacity agreement specifying a certain number of bioreactor runs per month. Clients submit experimental designs; then Culture executes them in its 250-mL cloud-connected bioreactors. Culture’s Console analytics platform presents the resulting data in real time, and process samples are sent to clients monthly.
Such a business model combines the advantages of in-house and contract laboratory services. Clients maintain control over their experimental designs and intellectual property. Culture’s process monitoring infrastructure also affords considerable insight into how studies are performed. But because experiments are outsourced, clients drive down their own costs for staffing and facilities maintenance.
Whereas contract manufacturers can require six months to one year of lead time, Culture often can initiate technology transfer within a month. That can help companies with little internal bioreactor capacity to start programs quickly. Organizations with significant capacity can leverage that infrastructure to conduct additional studies. Culture’s early stage offerings include clone screening, product quality assessment, baseline process development, media and feed optimization, and assessment of critical process parameters. Culture supports commercialization efforts with product characterization and validation testing.
Leveraging the Cloud: Culture’s single-use bioreactors operate at working volumes of 80–250 mL and feature considerable automation and monitoring capabilities. Feeds are delivered by peristaltic pumps with scale-feedback control, and automated triggers enable dynamic feeding strategies. Bioreactors are fed independently, so each run can execute a distinct protocol using a different feed composition. Gas delivery is regulated by mass-flow controllers.
In the Console platform, scientists can enter experimental parameters, access data, view reactor images, and make real-time process changes. The software can generate time-series figures with grouping and dynamic graphing capability, and users can separate or overlay graphs within and across experiments. Particular graphs now can be pinned for easy access using a new “workspaces” tool. Data alternatively can be exported for off-platform analysis. Pascoe noted that Console access does not exact a per-seat charge; data can be shared with colleagues by providing login details.
Achieving Reproducibility: Pascoe shared a case study in which her company helped a customer scale up production using two CHO cell lines. Culture ran two workflows for both cell lines. The first process called for a three-day seed train; the second specified a four-day train and applied improved gassing and pH controls. The cell lines required slightly different initial pH levels. Otherwise, cultures all ran for 14 days at the same temperature, dissolved oxygen (DO), and postshift pH levels using the same feed strategy.
Results from those studies showed that both cell lines grew at similar rates and densities whether they were cultured in 250-mL cloud-connected bioreactors or the customer’s 1-L glass benchtop vessel — although Culture’s reactors maintained higher viability rates for longer. That was true especially for batches run in the second process. Product, metabolite, and osmolality profiles were consistent across scales for each cell line and process.
Fostering Innovation: By working with Culture, companies not only gain bioreactor capacity, but also enable their own staff to focus on experimental design and data analysis. That could free up time and resources for further process and product innovation.
Questions and Answers
Can Culture’s bioreactors perform on-line biomass measurement? They can record many parameters, including biomass, viable cell density, and viable cell count. Culture is happy to use different sensors depending on client needs.
What kinds of companies and processes can Culture accommodate? Culture has worked with many companies across the food, agriculture, industrial biotech, and pharmaceutical industries using bacterial, fungal, and CHO cell cultures. Customers have included small companies with little capacity and large organizations needing to run additional studies. This year, Culture will expand its services to other mammalian cell lines.