Single-use biomanufacturing systems promise to reduce the risk of cross-contamination, provide low-cost scaleup, and allow multiple products to be manufactured at a single site with minimal validation issues. While all of this is true, they are not necessarily plug-n-play. Instead, deploying a single-use system in a bioproduction process requires operator training and some forethought, according to presenters at IQPC’s “Disposable Solutions for Biomanufacturing” conference held earlier this month.
Merck Serono is testing several single-use bioreactors at a production site in Martillac, France. “The site has performed 13 fed-batch runs with mammalian cells using four different technologies of single-use bioreactors,” explained Aurore Poles-Lahille, assistant scientist for new technologies and manufacturing support. Others are being tested now for cell seeding and clinical material applications.
The benefit, Poles-Lahille said, is that disposable bioreactors decrease the lead time between runs from fifty hours to about one hour. “This is especially important for seeding applications, where bioreactors are only used for a few days,” she explained. They also decrease the consumption of energy, water, steam, and cleaning agents.
“Deploying single-use bioreactors is not really difficult. The challenge is managing different disposable elements simultaneously—culture media, feed and bioreactor bags, in addition to aseptic connectors and disposable probes,” she said. “One needs to connect these elements to properly grow the cells, so if you do not have a welder, a sealer, or have not been well-trained, contamination or bag disruptions can easily occur.”
Beyond extensive on-site training, Poles-Lahille recommended that users analyze the bioreactors and the strategies to manage the connections between the media and feed bags, filters, and cell inoculums. “Extra sterile tubing to weld tubing from bags to tubing on the bioreactor may be necessary, as well as the preparation of extra sterile tubing that is compatible with long-term pumping for pH regulation.”
Single-use systems offer a low-cost route to early-stage development. “For small-scale and early-stage products, disposable systems are easier, faster, and cheaper, because you don’t have large capital expenditures and you can change out all the equipment and use the same process platform for other products without the risk of cross-contamination,” noted Tony Hitchcock, head of manufacturing technologies at RecipharmCobra Biologics.
“This is especially critical for novel therapeutics such as viral gene-therapy vectors and other products destined for first-in-man studies.”
“Because disposable bioreactors range in size from 10 mL to 2,000 L, they can be used for process development, seeding stainless steel bioreactors in a GMP facility, or to perform a scaleup of a process,” Poles-Lahille added. “They are attractive for optimizing lead time between production runs and to minimize the use of utilities.”
They also can be automated to some degree. According to Bruce Rawlings, senior marketing manager of Allegro single-use systems at Pall, the approaches to automating single-use processing solutions are similar to those of stainless steel systems, but the technologies are mainly plastic.
“Automation becomes an issue at larger scale. Pinch and control valves for one-inch flexible tubing are not yet available or are prohibitively expensive to consider as a single-use approach. Also, some sensor technologies are either limited in range of measurement or relatively expensive compared to other single-use components, so are not appropriate for all applications.”
“But, in general, if the scale fits for the available technologies, there are not too many issues with automating the basic features of fluid-management systems in upstream and downstream processing.”