Advances in surfactants are preventing foaming and reducing shear in the mammalian cell cultures used to produce monoclonal antibodies and viral vectors. One of the newest, Peptonic ih-T1010 (the generic term for this family of peptide and peptoid mimetics of poloxamers), is emerging as a viable alternative to poloxamer surfactants.
“Peptonics offer biopharmaceutical manufacturers a more chemically defined alternative to conventional poloxamer surfactants, with the potential for greater reproducibility and process robustness while preserving the key performance metrics that matter in practice—namely, cell growth, viability, productivity, and product quality,” Stefano Menegatti, PhD, professor, North Carolina (NC) State University, tells GEN. “Just as importantly, the strong foam suppression we observed suggests a meaningful opportunity to reduce antifoam use and simplify upstream operations without compromising downstream affinity capture.”
In a recent paper, researchers from Merck, KBI Biopharma, Chromagenix, and NC State University investigated the use of Peptonic ih-T1010 as a surfactant for CHO and HEK293 cell cultures in fed-batch reactors to produce monoclonal antibodies (mAbs) and adeno-associated viral (AAV) vectors.
The team, led by Menegatti, reported that CHO cell densities and final mAb titers were comparable to those of poloxamer 188, the industry-standard surfactant. They noted “no significant differences [between the two surfactants] in product glycosylation or aggregation profiles.”
Results using Peptonic ih-T1010 as a surfactant for HEK293 cell cultures were also positive. Both the peptonic and poloxamer surfactants produced comparable titers, and cell viability was above 90% for each. The performance of affinity resins was not affected.
Notably, the peptonic surfactant created only negligible quantiles of foam in the CHO and HEK293 cell cultures. This enabled the team to eliminate the defoaming step, which can inhibit cell growth and increase filter fouling. Because no antifoam agents were needed, downstream purification is simplified, and the potential for process variability and cytotoxicity is reduced.
The research was performed using fed-batch cultures but is equally applicable to continuous bioprocessing, Menegatti says. “This is one of the most exciting implications of the platform. The combination of defined composition, low foaming, and downstream compatibility makes peptonics a promising candidate for perfusion and other continuous or intensified formats, especially for processes where tight control of the culture environment and raw-material consistency are essential,” Menegatti points out.
“For secreted biologics such as antibodies, that opportunity is especially clear. As continuous or intensified production modes for viral vectors mature, I believe the same design logic could become highly relevant there as well,” he adds.
The scientists call peptonics “a promising alternative to conventional surfactants.” That’s because surfactants that protect cultured cells from mechanical stress play a key role in maintaining optimal culture environments that are vital in biologics manufacturing.
For peptonics to realize its potential, pilot studies are needed, Menegatti says. “Our data are highly encouraging and support the view that further work on scale-up, supply consistency, regulatory comparability, and direct validation in continuous manufacturing settings should provide the remaining evidence needed for broader industrial adoption.”
