Another important trend in cell culture is the growing use of disposables. Denise DeTommaso, marketing manager of biodisposables at SAFC Biosciences, said that single-use systems are desirable because they are flexible, light, transportable, and allow issues associated with outsourcing, space, cleaning, validation, and contamination risk to be addressed. They are now being used at all stages of production. At SAFC, there are four facilities where liquid is manipulated, and one of these has been adapted from hard pipe to disposables.
DeTommaso described some of the challenges in implementation, which is a stepwise process. “You must get the engineering and validation people involved early on,” she said. Other important steps include identifying vendors, describing the system, gathering technical data, making a prototype, and finally, full implementation. SAFC has thus developed a 100% disposable manifold, which is flexible and requires no CIP/SIP. It is now looking at a disposable aseptic bag-filling machine. Drawbacks of disposables include lead times, the economics of large bags, and logistics when multiple bags and multiple locations are involved.
SAFC has looked at a hybrid manifold that is stainless steel with a disposable connection. There is a significant difference in clean time between stainless steel (6.5 hours) and hybrid/disposables (4 hours each).
Scale-up is another key challenge in cell culture. Allen Gross, SAFC Biosciences’ marketing manager, described how the company faces these by integrating and overlapping key scale-up components: cell-line selection, medium optimization, process development, and downstream development. “When these are segmented, it increases overall development time,” Gross pointed out.
SAFC uses laser-enabled analysis and process (LEAP) for clonal selection, which is otherwise a bottleneck. This uses high-throughput cell imaging and laser-mediated cell manipulation, which allows failures to be discarded earlier.
Another cell line development technology, CellXpress™, capitalizes on the tracking capacity of LEAP and allows high producing clones to be chosen for medium optimization. The DOE/matrix approach to medium optimization gives a better focus on the components for cell growth and for cell productivity, which tend to be different. Meanwhile, it should always be remembered that even minor modifications in process can have major downstream implications. “That is why we strongly believe that the purification group should be involved from the start,” said Gross.
Putting all this together requires professional project management; it is also important to try to understand the synergies between the different components of a cell culture process. “Integrating improvements decreases the development cycle by incorporating a multifactorial approach that capitalizes on the synergies between each development segment,” concluded Gross.