Depth filtration or centrifugation? The choice is mainly a matter of economics. Depth filtration makes sense up to about 4,000 L, depending on the process, after which most biomanufacturers turn to centrifugation.
A number of factors affect economy, explains Paul Beckett, Eng.D., technology consultant at EMD Millipore. “It could be as simple as footprint. A facility may simply lack the space for the number of filters they need for their feed volumes. This is why large processes overwhelmingly use centrifugation as their primary clarification method.”
Centrifugation does not generate a fully clarified feedstream at production scale, as it does in the laboratory, which leads to what Dr. Beckett refers to as an “endless challenge.” At industrial scale, disk stack centrifugation provides around 90% clarification—not clean enough for practical membrane filtration. Thus, centrifugation-based clarification requires a secondary depth filtration step.
Even at small scale, the economics of depth filtration depend strongly on filter capacity. The 4,000 L barrier is based on an expected capacity of 150 L/m2 of filter area but, as noted, capacity may vary greatly dependent upon process stream and conditions.
Not all clarification decisions are based solely on economics. Many bioprocessors, particularly contract manufacturers, value the flexibility and speed that single-use equipment provides, and thus avoid centrifugation. “But eventually, they may reach a point where they are spending so much on filters that they might be better off with a centrifuge,” says Dr. Beckett.
For large manufacturers, a centrifuge that is already in use proves to be more economical. For smaller facilities, depth filters allow rapid validation. “Suppliers have done most of the work, and filters facilitate manufacturing speed,” continues Dr. Beckett. “Qualifying and validating a centrifuge to tight timelines can prove challenging.”
If a batch or project turns out to be larger than expected, processors can simply add more filters. When a batch is too big for a centrifuge, processors must install a much larger centrifuge or work in batches, which is expensive and time consuming and may compromise product quality. Additionally, notes Dr. Beckett, “CMOs pass filtration costs on to their clients. If they use centrifugation, the capital costs fall on them.”