An Integrated Approach for Next-Generation Bioprocessing

There is a lot of interest around process analytics, software automation, and single-use components. Additionally, the perfusion bioreactor and continuous capture have already received lot of attention. Supporting processes and additional unit operations will become increasingly important focus for manufacturers looking to cut costs, mitigate risk, and become more efficient.

On the upstream side, reducing risk through the use of a high cell density cryopreservation in the seed train, which in turn, allows separating a process intermediate from the seed train, perhaps performing some operations off site, and enabling closed processing of the seed train once on site. Another area for potential improvement is using perfusion in the N-1 bioreactor, allowing a far higher seed density into the final (production) bioreactor and, therefore, the same productivity in a shorter production time.

One by product of more efficient, intensified processes is higher titers. Downstream buffer volume increases linearly with bioreactor titer, and that greater volume must be accommodated, often without any increase in available space. The automated skid-mounted BioContinuum platform uses buffer concentrates of 10×, 20×, and even 50× to provide all the chemical composition in a much smaller footprint.

Concentrates are QC released prior to use and diluted with the plant’s own water for injection into hold vessels. The 1× buffers can then be transferred around the facility. Process intensification via buffer delivery is fast and flexible; avoids powder, dust, and debris; and is “incredibly accurate and precise.” And best of all, it reduces labor costs and increases operator safety.

Companies looking to intensify their processes, the final dream goal, the final step, is going fully continuous upstream: having a very high cell density process, which is run consistently, for a long period of time.

Continuous processing can help a bio manufacturer achieve many laudable goals, including greater efficiency, flexibility, and robustness (by reducing the number of steps and holds); smaller equipment and facility footprints; better product quality; and real-time product release. The key is an integrated approach. Critical quality attributes (CQAs) need to be identified, and the functional relationships that link the critical material attributes (CMAs) and critical process parameters (CPPs) to the product CQAs need to be understood.

Knowing the product—including the CQAs of both the drug and its excipients—and how it’s made, and the potential impact of the CQAs on safety and efficacy, can allow more flexibility in the regulatory process. The bio manufacturer can demonstrate that it knows and can control what matters.

The industry is looking forward to produce huge amounts of biologics to treat different diseases and indications including cancer, and continuous operation will probably be the best approach to produce such large quantities. Merck is in a right position to support the Biopharma customers to realise their DREAM!