The biopharmaceutical industry continues to need to facilitate faster, lower cost approaches for manufacturing biologics such as monoclonal antibodies (mAbs) for treating chronic and life-threatening conditions, as well as infectious diseases. Unfortunately, many biologics-based treatments are not accessible to patients worldwide due to issues including affordability. Alongside affordability there are also challenges which are hampering the speed of delivery of biologics-based drugs including long lead times for designing and building conventional manufacturing facilities, which can impact manufacturing costs. These drivers are fueling technology innovations to improve facility utilization for multi-product use and provide easy-to-install facilities for domestic manufacturing which could improve efficiency and increase yields. Increasing productivity from each production batch means fewer process runs often at smaller scale, all of which can reduce the cost of goods (CoGs) for producing biologics.

Traditionally, to increase drug substance/ product mass biopharmaceutical companies and CDMOs have produced larger amounts of unpurified product by scaling their fed-batch cell culture processes to 10,000 L, 15,000 L, 20,000 L or 30,000 L stainless steel bioreactors using process transfer into increasingly larger vessels.

Scaling-up a process, for example, from a 2,000L to a 20,000L bioreactor along with the associated downstream processing step involves considerable risks, resources, and costs because not all unit operations scale-up linearly. This often means that multiple engineering runs are performed prior to Performance Qualification (PPQ) to de-risk the PPQ campaign. These engineering runs can be extremely expensive and time consuming.

Additionally, working at larger scale requires the entire facility to be scaled with larger and often inflexible downstream unit operations to purify a large amount of product mass. This requires different skills sets and can even mean transferring the process to a new, larger facility, as well as training new staff.

In CDMOs or biopharmaceutical firms an alternative approach is to multiplex, or scale-out, the upstream process, with for example a “six pack” strategy using 6 x 2000 L SU bioreactors. Although scale-out has less scale-up risks, managing parallel production bioreactors creates complexity and downstream challenges remain due to the large amount of product mass that needs to be purified. Additionally, even though the capital expenditure might be lower, the high number of SU bioreactors required increases operating costs.

An alternative strategy which is increasingly gaining traction, is to use continuous manufacturing. At Just – Evotec Biologics, we have developed an integrated, continuous bioprocessing platform, based on intensified perfusion cell culture, to provide a highly flexible and economic alternative to the previously described scale-up or scale-out approaches for increasing mass output of drug substance. With continuous processing the duration of the bioreactor perfusion, rather than bioreactor size (scale-up) or number (scale-out), is the principal variable which can be adjusted to increase mass output. Using our continuous processing platform means the mass output can be ‘tuned’ to precise requirements with only modest increases in bioreactor volume.

The other major benefit is that the product is purified continuously so that equipment remains compact and flexible and covers a much wider dynamic range than traditional facilities, eliminating the need to scale up the process as the drug advances through clinical development to commercial launch. This approach avoids the traditionally accepted risks, as well as the additional cost and resources associated with, for example, having to scale up and transfer an early phase clinical scale process to a larger scale bioreactor in a different facility to support late phase clinical and commercial needs. This can help reduce the critical path timeline to clinic, as well as de-risk the path to market for biologics.

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