Patients around the world have limited or restricted access to biopharmaceutical medicines. Reducing production costs while still maintaining high quality standards will help increase the affordability of biologics and ensure more patients benefit from these life-saving medicines.
Traditional biomanufacturing facilities have failed to deliver biopharmaceutical products with sufficiently low Cost of Goods Manufactured (COGM) to allow greater patient access. These facilities have been built with fixed capacity and a focus on large-scale fed-batch manufacturing. Scaling-up processes to large-scale fed-batch manufacturing facilities involves considerable risk, resource, and upfront costs. Such facilities often lack flexibility which limits the products that can be produced within them and can leave valuable production assets idle for periods of time.
Manufacturing costs link directly to capacity utilization and product demand. There is a historical precedent within the biopharmaceutical industry of operating with excess capacity but we must recognise this comes with a financial penalty. We must address this challenge if we are to respond to global healthcare emergencies, changes in the way healthcare systems are managed and greater demand for global access to biotherapeutics.
Continuous Bioprocessing Platforms and Modular Facility Designs
The industry needs new flexible biomanufacturing concepts to quickly react to market fluctuations and achieve a higher predictability of costs. Modern biopharmaceutical productions facilities use building and manufacturing technologies, such as modular construction, to minimize clean room space utilization and reduce footprints. They allow faster speed to market with a lower upfront capital investment and are readily expandable when product demand is better understood. Continuous manufacturing platforms can be integrated into these facilities for low-cost bioprocessing using mammalian cell hosts in perfusion bioreactors linked to continuous downstream trains. Production costs remain low irrespective of facility mass output, the product quality attributes are consistent and manufacturing footprints are minimized.
Just-Evotec Biologics has developed a low-cost manufacturing facility design utilizing modular cleanroom pod technology that we call J.POD®. The J.POD facility design features individual pre-fabricated cleanroom pods arranged in a controlled, non-classified ballroom to minimize the cleanroom footprint of operations that would have previously taken place in a large ballroom. Media and buffer preparations, cell expansion, upstream, downstream and post viral are all housed in separate pods. The design minimizes fixed utility infrastructure and instead relies on single-use continuous upstream and downstream operations.
Biomanufacturing Facility Cost Comparisons
We developed process models for a fed-batch process in a traditional stainless-steel facility, a fed-batch process in a single-use facility and three continuous processes in a J.POD facility. The models were created using the Biosolve software (Biopharm Software Ltd) to show the benefit of the J.POD facility design on the COGM of an antibody biologic. We used Net Present Cost (NPC) to compare scenarios. NPC estimates cash flows by computing operational costs and discounting over time using a capital parameter. It does not include revenues in the accounting of cash flows and assumes capital costs are sunk costs incurred at the beginning of the project.
Figure 1 shows the expected costs from operating the different facility types and assumes their throughput increases at a rate of 250 kg/year up until a peak value. The range selected was representative of market demands for typical biopharmaceutical manufacturing facilities. Jumps in the NPC correspond to points when the capacity of a facility is reaches and new builds are needed.
We can draw the following conclusions from the results.
Driving Up Access to Biotherapeutic Medicines
We believe that modern biomanufacturing facilities must have smaller processing spaces, higher production throughputs and lower production costs. Modelling shows how our J.POD facilities have the lowest initial build and operating costs as well as the ability to control operating costs. These facilities are outperforming older manufacturing platforms in terms of cost and utilization. They are becoming an essential component of strategies for reducing costs and driving up access to biotherapeutic medicines.