Cost modelling comparison of adherent multi-trays with suspension and fixed-bed bioreactors for the manufacturing of gene therapy products

Abstract

There is huge pressure on biomanufacturing facilities due to high demand for gene therapy products such as recombinant adeno-associated viral (AAV) vectors made under current good manufacturing practice (GMP) conditions. The constraints of the scale-up process are rarely taken into consideration during clinical process development, with many facilities simply scaling-out adherent cell stack protocols, procedures, and test methods. In order to demonstrate the importance of cost economics linked to the choice of scale-up processes, this study provides a detailed cost modeling analysis comparing viral vector production in adherent cells in cell stacks to viral vectors produced in bioreactors, either in suspension using a stirred bioreactor or adherently in fixed-bed bioreactor. The results show that single-use bioreactors allow the cost of installed capital and labor to be reduced significantly and that fixed-bed bioreactors with optimized production protocols offer the greatest experimental robustness and the best opportunity for increased productivity in a manufacturing facility.

Production of Modified Vaccinia Ankara Virus by Intensified Cell Cultures: A Comparison of Platform Technologies for Viral Vector Production

“…A recent study evaluating different production platforms for adeno‐associated virus estimated DSP costs to be equal to about 40% of the overall cost of good per dose for a 1000 L suspension cell culture in batch. [ 55 ] However, in this case, neither the DSP technique and DSP yield nor DSP costs per dose were influenced by the intensification of the USP. Thus, the overall impact of DSP on the economical modelling was considered to be negligible.…”

A high cell density perfusion process for Modified Vaccinia virus Ankara production: Process integration with inline DNA digestion and cost analysis

“…Intensification can be achieved with bioreactors coupled to devices for harvesting of infectious units with subsequent continuous purification. A techno‐economic analysis could provide insights about cost differences between a batch and a perfusion process for viral vector production (Cameau et al, 2019; Gränicher et al, 2020; Pearson, 2020), similarly to recombinant protein production (Klutz et al, 2016; Lim et al, 2006; Pleitt et al, 2019; Pollock et al, 2013). This could allow identifying key factors and bottlenecks allowing cost‐savings.…”

Evolution of culture systems for viral vector production: advantages, challenges and cost considerations

“…systems [2]. The study also showed that in some conditions, there are potential cost benefits to adherent methods.…”