Adaptive combination of SSB and SUB equipment to master complexity in clinical manufacturing in the clinical supply center

Today’s clinical manufacturing of complex monoclonal antibodies under GMP conditions needs to be highly adaptive in order to face the requirements of constant acceleration of processes. The main challenge of the clinical supply center (CSC) in Penzberg (Germany) is to successfully master the complexity of producing different products in different phases (clinical phase I – III) with different process versions. New products for clinical phase I have different requirements than older products, as well as products in later phases or resupplies. In addition, the actual change to more intensified processes will increase the complexity even more. The CSC is equipped with a variety of bioreactors in different sizes and types. Stainless steel as well as single use bioreactors, which were installed over the past 25 years. In order to face the main challenge, it is mandatory to create a framework that allows the adaptive combination of standard (SSB) and new technologies (SUB). To realize that, SUBs and SSBs are treated equally. SUBs have the advantage to be used more flexible than SSBs because of less preparation time and an easier adaption to intensified processes (like perfusion modules in the N-1 bioreactor). Furthermore, SUBs can be easily connected to every existing bioreactor type (SSB as well) via hose connections. This all offers the chance to utilize existing bioreactor racks more efficient with less slack time. An adaptive combination is also faster and more favorable than just replacing existing with new equipment. The poster shows the successful implementation of the adaptive combination in the CSC, by adding SUBs with increasing volume to the facility (starting with 250L and ending with 2000L production volume) and apply them for existing and new processes. The intensified usage of SUB equipment shortens the upgrade time to adapt to future needs (e.g. switch to perfusion technology). With this flexible setup the multi-product-GMP facility in Penzberg is perfectly prepared for actual and upcoming challenges

Comparative study for the production of MABs in single-use (SUB) vs. stainless-steel bioreactors (SSB) based on product quality and stress factorsComparative study for the production of MABs in single-use (SUB) vs. stainless-steel bioreactors (SSB) based on product quality and stress factors

Today’s clinical manufacturing of monoclonal antibodies (MABs) in a multi-product GMP facility needs to be highly flexible in order to support the R & D’s quick changing pipeline. One main challenge is to plan production in a multi-equipment GMP facility that offers a wide range of different types of bioreactor systems and scales. While stainless steel bioreactors (SSB) have been used as the standard bioreactor type for years, over the past decade, single-use bioreactors (SUB) have been installed and are well accepted in modern biopharmaceutical manufacturing facilities. SUB’s provide several advantages e.g. reduced investment costs, easy product changeover, increased productivity through shortened unit operation times and less manpower. Despite these benefits it is absolutely mandatory to ensure that the production of monoclonal antibodies in SUB’s is comparable to the production in SSB’s concerning product quality and stress indicators. The aim of this study was to analyze data of cell culture runs performed in SSBs and SUBs to make a statement regarding comparability. For that purpose data from ten different antibody projects, which are representative of former and future products from R & D’s pipeline, were considered in the analysis. The total data package comprised 75 different cell culture runs. The focus was on product quality attributes e.g. purity, charge heterogeneity as well as on stress indicators such as specific productivity, viable cell density, viability and LDH levels. Equivalence ranges, i.e. differences that are deemed acceptable, were defined prior to statistical analysis. The results demonstrate that all the investigated cell culture stress indicators and product quality attributes are comparable between the single-use and stainless-steel bioreactor systems. To sum up, either system can be used for the clinical manufacturing of monoclonal antibodies. Therefore, this study supports a highly flexible utilization of single use and stainless steel bioreactors within a multi equipment GMP facility and helps to increase production speed