Scaling up parameters for stirred tank bioreactors (STR) supported by soft dynamic systems

Introduction: Stirred tank bioreactors (STRs) are widely used in the upstream (USP) in the production of therapeutic proteins and vaccines.For commercial production, suitable scale-up (SUP) criteria parameters from tech transfer projects and process development are essential.Scalable parameters (SP) such as tip speed (TP), power per volume (PV), and gas velocity (GV) are used to achieve engineering parameters (EP) like mixing time, shear stress, and kla.However, it's crucial to minimize any impact on biological and critical process attributes.Objectives: Determine the key scalable parameters for scaling up STRs to guarantee EPs and analyze its effects on other scalable and engineering parameters and biological attributes through a soft dynamic system based on enlace causal (EC). Methodology:The methodology involved the following steps: Classify parameters used in the SUP as operation (OP), scalable (SP), EP, and biological attributes (BA).Conduct EC of parameters using Vensin software supported by a simulation of a single use 200L STR.Identify the reinforcing (RL) and balancing loops (BL) and analyze them to identify the main EP and its cause-and-effect parameter tree.Establish the key parameter for scaling up SRT based on its cause and effects. Results:The outcomes show that 6 loops were identified, where the Kla is the EP that appears most, specifically 4 of them, where half are RL loops, and the other ones are BL.The Kla, such as an EP often to be reached out, depends on large SPs.Analyzing these variables, PV is the SP that has the most effects on other variables, including Kla, emphasizing that it is the SP that can offer the greatest visibility to the other ones. Conclusion:Considering the effects on other parameters, the PV is the most recommendable SP to be used to SUP an STR, setting up an adequate OP-in this case, the stirrer speed.Additionally, due to its effects on the main EP identified as kla, which participates in most loops discovered based on EC, its use is further reinforced.Therefore, the PV can be applied to achieve the previously established kla and provide a mapping of its effects on variables like shear stress, Kolmogorov scale, OTR, and others that can impact BAs such as cell growth and yield.