TFF is typically performed to formulate biologic therapeutics to high protein concentrations by ultrafiltration (UF) as well as diafiltration (DF) steps. During the process, protein concentrations are typically measured by at-line analytics to estimate process progression and to initiate the next processing step. High viscosities, at protein concentrations greater than 100 g/L, pose however challenges to the sample measurement process with the risk of inaccurate concentration determination.
A novel single-use inline viscometer, based on magnetic levitation, was integrated into the feed stream of a commercially available TFF device. A reliable calibration protocol was developed to generate a prediction model for protein concentration based on inline temperature and viscosity measurements. Subsequently, real-time monitoring of protein concentration via the viscometer during the TFF operation enabled accurate process control during the UF and DF steps, without the need to sample the process.
This study proves that inline viscometer technology based on magnetic levitation is a viable solution to determine protein concentration without compromising product quality. Real-time viscosity information in combination with a protein concentration prediction model has the potential to increase the control of TFF operations and improve process performance.