Continuous background correction of refractive index signal to improve monoclonal antibody concentration monitoring during UF/DF and SPTFF operations

Webster, Thaddaeus A.; Turner, K.S.; DuBois, Caitlin; MacDougall, Ryan F.; Mason, Carrie

doi:10.1007/s00449-021-02683-8

Cited by 1 publication

(1 citation statement)

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“…Webster et al described the use of a K‐Patents refractive index meter to monitor protein concentrations during UFDF and SPTFF benchtop experiments. [ 13 ] The PR‐23‐refractometer was chosen as the inline technology for this study after initial development work showed the instrument's accuracy in measuring protein concentration. Additionally, the instrument has a history of being used in industrial applications and is well suited for integration into commercial scale TFF operations.…”

Section: Introductionmentioning

confidence: 99%

Refractive index as a process analytical technology to measure real time protein concentration for monitoring and control of commercial scale tangential flow filtration operations

Lam

McCann

Loman

et al. 2023

J Adv Manuf & Process

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Biological therapeutics are increasingly being formulated to high protein concentrations to decrease drug substance storage space and increase the flexibility of administration to patients. With the higher protein concentration targets comes added challenges to the downstream purification manufacturing process. Tangential flow filtration (TFF) operations are typically performed to reach target protein concentration. TFF operations for a given drug substance may include an Ultrafiltration and Diafiltration (UFDF) step, or a UFDF step followed by a single pass tangential flow filtration (SPTFF) step. Whether a TFF step achieves a target protein concentration is determined by at‐line protein concentration measurements performed at the completion of a process step. If the measured protein concentration is outside the specified range, the unit operation may need to be restarted, reprocessing may need to be performed, or a batch may need to be terminated. Out of specification protein concentration measurements may be a result of the TFF operation or sample measurement. Increased viscosities associated with high concentration TFF operations pose added challenges to the TFF process and sample measurement. Implementation of an inline process analytical technology (PAT) to monitor real‐time protein concentration during TFF operations has the potential to improve the accuracy of the operations in achieving target protein concentrations. This will result in improved process consistency and efficiency, increased operator confidence and decreased likelihood of batch failures. This paper studies the performance of a K‐Patents PR‐23 refractometer (Vaisala) as a PAT to monitor and control the UFDF and SPTFF unit operations of a commercial scale monoclonal antibody purification process.

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Section: Introductionmentioning

confidence: 99%