Current manufacturing and development processes for therapeutic
monoclonal antibodies demand increasing volumes of analytical testing
for both real-time process controls and high-throughput process
development. The feasibility of using Raman spectroscopy as an in-line
product quality measuring tool has been recently demonstrated and
promises to relieve this analytical bottleneck. Here, we resolve manual
calibration effort by engineering an automation system capable of
collecting Raman spectra on the order of hundreds of calibration points
from two to three stock seed solutions using controlled mixing. We used
this automated system to calibrate multi-product quality attribute
models that accurately measured product concentration and aggregation
every 9.3 seconds using an in-line flow-cell. We demonstrate the
application of a non-linear calibration model for monitoring product
quality in real-time during a biopharmaceutical purification process
intended for clinical and commercial manufacturing. These results
demonstrate potential feasibility to implement quality monitoring during
GMP manufacturing as well as to increase CMC understanding during
process development, ultimately leading to more robust and controlled
manufacturing processes.