Automated calibration and in-line measurement of product quality during
therapeutic monoclonal antibody purification using Raman spectroscopy
- Jiarui Wang,
- Jingyi Chen,
- Juergen Hubbuch,
- Joey Studts,
- Gang Wang
Jingyi Chen
Boehringer Ingelheim Pharma GmbH & Co KG Biberach
Author ProfileJoey Studts
Boehringer Ingelheim Pharma GmbH & Co KG Biberach
Author ProfileGang Wang
Boehringer Ingelheim Pharma GmbH & Co KG Biberach
Author ProfileAbstract
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.07 Jan 2023Submitted to Biotechnology and Bioengineering 07 Jan 2023Submission Checks Completed
07 Jan 2023Assigned to Editor
07 Jan 2023Review(s) Completed, Editorial Evaluation Pending
26 Jan 2023Reviewer(s) Assigned
05 Mar 2023Editorial Decision: Revise Major
11 May 20231st Revision Received
13 May 2023Submission Checks Completed
13 May 2023Assigned to Editor
13 May 2023Review(s) Completed, Editorial Evaluation Pending
11 Jul 2023Editorial Decision: Accept