Process Analytical Technologies and Data Analytics for the Manufacture of Monoclonal Antibodies

Murali K Maruthamuthu; Scott R Rudge; Arezoo M Ardekani; Michael R Ladisch; Mohit S Verma

doi:10.1016/j.tibtech.2020.07.004

Process Analytical Technologies and Data Analytics for the Manufacture of Monoclonal Antibodies

Trends Biotechnol. 2020 Oct;38(10):1169-1186. doi: 10.1016/j.tibtech.2020.07.004. Epub 2020 Aug 21.

Authors

Murali K Maruthamuthu¹, Scott R Rudge², Arezoo M Ardekani³, Michael R Ladisch⁴, Mohit S Verma⁵

Affiliations

¹ Birck Nanotechnology Center, Purdue University, West Lafayette, IN 47907, USA; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA.
² RMC Pharmaceutical Solutions, Inc., Longmont, CO 80501, USA.
³ School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA.
⁴ Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; Laboratory of Renewable Resources Engineering, Purdue University, West Lafayette, IN 47907, USA. Electronic address: ladisch@purdue.edu.
⁵ Birck Nanotechnology Center, Purdue University, West Lafayette, IN 47907, USA; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA. Electronic address: msverma@purdue.edu.

Abstract

Process analytical technology (PAT) for the manufacture of monoclonal antibodies (mAbs) is defined by an integrated set of advanced and automated methods that analyze the compositions and biophysical properties of cell culture fluids, cell-free product streams, and biotherapeutic molecules that are ultimately formulated into concentrated products. In-line or near-line probes and systems are remarkably well developed, although challenges remain in the determination of the absence of viral loads, detecting microbial or mycoplasma contamination, and applying data-driven deep learning to process monitoring and soft sensors. In this review, we address the current status of PAT for both batch and continuous processing steps and discuss its potential impact on facilitating the continuous manufacture of biotherapeutics.

Keywords: continuous manufacturing; monoclonal antibodies; process analytical technology; sensors; spectrometry; spectroscopy.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antibodies, Monoclonal* / analysis
Antibodies, Monoclonal* / chemistry
Bioreactors*
CHO Cells
Cell Culture Techniques*
Computational Biology / methods*
Cricetinae
Cricetulus
Drug Contamination / prevention & control
Humans
Technology, Pharmaceutical*

Substances

Antibodies, Monoclonal