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Cited by 31Spectroscopy and Chemometric AnalysesProtein purification and stabilitySpectroscopy Techniques in Biomedical and Chemical Research

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Near Infrared Spectroscopy as a PAT tool for monitoring and control of protein and excipient concentration in ultrafiltration of highly concentrated antibody formulations

Thakur, Garima, Hebbi, Vishwanath, Rathore, Anurag S.·2021·International Journal of Pharmaceutics
DOI 10.1016/j.ijpharm.2021.120456
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Abstract

Excipient concentrations are critical quality attributes of monoclonal antibody (mAb) drug products and affect their safety and efficacy. In manufacturing processes, mAb products are formulated into the buffer containing the desired excipients using ultrafiltration (UF) and diafiltration (DF). Control of excipient concentrations is a challenge during high concentration UF due to electrostatic interactions which lead to excipient concentration drifts. This challenge is of increasing importance due to the growing preference towards high concentration subcutaneous drug formulations over conventional intravenous formulations in the biotherapeutic industry. Excipient concentrations are currently measured using offline RP-HPLC which is time-consuming and not suited for real time control. We propose a novel process analytical technology (PAT) tool for monitoring and control of mAb and excipients in high concentration UF using Near Infrared Spectroscopy (NIRS). The NIRS is able to monitor concentrations within ±1% for mAb and ±2% for two common excipients, L-histidine and acetate. A Python-based controller uses real time concentration data to deliver concentrated excipient stock solutions to the UF reservoir whenever the excipient concentrations drift out of range. The PAT control system is able to achieve the target formulation without manual intervention or at-line analysis and is well-suited for implementation in mAb manufacturing platforms.

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Metadata

Authors
Thakur, G., Hebbi, V., & Rathore, A. S.
Affiliations
Indian Institute of Technology Delhi (IN)
Corresponding author
Rathore, Anurag S.
ORCID
Venue
International Journal of Pharmaceutics
Publisher
Elsevier BV
Published
2021-05
Volume
600
Pages
120456
ISSN
0378-5173 (ISSN-L)
DOI
10.1016/j.ijpharm.2021.120456
OpenAlex
W3134015480
Cited by
31
References
0
Citations by year
2026: 5 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 2 · 2021: 3
FWCI
1.60
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • International Journal of Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Department of Biotechnology Ministry of Science and Technology
  • Department of Science and Technology
  • Ministry of Human Resource Development (21\u2013105/2015\u2010TS.II/TC)
  • Tata Consultancy Services Ltd
  • Council of Scientific and Industrial Research, India (09/086(1225)/2015-EMRI)
Topics
  • Physical Sciences › Chemistry › Analytical Chemistry › Spectroscopy and Chemometric Analyses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
Keywords
near-infrared spectroscopy, process analytical technology, ultrafiltration, diafiltration, monoclonal antibodies, real-time process control, histidine, acetate, electrostatic interactions, biopharmaceutical manufacturing
MeSH terms
Antibodies, Monoclonal, Excipients, Technology, Ultrafiltration, Spectroscopy, Near-Infrared

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