At-line NIR spectroscopy as effective PAT monitoring technique in Mab cultivations during process development and manufacturing

Christian Hakemeyer, Ulrike Strauss, Silke Werz, Gledson E. Jose, Francisca Folque, Jose C. Menezes

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The application of at-line NIR transmittance spectroscopy on supernatant samples from Chinese Hamster Ovary Cells (CHO) based monoclonal antibody (Mab) cultivation processes spanning several scales from 2.5 L to 1000 L, cell-lines and development years is described. The collected and preprocessed spectra were used to do process state estimation and to obtain several culture parameters. Multivariate process trajectories were computed from NIR spectra acquired at-line. These were used to enhance process understanding across different scales up to industrial scale, assess batch-to-batch variability, and examine the relative importance of different sources of process variability. Many parameters of interest in industrial cell culture, like nutrient or product concentrations can be reliably estimated by NIRS with an accuracy of 15% or better, compared to reference methods General calibrations (scale and cell-line independent) are valid across a range of process conditions and different feed regimes. The proposed approach is therefore applicable throughout process development as well as to existing large-scale validated CHO bioprocesses for continuous improvement. (C) 2012 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)12-21
Number of pages10
JournalTalanta
Volume90
DOIs
Publication statusPublished - 15 Feb 2012

Keywords

  • at-line NIR spectroscopy
  • monoclonal antibody cultivations
  • PAT
  • scale-independent models
  • continuous improvement

Fingerprint Dive into the research topics of 'At-line NIR spectroscopy as effective PAT monitoring technique in Mab cultivations during process development and manufacturing'. Together they form a unique fingerprint.

  • Cite this