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

35 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.

LanguageEnglish
Pages12-21
Number of pages10
JournalTalanta
Volume90
DOIs
Publication statusPublished - 15 Feb 2012

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Near-Infrared Spectroscopy
State estimation
Cricetulus
Cell culture
Nutrients
Ovary
Monoclonal Antibodies
Cells
Trajectories
Spectroscopy
Calibration
Cell Line
Monitoring
Cell Culture Techniques
Food

Keywords

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

Cite this

Hakemeyer, Christian ; Strauss, Ulrike ; Werz, Silke ; Jose, Gledson E. ; Folque, Francisca ; Menezes, Jose C. / At-line NIR spectroscopy as effective PAT monitoring technique in Mab cultivations during process development and manufacturing. In: Talanta. 2012 ; Vol. 90. pp. 12-21.
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At-line NIR spectroscopy as effective PAT monitoring technique in Mab cultivations during process development and manufacturing. / Hakemeyer, Christian; Strauss, Ulrike; Werz, Silke; Jose, Gledson E.; Folque, Francisca; Menezes, Jose C.

In: Talanta, Vol. 90, 15.02.2012, p. 12-21.

Research output: Contribution to journalArticle

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