title: The use of NIR as a multi-parametric in situ monitoring technique in filamentous fermentation systems.
abstract: The use of Fourier transform near infrared (FT-NIR) spectroscopy for simultaneous determination of multiple properties in an active pharmaceutical ingredient (API) fermentation process is described, together with procedures for developing accurate NIR calibrations with a performance independent of scale and the specific bioreactor used. Measurements were made in situ, by insertion of transflection probes into pilot and industrial bioreactors providing direct contact with the fermentation culture media. The ultimate goal was to establish methods for real time process monitoring aimed at enhanced process supervision, fault detection diagnosis and control of bioreactors. The in situ acquired spectra were related to lab results of samples taken from the reactors during the course of the manufacturing process. Suitable spectral wavenumber regions were selected and calibration models based on partial least squares (PLS) were developed. The root mean square errors of prediction for API content, viscosity, nitrogen source and carbon source concentration were all within acceptable ranges as compared to the off-line lab measurements, respectively, 0.03% (w/w), 150 cp, 0.01% (w/w), and 0.4% (w/w).
authors.affiliation: Institute of Biotechnology & Bioengineering, IST, Centre for Biological and Chemical Engineering, Technical University of Lisbon, Av. Rovisco Pais, P-1049-001 Lisbon, Portugal. bsel@ist.utl.pt
authors.forename: Licínia O
authors.initials: LO
authors.lastname: Rodrigues
authors.forename: Luís
authors.initials: L
authors.lastname: Vieira
authors.forename: Joaquim P
authors.initials: JP
authors.lastname: Cardoso
authors.forename: José C
authors.initials: JC
authors.lastname: Menezes
mesh_terms: D019149:Bioreactors; D002138:Calibration; D002244:Carbon / Q000032:analysis*; D003470:Culture Media / Q000737:chemistry*; D005285:Fermentation; D016018:Least-Squares Analysis; D025282:Mycelium / Q000378:metabolism; D009584:Nitrogen / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014783:Viscosity
chemical_list: D003470:Culture Media; D004364:Pharmaceutical Preparations; D002244:Carbon; D009584:Nitrogen