Estimation of raw material performance in mammalian cell culture using near infrared spectra combined with chemometrics approaches

Understanding variability in raw materials and their impacts on product quality is of critical importance in the biopharmaceutical manufacturing processes. For this purpose, several spectroscopic techniques have been studied for raw material characterization, providing fast and nondestructive ways to measure quality of raw materials. However, investigations of correlation between spectra of raw materials and cell culture performance have been scarce due to their complexity and uncertainty. In this study, near‐infrared spectra and bioassays of multiple soy hydrolysate lots manufactured by different vendors were analyzed using chemometrics approaches in order to address variability of raw materials as well as correlation between raw material properties and corresponding cell culture performance. Principal component analysis revealed that near‐infrared spectra of different soy lots contain enough physicochemical information about soy hydrolysates to allow identification of lot‐to‐lot variability as well as vendor‐to‐vendor differences. The identified compositional variability was further analyzed in order to estimate cell growth and protein production of two mammalian cell lines under the condition of varying soy dosages using partial least square regression combined with optimal variable selection. The performance of the resulting models demonstrates the potential of near‐infrared spectroscopy as a robust lot selection tool for raw materials while providing a biological link between chemical composition of raw materials and cell culture performance. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012

[1]  J. Pons,et al.  Exploring blocking assays using Octet, ProteOn, and Biacore biosensors. , 2009, Analytical biochemistry.

[2]  Katie F Wlaschin,et al.  Recombinant protein therapeutics from CHO cells : 20 years and counting , 2007 .

[3]  H. Katinger,et al.  Plant Protein Hydrolysates: Preparation of Defined Peptide Fractions Promoting Growth and Production in Animal Cells Cultures , 2000, Biotechnology progress.

[4]  C. Spiegelman,et al.  Theoretical Justification of Wavelength Selection in PLS Calibration:  Development of a New Algorithm. , 1998, Analytical Chemistry.

[5]  T. Bibila,et al.  In Pursuit of the Optimal Fed‐Batch Process for Monoclonal Antibody Production , 1995, Biotechnology progress.

[6]  Eric R. Ziegel,et al.  The Elements of Statistical Learning , 2003, Technometrics.

[7]  Alan G. Ryder,et al.  Rapid characterization and quality control of complex cell culture media solutions using raman spectroscopy and chemometrics , 2010, Biotechnology and bioengineering.

[8]  Jon Brumbaugh,et al.  DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION , 2000 .

[9]  R. Schimke,et al.  Cell line-specific differences in the control of cell cycle progression in the absence of mitosis. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Jaeseung Yoon,et al.  Improved recombinant gene expression in CHO cells using matrix attachment regions. , 2004, Journal of biotechnology.

[11]  Margaret A. Nemeth,et al.  Multi- and Megavariate Data Analysis , 2003, Technometrics.

[12]  F Gòdia,et al.  Improvement of CHO Cell Culture Medium Formulation: Simultaneous Substitution of Glucose and Glutamine , 2000, Biotechnology progress.

[13]  Andrew Whitehead,et al.  Variation within and among species in gene expression: raw material for evolution , 2006, Molecular ecology.

[14]  Mohamed Al-Rubeai,et al.  Selection methods for high-producing mammalian cell lines. , 2007, Trends in biotechnology.

[15]  A S Rathore,et al.  Process analytical technology (PAT) for biopharmaceutical products , 2010, Analytical and bioanalytical chemistry.

[16]  Canghai Lu,et al.  A T-flask based screening platform for evaluating and identifying plant hydrolysates for a fed-batch cell culture process , 2007, Cytotechnology.

[17]  Programmierbarer Thermoblock,et al.  From industry , 1991 .

[18]  A S Rathore,et al.  Process analytical technology (PAT) for biopharmaceutical products: Part I. concepts and applications , 2010, Biotechnology and bioengineering.

[19]  Hongdong Li,et al.  Key wavelengths screening using competitive adaptive reweighted sampling method for multivariate calibration. , 2009, Analytica chimica acta.

[20]  Sung Hyun Kim,et al.  Development of serum-free medium supplemented with hydrolysates for the production of therapeutic antibodies in CHO cell cultures using design of experiments , 2009, Applied Microbiology and Biotechnology.

[21]  Heng Tao Shen,et al.  Principal Component Analysis , 2009, Encyclopedia of Biometrics.

[22]  M. Riley,et al.  Simultaneous Measurement of 19 Components in Serum‐Containing Animal Cell Culture Media by Fourier Transform Near‐Infrared Spectroscopy , 2001, Biotechnology progress.

[23]  Christopher Jones,et al.  Quality control and analytical techniques for biopharmaceuticals. , 2011, Bioanalysis.

[24]  Guoxiang Chen,et al.  Combined approach of NMR and chemometrics for screening peptones used in the cell culture medium for the production of a recombinant therapeutic protein. , 2007, Biotechnology and bioengineering.

[25]  A. Lubiniecki.  Historical reflections on cell culture engineering , 1998, Cytotechnology.

[26]  T. Næs,et al.  The Effect of Multiplicative Scatter Correction (MSC) and Linearity Improvement in NIR Spectroscopy , 1988 .

[27]  Anurag S Rathore,et al.  Application of near‐infrared (NIR) spectroscopy for screening of raw materials used in the cell culture medium for the production of a recombinant therapeutic protein , 2009, Biotechnology progress.

[28]  N. Chung,et al.  Usability of size-excluded fractions of soy protein hydrolysates for growth and viability of Chinese hamster ovary cells in protein-free suspension culture. , 2007, Bioresource technology.

[29]  B. Kowalski,et al.  Partial least-squares regression: a tutorial , 1986 .

[30]  E. Mandine,et al.  Evidence that monoclonal antibody production kinetics is related to the integral of the viable cells curve in batch systems , 1988, Biotechnology Letters.

[31]  Wojtek J. Krzanowski,et al.  Cross-Validation in Principal Component Analysis , 1987 .

[32]  Israel Schechter,et al.  Wavelength Selection for Simultaneous Spectroscopic Analysis. Experimental and Theoretical Study , 1996 .

[33]  Jerry Workman,et al.  Practical guide to interpretive near-infrared spectroscopy , 2007 .

[34]  Melvin E Andersen,et al.  Dose-dependent transitions in mechanisms of toxicity: case studies. , 2004, Toxicology and applied pharmacology.

[35]  Yeon‐Gu Kim,et al.  Assessment of cell engineering strategies for improved therapeutic protein production in CHO cells , 2008, Biotechnology journal.

[36]  H Li,et al.  Gamma-interferon production and quality in stoichiometric fed-batch cultures of Chinese hamster ovary (CHO) cells under serum-free conditions. , 1997, Biotechnology and bioengineering.

[37]  Alan G. Ryder,et al.  Prediction of cell culture media performance using fluorescence spectroscopy. , 2010, Analytical chemistry.

[38]  Jose C. Menezes,et al.  Predicting mab product yields from cultivation media components, using near‐infrared and 2D‐fluorescence spectroscopies , 2011, Biotechnology progress.