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Bioreactor Process Parameter Screening Utilizing A Plackett-Burman Design For A Model Monoclonal Antibody.

Cyrus D Agarabi, John E. Schiel, Scott Lute, Brittany Chavez, Michael T. Boyne, Kurt Brorson, Mansoor Khan, Erik K. Read
Published 2015 · Medicine, Chemistry
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Consistent high-quality antibody yield is a key goal for cell culture bioprocessing. This endpoint is typically achieved in commercial settings through product and process engineering of bioreactor parameters during development. When the process is complex and not optimized, small changes in composition and control may yield a finished product of less desirable quality. Therefore, changes proposed to currently validated processes usually require justification and are reported to the US FDA for approval. Recently, design-of-experiments-based approaches have been explored to rapidly and efficiently achieve this goal of optimized yield with a better understanding of product and process variables that affect a product's critical quality attributes. Here, we present a laboratory-scale model culture where we apply a Plackett-Burman screening design to parallel cultures to study the main effects of 11 process variables. This exercise allowed us to determine the relative importance of these variables and identify the most important factors to be further optimized in order to control both desirable and undesirable glycan profiles. We found engineering changes relating to culture temperature and nonessential amino acid supplementation significantly impacted glycan profiles associated with fucosylation, β-galactosylation, and sialylation. All of these are important for monoclonal antibody product quality.
This paper references
Chemometric evaluation of on-line high-pressure liquid chromatography in mammalian cell cultures: analysis of amino acids and glucose.
Tina M. Larson (2002)
Robin L. Plackett (1946)
Application of quality by design elements for the development and optimization of an analytical method for protamine sulfate.
David Awotwe-Otoo (2012)
Integrating Process Scouting Devices (PSDs) With Bench-Scale Devices: Challenges and Opportunities for Mammalian Cell Culture
José R Vallejos (2011)
A Nonfucosylated Anti-HER2 Antibody Augments Antibody-Dependent Cellular Cytotoxicity in Breast Cancer Patients
Eiji Suzuki (2007)
LC-MS/MS biopharmaceutical glycoanalysis: identification of desirable reference material characteristics
John E. Schiel (2012)
Biological responses of hybridoma cells to hydrodynamic shear in an agitated bioreactor.
Ibrahim M. Abu-Reesh (1991)
Process parameter shifting: Part I. Effect of DOT, pH, and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors.
Evelyn Trummer (2006)
Fermentanomics informed amino acid supplementation of an antibody producing mammalian cell culture.
Erik K. Read (2013)
Quality by design for biopharmaceuticals
Anurag Singh Rathore (2009)
Application of a continuous bioreactor cascade to study the effect of linoleic acid on hybridoma cell physiology.
Dominik Kisztelinski (2006)
Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1.
Shigeki Matsumiya (2007)
On the evaluation of gasliquid interfacial effects on hybridoma viability in bubble column bioreactors. Developments in biological standardization
A Handa (1987)
Impact of dynamic online fed-batch strategies on metabolism, productivity and N-glycosylation quality in CHO cell cultures.
Danny Chee Furng Wong (2005)
Successful transfer and 200fold scale-up of a r-CHO cell fed-batch process using a new cGMP compliant basal and feed medium combination
J Mitschelen (2008)
Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro.
Jason Hodoniczky (2005)
Effect of hydrocortisone on the production and glycosylation of an Fc-fusion protein in CHO cell cultures.
Yolande Rouiller (2012)
Temperature reduction in cultures of hGM-CSF-expressing CHO cells: effect on productivity and product quality.
Mariela Bollati-Fogolín (2005)
Advances in clone selection using high-throughput bioreactors.
Bhargavi Kondragunta (2010)
Genomic analysis of a hybridoma batch cell culture metabolic status in a standard laboratory 5 L bioreactor.
Bhargavi Kondragunta (2012)
Quality by Design (QbD), Biopharmaceutical Manufacture
Rakhi B. Shah (2010)
The effect of fatty acids on hybridoma cell growth and antibody productivity in serum-free cultures. Journal of biotechnology
M Butler (1995)
Identification of cell culture conditions to control N-glycosylation site-occupancy of recombinant glycoproteins expressed in CHO cells.
Martin Gawlitzek (2009)
Murine immune response to the Neisseria meningitidis group C capsular polysaccharide. II. Specificity.
Leonard J. Rubinstein (1988)
Evaluation of butyrate-induced production of a mannose-6-phosphorylated therapeutic enzyme using parallel bioreactors.
Chikkathur N. Madhavarao (2014)
Designing in quality: Approaches to defining the design space for a monoclonal antibody process
A Banerjee (2010)
Development of a serum-free medium for the production of erythropoietin by suspension culture of recombinant Chinese hamster ovary cells using a statistical design
GM Lee (1999)
Controlling glycation of recombinant antibody in fed-batch cell cultures.
Inn H Yuk (2011)
Post-translational structural modifications of immunoglobulin G and their effect on biological activity
Laura K Hmiel (2014)
Unsaturated fatty acids enhance cell yields and perturb the energy metabolism of an antibody-secreting hybridoma.
Michael L. Butler (1997)
In Vivo Crystallization of Human IgG in the Endoplasmic Reticulum of Engineered Chinese Hamster Ovary (CHO) Cells
Haruki Hasegawa (2011)
Industry and regulatory experience of the glycosylation of monoclonal antibodies.
Erik K. Read (2011)
The Absence of Fucose but Not the Presence of Galactose or Bisecting N-Acetylglucosamine of Human IgG1 Complex-type Oligosaccharides Shows the Critical Role of Enhancing Antibody-dependent Cellular Cytotoxicity*
Toyohide Shinkawa (2003)
On the evaluation of gas-liquid interfacial effects on hybridoma viability in bubble column bioreactors.
Arimichi Handa (1987)
The effect of fatty acids on hybridoma cell growth and antibody productivity in serum-free cultures.
Michael L. Butler (1995)
The effect of the removal of sialic acid, galactose and total carbohydrate on the functional activity of Campath-1H.
Pdw Boyd (1995)
NIST/SEMATECH e-Handbook of Statistical Methods
W. K. C. Guthrie (2005)
Temperature shift as a process optimization step for the production of pro-urokinase by a recombinant Chinese hamster ovary cell line in high-density perfusion culture.
Zhaolie Chen (2004)
A quality by design (QbD) case study on liposomes containing hydrophilic API: II. Screening of critical variables, and establishment of design space at laboratory scale.
Xiaoming Xu (2012)
Effect of Dissolved Oxygen Concentration on Monoclonal Antibody Production in Hybridoma Cell Cultures
Tatsuya Ogawa (1992)
Enhanced binding affinity for FcgammaRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity.
Kazuhiro Masuda (2007)
Defining process design space for monoclonal antibody cell culture.
Susan Fugett Abu-Absi (2010)
System-wide Genomic and Biochemical Comparisons of Sialic Acid Biology Among Primates and Rodents
Tasha K. Altheide (2006)
Development of a serum-free medium for the production of erythropoietin by suspension culture of recombinant Chinese hamster ovary cells using a statistical design.
Gina M. Lee (1999)
Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett-Burman design.
Ziyaur Rahman (2010)
Automated dynamic fed-batch process and media optimization for high productivity cell culture process development.
Franklin Lu (2013)
Effect of low culture temperature on specific productivity, transcription level, and heterogeneity of erythropoietin in Chinese hamster ovary cells.
Sung Kwan Yoon (2003)
Glucose-based optimization of CHO-cell perfusion cultures.
J E Dowd (2001)
Assembly of asparagine-linked oligosaccharides.
Rosalind Kornfeld (1985)
8 – Two-level Fractional Factorial Designs
William P. Gardiner (1998)
Kinetic analysis of hybridoma cell culture in a protein-free medium: Substrate and agitation effects
Lorea Legazpi (2005)

This paper is referenced by
Protein aggregation during bioprocessing of monoclonal antibodies in mammalian cell culture
Albert Paúl (2017)
How the Critical Path Initiative Addresses CDER’s Regulatory Science Needs
Mark Geanacopoulos (2015)
Development of Glycoanalytical Methods for Characterization of Biosimilar Monoclonal Antibodies
Katharina Yandrofski (2018)
Prediction of N-linked Glycoform Profiles of Monoclonal Antibody with Extracellular Metabolites and Two-Step Intracellular Models
Sha Sha (2019)
Recombinant antibody production evolves into multiple options aimed at yielding reagents suitable for application-specific needs
Ario de Marco (2015)
Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA's Office of Pharmaceutical Quality.
Adam C. Fisher (2016)
Simulation-based process analysis and optimization for continuous pharmaceutical manufacturing
Zilong Wang (2018)
Exploring the linkage between cell culture process parameters and downstream processing utilizing a plackett‐burman design for a model monoclonal antibody
Cyrus D Agarabi (2017)
Multivariate data analysis of growth medium trends affecting antibody glycosylation
David N Powers (2019)
Real‐time quantification and supplementation of bioreactor amino acids to prolong culture time and maintain antibody product quality
David N Powers (2019)
Optimization of a Coupling Process for Insulin Degludec According to a Quality by Design (QbD) Paradigm
Lei Nie (2018)
Heterologous recombinant expression of non-originator NISTmAb
Lila Kashi (2018)
Hybridoma cell-culture and glycan profile dataset at various bioreactor conditions
Hemlata Bhatia (2016)
Identification of process conditions influencing protein aggregation in Chinese hamster ovary cell culture.
Albert J Paul (2018)
A statistical approach to improve compound screening in cell culture media.
Eduard Puente-Massaguer (2019)
Impact Factors in the Process Development for Therapeutic Antibodies
Xiaopei Cui (2018)
Investigation of the interactions of critical scale-up parameters (pH, pO2 and pCO2) on CHO batch performance and critical quality attributes
Matthias Brunner (2016)
Metabolic flux control in glycosylation.
Andrew G. McDonald (2016)
Impact of media and antifoam selection on monoclonal antibody production and quality using a high throughput micro‐bioreactor system
Sai Rashmika Velugula-Yellela (2018)
Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations
Brittany Chavez (2016)
Purification and Analytics of a Monoclonal Antibody from Chinese Hamster Ovary Cells Using an Automated Microbioreactor System.
Sai Rashmika Velugula-Yellela (2019)
N-Glycosylation Design and Control of Therapeutic Monoclonal Antibodies.
Sha Sha (2016)
Therapeutic Fc fusion protein misfolding: A three-phasic cultivation experimental design
Atefeh Ghorbani Aghdam (2019)
Opportunities and challenges of real-time release testing in biopharmaceutical manufacturing.
Mo Jiang (2017)
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