Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations
Abstract
Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 24full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Therefore, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.
- Authors:
-
- Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality's (OPQ) Division II
- Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality's (OPQ) Division of Product Quality Research, Office of Testing
- Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality's (OPQ) Division II
- Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality's (OPQ) Division of Pharmaceutical Analysis, Office of Testing and Research
- Publication Date:
- Research Org.:
- Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); US Food and Drug Administration (FDA)
- OSTI Identifier:
- 1376192
- Grant/Contract Number:
- CDER-Grant-No.1500
- Resource Type:
- Accepted Manuscript
- Journal Name:
- BioMed Research International
- Additional Journal Information:
- Journal Volume: 2016; Journal ID: ISSN 2314-6133
- Publisher:
- Hindawi
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Chavez, Brittany K., Agarabi, Cyrus D., Read, Erik K., Boyne II, Michael T., Khan, Mansoor A., and Brorson, Kurt A. Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations. United States: N. p., 2016.
Web. doi:10.1155/2016/2074149.
Chavez, Brittany K., Agarabi, Cyrus D., Read, Erik K., Boyne II, Michael T., Khan, Mansoor A., & Brorson, Kurt A. Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations. United States. https://doi.org/10.1155/2016/2074149
Chavez, Brittany K., Agarabi, Cyrus D., Read, Erik K., Boyne II, Michael T., Khan, Mansoor A., and Brorson, Kurt A. Fri .
"Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations". United States. https://doi.org/10.1155/2016/2074149. https://www.osti.gov/servlets/purl/1376192.
@article{osti_1376192,
title = {Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations},
author = {Chavez, Brittany K. and Agarabi, Cyrus D. and Read, Erik K. and Boyne II, Michael T. and Khan, Mansoor A. and Brorson, Kurt A.},
abstractNote = {Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 24full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Therefore, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.},
doi = {10.1155/2016/2074149},
journal = {BioMed Research International},
number = ,
volume = 2016,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 2016},
month = {Fri Jan 01 00:00:00 EST 2016}
}
Web of Science
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Formulation and Delivery Issues for Monoclonal Antibody Therapeutics
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Optical sensor enabled rocking T-flasks as novel upstream bioprocessing tools
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A case study in converting disposable process scouting devices into disposable bioreactors as a future bioprocessing tool
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- Vallejos, José R.; Uplekar, Shaunak; da Silva, João F.
- Biotechnology and Bioengineering, Vol. 109, Issue 11
Genomic analysis of a hybridoma batch cell culture metabolic status in a standard laboratory 5 L bioreactor
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- Kondragunta, Bhargavi; Han, Jing; Joshi, Bharat H.
- Biotechnology Progress, Vol. 28, Issue 5
Fermentanomics informed amino acid supplementation of an antibody producing mammalian cell culture
journal, April 2013
- Read, Erik K.; Bradley, Scott A.; Smitka, Tim A.
- Biotechnology Progress, Vol. 29, Issue 3
Fermentanomics: Relating quality attributes of a monoclonal antibody to cell culture process variables and raw materials using multivariate data analysis
journal, August 2015
- Rathore, Anurag S.; Kumar Singh, Sumit; Pathak, Mili
- Biotechnology Progress, Vol. 31, Issue 6
Advances in clone selection using high-throughput bioreactors
journal, January 2010
- Kondragunta, Bhargavi; Drew, Jessica L.; Brorson, Kurt A.
- Biotechnology Progress
An Industry Perspective on the Monitoring of Subvisible Particles as a Quality Attribute for Protein Therapeutics
journal, August 2010
- Singh, Satish K.; Afonina, Nataliya; Awwad, Michel
- Journal of Pharmaceutical Sciences, Vol. 99, Issue 8
Subvisible Particle Counting Provides a Sensitive Method of Detecting and Quantifying Aggregation of Monoclonal Antibody Caused by Freeze-Thawing: Insights Into the Roles of Particles in the Protein Aggregation Pathway
journal, February 2011
- Barnard, James G.; Singh, Satish; Randolph, Theodore W.
- Journal of Pharmaceutical Sciences, Vol. 100, Issue 2
Formulation Development of Therapeutic Monoclonal Antibodies Using High-Throughput Fluorescence and Static Light Scattering Techniques: Role of Conformational and Colloidal Stability
journal, April 2011
- Goldberg, Deborah S.; Bishop, Steven M.; Shah, Ambarish U.
- Journal of Pharmaceutical Sciences, Vol. 100, Issue 4
Bioreactor Process Parameter Screening Utilizing a Plackett-Burman Design for a Model Monoclonal Antibody
journal, June 2015
- Agarabi, Cyrus D.; Schiel, John E.; Lute, Scott C.
- Journal of Pharmaceutical Sciences, Vol. 104, Issue 6
Formulation and delivery issues for monoclonal antibody therapeutics
journal, August 2006
- Daugherty, Ann L.; Mrsny, Randall J.
- Advanced Drug Delivery Reviews, Vol. 58, Issue 5-6
Influence of pH, buffer species, and storage temperature on physicochemical stability of a humanized monoclonal antibody LA298
journal, February 2006
- Zheng, Jack Y.; Janis, Linda J.
- International Journal of Pharmaceutics, Vol. 308, Issue 1-2
Spectroscopic evaluation of the stabilization of humanized monoclonal antibodies in amino acid formulations
journal, April 2007
- Tian, Fei; Middaugh, C. Russell; Offerdahl, Tom
- International Journal of Pharmaceutics, Vol. 335, Issue 1-2
Quality by design: Impact of formulation variables and their interactions on quality attributes of a lyophilized monoclonal antibody
journal, November 2012
- Awotwe-Otoo, David; Agarabi, Cyrus; Wu, Geoffrey K.
- International Journal of Pharmaceutics, Vol. 438, Issue 1-2
Understanding the Role of Arginine as an Eluent in Affinity Chromatography via Molecular Computations
journal, March 2011
- Shukla, Diwakar; Zamolo, Laura; Cavallotti, Carlo
- The Journal of Physical Chemistry B, Vol. 115, Issue 11
Works referencing / citing this record:
Exploring the linkage between cell culture process parameters and downstream processing utilizing a plackett-burman design for a model monoclonal antibody
journal, November 2016
- Agarabi, Cyrus D.; Chavez, Brittany K.; Lute, Scott C.
- Biotechnology Progress, Vol. 33, Issue 1
Overview of Antibody Drug Delivery
journal, July 2018
- Awwad, Sahar; Angkawinitwong, Ukrit
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