Abstract
Recent trends in the pharmaceutical sector are changing the way protein purification processes are designed and executed, moving from operating the process in a fixed point to allowing a permissible region in the operating space known as design space. This trend is driving product development to design quality into the manufacturing process (Quality by Design) and not to rely exclusively on testing quality in the product. A typical purification step has numerous operating parameters that can impact its performance. Therefore, optimization and robustness analysis in purification processes can be time-consuming since they are mainly grounded on experimental work. A valuable approach consists in the combination of an adequate risk analysis technique for selecting the relevant factors influencing process performance and the design of experiment methodology. The latter allows for many process variables which can be studied at the same time; thus, the number of tests will be reduced in comparison with the conventional approach based on trial and error. These multivariate studies permit a detailed exploration in the experimental range and lay the foundation of Quality by Design principles application. This article outlines a recommended sequence of activities toward the establishment of an expanded design space for a purification process.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
FDA. U.S. Department of Health and Human Services (2006) Guidance for industry: Q8 pharmaceutical development
FDA. U.S. Department of Health and Human Services (2006) Guidance for industry: quality systems approach to pharmaceutical cGMPs
García-Muñoz S, Dolph S, Ward HW II (2010) Handling uncertainty in the establishment of a design space for the manufacture of a pharmaceutical product. Comp Chem Eng 34:1098–1107
Rathore A, Mhatre R (2009) Quality by design for biopharmaceuticals. Wiley, Hoboken, NJ
Rathore A, Winkle H (2009) Quality by design for biopharmaceuticals. Nat Biotechnol 27:26–34
ICH (2009) Pharmaceutical development ICH Q8 (R2). International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use
Rathore A (2009) Roadmap for implementation of quality by design (QbD) for biotechnology products. Trends Biotechnol 27:546–553
Jiang C, Falnsburg L, Ghose S et al (2010) Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: application of quality by design (QbD) principles. Biotechnol Bioeng 107:985–997
Knevelman C, Davies J, Allen L et al (2010) High-throughput screening techniques for rapid PEG-based precipitation of IgG4mAb from clarified cell culture supernatant. Biotechnol Prog 26:697–705
Didier C, Forno G, Etcheverrigaray M et al (2009) Novel chemometric strategy based on the application of artificial neural networks to crossed mixture design for the improvement of recombinant protein production in continuous culture. Anal Chim Acta 650:167–174
Abu-Absi SF, Yang L, Thompson P et al (2010) Defining process design space for monoclonal antibody cell culture. Biotechnol Bioeng 15:894–905
Paillet C, Forno G, Soldano N et al (2011) Statistical optimization of influenza H1N1 production from batch cultures of suspension Vero cells (sVero). Vaccine 29:7212–7217
Myers RH, Montgomery DC, Anderson-Cook CM (2009) Response surface methodology: process and product optimization using designed experiments. Wiley, Hoboken, NJ
Seely R, Haury J (2005) Applications of failure modes and effect analysis to biotechnology manufacturing processes. In: Rathore A, Sofer G (eds) Process validation in manufacturing of biopharmaceuticals. Taylor & Francis, Boca Raton, FL, pp 13–29
Godavarti R, Petrone J, Robinson J et al (2005) Scale-down models for purification processes: approaches and applications. In: Rathore A, Sofer G (eds) Process validation in manufacturing of biopharmaceuticals. Taylor & Francis, Boca Raton, FL, pp 69–142
Evans DR, Macniven RP, Labanca M et al (2008) Purification of an Fc-fusion biologic: clearance of multiple product related impurities by hydrophobic interaction chromatography. J Chromatogr A 1177:265–271
Li M, Su E, You P et al (2010) Purification and in situ immobilization of papain with aqueous two-phase system. PLoS One 5:e15168
Amadeo I, Mauro L, Ortí E et al (2011) Determination of robustness and optimal work conditions for a purification process of a therapeutic recombinant protein using RSM. Biotechnol Prog 27:724–732
Zhao Y, Kang L, Gao S et al (2012) Peg precipitation coupled with chromatography is a new and sufficient method for the purification of botulinum neurotoxin type B. PLoS One 7:e39670
Costa FS, Bruns R, Paranhos da Silva E et al (2007) Statistical designs and response surface techniques for the optimization of chromatographic systems. J Chromatogr A 1158:2–14
NIST/SEMATECH (2012) e-Handbook of statistical methods, http://www.itl.nist.gov/div898/handbook. Accessed 26 November 2012
Derringer G, Suich R (1980) Simultaneous optimization of several response variables. J Qual Technol 12:214–219
PDA (2005) PDA technical report 42. Process validation of protein manufacturing. PDA Publications, Bethesda, MD
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Amadeo, I., Mauro, L., Ortí, E., Forno, G. (2014). Establishment of a Design Space for Biopharmaceutical Purification Processes Using DoE. In: Labrou, N. (eds) Protein Downstream Processing. Methods in Molecular Biology, vol 1129. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-977-2_2
Download citation
DOI: https://doi.org/10.1007/978-1-62703-977-2_2
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-976-5
Online ISBN: 978-1-62703-977-2
eBook Packages: Springer Protocols