Abstract
This chapter outlines the basic parameters and considerations for the development of a drug substance (DS) formulation, using ultrafiltration (UF) and diafiltration (DF) operations, under the principles of quality by design (QbD). Topics of discussion will include the quality target product profile (QTPP), potential critical quality attributes (CQAs), relevant risk assessment tools, critical process parameters (CPPs) and how they are determined or studied, design space definition, and control strategies. As this operation is complex and very responsive to specific product molecule characteristics, a baseline process example will be discussed. Further process examples are provided to describe process considerations and adjustments that may be required due to specific molecule characteristics or behavior.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bird RB, Stewart WE et al (2002) Transport phenomena. Wiley
Brunkow R, Delucia D et al (1996) Cleaning and cleaning validation: a biotechnology perspective. PDA. Bethesda, MD
Burns DB, Zydney AL (2001) Contributions to electrostatic interactions on protein transport in membrane systems. AIChE J 47(5):1101–1114
EMD Millipore (1991) Maintenance procedures for pellicontm cassette filters. Lit. No. P17512, 1991
EMD Millipore (1999) Protein concentration and diafiltration by tangential flow filtration. Lit. No. TB032, Rev. B, 1999
He F, Woods CE et al (2010) Screening of monoclonal antibody formulations based on high-throughput thermostability and viscosity measurements: design of experiment and statistical analysis. J Pharm Sci 100(4):1330–1340
International conference on harmonization of technical requirements for registration of pharmaceuticals for human use, ICH harmonized tripartite guideline pharmaceutical development, Q8(R2), Current Step 4 version, August 2009
Luo R, Waghmare R et al (2006) Highconcentration UF/DF of a monoclonal antibody. Bioprocess Int 4:44–46
Lutz H, Raghunath B (2007) Ultrafiltration process design (Chap. 10). Shukla AA et al (eds) Process scale bioseparations for the biopharmaceutical industry. CRC Press, Boca Raton
Maa Y-F, Hsu CC (1996) Effect of high shear on proteins. Biotechnol Bioeng 51(4):458–465
Manning M, Chou D et al (2010) Stability of protein pharmaceuticals: an update. Pharm Res 27(4):544–575
Middaugh CR, Volkin DB (1992) Protein solubility. Ahern TJ, Manning MC (eds) Stability of protein pharmaceuticals. Part A: chemical and physical pathways of protein degradation. Plenum, New York, 109–134
Monkos K (1996) Viscosity of bovine serum albumin aqueous solutions as a function of temperature and concentration. Int J Biol Macromol 18(1–2):61–68
Monkos K, Turczynski B (1999) A comparative study on viscosity of human, bovine and pig IgG immunoglobulins in aqueous solutions. Int J Biol Macromol 26(2–3):155–159
Rupley JA (1968) Comparison of protein structure in the crystal and in solution: IV. Protein solubility. J Mol Biol 35(3):455–476
Shire SJ, Shahrokh Z et al (2004) Challenges in the development of high protein concentration formulations. J Pharm Sci 93(6):1390–1402
Stoner MR, Fischer N et al (2004) Protein–solute interactions affect the outcome of ultrafiltration/diafiltration operations. J Pharm Sci 93(9):2332–2342
van Reis R, Zydney A (2007) Bioprocess membrane technology. J Memb Sci 297(1–2):16–50
Virkar PD, Narendranathan TJ et al (1981) Studies of the effect of shear on globular proteins: extension to high shear fields and to pumps. Biotechnol Bioeng 23(2):425–429
Winter C, Mulherkar P et al (2008) Formulation strategy and high temperature UF to achieve high concentration. rhuMAbs. Recovery of Biological Products XIII
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Shultz, J., Lutz, H., Rao, S. (2015). Quality by Design as Applied to Drug Substance Formulation Using Ultrafiltration and Diafiltration. In: Jameel, F., Hershenson, S., Khan, M., Martin-Moe, S. (eds) Quality by Design for Biopharmaceutical Drug Product Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 18. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2316-8_10
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2316-8_10
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-2315-1
Online ISBN: 978-1-4939-2316-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)