Abstract
A systematic work process has been defined that strengthens the critical interface between discovery research and formulation development for the early identification of suitable protein candidates to be moved into formulation development and assess their developmentability/manufacturability potential. This predevelopment risk-based approach is essential for (i) understanding the solution behavior of therapeutic proteins, (ii) identifying preliminary critical quality attributes, (iii) optimizing liquid formulations earlier, and (iv) aligning with the quality by design requirements directed by industry guidelines, namely, ICH Q8(R2), Q9, and Q10.
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
Aalberse R, Schuurman J (2002) IgG4 breaking the rules. Immunology 105:9–19
Choh S, Cross D, Wang C (2011) Facile synthesis and characterization of disulfide-cross-linked Hyaluronic acid hydrogels for protein delivery and cell encapsulation. Biomacromolecules 12:1126–1136
Code of federal regulations (2012) Design Controls, 21 CFR Sect. 820.30.
Friess W, Uludag H, Foskett S et al (1999a) Bone regeneration with recombinant human bone morphogenetic protein-2 (rhBMP-2) using absorbable collagen sponges (ACS): influence of processing on ACS characteristic and formulation. Pharm Dev Technol 4:387–396
Friess W, Uludag H, Foskett S et al (1999b) Characterization of absorbable collagen sponges as rhBMP-2 carriers. Int J Pharm 187:91–99
Geiger M (2001) Porus collagen composite carriers for bone regeneration using recombinant human bone morphogenetic protein-2 (rhBMP-2). Dissertation, Friedrich-Alexander-Universitat
Gibson T, McCarty K, McFadyen I et al (2011) Application of a high-throughput screening procedure with PEG-induced precipitation to compare relative protein solubility during formulation development with IgG1 monoclonal antibodies. J Pharm Sci 100:1009–1021
Giteau A, Venier-Julienne M, Aubert-Pouessel A et al (2008) How to achieve sustained and complete protein release from PLGA-based microparticles. Int J Pharm 350:14–26
Guziewicz N, Trierweiler G, Johnson K et al (2008) Probing the solution behavior of proteins by differential scanning calorimetry: applications to pre-formulation and formulation development. In: Reese E, Spotts S (eds) Proceedings of the 2007 Current Trends in Microcalorimtry. MicroCal LLC, Northampton, pp 127–153
Guziewicz N, Best A, Perez-Ramirez B et al (2011) Lyophilized silk fibroin hydrogels for the sustained local delivery of therapeutic monoclonal antibodies. Biomaterials 32:2642–2650
Haidar Z, Hamdy R, Tabrizian M (2009) Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part B. Delivery systems for BMPs in orthopaedic and craniofacial tissue engineering. Biotechnol Lett 31:1825–1835
Hall C, Abraham G (1984) Reversible self-association of a human myeloma protein. Thermodynamics and relevance to viscosity effects and solubility. BioChemistry 23:5123–5129
Hayter J, Robertson D, Gaskell S et al (2003) Proteome analysis of intact proteins in complex mixtures. Mol Cell Proteomics 2:85–95
He F, Becker G, Litowski J et al (2010a) High-throughput dynamic light scattering method for measuring viscosity of concentrated protein solutions. Anal Biochem 399:141–143
He F, Phan D, Hogan S et al (2010b) Detection of IgG aggregation by a high throughput method based on extrinsic fluorescence. J Pharm Sci 99:2598–2608
He F, Woods C, Trilisky E et al (2011) Screening of monoclonal antibody formulations based on high-throughput thermostability and viscosity measurements: design of experiment and statistical analysis. J Pharm Sci 100:1330–1340
ICH (1999) Specifications: test procedures and acceptance criteria for biotechnological/biological products. Q6B. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q6B/Step4/Q6B_Guideline.pdf. Accessed 1 Oct 2012
ICH (2005) Quality risk management Q9. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q9/Step4/Q9_Guideline.pdf. Accessed 1 Oct 2012
ICH (2008) Pharmaceutical quality system. Q10. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf. Accessed 1 Oct 2012
ICH (2009) Pharmaceutical development Q8(R2). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf. Accessed 1 Oct 2012
Jezek J, Rides M, Derham B et al (2011) Viscosity of concentrated therapeutic protein compositions. Advan Drug Deliv Rev 63:1107–1117
Jiskoot W, Randolph T, Volkin D et al (2012) Protein Instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release. J Pharm Sci 101:946–954
Kowalkowski T, Buszewski B, Cantado C et al (2006) Field flow fractionation: theory, techniques, applications and the challenges. Crit Rev Anal Chem 36:129–135
Kumar S, Singh S, Wang X et al (2011) Coupling of aggregation and immunogenicity in biotherapeutics: T and B-cell immune epitopes may contain aggregation-prone regions. Pharm Res 28:949–961
Li X, Zhang Y, Yang R et al (2000) Influence of process parameters on the protein stability encapsulated in poly-DL-lactide-poly (ethylene glycol) microspheres. J Control Release 68:41–52
Li Y, Weiss W, Roberts C (2009) Characterization of high molecular-weight nonnative aggregates and aggregation kinetics by size exclusion chromatography with inline multi-angle laser light scattering. J Pharm Sci 11:3997–4016
Liu J, Nguyen M, Andya J et al (2005) Reversible self-association increases the viscosity of a concentrated monoclonal antibody in aqueous solution. J Pharm Sci 94:1928–1940
Liu W, Switf R, Torraca G et al (2010) Root cause analysis of Tungsten-induced protein aggregation in pre-filled syringes. PDA J Pharm Sci Technol 64:11–19
Manabe T, Okino H, Maeyama R et al (2004) Novel strategic therapeutic approaches for prevention of local recurrence of pancreatic cancer after resection: trans-tissue, sustained local drug delivery systems. J Control Release 100:317–330
Morin R, Kaplan D, Perez-Ramirez B (2006) Bone morphogenetic protein-2 binds as multilayers to a collagen delivery matrix: an equilibrium thermodynamic analysis. Biomacromolecules 7:131–138
Overcashier D, Chan E, Hsu C (2006) Technical considerations in the development of pre-filled syringes for protein products. Am Pharm Rev 9:77–83
Perez-Ramirez B, Steckert J (2005) Probing reversible self-association of therapeutic proteins by sedimentation velocity in the analytical ultracentrifuge. Methods Mol Biol 308:301–318
Perez-Ramirez B, Guziewicz N, Simler R (2010) Preformulation research: assessing protein solution behavior during early development. In: Jameel F, Hershenson S (eds) Formulation and process development strategies for manufacturing biopharmaceuticals. Wiley, Hoboken, pp 119–146
Sahoo S, Ang L, Goh J et al (2009) Growth factor delivery through electrospun nanofibers in scaffolds for tissue engineering. J Biomed Mater Res 93:1539–1550
Saluja A, Fesinmeyer R, Hogan S et al (2010) Diffusion and sedimentation interaction parameters for measuring the second virial coefficient and their utility as predictors of protein aggregation. Biophys J 99:2657–2665
Scherer T, Liu J, Shire S et al (2010) Intermolecular interactions of IgG1 monoclonal antibodies at high concentrations characterized by light scattering. J Phys Chem B 114:12948–12957
Simler R, Walsh G, Mattaliano R et al (2008) Maximizing data collection and analysis during preformulation of biotherapeutic proteins. BioProcess Int 6:38–45
Sinha V, Trehan A (2003) Biodegradable microspheres for protein delivery. J Control Release 90:261–280
Stamatis D (2003) Failure mode and effects analysis: FMEA from theory to execution, 2nd edn. ASQ Quality Press, Milwauke
Van Tomme S, Storm G, Hennink W (2008) In situ gelling hydrogels for pharmaceutical and biomedical applications. Int J Pharm 355:1–18
Wakankar A, Borchardt R (2006) Formulation considerations for proteins susceptible to asparagine deamidation and aspartate isomerization. J Pharm Sci 95:2321–2336
Wakankar A, Borchardt R, Eigenbrot C et al (2007a) Aspartate isomerization in the complementary-determining regions of two closely related antibodies. BioChemistry 46:1534–1544
Wakankar A, Borchardt R, Eigenbrot C et al (2007b) Aspartate isomerization in the complementary-determining regions of two closed related monoclonal antibodies. BioChemistry 46:1534–1544
Yadav S, Shire S, Kalonia D (2010) Factors affecting the viscosity in high concentration solutions of different monoclonal antibodies. J Pharm Sci 99:4812–4829
Zhao H, Graf O, Milovic N et al (2010) Formulation development of antibodies using robotic system and high-throughput laboratory (HTL). J Pharm Sci 99:2279–2294
Zhu G, Mallery S, Schwendeman S (2000) Stabilization of proteins encapsulated in injectable poly (lactide-co-glycolide). Nat Biotechnol 18:52–57
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
Perez-RamÃrez, B., Guziewicz, N., Simler, R., Sreedhara, A. (2015). Approaches for Early Developability Assessment of Proteins to Guide Quality by Design of Liquid Formulations. 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_6
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2316-8_6
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)