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Analytical Characterization and Predictive Tools for Highly Concentrated Protein Formulations

  • Andrea Allmendinger
  • Stefan Fischer
  • Robert Mueller
Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 38)

Abstract

This chapter focuses on different aspects of development and characterization of highly concentrated protein formulations. This includes the introduction of predictive tools used during early development, specific challenges for analytical methods, and extended characterization of rheological and structural properties. The application of predictive tools during clinical lead selection and early-stage development helps to assess whether a selected clinical candidate may successfully pass the challenges of a high-concentration product in later development. In particular, parameters like B22 (second virial coefficient) and kD (diffusional interaction parameter) are described and underlying principles, technologies, limitations, and applicability to highly concentrated formulations are elaborated. The specific challenges of high-concentration protein formulations with respect to analytical characterization are discussed in detail and practical recommendation is given. Different common techniques to measure viscosity are described including dependencies on protein concentration, temperature, and shear stress. Structural characterization of highly concentrated protein formulations requires analytical tools capable to measure in the non-diluted regime. Only a limited number of analytical techniques are available for this challenging task like small-angle scattering techniques (SAS) and quartz crystal impedance analysis (QCIA)/microbalance with dissipation monitoring (QCM-D). These techniques are described, and measuring principle, applications in literature as well as limitations are outlined.

Keywords

High-concentration protein formulation Protein–protein interaction Analytical characterization Non-ideality Second virial coefficient Diffusion coefficient Rheology Viscosity Protein aggregation Opalescence Small-Angle scattering techniques 

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Andrea Allmendinger
    • 1
  • Stefan Fischer
    • 1
  • Robert Mueller
    • 1
  1. 1.Pharmaceutical Development & Supplies, PTD Biologics EuropeF. Hoffmann-La Roche Ltd.BaselSwitzerland

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