Systematic investigation of the effect of lyophilizate collapse on pharmaceutically relevant proteins, part 2: stability during storage at elevated temperatures.

The objective of this work was to investigate the effect of lyophilizate collapse on the stability of freeze-dried protein pharmaceuticals. In the first part of this study, it was shown that collapse has no negative impact either on the properties of the freeze-dried cake or on protein stability [Schersch K, Betz O, Garidel P, Muehlau S, Bassarab S, Winter G. 2010.

Development of a pilot-scale manufacturing process for protein-coated microcrystals (PCMC): mixing and precipitation - part I.

A novel protein-coated microcrystal (PCMC) technology offers the possibility to produce dry protein formulations suitable for inhalation or, after reconstitution, for injection. Micron-sized particles are hereby produced by co-precipitation via a rapid dehydration method. Thus, therapeutic proteins can be stabilised and immobilised on crystalline carrier surfaces.

A critical evaluation of self-interaction chromatography as a predictive tool for the assessment of protein-protein interactions in protein formulation development: a case study of a therapeutic monoclonal antibody.

The aim of this study was to establish and evaluate a screening method for the physical characterization of protein-protein interactions of therapeutic proteins based on the determination of the osmotic second virial coefficient (B(22)). B(22) of an IgG1 was measured by self-interaction chromatography (SIC) and was compared to data obtained from static light scattering (SLS). As assessed by Fourier transform infrared spectroscopy (FTIR), the protein coupling to chromatography particles had no relevant influence on the three-dimensional native structure of the IgG1.

Correlation of protein-protein interactions as assessed by affinity chromatography with colloidal protein stability: a case study with lysozyme.

Lysozyme-lysozyme interactions were assessed in the native state at 25 degrees C as well in the denatured state at 80 degrees C by affinity chromatography in order to measure the osmotic second virial coefficient (B). This parameter allows us to better understand protein aggregation pathways and colloidal protein stability. Repulsive interactions (B > 0) were weakened for both protein states by increasing salt concentration and by increasing the pH value toward lysozyme pI.

A rapid, sensitive and economical assessment of monoclonal antibody conformational stability by intrinsic tryptophan fluorescence spectroscopy.

Steady-state intrinsic tryptophan fluorescence spectroscopy is used as a rapid, robust and economic way for screening the thermal protein conformational stability in various formulations used during the early biotechnology development phase. The most important parameters affecting protein stability in a liquid formulation, e. g.