Munich-based company Coriolis PharmaServices GmbH is using NanoSight’s
LM-20 nanoparticle characterization system to investigate the aggregation behaviour
of protein drugs and vaccines.
Coriolis is a contract research organization for the formulation and analytics
of pharmaceutical proteins and vaccines for their customers from national and
international pharmaceutical companies. A special focus during formulation development
is set on the characterization of subvisible particles and aggregation. The
main application requirement for the NanoSight system is to measure the number
and the size distribution of aggregates in pharmaceutical protein formulations
and of vaccines, e.g. virus-like particles. Protein aggregation is a major stability
issue and can result in reduced biological activity and enhanced immunogenicity
of the product. Therefore, it is important to analyze the aggregation behaviour
of pharmaceutical proteins and develop methods and formulations that avoid aggregation
already at the beginning of formulation development.
Coriolis uses a variety of instrumental techniques to quantify and size aggregates,
depending on the size range of interest. Dynamic light scattering is ideal to
analyze monodisperse systems, e.g. 5-20 nm range, but once the aggregates start
to form and grow (in the hundreds of nm range), nanoparticle tracking analysis
(NTA) from NanoSight gives a real distribution picture. For samples in the µm
range, microflow imaging (MFI) and light obscuration are used.
In contrast to DLS, NTA works well with polydisperse samples giving an estimation
of the total concentration of particles and the possibility to distinguish different
size populations, e.g. 60 and 100 nm particles. This is not possible by DLS
due to the poor resolution.
Speaking at the recent National Biotech Conference 2010 in San Francisco, the
Coriolis team under Dr Michael Wiggenhorn reported that to achieve a comprehensive
characterization of nanoscale particulates in protein formulations, it is important
to combine techniques that operate in that range. However, the ability of NTA
to provide a real-time image of samples permits the analysis of potentially
occurring difficulties during the measurement which is not possible using DLS.