|
Images of Protein Aggregates |
Particle Measurement in Pharmaceutical Applications
Analyzing Formulation Stability Using MFIThe study of particles in parenteral (or injectable) formulations is required at every step of the drug development process from research to formulation development to manufacturing to quality control of the finished product. Micro-Flow Imaging (MFI) measures particles in both the subvisible and visible ranges (from 0.75 to 300µm) and is used throughout the drug development process. Unlike "small molecule" drugs, many bio-pharmaceuticals contain proteins which have a tendency to fold and aggregate into larger structures ranging from nanometers to hundreds of microns. The aggregates are irregular in shape, near-transparent, fragile and deform easily in response to various stresses. In addition, protein aggregation is not a static phenomenon so their size and morphology will change in response to age, handling and storage conditions. In fact, the shelf life of many protein-based parenteral drug formulations is determined by their propensity to form aggregates.
The chart summarizes an experiment in which multiple aliquots from a bio-pharmaceutical sample were analyzed by a validated cGMP laboratory using USP compendial method 788. The same sample was analyzed using MFI with the results shown – in this case for particles ≥10µm.
|
It is these near-transparent protein aggregates, and the ability to distinguish them from other particles, which pose a significant challenge to obscuration-based particle analysis instruments. In comparison, MFI is an imaging-based method (i.e. flow microscope) and has higher detection sensitivity. This has been demonstrated in repeated experiments showing that, in a side-by-side comparison, MFI can detect protein aggregates at a rate that is several orders of magnitude higher than obscuration. In addition, MFI delivers the added benefits of particle images and morphology to provide additional insights into the physical characteristics of particles.