Subvisible particle analysis by light obscuration
Coriolis Pharma is a leading contract laboratory providing analytical service of protein aggregation testing including light obscuration analysis. This service is also available under GMP.
Light obscuration (LO) is the compendial method of choice listed in the pharmacopeias (Ph. Eur. 2.9.19 and USP <788>) for the analysis of subvisible particles in parenteral products. The sample is drawn into the system through a needle and particles passing a laser beam block a certain amount of light and produce a “shadow” on a light-sensitive detector. The area of this shadow is then converted to the equivalent circular diameter of the particle. The current compendial methods for light obscuration require a sample volume of 25 mL which is often not feasible in the development of therapeutic protein products.
At Coriolis, we typically use low volume methods for the analysis of smaller volumes, which gives the advantage to assess also vial to vial variations. For more details see our publication ("Pharmaceutical feasibility of sub-visible particle analysis in parenterals with reduced volume light obscuration methods"). Low volume light obscuration methods are currently in the process of being implemented in the pharmacopeias (USP <787> draft).
The main advantage of light obscuration is the high sampling efficiency as the whole sample volume is analyzed completely during the measurement. A disadvantage is the susceptibility to refractive index influences as light obscuration is based on the interaction of particles with light.
We have recently published a paper discussing "How subvisible particles become invisible—relevance of the refractive index for protein particle analysis".