Particulate matter in injections is defined as extraneous particles, unintentionally present in the end product. These contaminants can come from various sources, including the environment, packaging materials and undissolved formulation ingredients. Particulate matter can be harmful when introduced into the bloodstream. Therefore, the US Pharmacopeia places limits on the amount of sub-visible particles that are allowed in injections based on these risks, as described in USP1. The chapter contains two test methods for particulate matter which are the Light Obscuration Particle Count Test and the Microscopic Particle Count Test which determine the amount of particles in the final product, even in the sub-visible (1 – 100 µm) range. Although, the quantification of the particulate present in the sample does allow for adherence to guidelines and improve safety of released drug product, it does not aid in the determination of the particulate’s origin.
Characterization of the particulate present in a sample can lead to source determination of the contaminants, and thus lead to the eventual improvement of the manufacturing and packaging processes. Orthogonal methods to the recommended methods, such as automated Raman spectroscopy and automated scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), allow for the characterization of particulate down to 2µm. Raman spectroscopy characterizes the organic and some inorganic particulate, while SEM-EDS characterizes the inorganic and metallic particulate present in a sample. The automation of the methods allows for the identification of an entire population of particles, versus a handful of particulate that can be analyzed manually. The automated methods also allow for the characterization of particulate from 2-50um, which are not able to be manually manipulated and prepared onto the appropriate substrates for traditional manual analysis methods.
The ability to characterize particulate when a failing result is obtained for counting/sizing is what will aid the investigator in determining the source of the particulate. Required compliance with the USP standard makes the quantification of foreign particulate matter a critical component in biopharmaceutical drug industry quality control and testing. A threepronged approach advocates testing by light obscuration for quantification of the particulate present in a sample, followed by automated Raman spectroscopy and automated SEM-EDS to characterize the population of particulate.