Did you know that subvisible particles (SVPs) are the leading cause of drug product recalls? Despite being tiny, these subvisible particles have a big impact on biologic, cell, and gene therapies – not only limiting a product’s shelf life, but also comprising patient safety. For this reason, injectable drugs face strict requirements to be virtually free of SVPs requiring subvisible particle testing, a method used in pharmaceutical quality control to detect and quantify particles that are not easily visible to the naked eye.
Researchers need a complete understanding and control of physical stability throughout every stage of the manufacturing process. There are a number of factors that contribute to instability and aggregation of biologics including “shear from pumping operations, suboptimal storage temperatures, freeze-thaw cycling, air-water interfaces, and exposure to various surface chemistries.”1 While aggregates can range in both size and solubility, current efforts have focused on insoluble, subvisible particles ranging ~0.1–100 µm, mainly due to the fact that subvisible particles have been shown to “possibly illicit undesired immune responses.”1
Recently, USP 1788 was revised to update and improve USP 788, the primary governing standard for particle analysis of injectables. USP 788 provides an overview of two methods that can be used to determine particulate matter: Light Obscuration (LO) Particle Count Test and Microscopic Particle Count Test. Now, in addition to light obscuration and membrane microscopic methods, USP 1788 provides new guidance on the use of flow microscopy for the determination of particulate matter. USP 1788 revision reinforces the idea that complementary, orthogonal tests must be paired with light obscuration when used alone.