Visible particles are one of the most important sample attributes to monitor when developing and manufacturing biopharmaceuticals and other parenteral drug products. These objects are large enough to be seen by the unaided human eye under appropriate conditions. The presence of visible particles in an injectable drug product is a significant product quality concern, leading to withheld drug product units and batches if caught during lot release or recalls if observed in the clinic. Visible particulates may also pose safety risks for patients, ranging from capillary embolism to immune reactions.
Download: "Quantitative & Consistent Visible Particle Analysis using Flow Imaging Microscopy"
USP <790> Requirements for Visible Particulates in Injectable Drugs
Pharmacopeia chapters such as USP <790>, EP 2.9.20, and JP 6.06 require all parenteral therapies to be “essentially free” or “practically free” of visible particulate matter. This requirement is often met during quality control using visual inspection, a process typically involving trained analysts viewing each drug product unit to check for particles.
Visual inspection is a probabilistic assay since it is not guaranteed that visible particles present in the sample will be observed during testing. Some may fall into the “gray zone”, indicating that they are highly unlikely to be detected during testing due to their size, shape, or optical properties. As a result, visible particles may be present in the final drug product even with 100% visual inspection. It can therefore be helpful to use orthogonal tests to monitor injectable therapies for particulates.
Using Flow Imaging Microscopy to Monitor for Visible Particles
Our application note, "Quantitative and Consistent Visible Particle Analysis in Biologics using Flow Imaging Microscopy", introduces FlowCam, a flow imaging microscopy (FIM) instrument capable of monitoring visible, gray zone, and even subvisible particulate matter in biotherapeutics. Case studies are presented to demonstrate how FlowCam can be used to detect visible and gray zone particles in protein therapy samples and gain insight into the types of particulates present. Applications for these measurements in biologic development and manufacturing are also discussed.
Capturing flow imaging microscopy data alongside standard visual inspection measurements ensures that researchers have an accurate and complete understanding of visible and gray particles in their samples. This data can be used to minimize the amount of particulate matter in each unit of an injectable therapy, reducing the number of withheld units and batches, minimizing the risk of product recalls, and improving the performance of the drug for patients.
