Micro Flow Imaging Technology for Parenteral Applications

MFI™ for Parenteral Drugs

USP Chapter 788 (Particulate Matter in Injections) describes physical tests to be performed for the purpose of enumerating subvisible particles within specific size ranges. Recently the FDA has published a Stimuli Article (reference USPC 30 (6) Pages 2272-2280) demonstrating that advances in apparatus and quality control merit reducing the permissible particle counts within the specified size ranges. Chapter 788 identifies light obscuration and microscopy as the procedures for determining particle counts within the specified size ranges.

Since USP <788> was first published, advances in detection technology and analytical methods for enumerating sub-visible particles have emerged. One technique that provides measurable benefits for the parenteral drug industry is flow microscopy. The technique is applicable for both subvisible and visible particles. The principle of operation of this technology is to integrate the functions of microscopy, digital imaging, fluidics and image analysis to automatically enumerate and characterize (in terms of size, shape and transparency) particulate matter in liquid samples.

MFI™ is such a flow microscopy technique, and operates by capturing images of suspended particles in a flowing stream. The images are used to produce a particle database including count, size, transparency and shape parameters. The database can be interrogated to produce particle size distributions and isolate sub-populations using any measured parameter. Particle images are also stored for further investigation and analysis. The sample volume in each frame is precisely defined by the flow cell geometry so particle concentrations are determined absolutely.