In addition to protein denaturing, there are other causes of particle formation, such as the introduction of cellulose fibers during cleaning processes, friction with metal or Teflon, materials such as silicone oil or rubber, which are part of the primary packaging systems. The particle sizes extend from sub-visible (nanometer to the low micrometer range) to visible (about 100 - 150 µm).
The current standard technique to determine sub-visible particles is the measurement using a Hiac Royco. This instrument can count the number and size of sub-visible particles in the 1-100 µm range. Characterizing or identifying the particles is not possible. The standard procedure to determine visible particles is a manual visual control of the filled units and the subjective description of whatever visible contamination shows up.
Different analytical technologies have advanced the science on particle analysis and can deliver extensive particle characterization and identification:
MFI combines the possibilities of digital microscopy with modern microfluidics. This generates high-resolution images of sub-visible particles between 1 µm and 70 µm in size. Determining the number and size of the particles is then possible, as is particle characterization using modern application software via the morphology of the particles.
Resonant mass measurement:
Resonant mass measurement is a technique using the Archimedes system to detect sub-micrometer particles in a sample. A 50 nm – 5 µm particle flowing through a microfluidic channel changes the resonating frequency of a measurement needle, or cantilever, which allows the measurement of the buoyant mass, dry mass and size of the particle. Detecting particles with different buoyancy allows us, for example, to distinguish between protein aggregates and drops of silicone in a drug.
Digital microscope coupled with Raman spectroscopy:
The Morphologi G3-ID offers a unique technology: it combines the automated static imaging functions of a modern, high-resolution microscope, with the chemical identification of individual particles using Raman spectroscopy. This process can be used to classify a wide range of particle sizes (1 µm – 1000 µm) according to size and morphology, and to identify them chemically using the Raman spectrum.
Lab-scale digital visual inspections:
The ETAC Proview is a computer-based automated inspection system for use in research and development. It objectifies manual characterization by taking and saving high-resolution photos or movies of the filled units. With the help of innovative application software the visible mobile or immobile particles in each unit can be evaluated very precisely.