Parenteral drugs administered by injection to patients should be essentially free of visible particles. Sub-visible particles in parenteral drugs are detected using a light obscuration particle counter, microscopic inspection on a filter, or both. The light obscuration particle count test applies to large volume injections with total volume >100 mL unless specified in the individual monograph. The test applies to single does or multiple dose injections of solutions or solutions constituted from sterile solids containing <100 mL (small volume parenterals) where a test for particulate matter is required in the individual monograph.
The Accusizer 780 SIS meets all USP <788> system requirements including:
• Method: light obscuration
• Sensor concentration limits
• Sensor dynamic range
• Sample volume accuracy
• Calibration method
• Sensor resolution
• Particle counting accuracy
Test procedure: Follow the instruction provided in USP<788> for sampling and liquid preparation, pooling units if required. Degas the sample if required. Place the sample beaker on the Accusizer 780 SIS system and begin the measurement – all of which is automated. The drug product meets the requirement if the average number of particles/mL does not exceed the stated limits shown below:
|>10 µm||>25 µm|
|SVP||6000||600 per container|
The Accusizer software also has built in Pass/Fail criteria tables that will allow users to define up to 32 Pass/Fail parameters based on size and particle counts greater than that size. The table below is based on the USP <788> criteria of 10 and 25 microns for small volume injectables.
If the average number of particles exceeds this limit, then the user must perform the microscopic particle count test.
Advantages of the Accusizer 780 SIS system for this test over older particle counters like the Hiac include:
• Greater particle size resolution – into 512 channels
o Better definition of particle size range can help identify sources of contamination
• Enhanced sensor performance
o A wider dynamic range allows for testing at smaller sizes
o The standard sensor covers 0.5-400 µm