Study Outline
Automatic HIAC ROYCO method USP <788>
The procedure is taken from the United States Pharmacopeia Method <788>, which gives criteria for injectable solutions.
Solutions are mixed by rapidly inverting 20x, allowing the solutions to degas, then analyzing on liquid particle counter.
Devices are extracted with PFW by flushing, rinsing, or orbital shaking. The extracts are degassed and tested on the liquid particle counter. There are currently no requirements for medical devices.
The particle counter withdraws not less than three aliquots, of not less than 5 mL. The liquid particle counter is capable of calculating the average cumulative counts, average differential counts, average cumulative counts per mL, and the average differential counts per mL. It will automatically omit the data from the first run.
The size ranges used for USP testing are ≥10-25 μm and ≥25 μm. The liquid particle counter is capable of sizing and counting particles ranging from 2.0 μm to 150 μm. It will count particles larger than 150 μm, but will not be able to size them. Sponsors may select any particle size range(s) between 2.0-150 μm appropriate for the test sample.
Acceptance Criteria:
Large volume parenterals (containers with >100 mL) for single-dose large-volume injection:
≥10 μm Not more than 25/mL
≥25 μm Not more than 3/mL
Small volume parenterals (100 mL or less per container):
≥10 μm Not more than 6,000/container
≥25 μm Not more than 600/container
Microscopic Method USP <788>
Some injections cannot be tested by light obscuration (Stage 1) for technical reasons. Documentation demonstrating that the light obscuration procedure is incapable of testing the injection or produces invalid results is required. Examples of such products are emulsions, colloids, liposomal preparations, and products that produce air or gas bubbles when drawn into the sensor, such as bicarbonate-buffered formulations. For these products, microscopic testing may be used exclusively.
The procedure is taken from the United States Pharmacopeia Method <788>, which gives criteria for injectable solutions.
Devices are extracted with particulate free water by flushing, rinsing, or orbital shaking. Solutions, wether device effluent or liquid sample are filtered through pre-cleaned 0.45mm pore membrane filters.
The membrane filters are placed into petri slides and placed onto a microscope, at 100X magnification, which contains a calibrated graticule in the eye piece. Using a fiber optic light at a 0-10E angle, the particulates on the surface of the membrane are counted according to their size as measured by the graticule micrometer.
Acceptance Criteria:
Large volume parenterals (containers with >100 mL) for single-dose large-volume injection:
≥ 10µ Not more than 12/mL
≥ 25µ Not more than 2/mL
Small volume parenterals (100 mL or less per container):
≥ 10µ Not more than 3,000/container
≥ 25µ Not more than 300/container
Sample Requirements
USP requirements state that, "the number of test specimens must be adequate to provide statistically sound assessment of whether a batch or other large group or units represented by the test specimens meets or exceeds the limits.
For small volume injections where the individual unit volume is 25 mL or more, fewer than 10 units may be tested, based on the definition of an appropriate sampling plan". If the volume is <25ml, pool 10 or more units.
For large volume injections, individual units are tested.
Nelson Experts:
- Ryan Lunceford 801-290-7795, 800-826-2088
