Unless otherwise directed in the individual monograph, the drug content of the minimum delivered doses (minimum number of sprays per nostril as described on the label, or instructions for use) collected at the beginning of unit life (after priming as described on the label, or instructions for use) and at the label claim number of metered sprays, from each of 10 separate containers, must meet the following acceptance criteria: not more than 2 of the 20 doses are outside the range of 80% to 120% of label claim, and none are outside the range of 75% to 125% of label claim, while the mean for each of the beginning and end doses falls within the range of 85% to 115% of label claim. If 36 doses of the 20 doses collected are outside of 80% to 120% of the label claim, but none are outside of 75% to 125% of label claim, and the means for each of the beginning and end doses fall within 85% to 115% of label claim, select 20 additional containers for second-tier testing. For second-tier testing, the requirements are met if not more than 6 of the 60 doses collected are outside the range of 80% to 120% of label claim, none are outside the range of 75% to 125% of label claim, and the means for each of the beginning and end doses fall within the range of 85% to 115% of label claim.
SAMPLING FOR DELIVERED-DOSE UNIFORMITY OF METERED-DOSE NASAL SPRAYS
General Sampling Procedure
To ensure reproducible in-vitro dose collection, it is recommended that a mechanical means of actuating the pump assembly be employed to deliver doses for collection. The mechanical actuation procedure should have adequate controls for the critical mechanical actuation parameters (e.g., actuation force, actuation speed, stroke length, rest periods, etc.). The test must be performed on units that have been primed according to the patient-use instructions. The test unit should be actuated in a vertical or near vertical, valve-up, position. The two doses collected at the beginning and end of the container life should be the dose immediately following priming and the dose corresponding to the last label claim number of doses from the container.
For suspension products, the delivered dose should be delivered into a suitable container (e.g., scintillation vial) in which quantitative transfer from the container under test can be accomplished. A validated analytical method is employed to determine the amount of drug in each delivered dose, and data are reported as a percent of label claim. For solution products, the delivered dose can be determined gravimetrically from the weight of the delivered dose, and the concentration and density of the fill solution of the product under test.