Q: Do the FP monographs call for any unusual testing methods?
A: According to the FP monographs, the 28.3 L/min version of the ACI (Stages 0 to 7, plus filter stage) should be used for both powder and aerosol methods despite the fact that the powder method specifies testing at 60 L/min. This requirement probably derives from the fact that the original method predates the development of the 60 L/min and 90 L/min modified versions of the ACI called for in the current general USP chapter.
The FP inhalation powder monograph also requires that DDU measurements be conducted for a duration consistent with the withdrawal of a 2 L volume of air, which is generally considered to be representative of the typical lung capacity of an asthma or COPD patient. For APSD measurements, the duration called for is the equivalent of the withdrawal of 3 L, likely due to the need to achieve adequate volume changes in the ACI.
This sort of accurately-timed flow control can be achieved using flow control set-ups specified in USP <601> for testing DPIs with a fast-acting solenoid valve. A breath actuation controller is also suitable since sonic flow conditions are not specified in this particular method.
ACI setup for FP testing
Q: Do product-specific guidances for other inhaled drugs require special test equipment?
A: The FDA has issued product-specific draft guidance for a number of active ingredients including albuterol (salbutamol), budesonide, and FP/salmeterol that are used globally for the treatment of asthma and COPD and are consequently routine targets for generic development.
Where these guidances specify equipment, it is generally identical to that described in the general chapters of the pharmacopoeias for OIP testing, specifically, the existing dose uniformity sampling apparatus (DUSA) designs, the ACI and/or Next Generation Impactors (NGI). The ACI and NGI are currently the mainstays of cascade impactor testing and with a good number of stages (8 and 7 respectively) they give good APSD measurement resolution.
It is important to note that the USP is an independent organization and while it may, in many cases, reflect US regulatory thinking, it is not obliged to do so. Furthermore, not all relevant pharmacopoeias are harmonized with the European Pharmacopoeia (Ph. Eur.) and USP. Indeed the USP and Ph. Eur. are not fully harmonized themselves with respect to orally inhaled and nasal drug products.
