In fact, it appears that we can do a better job at discriminating small shifts in inhaler emitted aerosol APSD applying EDA, than we are doing now with cascade impactor stage groupings. The signal you are seeking to detect from stage grouping information is confounded by the fact that when API mass moves from one stage grouping to its neighbor in either direction, the movement is connected (as the mass on group A decreases, the same absolute change is seen as an increase in group B). The two metrics (sum and ratio of large and small particle mass comprising the impactor-sized mass) are less dependent of each other, thereby allowing greater discriminating ability for small shifts in APSD.
This outcome is potentially a win-win situation for all stakeholders. However, IPAC-RS (and I’m very supportive of their cautious approach) want to complete the task of validating both concepts, so that by the time that those involved with developing pharmacopeial monographs as well as the regulatory agencies, both fully understand the limitations as well as the effectiveness of each concept and have confidence that consumer and producer risk is going to be reduced as the result of their implementation.
I believe that we are currently in a “chicken-and-egg” situation with respect to implementing either or both AIM and EDA. The regulatory people have indicated they are willing to review submissions containing such data, but pharmaceutical companies in general are unwilling to test the water and be the first to seek approval under such circumstances.
This is where industry-wide groups, such as IPAC-RS and EPAG can assist with well-designed experiments making use of data from currently marketed products (blinded if necessary) that demonstrate effectiveness of these new approaches. So, at the end of the day, I think that when the water has been tested, so-to-speak, and the regulators accept such data, these concepts will move into widespread adoption.
However, at the core, these concepts have to be based on good science. I note that one of the mottos of IPAC-RS has been: “doing the right thing properly,” and that principle summarizes what they (and other groups such as EPAG) are trying to do with AIM and EDA concepts.
