The AIM and EDA Concepts: Why They Are Needed and How They Fit Together - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 122

changes relating to OIP APSD as a function of elapsed time relative to the properties
measured at stability start is the main objective, a well-designed stability study
involving rapid AIM-EDA-based assessments offers the potential as a fi t-for-pur-
pose methodology in this application. Finally, the ability to make measurements in
a given time that are more useful in the batch disposition decision-making process
than the determination of equivalent metrics from fewer full-resolution CI measure-
ments could be benefi cial in the context of defi ning design and control spaces in the
quality-by-design paradigm [ 21 , 22 ] that is currently being encouraged by regula-
tory agencies [ 23 ].
As a signifi cant by-product, AIM-based methods, by virtue of their relative sim-
plicity, have the potential to improve product batch disposition decision-making by
allowing more samples from the lot (coverage) to be evaluated in a given time
period and, importantly, by improving the signal-to-noise ratio, thanks to EDA met-
rics [ 24 ]. AIM-based methods also overcome the problem that for products with
narrow particle-size distributions (small GSD ), several stages of full-resolution CIs
capture little or no active pharmaceutical ingredient (API), reducing the overall pre-
cision of the method [ 25 ]. Furthermore, Tougas et al. observed that there is the
potential that accurate and precise measurements may be made possible with the
clinical dose (typically 1-2 actuations of the inhaler), rather than after several actua-
tions, as is typical with full-resolution systems to acquire suffi cient drug deposits on
stages collecting particles at the periphery of the APSD to permit acceptably accu-
rate and precise assay of the API collected at these locations [ 18 ]. However, the
variability will be altered when the dose number changes, so this must be handled
with care.
In summary, moving away from full-resolution CI measurements and associated
stage groupings towards product-specifi c EDA metrics for routine quality control,
Tougas et al. observed that the latter approach has the following advantages [ 24 ]:
1. Easier operation of an AIM system.
2. Similar sensitivity to APSD changes compared to current methods.
3. Fewer false-positive results.
4. More sensitive measures are available for detecting shifts in position and ampli-
tude (area under the curve) of an APSD, leading to better diagnostic capability
and predictability.
5. Fewer inhaler actuations per CI measurement are possible due to the acquisition
of suffi cient mass in fewer subfractions, which has the potential to reduce errors,
experimental uncertainty, and makes it potentially possible to test APSD with the
prescribed dose, at least for moderate- and low-potency formulations.
6. Less time is required per CI measurement, making it possible to design suffi -
ciently powerful experiments for assessing product and CI method variability on
a sound statistical basis.
These advantages, together with others that have become apparent since the orig-
inal assessment, are summarized in Table 5.1 . However, since the article by Tougas
et al. was published, it has become evident that many pharmaceutical companies are
also examining the potential for AIM-based measurements for rapid screening of