Conclusions - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 406

data reduction. This chapter continues the theoretical assessment of
the EDA concept, examining the comparison with the stage grouping
approach as recommended by the FDA. Three different assessment
APSD data techniques are presented and sample data analyzed; these
are measurement system analysis (MSA), operating characteristic
curves (OCCs), and principal component analysis (PCA). In the case
of both MSA- and OCC-based techniques, an IPAC-RS blinded data-
base containing several thousand individual CI-generated APSDs
derived from eight different types of marketed OIPs (a collection of
MDI and DPI products) has been used to provide examples that dem-
onstrate the superiority of EDA. Likewise, a smaller, but still signifi -
cant, database comprising 1,738 NGI APSDs has been used with
PCA, again confi rming the advantage of EDA.
Chapter 9 : The underlying reasons why EDA is able to detect changes to APSDs
based on shifts in MMAD and/or AUC are explored, including a theo-
retical assessment to establish plausible scenarios in which this con-
cept might fail. Findings from failure modes and effects analyses
(FMEA) are presented. These analyses have identifi ed the relation-
ships for the risk dependence of the CI data analysis method for detec-
tion of important APSD shifts associated with different potential
causes during the various stages in the production of both MDI and
DPI forms of OIP. This chapter concludes by examining the relative
performance between EDA- and FDA-type stage groupings with two
case studies, both involving product previously marketed or currently
available in the USA. In both instances, EDA was found to possess
greater potential for discriminating APSD change in a robust manner.
Chapter 10 : The focus in this chapter is the establishment of strengths and limita-
tions of all the various AIM-based CI techniques that have been devel-
oped by many different and independent contributing groups of
researchers on this topic since 2007. Every class of OIP has at some
time been evaluated with one or more AIM-based apparatus, mostly
with successful outcomes compared with common APSD-derived
metrics determined by a reference full-resolution CI method. However,
there are several practical precautions that need to be considered, in
particular the following:
1. Mitigation of particle bounce and re-entrainment, a phenomenon
that can be more evident with AIM-based apparatuses
2. The provision of comparable conditions for the evaporation of low-
volatile species (i.e., ethanol) that are associated with certain OIPs
in the AIM-based apparatus as exist within the full-resolution CI
3. The maintenance of comparable dead space within the abbreviated
system to that in the full-resolution CI so that the fl ow rate-time
curves for DPI testing are also similar