Verification of the EDA Concept Through an Assessment of Theoretical Failure Modes, Failure Mode Analysis, and Case Studies with Real Data - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 261

Fig. 9.12 Mapping of relative severity of factors that could infl uence the APSD of an OIP
( From [ 9 ] —used with permission )
Once this framework was in place, Glaab et al . [ 9 ] proceeded to locate the factors
associated with DPI (Fig. 9.13 ) and MDI products (Fig. 9.14 ). Items assigned to
quadrant I represent the highest risk given that they are dependent upon CI for
detection and could conceivably lead to catastrophic product failure. The risk
associated with items placed in other quadrants was believed to be mitigated either
by other means of detection method (quadrant II), by the inconceivability of
resulting in catastrophic product failure (quadrant IV), or by both considerations
(quadrant III).
They concluded that the likelihood that the factors identifi ed above infl uencing
the APSD of an aerosol emitted by an OIP for product release testing depends not
only on the individual product but also on its developmental status towards com-
mercialization. At late stage development, the majority of the factors identifi ed in
this risk assessment should be controlled within well-defi ned process parameters,
supported by rigorous implementation of quality assurance procedures and compli-
ance within quality control parameters.
However, there are some APSD changes which are detectable only by cascade
impaction, primarily because this method, although cumbersome and exacting in
terms of analyst performance, directly determines mass of API(s) present in terms
of aerodynamic particle size.
This exercise forms a useful complement to the theoretical analysis of aerosol
APSD changes presented earlier in the chapter, by providing a framework whereby
it is possible to assess in some detail the risk of EDA failure when developing
APSD-assessment methodology for a given OIP.