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 260

Fig. 9.11 Control strategy breakdown by process in OIP design and manufacture ( From [ 9 ] —used
with permission )
They appreciated that conducting a classical risk assessment of each factor in a way
that was generic to all products in a particular class of OIP was not a practical
proposition. They assumed that all the causal factors identifi ed had the potential to
impact the aerosol APSD. However, they recognized that it was diffi cult to general-
ize the severity of the consequences, since they were likely to be unique to the
magnitude of the APSD shift related to each potential causative factor.
Glaab et al . also recognized that it would be a challenging prospect to quantify
the effect on product performance with particular patient groups or even individual
patients. In light of these limitations, the risk evaluation was concluded by address-
ing the following questions:
1. How dependent on cascade impaction is the detection of the APSD change?
2. How likely will this change lead to catastrophic product failure?
They responded to each of these questions in general terms, based upon indi-
vidual experience of the authors. In a further simplifi cation of the assessment, they
evaluated the likelihood of a catastrophic product failure resulting from a given fac-
tor as either conceivable or inconceivable, with no intermediate conditions. In a
similar way, they assessed factors as either likely to be detected by tests other than
CI or likely to only be detected by a CI-based test.
Given this approach, it was possible to position the factors relative to quadrants
defi ned by two orthogonal axes representing the potential for catastrophic product
failure in relation to the dependence on the CI method for its detection in terms of a
discernable APSD shift (Fig. 9.12 ).