Product Life Cycle Approach to Cascade Impaction Measurements - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 138

5. Establish acceptable limits and associated acceptance criteria for ISM , LPM and
SPM for the product with the same AIM-QC CI procedure that will be used later
in product quality control.
6. In designed experiments undertaken during product and method development,
use full resolution CI data to identify possible in-vitro failure modes of the sort
that have been identifi ed by looking at underlying physical causes and through
case study assessments, described in Chaps. 3 and 9 respectively. In other words,
undertake the following:

(a) Establish ways that an APSD could potentially change and determine asso-
ciated root causes. Such sources might include manufacturing trends, dimen-
sions of the device components, analytical instrumentation, and methods,
etc.
(b) Develop control strategies to mitigate identifi ed risks and potential failure
modes, and evaluate the ability of the chosen QC (EDA) metrics to detect
signifi cant changes. These insights should be helpful for setting product-
appropriate specifi cations for the EDA metrics, and later on, during com-
mercial production, for OOS investigations.

7. Use full-resolution CI based measurements as part of an in-depth investigation
of any OOS results as well as when any changes are introduced.

6.4.2.2 During the OIP Commercial Phase

1. Release the commercial product against the already established QC specifi ca-
tions based on LPM/SPM and ISM .
2. Continue stability testing of the product using the QC metrics and specifi cations
for LPM/SPM and ISM .
3. Bring in full-resolution CI measurements for an OOS investigation, i.e., to
explore the nature of a change that was detected by EDA, or any time that unex-
pected or unusual trends are observed (e.g., increase in variability). Note that
since the EDA metrics have the ability to detect changes quickly (due to the high
sensitivity of EDA to changes), they can serve as an effi cient trigger for such
action.

6.4.2.3 Post-approval and Device Changes

1. Use full-resolution APSD measurements and possibly AIM-QC and/or AIM-
pHRT systems as part of the change management process, for instance, when
substantial changes to the device, formulation, or manufacturing process are
considered or introduced. The option and choice of the AIM system would be
determined by the sponsor's risk assessment of the change.