Product Life Cycle Approach to Cascade Impaction Measurements - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 140

Table 6.1 Uses of full resolution and AIM-based CI systems in OIP lifecycle management: the right impactor for the right purpose. (a) In product development ( From [ 11 ] —used
with permission ); (b) in commercial production ( Developed based on [ 11 ]); (c) in post-approval changes ( Developed based on [ 11 ]); (d) in add-on device development ( Developed
based on [ 11 ] )
Impactor type/lifecycle stage
(goal of APSD testing)

AIM-QC system with EDA metrics ( LPM/SPM
and ISM )

AIM-pHRT system ( CPM , FPM and
EPM ) Full resolution impactor

(a) Product development
( Goal: establish a target
APSD profi le for a safe
and effective product )

Defi ne APSD of product for the clinical batches
Identify failure modes for the APSD
Use full-resolution for OOS investigations and
justifi cation of changes
In order to prepare for routine use of AIM-QC, also
conduct studies to select optimal boundary
between LPM and SPM (e.g., near MMAD or to
maximize sensitivity to signifi cant failure modes)

Use as a screening tool in early development
In order to prepare for routine use of AIM-QC,
also conduct studies to:
1. Establish correlation of LPM and SPM to
full- resolution APSD
2. Determine appropriate specifi cations for
LPM/SPM and ISM (e.g., as 90 % confi dence
intervals on the LPM/SPM and ISM values
observed with a representative sample of
product)

Use as a screening tool in early
development
Conduct studies to establish correlation
of CPM , FPM , and EPM to
full-resolution APSD. This
information will provide support
for the subsequent use of the
selected AIM-pHRT confi guration
by establishing an IVIVR or IVIVC

(b) Commercial production
( Goal: confi rm that the
APSD of commercial
batches is the same as
that of clinical batches )

Use full-resolution APSD for OOS investigations Use AIM-QC for routine quality control

(release and stability)

(c) Post-approval changes
(e.g. supplier change)
( Goal: demonstrate
sameness of APSD )

If, for product registration, it has already been proven
that data from the AIM-QC were equivalent to
those from full resolution CI, simply demonstrate
that the results are still equivalent
Use full-resolution APSD for complete justifi cation
of change only if the regulatory agency requires
such a demonstration

Use AIM-QC as a rapid indicator of the same
quality

Once an IVIVR or IVIVC has been
established, use AIM-pHRT as a
rapid indicator that clinically
relevant fractions have not changed

(d) Add-on device
development
( Goal: minimize
oropharyngeal
deposition )

Provides baseline data to compare with OIP alone Use AIM-pHRT to optimize add-on

devices, ensuring clinically
equivalent performance to that of
OIP without add-on device