The Regulatory and Compendial Pathways to Acceptance for AIM and EDA Concepts - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 355

system, as discussed in Chap. 10 , with some refi nements to make its cutoff size
between coarse and fi ne fractions more fl exible at its operating fl ow rate of 60 L/min
[ 15 ]. However, its status has been under review in recent years as the result of the
exclusive requirement for higher resolution CI measurements in product license
submissions, e.g., NDAs in the USA or MAAs in the EU [ 16 ]. The EMA guideline
covering the pharmaceutical quality of inhalation and nasal products allows the use
of alternative impactors if justifi ed and validated [ 9 ]. An alternative strategy, also
presented in Chap. 10 , might therefore be to develop a reduced (say 2- or 3-stage)
version of the MSLI (Apparatus 4 of the Ph. Eur. and C of the USP). However, such
a strategy will require someone to undertake the necessary development work and
associated business risk that the reduced MSLI may not get adopted as an AIM
apparatus.

11.3 Gaining Acceptance for AIM and EDA

11.3.1 Framework for Acceptance

AIM apparatuses can provide aerodynamic particle size data with the following
properties:

(a) A measure of API mass that is equivalent to the “fi ne”-particle dose “(mass),”
as defi ned at a cut point of 5

m aerodynamic diameter. This size limit would
be required within the framework of the current Ph. Eur. monograph 2.9.18. The
“fi ne”-particle “dose” using a full CI is currently derived by interpolation using
the cumulative under size log-normal plot. If the AIM apparatus did not have a
cut point precisely at 5

μ

m, then an alternate interpolation approach may be
possible or justifi cation that the AIM data provides equivalent APSD at its near
5

μ

m cut point when compared to the current Ph. Eur. approach for full-
resolution CI data interpolation.
(b) A cut point close to or precisely at the MMAD of the OIP-emitted aerosol. If
such data were to become accepted in a quality control environment, then the
EDA approach would be pertinent to defi ne the size-pertinent metrics (i.e.,
LPM/SPM ratio and ISM ) and set subsequent specifi cations (Chaps. 5 and 6 ) .
This option is incompatible with the current EMA requirement to report fi ne-
particle dose <5

μ

m aerodynamic diameter [ 9 ].
(c) Cut-point sizes other than 5

μ

m, based on
the cut-point size of stage 2 of the ACI when operated at 28.3 L/min). Acceptance
of alternatives to 5

μ m aerodynamic diameter (i.e., 4.7 μ

m to distinguish fi ne from coarse mass fractions of the dose
would be more aligned with the current USP requirements.

μ

Given these considerations, it is therefore imperative that a clear understanding
of the purpose(s) for which AIM is being used, and the implications that these
purpose(s) have on the use of the CI-generated data, become well understood