The Regulatory and Compendial Pathways to Acceptance for AIM and EDA Concepts - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 356

and accepted as early as possible by stakeholders. At least one pharmaceutical
manufacturer has expressed the desire (in Europe) for there to be product-specifi c
specifi cations with respect to APSD metrics, when justifi ed and approved, in
particular more fl exibility in the future with respect to the 5

μ m upper size limit

for fi ne-particle mass.
There are some key requirements that must be satisfi ed for AIM (or EDA) to
become an accepted approach, irrespective of the reasons for adopting AIM that
have been outlined in previous chapters. These requirements extend beyond the
ordinary “method validation” requirements that would be an integral part of demon-
strating the method suitability, as it is fundamental that AIM (or EDA) is verifi ed to
be “fi t for purpose.” Without such evidence, it is unlikely that any regulatory agency
or compendial committee would accept these new approaches, regardless of the
merits that have been already explained in previous chapters.
In this context, it is worth noting that “fi t for purpose” does not necessarily mean
that AIM (or EDA) would be deemed applicable to every inhaled dosage form or
device, either now or in the future. For example, it may not be appropriate for for-
mulations and/or devices that produce a very narrow APSD ( GSD 1.2 equivalent

to near monodisperse). Hence, the applicability of either the AIM concept or an
actual AIM apparatus used will have some relationship with the specifi cation for the
APSD that is specifi ed for the product in its target product profi le (TPP).
Potential strategies that will lead to demonstration of “fi tness for purpose” for
AIM and EDA are discussed in Sects. 11.3.2 and 11.4 , respectively. Following dem-
onstration of the “fi tness for purpose,” a series of activities, including publication of
detailed methodology and data, comparative data analysis using various current
and AIM approaches, peer-reviewed literature and conference presentations, and
pharmacopeia stimuli to revise and draft monographs, will all result in an evidence-
based, industry and regulatory agency-challenged approach. Under such circum-
stances, new robust AIM methods can eventually become approved pharmacopeial
methods.

≤

11.3.2 Strategy for AIM “Fit for Purpose”

The key parts of the strategy to show AIM “fi t for purpose” are illustrated in
Fig. 11.1 .

(a) Calibration data for the apparatus confi guration:
It is reasonable to expect that either calibration data with full traceability to the
international length standard or at least justifi cation for the claimed cut-point
sizes for that confi guration would be provided for each particular AIM appara-
tus confi guration proposed for adoption. These data are likely to be provided
either by the apparatus manufacturer or less probably by a pharmaceutical com-
pany, given the complexity of the process. A highly desirable approach is the
so-called archival calibration, in which a reference CI is calibrated, having