The Regulatory and Compendial Pathways to Acceptance for AIM and EDA Concepts - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 354

Currently, the subsequent investigation can be diffi cult when using a full-
resolution CI and an out-of-specifi cation result is obtained [ 13 ], as there are many
sources of potential error. However, if an AIM approach is used as a front line batch
release method, then an important additional consideration is the availability of
using the full-resolution CI as the primary diagnostic aid in the event of an out-of-
specifi cation AIM-EDA determination. This consideration is in addition to the
application of a logical fault-tree approach for anomalous CI measurements, similar
to that described for CI mass balance determination and discussed in Chap. 4 [ 14 ].
However, care would be needed in the setting of specifi cations to avoid different
requirements pertaining to metrics determined by abbreviated or full-resolution CI
systems, unless such a situation was unavoidable, but a demonstrable benefi t was
nonetheless available using an AIM-based approach.

11.2 Pharmacopeia Requirements

An important focus of the pharmacopeias is the provision of authoritative mono-
graphs for the assessment of drug product quality. European Union directives
2001/82/EC, 2001/83/EC, and 2003/63/EC (amended), on medicines for human and
for veterinary use, maintain the mandatory character of European Pharmacopoeia
(Ph. Eur.) specifi cations on medicines for marketing authorization applications for
OIPs. In contrast, the US Pharmacopeial (USP) Convention is a nongovernmental
body responsible for the USP-NF. However, the FDA, although working closely
with the USP, is not obliged to use USP specifi cations or test methodologies in
developing or application of the FDA guidance documents.
Both European and US pharmacopeial monographs associated with the measure-
ment of particle size from OIPs describe a range of full-resolution CI apparatuses,
with the exception of Apparatus A of the Ph. Eur., which is the Twin (Glass)
Impinger (TI) (Table 11.1 ). This apparatus could possibly be used as an AIM-based

Table 11.1 Current compendial apparatuses for the assessment of aerosols from OIPs
Apparatus US Pharmacopeia European Pharmacopoeia

Glass “Twin Impinger” (TI) Not used Apparatus A for pMDIs,

DPIs, and nebulizers

Andersen 8-stage without
pre-separator (ACI)

Apparatus 1 for pMDIs Apparatus D for pMDIs

Marple Miller Model 160 (MMI) Apparatus 2 for DPIs Not used

Andersen 8-stage with
pre-separator (ACI)

Apparatus 3 for DPIs Apparatus D for DPIs

Multi-stage liquid impinger (MSLI) Apparatus 4 for DPIs Apparatus C for pMDIs

and DPIs

Next generation pharmaceutical
impactor (NGI)

Apparatus 5 for DPIs
Apparatus 6 for pMDIs

Apparatus E for pMDIs
and DPIs