Product Life Cycle Approach to Cascade Impaction Measurements - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 131

over the product life cycle, and how the entire body of APSD data is interlinked to
enable those transitions (e.g., by establishing correlations or by establishing typical
profi le parameters), thereby enhancing product knowledge, appropriate control, and
comparisons between innovator and generic OIPs.

6.1 Choosing an AIM System Suitable for Purpose

The reasons for making APSD measurements vary throughout the product life cycle, as
has been described in detail in Chap. 5 , and a summary of the goals and recommended
CI system for different life cycle stages was presented in Table 5.2 . These consider-
ations include discovery and screening of early candidate formulations, followed by
development and characterization of lead candidates, introduction of the technique for
QC in commercial production, and fi nally, demonstration of in vitro equivalence for
modifi ed versions of the original OIP or follow-on (generic) copies of the product. At
each of the life cycle stages, a suitable APSD measurement system, together with data
analysis procedure, must be employed, while appropriate continuity should be built in,
to allow the justifi cation of, and to enable switches between, different systems.
The present chapter addresses the considerations for choosing an AIM-based
approach, recognizing at the outset that such a system would be used to augment
and not replace the need for some APSD measurements by full-resolution CI. There
are many different AIM-based confi gurations that are currently available, some of
which are available “off the shelf,” such as the FSA (Copley Instruments Ltd,
Nottingham, UK), FPD (Westech Instruments Services, Upper Stondon, Beds.,
UK), and the FSI (MSP Corp., St Paul, MN, USA). Other systems must be con-
structed from existing components of the full-resolution system, as can be done
with the ACI, or by relocating stages within the existing fl ow path, as is possible
with the NGI. Even when an off-the-shelf apparatus is selected, there are still further
considerations to be made before use, such as the selection of the most appropriate
cut-point size(s) for the stage(s) in the reduced system. These, and other related
decisions, are the topic of the remainder of the chapter.

6.2 Selecting Size Ranges for an AIM-Based Apparatus

When selecting an AIM apparatus, OIP-appropriate size ranges should be chosen,
based on the full-resolution APSD data that are already available for the product,
and to the extent possible, be directed by the clinical importance of specifi c size
ranges of that product [ 1 ]. If an AIM-based system is being considered for candi-
date formulation screening in early stage OIP development, it may be necessary to
experiment with more than one confi guration, depending upon the expected shifts
in APSD that may be encountered in such preliminary work.
For an AIM-QC system, where the goal is to maximize sensitivity to any APSD
change (increased area under the curve, shift in MMAD , and/or change in shape of
the APSD profi le), the boundary between LPM and SPM should be chosen as near