Biomedical Engineering Reference
In-Depth Information
9.1
Introduction
EDA, being a new concept, will require a period of time to allow for confi dence
building, based on the experience of individual organizations involved with the OIP
life cycle. The acceptance by regulators that this approach is valid, whether
approached simply using one of the existing compendial full-resolution CIs or aug-
mented by measurements obtained with an appropriately validated AIM-based
apparatus, will require a body of validated evidence in which all possible scenarios
that might result in failure have been assessed. This chapter begins the process of
acceptance by looking at the EDA concept from two different viewpoints:
1. Theoretical considerations, probing the EDA approach beyond conditions that
are likely in association with currently marketed OIPs, by considering hypotheti-
cal scenarios in which this methodology might fail to have suffi cient discrimi-
nating power to detect APSD changes that may be important in terms of product
performance;
2. Practical considerations, involving an examination of several case studies
involving OIP products whose brand names are blinded, that are either in pro-
duction or in development.
9.2
How EDA Detects APSD Changes
Before looking at hypothetical scenarios in which EDA might fail (Sect. 9.3 ), a
failure modes analysis for EDA (Sect. 9.4 ), and actual case studies (Sect. 9.5 ), it is
worthwhile reviewing again in brief how EDA works to detect changes in APSDs of
OIP-generated aerosols.
One of the two EDA metrics, ISM , represents the ability to determine the area
under the curve of the APSD when presented in differential mass-weighted form.
The other EDA metric, the ratio LPM / SPM , enables shifts in the measure of central
tendency (i.e., either the mass-weighted mean diameter or more usually and
conveniently the MMAD value) to be observed with respect to the size axis scaled
as aerodynamic diameter. Taken together, the combination of these metrics enables
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