Good Cascade Impactor Practices - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 80

Chapter 4
Good Cascade Impactor Practices

Jolyon P. Mitchell

Abstract The CI-based methods for measuring the APSD properties of OIP-
produced aerosols are complex, exacting, and laborious to undertake. Yet they are
the only accepted methods by regulatory agencies worldwide for determining par-
ticle aerodynamic size-related properties. In 2003, a group within the Product
Quality Research Institute (PQRI), a body set up by pharmaceutical industry, the
FDA, and academia to explore complex scientific and regulatory problems, devel-
oped a guide to good cascade impactor practices (GCIP). This chapter contains a
review of the essence of their work, augmented by developments that have taken
place since the original article was published.

4.1 Intrinsic Variability Associated with CI Methodologies

The multistage CI is well known to be both a complex and labor-intensive apparatus,
whatever compendial variant is used in OIP aerosol aerodynamic particle size
assessment. In discussions within the European Pharmaceutical Aerosol Group
(EPAG) following the development of the NGI, the comment was made on several
occasions that a technician, well trained in the “art” of cascade impaction is highly
sought after and difficult to replace. More seriously, the difficulty in replicating CI
measurements undertaken in the same laboratory or when transferring a method to
another laboratory is a significant hindrance to both OIP development and quality
control processes. In 2004, Nichols reported a survey of members of the EPAG in con-
nection with what they viewed as contributors to variability in CI-based measure-
ments [ 1 ]. These estimates of causes of measurement variability that were based on
individual experience rather than a formal work study and statistical analysis