INSTRUMENT VALIDATION FOR REGULATED STUDIES - Flow Cytometry in Drug Discovery and Development - page 259

13

INSTRUMENT VALIDATION FOR
REGULATED STUDIES

J OHN F ERBAS AND M ICHELLE J. S CHROEDER

13.1 INTRODUCTION

When flowcytometers are used in preclinical and clinical studies, a variety of assurance
levels can be exercised to prove that the data are reliable, reproducible, andwith defined
precision and relative accuracy. The variety of levels of regulatory oversight can be
categorized as Good Laboratory Practices (GLPs) or Good Clinical Practices (GCPs)
when investigational agents are administered in the setting of a preclinical or clinical
study, and as CLIA (Clinical Laboratory Improvement Amendments) derived
processes when the data have diagnostic value. Although overlap in principle exists
between CLIA, GLP, and GCP efforts, laboratories that operate without a fundamental
understanding of the similarities and differences of the oversight processes could
inadvertently place studies at risk. It is often the case that a CLIA-certified flow
cytometry laboratory prepares and analyzes specimens from persons who received an
investigational agent, but it is inappropriate to assume that CLIA regulatory practices
provide appropriate coverage for the GLPs or GCPs (and visa versa). Moreover, the
need to understand and comply with 21CFR Part 11 requirements [1] is mandated for
GLP studies and may be applied with discretion to GCP investigations (see below), but
CLIA processes are not governed by these requirements.
Practices common to one approach are not interchangeable with another. For
example, specific documentation of processes defined by IQ (installation qualifica-
tion), OQ (operation qualification), PQ (performance qualification), and UAT (user
acceptance testing) do not reside in the CLIAnomenclature, but are very important for
GLP efforts. For those involved in biomarker investigations, where “intended use”