Biomedical Engineering Reference
In-Depth Information
12
REGULATORY COMPLIANCE AND
METHOD VALIDATION
C ARLA G. H ILL ,D IANNA Y. W U ,J OHN F ERBAS ,V IRGINIA L ITWIN , AND
M ANJULA P. R EDDY
12.1
INTRODUCTION
Philosophies surrounding method validation for flow cytometric assays conducted in
the biopharmaceutical space are varied. The extent of method validation appropriate
for a particular assay is a function of intended use and the stage of the drug
development where the assay will be utilized. Likewise, determining which regu-
latory guidelines are applicable to a given flow cytometric method along the
continuum of drug discovery and development adds to challenges to the validation
process (because different regulatory guidelines apply in the lifecycle of potential
clinical candidates). The portfolio of regulatory requirements that may be exerted in
the discovery and development work stream is illustrated in Figure 12.1.
While considering the content for this chapter, the need to convey and discuss the
gray spaces and adjustments in regulatory oversight as a function of the development
and commercialization process was quite clear; the vast majority of cytometerists in
industry do find themselves holding an overarching role that spans across develop-
ment stages (which can be less frequent for other types of assays). While we all aspire
to execute studies in full compliance of regulatory specifications, we also realize that
guidance was originally written for toxicology and safety pharmacology methods,
such as mass spectrometry to detect drug metabolites. So, although issues including
the lack of true accuracy standards and sample stability of, for example, whole blood
can be disconcerting - and perhaps even incongruous with method validation as
applied to other assay types - effective approaches to minimize risk and generate data
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