VALIDATION AND REGULATORY COMPLIANCE - Flow Cytometry in Drug Discovery and Development - page 234

PART III

VALIDATION AND REGULATORY
COMPLIANCE

V IRGINIA L ITWIN AND P HILIP M ARDER

Among the most challenging aspects of incorporating flow cytometry into the drug
development process is validating methods and instrumentation in accordance with
regulatory requirements and within the aggressive timelines associated with present
day drug development.
In drug discovery laboratories, flow cytometry screening methods are implemen-
ted in order to increase both throughput and selectivity (reviewed in Chapter 4). Given
that this stage of the drug development lifecycle is not regulated, methods, in general,
are not subjected to formal validation. Nevertheless, high quality, specificmethods are
essential in order to obtain successful outcomes.
Preclinical toxicology laboratories develop awide variety of flowmethods for the
purpose of both evaluating the safety of a new compound and assessing pharma-
codynamic effects in animal models (reviewed in Chapter 6). Safety assessment
laboratories are required to follow GLP regulations. However, the appropriate
regulatory requirements for nonsafety-related biomarker methods (e.g., pharma-
codynamic and exploratory biomarkers) are less clear. The primary reason for
including biomarkers in drug development and translational medicine programs is
to support a more informed level of decision making, thereby lowering the risk of
failure during clinical trials. To meet these objectives, methods must undergo
rigorous validation.
Both chapters in Part III examine the current regulations and guidelines. Chapter 12
focuses on the important considerations for assay development and validation, while
Chapter 13 discusses the benefits and objectives of instrument validation.