Biomedical Engineering Reference
In-Depth Information
with the confidence of its scientific integrity have been developed and are the topic of
this chapter.
Clinical Development
Drug Discovery
Preclinical
Early
phase I, II
Late
phase III, IV
Safety
Clinical immunogenicity
Biomarker implementation
Target engagement
Compound screening
Mechanism of action
Biomarker discovery
Toxicology
Immunogenicity
Biomarker development
High-quality assay
GLP
GLP-like
Fit-for-Purpose
GCLP
Non-GLP
FDA
CLIA
FIGURE 12.1
Drug development stages and regulatory oversight.
12.2 REGULATORY COMPLIANCE
The versatility of flow cytometry platform begs for its inclusion in campaigns to
identify new drug targets or to discover potential biomarkers. There is an additional
appeal, as this same platform can effectively support downstream efforts in the
mechanism of action and biochemical coverage studies. While no specific regulatory
guidelines are called out in this early stage, missteps cause a high impact because of
their 1:1 influence on the downstream path. Although not absolute, the principles of
validation are therefore regarded by many to represent an insurance policy against
errant data sets derived from suboptimal specimen processing and data collection.
Indeed, those with experience in the field frequently find themselves raising the
warning flag that a flow cytometer will generate data regardless of the quality of
the specimen. Application of a limited set of validation exercises - even in this early
stage - will illuminate problems before they impact programs.
Regulatory practices for preclinical studies, on the other hand, are unambiguous.
For toxicology studies designed to characterize lead compoundswith data sets eligible
for regulatory review, the need to implement Good Laboratory Practices (GLPs) is
nonnegotiable. Although some performflowcytometry as a “non-GLP component of a
GLP study,” most regard this as an inadvisable practice. In this latter setting, a better
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