Translating Biomarker Discovery into Companion Diagnostics through Validation and Regulatory Consideration - Genomic Biomarkers for Pharmaceutical Development - page 160

7.4 ASSAY DEVELOPMENT AND VALIDATION IN
DRUG DIAGNOSTIC CO-DEVELOPMENT

7.4.1 Overview
The process and evolution of an assay from its initial discovery to a form with potential
clinical applicability is difficult to generalize, as there are many technical aspects that may
dictate deviation from the standard process. The draft Drug Diagnostic Co-Development
Concept Paper of April 2005 [3] presents the following ideal assay development progression
( Fig. 7.2 ):
The timing, target selection, and validation presented here are very pre-clinically driven,
which is not likely feasible as validation and hypothesis generation require a significant
amount of patient data. However, with the diversity of biomarker analytes and potential
applications, there is a general evolution that most assays encounter, and therefore we will
approach the validation of an assay using the general evolution as a standard flow. For our
purposes, we will define the evolution of a companion diagnostic assay as falling into the
following categories:

1. Research Assay - the assay in its initial discovery stage
a. Platform and assay layout may not be ideal for clinical application
b. Assay components are often research use only
c. Assays have not been validated, often still in 'off the shelf' format
d. Applied to early pre-clinical and early-stage clinical development samples in
hypothesis generation and testing phase

Platform change

Market assay
validation

Analytical validation
diagnostic kit

Clinical validation diagnostic
kit; final platform

Prototype
design or
discovery

FDA filling/
approval &
launch

Clinical

Basic
research

Preclinical
development

Phase 1 Phase 2 hase 3

Target
selection

Indentification of
stratification

Clinical utility for
stratification

Label considerations
based on trial

Target
validation

Label considerations
based on marker status

Clinical validation
for

Analytical

Section

Pre-clinical

Section

Clinical

Section

Clinical

Section

FIGURE 7.2 This figure, taken from the Drug Diagnostic Co-Development Concept Paper, represents an ideal
timing scenario and level of validation for an assay as it progresses through development into a companion diag-
nostic in concert with therapeutic development time lines.