Biomarker testing and validation in the drug development process is an essential element and a crucial tool for the decision-making process.

1. Biomarker Validation and Testing: FDA
Evidentiary Framework Drafts Guidance
Biomarker testing and validation in the drug development process is an essential
element and a crucial tool for the decision-making process. However, initially, these
biomarkers were process-specific, and there was no prescribed regulatory process to
ascertain the broader use of these ​biomarker assays​ for programs apart from the
specific drug programs they were used for.
This guidance aims to cover the regulatory gap observed in terms of the extended use
of biomarkers beyond specific programs.
Components of the Evidentiary Framework

2. There are four main components involved in the evidentiary framework considered while
determining the evidence that is required for a biomarker to qualify:
● Details of the need for drug development
● Defining the context of use (COU)
● In the case of qualification, considering the possible benefits and risks
● Evidence to support qualification
Needs Assessment
This section illustrates why a biomarker is required for drug development. It describes
the following aspects:
● How the use of a biomarker promotes drug development
● Current landscape of drug development
● Use and limitations of biomarkers
● Use and development of other drug development tools
● Value addition with a novel biomarker
● Analysis of unmet medical needs Bangkok
● Other factors deemed necessary by FDA
Context of Use
The COU describes the precise use of a biomarker in drug development. There are two
components that come under it:
● Biomarker Category
● Monitoring biomarker

3. ● Diagnostic biomarker
● Prognostic biomarker
● Pharmacodynamic or response biomarker
● Predictive biomarker
● Safety biomarker
● Susceptibility/risk biomarker
● Proposed use in drug development
● Purpose of use
● Proposed stage in which it will be used
● Clinical trial population
● Therapeutic mechanism of action
Risk and Benefits Assessment
It is important to provide clear and objective descriptions are of the foreseeable risks
and benefits as well as risk alleviation strategies for the purpose of biomarker
qualification.
Following are the pointers that can help characterize the same:
● Value addition of the biomarker to ​drug development
● Tools available for the use of the biomarker
● Anticipated consequences in case the biomarker proves to be unsuitable
● Tools to mitigate risks in case the biomarker fails to perform as intended
Evidence to support qualification

4. The evidence necessary for qualification depends on the COU of a biomarker and its
benefits and risks. The strength of evidence required for qualification depends in two
factors:
● In case the benefits outweigh the risks or if there are acceptable
approaches for risk mitigation the required strength could be lower.
● In case the benefits outweigh the risks negligibly, the expected strength of
evidence should be higher.
Apart from these essential components, there are other considerations essential for
biomarker qualification such as Analytical Considerations and Statistical Considerations.
This information is very important in case you want to make use of existing biomarkers
for a different process. The available information helps reduce the time taken for
biomarker qualification.
This FDA guidance does not create a legal responsibility and provides
recommendations only. The full draft is available for review on the FDA website.