The FDA released the Evidentiary Framework Drafts Guidance for biomarker validation and testing in December 2018.
Table of Contents
Purpose of the Evidentiary Framework
Biomarker testing and validation in the drug development process is an essential and crucial tool for the decision-making process. However, these biomarkers were initially 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
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
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
- The 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. Two components come under it:
- Biomarker Category
- Monitoring biomarker
- 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
- The therapeutic mechanism of action
Risk and Benefits Assessment
It is important to provide clear and objective descriptions 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
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 on 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.
Biomarker validation and testing is a crucial aspects of the drug development process. Biomarkers are measurable indicators of biological processes or responses to a drug, and they can be used to guide drug development and clinical trials. The FDA has recently released draft guidance on the evidentiary framework for biomarker validation and testing. This guidance provides a framework for developing and validating biomarkers that can be used in drug development and regulatory decision-making.
The FDA’s guidance emphasizes the need for rigorous validation of biomarkers to ensure their accuracy and reliability. The guidance outlines a process for biomarker qualification, which involves demonstrating that a biomarker is “fit for purpose” for a specific use. This process involves establishing analytical and clinical performance characteristics, demonstrating the biomarker’s clinical relevance, and establishing the biomarker’s reproducibility and stability.
The guidance also emphasizes the importance of a collaborative approach to biomarker development and validation, involving stakeholders from academia, industry, and regulatory agencies. The FDA encourages the use of public-private partnerships to facilitate biomarker development and validation.