Biomarker Qualification: FDA Explains Process and Opportunities for Engagement

In a set of newly released presentations, officials from the US Food and Drug Administration (FDA) explain changes to the agency's biomarker qualification program and detail early opportunities for biomarker developers to engage with FDA.

"A qualified biomarker can be used in multiple drug development programs without the need for [the Center for Drug Evaluation and Research] CDER to reconfirm the suitability of the biomarker's qualified context of use," said Marianne Noone, a regulatory project manager at CDER's Office of Translational Sciences.

To date, FDA says it has qualified six biomarkers and received 20 submissions to the program.

FDA's biomarker qualification program was recently updated to meet requirements set by the 21st Century Cures Act, which calls on FDA to issue guidance detailing a formal multi-stage process for biomarker qualification with set time frames for the review of letters, qualification plans and full qualification packages.

Under the process, biomarker qualification begins when a developer submits a letter of intent to FDA detailing information about the biomarker, its context of use, how it will be measured and the need it is meant to address. Then, Noone said, FDA will accept or deny the submission based on whether the biomarker "has the potential to address an unmet medical need in drug development."

After the letter of intent is accepted, the developer must then submit a qualification plan to FDA that details the proposed plan to generate evidence in support of the biomarker for the proposed context of use.

"The [qualification plan] should include detailed information on the suitability of the biomarker measurement method, as well as summary data on completed studies and study designs for planned future studies to confirm the usefulness of the biomarker in drug development," Noone said.

Once approved, the developer will then be instructed to complete and submit their full qualification package, which Noone said should include "all accumulated data to support the biomarker." FDA will then issue a determination of whether the biomarker is suitable in the same context of use in any drug development program.

Noone also notes that biomarker developers may enter the process at any of the three stages based on the level of evidence they have to support their biomarker.

Early Engagement With FDA

In a separate presentation, Kylie Haskins, a scientific lead at the Office of Translational Sciences, said there are two main opportunities for biomarker developers to interact with FDA before moving to the formal biomarker qualification program.

The first is by requesting a Critical Path Innovation Meeting (CIPM), which offers an early opportunity for developers to meet with the agency to discuss the potential of the proposed biomarker before it's ready for submission to the biomarker qualification program and may cover scientific, medical and regulatory issues.

Beyond that, the next way developers can interact with FDA is by requesting a letter of support for their biomarker. So far, FDA has issued letters of support for 14 biomarkers, the most recent of which is for a biomarker aimed at identifying patients in clinical trials for mild traumatic brain injury who are more likely to develop a long-term disability.

To obtain a letter of support, developers should provide FDA with a description of the biomarker and how it will be used, measured and assessed, as well as a rationale for how the biomarker is useful.

According to Haskins, letters of support do not connote qualification or offer an endorsement of specific biomarker tests, but can be useful in demonstrating FDA's support for further development of the biomarker.

Opportunities to Engage With the FDA About Qualification During Biomarker Development

The Biomarker Qualification Process: A Roadmap for Requestors

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