Hello and welcome. I’m Dr. Chris Leptak, with the Office of New Drugs and FDA’s Center for Drug Evaluation and Research, and I’m also the OND Co-Director for the Biomarker Qualification Program. In this module, we’ll briefly introduce several sources of biomarker information that can impact drug development and potentially facilitate a drug approval.
When deciding how to use biomarkers in drug development programs, there are three primary sources for biomarker evidence that can be considered by FDA to inform regulatory decisions. Those three pathways are scientific community consensus, a specific drug development and approval process, and CDER’s Biomarker Qualification Program.
Data that informs scientific community consensus is primarily gleaned from published scientific studies that can lead to improved scientific understanding of a disease or a biologic process. This information undergoes scrutiny by multiple stakeholder groups and is a good source for hypothesis generation for the role of a given biomarker.
A challenge, however, is that this information accrues over time, is many times not gathered with a common intent, and is shared in such a way that comparing information across publications is difficult. Using this source of information alone can be difficult to determine the clinical utility of a biomarker from disparate scientific research efforts.
The specific drug approval process involves the use of a biomarker as part of the development of a specific investigational new drug or a biologic. Regulatory acceptance of biomarkers through this development process is intended for biomarkers that will be used for a specific candidate drug.
The information for a given drug program can be used by other drug companies if the biomarker ultimately proves to have more generalized applicability. An example of a biomarker accepted through this pathway is the EGFR status, which is a predictive biomarker for EGFR-targeted therapy in lung cancer.
CDER’s Biomarker Qualification Program can establish a biomarker’s value for a particular context of use in drug development and for regulatory review. A biomarker, once qualified for a particular context of use, will be publicly available and can be applied to any drug development program for which the context of use is appropriate and without the need to re-review the information. An example of a biomarker accepted through qualification is total kidney volume, which is a prognostic biomarker for polycystic kidney disease.
Each pathway has strengths and limitations that sponsors should take into account, given the particular reasons and circumstances for using a biomarker in drug development, including what resources are available, the type of biomarker, and opportunities for collaboration with others.
Emerging regulatory experience with these various pathways and data sources suggests that some types of biomarkers may be more appropriate for one pathway over another; however, this choice is not always clear, particularly in early development stages. More clarity is needed as to when regulatory acceptance of biomarkers would follow one path or another.
Ultimately, since biomarker development is a voluntary activity, the developer retains the choice of which pathway to pursue. Whether the drug developer is a company or a consortium, and regardless of which pathway is selected for applying biomarkers in a drug development program, consulting the FDA is a critical step to achieve success.
To learn more, please visit CDER’s website.