Background on biomarkers

• Biomarkers are a vital tool for disease diagnosis, patient risk assessment and drug development. The FDA describes biomarkers as defined, measurable characteristics of the body that indicate biological and pathogenic processes, or the response to an intervention such as a medical product. While clinical assessments can capture how a patient feels, functions or survives, biomarkers provide researchers with a valuable window into the body’s inner workings. These tests can be molecular, histologic, radiographic or physiologic.
• Biomarkers have a variety of purposes. They can diagnose, such as how sweat chloride is used to confirm cystic fibrosis; determine risk, as BRCA gene mutations do for assessing the likelihood of breast cancer; or monitor disease status, as prostate-specific antigen levels indicate tumor burden in people with prostate cancer. They’re also used to watch for treatment side effects and to measure drug response.
• Measuring drug response is a particularly important use case, allowing biomarkers to be used as clinical trial objectives, including as “surrogate endpoints,” which are meant to be predictive of clinical benefit. One example in oncology is objective response rate: Researchers assess whether a treatment shrinks the size of a target tumor under the assumption that reductions will correlate in some fashion with longer survival. The FDA maintains a list of surrogate endpoints that have supported traditional or accelerated drug approvals.
• The FDA validates biomarkers in several ways. They can be confirmed through the agency’s review and approval of a new drug or biological product, or through a qualification process the agency established in 2007. This process was formalized in 2016 through the 21st Century Cures Act, which established a three-stage pathway for groups to submit prospective biomarkers for FDA verification within a specific context of use. Once qualified this way, a biomarker can be incorporated into any drug development program to support regulatory approval. The FDA may also more generally evaluate scientific consensus around a biomarker measure and its clinical utility.

Sluggish validation process has prompted calls for reform

• The Biomarker Qualification Program is meant to address a market failure of sorts. “One of the problems with biomarkers is there’s really no one in charge of developing them,” explained JANET WOODCOCK, a former top FDA official, in a 2016 video on an FDA webpage about biomarker development. The BQP was designed to offer a more structured and transparent alternative to sponsors validating biomarkers via individual drug submissions. As detailed in a 2020 final guidance, developers first submit a letter of intent, which the FDA reviews for up to three months and decides whether to accept. If the letter is accepted, developers are tasked with assembling a qualification plan, which the FDA aims to review within six months after submission. An accepted qualification plan is then expanded into a full qualification package, which the FDA aims to assess within 10 months after filing.
• The FDA has qualified only 11 biomarkers through the BQP, and most were qualified prior to 21st Century Cures’ December 2016 enactment, according to a database maintained by the agency. Five were qualified to assess safety, one is validated as a surrogate endpoint and the remaining five are either prognostic, diagnostic or meant to measure or monitor disease. The FDA validated three biomarkers in November and December 2025, but before that, the most recent qualification was in 2018.
• Sluggish utilization of the program has spurred criticism that it may not be as effective as intended. An analysis by Friends of Cancer Research published Oct. 28, 2025, in Therapeutic Innovation & Regulatory Science characterized the program as slow-moving. Median times for FDA review of letters of intent and qualification plans were more than double the agency’s respective three- and six-month goals, according to their analysis. (The law does not hold the agency to any statutory review timelines.) Sponsor development of qualification plans is also slow, taking a median of more than two-and-a-half years among the programs that had analyzable timeline data. “These trends demonstrate the program may not be well-suited for advancing novel response biomarkers,” the Friends researchers wrote. More resources might help, the paper concluded, noting that there are no dedicated funds tied to the BQP through user fees, for instance. [Read AgencyIQ’s analysis of Friends’ research here.]
• The program’s shortcomings were further highlighted during a meeting hosted by Friends on Feb. 5, 2026, which discussed circulating tumor DNA and artificial intelligence-enabled tumor assessments. Several panelists at the meeting said long review times have diminished the program’s attractiveness. PathAI, which in December 2025 secured qualification of a biomarker for assessing liver biopsies of people with metabolic-dysfunction associated steatohepatitis, began the process more than five years ago, for example. The BQP’s lack of dedicated resources “materialized in long gaps in time between the various stages of the qualification program,” said MICHAEL MONTALTO, a vice president of precision medicine at Amgen who was previously chief scientific officer at PathAI. Development was further slowed by “not really understanding what the agency would accept for validation,” he said. Montalto and other panelists indicated they thought the program should be reformed or at least strengthened. [Read AgencyIQ’s full analysis of the February Friends meeting here.]

New FDA incubator aims to improve biomarker development

• The FDA on May 12, 2026, revealed a new regulatory science initiative to validate biomarkers by collecting data from various sources. Disclosure of the initiative, referred to by the FDA as a biomarker incubator, came via a request for information related to a pilot project for aggregating data on biomarkers of drug-induced kidney injury. The agency is also seeking input on the “scope and direction” of the incubator and requesting submission of data that would support the pilot, which the Center for Drug Evaluation and Research is running. Comments will be accepted through mid-July.
• The incubator is meant to “complement” the FDA’s existing qualification process, according to the RFI. While that process provides a structured review pathway, the RFI notes that “FDA may identify a need to characterize a biomarker to inform regulatory decision-making where qualification activities are not being considered.” In these cases, FDA staff are tasked with collating data from different sources to establish the relationship between prospective biomarkers and outcomes. This can prove challenging because of differences and limitations in data sources, as well as unvalidated assays and dissimilar submission formats. “Therefore, CDER is seeking to develop infrastructure that could help us understand best practices for biomarker data generation, streamline processes for requesting voluntary data submission, and create a platform to analyze data,” the RFI states.
• The kidney biomarker pilot is CDER’s initial attempt under the incubator initiative to develop this infrastructure. It will build a biomarker data repository created by the Critical Path Institute, which in 2018 helped secure qualification of a panel of biomarkers that can aid detection of kidney tubular injury. C-Path’s repository has been collecting data on urinary kidney safety biomarkers, and through the pilot, the FDA aims to support that work by gathering similar data that’s either been previously submitted to the agency or generated but not yet submitted. The agency is specifically interested in the biomarkers cystatin C, osteopontin, kidney injury molecule-1, macetyl-β-D-glucosaminidase, lipocalin-2/neutrophil gelatinase-associated lipocalin, and apolipoprotein J/clusterin. The RFI indicates the FDA has already begun collecting some of this data.
• Through the RFI, the FDA is requesting “any shareable human data” on urinary kidney safety biomarkers that haven’t already been submitted to either the agency or C-Path’s repository. The agency seeks deidentified subject-level data and information on the “experiences and challenges” in using these markers to develop drugs. Sponsors – whether in industry or academia – can submit relevant data under an existing Investigational New Drug application or a new pre-IND submission, or they can suggest another submission approach. The RFI outlines the agency’s preferred data structure format and provides general guidelines on the information to include.
• The FDA is also interested in feedback on questions that go beyond the kidney biomarker pilot. The RFI asks whether there are barriers to data sharing that could be reduced in the future and seeks input on specific, as-yet unaccepted biomarkers that could be supported by aggregation of data across multiple programs. The FDA also signaled it’s considering holding public workshops and asked for comment on topics “that may be of value for public discussion.”

Analysis

• The RFI suggests the FDA is interested in improving its capabilities to evaluate biomarkers beyond its existing qualification process. Biomarkers needed for regulatory decision-making may not be in that qualification pipeline, the RFI notes, and the FDA may therefore have to take on some of the work itself. “Ultimately, improving CDER’s ability to evaluate novel biomarkers could facilitate the generation of higher quality biomarker data, expanded use of novel biomarkers, more consistent interpretation of findings from biomarker studies, and development of novel endpoints that can support a range of regulatory and drug development decisions,” the RFI states. One of the pilot’s objectives, for instance, is to create a “process and platform” that would allow the FDA to identify, request, receive, store and analyze data supporting biomarkers. The RFI’s general questions, meanwhile, suggest the agency wants to build consensus around how it can help facilitate data sharing.
• Data sharing challenges were the focus of a recent Rare disease Innovation, Science and Exploration, or RISE, workshop held by the agency’s Rare Disease Innovation Hub. While the meeting was focused on rare diseases, participants spoke of how sharing biomarker data could help advance development of drugs for these kind of conditions. ALLYSON BERENT, chief science officer at the Foundation for Angelman Syndrome Therapeutics, noted that patient groups often bear the cost and effort of advancing new biomarkers as industry sponsors often don’t share data they collect in their development programs. [Read AgencyIQ’s full analysis of the RISE meeting here.]
• The incubator initiative comes as lawmakers and stakeholders consider FDA reforms that could be included in legislation to reauthorize drug and device user fees next year. These must-pass bills are often a vehicle for other policies related to the agency and therefore attract reform proposals in the run-up to congressional consideration. For instance, a March 2026 report from the Reagan-Udall Foundation for the FDA outlines policies designed to improve regulatory flexibility for rare disease treatments, including a plan for tiered biomarker qualification. [Read AgencyIQ’s analysis of the report here.] Friends, which has sought to strengthen the FDA’s biomarker program, will host a Virtual Hill Briefing in June to “highlight practical opportunities” for the FDA and Congress to do so. However, the timeline for the incubator initiative to generate learnings that could shape legislative reforms is relatively short; the current cycle of drug and device user fees expires in September 2027. [Read AgencyIQ’s tracker of FDA reform proposals here.]

To contact the author of this item, please email Ned Pagliarulo ( npagliarulo@agencyiq.com).
To contact the editor of this item, please email Jason Wermers ( jwermers@agencyiq.com).

Key documents and dates

• Request for Information: Biomarker Incubator: Urinary Kidney Safety Biomarkers (published May 13, 2026)
• Submit comments through July 13, 2026.

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