The Prescription Drug User Fee Act (PDUFA) allows the U.S. Food and Drug Administration (FDA) to collect fees from drug sponsors that streamline reviews of new drug applications, promoting timely patient access without compromising safety. When the Act is reauthorized every five years, industry and FDA discuss goals to support and improve the drug review process.
With PDUFA negotiations for the 2027 reauthorization now underway, a recent PDUFA stakeholder discussion flagged the Biomarker Qualification Program (BQP) as an area in need of greater predictability, flexibility, and transparency. In light of these ongoing discussions, our recent publication outlines targeted recommendations to modernize and strengthen this key program, offering timely considerations that could help inform the current PDUFA negotiation process.
Click here to read the full manuscript, “Hurry and Wait: Timelines and Takeaways from the Biomarker Qualification Program.”
Below, we’ve included a companion blog post to provide context, including a shorter, more accessible summary of the manuscript findings.
What Are Biomarkers, and Why Do They Matter?
Biomarkers are measurable substances or biological signals that serve as indicators of a patient’s health or response to treatment, in drug development.
Biomarkers serve a wide range of purposes, including:
- Diagnosing diseases
- Monitoring disease activity over time
- Measuring how the body responds to a drug
- Detecting early signs of drug toxicity
- Indicating which patients may be more susceptible to risk
A key goal in oncology drug development is to enable earlier access to effective novel therapies, which requires methods to assess treatment benefit sooner. Biomarkers can be used as early endpoints or surrogate endpoints in clinical trials, which are substitute measures likely to predict important clinical outcomes such as survival or quality of life. In cancer research, clinical trials often use overall survival (OS) as a measure of drug efficacy. As patients live longer, trials that rely on OS take much longer to finish, slowing access to new treatments that could benefit patients. Surrogate endpoints can provide earlier signals of benefit and help speed drug development. As such, the development and qualification of new surrogate biomarkers is increasingly important.
How the Biomarker Qualification Program (BQP) Works
One of the key mechanisms for integrating novel biomarkers into drug development is the FDA’s BQP. Established in 2007, the BQP allows researchers and organizations to work with the FDA Center for Drug Evaluation and Research (CDER) to evaluate biomarkers. Once qualified through the program, the biomarkers can be used as tools within a qualified context of use (COU), not just for a single drug product.
The BQP process includes three stages:
- Letter of Intent (LOI): The sponsor formally proposes the biomarker for a specific COU to the FDA.
- Qualification Plan (QP): The sponsor outlines how the biomarker will be studied and validated.
- Full Qualification Package (FQP): The final evidence package used by the FDA to determine whether the biomarker is “qualified” for its intended use.
In 2016, Section 507 of the 21st Century Cures Act aimed to accelerate biomarker development by formalizing and revising the BQP. In 2020, the FDA released a final guidance document, providing target time frames for each phase of the BQP to help streamline the approval of novel biomarkers, specifying a target time frame of 3 months for the LOI phase, 6 months for the QP phase, and 10 months for the FQP phase.
What We Found in Our Analysis
We analyzed all biomarker qualification projects listed in FDA drug development tool databases as of July 1, 2025, focusing on how many biomarkers entered the BQP, their characteristics, how far they advanced, and how long each step took.
How Many Biomarkers Entered the BQP?
- 99 projects were listed under the BQP
- 61 projects (62%) were accepted into the BQP
Characteristics of the 61 Accepted Biomarkers:
By designated purpose:
- 30% were designed to monitor drug safety
- 21% were designed to help with diagnosis
- 20% were designed to study the effects of a drug on the body
- 20% were designed to predict the likelihood of disease progression
By method of assessment:
- 46% were molecular assays (i.e., detection of genes or proteins)
- 39% were radiologic or imaging-based
By intended use:
- 49% were intended to measure disease activity or condition
- 49% were intended to measure a patient’s response to a drug
Surrogate endpoints:
- Only five (8%) were intended for use as surrogate endpoints
How Many Biomarkers Reached Qualification?:
Despite 61 projects accepted into the BQP, as of July 2025, only eight biomarkers (13%) achieved full qualification. Interestingly, all eight projects were reviewed before the phased qualification process was established by the 21st Century Cures Act.
Among the qualified biomarkers:
- 50% were biomarkers designed to monitor drug safety
- 88% relied on molecular assay assessments
Other notable trends were:
- Almost half of the accepted projects have not yet progressed beyond the LOI stage
- Four projects were withdrawn or rescinded before reaching qualification
Review Timelines:
Actual review times substantially exceeded the target timelines specified in the FDA’s 2020 guidance on participating in the BQP.
LOI reviews:
- Target time frame: 3 months
- Median actual time frame: 6 months
- Median actual time frame of projects accepted into the BQP post-2020 FDA guidance: 13.4 months
QP reviews:
- Target time frame: 7 months
- Median actual time frame: 14 months
Time to develop a Qualification Plan:
- Median actual time frame: 31 months
- Median actual time frame for surrogate biomarkers: 47 months
What Do These Data Tell Us?
Although the BQP was created to provide a structured, transparent mechanism for developing and approving biomarkers, its real-world impact has been limited. In our analysis of the program from 2007 through July 2025, only eight biomarkers successfully reached qualification, and none did so under the modern framework established by the 21st Century Cures Act. Since the completion of our analysis, FDA has qualified an additional biomarker through the program, reflecting continued interest and incremental progress.
The program appears somewhat more effective for certain biomarker types, such as safety biomarkers, but it has been far less successful for other biomarkers with potential for high-impact in drug development—especially surrogate endpoints.
How Can the BQP Be Improved?
We recommend several changes that could strengthen the BQP and accelerate novel biomarker development:
Targeted refinements to the qualification process
Clearer guidance, greater transparency, and structured checkpoints with FDA could help sponsors move through the process more efficiently.
Dedicated and sustainable funding
With PDUFA negotiations underway, securing resources that specifically support the BQP may enable more timely review and deeper FDA engagement.
Stronger collaboration
Expanded dialogue between FDA and stakeholders could help prioritize the most impactful biomarkers and guide their development.