How the FDA’s CNPV Program Is Reshaping Trial Operations and Accelerated Review Strategies

The FDA’s Commissioner’s National Priority Voucher (CNPV) Program is introducing one of the most aggressive regulatory timelines in modern drug development, granting eligible sponsors a one-to-two-month review in exchange for meeting critical national health needs. This new, accelerated pathway demands early integration across biostats, regulatory, medical writing, CMC, and site operations, with data quality and submission readiness achieved months earlier than a standard New Drug Application (NDA). In this exclusive Q&A, John Kirk, principal regulatory specialist at Veristat, discusses how sponsors and contract research organizations (CROs) must rethink planning, communication, and cross-functional execution to succeed under CNPV expectations.

ACT: How do you expect the CNPV Program’s 1-2 month review timeline to influence operational planning for clinical trials, particularly around data readiness and submission strategy?

Kirk: To date 15 vouchers have been awarded as the sponsors had development projects in their respective pipelines that met at least one of the priorities of the CNPV pilot project (i.e., addressing a public health crisis, addressing a large, unmet medical need, increasing affordability, etc.).

To use a voucher for the short review period, sponsors must submit the CMC section of the marketing application at least 60 days before submitting the complete application. This means that manufacturing must be commercially ready sooner than necessary for a standard NDA. Also, clinical trials needed for the marketing application (or efficacy supplement) must be completed on time and be of high quality to facilitate review and pre-approval inspections. Finally, the short review period could result in information requests that must be addressed on very short notice. Otherwise, it is possible that FDA could request additional time to complete their review.

All these factors require strategic operational preparations to build the marketing application and be positioned to execute the review process in a tightly concatenated fashion. In our experience, sponsors who successfully navigate these compressed timelines integrate their biostatistics, regulatory, and medical writing teams from the outset, creating a unified approach where data flows seamlessly from analysis through narrative to submission, rather than treating these as sequential handoffs.

ACT: The CNPV promotes enhanced communication and rolling review. What operational shifts will sponsors and CROs need to make to support this more iterative regulatory engagement?

Kirk: The enhanced communications and rolling review for the CNPV pilot program are essentially the same as for ‘Breakthrough Therapy’ designation. In both programs, FDA senior staff are more involved with the development of the new treatment option and can be proactive and frequent in their requests for information. And in return, FDA staff are more responsive to sponsor’s needs. It is critical that sponsors and regulators collaborate closely to keep the program moving forward as fast as possible.

ACT: Given the multidisciplinary, tumor-board style review process, how might trial teams adjust cross-functional workflows such as safety, biostats, and medical writing to meet accelerated expectations?

Kirk: The CNPV pilot study grants one-to-two-month reviews of NDAs (and efficacy supplements), requiring sponsors to react to queries quickly. Similarly, at Veristat, we have faced 24-hour turnarounds to FDA queries—and success always depends on our regulatory, biostatistics, and medical writing teams seamlessly functioning as a single unit. We've found that the ability to provide comprehensive responses quickly often comes down to having established workflows where team members already understand each other's processes and can mobilize fast. Rapid response teams by functional area are also necessary, with clear escalation paths and pre-aligned decision-making authority to avoid bottlenecks.

ACT: What challenges do you foresee for trial sites and CROs in preparing high-quality data packages earlier, and how might the CNPV Program incentivize cleaner, real-time data during study conduct?

Kirk: Sponsors will require well-organized vendors and partners, and pre-audited study sites to ensure high-quality datasets. A seamless communication network will be essential. The incentives offered by the CNPV pilot program include the promise of a short review, an open channel to always have clarity on what is needed to facilitate the review and a collaborative relationship with the FDA review team.

ACT: For sponsors aiming to qualify for a CNPV, what early-phase operational decisions—protocol design, endpoints, patient selection—become more critical to ensure the eventual submission can support an accelerated review?

Kirk: The FDA takes a broad view when determining the appropriateness of receiving accelerated approval (AA) pathway in the CNPV pilot program. The agency considers the severity and prevalence of the condition as well as the availability of alternative treatments. Essentially, AA is granted based on treatment effects on a biomarker that has been qualified as a surrogate endpoint that is reasonably likely to predict clinical benefit. Importantly, the FDA must agree on the endpoint to be used as the basis of approval.

Changes observed upon treatment will occur much sooner than traditional clinical outcomes, such as survival. The biomarker itself is not a clinical outcome; however, changes in the biomarker upon treatment need to capture clinical benefit that is reflected in the long term. To qualify an endpoint for AA, the specific marker must be thoroughly evaluated based on the relationship between the disease, the endpoint, and the desired effect. Marketing approval based on a surrogate endpoint can occur substantially sooner than under a standard approval based on known clinical outcomes, so sponsors must invest in studies that characterize the predictive value of a given biomarker. It will be necessary to show evidence of the link between the surrogate endpoint and the ultimate clinical outcome.

Early-phase strategic and operational decisions are important when considering AA. Not all products are associated with plausible biomarkers and many that do have measurable biomarkers cannot show their predictive value for clinical benefit, so early assessments need to be made on amenability to AA. Also, consultation with FDA review teams is critical for development programs where a sponsor intends to use a novel surrogate or intermediate clinical endpoint as the basis for AA.

In our experience, early planning and close partnership between the sponsor and CRO are critical to success. The complexity of AA requirements means that strategic decisions made in early development can significantly impact the viability of the accelerated pathway years later. We've found that bringing regulatory, clinical, and biostatistics expertise together during initial protocol design helps sponsors avoid costly pivots later in development.

Veristat has supported multiple guidance meetings to discuss AA, including attending Type C meetings alongside sponsors to provide real-time strategic input. These meetings are often pivotal moments where FDA feedback can reshape entire development programs. Having experienced team members who understand both the scientific nuances and regulatory expectations, and who can think quickly during these discussions, help sponsors maximize the value of these limited FDA interactions.

The collaborative approach extends beyond meetings themselves. For instance, Veristat works with sponsors to anticipate FDA questions, prepare comprehensive briefing packages, and develop contingency strategies for various scenarios. This preparation has proven invaluable when FDA raises unexpected concerns or suggests alternative development approaches.