What is a priority review, and how is it obtained?

Introduction to Priority Review

Definition and Purpose
A priority review is a regulatory designation by the U.S. Food and Drug Administration (FDA) that accelerates the review process for New Drug Applications (NDAs) or Biologics License Applications (BLAs) for products that offer major advances in treatment or meet significant unmet medical needs. This designation allows the FDA to complete its review of an application much faster than the standard review process, with target review times shortened to six months for priority reviews compared to ten months or more for standard reviews. The purpose of a priority review is to expedite patient access to new therapies that address serious or life‐threatening conditions, thereby improving public health outcomes by ensuring that innovative treatments reach patients faster. Moreover, priority review is intended to focus the FDA’s limited evaluation resources on promising treatments that can significantly advance clinical practice or address critical gaps in current therapy.

Historical Context and Development
The concept of priority review emerged in the early 1990s as part of the FDA’s efforts under the Prescription Drug User Fee Act (PDUFA) to streamline the drug approval process by establishing two tiers of review—Priority Review and Standard Review—based on the therapeutic value of the product. Initially implemented in 1992, the priority review program was designed to offer an expedited review timeline for drugs that demonstrate the potential for significant improvement in patient care, particularly for conditions where no adequate therapy exists. Over time, this program has evolved with regulatory updates and amendments that have refined eligibility criteria, target review times, and operational guidelines, thereby continually adapting the regulatory framework to advances in science, changes in disease epidemiology, and emerging public health needs. As a result, priority review has become a critical component of the FDA’s regulatory strategy, incentivizing pharmaceutical companies to invest in developing innovative treatments for serious conditions.

Criteria for Priority Review

Eligibility Requirements
To qualify for a priority review designation, an investigational drug or biologic must demonstrate significant potential to provide a major improvement in safety or efficacy relative to available therapies or offer a treatment option for a condition that currently has no adequate therapy. Specifically, the product must target a serious or life‐threatening condition and show promising evidence—often from early clinical or even preclinical data—that supports its potential for substantial clinical benefit. In many cases, the determination is based on whether preliminary clinical data indicate that the product could address an unmet medical need or offer an alternative when existing treatments fall short in terms of efficacy, safety, or overall patient benefit. The FDA assesses each application on a case‐by‐case basis, considering factors such as the disease severity, the magnitude of improvement offered by the new therapy, and the availability of existing treatments that could serve as comparators in clinical trials. In practice, drugs that exhibit breakthrough characteristics or are designed for orphan indications often meet these eligibility requirements, although the priority review program operates under its own set of criteria distinct from other expedited programs.

Comparison with Standard Review Process
The standard review process is characterized by a longer evaluation timeline, typically taking the FDA around ten months from the submission of a new application to review and act on the submission. In contrast, a priority review shortens this timeline to approximately six months, thereby accelerating the process of bringing therapeutically innovative products to market. For drugs that qualify for priority review, the FDA commits additional resources and a more intensive review process that emphasizes the potential clinical benefits of the product. While both processes require the same rigorous scientific and regulatory standards to be met, the priority pathway is specifically reserved for products that have the potential to significantly impact patient outcomes or address critical gaps in therapy. This expedited timeline, however, does not imply a relaxation of safety or efficacy standards, and manufacturers must still provide robust data to support their claims.

Process of Obtaining a Priority Review

Application Procedure
The process of obtaining a priority review designation begins with the submission of a New Drug Application (NDA) or Biologics License Application (BLA) to the FDA. During the initial screening stage, the FDA evaluates the submitted data to determine whether the product qualifies for priority review based on the established eligibility criteria, such as the severity of the condition addressed and the magnitude of the benefit demonstrated in early trials. Early in the submission process, sponsors may also communicate with the FDA through pre-submission meetings to discuss the potential eligibility and to clarify the types of data required to support a priority review designation. In many cases, the manufacturer must provide evidence from clinical or robust non-clinical studies that indicate a promising therapeutic profile compared to existing treatments or an absence of adequate treatment options. This evidence plays a critical role in the FDA’s decision-making process, as it outlines the rationale for expedited review and underscores the product’s potential impact on public health. Importantly, the designation is obtained at the time of filing the NDA or BLA, and specific timelines—such as the six-month review period—start counting once the application is accepted by the FDA.

Evaluation and Decision-Making
After the submission, the FDA conducts an initial evaluation to verify that the application is complete and meets regulatory requirements before initiating its rigorous review process. During this phase, the FDA assesses the preliminary data submitted to determine whether the product has demonstrated the potential for a meaningful improvement in treatment outcomes, which is a necessary condition for priority review. The evaluation involves detailed consideration of the clinical trial design, the endpoints used to measure efficacy, and the statistical strength of the findings, all of which contribute to an overall judgment of the product’s therapeutic value. The decision-making process is multi-layered, involving scientific and regulatory experts within the FDA who weigh the evidence against the priority review criteria, taking into account both the clinical need and the product’s demonstrated advantages over existing therapies. In many cases, if the preliminary data convincingly demonstrate a significant improvement or a novel approach to treatment, the FDA grants the priority review designation, effectively accelerating the subsequent review cycles and allocating resources more intensively towards the application. Ultimately, the FDA’s decision is communicated to the sponsor along with the target review timeframe, which then guides the later stages of the regulatory process.

Impact and Implications

Benefits for Drug Developers
For pharmaceutical companies and drug developers, obtaining a priority review designation confers several strategic and financial benefits. By accelerating the FDA review process, companies can bring their innovative products to market faster, thereby potentially securing a competitive market advantage and extending periods of market exclusivity. The shortened review timeline also means that companies can generate revenue more quickly, which can be particularly valuable in areas with high unmet medical needs or where there is intense competition for innovative therapies. Additionally, the priority review designation is often viewed as a strong signal of the product’s potential therapeutic value by investors and stakeholders, enhancing investor confidence and facilitating funding opportunities for further research and development. From a clinical perspective, the expedited process benefits patients by improving access to breakthrough treatments sooner than would be possible under the standard review process. These benefits collectively incentivize pharmaceutical companies to invest in areas of high unmet need, ultimately driving innovation in the drug development landscape.

Case Studies and Examples
Several case studies highlight the advantages that priority review can provide to drug developers. For instance, Novartis received a priority review designation for its MET inhibitor capmatinib, which is being evaluated for advanced non‑small cell lung cancer (NSCLC) with MET exon 14 skipping mutations—a patient population with particularly poor prognosis and no approved therapies specifically targeting this mutation. In this case, the priority review designation not only expedited the review process but also underscored the significant unmet need in this patient population, ultimately facilitating a faster market entry that could potentially improve clinical outcomes. Other examples include drugs designated under the FDA’s expedited pathways that have demonstrated breakthrough therapies in oncology and rare diseases, where the combination of priority review with programs like accelerated approval has led to more rapid patient access to life-saving treatments. Such examples illustrate that priority review is not only a regulatory designation but also an important business tool that can influence drug development strategies and market dynamics.

Challenges and Considerations

Common Challenges in Obtaining Priority Review
Despite the benefits associated with priority review, obtaining this designation is not without its challenges. One of the primary challenges is demonstrating sufficiently compelling evidence at the time of submission to justify expedited review. Since the FDA requires that the product provides a significant improvement over existing treatment options, manufacturers must design and conduct studies that generate robust and convincing data early in the development process. This can be particularly challenging for therapies targeting rare diseases or conditions where conducting large-scale clinical trials is more difficult due to the limited patient population. Additionally, the process of negotiating and aligning on the evidentiary standards for priority review during pre-submission meetings can be complex and resource-intensive, requiring close collaboration between the sponsor and the FDA. There is also the inherent risk that an application might ultimately not meet the requisite criteria despite initial expectations, leading to delays and increased development costs. These challenges underscore the need for strategic planning in the design of clinical trials and regulatory submissions to preempt potential issues in the priority review process.

Regulatory and Ethical Considerations
From a regulatory standpoint, the accelerated nature of the priority review process necessitates that the FDA maintain rigorous standards while working under tighter deadlines. This creates unique challenges for both the agency and the sponsors, as the review process must be both expedited and thorough, balancing the need for rapid patient access with the imperative for ensuring drug safety and efficacy. Ethically, priority review raises questions about how to fairly allocate regulatory resources, especially when multiple products compete for expedited review based on similar claims of therapeutic innovation. There is also the ethical responsibility to ensure that faster review times do not compromise the thoroughness of data evaluation, thereby safeguarding patient safety. In practice, the ethical and regulatory considerations are managed through stringent internal guidelines and multi-disciplinary review committees within the FDA, which seek to maintain a high standard of scientific rigor even under accelerated timelines. Such measures are designed to ensure that while the process is expedited, it does not lead to premature approvals or compromise the integrity of clinical trial data.

Conclusion
In summary, a priority review is an expedited FDA regulatory designation intended for drugs that offer considerable improvement in treatment safety or effectiveness or that fulfill an urgent need where no adequate therapy exists. This accelerated review process, which was introduced in the early 1990s and refined over subsequent decades, involves a strict set of eligibility criteria that require robust evidence of potential clinical benefit. To obtain a priority review, drug developers must submit an NDA or BLA accompanied by compelling clinical data and engage in pre-submission discussions with the FDA to clarify evidentiary requirements. The FDA then evaluates the application via a rigorous decision-making process designed to ensure that expedited review does not compromise the thoroughness of safety and efficacy assessments.

For drug developers, the benefits of a priority review are significant; they include the potential for a faster time-to-market, increased investor confidence, and the competitive edge that comes from being first to offer a breakthrough therapy. However, these benefits are tempered by several challenges, such as the difficulty of generating early convincing data, navigating complex regulatory negotiations, and ensuring that ethical and regulatory standards are not compromised by the expedited process. Real-world examples, such as the case of Novartis’ capmatinib for NSCLC, demonstrate how priority review can successfully accelerate the development of life-saving drugs.

Overall, the priority review designation represents an important balance between accelerating patient access to innovative treatments and maintaining rigorous standards of review to ensure drug safety and efficacy. By understanding the detailed criteria, application procedures, and potential challenges associated with obtaining priority review, sponsors can better navigate the regulatory landscape and contribute to advancements in public health. This comprehensive framework not only benefits pharmaceutical companies by shortening development timelines but also ultimately serves the broader goal of addressing critical unmet medical needs and improving healthcare outcomes.