Expedited Marketing Authorisation Application Pathways

Expedited regulatory pathways have been developed to address public health priorities, particularly where patients face serious or life‑threatening conditions and limited treatment options. Through different mechanisms, these expedited pathways allow earlier patient access to promising medicines while maintaining a positive benefit-risk profile and robust regulatory oversight (1). Data demonstrates these pathways can substantially reduce review timelines, shortening median approval times by approximately 225 days at the EMA and 121 days at the FDA (2), highlighting their importance as regulatory tools where unmet medical need exists. These pathways exist across ICH member states, although eligibility criteria and scope vary. This blog focuses on key EU and US pathways.

While the EMA and the US FDA operate with distinct regulatory frameworks, their expedited pathways share common principles. As highlighted in Clinigen’s recent webinar Expedited Regulatory Pathways: Strategies for an Optimised Path to Approval, these pathways form a regulatory “toolbox” designed to support innovation, patient access and promote close interaction between regulators and sponsors.

Core Principles of Expedited Pathways in EU and US

Across both the EU and the US, expedited pathways share several overarching characteristics:

• They are intended for medicines addressing serious or life‑threatening conditions or unmet medical needs
• They do not lower the bar for approval, but introduce regulatory flexibility where justified
• They may involve shortened review timelines, early and enhanced agency interaction, or approval based on limited clinical data

These shared principles underpin the various EMA and FDA pathways, even where eligibility criteria and procedural details differ.

Accelerated Reviews: EMA Accelerated Assessment and FDA Priority Review

In the EU, Accelerated Assessment is intended to shorten the marketing authorisation application (MAA) review timeline from 210 to 150 days for products considered to be of major interest to public health, typically through scientific innovation (3). Evidence shows that this pathway can significantly reduce overall assessment times, with median assessment durations reported to be 175 days shorter than standard procedures for products approved between 2019 and 2021 (4). Analyses further indicate that a significant proportion of the time saved is attributed to faster sponsor response times during clock-stops, rather than to reductions in regulatory review time alone (4,5). However, approximately 60% of products initially granted Accelerated Assessment reverted to standard timelines once major objections were raised during assessment over the same period (4).

A similar pathway exists in the US through the FDA’s Priority Review. This pathway reduces the FDA’s target review time for a new drug application or biologics licence application from 10 months to 6 months. It is granted to therapies that, if approved, would offer significant improvements in the safety or efficacy of the treatment, diagnosis, or prevention of serious conditions (6,7). Similarly to the EMA’s Accelerated Assessment, Priority Review does not reduce the evidence required for marketing approval, and the assessment outcome remains dependent on the completeness and quality of the submitted data. If substantial issues are identified during the review, the FDA retains full discretion to request additional regulatory interactions, limiting the overall time gained (6).

Since the evidence required for approval under these accelerated review pathways are the same as standard assessment (6,8), they are only realistic for products supported by robust data packages. Pharmaceutical companies must consider that, while successful use of Accelerated Assessment or Priority Review can result in faster regulatory approval and earlier patient access, poorly prepared applications risk losing accelerated status, leading to wasted resources and limited overall time gain.

Preliminary Approval: EMA Conditional Marketing Authorisation and FDA Accelerated Approval

While a complete dossier is required for accelerated reviews, Conditional Marketing Authorisation (CMA) in the EU allows sponsors to have a preliminary approval based on incomplete data where a positive risk-benefit can be demonstrated. To be granted CMA, the product must address a serious or life-threatening condition with unmet medical need (3,9). Generally, a CMA is supported by complete non‑clinical and quality data and less comprehensive clinical data. However, in response to public health threats, incomplete non-clinical and quality data may be accepted, reflecting the flexibility of this procedure when urgent access is justified (10). CMA was instrumental in enabling early access to COVID‑19 medicines, highlighting the critical role of expedited pathways during public health emergencies (11).

A closely related mechanism in the US exists through the FDA’s Accelerated Approval. This pathway allows products intended to treat serious or life‑threatening conditions to be approved based on surrogate endpoints that are reasonably likely to predict clinical benefit, where earlier access is considered to outweigh the uncertainty associated with incomplete clinical outcome data. This pathway aims to address unmet medical need and facilitate earlier patient access while confirmatory evidence is still being generated (6,12).

These pathways represent a unique opportunity for earlier market entry and provide patients with access to potentially life-changing treatments; in 2023, CMAs accounted for 23% of new active substance approvals by the EMA, while Accelerated Approval represented 16% of new drug approvals by the FDA (2). However, these preliminary approvals are accompanied by significant regulatory obligations. In the EU, CMA requires sponsors to fulfil specific post-authorisation obligations to confirm clinical benefit, which could include the completion of ongoing or new clinical studies and submission of additional data within defined timelines (3). CMA are granted for one year and are subject to annual renewal, creating an ongoing regulatory burden and introducing uncertainty for sponsors. Importantly, a CMA may be suspended or withdrawn if confirmatory data fail to support the initial benefit-risk assessment, such as when a post‑authorisation study does not meet its primary endpoint (13).

Similarly, the FDA’s Accelerated Approval pathway is dependent on the sponsor’s commitment to conduct post‑approval confirmatory trials to verify the anticipated clinical benefit. These studies are a core regulatory requirement and are expected to be underway at the time of approval or initiated promptly thereafter (6). Recent regulatory developments have placed increased emphasis on the timely completion of confirmatory trials, with the FDA clarifying its authority to take action where post‑approval obligations are delayed or fail to confirm benefit (14). Therefore, Accelerated Approval transfers a substantial proportion of risk into the post‑approval phase, and failure to generate confirmatory evidence may lead to modification of the indication or withdrawal of approval (6). Sponsors must carefully assess the robustness of surrogate endpoints and the feasibility of confirmatory trials within realistic timelines when considering this pathway.

Approval Based on Limited Data: EMA Exceptional Circumstances

For products where comprehensive efficacy and safety data cannot be generated, due to disease rarity or ethical constraints, EMA’s Exceptional Circumstances procedure is available (3). This pathway reflects a clear adaptation to public health priorities by enabling access to treatments that would otherwise be unobtainable for small patient populations. Approval under this pathway is granted with the expectation that comprehensive data will never be fully generated. Similar to other expedited pathways (EMA CMA and FDA Accelerated Approval), products granted authorisation through this procedure are required to implement specific post-authorisation measures, particularly around the safety of the product, which are reviewed annually (10). The strict eligibility criteria for this procedure suggests its utilisation is driven more by the nature of the disease than by regulatory strategy and may not be applicable for most development programmes. The use of this pathway remains rare, as highlighted by the fact that only two new medicines were authorised by the EMA under this route in 2025 (15).

There is no directly comparable FDA pathway where marketing authorisation is granted on a permanent basis with the explicit acknowledgement that a full data package cannot be completed.

Table 1. Overview of Expedited Approval Pathways in EU and US

Designations to Support Expedited Development

Alongside expedited approval pathways, regulators offer designations that support the development of medicines addressing serious conditions and unmet medical need through enhanced regulatory engagement.

The PRIority MEdicines (PRIME) scheme from EMA provides early and proactive support for medicines that demonstrate the potential to address an unmet medical need. PRIME focuses on early dialogue and scientific advice to optimise development plans and evidence generation, with the aim of ensuring that data generated are suitable for a high‑quality MAA. Key benefits include enhanced interaction with the EMA, early appointment of a rapporteur, and support to improve submission readiness. Medicines supported through PRIME may also be eligible for Accelerated Assessment at the time of MAA (16).

In the US, Fast Track Designation and Breakthrough Therapy Designation support development through increasing levels of FDA engagement. Fast Track is intended for medicines that treat serious conditions and address unmet medical need. It provides benefits such as more frequent FDA interactions and eligibility for rolling review of marketing applications, allowing sponsors to submit sections of a New Drug Application (NDA) or Biologics Licence Application (BLA) as they are completed, rather than waiting until the entire application is ready (17). Breakthrough Therapy Designation applies where preliminary clinical evidence indicates a substantial improvement over available therapies in serious conditions, and offers more intensive FDA guidance and organisational commitment, in addition to all Fast Track features (18). Neither designation lowers evidentiary standards for approval, but both aim to facilitate more efficient development and may allow eligibility for other expedited regulatory mechanisms (Accelerated Approval or Priority Review) where appropriate.

By facilitating early dialogue, increased access to guidance and, in some cases, eligibility for expedited mechanisms, these designations can help sponsors optimise evidence generation while maintaining established regulatory requirements.

Additional Initiatives For Expedited Development

In the EU, the EMA’s Innovation Task Force (ITF) provides sponsors with an opportunity for early dialogue for development programmes of innovative medicines. ITF meetings focus on identifying key scientific, regulatory, or technical challenges, helping sponsors anticipate regulatory considerations and clarify potential development pathways before engaging in formal procedures (19). Alongside this, the EU Innovation Network (EU-IN) aims to enhance collaboration between the EMA and national competent authorities (20). EU‑IN is particularly relevant where innovative development programmes raise complex issues, requiring more coordinated regulatory input across the EU.

The Real‑Time Oncology Review (RTOR) programme in the US allows sponsors of certain oncology medicines to submit key clinical efficacy and safety data to the FDA in advance of the complete marketing application, enabling the agency to begin its evaluation earlier and engage in more dialogue during the review process. This is intended to improve review efficiency and quality while maintaining the same standards for approval. Importantly, participation does not guarantee earlier approval or a positive regulatory outcome (21). Additionally, the Regenerative Medicine‑Advanced Therapy (RMAT) designation supports the development of eligible regenerative medicine therapies intended to treat serious or life‑threatening conditions. RMAT provides sponsors with the benefits associated with Fast Track and Breakthrough Therapy designation (22). Further discussion of emerging FDA approaches to supporting development in rare and ultra‑rare diseases, including the Rare Disease Evidence Principles process, is available in Clinigen’s blog A New Regulatory Process for Ultra-Rare Therapies - FDA Rare Disease Evidence Principles (RDEP) Process.

Strategic Implications and Conclusions

A key limitation across accelerated pathways is the disconnect that still exists between regulatory approval and patient access. While expedited procedures can accelerate marketing authorisation, health technology assessment (HTA) and reimbursement decisions often require more mature or comparative evidence than regulators. As a result, faster regulatory approvals do not necessarily translate into earlier or broader patient access. For regulatory professionals, this reinforces the importance of considering HTA and payer evidence expectations early in development when pursuing expedited approval strategies (23).

In this context, early dialogue mechanisms such as joint scientific consultations, which focus on aligning clinical study design and data expectations between regulators, HTA bodies and sponsors, can help reduce regulatory uncertainty and support more efficient evidence generation, as discussed in Clinigen’s webinar Joint Scientific Consultation: the balancing act of preparation across regulatory and market access.

Overall, expedited pathways can support public health priorities by facilitating earlier access to promising therapies, provided a positive benefit-risk balance is maintained. The effectiveness of these mechanisms depends on early and meaningful agency interaction, realistic assessment of product and data eligibility, and consideration of post-authorisation obligations. Equally important is the quality and strength of the submissions. When used appropriately, expedited pathways should be viewed as regulatory tools that require robust strategic planning and can support both innovation and timely patient access.

References

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