Lessons learned from first ten years of PRIME, and what to expect next

Ten years after its introduction, the European Medicines Agency’s (EMA) PRIME scheme has become one of Europe’s most important regulatory mechanisms for supporting promising medicines that may address serious conditions with unmet medical need. 

Its objective is straightforward but ambitious. It helps developers generate stronger evidence earlier, engage with regulators sooner and, where appropriate, move more efficiently towards marketing authorization assessment. EMA describes PRIME as early and proactive support designed to optimize the generation of robust benefit-risk data and to potentially reduce the time for regulatory review after filing for a Marketing Authorization Application (MAA) for medicines that may address unmet medical need.  

But PRIME should not be misunderstood as an easy route to faster approval. 

If anything, its first decade has shown that the programme’s credibility depends in part on its selectivity. PRIME applies a high evidentiary bar at an early stage of development, when there is inevitably more uncertainty than at the point of a marketing authorisation application. The criteria are aligned with the concept of accelerated assessment — major public health interest, particularly from the perspective of therapeutic innovation — but they are being applied earlier, with the expectation that preliminary clinical evidence, or in some cases proof-of-concept evidence for academic or small and medium-sized enterprise (SME) applicants, is strong enough to justify enhanced regulatory engagement.  

That distinction matters. PRIME is not intended for every promising asset. It is intended for medicines with credible potential to address serious unmet need and deliver meaningful therapeutic value. 

Around one in four PRIME eligibility requests have been granted, underlining that this is a selective scheme by design. That selectivity should not be viewed as a weakness. Regulatory capacity is finite, and early, intensive support is most valuable when focused on products where it can make a real difference for patients, developers and the healthcare system. 

Over its first decade, oncology has remained a prominent area within PRIME, but one of the encouraging features of the programme has been the breadth of disease areas represented, including orphan and highly specialised conditions. That breadth is important because unmet need is not confined to one therapeutic area. A successful PRIME model should continue to support innovation wherever the medical need is serious, the scientific rationale is strong and the evidence base is sufficiently credible. 

PRIME is not expected to be become easier to enter. However, based on Cencora’s experience supporting companies that have been considered for PRIME, the following insights will help companies effectively apply to and use the pathway as it continues to evolve. 

Timing of application  

One of PRIME’s greatest strengths is that it creates a framework for earlier and more structured interaction between developers and EMA. The programme can provide early dialogue, scientific coordination, iterative scientific advice, expedited follow-up advice and a submission readiness meeting.  

These tools are valuable because they allow companies to test whether their evidence-generation plans are robust enough before the formal marketing authorisation stage. They can help developers refine clinical strategy, address key scientific questions and understand where regulators may see gaps in the benefit-risk case. 

However, PRIME eligibility itself does not guarantee accelerated assessment, approval, or patient access. Its value depends on how effectively the developer uses the advice received and, of course, if the medicinal product will prove to be efficacious and safe at the end. 

This is why timing is critical. Applying too late, for example, when Phase III data is already available, may leave limited opportunity for EMA input to meaningfully reshape development. Applying too early can also be problematic if the company has not yet pressure-tested the development plan or generated sufficient evidence to support the unmet-need and therapeutic-innovation argument.  

The ideal moment is not simply “as early as possible.” It is when the science, the unmet-need rationale and the development strategy are mature enough for EMA engagement to add real value. 

Companies should be thinking early about the full development path and asking - what Phase I, Phase II and Phase III could look like, how measurement of efficacy signals might be incorporated into earlier trials, what endpoints will support the intended claims, and how the evidence package will evolve into something assessable, credible and persuasive.  

PRIME rewards early thinking, but not incomplete thinking.

Preparation for PRIME  

Before entering PRIME, developers should undertake a realistic assessment of whether the product truly meets the criteria. That assessment should look not only at the seriousness of the condition and the level of unmet need, but also at the strength of the evidence package, the plausibility of the mechanism of action and the maturity of the development strategy.  

In many cases, companies may benefit from seeking national scientific advice before entering the EMA pathway. This can be particularly useful where there are novel endpoints, unusual trial designs, complex manufacturing questions or scientific assumptions that would benefit from challenge.  

National advice can help companies “test the water” and understand where regulators may agree, disagree or raise questions. Once a company is within the EMA scientific advice route, the process can provide consistency and reliability, but there may be less opportunity for broader exploratory discussion with individual national authorities since they may refuse interaction once EMA scientific advice has been obtained.  

That is not a criticism of EMA. It reflects the practical reality of a system that must manage significant workloads and maintain consistency across EU member states. But it does reinforce the importance of doing the strategic thinking before entering PRIME. 

Developers should understand where the pain points are likely to be before they engage regulators. Those pain points may sit in clinical design, non-clinical evidence, CMC, mechanism of action, comparator selection, endpoint justification or benefit-risk interpretation.  

This is where experienced, external perspectives can be valuable. A “dry run” before regulator engagement can help identify weaknesses that internal teams may have normalised or underestimated. At Cencora, the most useful support is often not simply explaining the process, but helping teams pressure-test whether their evidence package, regulatory argument and development plan are ready for that process. 

That requires cross-functional expertise. PRIME readiness is rarely just a regulatory question. It is also a clinical, CMC, non-clinical, translational, access and global development question. The advantage of working with experienced, multidisciplinary teams is that they can identify issues that might only be visible to specialists, and they can do so early enough for corrective action to be meaningful.  

Use of rigorous science 

The strength of a PRIME application is not only a function of regulatory strategy. It depends on the quality of the underlying science. 

Non-clinical programmes should be designed to generate meaningful toxicity, proof-of-concept and mechanism-of-action data, not merely to satisfy minimum development requirements. This is particularly important for academic innovators and SME developers, where strong proof-of-concept evidence may be central to demonstrating that a product is ready for PRIME engagement.  

A clearly characterised mechanism of action can also help regulators understand the plausibility of benefit, anticipate safety questions and assess whether the proposed development plan is appropriate. Many targeted therapies are now built on strong biological rationales, but there are still programmes where the mechanism remains insufficiently clear. That can be a problem for PRIME because the programme is intended for products with credible potential to address unmet need, not for hypotheses that have not yet been adequately characterised.  

Promising science still needs to be rigorous science.

Future considerations

Looking ahead, PRIME’s evolution will likely focus on even more refined execution rather than looser entry criteria. EMA has already explored practical improvements, including regulatory roadmaps, development trackers, expedited scientific advice and submission readiness meetings. These are sensible developments because they move PRIME beyond a designation-based model towards a more active development-support model. 

There may also be value in more targeted opportunities for direct interaction, particularly where written advice does not allow sufficient nuance or real-time clarification. Written advice provides consistency, but complex scientific questions often benefit from discussion. Any expansion of interaction would need to be proportionate, given regulator workload, but carefully targeted dialogue could help developers interpret advice more effectively and address issues before they become obstacles.  

Global alignment will also become increasingly important. Many companies, particularly those headquartered in the United States, are more familiar with FDA milestone meetings and may focus first on the US regulatory pathway. PRIME can help bring EMA perspectives into development earlier and may help companies navigate areas where FDA and EMA expectations differ. 

This matters because few developers can afford to run separate pivotal programmes for each major regulator. Where advice differs, companies need to manage those differences carefully and constructively, rather than positioning one regulator’s view against another. PRIME can provide a useful framework for building greater regulatory certainty into global development planning.  

At the same time, regulatory acceleration must be considered alongside payer and health technology assessment expectations. As Europe gains more experience with Joint Clinical Assessment, developers will need to ensure that evidence generated for approval is also meaningful for access.  

A faster regulatory pathway can create tension if payer bodies require more comparative evidence than the development programme generates. Early alignment between regulatory and HTA perspectives will therefore become increasingly important for PRIME-enabled products. 

Conclusion  

Ultimately, the next decade of PRIME aims to continue help promising medicines move through regulatory assessment faster, but also to help them to reach patients with evidence packages that support both approval and access. 

PRIME has shown that earlier engagement can accelerate progress, but only when it is matched by earlier preparation and scientific rigor. For developers, that is the central message after ten years: do not treat PRIME as a shortcut. Treat it as a discipline.