It is called Scientific Advice and is a little-known but powerful tool to master Europe’s complex regulatory framework
We all know that bringing a new medicine to market is a complex process, and the early phases of research and clinical planning are decisive. Decisions made at this stage determine whether a product can progress through the European regulatory framework without costly delays or programme redesigns. Yet, many promising innovations, particularly those originating from SMEs and academic laboratories, struggle to translate their potential into approved medicines.
The obstacle rarely lies in a lack of innovation, but in avoidable misalignments with regulatory expectations, insufficiently justified methodologies, or evidence gaps identified too late in development. These issues frequently lead to requests for additional studies, extended assessment timelines, or even the need to overhaul clinical programmes. Such outcomes can significantly undermine market entry and return on investment.
What is less widely known is that the European Medicines Agency (EMA) offers a unique opportunity to cope with these risks. The Scientific Advice is a guidance tailored to the specific development strategy of a medicine or advanced therapy. This dialogue can resolve methodological uncertainties. It can also align trial design with regulatory expectations, and reduce the likelihood of critical objections during marketing authorisation. For developers, it can mean the difference between a streamlined regulatory path and years of additional work.
The evolving landscape of clinical trials
Over the past decade, scientific breakthroughs, evolving public health priorities, and a determined legislative effort have reshaped the European regulatory environment for medicinal products and modernised the EU pharmaceutical framework. The forthcoming revision of the general pharmaceutical legislation is redefining the evidentiary standards for new medicines in the EU. Alongside this reform, the EU is introducing targeted measures to address antimicrobial resistance and support the development of advanced therapy medicinal products (ATMPs). Plus, these measures aim to improve access to orphan and paediatric medicines.
Together, these initiatives are setting higher expectations for both the quality and the breadth of data required to support marketing authorisation applications. As a result, they signal a shift towards more comprehensive and strategically planned evidence packages. Moreover, regulators are increasingly encouraging the integration of adaptive trial designs and the use of real-world evidence. They are also promoting accelerated evaluation pathways for treatments addressing high unmet medical needs.
For smaller companies and academic teams, often the source of the most disruptive innovations, this rapidly evolving framework increases the need for direct, early interaction with regulators.
What Scientific Advice is and what is not
In this context, Scientific Advice has become one of the most effective channels to ensure that innovative projects are developed in line with regulatory expectations. It is a formal, prospective interaction with EMA experts to test the scientific and regulatory soundness of a development plan before committing to costly studies. It focuses on the methods and design choices a developer intends to use across quality, non-clinical, and clinical work packages. This tool also assesses whether those choices are likely to meet European regulatory expectations.
The outcome is not an approval and does not pre-judge results. Rather, it provides guidance that helps developers reduce avoidable uncertainty about how evidence will be assessed later during marketing authorisation. Scientific Advice addresses, indeed, how to generate evidence, not whether the evidence already collected is “enough.” It will not substitute eligibility decisions for separate EMA schemes, nor does it replace national ethics approvals or sponsor obligations under the Clinical Trials Regulation. When developers propose changes to conventional trial designs—such as using a different comparator, modifying the primary endpoint, or integrating real-world evidence to supplement a small trial—they seek Scientific Advice. This advice evaluates whether the overall plan remains scientifically coherent. It also highlights where developers need to make methodological adjustments to strengthen the plan.
How Scientific Advice works
Determining the right moment to seek Scientific Advice is as strategic as the questions posed. Developers can use the procedure at almost any point in the development lifecycle. But they maximise its value by influencing the scientific and regulatory course of a programme while it is still flexible. This approach allows developers to make adjustments without incurring major delays or sunk costs. For most projects, this means developers need to engage before they design and initiate pivotal trials. This often occurs at the transition from exploratory to confirmatory development, when key methodological decisions are still open to discussion.
Requests are submitted through IRIS, EMA’s portal for scientific procedures. Developers submit requests through IRIS, EMA’s portal for scientific procedures. The applicant frames a finite set of questions and provides a reasoned position for each, with the scientific justification and references that underpin the proposal. The value of the interaction depends on how clearly the developer articulates its target population, endpoints, comparators, and statistical framework. It also relies on a well-defined risk-mitigation strategy for known uncertainties, such as scientifically justifying deviations from existing guidelines.
Once validated, two coordinators from the Scientific Advice Working Party (SAWP) take responsibility for the request. They lead the assessment and consult discipline experts as needed, including in quality, non-clinical, clinical, biostatistics, and pharmacovigilance. Additionally, they can involve patients to ensure the proposed evidence plan is meaningful and proportionate from a real-world perspective. The SAWP formulates draft advice that is then adopted by the CHMP, which issues the final written outcome.
When the scientific issues are complex or benefit from direct exchange, EMA can offer a teleconference to clarify the applicant’s rationale and probe alternatives (for instance, on endpoint hierarchy or the selection of an external control). Where written material is sufficient, the interaction remains only written.
Before authorisation, the dialogue is confidential. However, once a medicine is authorised, EMA may publish information on the advice. This transparency lets stakeholders see how developers addressed key design issues without disclosing proprietary details, enhancing the learning loop for future developments.
The concrete benefits for developers
Scientific Advice delivers tangible benefits that extend well beyond regulatory compliance. That is true especially for companies and research groups operating in a competitive and highly regulated market. Its primary value lies in reducing uncertainty. By obtaining a prospective view from EMA assessors, developers can confirm whether their planned studies are likely to meet the scientific and legal requirements for marketing authorisation. This foresight allows teams to invest resources in generating data that is relevant, robust, and acceptable to regulators, avoiding costly duplication or redesign of trials.
How does Ema support SMEs?
One of the most measurable advantages is the mitigation of late-stage failures. Projects that enter pivotal trials with unresolved methodological questions risk facing major objections during the assessment phase.
This may potentially require conducting additional confirmatory studies. Such setbacks can add years to development timelines and substantially increase costs. By contrast, programmes that have integrated feedback from Scientific Advice at an early stage are more likely to progress through assessment smoothly.
They face fewer major delays or requests for supplementary evidence.
Moreover, the process strengthens a developer’s credibility with investors, partners, and other stakeholders. Demonstrating that EMA experts have reviewed a programme and that its design reflects regulatory input can de-risk the investment case. It can also improve access to funding.
Costs and incentives
The decision to seek Scientific Advice inevitably raises the question of cost, particularly for SMEs and academic groups operating under tight budgets. Although the standard fee for a multidisciplinary advice procedure can be substantial, the EU has established a structured system of incentives to make the service more accessible. This ensures that a broader range of developers can benefit from regulatory guidance.
The most significant of these is the EMA’s SME programme. This program offers significant fee reductions for companies that meet the EU definition of a small or medium-sized enterprise. Once SME status has been granted, the cost of Scientific Advice can drop by up to 90% compared to the standard rate. In some cases, particularly for micro-enterprises or public-sector institutions, the fee may be waived entirely.
To benefit from these measures, developers must register with the EMA’s SME Office before submitting a Scientific Advice request. To complete this process, the enterprise must first demonstrate that it meets the EU’s quantitative thresholds for staff headcount, turnover, and financial independence. Additionally, it must provide evidence of establishment within the European Economic Area (EEA). Non-EEA companies can still qualify if they operate through an EEA-based subsidiary or collaborate with an EU-registered SME.
For academic groups, while there is no dedicated SME status, certain national or EU funding mechanisms can cover the cost of Scientific Advice as part of a grant. In practice, this means that, consequently, even research consortia without a commercial structure can access regulatory guidance. As a result, they can do so without diverting resources from their core scientific activities. This broad access is critical to promoting a diverse and competitive innovation ecosystem. In such an environment, promising therapies from all sources can be developed in alignment with regulatory standards from the outset.
References: Murphy, A., Bere, N., Vamvakas, S., & Mavris, M. (2022). The added value of patient engagement in early dialogue at EMA: Scientific advice as a case study. Frontiers in Medicine, 8, Article 811855
