EMA’s new pre-submission interactions model pilot: A fundamental shift toward submission readiness and predictable reviews

Introduction 

In September 2026, the European Medicines Agency (EMA) launched a new 18-month pilot program designed to transform how sponsors prepare for centralized marketing authorisation applications (MAAs).¹ The new pre-submission interactions (PSI) model pilot introduces a more structured and collaborative approach between applicants, rapporteurs, and EMA before dossier submission. The pilot aims to improve submission readiness, identify potential assessment challenges earlier, and reduce delays caused by immature applications.  

The initiative reflects an important reality that regulators and industry have increasingly recognized: many delays during assessment are not caused by scientific disagreement, but by timing. Applications are sometimes submitted before datasets are sufficiently mature, resulting in avoidable clock stops, requests for substantial additional information, and prolonged review timelines. EMA's revised model seeks to address these challenges by introducing earlier and more transparent dialogue throughout the pre-submission phase.  

For sponsors developing innovative medicines, particularly in complex areas such as oncology, cell and gene therapies, rare diseases, and products relying on novel manufacturing platforms, the pilot represents one of the most significant procedural changes to EMA pre-submission activities in recent years. 

The strategic importance of early alignment 

Although the revised PSI model may appear to be merely an administrative enhancement, in practical terms, it indicates a broader regulatory evolution toward shared ownership of submission readiness. 

Under the current model, meaningful interactions between applicants and rapporteurs were limited to the pre-submission meeting – basically one single interaction with no follow-up. While scientific advice and other procedural interactions are available, sponsors often receive critical feedback regarding dossier maturity only after the assessment has formally started. By that point, delays may already be unavoidable. 

The new pilot changes this dynamic by creating structured touchpoints beginning as early as nine months before submission and culminating in a formal joint meeting, known as EUSTART (EU Submission, Timelines and Review Talk), approximately three months before filing.  

The pilot introduces:  

• Rapporteur allocation supported by an updated development status overview 
• Written pre-submission interactions at least five months before submission 
• A joint EUSTART meeting involving the applicant, rapporteurs, and EMA 
• Confirmation of the agreed submission date through a Letter of Intent two months before filing  

It helps create alignment on dossier maturity, submission timing and identify potential assessment risks before the application officially enters review. For sponsors, this means the question is no longer simply, "Can we submit?" but rather, "Are we collectively aligned that this application is ready for review?" 

The consequences of premature submission can be substantial. Applications with unresolved quality concerns, immature efficacy datasets, incomplete safety follow-up, or poorly justified manufacturing changes frequently need extended clock stops and additional requests for information. However, based on our experience, the CHMP has recently become restrictive in granting extended clock stops.  If the requested data cannot be provided within the procedure timelines, common risks include a negative opinion by the CHMP or a withdrawal by the company. EMA explicitly notes that the pilot is intended to identify such situations earlier and support alignment on realistic submission timelines.  

The broader regulatory context 

The pilot should also be viewed within the broader evolution of European medicines regulation. 

Across multiple initiatives, EMA has increasingly emphasized early interaction, proactive planning, and regulatory predictability. Examples include enhanced scientific advice pathways, PRIME support for innovative medicines, and efforts to improve assessment efficiency under increasing workload pressures. 

The PSI model pilot extends this philosophy into the pre-submission space. Instead of assessing dossier readiness retrospectively during review, regulators are seeking to evaluate readiness prospectively before submission. 

From a regulatory science perspective, this approach is logical. The quality of an assessment is heavily influenced by the quality and maturity of the initial dossier. Earlier transparency benefits both regulators and sponsors by reducing surprises during review. 

Potential benefits for sponsors 

Sponsors participating in the pilot may already realize several advantages: 

• Improved assessment predictability: The structured interactions create opportunities to identify critical gaps before submission rather than during assessment. This may reduce the likelihood of major review disruptions and facilitate more predictable procedural timelines. 
• Better resource planning: The pilot encourages earlier visibility into development readiness and submission planning. This can support better alignment across regulatory, clinical, CMC, biostatistics, and safety teams. 
• Stronger internal governance: The requirement to discuss dossier maturity with EMA and rapporteurs introduces a valuable external challenge mechanism. Internal enthusiasm to accelerate submission can sometimes outpace objective readiness. Independent regulatory perspectives can help organizations make more balanced decisions. 
• Enhanced rapporteur engagement: Early interactions may provide valuable opportunities to establish mutual understanding regarding the development program before formal assessment begins. 

The only potential risk is ignoring the changes that are coming. This pilot will test the waters, and we expect that it will be fully implemented and mandatory with the implementation of the new EU pharmaceutical legislation.  

In order to fully realize the benefits, sponsors should start preparing now.  

Short-term actions 

Sponsors planning centralized MAAs between February 2027 and September 2028 should evaluate whether participation in the pilot would be advantageous. EMA has indicated that participation is voluntary and open to applicants within this submission window.  

Organizations should begin assessing: 

• Submission readiness governance processes 
• Cross-functional alignment mechanisms 
• Availability of mature clinical, nonclinical, and CMC datasets 
• Regulatory risk assessment frameworks 

Medium-term actions 

Sponsors should strengthen dossier readiness evaluations beyond traditional milestone tracking. At Parexel, we have observed that successful submissions rarely depend solely on meeting development milestones. Instead, successful programs systematically evaluate whether the totality of evidence is sufficiently mature to support benefit-risk conclusions and withstand regulatory scrutiny. 

Companies should consider implementing: 

• Formal submission readiness reviews 
• Independent internal challenge sessions 
• Early identification of critical review risks 
• Cross-functional regulatory scenario planning 

Long-term implications 

The industry should not view this as merely a pilot. The approach may influence future EMA practices and become part of standard pre-submission expectations. Sponsors that adapt early may gain an advantage by embedding submission readiness principles more deeply into development planning. 

Conclusion 

EMA's PSI model pilot represents more than a procedural update. It reflects a strategic shift toward earlier collaboration, shared accountability, and proactive management of submission readiness. 

Parexel believes the most important message is not that sponsors should prepare more documents or attend additional meetings, but organizations should recognize that submission readiness has become a critical regulatory competency in the EU. 

Over the past decade, we have consistently observed that the most successful submissions are those where sponsors challenge themselves rigorously before regulators do. Programs that proactively identify weaknesses, align stakeholders, and establish realistic timelines tend to experience smoother assessments and achieve more predictable outcomes. The new PSI model institutionalizes this philosophy. 

Sponsors preparing future centralized MAAs should use this pilot not only as an opportunity to engage with EMA earlier, but also as a catalyst to strengthen internal readiness processes. Those that do so will be better positioned to reduce regulatory risk, improve timeline predictability, and ultimately accelerate patient access to innovative medicines. 

How Parexel can help  

Organizations considering participation in EMA's PSI pilot should evaluate their readiness now and establish a structured strategy for engaging with rapporteurs and EMA throughout the pre-submission period.Parexel supports sponsors throughout the product lifecycle, from development strategy and scientific advice through MAA submission and post-approval activities. With former regulators, former CHMP members, assessors, clinicians, statisticians, and CMC experts, we routinely conduct independent submission readiness assessments, helping clients identify and mitigate risks before formal regulatory review begins. 
 

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References 

1. EMA Pre-Submission Interactions Model Pilot [ema.europa.eu] 

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