EMA Pre-Submission Pilot Adds Earlier Dialogue to Curb Premature Filings

The European Medicines Agency (EMA) has announced a voluntary pilot that changes how applicants, rapporteurs and the Agency work together in the months before an initial marketing authorisation application (MAA) is filed. The EMA pre-submission pilot was published on 28 August 2026 and opens in September 2026, covering initial MAAs planned for submission between February 2027 and September 2028.

EMA’s stated problem is premature filing. Applications arrive before the data package is mature enough to support a robust benefit-risk assessment within the standard timelines, and those filings go on to cause delays, clock-stop extensions and the late submission of substantial new data. The pilot tests an earlier, more structured dialogue between the applicant, the appointed rapporteurs and EMA, with everyone sharing ownership of the intended submission date.

The objectives are to optimise submission readiness, identify premature applications and assessment issues early, align applicants and assessors on realistic timelines, and give all parties better visibility of planning before the formal application is filed.

Who can take part in the EMA pre-submission pilot

Participation is voluntary and limited to applicants planning an initial MAA between February 2027 and September 2028. Inclusion is not automatic: the applicant, the relevant rapporteurs and EMA must agree together which applications enter the pilot. Once an application is in, the parties are expected to follow the agreed process through to submission so EMA can measure the model against defined key performance indicators.

EMA will contact applicants that already have an initial MAA scheduled from February 2027 onwards. Applicants can also approach EMA first through their EMA Product Lead and agree participation with the rapporteurs and the Agency ahead of the relevant milestones. The eligibility request itself, made 18 months before the intended submission, is unchanged.

The revised five-step model

The pilot keeps the existing eligibility step and inserts earlier, more structured touchpoints between rapporteur appointment and filing.

Eligibility request: 18 months before filing, unchanged.
Request for rapporteur allocation plus a development status overview: 9 months before filing, submitted with an up-to-date overview that is the pilot’s annex to the rapporteurship request.
Written pre-submission interactions: 5 months before filing, using a revised PSI form through IRIS with the listed background documents. EMA provides written feedback within three weeks of a complete submission.
Joint pre-submission meeting (EUSTART): 3 months before filing, a joint meeting of applicant, rapporteurs and EMA on dossier maturity and submission readiness. EUSTART stands for EU Submission, Timelines and Review Talk.
Letter of intent: 2 months before filing, confirming the agreed submission date and filed through IRIS.

For the written PSI, applicants complete the revised EMA PSI form electronically and submit it through IRIS together with the background documents listed on the form. EMA’s product team returns consolidated written feedback within three weeks of a complete package. Major issues left open are expected to be addressed at the later joint meeting.

For the EUSTART meeting, the applicant organises the session and is encouraged to contact both the rapporteurs and EMA in a single email as soon as the PSI form is in, so a date can be locked. The guidance sets practical rules: a briefing package to all participants via Eudralink at least three weeks before the meeting, supporting slides at least one week before, and an applicant presentation capped at 20 minutes to leave room for discussion. The rapporteur chairs the meeting, which moves from welcome and introductions to the presentation and then to discussion. Rapporteurs give their view on dossier maturity, submission readiness and whether the intended date can be agreed. Exceptionally, rapporteurs may seek CHMP input, and the applicant should receive that feedback promptly. The applicant circulates minutes within two weeks, including the conclusion on maturity and the anticipated submission date. Further exchanges after the meeting are allowed where needed to settle the date.

What “submission readiness” means

A filing may be treated as insufficiently mature if the data package cannot support a robust benefit-risk assessment and an efficient procedure within the applicable timelines. EMA’s examples include significant missing or incomplete data; reliance on interim results that do not yet give a sufficiently complete view of benefit-risk; unresolved major quality, manufacturing or compliance issues; missing key supportive analyses or justifications; anticipated major objections likely to force extended clock-stops or extra data that cannot be generated inside standard timelines; and pending data expected during the procedure that could change the assessment outcome.

The EUSTART questions cover completeness of the confirmatory clinical, non-clinical and quality data; robustness and consistency of the evidence for the claimed indication; known GMP, quality and compliance issues; alignment with prior scientific advice; and whether substantial new data will still be needed after filing.

EUSTART discussion topics

The EUSTART document (EMA/189190/2026, dated 24 August 2026) is a structured checklist for the joint meeting. Its aims are to support a smoother assessment, reduce clock-stop extensions, avoid dossiers that are later padded with substantial new data, and lock an agreed submission date. The topics fall into five blocks.

General and regulatory points cover the legal basis; Article 10 bridging strategy; prior national competent authority or CHMP scientific advice, protocol assistance and any deviations; applicable guidelines and deviations; the claimed indication, orphan designation and other authorised products in the condition; PDCO opinion and PIP compliance and paediatric formulation; accelerated assessment; conditional marketing authorisation or authorisation under exceptional circumstances; new active substance status and the additional year of market protection; and the comprehensiveness of the data package and proposed post-authorisation commitments.

Quality and GMP points cover starting materials; commercial-batch use in confirmatory trials and comparability; specifications; nitrosamine risk investigations; medical devices that are co-packaged or integral and MDR or notified-body opinion; manufacturing and testing flow; batch-release sites; process and method validation; stability; manufacturing authorisations and EU or MRA GMP certificates for third-country sites; and the likely need for inspection of third-country sites during evaluation.

Non-clinical points cover the development overview; ICH S9 where applicable; literature toxicity data and its reliability and completeness; the environmental risk assessment; major preclinical concerns for the SmPC and RMP; and planned post-authorisation non-clinical measures.

Clinical and GCP points cover pharmacokinetic characterisation across special populations, drug-drug interactions and age and sex; PK/PD and model-informed drug development; the confirmatory data package, target population and posology consistency; biomarkers and companion diagnostics; estimands; non-inferiority or equivalence margins; final clinical study reports at filing versus later data cuts; GCP inspections and audits and their findings; planned inspections; major safety concerns; additional risk minimisation; post-authorisation monitoring; and the maturity of the product information at submission.

Submission-date points cover the planned date and known risks to it, plus ongoing or planned work whose results may become available during evaluation.

Regulatory, administrative and procedural points are expected to be raised in writing during the earlier PSI exchange, not parked for the joint meeting.

How this differs from the current model

The standard pre-authorisation Q&A still describes the live model for products not in the pilot. Under that model, MAA pre-submission interactions typically start about six to seven months before the intended filing. Applicants submit the MAA PSI form and a simplified briefing package through IRIS, EMA aims to return written comments within three weeks, and a teleconference or meeting is added only if issues remain or the case is complex. Rapporteur meetings are encouraged at national level. The letter of intent, or notification of intent, triggers rapporteur appointment and later reconfirms the date.

The pilot does not replace eligibility. What it adds is an earlier rapporteur-allocation package with a development-status annex at nine months, a written PSI checkpoint at five months, a systematic joint meeting at three months focused on maturity rather than only on administrative questions, and a letter of intent at two months that confirms a date already discussed with the assessors. Shared ownership of timing is the explicit design change.

What this means for applicants

Treat initial MAA plans between February 2027 and September 2028 as in scope for a conversation with the Product Lead now.
Build a nine, five, three and two-month internal calendar, not a single pre-submission meeting at six to seven months.
The nine-month rapporteur request needs a living development-status overview, not a placeholder.
The five-month written PSI is the place for legal, regulatory and administrative questions.
The three-month EUSTART meeting is a maturity negotiation. Arrive with a complete checklist response, a short slide deck and a defensible date.
Minutes and the two-month letter of intent should match what was agreed in the room.
If the package is still interim-heavy, has open GMP issues or will need major new analyses after filing, expect pressure to move the date rather than file and extend the clock.
Once in the pilot, dropping the process mid-stream undercuts the KPI exercise, so plan resourcing through to submission.

Source: Pre-submission interactions model pilot, European Medicines Agency.