EMA Guidance: Revised Pre-Submission Interactions Model

Sharan Murugan
16 minutes ago
4 min read

Preparing a marketing authorisation application (MAA) requires early planning, clear communication, and a sufficiently mature dossier. To strengthen this process, the European Medicines Agency (EMA) has introduced a revised Guidance on the "Pre-Submission Interactions (PSI) model" as part of a voluntary pilot phase.

The revised model aims to encourage earlier and more comprehensive dialogue between applicants, rapporteurs, and EMA. It focuses on improving submission readiness, identifying applications that may be premature, addressing potential assessment issues, and supporting alignment on the intended MAA submission timeline.

Purpose of the Revised PSI Model

The revised PSI model introduces a more collaborative approach to pre-submission planning. It establishes shared ownership between the applicant, rapporteurs, and EMA regarding submission timing and provides greater visibility of the preparation process.

The pilot is planned to run for 18 months, with applicants who plan to submit MAA applications between February 2027 and September 2028 eligible to participate. The applicant, rapporteurs, and EMA will jointly agree on which applications are included in the pilot.

For this guidance, PSI covers the period from the request for rapporteurs’ appointment through to submission of the MAA and excludes the eligibility step.

Key Stages of the Revised PSI Process

The eligibility request remains unchanged and should be submitted 18 months before the intended MAA submission date.

The request for allocation of rapporteurs should then be submitted 9 months before the intended MAA submission date.

The revised PSI consists of two main elements:

A written interaction with EMA.
A joint pre-submission meeting (PSM) involving the applicant, CHMP, PRAC or CAT rapporteur(s), and EMA.

Following the joint PSM, the applicant should submit the Letter of Intent (LoI) reflecting the agreed MAA submission date, at the latest 2 months before the initially intended submission date.

Request for Rapporteurs’ Allocation

Applicants should use the revised EMA PSI form and follow the instructions provided with it. The completed form must be submitted electronically through the IRIS portal, together with the background documents listed in the form.

The revised PSI form provides enhanced guidance and includes questions covering procedural, compliance, and regulatory affairs aspects. This information helps EMA identify topics that may require attention and supports effective validation guidance and evaluation of the application.

EMA product team feedback is expected to be provided in writing within 3 weeks of submission.

Applicants are also encouraged to engage early with both the rapporteurs and EMA when submitting the PSI form. Early contact can help facilitate agreement on a suitable date for the joint pre-submission meeting.

Preparing for the Joint Pre-Submission Meeting

Applicants are responsible for organising the joint PSM and should use the EUSTART list to support preparation.

The EUSTART document helps identify issues for discussion and allows rapporteurs to assess the maturity of the application. Applicants should address all relevant points raised in the document within their briefing package, including any open major issues identified during the EMA PSI.

The briefing package should be submitted through Eudralink to all participants 3 weeks before the meeting. The supporting presentation should be provided at least 1 week before the meeting.

The presentation should not exceed 20 minutes, allowing sufficient time for discussion. The meeting begins with introductory remarks, followed by the applicant’s presentation and discussion, and is chaired by the rapporteur.

Applicants should be prepared to address all relevant dossier-related issues.

Assessing Submission Readiness

A key objective of the revised PSI model is to determine whether an application is sufficiently mature for submission.

An application may be considered insufficiently mature when the available data package does not adequately support a robust benefit-risk assessment or an efficient assessment within the applicable timelines.

Potential concerns may include significant missing or incomplete data, reliance on interim results, unresolved major quality, manufacturing or compliance issues, missing supportive analyses or justifications, or anticipated major objections that could require substantial additional data or extended clock-stops.

Applicants are therefore encouraged to assess the overall maturity and completeness of their application before confirming the intended MAA submission date.

What Should Applicants Consider?

When evaluating submission readiness, applicants should consider the availability and completeness of pivotal clinical, non-clinical, and quality data.

They should also assess whether the available evidence is sufficiently complete, robust, relevant, and consistent to support the proposed indication and benefit-risk balance.

Other important considerations include:

Reliance on interim or evolving datasets that could affect the assessment outcome.
Known quality, manufacturing, or compliance issues.
Availability of key supportive analyses, validations, or justifications.
The need for substantial additional data generation during the procedure.
Alignment with previous scientific advice or regulatory interactions, where applicable.

The EUSTART questions document should be used to support preparation for the joint PSM and evaluation of submission readiness.

Rapporteur Feedback and Submission Timing

During the joint meeting, rapporteurs provide feedback on the questions and topics raised. They also provide their views on the degree of submission readiness and maturity of the application and whether the initially intended submission date can be agreed.

Where appropriate, further exchanges may take place after the meeting to support alignment on the submission date. Rapporteurs may also seek input from CHMP in exceptional circumstances, with the applicant receiving the CHMP feedback as soon as possible.

Following the meeting, the applicant provides the meeting minutes within 2 weeks, including conclusions on dossier maturity and the anticipated submission date.

Letter of Intent and Next Steps

After the joint pre-submission meeting, the applicant submits the Letter of Intent (LoI) through the IRIS portal.

The LoI should reflect the agreed MAA submission date and forms an important part of the planning process under the revised PSI model.

Through earlier dialogue, assessment of application maturity, and shared planning of submission timelines, the revised model is intended to improve submission readiness and make the timing of regulatory submissions more predictable.