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EMA Centralised Process Guide

Timeline, documentation requirements, and strategic guidance for EU marketing authorisation via the centralised procedure

Updated Q4 2025  |  BioPharmaWire Editors  |  Based on Regulation (EC) No 726/2004, EMA procedural guidance, and CHMP guidelines

The European Medicines Agency’s centralised procedure is the regulatory pathway for obtaining a single marketing authorisation (MA) valid across all 27 EU Member States, plus Iceland, Liechtenstein, and Norway. A product approved via the centralised procedure can be marketed across the EEA under a single set of conditions — one Summary of Product Characteristics (SmPC), one patient information leaflet (PIL), and one label. For most novel therapeutics targeting major disease areas, the centralised procedure is either mandatory or the most strategically appropriate route.

Is the Centralised Procedure Mandatory for Your Product?

The centralised procedure is mandatory for the following categories of products:

Medicinal products developed by means of biotechnological processes (recombinant DNA, controlled expression of genes, hybridoma and monoclonal antibody methods)

Advanced therapy medicinal products (ATMPs): gene therapy, somatic cell therapy, tissue-engineered products

Orphan medicinal products designated under Regulation (EC) No 141/2000

New active substances for: HIV/AIDS, cancer, neurodegenerative disorders, diabetes, autoimmune diseases, other immune dysfunctions, viral diseases

The centralised procedure is optional (but available) for: new active substances not listed above; medicinal products constituting a significant therapeutic, scientific, or technical innovation; products in the interest of patients at EU level; generics of centrally authorised reference products.

Note:  Post-Brexit, the UK MHRA no longer participates in the centralised procedure. A separate UK Marketing Authorisation Application must be filed with the MHRA. EMA and MHRA have agreements for information sharing but run independent assessments.

Key Bodies and Roles

CHMP — Committee for Medicinal Products for Human Use

The scientific committee responsible for evaluating MAAs and issuing opinions. Composed of one member and one alternate per EU Member State, plus EEA representatives. The CHMP assigns a rapporteur and co-rapporteur for each application — these two members lead the assessment and coordinate with their national competent authorities (NCAs).

Rapporteur and Co-Rapporteur

The rapporteur is the primary scientific reviewer. They coordinate a team at their NCA to conduct the detailed review. The co-rapporteur provides an independent second assessment. For novel or high-risk products, the rapporteur and co-rapporteur are typically from different Member States with complementary expertise. Sponsors cannot select their own rapporteurs but can indicate desired expertise areas.

EMA Secretariat

Manages administrative processes, coordinates meetings, and maintains the EMA portal. The Product Team Leader (PTL) at EMA is the sponsor’s primary administrative contact throughout the procedure. Scientific questions go to the rapporteur; procedural questions go to the PTL.

COMP — Committee for Orphan Medicinal Products

Responsible for orphan designation decisions. If a product carries orphan designation, COMP may provide input to the CHMP assessment on the orphan condition and criteria. Orphan designation must be maintained at the time of MAA submission to receive OD benefits.

CAT — Committee for Advanced Therapies

For ATMPs (gene therapy, cell therapy, tissue engineering), CAT conducts the primary scientific assessment before CHMP issues its opinion. CAT involvement adds complexity and typically requires earlier pre-submission engagement with EMA.

Centralised Procedure Timeline — Standard Application (210 Active Days)

Note:  The 210-day clock counts active assessment days only. Clock stops during the period when sponsors are preparing responses to the List of Questions (LoQ) and List of Outstanding Issues (LOOI). Total elapsed calendar time from submission to EC decision is typically 12-18 months for a standard application.

Timeline	Milestone	Responsibility	Key Actions & Notes
PRE-SUBMISSION PHASE
T-12 months	Strategic decision: Centralised vs national	Sponsor	Determine if product falls under mandatory or optional centralised scope. Mandatory: new active substances for oncology, rare disease, HIV/AIDS, neurodegenerative, diabetes, autoimmune, viral diseases. Optional: other new active substances, generics of centrally approved products.
T-9 months	Request for pre-submission meeting (MSPD)	Sponsor / EMA	Request a Meeting with EMA Scientific and Product Development (MSPD) team. Discuss development program, CTA strategy, scientific advice needs. Not mandatory but strongly recommended for novel or complex products.
T-9 months	Scientific advice / Protocol assistance	CHMP / Sponsor	Formal scientific advice (SA) from CHMP is non-binding but significantly reduces risk. Protocol assistance (PA) for orphan medicines. SA requests submitted via EMA portal; procedure takes ~70 days.
T-6 months	Letter of Intent (LOI)	Sponsor	Submit LOI to EMA 6 months before intended MAA submission date. Required to initiate administrative validation process. Include product name, active substance, therapeutic indication, and proposed submission date.
T-3 months	Pre-submission meeting	EMA / CHMP rapporteurs	EMA will assign CHMP rapporteur and co-rapporteur at this stage. Pre-submission meeting to discuss dossier readiness, outstanding issues, and CHMP composition. Request specific CHMP expertise if relevant.
T-1 month	Orphan designation confirmation	EMA COMP / Sponsor	If seeking orphan designation, confirm COMP opinion received before MAA submission. Orphan designation must be in place at time of MAA filing to receive OD-related fee reductions and 10-year market exclusivity.
SUBMISSION & VALIDATION (DAY 0 TO DAY 14)
Day 0	MAA submission	Sponsor	Submit complete dossier in eCTD format via EMA eSubmission portal. Dossier must include all CTD modules (1-5). Module 1 is EU-specific (administrative). Modules 2-5 follow ICH CTD structure. Pay application fee at submission.
Day 1-14	Administrative validation	EMA	EMA validates the application for completeness. Common validation failures: missing translations of Module 1 documents, incomplete SmPC/PIL, missing risk management plan, fee payment issues. Validation failure resets the Day 0 clock.
Day 14	Validation confirmation	EMA	Confirmation of valid application triggers the formal 210-day assessment clock. CHMP rapporteur and co-rapporteur assessment begins.
ASSESSMENT PHASE 1: INITIAL REVIEW (DAY 0 TO DAY 120)
Day 0-70	Rapporteur & co-rapporteur assessment	CHMP rapporteurs	Lead rapporteur and co-rapporteur independently review the dossier and prepare preliminary assessment reports. Additional experts (CAs, SAG members) may be consulted for complex issues.
Day 70	Rapporteur & co-rapporteur reports circulated	CHMP	Assessment reports circulated to all CHMP members. CHMP members may raise additional questions or concerns beyond rapporteur reports.
Day 80	CHMP Day 80 list of questions (LoQ)	CHMP	CHMP consolidates all questions into a single List of Questions. Divided into Major Objections (MOs) and Other Concerns (OCs). MOs represent issues that could prevent approval if unresolved. Clock stops here — sponsor response time excluded from 210 days.
Day 80 + 3-6 months	Sponsor response to LoQ	Sponsor	No fixed timeline for response — sponsor works to own schedule, but EMA expects response within 3-6 months for standard applications, 1-3 months for conditional/accelerated. Response must address every question. Clock resumes on receipt of response.
ASSESSMENT PHASE 2: RESPONSE REVIEW (DAY 120 TO DAY 210)
Day 120	Joint rapporteur assessment of responses	CHMP rapporteurs	Rapporteurs assess sponsor responses. If all MOs resolved: proceed to Day 150 opinion. If outstanding MOs remain: oral explanation or second round of questions (second LoQ) issued.
Day 150	CHMP Day 150 assessment report	CHMP	Updated assessment reports circulated. If no outstanding major objections, CHMP moves toward positive opinion. If second LoQ issued, clock stops again for sponsor response.
Day 150-210	Oral explanation (if needed)	Sponsor / CHMP	Sponsor may be invited to present to CHMP in person to address outstanding scientific questions. Rare but used for complex or controversial applications. Typically held in Amsterdam at EMA offices.
Day 210	CHMP opinion	CHMP	CHMP adopts positive or negative opinion by consensus or qualified majority vote. Positive opinion includes final SmPC, PIL, and EPAR. Negative opinion includes grounds; sponsor may request re-examination within 15 days.
POST-OPINION: EUROPEAN COMMISSION DECISION
Day 210 + 15 days	Re-examination request deadline	Sponsor	If CHMP opinion is negative, sponsor has 15 days to request re-examination. Re-examination triggers an additional ~60 day procedure with an independent expert group (Benefit-Risk Methodology Working Party).
Day 210 + 67 days	EC Decision	European Commission	EC issues marketing authorisation decision based on CHMP opinion. Standard timeline is 67 days post-opinion. Decision is valid in all 27 EU Member States plus Iceland, Liechtenstein, and Norway (EEA).
Post-EC decision	Market launch readiness	Sponsor	Country-specific pricing and reimbursement negotiations begin post-EC decision (not coordinated centrally). Product must be commercially available in each Member State within agreed timeframes or authorisation may lapse.

 

 

Accelerated Pathways and Special Designations

EMA offers several mechanisms to accelerate assessment or enable earlier access for products addressing unmet medical need.

Pathway	Eligibility	Key Feature	Timeline Impact	How to Apply
Accelerated Assessment	Products of major public health interest, particularly innovation or therapeutic innovation	Reduces Day 120 to Day 90; overall 150-day procedure	Saves ~60 days vs standard. Clock still stops for LoQ response — real-world benefit varies by sponsor response speed	Request at Letter of Intent stage. CHMP decides at Day -50 meeting. Sponsor must commit to dossier readiness at Day 0
Conditional Marketing Authorisation	Unmet medical need; benefit-risk positive but comprehensive data not yet available	Approval on less complete data with annual renewal and post-authorisation commitments	No timeline reduction but enables earlier access. Annual renewal until comprehensive data submitted. Can convert to full MA	Eligibility discussed at pre-submission meeting. Include justification for conditional approval in Module 1.8 of dossier
Exceptional Circumstances	Rare conditions where comprehensive data cannot be expected (e.g. ultra-rare disease, ethical impossibility of RCTs)	Permanent authorisation under exceptional circumstances with specific obligations	No timeline reduction. Annual benefit-risk review required. Cannot convert to full MA — permanent exceptional status	Must demonstrate why comprehensive data cannot be provided. Discuss with CHMP via scientific advice before application
PRIority MEdicines (PRIME)	Unmet medical need in Phase 1 or later. Not limited to centralised procedure candidates	Early EMA engagement, dedicated CHMP contact, free scientific advice, rolling review option	No formal timeline reduction but early engagement significantly reduces late-stage surprises. Rolling review can reduce Day 0-210 substantially	Apply after Phase 1 proof-of-concept. Submit PRIME request via EMA portal. Decision within 3 months of request
Rolling Review	Promising medicines during public health emergencies or for PRIME-designated products	CHMP reviews data packages as they become available before formal MAA submission	Formal 210-day clock still starts at Day 0 but significant pre-review means Day 80 LoQ typically much shorter	Request rolling review via EMA. Data packages submitted in agreed tranches. Used extensively during COVID-19 vaccine approvals

 

 

Dossier Structure: What the EMA Expects

Module 1 — Administrative Information (EU-Specific)

Module 1 is not part of the ICH CTD and is specific to the EU. It includes: application form (eAF), SmPC, PIL, labelling, product information translations (required in all EEA languages by Day 210), fee declaration, environmental risk assessment, information on paediatric studies (PIP compliance or waiver/deferral), and the risk management plan (RMP). The RMP is a mandatory EU requirement with no direct equivalent in a US NDA/BLA — allocate significant preparation time.

Module 2 — Quality, Nonclinical, and Clinical Summaries

Written summaries and tabulated summaries of the complete data package. The quality overall summary (QOS), nonclinical overview, and clinical overview are critical documents that must tell a coherent scientific story. CHMP reviewers read Module 2 before the full study reports in Modules 4 and 5 — the narrative quality here significantly influences the assessment trajectory.

Module 3 — Quality (CMC)

Pharmaceutical development, manufacturing, controls, reference standards, container closure systems, stability. EU GMP certification for manufacturing sites is required and must be current. EMA may conduct GMP inspections as part of the assessment — plan for this, particularly for novel manufacturing processes or sites not previously inspected by an EU authority.

Module 4 — Nonclinical Study Reports

Full study reports for all pharmacology, pharmacokinetics, and toxicology studies. ICH M3(R2) defines the nonclinical package required before filing. For ATMPs and biologics, additional guidelines apply (ICH S6, EMA ATMP guidelines). Ensure all studies are conducted under GLP where required — EMA distinguishes clearly between GLP and non-GLP studies.

Module 5 — Clinical Study Reports

Full clinical study reports for all trials conducted. For EU submissions, the CONSORT reporting standard is expected for randomised trials. Integrated summaries of safety (ISS) and efficacy (ISE) are strongly recommended and expected for any application with more than a handful of studies. CHMP increasingly scrutinises the statistical analysis plan pre-specified vs post-hoc analyses — ensure statistical methodology is clearly documented.

Risk Management Plan (RMP): EU-Specific Requirement

The RMP is a mandatory component of every centralised MAA and has no direct US equivalent. It covers: safety specification (known and potential risks, missing information), pharmacovigilance plan (routine and additional activities), and risk minimisation measures (routine and additional, such as educational materials, controlled distribution programs). The RMP is reviewed by the Pharmacovigilance Risk Assessment Committee (PRAC) in parallel with CHMP assessment. Budget significant time and regulatory expertise for RMP development — it is one of the most common sources of Day 80 questions.

 

Common Pitfalls in EMA Centralised Applications

Tip:  Start paediatric investigation plan (PIP) compliance early. PIP decisions from the PDCO take 6-18 months. A missing PIP compliance decision at submission is a Day 0 validation failure.

Tip:  Translations of product information (SmPC, PIL, label) into all EEA languages must be ready by Day 150, not Day 210. Engage translation vendors early — 24 language versions is a significant undertaking.

Tip:  The environmental risk assessment (ERA) is frequently underestimated. Pharmaceuticals with environmental persistence or ecotoxicity concerns require Phase II ERA data. Failing to conduct ERA studies before submission is a common source of Day 80 major objections.

Tip:  GMP certificates for all manufacturing sites must be current at the time of submission and throughout the assessment. Sites not previously inspected by an EU authority may require a pre-approval inspection — coordinate with EMA at least 12 months before submission.

Tip:  If planning simultaneous US and EU submissions, align the submission timeline carefully. A US approval before EU opinion is not unusual, but conflicting label language between FDA and EMA can create complications — particularly for safety and indication wording.

This guide is an editorial product of BioPharmaWire based on publicly available EMA procedural guidance and EU pharmaceutical legislation as of Q4 2025. Procedural timelines and requirements are subject to change. This document does not constitute regulatory or legal advice. Sponsors should consult qualified EU regulatory affairs professionals and refer to current EMA guidance before initiating a centralised procedure application.