Marketing Authorisation Application: Your Complete Guide to EMA Drug Approval
A marketing authorisation application (MAA) is the formal regulatory submission to the European Medicines Agency requesting EU drug approval, with an 85% approval rate and 210-day active assessment timeline.
A marketing authorisation application (MAA) is the formal submission to the European Medicines Agency (EMA) requesting approval to market a medicinal product in the European Union. The MAA contains comprehensive data demonstrating the quality, safety, and efficacy of the medicine and forms the basis for the Committee for Medicinal Products for Human Use (CHMP) scientific assessment.
For pharmaceutical and biotech companies targeting the European market, the MAA represents the critical regulatory milestone between clinical development and commercial launch. A well-prepared marketing authorisation application can mean the difference between timely market access across 27 EU member states and costly delays that impact patients and revenue.
In this guide, you will learn:
- How the MAA application process works through the centralised procedure
- Complete content requirements for each eCTD module in your MAA submission
- EMA marketing authorization timelines from validation to European Commission decision
- Key differences between MAA vs NDA submissions for global regulatory planning
- Practical strategies for preparing a successful marketing authorisation application
What Is a Marketing Authorisation Application?
Marketing Authorisation Application (MAA) - A comprehensive regulatory dossier submitted to the European Medicines Agency demonstrating a medicinal product's quality, safety, and efficacy to obtain EU-wide marketing authorization. The MAA follows eCTD format and is assessed by CHMP with final approval granted by the European Commission.
A marketing authorisation application is the regulatory dossier submitted to the European Medicines Agency seeking approval to place a medicinal product on the EU market. The MAA must demonstrate that the product's benefits outweigh its risks for the proposed indication and that the manufacturing process ensures consistent quality.
Key characteristics of a marketing authorisation application:
- Submitted in eCTD (electronic Common Technical Document) format
- Evaluated by CHMP with rapporteur and co-rapporteur from EU member states
- Covers quality (CMC), non-clinical, and clinical data in five standardized modules
- Results in a CHMP opinion followed by European Commission marketing authorization decision
According to EMA annual reports, the Agency receives approximately 100-120 marketing authorisation applications through the centralised procedure each year, with an approval rate of approximately 85% for applications reaching Day 180 assessment.
The marketing authorisation application process differs fundamentally from FDA's NDA pathway. While FDA directly approves drugs, EMA provides scientific recommendations through CHMP, and the European Commission grants the final marketing authorization valid across all EU member states.
Types of EMA Marketing Authorization Procedures
Understanding the different authorization pathways helps you select the most appropriate route for your MAA application. The procedure you choose depends on your product type, target markets, and regulatory strategy.
Centralised Procedure (CP)
The centralised procedure is the primary pathway for marketing authorisation applications at EMA. This procedure results in a single authorization valid throughout the EU.
Mandatory for:
- Biotechnology-derived products (recombinant DNA, monoclonal antibodies)
- Advanced therapy medicinal products (ATMPs)
- Orphan-designated medicinal products
- Products for HIV/AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune disorders, and viral diseases
- New active substances for rare diseases
Optional for:
- Products with significant therapeutic innovation
- Products in the interest of public health at EU level
- Generic/hybrid applications referencing centrally authorized products
Decentralised Procedure (DCP)
The decentralised procedure allows simultaneous authorization in multiple EU member states for products not requiring centralised authorization:
| Feature | Centralised Procedure | Decentralised Procedure |
|---|---|---|
| Scope | Entire EU + EEA | Selected member states |
| Assessment body | CHMP at EMA | Reference Member State (RMS) |
| Timeline | 210 days + EC decision | 210 days + national decisions |
| Single application | Yes | Yes |
| Mandatory products | Biologics, orphan drugs, ATMPs | Not applicable |
| Fee structure | EMA fees | National fees (typically lower) |
Mutual Recognition Procedure (MRP)
The mutual recognition procedure extends an existing national authorization to additional EU member states. This pathway is used when a product already has authorization in one member state.
National Authorization
Individual member states can grant national marketing authorizations for products not seeking EU-wide approval. This pathway is rarely used for innovative products but may suit products with limited geographic ambitions.
MAA Application Content Requirements
A complete marketing authorisation application follows the eCTD format established by ICH guidelines. Understanding each module's requirements is essential for MAA submission success.
Module 1: Administrative and Product Information
Module 1 contains region-specific administrative information for the EMA marketing authorization:
| Document | Purpose | Key Requirements |
|---|---|---|
| Application form | Formal request | Company details, product identification, legal basis |
| Summary of Product Characteristics (SmPC) | Prescribing information | Indication, dosing, contraindications, warnings |
| Labeling | Package information | Text for outer and immediate packaging |
| Package leaflet | Patient information | User-friendly product information |
| Expert statements | Quality/clinical expertise | Signed declarations from qualified experts |
| Environmental risk assessment | Environmental impact | Required for products with potential environmental release |
The Summary of Product Characteristics (SmPC) is one of the most critical documents in your MAA application. It forms the basis for the product label and requires extensive negotiation with CHMP during the assessment procedure.
Module 2: Common Technical Document Summaries
Module 2 provides high-level summaries of the technical information contained in Modules 3, 4, and 5:
Module 2.1: Table of Contents
- Complete navigation structure for the entire MAA
Module 2.2: Introduction
- Brief product overview and application context
Module 2.3: Quality Overall Summary (QOS)
- Comprehensive summary of Module 3 CMC data
- Drug substance and drug product manufacturing
- Control strategy and specifications
Module 2.4: Nonclinical Overview
- Integrated analysis of pharmacology and toxicology
- Safety assessment conclusions
Module 2.5: Clinical Overview
- Critical analysis of clinical data
- Benefit-risk assessment
- Discussion of clinical pharmacology, efficacy, and safety
Module 2.6: Nonclinical Written and Tabulated Summaries
- Detailed summaries of all nonclinical studies
- Standardized tables for pharmacology and toxicology data
Module 2.7: Clinical Summary
- Biopharmaceutics and associated analytical methods
- Clinical pharmacology studies
- Clinical efficacy summary
- Clinical safety summary
Module 3: Quality (CMC)
Module 3 contains all quality data for both drug substance and drug product:
| Section | Content | Assessment Focus |
|---|---|---|
| 3.2.S Drug Substance | Manufacturing process, characterization, specifications | Process control, impurity profile |
| 3.2.P Drug Product | Formulation, manufacturing, stability | Product consistency, shelf life |
| 3.2.A Appendices | Facilities, excipients, novel excipients | GMP compliance, excipient quality |
| 3.2.R Regional Information | CEPs, TSE certificates | EU-specific requirements |
Module 3 quality deficiencies account for approximately 30% of major objections in MAA assessments, according to EMA analysis. Ensuring robust CMC data before submission significantly improves approval probability.
Module 4: Nonclinical Reports
Module 4 contains complete nonclinical study reports:
- Pharmacology studies (primary, secondary, safety pharmacology)
- Pharmacokinetics (ADME studies)
- Toxicology (single-dose, repeat-dose, genotoxicity, carcinogenicity)
- Reproductive and developmental toxicity
- Local tolerance studies
Module 5: Clinical Study Reports
Module 5 contains all clinical study reports and data:
| Section | Content |
|---|---|
| 5.2 | Tabular listing of all clinical studies |
| 5.3.1 | Biopharmaceutic studies |
| 5.3.2 | Studies pertinent to pharmacokinetics using human biomaterials |
| 5.3.3 | PK studies and PD studies in healthy subjects |
| 5.3.4 | PK and PD studies in patients |
| 5.3.5 | Efficacy and safety studies |
| 5.3.6 | Post-marketing reports |
| 5.4 | Literature references |
The MAA Submission Process Step by Step
Understanding the complete MAA application timeline helps you plan resources and set realistic expectations for EU market access.
Pre-Submission Phase (6-12 Months Before Filing)
Before submitting your marketing authorisation application, several preparatory steps optimize your chances of success:
Scientific Advice:
- Request EMA scientific advice on development strategy
- Address quality, non-clinical, and clinical questions
- Protocol assistance available for orphan-designated products
Pre-Submission Meeting:
- Discuss procedural aspects with EMA Product Team
- Clarify submission requirements and format
- Review conditional requirements or accelerated pathways
Notification of Intent:
- Submit at least 7 months before planned submission
- Declare product type, procedure, and expected data
- Enables CHMP slot allocation and rapporteur appointment
Submit your notification of intent as early as possible, ideally 9-12 months before planned filing. This allows EMA to assign experienced rapporteurs in your therapeutic area, which can significantly improve assessment quality and reduce unexpected questions.
MAA Validation (Days -10 to Day 1)
EMA validates your MAA submission within 10 calendar days:
| Validation Check | Requirement | Consequence of Failure |
|---|---|---|
| Completeness | All required documents present | Validation refused |
| Format | eCTD technical compliance | Technical rejection |
| Fees | Payment or fee waiver documentation | Validation delayed |
| Legal basis | Appropriate authorization pathway | Application rejected |
| SME status | SME registration if claiming reductions | Fee recalculation |
Approximately 5-10% of MAA submissions fail initial validation due to technical or administrative deficiencies. Using validated eCTD publishing software and pre-submission checklists significantly reduces validation failure risk.
Assessment Phase (Days 1-210)
The CHMP assessment procedure spans 210 active days, divided into distinct phases:
Days 1-80: Initial Assessment
- Rapporteur and co-rapporteur prepare assessment reports
- Parallel assessment of quality, non-clinical, and clinical sections
- Identification of preliminary concerns and questions
Day 80: List of Questions (LoQ)
- CHMP adopts consolidated list of questions
- Major objections and other concerns identified
- Clock stops for sponsor response preparation
Clock Stop 1: Response Preparation
- Sponsor prepares responses to Day 80 questions
- Standard: 3 months; Extended: 6 months
- Opportunity to conduct additional analyses or provide clarifications
Days 81-180: Continued Assessment
- Rapporteurs evaluate sponsor responses
- Joint assessment report prepared
- Remaining issues identified
Day 180: List of Outstanding Issues (LoOI)
- CHMP adopts list of outstanding issues
- Final opportunity for sponsor to address concerns
- Clock stops for response preparation
Clock Stop 2: Final Response
- Standard: 1 month response time
- Focused responses to remaining issues
- Oral explanation may be scheduled
Days 181-210: Final Assessment
- Rapporteurs complete final evaluation
- CHMP discussion and opinion
- Day 210: CHMP Opinion adopted
MAA Assessment Timeline Summary
| Phase | Timeline | Key Milestone |
|---|---|---|
| Pre-submission notification | Month -7 | Intent declared |
| Validation | Days -10 to 1 | MAA accepted |
| Initial assessment | Days 1-80 | LoQ issued |
| Clock stop 1 | 3-6 months | Responses prepared |
| Continued assessment | Days 81-180 | LoOI issued |
| Clock stop 2 | 1 month | Final responses |
| Final assessment | Days 181-210 | CHMP Opinion |
| European Commission decision | +67 days | MA granted |
European Commission Decision (Days 211-277)
Following positive CHMP opinion, the European Commission makes the final authorization decision:
- Standing Committee review (member state consultation)
- Commission Decision adopted (typically within 67 days)
- Marketing authorization granted
- Publication in Community Register
The total timeline from MAA submission to European Commission decision is approximately 12-15 months under standard procedures, including clock stops. Accelerated assessment reduces active assessment to 150 days but does not accelerate the Commission decision phase.
EMA Marketing Authorization Fees
Understanding the fee structure for EMA marketing authorization helps you budget appropriately for your MAA submission.
MAA Fees Under EU Regulation 2024/568 (Effective January 2025)
Under the new EU fee regulation effective January 1, 2025, EMA MAA fees are structured across 9 fee levels based on legal basis and active substance type:
| Fee Type | Amount (EUR) | Notes |
|---|---|---|
| New active substance MAA (highest tier) | Up to 865,200 | Full dossier, centralised procedure |
| New active substance MAA (lowest tier) | From 172,800 | Depends on legal basis and substance type |
| Extension of MAA (with clinical/nonclinical data) | 196,800 | Extension of indication with new data |
| Type II variation (extension of indication) | 163,200 | Major variation |
| Scientific advice (initial) | Variable | Recommended before MAA |
| Inspection fees | Variable | Per inspection required |
Annual Fees
Once your product is authorized, annual fees apply:
| Fee Type | Amount (EUR) | Timing |
|---|---|---|
| Annual fee (standard) | 232,400 | Due annually |
| Annual fee (generic/hybrid/informed consent) | 60,300 | Due annually |
| Annual fee (similar biologic) | 18,100 | Due annually |
| Pharmacovigilance fee | 230 per chargeable unit | Separate from annual fee |
| Variation fees | Variable | Per change submitted |
Fee Reductions for SMEs
Small and medium enterprises receive significant MAA fee reductions:
| SME Category | Fee Reduction | Eligibility |
|---|---|---|
| Micro enterprise | 90% | <10 employees, <EUR 2M turnover |
| Small enterprise | 65% | <50 employees, <EUR 10M turnover |
| Medium enterprise | 40% | <250 employees, <EUR 50M turnover |
Fee reductions for SMEs can substantially reduce MAA costs. Additionally, orphan and paediatric applications may qualify for full fee waivers under the new regulation.
Fee Reductions for Special Cases
| Category | Reduction | Conditions |
|---|---|---|
| Orphan designation | 100% (Protocol Assistance) | Valid orphan designation |
| Academic sponsors | Case-by-case | Non-commercial development |
| WHO essential medicines | Variable | Products on WHO list |
| Pandemic products | Potential waiver | Declared health emergency |
MAA vs NDA: Comparing EU and US Drug Approval
For companies pursuing global regulatory strategies, understanding the MAA vs NDA differences is essential for coordinated development and submission planning.
Fundamental Differences: MAA vs NDA
| Aspect | MAA (EMA/EU) | NDA (FDA/US) |
|---|---|---|
| Regulatory authority | EMA recommendation + European Commission decision | FDA direct approval |
| Geographic scope | 27 EU member states + EEA | United States only |
| Review timeline (standard) | 210 active days + EC decision | 10 months (PDUFA date) |
| Review timeline (accelerated) | 150 active days | 6 months (priority review) |
| Clock stops | Standard practice | Limited use |
| Committee structure | CHMP (multi-country assessors) | Single review division |
| Application format | eCTD | eCTD |
| Fee (standard) | EUR 172,800-865,200 (varies by category) | $4,682,003 (FY 2026) |
MAA vs NDA Content Comparison
While both MAA and NDA use the eCTD format, regional requirements differ:
| Module | MAA Specific | NDA Specific |
|---|---|---|
| Module 1 | EU SmPC, EU labeling, ERA | US Prescribing Information, 356h form |
| Module 2 | Same structure | Same structure |
| Module 3 | CEPs accepted, EU GMP | FDA facility registration, US GMP |
| Module 4 | Same structure | Same structure |
| Module 5 | Same clinical data | Same clinical data |
Assessment Process: MAA vs NDA
| Process Element | MAA | NDA |
|---|---|---|
| Pre-submission interaction | Scientific advice, pre-submission meeting | Type B meeting, pre-NDA meeting |
| Validation period | 10 days | 60 days (refuse to file period) |
| Primary assessment | 80 days to Day 80 LoQ | Filing through mid-cycle review |
| Major issues | Day 80 List of Questions | Complete Response Letter (if issues) |
| Sponsor response | Clock stop (3-6 months) | Rolling responses possible |
| Oral explanation | Available at Day 180 | Advisory Committee meeting |
| Final decision | CHMP Opinion + EC decision | PDUFA date action |
| Appeal process | Re-examination procedure | Formal dispute resolution |
Timeline Comparison: MAA vs NDA
| Milestone | MAA Timeline | NDA Timeline |
|---|---|---|
| Submission to first feedback | 80 days | ~6 months |
| Total active assessment | 210 days | 10 months |
| Including clock stops | 12-18 months total | 10-14 months total |
| Expedited pathway | 150 days (accelerated) | 6 months (priority) |
| Post-decision to market | Immediate | Immediate |
FDA NDA fees are approximately 11 times higher than EMA MAA fees. However, the US market represents approximately 45% of global pharmaceutical revenue, making FDA approval critical for commercial success despite higher costs.
When to Pursue MAA vs NDA First
Consider MAA-first when:
- Lower fees are critical for cash-constrained companies
- European epidemiology or clinical trial sites favor EU data
- Conditional MA pathway offers earlier access
- Price referencing benefits from EU launch first
Consider NDA-first when:
- US market is primary commercial target
- Breakthrough Therapy designation provides advantages
- Single decision-maker simplifies planning
- First-mover US advantage justifies higher fees
Consider parallel MAA and NDA when:
- Global launch timing is critical
- Resources support simultaneous submissions
- Product addresses significant unmet need in both regions
- Data package supports both regulatory requirements
Preparing a Successful MAA Submission
Best practices for MAA preparation increase your probability of approval and reduce assessment delays.
Pre-Submission Preparation Checklist
Before finalizing your marketing authorisation application, verify these elements:
| Element | Requirement | Action |
|---|---|---|
| Scientific advice | Address all prior advice | Document implementation or deviations |
| Quality dossier | Complete and consistent | Final stability data, batch analysis |
| Clinical data | All pivotal studies complete | CSRs finalized, safety database locked |
| Risk management | RMP prepared | Initial RMP for Day 1 submission |
| Pediatric requirements | PIP/waiver in place | PDCO decision documented |
| Orphan designation | Valid if applicable | Maintain orphan criteria |
| eCTD compliance | Technical validation | Use validated publishing software |
Common MAA Deficiencies to Avoid
EMA analysis of MAA assessments identifies recurring deficiency patterns:
Quality (Module 3) Issues:
- Incomplete manufacturing process validation
- Inadequate specification justification
- Missing comparability data for process changes
- Insufficient stability data supporting shelf life
Clinical (Module 5) Issues:
- Inadequate demonstration of efficacy
- Safety database too small for chronic use products
- Missing subgroup analyses
- Incomplete adverse event narratives
Regulatory (Module 1) Issues:
- SmPC not consistent with clinical data
- Labeling text errors or inconsistencies
- Missing or incomplete environmental risk assessment
- Expert statement deficiencies
Managing Clock Stops Effectively
Clock stops represent critical opportunities to strengthen your MAA:
Day 80 Clock Stop:
- Request full 3-month standard time (6 months if needed)
- Address all questions, not just major objections
- Provide complete data, not promises of future data
- Consider additional analyses to support benefit-risk
Never underestimate your clock stop needs. Requesting 6 months initially and finishing early looks better than requesting an extension. Extensions signal to assessors that you may have underestimated your data gaps.
Day 180 Clock Stop:
- Focus on remaining outstanding issues
- Prepare for potential oral explanation
- Have backup positions for negotiable issues
- Ensure SmPC wording addresses safety concerns
Post-Authorization Requirements
Marketing authorization is not the end of your regulatory journey. Understanding post-authorization obligations ensures maintained compliance.
Pharmacovigilance Obligations
| Requirement | Timeline | Content |
|---|---|---|
| PSUR/PBRER | Per RMP schedule | Periodic safety update reports |
| Signal detection | Continuous | Ongoing safety monitoring |
| PASS | As specified in RMP | Post-authorization safety studies |
| PAES | As specified | Post-authorization efficacy studies |
Variation Management
Changes to your authorized product require variation applications:
| Variation Type | Description | Timeline |
|---|---|---|
| Type IA | Minor, immediate implementation | Do and tell |
| Type IB | Minor, 30-day notification | Do and tell |
| Type II | Major changes | Prior approval (60-90 days) |
| Extension | New forms, strengths, routes | Full assessment |
Renewal and Maintenance
| Activity | Requirement | Timing |
|---|---|---|
| First renewal | 5 years post-authorization | Comprehensive review |
| Annual fee | Payment required | Each year |
| SmPC updates | As required by new data | Variation procedure |
| Sunset clause | Marketing within 3 years | Authorization lapses if not marketed |
Plan your first variation submission within the first year after authorization. Agencies expect product lifecycle management, and demonstrating proactive commitment to your product through quality improvements or label updates builds regulatory goodwill for future interactions.
Key Takeaways
A marketing authorisation application (MAA) is the regulatory dossier submitted to the European Medicines Agency requesting approval to market a medicinal product in the European Union. The MAA contains comprehensive data on quality, safety, and efficacy organized in the eCTD format. Following positive CHMP scientific opinion, the European Commission grants marketing authorization valid across all 27 EU member states plus EEA countries.
Key Takeaways
- Marketing authorisation application is the EU pathway to drug approval: The MAA enables market access across 27 EU member states through a single CHMP assessment and European Commission decision.
- MAA assessment takes 210 active days plus clock stops: Total timeline from submission to EC decision typically spans 12-18 months, with accelerated assessment reducing active time to 150 days for qualifying products.
- EMA fees are significantly lower than FDA: MAA fees of approximately EUR 357,600 compare favorably to FDA NDA fees exceeding $4.4 million, with SME reductions of up to 90% available.
- Quality deficiencies cause the most MAA delays: Robust Module 3 CMC data and complete manufacturing validation significantly improve assessment outcomes and reduce clock-stop duration.
- Global strategies benefit from coordinated MAA and NDA planning: Parallel submissions can achieve synchronized US and EU launches, while regional differences require attention to Module 1 variations.
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Next Steps
Understanding the marketing authorisation application process is essential for any company seeking to bring medicines to European patients. From pre-submission planning through post-authorization maintenance, each phase requires careful attention to regulatory requirements and timelines.
Organizations managing regulatory submissions benefit from automated validation tools that catch errors before gateway rejection. Assyro's AI-powered platform validates eCTD submissions against FDA, EMA, and Health Canada requirements, providing detailed error reports and remediation guidance before submission.