Drug Development Consulting in Europe: From IND to Marketing Authorisation

The average time from first-in-human clinical trial to EU marketing authorisation for a new chemical entity is 10 to 12 years. The average cost exceeds €1 billion. These numbers reflect the full development programme for a novel drug — but they also reflect the cumulative cost of regulatory missteps, clinical trial failures, and strategic decisions made without adequate regulatory guidance.

Drug development consulting in Europe is not about navigating bureaucracy. It’s about making better decisions at each stage of development — decisions that increase the probability of regulatory success and reduce the time and cost of reaching the market.

The EU Drug Development Pathway: Key Stages

Stage 1: Pre-Clinical Development

Before any clinical trial can begin, a drug candidate must demonstrate sufficient pre-clinical evidence of safety and pharmacological activity to justify human exposure. EU regulatory requirements for pre-clinical studies are set out in EudraLex Volume 10 and the ICH guidelines (M3, S1-S9 series).

Key pre-clinical milestones:

• In vitro pharmacology: Receptor binding, enzyme inhibition, cell-based assays demonstrating the mechanism of action
• In vivo pharmacology: Efficacy studies in relevant animal models
• Pharmacokinetics (PK): Absorption, distribution, metabolism, excretion (ADME) studies in at least two species
• Toxicology: Acute toxicity, repeat-dose toxicity (minimum 2 weeks for a 2-week clinical trial, scaling up to 9 months for long-term clinical trials), genotoxicity, safety pharmacology

The pre-clinical package required to support a first-in-human (FIH) clinical trial is defined by ICH M3(R2). For an oncology product, the requirements differ from those for a non-oncology product — ICH S9 provides specific guidance for anticancer pharmaceuticals.

Regulatory consulting role at this stage: Advising on the pre-clinical study design to ensure it meets regulatory requirements; identifying gaps in the pre-clinical package before clinical trial application; preparing the non-clinical overview for the CTD.

Stage 2: Clinical Trial Application (CTA)

To conduct a clinical trial in the EU, a sponsor must submit a Clinical Trial Application (CTA) through the CTIS portal under the EU Clinical Trial Regulation (EU) No 536/2014.

The CTA requires:

• Full clinical trial protocol
• Investigator’s Brochure (IB)
• IMP (Investigational Medicinal Product) dossier — quality, non-clinical, and available clinical data
• GMP compliance documentation for the IMP
• Ethics committee documentation

The Reporting Member State (RMS) assesses Part I (scientific aspects) within 30 to 45 days. Each Concerned Member State assesses Part II (national aspects, including ethics) within 30 days.

Regulatory consulting role: Selecting the optimal RMS; preparing the IMP dossier; writing the clinical trial protocol to meet both scientific and regulatory requirements; managing the CTIS submission process.

Stage 3: Phase I Clinical Trials

Phase I trials assess safety, tolerability, and pharmacokinetics in a small number of subjects (typically 20 to 80). For oncology products, Phase I trials are often conducted in patients rather than healthy volunteers, and may include preliminary efficacy assessments.

EU-specific considerations for Phase I:

• The Qualified Person (QP) must certify each batch of IMP before use in the trial
• Serious adverse events must be reported to CTIS within 7 days (fatal/life-threatening) or 15 days (other)
• The trial must be registered in CTIS before the first subject is enrolled

Stage 4: Phase II Clinical Trials

Phase II trials assess preliminary efficacy and optimal dosing in a larger patient population (typically 100 to 300). Phase II results inform the design of the pivotal Phase III programme.

Scientific advice from EMA: For products intended for centralised procedure authorisation, sponsors can request scientific advice from EMA’s CHMP at any stage of development. Scientific advice is not binding, but it provides valuable guidance on the acceptability of the clinical programme design. EMA scientific advice is particularly valuable before committing to the Phase III programme design.

Regulatory consulting role: Preparing scientific advice requests; analysing Phase II results to inform Phase III design; preparing end-of-Phase II briefing documents.

Stage 5: Phase III Clinical Trials

Phase III trials are the pivotal efficacy and safety studies that form the primary basis for the marketing authorisation application. They typically enrol 1,000 to 10,000+ patients and run for 2 to 5 years.

EU-specific considerations for Phase III:

• The trial must be conducted in compliance with ICH E6(R2) Good Clinical Practice (GCP)
• The protocol must be approved through CTIS before any site initiates the trial
• Substantial modifications to the protocol require prior authorisation
• Annual progress reports must be submitted to CTIS

Stage 6: Marketing Authorisation Application (MAA)

The MAA is submitted in CTD format. For products seeking centralised authorisation, the application is submitted to EMA. The assessment timeline is 210 active days, typically resulting in a CHMP opinion approximately 12 to 15 months after submission.

The MAA includes:

• Module 3: Complete quality documentation (drug substance and drug product)
• Module 4: Complete non-clinical study reports
• Module 5: Complete clinical study reports

Common reasons for MAA failure or delay:

• Insufficient clinical evidence of efficacy (inadequate primary endpoint, underpowered study)
• Safety concerns not adequately addressed in the risk management plan
• Quality deficiencies in Module 3 (manufacturing process not adequately characterised, specifications not justified)
• Non-clinical concerns not adequately addressed

Regulatory consulting role: Managing the MAA preparation; coordinating Module 3 writing with the manufacturing team; preparing clinical overviews and summaries; managing the assessment process and responses to CHMP questions.

Stage 7: Post-Approval

After marketing authorisation, the work continues:

• Pharmacovigilance: Ongoing safety monitoring, PSUR submission, signal detection
• Variations: Managing post-approval changes through the EU variation system
• Renewals: Five-year renewal application
• Risk Management Plan (RMP): Updating and implementing the RMP
• Post-authorisation studies: Conducting any PASS or PAES required as conditions of the authorisation

How Long Does EU Drug Development Take?

Stage	Typical Duration
Pre-clinical development	3–6 years
Phase I	1–2 years
Phase II	2–4 years
Phase III	3–6 years
MAA preparation and submission	1–2 years
EMA assessment	12–15 months
Total (new chemical entity)	10–15 years

For products with breakthrough therapy designation or PRIME (Priority Medicines) designation from EMA, accelerated timelines are possible. EMA’s PRIME scheme provides enhanced scientific support and faster assessment for products that address unmet medical needs.

The Value of Early Regulatory Engagement

The most common mistake in EU drug development is treating regulatory affairs as a late-stage activity — something to worry about when the clinical data is ready. This approach consistently results in:

• Clinical programmes that generate data that doesn’t meet regulatory requirements
• Manufacturing processes that are not adequately characterised for a CTD submission
• Phase III designs that are underpowered or use endpoints that regulators won’t accept

Early regulatory engagement — including EMA scientific advice, pre-submission meetings with national authorities, and regulatory strategy development before Phase II — is the single most effective investment in reducing the risk and cost of EU drug development.

At Care Europe, we provide drug development consulting for companies at all stages of the EU regulatory pathway, from pre-clinical strategy through post-approval lifecycle management. Contact us at [email protected].