For an emerging biotech, the European pathway has too many moving parts to commit to all at once. The most capital-efficient approach treats it as a series of decision gates — each backed by analytical work, structured around a binary stop / go / defer logic, and tied to a specific information trigger. You commit to the next bite, not the whole plate.
Below is the ten-gate map we use at Mirava Bio to take a rare disease, ATMP or cell & gene therapy from late-Phase 2 readiness to its first signed pricing and reimbursement agreement in Europe.
The three phases
The journey spans three broad phases: Late Phase 2 (readiness and scenario planning), EMA / National HTA / Early Access (the regulatory and access engine), and the Pricing Agreement (commercial close).
Gate by gate
G1 — Readiness & Scenarios
A cross-functional readiness scorecard, a decision-gate map, and a 5-year European P&L modelled across Bear / Base / Optimistic scenarios. This is decision-quality clarity for the Board before any structural commitment.
G2 — ODD & PRIME Strategy
EU Orphan Drug Designation maintenance, PRIME eligibility re-assessment, and a derogation dossier positioned against competitors.
G3 — JSC & PIP Alignment
Joint Scientific Consultation on the PICO question, and PDCO engagement on the Paediatric Investigational Plan.
G4 — CMC Bridge & QP
Module 3 EU adaptation, vector potency and comparability work, QP designation and the batch-release pathway — the operational backbone that US-focused programmes often defer too long.
G5 — Pricing Architecture
A payer perception audit, a defensible pricing corridor, IRP (international reference pricing) firewall design, and an outcomes-based agreement or annuity framework.
G6 — Early Access (first EU revenue) ★
France’s Accès Précoce, Italy’s Law 648/96, Germany’s §2 SGB V and Switzerland’s Art. 71a-d KVV can generate chargeable revenue before marketing authorisation — while real-world evidence begins feeding later HTA submissions.
G7 — MAA + Parallel JCA
Full CTD compilation, with the mandatory Joint Clinical Assessment running in parallel under the EU HTA Regulation.
G8 — CHMP Opinion & EU MA
CHMP / CAT review, response strategy, the European Commission decision, and activation of orphan exclusivity.
G9 — National HTA Dossiers
G-BA AMNOG (Germany), HAS / Transparency Committee (France), AIFA CTS/CPR (Italy), NICE HST (UK).
G10 — P&R Agreements Signed ★
GKV-SV, CEPS, AIFA, NHSE — confidential net pricing, managed-entry agreements, and IRP-safe sequencing.
Why decision gates matter
Each gate is reversible by design. You commit only the resources warranted by the information available, and stop, go or defer at every milestone — while retaining ownership, pricing authority and strategic control throughout.