As specialists in regulatory affairs for pharmaceutical developers, particularly those outside the EU, Pharma Design Limited has extensive experience guiding clients through the complexities of Advanced Therapy Medicinal Product (ATMP) Marketing Authorisation Applications (MAAs). Drawing from recent consultations on gene therapies, this article outlines the key processes for EMA and MHRA filings, emphasizing structured preparation to ensure efficient submissions.
Understanding the ATMP MAA Landscape
ATMPs, such as gene therapies, require centralized authorisation via the EMA for EU-wide approval, with parallel or recognition routes for the UK post-Brexit. The dossier follows the Common Technical Document (eCTD) format, with ATMP-specific adaptations for quality, non-clinical, and clinical data (e.g., enhanced biodistribution studies, long-term follow-up per EMA/149995/2008 guideline).
Step-by-Step Preparation and Filing
- Pre-Submission Planning (6-12 Months Before Filing):
- Confirm eligibility: For EMA, submit a centralized procedure eligibility request 7-18 months pre-MAA (decision in 4-8 weeks). For MHRA, notify intent 3 months pre-submission.
- Request scientific advice: Joint EMA/HTA consultations (via HTACG) or MHRA advice to align evidence generation. Documents needed: Briefing package, questions form (no eCTD required).
- Establish legal entities: Set up EU/UK representation or limited companies for fee reductions (e.g., SME waivers).
- Dossier Compilation (3-6 Months Before Filing):
- Use eCTD for both EMA/MHRA: Modules 1-5, with ATMP focus on viral vector safety (ICH Q5A/D), risk management plan (RMP per GVP Module V), and environmental risk assessment (for GMOs).
- Key additions: Paediatric Investigation Plan (PIP) compliance check (submit 2 months pre-MAA to EMA; 60 days to MHRA).
- Orphan designation: Integrated in MAA for MHRA; pre-MAA for EMA.
- Pre-Submission Meetings (6-7 Months for EMA; ~90 Days for MHRA):
- No eCTD needed: Submit forms, draft justifications (e.g., accelerated assessment), and briefing docs via portals/email.
- Discuss trade names, rapporteurship (CAT/CHMP for ATMPs), and timelines.
- MAA Filing:
- EMA: Submit via eSubmission Gateway; accelerated assessment request 2-3 months pre-filing.
- MHRA: Via Submissions portal; no letter of intent but pre-notification form.
- Timeline: EMA standard 210 days (150 accelerated); MHRA similar.
- Post-Submission: Address queries; maintain via variations.
Optimizing HTA Preparation and Joint Meetings for ATMP Success in Europe
Health Technology Assessment (HTA) is crucial for ATMP reimbursement post-authorisation. Pharma Design Limited assists developers in integrating HTA early, including joint regulatory-HTA consultations, to enhance market access.
HTA Landscape for ATMPs
From 2025, Joint Clinical Assessments (JCA) are mandatory for ATMPs under EU HTA Regulation, running parallel to EMA MAA. National HTAs (e.g., NICE in UK) follow, but early joint advice de-risks.Joint Meetings and Preparation
- Request Joint Scientific Consultation (JSC):
- EMA/HTACG: Submit during open periods (e.g., January-February 2026) via HTA IT Platform. Documents: JSC Submission Request Template (justifies need).
- MHRA/NICE: Request via MHRA form (rolling basis); no ILAP required for basic joint.
- Documents Needed: Briefing package (questions on evidence, endpoints), draft decision problem (population, intervention, comparators, outcomes).
- Timeline: JSC: 6-9 months (request to report); MHRA/NICE: 2-4 months.
- HTA Dossier Preparation: Build cost-utility models (QALYs, 3.5% discount, NHS/PSS perspective) using tools like Excel/Python. For ATMPs, emphasize QALY gains from functional improvements (e.g., vision preservation).
- Integration with MAA: Use JSC feedback in pre-submission meetings; align with accelerated pathways.
Our expertise has helped clients secure favorable HTA outcomes in UK and EU, showcasing the value of early joint engagement. Reach out for support.