Orphan Medicinal Products and Rare Disease Medicines at BfArM

EU Orphan Regulation Framework

The EU Orphan Regulation (Regulation (EC) No 141/2000) aims to stimulate development of medicines for rare diseases affecting fewer than 5 in 10,000 persons in the EU. In Germany, BfArM supports implementation for nationally authorised, decentralised, and mutual recognition procedures, while contributing to centralised orphan designations via the EMA Committee for Orphan Medicinal Products (COMP). Orphan status provides incentives such as protocol assistance, fee reductions, and 10 years of market exclusivity upon authorisation. Medicines for rare diseases - BfArM

Orphan Designation Process

• Applicants request orphan designation from EMA COMP before marketing authorisation application.
• BfArM provides scientific advice on orphan eligibility, including prevalence justification (≤5/10,000 in EU), medical plausibility, and significant benefit over existing treatments.
• National support: BfArM offers early dialogue and advice for products intended for national/DCP/MRP routes.
• Once designated, orphan status is maintained throughout development and authorisation.

Incentives and Support Measures

• Fee reductions: Significant reductions or waivers for orphan designated products at EMA and national level (including BfArM procedures).
• Protocol assistance: Scientific advice from EMA/COMP or national authorities (BfArM) on quality, non-clinical, and clinical aspects.
• Market exclusivity: 10 years upon centralised authorisation; national procedures may benefit from equivalent protections.
• Paediatric orphan products may qualify for additional 2 years of exclusivity if PIP compliant.

Authorisation Pathways for Orphan Medicines

• Centralised procedure via EMA is common for orphan medicines to ensure EU-wide access.
• BfArM handles national, DCP, and MRP orphan applications, ensuring consistency with EU orphan criteria.
• Orphan products often use conditional marketing authorisation or exceptional circumstances authorisation due to limited data from small populations.

Practical Guidance for Applicants

• Early engagement with BfArM recommended for scientific advice on orphan strategy, study design, and data requirements.
• BfArM supports use of adaptive trial designs, real-world evidence, and extrapolation to address small patient numbers.
• Applicants should monitor COMP opinions and BfArM guidance for updates on rare disease policies.

BfArM’s support for orphan medicines helps address unmet medical needs in rare diseases, promoting innovation and patient access through regulatory flexibility and incentives aligned with EU orphan policy. Medicines for rare diseases - BfArM