Enacted in 1983, this designation provides the foundational regulatory and financial framework for rare disease development. It also established the Orphan Product Grants Program to provide funding.

Real-world precedent: Eteplirsen (Exondys 51) for DMD received ODD and orphan exclusivity, which supported development in a very small mutation-defined subset of DMD patients.

Gaining rapid, ad-hoc FDA communication (beyond formal meetings) to resolve specific development issues like clinical trial design, control groups, or patient populations.

This program (initiated in 2024) is designed to facilitate novel drug development and generate high-quality data to support an application.

Gaining approval for diseases with very small patient populations (and significant unmet need) where traditional trial evidence is difficult to generate.

Rare Disease Endpoint Advancement (RDEA) Pilot

Gaining expert statistical feedback on complex adaptive, Bayesian, or other novel clinical trial designs.

While not specific to rare diseases, this program is highly relevant for pediatric rare disease trials where traditional designs are often not feasible.

Aligning on complex scientific challenges and novel trial approaches, especially for issues common to multiple diseases or classes of diseases.

Accessing CDER’s collected expertise on innovative scientific design, regulatory policy, and stakeholder engagement.

Ensuring the patient perspective is integrated into the regulatory review of biologics (e.g., cell and gene therapies).

This program focuses on:

• Applying flexible and feasible regulatory approaches during review, 
• Helping craft and implement relevant regulatory policies and procedures, and 
• Collaborating across FDA centers, other federal agencies, international regulators, and external organizations on cross-cutting activities, programs, and initiatives.

RDCA-DAP (Rare Disease Cures Accelerator-Data and Analytics Platform)

This data platform, run by the Critical Path Institute, provides a centralized infrastructure to standardize and share data in the pre-competitive space.

Orphan Medicinal Product Designation (EU OMP / ODD)

Based on Regulation (EC) 141/2000, orphan designation is granted via EMA’s COMP and confirmed by the European Commission. Incentives include 10-year market exclusivity (extendable to 12 years), reduced fees, and support for evidence generation.

A PIP is a mandatory development plan for new medicines (including orphans) that defines your pediatric studies, timelines, and waivers/deferrals, reviewed by the PDCO. Successful completion can extend orphan exclusivity from 10 to 12 years or grant other rewards and is a key pre-requisite for EU MAA.

PUMA is a dedicated MA for products intended only for pediatric use, typically for off-patent drugs needing pediatric-specific formulations/indications. Incentives include 10 years of data and market protection and partial fee exemptions, making pediatric reformulations viable even in small populations.

Scientific advice gives EMA feedback on clinical, nonclinical and quality plans; protocol assistance is a special, incentivised version for orphan-designated medicines. Orphan sponsors (and some academic developers) can access fee reductions or waivers.

PRIME offers early and enhanced interaction (including a CHMP rapporteur, frequent SA, and iterative feedback) to optimize development and speed evaluation. It is particularly relevant for transformative rare-disease therapies (e.g., ATMPs, gene therapies) that can credibly address major unmet need in small populations.

The ITF is EMA’s early-innovation front door, offering informal, science-focused dialogue on novel technologies (e.g., DHT-based endpoints, gene editing, AI-based diagnostics). These meetings are ideal before formal scientific advice, when you’re still shaping platform, endpoint, or DHT strategies in rare pediatric settings.

EMA’s qualification pathway can lead to a CHMP opinion or advice on innovative methods (e.g., imaging biomarkers, composite COAs, digital mobility measures) with a defined context of use. They are especially valuable for shared disease platforms or consortia where multiple sponsors may rely on the same endpoint or modelling approach.

Conditional Marketing Authorisation (CMA)

CMA allows earlier approval when benefit-risk is positive but data are incomplete, provided the medicine addresses an unmet medical need and you agree to specific obligations and timelines.

EMA can grant accelerated assessment on request (typically 2–3 months pre-MAA); it’s reserved for medicines addressing unmet needs, often in rare diseases.

EMA may grant MA “under exceptional circumstances” when comprehensive data cannot realistically be obtained, with ongoing obligations and annual reassessment.

The Rare Diseases Clinical Trials Toolbox (ECRIN/EJP RD) provides structured guidance, checklists and examples on design options, registries, data standards, and feasibility in rare diseases. Designed explicitly to address scarce patients, fragmented expertise, and complex trial logistics across multiple EU states.

European Platform on Rare Disease Registration (EU RD Platform & ERDRI)

The EU RD Platform (JRC) tackles fragmentation of rare-disease registries, providing tools and the ERDRI “Set of Common Data Elements” to harmonise core data. By aligning to these CDEs, you make it easier to pool registry data, support external controls, and meet regulators’ expectations for interoperable RWD.

24 ERNs connect over 1,600 specialised centres in 27 Member States and Norway, organised by disease clusters (e.g., ERN-RND, EURO-NMD, ERN Skin, metabolic ERNs). ERNs are ideal partners for site selection, feasibility, expert consensus on endpoints, and cross-border care logistics in pediatric rare-disease trials.