Encouraging innovation is an overarching objective of the European Medicines Agency (EMA), with significant emphasis on supporting the development of medicines for rare diseases. With 36 million people in the European Union living with a rare disease, the EU offers various incentives to encourage the development of designated orphan medicines.
What are these programmes and how can you take advantage of them?
Orphan drug designation (ODD)
The EU’s Orphan Drug Designation (ODD) process is designed to encourage early engagement with the EMA and facilitate faster access to medicines for rare disease patients. There are a range of incentives for orphan medicines, including scientific advice and protocol assistance, market exclusivity for 10 years (which can extend to 12 years with a fully compliant paediatric investigation plan), and fee reductions. Achieving orphan designation requires demonstrating the prevalence of the disease as ‘rare’, and that the therapy has potential to address an unmet need or offers significant benefit over existing therapies.
Small-Medium Enterprise (SME)
If the sponsor of an orphan medicine is also an EMA-registered SME, additional support is available, including fee reductions for regulatory procedures and scientific advice. Both the Committee for Orphan Medicinal Products (COMP) and the SME Office at the EMA are incredibly helpful if engaged appropriately, at the right time, and with the right questions.
PRIME
The EMA’s priority medicines (PRIME) programme was established to support the development of medicines that address an unmet medical need in the EU. PRIME designation is more difficult to obtain than the ODD, requiring robust preliminary clinical evidence. However, once designated, sponsors receive early and enhanced regulatory support, including a Committee for Medicinal Products for Human Use (CHMP) rapporteur and frequent scientific advice interactions. PRIME helps optimise regulatory pathways and streamline development, accelerating patient access to important new treatments.
Early Access Programs
These offer opportunities to provide patients with life-saving medicines before they receive marketing authorisation application (MA) approval. Developers can also take advantage of these programmes to gather real-world data or non-clinical trial data and to bring product awareness to specialist investigators and centres in Europe.
Each EU country has its own system, and local regulatory support is essential to navigate requirements. France, in particular, is a leader in early access and is considered to be the pioneer of these types of programmes, known there as the AAP (Autorisation d’accès précoce) and AAC (autorisation d’accès compassionel).
Additional EMA Pathways
Several other regulatory mechanisms support rare disease drug development:
- Conditional Marketing Approval (CMA) – approval of an MAA based on limited preliminary data (e.g. where clinical trials have low patient numbers or other limiting factors common to rare diseases), with specific conditions for post marketing studies and data collection agreed between the MAH and EMA. CMA is available for medicines addressing unmet medical needs for serious diseases, but subject to annual reassessment that the product is meeting the agreed conditions.
- Accelerated Assessment – reduces the standard EMA review timeline from 210 days to 150 days but requires justification of a major public health interest.
- Innovation Task Force (ITF) – provides early-stage regulatory guidance and can advise on eligibility for PRIME designation.
- Paediatric Investigation Plans (PIP) – While not a pathway as such, it is a mandatory procedure and vital component to consider in any orphan regulatory strategy, since 75% of rare diseases affect children.
Engage EMA early on
Above all, early engagement is key. The more innovative the product or potential trial designs, the rarer the disease, and the less experience a sponsor’s internal team has in the EU, the earlier you should be thinking about talking to the EMA and finding local regulatory support.
It’s important to first understand the regulations in the EU and investigate which incentives are available for your products, and which procedures will be mandatory. SME, Orphan, and PRIME designations all come with what might be termed “procedural assistance” from groups within EMA who assist sponsors navigating EMA processes, regulations and procedures.
SME is a good starting point for smaller companies, which, combined with access to local expertise, can help sponsors understand and start to outline a good regulatory strategy for the EU. The ITF is also a great option for very early discussions with the EMA for highly innovative/novel products, and these are best utilised whilst still in pre-clinical phases.
It’s never too late
Even if your programme is further along in development, it’s never too late to engage. In this situation, start with a thorough due diligence of where you are in your development and evidence generation, and what gaps need to be addressed to meet the requirements of the EU regulators. From there, build a plan to leverage support incentives (ODD, SME etc.) and scientific advice meetings, paediatric considerations (PIP), to resolve gaps and issues related to product quality and purity, clinical study design (such as endpoints, inclusion criteria, statistical methods), and PK/PD and in vitro/in vivo testing.
And make sure you have local expertise to help you understand the different regulations and standards and to help adapt the language used in non-EU markets to align with European regulatory language.
The range of incentives and support mechanisms offered by the EMA does seek to encourage development of medicines for rare disease. By taking advantage of these and engaging with the agency early on, sponsors can better navigate a complex regulatory landscape and bring these vital treatments to patients faster.
Contact us at IDEA Regulatory to find out how we can help you determine the best programme for your innovative product.
The more innovative the product or potential trial designs, the rarer the disease, and the less experience a sponsor’s internal team has in the EU, the earlier you should be thinking about talking to the EMA and finding local regulatory support.