Early Access Programs – an Overview for the United States (FDA) and Europe (EMA)

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have recognised that paradigms of drug development, which are feasible for common diseases, may not be feasible for rare diseases and that transformative orphan, specialty and advanced therapeutics often defy traditional regulatory routes.

The EMA’s Support for Early Access and the FDA’s Expedited Programs facilitate and accelerate development and marketing authorisation with the aim to foster patients’ timely access to new medicines that address unmet medical needs.

The focus of early access, both in the United States and Europe, is on life-threatening and debilitating diseases with a major impact on quality of life, and on medicines with a credible promise of significant improvements in clinical benefit and patient-relevant outcome(s).

The below table provides an overview of the EMA’s and the FDA’s early access programs and represents the current regulatory context – for Europe and the United States – within which an early access strategy for an innovative medicine is developed.

While the FDA’s programs are well established, certain of the EMA’s early access tools have been launched more recently. These innovative initiatives emphasise early dialogues, the involvement of multiple stakeholders, iterative development in a life-cycle approach, and an expanded toolbox for evidence generation, with pragmatic and real-world studies complementing RCTs in areas where the collection of data via traditional routes is difficult.

The key features of early access are notably similar in both jurisdictions:

• Enhanced early agency interaction to identify potential for accelerated development.
• Dedicated agency resources, including access to senior management.
• Reinforced scientific advice, early and frequent dialogues on study design, protocol development, surrogate and intermediate clinical endpoints, post-authorisation, pragmatic and real-world studies, patient- and HTA- relevant endpoints, rolling and priority review, accelerated assessment and approval.
• Earlier marketing authorisation, allowing for a more rapid pace of drug development, involving fewer, smaller, shorter clinical trials and on the basis of less complete data. Comprehensive evidence generation post-authorisation within an agreed timeframe.
• Earlier market access, facilitated through a centralised compassionate use opinion by the EMA (CHMP), for unauthorised products, aimed at harmonising the conditions of use, distribution and the target population across the EU.
• Accelerated review of the marketing application, reduced assessment timelines.
• Orphan drug designation, providing access to a number of incentives.

There is substantial crossover in terms of objectives and features between the programs and they can be used in combination. For example, a product eligible for fast track in the US may be eligible for accelerated approval and priority review. In Europe, a medicine benefitting from PRIME support may also qualify for conditional marketing authorisation. Additionally, drugs benefitting from early access are those eligible to the EMA centralised procedure and a single marketing authorisation.

Early access is applicable to both orphan and non-orphan medicines in both jurisdictions, although the programs are more accepted for orphan drugs. Orphan drug designation is not an early access tool per se, and orphan medicines do not automatically qualify for accelerated procedures. Nevertheless, orphan drugs are highly likely to be eligible for early access. Therefore, the feasibility of orphan designation should be considered as part of any early access strategy, and equally, the potential benefits of early access should be considered as part of the decision to seek orphan designation.

Additionally, there are several EMA/FDA collaborations with the potential to speed up access:

• Parallel scientific advice (PSA), due to limited resources, the scope of this program is limited to potential breakthrough products in diseases with little experience, including orphan drugs and fast track products in the US.
• Common application for orphan designation of the same medicinal product for the same use in both jurisdictions with a single form for the EMA and FDA.
• Rare diseases cluster, aimed at boosting medicine development for rare diseases. The agencies will exchange experiences and best practices on topics including trial design, endpoints, development support, risk management strategy, and post-marketing study design, in particular in the context of early access mechanisms.

It should be noted that early access does not alter the current FDA standards of approval, nor the EMA’s data quality standards and risk/benefit basis. The agencies will review the full data submitted to determine whether drugs are safe and effective for their intended use before accelerated and conditional approval for marketing.

Acceleration is justifiable only where the benefit to public health of the immediate availability on the market outweighs the risk inherent in the fact that additional data are still required.

About ORPHA Strategy Consulting

In rare diseases and for transformative medicines, early access strategies, benefit/risk and value demonstrations are often uncharted terrain, requiring highly specific expertise and experience. ORPHA Strategy’s principal, David Schwicker (Biography), has industry consulting expertise spanning more than 25 years, and has gained a unique understanding of how early access programs, initiatives, and rare disease and orphan drug incentives can benefit a client’s transformative medicine to prospectively accelerate marketing authorization and market access. To this is added a focus on innovative development pathways that emphasise the use of real-world evidence.

Thank you for your interest. To start a strategic discussion on early access, please contact:

David Schwicker, Managing Director, ORPHA Strategy Consulting, Basle, Switzerland, +43 664 7345 25 14, [email protected]

Copyright ORPHA Strategy Consulting, 2017. ORPHA Strategy regularly publishes Executive Briefings, which focus on news and current trends in early access, adaptive development pathways, transformative medicines, orphan drugs and designations, rare diseases, and real-world patient-centered evidence. They are available for download here:

Executive Briefings

Further Information

Further information on current early access tools, programs, and initiatives is available here: Early Access