Europe is lagging behind Asia-Pacific and North America in providing patient access to Advanced Therapy Medicinal Products (ATMPs). Since 2009, 7 out of 25 European Union (EU) approved ATMPs were withdrawn or not renewed, primarily due to commercial reasons. On the other hand, access to ATMPs through the hospital exemption (HE) pathway has increased among EU Member States. Reports suggest that there are at least 32 ATMPs available in individual Member States via the HE pathway. The HE pathway can be a valuable tool for patient access to ATMPs in certain circumstances. However, if not implemented correctly, it could pose a challenge for long-term development and equal access to safe and effective ATMPs.
In this two-part blog series, the first part explores the concept of the hospital exemption pathway, along with the challenges and opportunities it entails. The second part delves into the variability in HE implementation and its impact on the access and pricing of centrally approved ATMPs.
What is the Hospital Exemption pathway?
The EU Regulation 1394/2007 makes it mandatory for ATMPs to obtain marketing authorisation via the centralised procedure, subjecting them to high regulatory standards. This includes compliance with Good Manufacturing Practice (GMP) standards and conducting pivotal clinical trials to demonstrate safety and efficacy. As a result, ATMP developers, that are often small biotech companies and academic institutions, face a significant regulatory burden to gather sufficient data to support HE approval.
To address this issue, an ‘HE’ was introduced in the regulation for EU Member States to permit the use of ATMPs without centralised marketing authorisation in their territories under certain circumstances. The HE can only be applied to ATMPs that are:
- Prepared for an individual patient
- Administered in a hospital setting under the responsibility of a medical practitioner
- In compliance with an individual medical prescription
- Produced on a non-routine basis
- Used within the same Member State
The regulation requires competent authorities of the Member States to authorise the ATMPs under the HE pathway, ensuring compliance with the equivalent requirements of GMP, traceability and pharmacovigilance, that apply to centrally authorised ATMPs.
Challenges of the Hospital Exemption pathway
In practice, there is high variability among the European countries in implementing the HE regulation due to inconsistent interpretation and specific requirements of each country. Furthermore, the recent proposal for revision of the EU pharmaceutical legislation does not help in addressing this considerable degree of inconsistency in implementation of HE. This variability has led to differences in patient access to ATMPs across European countries, as some countries apply more liberal policies than others.
In addition, the availability of ATMPs via the HE pathway is limited to certain hospitals or medical centres, potentially creating inequalities in access to life-saving treatments across Europe.
One of the primary concerns is patient’s safety due to availability of HE ATMPs with limited data on risk/benefit analysis. The implementation of HE regulation. Differences among Member States in terms of deviating from the expected standard GMP regulation
Assessment of safety, efficacy and post-marketing surveillance are limited under HE leaving room for unknown long-term risks associated with these ATMPs, thus potentially undermining the provision of safe, high-quality health care to European citizens.
HE ATMPs can offer a potential cost-saving advantage over centrally approved treatments, making them more affordable for patients and healthcare systems. However, one of the factors driving the lower cost of HE ATMPs could be lack of rigorous clinical trial process and regulatory requirements expected by the Member State. Furthermore, treatment with an HE ATMP could render a patient ineligible for a future clinical trial, inevitably forcing physicians to choose between using HE at the time of need or, waiting for centrally approved ATMP with robust safety data to be approved at a later stage. In this way, the local availability of low cost HE ATMPs may hamper the use of centrally authorized ATMPs, and ultimately limiting broad patient access to safe and effective innovations.
Opportunities of the Hospital exemption pathway
if implemented correctly , the HE pathway offers:
The HE pathway is a crucial way of providing seriously ill patients with access to treatments that may not be available through other channels, particularly for rare diseases where no approved treatments or commercially feasible options exist.
Plus, the HE pathway can play a crucial role in generating real-world data for evaluating the safety and efficacy of ATMPs in clinical development. The generated information provides valuable clinical data that may expedite the approval process of an ATMP.
In February 2023, the EMA started a pilot to offer enhanced regulatory support to ATMPs that address unmet clinical needs and are developed by non-profit or academic organisations. Under the pilot, up to five ATMPs will be selected by the end of 2024, with the initial results being expected by 2027-2028. EMA will guide the selected participants through the centralized regulatory process, including manufacturing best practices and clinical development planning that meets regulatory standards.
In practice the pilot will mostly support EU-wide authorisation of ATMPs that have followed the HE pathway. The pilot’s first participant, ARI-0001 marks a crucial step towards improving equitable access across Europe and accelerating the development and availability of new and safe treatments. treatments.
Need for overcoming challenges and seizing the opportunities
In summary, the HE pathway for ATMPs comes with both challenges and opportunities. There are opportunities of meeting the unmet medical need, generate clinical evidence in real-world and pathway for accelerated approval, however, there are challenges of unequal access across Europe, concerns around safety and effectiveness and disincentive for future development of centrally approved ATMPs in few markets. Check out the second blog of this two-part blog series that discuss the disincentive part in detail by examining impact of HE ATMPs on the access and pricing of centrally approved ATMPs in few markets.
More alignment is needed to ensure that the HE ATMP pathway is used to fill gaps where commercial ATMPS are lacking, while harmonising it’s application and interpretation across Europe, to ensure sustainable and equal access to safe and potentially lifesaving treatments.
