Application of the ATMP Hospital Exemption in the EU

Summary

• The Hospital Exemption has a legitimate role to play in meeting unmet patient needs. Equally, action should be taken to ensure that the use of the exemption does not undermine the rights of patients to safe and effective treatment.

• The Hospital Exemption should be interpreted and implemented in a strict and fully harmonised manner by all EU Member States, recognising that the exemption should only be applied in the absence of centrally authorised medicinal products. Commission guidance should support National Competent Authorities in achieving harmonisation.

• Measures should be adopted to improve transparency of the use of the Hospital Exemption, including though the establishment of a register of exempted products and the adoption of a harmonised Informed Consent Form.

• To safeguard incentives for innovation, steps should be taken to ensure the Hospital Exemption cannot be used an alternative route to market for developers of ATMPs.

The ATMP Regulation and the ‘Hospital Exemption’

Article 28 of Regulation 1394/2007/EC (hereafter, the ATMP Regulation) on advanced therapy medicinal products (ATMPs), referred to as the 'Hospital Exemption' (HE), foresees the exclusion of certain ATMPs from the scope of Directive 2001/83/EC on medicinal products for human use. Instead, national procedures regulate the preparation and manufacturing of such medicinal products. These products are defined in the ATMP Regulation as: "ATMPs prepared on a non-routine basis according to specific quality standards, and used within the same Member State in a hospital under the exclusive professional responsibility of a medical practitioner, in order to comply with an individual medical prescription for a custom-made product for an individual patient".

The HE allows Member States to permit the manufacture and use of ATMPs in their territories without fulfilling the requirement for submitting a marketing authorisation application to be assessed by the Committee for Advanced Therapies (CAT) and Committee for Medicinal Products for Human Use (CHMP) within the EMA and an authorisation to be granted by the European Commission. Member States must ensure that the manufacture of ATMPs under the HE is authorised by the National Competent Authority and that manufacturing, traceability, pharmacovigilance and specific quality standards are equivalent to those provided for at EU level for ATMPs which are granted a centralised marketing authorisation. The HE products must be produced in GMP-authorised sites.

Ensuring appropriate use of the Hospital Exemption

The ATMP Regulation and the related legislative framework for medicines is designed to facilitate access to ATMPs while ensuring the necessary level of public health protection for patients, as well as fostering and incentivising the research, development, and authorisation of innovative ATMPs. As such, EuropaBio is generally supportive of appropriate use of this exemption in cases of individual patients with unmet clinical needs and where no centrally approved treatment exists.

While the HE has an important and legitimate role to play in this context, EuropaBio believes that action is required to prevent instances of inappropriate use which go beyond the intent of the ATMP Regulation. Actions are required to address three key challenges:

1. The HE has been interpreted and implemented inconsistently across the EU
2. There is a lack of transparency about how the HE is used
3. Excessive and unjustified use of the HE may create a barrier to innovation.

This paper addresses these challenges in turn and provides recommendations for action. EuropaBio believes that the failure to address these challenges could undermine the effectiveness of the regulatory framework set out by the ATMP Regulation, and, ultimately, undermine the rights of patients to safe and effective treatments. EuropaBio calls on the European Commission to:

• Clarify that the use of the HE should be restricted to the scenarios stipulated in the ATMP Regulation – for individual patients, within one Member State and on a non-routine basis. As regulatory exemptions should be interpreted conservatively by default, the Commission should make clear that any medicinal products approved pursuant to the ATMP Regulation should take precedence. There should be a harmonised strict interpretation and implementation by the EU Member States to recognise that the HE should only be applied in the absence of centrally authorised products.

• Collaborate with the EMA, Heads of Medicines Agencies and National Competent Authorities, to provide clear harmonised guidance which ensures consistent interpretation and use of the HE across all Member States. This guidance should:

o Provide an unambiguous and standardised definition of "non-routine" use and “within the same Member State”.
o Clarify how quality and PCV standards should be met.
o Make clear that Member States should ensure that GMP standards for HE products are equivalent to those for authorised ATMPs.

• Work with National Competent Authorities and involve EU-funded programmes to establish a register of exempted medicinal products which monitors how these products are used and provides appropriate information relating to their safety and efficacy. Alternatively, National Competent Authorities should maintain a registry of sites, and require individual sites to contribute to a registry providing appropriate information relating to safety and efficacy. We recommend that there is a provision included within Commission guidance that ensures transparency relating to clinical data.

• Work with National Competent Authorities to introduce a harmonised Informed Consent Form that must be completed prior to treatment for all exempted medicinal products.

• Work with National Competent Authorities to ensure that the HE is not being used by developers of ATMPs as an alternative to the centralised approval pathway as set out in the ATMP Regulation.

Conclusion

By putting forward these recommendations, EuropaBio and its members would like to engage the European Commission and all relevant stakeholders in a discussion on the future use of the HE in the context of the new EU Pharmaceutical Strategy and its accompanying actions.

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