EU pharma package: ATMPs under hospital exemption

The pharmaceutical legislative package recently published by the European Commission (composed of a proposal of Directive - "Directive proposal" - and a proposal of Regulation - "Regulation proposal") maintains the hospital exemption from marketing authorisation for ATMPs under certain conditions.

The Directive proposal clarifies the legal framework regarding the use of advanced therapy medicinal products ("ATMPs") under hospital exemption.

As a preliminary point, it should be reminded that Directive 2001/83/EC, in its Article 3, defines ATMPs under hospital exemption, as ATMPs prepared :

• On an ad hoc basis and according to specific good practice requirements;

• Used within the same Member State, in a hospital, under the exclusive professional responsibility of a physician;

• In order to meet an individual medical prescription for a custom-made product for a determined individual patient.

Such Article of the Directive currently into force also mentions that the manufacture of ATMPs under hospital exemption must be authorised by the competent authority of the Member States. Member States are also required to ensure compliance with the requirements of traceability, pharmacovigilance and quality standards for ATMPs.

The European Commission has however observed that the application of this hospital exemption can differ considerably from one Member State to another.

The Directive proposal, although it also excludes from its scope the provisions relating to ATMPs under hospital exemption, introduces some modifications aimed at improving the application of hospital exemptions for ATMPs. Such modifications does not bring any changes to the definition of ATMPs under hospital exemption.

The information related to manufacturing authorisations of ATMPs under hospital exemption

The Directive proposal provides, in the same way as Directive 2001/83/EC, that the manufacture of ATMPs under hospital exemption, must be authorised by the competent authorities of the Member States. The novelty here lies in the fact that Member States are now required to notify the EMA of any such authorisation, as well as any subsequent changes.

A territoriality criterion has also been introduced in the proposal, insofar as the application for authorisation must henceforth be submitted to the competent authority of the Member State in which the hospital is located.

Moreover, the Member States should also inform the EMA and the competent authorities of others Member States in the case the exemption authorisation is revoked due to safety or efficacy concerns.

Collection and report of data related to ATMPs under hospital exemption

The holder of the authorisation to manufacture ATPMs according an hospital exemption would have the obligation, according to the Directive proposal, to collect and report data to the competent authority of the concerned Member State related to its use, safety and efficacy.

The Member States should ensure that the holders of exemption authorisation proceed to this report at least once a year and should examine these data and verify the compliance of ATMPs under the hospital exemption with the requirements concerning the manufacturing and traceability.

Such data should be communicated by the competent authority of each Member State to the EMA. A repository of such data would be implemented and operated by the EMA with the help of the competent authorities of Member States and the European Commission

Report of the EMA concerning ATMPs under hospital exemption

On the basis of the data of the ATMPs under hospital exemption collected by the different Member States, the EMA should provide the European Commission with reports regarding the manufacturing authorisations related to those products.

Such reports would have to be regularly communicated to the European Commission by the EMA.

In its current version, the Directive proposal does not introduce any change that could have a major impact on the management of manufacturing authorisations for ATMPs under hospital exemption.

However, the modifications made by the Directive proposal suggest a strong willingness, through the collection of data, to reinforce the management of these products by the Member States and, through the communication with the EMA, to further harmonise the rules governing ATMPs under hospital exemption.