Support specific to ATMPs’ development at EMA level

The services and procedures put in place by EMA are designed to help developers to enter into early contact with the agency and overcome the challenges a developer may encounter when trying to bring an ATMP medicine on the European Union market. 

The main challenge here is the complexity of implementing legislative and regulatory requirements as well as to develop appropriate guidance for ATMPs’ development in accordance with their scientific and technical specificities. It implies first to know whether a medicine will fall or not within the legal category of ATMPs, and if so, what type of ATMPs it is. Despite the legislative definitions and the EMA’s guidance, such classification remains difficult to anticipate due to the specificities of each ATMP. Thus, it is established on a case-by-case basis and the recommendation of CAT on ATMP classification is of paramount importance.

Another challenge to consider is the status of the medicines’ developer as the various schemes are not always available for all types of stakeholders, given that they sometimes depend on different legislative requirements or incentives, and they are not necessarily involved in the same stage of the medicines’ development life cycle. EMA needs to adapt the support to the different actors involved with the goal of fostering research and the development of new medicines to enable patient’s access to ATMPs, in accordance with the applicable legislative provisions. In such context and contrary to big pharma, SMEs have less resources to be dedicated to regulatory issues in particular, while academia has often considered to be far from the EMA given its main focus on proof of concept, pre-clinical and clinical studies in the early part of medicines’ life cycle.

Apart from finding new ways to allow dialogue between EMA and developers which is one of the main challenges faced by EMA considering its limited human resources, communicating on the existing procedures and services available to support the development of medicine is also fundamental. Despite the organisation of events by EMA, such as stakeholders’ meetings, its very complete website, and its participation in congresses, many stakeholders have no full knowledge of the available tools for early interactions with EMA. 

EMA created several early interaction procedures to accompany medicine developers into navigating the legal requirements at any stage of a medicinal product life cycle, especially in order to obtain and maintain marketing authorisation. The available procedures for early interactions between stakeholders and regulators are meant to foster early patient’s access to medicines. 

In addition to the services and procedures available for all medicines or for innovative medicines, procedures specific to ATMPs have been established to support their development in accordance with their scientific and technical specificities. These procedures help to navigate the complex legislative landscape as well as the numerous scientific and regulatory guidance adopted at the European Union level.

Some procedures and incentives have been established in accordance with the legislative requirements, here the EU Regulation on ATMPs (Regulation (EU) 1394/2007): Scientific recommendation on ATMP classification and ATMP certification procedure, as well as fee reductions or waivers.

Another pilot procedure has been developed by EMA on its own initiative to identify and provide support specifically to academia and and non-profit organisations: the ATMP pilot for Academia and non-profit organisations. The ATMP pilot has been launched in September 2022, and first-results are expected in 3 to 4 years. This new opportunity for interaction between academia and the EMA will help the EMA to identify how to better support academic developers in translating basic research developments into medicines. (See: Translational science)

1. Procedure for all ATMPs’ developers: Scientific recommendation on ATMP classification 

This procedure aims to know if a medicine does fall or not within the legal category of ATMPs, and if so, what type of ATMPs it is, in accordance with EU legal definitions. The submission is made to the EMA, and the CAT is delivering these recommendations after consultation with the European Commission and within 60 days after receipt of the request. (Article 17 of Regulation (EC) N° 1394/2007). 

This procedure is voluntary and free of charge.

The application includes two forms (one on administrative information and one on classification request and briefing information) that shall be sent via email to the EMA at specific submission dates. Forms, dates of submission and further information including guidance documents on classification, are available on the EMA’s dedicated webpage here.

Moreover, in order to anticipate on the potential classification of a medicine as an ATMP, it may be useful to consult the previous CAT’s summaries of scientific recommendations on ATMPs classification that are available on the EMA’s dedicated webpage here.

2. Specific Procedure for SMEs status’ holders developing ATMPs: the ATMP certification procedure

The certification procedure is dedicated to SMEs status’ holders, to know more on the conditions and on how to obtain this status, please see the SMEs’ status section in Practical steps within the entry ‘Support for innovative medicines’ development at the EMA level’ and the dedicated EMA’s webpage here.

The certification procedure aims to incentivise SMEs to conduct quality and non-clinical studies on ATMPs, especially for those which would not have the necessary resources to develop such medicines to the end of the commercialisation pathway. Although it is independent from any marketing authorization application, it also aims “at facilitating the evaluation of any future application for clinical trial and marketing authorisation based on the same data. For this reason, the evaluation of an application for certification should be conducted in accordance with the same scientific and technical requirements as those applicable to a marketing authorisation application”. (Recital 3 of Commission Regulation (EC) No 668/2009 of 24 July 2009).

The certification procedure involves a scientific assessment by CAT of quality data and, when available, non-clinical data which have been generated by SMEs at any stage of the ATMP development process. To achieve this assessment, CAT may request supplementary information and/or, upon acceptance from the applicant, a site visit of the premises where the ATMP concerned is being developed. 

After this assessment, CAT will issue a recommendation upon which the EMA issues a certification.

The procedure can be divided into two phases:

• A pre-submission phase request for ATMP certification:
  • The sponsor has to create an EMA account on the EMA Account Management portal and submits an application written in English through the EMA Services Desk platform. 
  • The sponsor needs to notify the EMA of their intention to submit a request for the procedure by completing the ‘Intent to submit’ pre-submission request form 
  • The developer needs to ask for an ‘ATMP certification’ under the `type of question’ tab to send out a pre-submission request to EMA.
  • The pre-submission request form for ATMP certification is available here as well as the list of annexes the sponsor needs to complete their submission with. 
• A phase of submission of the ATMP certification dossier of quality, and if available, non-clinical data
  • First, the EMA assesses the validity of the application (i.e. the application includes all the data required by article 2 of Commission Regulation (EC) No 668/2009 of 24 July 2009). Additional data are required for combined ATMPs (article 4 of Commission Regulation (EC) No 668/2009 of 24 July 2009)
  • If the request is validated by the EMA through the platform, then the sponsor can submit the same dossier via Eudralink to the CAT members and the EMA service desk as a submission for ATMP certification. 
  • Upon receipt of valid application, the procedure from the evaluation to the certification takes 90 days, excluding potential clock-stops due to the request of supplementary information or site visits.

The submission deadlines and further information are available on the EMA’s webpage dedicated to the certification procedures for SMEs. 

As of 1 May 2023, one of these two fees is due to the EMA for certification of quality and non-clinical data relating to ATMPs developed by SMEs: 

• EUR 77,900 for the evaluation of an application relating to quality and non-clinical data;
• EUR 51,800 for the evaluation of an application relating to quality data.

3. Specific Procedure for academia and non-profit organisations developing ATMPs: the ATMP pilot for Academia and non-profit organisations 

The ‘ATMP pilot’ aims at providing an increased support for developers of promising ATMPs to meet regulatory requirements regarding quality, safety, and efficacy, and if needed until the submission of marketing authorisation applications. Up to five ATMPs’ developers will be selected by the end of 2024, and will benefit from this specific support from the EMA as well as from the fee incentives applicable to SMEs developers. 

The admissibility of the application depends on different criteria that are detailed in the EMA, Q&A on EMA pilot offering enhanced support to academic and nonprofit developers of Advanced Therapy Medicinal Products (ATMPs). For instance, the ‘ATMP pilot’ is exclusively meant for Academic or non-profit organisations developing ATMPs. 

The application form includes the applicant details, ATMP product type, Stage of development of the ATMP (Non-Clinical, Exploratory Clinical, Confirmatory Clinical or Other to be specified), as well as information on the product. The latter notably questions whether the developer has already entered into early interaction with the EMA for the ATMP concerned to enter the pilot, and if so, to specify the procedures and schemes used. This can have an impact on the application: for example, the PRIME designation exempts the sponsors from having to give a detailed overview of the development plan for the medicinal product. 

Last but not least, for products without PRIME designation, the applicant has to provide justification for an unmet medical need and the overview for development plan. 

Interested academia and non-profit organisations can find and download the application form in word format on the section dedicated to the ATMP pilot on the EMA’s website here. 

The EMA held multiple webinars on support for academia and non-profit ATMPs’ developers to explain how the pilot will be implemented. The interested developers can watch the latest webinar on the ATMP pilot here, hosted by the EMA on 8 February 2023. 

For further information on this pilot, please consult the section dedicated to the ATMP pilot on the EMA’s website here. The EMA can also be contacted via this email address advancedtherapies@ema.europa.eu. This email is also the one for developers to send their application for the ATMP pilot. 

Published: 17/08/2023

Author:

Auxane Delage, EuroGCT information officer on Ethical, Legal and Societal Issues

Aurélie Mahalatchimy, EuroGCT WP4 Convenor, UMR 7318 DICE CERIC, Aix-Marseille University, CNRS, Aix-en-Provence- France

Reviewed by:

Under internal review by EuroGCT Research and Innovation Working Group