CAT scientific recommendations on classification 

Introduction

The Committee for Advanced Therapies (CAT) scientific recommendations on classification is a procedure at the European Medicines Agency (EMA) designed to help developers determine if the product they are developing is an Advanced Therapy Medicinal Product (ATMP) and if so, which type of ATMP it is. This procedure answers on a case-by-case basis the question of if a medicinal product answers the scientific characteristics of an ATMP in regards to EU legislation (Regulation (EC) n°1394/2007 on ATMP and Directive 2009/120/EC amending Annex I of Directive 2001/83/EC). This procedure has been established to support the development of ATMPs, in accordance with Article 17 of Regulation (EC) N° 1394/2007.

According to this article 17 of the ATMP regulation, scientific recommendation on ATMP classification is available for “any applicant developing a product based on genes, cells or tissues”. The EMA will deliver a recommendation after consulting with the European Commission (EC) and within a 60-day period from receiving a valid request.

The CAT is the EMA’s committee in charge of providing advice on whether a product falls within the definition of an ATMP (Article 23b) of Regulation (EC) No 1394/2007).

The result of the recommendation on advanced therapy classification for each request is made public in a summary provided by the EMA except for the parts that are protected by commercial confidentiality. The list of medicines that the CAT has assessed and recommended classifying as ATMPs or not since March 2019 is available here on the EMA website.

Looking at the previous CAT scientific recommendations on ATMP classification is helpful in order to know whether the medicine being developed is an ATMP or not. Nevertheless, given that the classification as an ATMP impacts on the applicable regulatory pathways, and the sub-type of ATMPs impacts on the applicable guidance, it is strongly recommended to apply for a CAT scientific recommendation on ATMP classification. This is even recommended in case of high doubt on the classification. Moreover, a strong incentive is that this procedure is free of charge. This classification can also allow developers to access other existing incentives, such as support for medicines that fall into the category of ATMPs.

The CAT scientific recommendations on ATMP classification are not binding as long as changes in the product development (e.g. new substantial manipulation of the tissues and cells in the product development) may impact on the classification.

Despite not being binding, CAT scientific recommendations on ATMP classification are generally followed by National Medicines Agencies: e.g. the CAT recommends that the product is an ATMP. But it is prepared on a non-routine basis. The relevant National Medicines Agencies will consider to apply the ATMP hospital exemption pathways if the conditions are met.

Main actors

European Medicines Agency: The European Medicines Agency (EMA) is an agency of the European Union whose goal is to protect and promote human and animal health. The agency is responsible for the scientific assessment of Advanced Therapy Medicinal Products to be marketed within the European Union and the European Economic Area , including in the context of expediting marketing authorisations pathways. The Agency provides a number of incentives and procedures for medicines’ developers to support market access of quality medicines with a positive benefit/risk balance as regards as their safety and efficacy criteria for the final safety and health protection of patients.

Committee for Advanced Therapies (CAT) at the European Medicines Agency: The Committee for Advanced Therapies can be consulted by the European Medicines Agency or the European Commission on any matter related to ATMPs. Within the EMA, its main responsibility is to provide opinions regarding ATMP marketing authorisation applications. It also contributes to scientific advice, in cooperation with the SAWP, where Advanced Therapy Medicinal Products are concerned. The CAT is also responsible for every other procedure that has been developed to support ATMP’ development: scientific recommendation on ATMP classification, ATMP certification procedure, ATMP Pilot Academia. More on CAT on EMA website here.

Medicines’ developers: Medicine developers are the target of early interaction with regulators such as the European Medicines Agency (EMA). Medicines’ developers can be academia, industry, or non-profit organisations although they are generally from the industry sector (mainly big pharma but also SMEs) given the resources necessary for the commercialisation of medicines.

Definitions

Advanced Therapy Medicinal Products (ATMPs): Biological medicines for human use that are based on genes, cells or tissue engineering, and that comply with the legal definitions of gene therapy medicinal products, somatic cell therapy medicinal products, tissue engineered products, and combined ATMPs as provided by article 2 of Regulation 1394/2007 on ATMPs.

Scientific recommendation on ATMP classification: A specific procedure established by the EU regulation on ATMP for ATMPs’ developers to consult the EMA to know if a product they are developing is an Advanced therapy Medicinal Product (ATMP) or not, and if so, which type it is, in accordance with EU legal definitions. At the EMA, 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)

Challenges

The main challenge here is the difficulty of implementing the right legislative and regulatory requirements as well as the appropriate guidance for medicines’ development, especially ATMPs given their scientific and technical specificities, without regulatory support. While it is necessary to know whether a medicine will fall or not within the legal category of ATMPs, and if so, what type of ATMPs it is, such classification remains difficult to anticipate due to the specificities of each ATMP, and despite the existing legislative definitions and EMA’s guidance. Thus, the CAT scientific recommendation on ATMP classification is a very useful and supportive regulatory procedure. As proof, it is the most frequently used procedure among CAT’s activities since its establishement: 675 adopted recommendations out of 682 submitted by October 2024, in accordance with the “2024-10 CAT quarterly highlights and approved ATMPs Aug-Oct 2024”.

However, the future of this procedure is being partially at stake. Indeed, in accordance with the European Commission’ s proposal for a full reform of the EU pharmaceutical legislation, the CAT would become a working party and would not be a permanent scientific committee at the EMA anymore. In that context, the CAT scientific recommendation on ATMP classification would be replaced by a general procedure of EMA’s scientific recommendation on regulatory status. The latter would not be dedicated to ATMPs, but would cover medicines at large, including ATMPs. It should be highlighted that this is a reform’s proposal only, and that it can still change along the legislative process of revision. The latter can take a few years, and the potential change will be applicable only if it is included in the final version of the text, when it will be adopted. (I. Fausch, A. Mahalatchimy, “Advanced Therapy Medicinal products”, 2025, In press)

Opportunities and incentives

As explained above, the CAT scientific recommendation on ATMP classification is in itself an incentive and an opportunity for medicines’ developers, especially ATMPs’ developers.

Specifically, the classification procedure determines if a medicinal product falls under the qualification of ATMP, the CAT therefore tests if the necessary criteria are met by the product. The CAT gives the proper legal qualification to the product. It gives an explanation of the main characteristics of the product regarding the legal requirements and the criteria to be defined as an ATMP. Where it is an ATMP, the CAT scientific recommendation will also highlight what is its specific sub-type.

There are four sub-types of medicines that are categorised as ATMPs: Gene Therapy Medicinal Product (GTMP), somatic Cell Therapy Medicinal Product (sCTMP), Tissue Engineered Product (TEP), and combined Advanced Therapy Medicinal Product (combined ATMP).

Practical steps

1/ To consult the existing guidance on ATMP classification and the published scientific recommendations

Reflection paper on classification of advanced therapy medicinal products, 21 May 2015 EMA/CAT/600280/2010 rev.1 Committee for Advanced Therapies (CAT).
Procedural advice on the provision of scientific recommendation on classification of ATMPs in accordance with article 17 of regulation (EC) no 1394/2007, 5 November 2021, EMA/CAT/99623/2009 Rev.2 Committee for Advanced Therapies (CAT).
To look at the published CAT scientific recommendations on ATMP classification, available here on the EMA website

2/ To start the procedure for the Scientific recommendation on ATMP classification

Type of applicant

All types of developers can request a scientific recommendation on ATMP classification procedure.

Type of procedure

The procedure is voluntary but it is strongly advised to apply for it, in case of doubt on ATMP classification.

Cost

The recommendation on classification procedure is free of charge.

Timetable

The Committee for Advanced Therapies meets once a month at the EMA in Amsterdam, the agenda of the meetings is available on EMA’s website since December 2013.

The application shall be submitted in accordance with specific submission dates, available on the EMA’s dedicated webpage here.

Application steps

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.

Role of the CAT members

Chair and Co-chair of the CAT

The chair and Co-chair of the CAT have specific responsibilities in regards to the recommendation on advanced therapy classification procedure. Mainly they have a supervision role and the responsibility falls onto them to ensure with the rest of the CAT and the EMA secretary “the regulatory and scientific consistency of the CAT scientific recommendation on advanced therapy classification;”

(06 October 2022 EMA/CAT/454446/2008 rev. 5 Committee for Advanced Therapies Committee for Advanced Therapies (CAT) Rules of Procedure).

Written procedure at CAT

Preliminary version of the CAT scientific recommendation on advanced therapy classification after being approved by the chair can be submitted by the EMA secretariat to the CAT for adoption in accordance with the legal timeframes of the evaluation (Article 9 of the Committee for Advanced Therapies Committee for Advanced Therapies (CAT) Rules of Procedure)

When serious objections arise, the chair can also decide if the written procedure and the adoption of scientific recommendation on advanced therapy classification should be postponed to the next CAT meeting.

Interactions with regulators

This procedure is in itself allowing to interact with the EMA, especially the CAT, on the specific topic of ATMP classification regarding a given product.

European Union Legislation

Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, OJ L 311, 28.11.2001, p. 67-128, CELEX number: 32001L0083.

Original text (available in the 24 official languages of the EU)
Current version with last amendments (available in the 24 official languages of the EU)
Document summary (available in the 24 official languages of the EU)

Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 (Text with EEA relevance), OJ L 324, 10.12.2007, p. 121-137, CELEX number: 32007R1394

Original text (available in the 24 official languages of the EU)
Current version with last amendments (available in the 24 official languages of the EU)
Document summary (available in the 24 official languages of the EU)
Original text
Current version with last amendments (available in the 24 official languages of the EU)

Article 17 of Regulation (EC) No 1394/2007

“Scientific recommendation on advanced therapy classification

1. Any applicant developing a product based on genes, cells or tissues may request a scientific recommendation of the Agency with a view to determining whether the referred product falls, on scientific grounds, within the definition of an advanced therapy medicinal product. The Agency shall deliver this recommendation after consultation with the Commission and within 60 days after receipt of the request.

2. The Agency shall publish summaries of the recommendations delivered in accordance with paragraph 1, after deletion of all information of commercial confidential nature.”

Directive 2009/120/EC of the European Commission of 14 September 2009 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products (Text with EEA relevance), OJ L 242, 15.9.2009, p. 3–12, CELEX number: 32009L0120

Original text
Current version with last amendments (available in the 24 official languages of the EU)

European Union Guidance and documents

Procedural advice on the provision of scientific recommendation on classification of advanced therapy medicinal products in accordance with article 17 of regulation (EC) no 1394/2007, 5 November 2021, EMA/CAT/99623/2009 Rev.2 Committee for Advanced Therapies (CAT). (under revision - November 2020)

Reflection paper on classification of advanced therapy medicinal products, 21 May 2015 EMA/CAT/600280/2010 rev.1 Committee for Advanced Therapies (CAT).

Proposal for a Directive of the European Parliament and the Council on the Union code relating to medicinal products for human use, and repealing Directive 2001/83/EC and Directive 2009/35/EC, 26.4.2023, COM(2023) 192 final. (NOT APPLICABLE, ONGOING REVISION PROCESS)

Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006, COM/2023/193 final. (NOT APPLICABLE, ONGOING REVISION PROCESS)

Relevant literature

Advanced Therapy Medicinal products, I. Fausch, A. Mahalatchimy, in S. Garben, L. Gormley, The Oxford Encylopedia of EU Law [OEEUL], (01/2025), In Press.

The advanced therapy classification procedure. Voltz-Girolt, C., Celis, P., Boucaumont, M. et al., Bundesgesundheitsbl. 54, (2011): 811–815.

Cell-based product classification procedure: What can be done differently to improve decisions on borderline products? Izeta, A., Herrera, C., Mata, R., Astori, G., Giordano, R., Hernández, C., & Cuende, N., Cytotherapy, 18(7), (2016): 809-815.

Classification of cell-based medicinal products and legal implications: An overview and an update. Scherer,J., & Flory, E., Bundesgesundheitsblatt-Gesundheitsforschung-Gesundheitsschutz, 58, (2015): 1201-1206.

European regulatory tools for advanced therapy medicinal products. Flory, E., & Reinhardt, J., Transfusion Medicine and Hemotherapy, 40(6), (2013): 409-412.

Overview of comments received on 'Procedural Advice on the Provision of Scientific Recommendation on Classification of Advcanced Therapy Medicinal Products in accordance with Article 17 of Regulation (EC) No.1394/2007 (EMA/CAT/99623/2009), 17th February 2010 EMA/CAT/106109/2010 Committee for Advanced Therapies (CAT).

Overview of comments received on 'Reflection Paper on classification of advanced therapy medicinal products'(EMA/CAT/600280/2010 rev. 1), 28 May 2015 EMA/CAT/224106/2015 Committee for Advanced Therapies (CAT).

Acknowledgements

Published: 03/11/2024

Authors:

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

Torna in alto

Domande frequenti

Glossario

Seleziona una lingua

Condizione

Tema