Advanced therapy medicinal products: Overview

Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells. They offer groundbreaking new opportunities for the treatment of disease and injury.

ATMPs can be classified into three main types:

• gene therapy medicines: these contain genes that lead to a therapeutic, prophylactic or diagnostic effect. They work by inserting 'recombinant' genes into the body, usually to treat a variety of diseases, including genetic disorders, cancer or long-term diseases. A recombinant gene is a stretch of DNA that is created in the laboratory, bringing together DNA from different sources;
• somatic-cell therapy medicines: these contain cells or tissues that have been manipulated to change their biological characteristics or cells or tissues not intended to be used for the same essential functions in the body. They can be used to cure, diagnose or prevent diseases;
• tissue-engineered medicines: these contain cells or tissues that have been modified so they can be used to repair, regenerate or replace human tissue;

In addition, some ATMPs may contain one or more medical devices as an integral part of the medicine, which are referred to as combined ATMPs. An example of this is cells embedded in a biodegradable matrix or scaffold.

For detailed definitions of the different groups of advanced therapy medicinal products, refer to Regulation (EC) No 1394/2007 and Directive 2001/83/EC.

In April 2020, EMA'sCommittee for Advanced Therapies (CAT) advised patients and the general public to beware of unproven cell-based therapies.

• EMA warns against using unproven cell-based therapies  (28/04/2020)

Healthcare providers should explain the benefits and risks of the cell-based therapies that they are providing to patients, as well as confirming that regulatory authorities have approved their use.

Anyone with doubts can contact EMA or their national competent authority.

The CAT’s statement replaces a statement it issued in 2010 following reports of unregulated stem-cell therapies being offered to patients.

• Legal framework: Advanced therapies
• Meetings with stakeholders and other organisations

All advanced therapy medicines are authorised centrally via the European Medicines Agency (EMA). They benefit from a single evaluation and authorisation procedure.

As with all medicines, the Agency continues to monitor the safety and efficacy of advanced therapy medicines after they are approved and marketed. The Agency also gives scientific support to developers to help them design pharmacovigilance and risk management systems used to monitor the safety of these medicines.

In October 2017, the European Commission and EMA published a joint action plan on ATMPs, which aims to streamline procedures and better address the specific requirements of ATMP developers.

It contains several actions for the European Commission and EMA.

In February 2018, as part of the joint action plan, EMA published

• an update to the procedural advice on the evaluation of ATMPs. For more information, see Marketing-authorisation procedures for advanced therapies;
• a draft revised guideline on safety and efficacy follow up and risk management of ATMPs. For more information, see Pharmacovigilance for advanced therapies.

The action plan takes into account the ideas collected at an EMA-hosted multi-stakeholder workshop to explore solutions to challenges in the development of ATMPs.

Academic and non-profit organisations involved in developing promising advanced therapy medicines (ATMPs) can apply for EMA's increased support in meeting regulatory requirements. 

Up to five ATMP developers targeting unmet clinical needs will receive dedicated assistance that includes:

• Guidance throughout the regulatory process, from manufacturing best practice to clinical development and follow-up planning on efficacy or safety issues
• Fee reductions and waivers 

This EMA pilot aims to assess the level of regulatory support needed to boost the number of advanced therapy medicines that reach patients in the European Economic Area.

It was launched in September 2022. Initial results are expected after three to four years.

For more information about the pilot, those interested can also use the email address above to write to EMA, or they can contact their national competent authorities.

EMA hosted a webinar on the pilot on 8 February 2023.

It aimed to:

• Introduce the pilot, the supporting materials and how to apply
• Facilitate a questions and answers session

A recording of the webinar is available below:

Online training modules are available to help ATMP developers navigate the regulatory environment for these types of medicine.

Developers can access these modules for free via the TransMed Academy (login required).

The modules cover the following subjects:

• How to apply for ATMP classification
• How to apply for an environmental risk assessment for ATMPs containing genetically modified organisms
• Scientific advice for ATMPs
• ATMP certification
• Quality as a critical step in clinical development of ATMPs

Recorded webinars are also available on Youtube:

• Navigating the regulatory requirements for ATMPs
• Scientific advice for advanced therapy medicinal products: What and when to ask
• Support for academic and non-profit ATMP developers

EMA has produced these training materials together with EATRIS as part of the ADVANCE EU training project targeting ATMP developers.

The Agency's Committee for Advanced Therapies (CAT) plays a central role in the scientific assessment of advanced therapy medicines. It provides the expertise that is needed to evaluate advanced therapy medicines.

During the assessment procedure, the CAT prepares a draft opinion on the quality, safety and efficacy of the advanced therapy medicine. It sends this to the Committee for Medicinal Products for Human Use (CHMP). Based on the CAT opinion, the CHMP adopts an opinion recommending or not the authorisation of the medicine by the European Commission. The European Commission makes its final decision on the basis of the CHMP opinion.

The CAT also:

• gives recommendations on the classification of advanced therapy medicines;
• evaluates applications for certification of quality and non-clinical data for SMEs, following which the Agency issues a certificate;
• contributes towards giving scientific advice on advanced therapy medicines;
• is involved in any procedure regarding the provision of advice for undertakings on the conduct of efficacy follow-up, pharmacovigilance and risk management systems of ATMPs;
• advises, at the request of the CHMP, on any medicinal product which may require, for the evaluation of its quality, safety or efficacy, expertise in ATMPs;
• assists scientifically in the elaboration of any documents related to the fulfilment of the objectives of Regulation (EC) No 1394/2007;
• contributes towards an environment that encourages the development of advanced therapy medicines;
• provides, at the request of the European Commission, scientific expertise and advice for any initiatives related to the development of innovative medicines and therapies.

Stem cells are naturally occurring cells in the body that have the ability to divide and produce a range of different cell types. Stem cells are important in the growth and development of the body, as well as in repair after injury. 

Stems cells are categorised as ATMPs when these cells undergo substantial manipulation or are used for a different essential function. They can be somatic-cell therapy products or tissue-engineered products, depending on how the medicine works in the body.

EMA follows research into the use of stem cells in medicines very closely and is responsible for assessing marketing authorisation applications for medicines containing stem cells.

The Agency has been advising developers of stem cell-based medicines for a number of years:

• the CAT has classified a number of medicines containing stem cells as ATMPs;
• the Scientific Advice Working Party has given advice on the development of at least seven medicines containing stem cells;
• the Committee for Orphan Medicinal Products (COMP) has granted orphan designation to a number of medicines containing stem cells for the treatment of rare diseases.
• in December 2014, EMA recommended the first ATMP containing stem cells for approval in the European Union.

In February 2011, the Agency published a reflection paper on stem cell-based medicinal products . The paper stressed the fact that developers of stem-cell based medicines need to pay close attention to the way the medicines are manufactured, to ensure that the final medicine is as consistent and reproducible as possible. Pre-clinical and clinical testing also needs to take account of the cells' properties, ensuring that the possible risks of tumour development and rejection by the body are studied adequately and balanced against their benefits for patients.

The reflection paper was adopted by the CAT on 14 January 2011. This followed a public consultation between March and June 2010 and discussion at a public workshop in May 2010 involving 230 participants from academia, industry and regulatory authorities.

For more information, see the draft reflection paper and the overview of comments received .