Advanced Therapy Medicinal Products FAQs

Frequently asked questions for Advanced Therapy Medicinal Products (ATMPs).

What are ATMPs?

ATMPs are ‘innovative, regenerative therapies which combine aspects of medicine, cell biology, science and engineering for the purpose of regenerating, repairing or replacing damaged tissues or cells’.
An ATMP is defined as either:

(a) a gene therapy ‘medicinal product’
(b) a somatic cell therapy ‘medicinal product’
(c) a tissue engineered product – a product that:

• contains or consists of cells or tissues that have either been subject to ‘substantial manipulation’ or that are not intended to be used for the same essential function(s) in the recipient as in the donor

and

• is presented as having properties for treating or preventing disease in patients.

Further details on these categories can be found in the list of ATMP definitions.

Where can I find information about legislation concerning ATMPs?

Directives and Regulations relevant to the licensing of ATMPs are:

Directive 2001/83/EC

Directive 2009/120/EC

Regulation (EC) No 726/2004

Regulation (EC) No 1394/2007 (‘The ATMP Regulation’)

What is a medicinal product?

According to the Medicines Directive a ‘medicinal product’ is any substance or combination of substances presented for treating or preventing diseases in patients, or which may be given to patients with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in patients.

‘The ATMP Regulation’ provides a framework clarifying when products containing cells or tissues will be regulated as medicinal products (and as ATMPs in particular). If a product falls within the scope of the Regulation then any market authorisation for such a product is granted by the European Medicines Agency (EMA). However there are a number of exemptions from the requirement for a market authorisation, and the Medicines and Healthcare products Regulatory Agency (MHRA) will be able to advise on these.

If I have a product already on the market when do I have to comply with the ATMP Regulation (which came into force on 31 December 2008)?

Existing products

For an existing product which is already on the market and which is a gene therapy or a somatic cell therapy product (see ATMP definitions) you must comply with the ATMP Regulation by 30 Dec 2011; and an exemption applies until this date (Article 29).

If the product in question is a Tissue Engineered Product (see ATMP definitions) which was on the market by December 2008 you must comply by 30 Dec 2012 and an exemption applies until this date (Article 29).

How do I know if my product is an ATMP?

Applicants should contact the Medicines and Healthcare products Regulatory Agency (MHRA) for classification of a potential ATMP. The MHRA will also be able to advise you further, including on the applicability of any exemptions to market authorisation.

If the product is not considered an ATMP by the MHRA / EMA but contains human tissues or cells it will be regulated entirely by the HTA under the Human Tissue (Quality and Safety for Human Application) Regulations 2007 (the ‘Quality and Safety Regulations’) for donation, procurement, testing, processing, storage, distribution and import / export.

What aspects of ATMPs are regulated by the HTA?

Products classified as ATMPs (both MPs and IMPs) will be regulated by the HTA only as far as donation, procurement and testing of human tissues and cells are concerned. The MHRA will regulate the manufacture, storage and distribution of these products.

Are there any exemptions to market authorisation for ATMPs?

Yes, products may be eligible for production under a specials exemption or hospital exemptions can only be granted to products distributed in the country of production.

Further guidance can be obtained on the MHRA website. The MHRA will be able to advise you on which licenisng regime is most appropriate for your circumstances.

How does the ATMP regulation affect Embryonic Stem Cell Derived Products (ATMP Regulation paragraph 7)?

Stem-cell (gamete-derived) cell based products that involve the destruction of a human embryo in their formulation are initially licensed by the Human Fertilisation and Embryology Authority (HFEA). At the point where the embryo has been destroyed and cells are harvested these human cells would fall under the remit of the HTA. The development of a product using these cells is under the remit of the HTA until such time as the MHRA classifies the product as an Investigational Medicinal Product (IMP) or the product is classified as an ATMP. Once this classification has been confirmed the manufacture, clinical trial approval and marketing approval (for IMPs) are under the remit of the MHRA and not the HTA.

How will specific somatic cell therapies be regulated?

During the development of your novel somatic cell therapy, you should contact the MHRA to seek classification as a MP or an IMP. If your product is not classified as either of these, then the product will be wholly regulated by the HTA for all licensable activities. If your product is classified as a MP or IMP, then only the donation, procurement and testing will be regulated by the HTA.

Peripheral Blood Stem Cells (PBSCs)

All activities involving the donation, testing, procurement, processing and storage of PBSCs fall under the remit of the HTA as defined in the Quality & Safety Regulations Paragraph 5 (1).

How will specific gene therapies be regulated?

Gene therapies that use naked DNA and that do not use human cells during processing are outside the remit of the HTA. Such therapies are governed by the MHRA under Directive 2001/83/EC.

However, gene therapies involving the procurement, expansion and transfection of patient’s cells for autologous re-implantation must be undertaken in a HTA licensed establishment.

In both cases all activities including the donation, testing, procurement, processing and storage of human cells during the development of products that contain human cells or tissues must take place in an establishment that is licensed by the HTA as well as being licensed by the MHRA if classified as a MP or an IMP.

How do I apply for marketing approval for a device that may contain an ATMP?

Combined ATMPs (see Definitions) will be evaluated by the European Medicines Agency (EMA). The application for a marketing authorisation or a combined ATMP which contains a medical device should include evidence that the device meets the essential requirements laid down in Annex 1 to Directive 93/42/EEC or 90/385/EEC, as the case may be and, where available, the results of an assessment by a notified body in accordance with the medical devices legislation. The EMA shall recognise the results of that assessment in its evaluation of the ATMP. If the application does not include the results of a notified body’s assessment, the EMA will seek a notified body’s assessment unless the Committee for Advanced Therapies (CAT) advised by its experts for medical devices, decides that the involvement of a notified body is not required. Where such a device contains human cells the donation, procurement and testing of these cells falls under the remit of the HTA even if classification of the combination device has been given by the EMA.

How do I get information from the European Medicines Agency?

The EMA has published  guidance regarding the ATMP Regulation on its website.

Is there any further guidance or information for small and medium sized enterprises (SMEs)?

SMEs developing ATMPs can approach the European Medicines Agency for advice and guidance through the SME office or the Innovation Task Force (ITF). The activities of the ITF include ATMPs, but also other emerging therapies and technologies.

One of ITF objectives is to establish a platform for early informal dialogue with companies, particularly SMEs, to proactively identify scientific, legal and regulatory issues. To this end, SMEs may request a briefing meeting with the ITF to discuss legal, regulatory or scientific issues for selected product(s) in development. These may be organised in cooperation with specialised EMA Committees / Working Parties. In addition, the ITF can provide regulatory advice to applicants on the eligibility for access to EMA procedures (such as scientific advice and the centralised procedure for marketing authorisation) as a medicinal product (e.g. when there are uncertainties as to whether a product would qualify as a medicinal product).
 
Further information on how to contact the ITF, including forms for requesting briefing meeting and eligibility to EMA procedures, is available on the EMA website. General queries can be sent to the ITF secretariat: ITFsecretariat@EMA.europa.eu.

Any general enquiries regarding guidance or special arrangements for SMEs should be directed to smeoffice@EMA.europa.eu.