Advance Therapy Medicinal Products FAQs

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

Are there any exemptions to the Regulation for products developed prior to 31 December 2008?

Yes, the Specials Exemption (Article 5, 2001/83).

In order to fulfil the requirements for the Specials Exemption the therapy must be:

• to fulfil special needs
• supplied in response to bona fide, unsolicited order
• formulated in accordance with specifications of a healthcare professional
• for use by his/her individual patients under his/her direct responsibility

* Importantly this exemption allows export outside the member state and the use of the same treatment for multiple patients which the hospitals exemption (below) does not.

Although exempt from the Medicines legislation any product that contains human cells or tissues needs to be produced by an establishment that is licensed by the HTA for procurement donation and testing of those cells or tissue.  Manufacture of the product needs to be on premises licensed by the MHRA.

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 that is already on the market that is a gene therapy or a somatic cell therapy as defined in Annex 1 2001/83/EC (see ATMP definitions) you must comply with the Regulation by 30 Dec 2011; and an exemption applies until this date (Article 29 -1,2).

If the product in question is a Tissue Engineered P roduct (see ATMP definitions) as defined in Annex 1 2001/83/EC that was on the market by December 2008 you must comply by 30 Dec 2012 and an exemption applies until this date (Article 29 -1,2).

For an ATMP that contains human cells or tissues the donation, procurement and testing of those cells or tissue needs to be licensed by the HTA.

Are there any exemptions to the Regulation for products on the market prior to 31 December 2008?

Yes, the Hospitals Exemption (Article 28 – amending 2001/83)

The exemption to the ATMP Regulation requires that the therapy:

• is prepared - on a non-routine basis, according to specific quality standards, and
• is used with the same member state, and
• is used under the exclusive professional responsibility of a medical practitioner, to comply with an individual prescription, and
• is custom made for an individual patient.

Although exempt from the ATMP legislation any product that contains human cells or tissues needs to be licensed by the HTA for donation procurement and testing of those cells or tissue. An MHRA licence would be required for the manufacture and marketing of the product.

How does the ATMP regulation affect Embryonic Stem Cell Derived Products (para. (7) –Reg. 1394/2007)?

Stem-cell (gamete-derived) cell based products that involve the destruction of a human embryo in their formulation are initially licensed by the 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 Medicinal Product (MP) or an Investigational Medicinal Product (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 licensed by the HTA.

Peripheral Blood Stem Cells

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

How will specific gene therapies be regulated?

Gene therapies that use naked DNA and that do not utilise 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 an MP or IMP.

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

Combined ATMPs will be evaluated by the EMEA. 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 EMEA 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 EMEA 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 EMEA.

How do I get information from the EMEA?

The EMEA has published significant guidance regarding the ATMP Regulation on its website - access the EMEA website.

Is there any further guidance or information for Small and Medium sized Enterprises (SMEs)?

SMEs developing ATMPs can approach the EMEA 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 their pipeline. These may be organised in cooperation with specialised EMEA Committees/Working Parties. In addition, the ITF can provide regulatory advice to applicants on the eligibility for access to EMEA 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 EMEA procedures, is available on the EMEA website. General queries can be sent to the ITF secretariat: ITFsecretariat@emea.europa.eu.

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