How we regulate advanced therapy medicinal products

Regulation on advanced therapy medicinal products/tissue engineering
Agreement was reached on a Regulation on advanced therapy medicinal products/tissue engineering at the Health Council on 31 May 2007. The new Regulation (No 1394/2007) was published in the Official Journal of the European Communities on 10 December 2007 and entered into force on 30 December 2007. The Regulation will apply one year after the entry into force date (30 December 2008). A copy of the Regulation is available below:
› Regulation (EC) No 1394/2007 (104Kb)

Q&A guidance on the new Regulation is available below:
› Questions and Answers on Regulation (EC) No 1394/2007 (28Kb)

The main provisions contained in the Regulation are:

• Tissue engineered products (TEPs) falling within the definition of medicinal product will be grouped with gene therapy and somatic cell therapy medicinal products and called advanced therapy medicinal products (ATMPs) ;
• under the Regulation, a TEP contains or consists of engineered cells or tissues and is presented as having properties for treating or preventing disease in human beings;
• a centralised Community marketing authorisation procedure will apply to ATMPs;
• ATMPs which are prepared on a non routine basis and used within the same Member State in a hospital in accordance with a medical prescription for an individual patient will be exempt from the Regulation;
• a committee for advanced therapies (CAT) will be established within the European Medicines Agency (EMEA) to provide scientific advice on ATMPs of which at least two members must have medical devices expertise;
• for combination advanced therapy medicinal products, the device element will have to conform with the essential requirements as in devices legislation, the overall product will be evaluated by the EMEA;
• where the medical device or implantable device has already been assessed by a notified body, the EMEA will recognise the results of that assessment in its evaluation of the product concerned;
• where a notified body’s assessment has not taken place, the EMEA will seek an opinion from a notified body unless the devices experts on the CAT advise that an opinion is not required;
• the Tissues and Cells Directive (2004/23/EC) will apply to donation, procurement and testing of human tissues and cells contained in ATMPs;
• detailed guidelines in line with the principles of good manufacturing practice specific to ATMPs will be published by the Commission;
• specific technical guidelines will be developed for ATMPs;
• there will be specific labelling and packaging requirements for ATMPs;
• post-authorisation monitoring will be required via pharmacovigilance and risk management;
• the Regulation recognises that there is no consensus among Member States upon which harmonised decisions could be taken on the use or prohibition of embryonic stem cells so the option of prohibition or restriction of products containing particular kinds of cells will remain a national responsibility;
• a range of incentives for small and medium sized enterprises (SMEs) including a reduction in fees payable to the EMEA for provision of scientific advice and deferral of fees until notification of final decision; and
• there will be 3 or 4 years transitional protection for products legally on the market at the time the Regulation applied.

ATMPs which are prepared on a non routine basis and used in a hospital
Under the Regulation, products which are prepared on a non routine basis and used within the same Member State in a hospital in accordance with a medical prescription for an individual patient will be exempt from the Regulation. Exempted products will need to comply with manufacturing, quality and pharmacovigilance standards which will be defined at national level.

The MHRA is responsible for developing the national arrangements for the UK. A consultation exercise on proposed arrangements that may apply in the UK was launched on 23 July 2008. The consultation documents can be accessed below:
› Public consultation (MLX 353): Consultation on advanced therapy medicinal products

EMEA guidance
Market approval for ATMPs will be through a centralised procedure administered by the EMEA. In preparation for this, the European Commission asked EMEA to develop appropriate guidance. The EMEA consulted on a draft guideline on market authorisation applications for human cell based medicinal products in 2007. Further guidance is currently being developed by the EMEA.

Background to the Regulation
The European Commission adopted formal proposals for a Regulation on advanced therapy medicinal products/tissue engineering in November 2005.
The Commission’s proposal and related documents are available on the Commission’s website (external link).

The Commission’s proposals were developed following consultation exercises which took place in 2002, 2004 and 2005. Further information about the Commission’s consultation exercises is available on their website.

Negotiations on the proposed Regulation were launched in January 2006 under the Austrian Presidency. The European Parliament (EP) voted in plenary on the proposed Regulation on 25 April 2007. Political agreement was reached on the proposed Regulation at the Health Council on 31 May 2007.

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 tissue/cells. The use of this technology has already led to the development of products that are used clinically for the treatment of burns or ulcers and cartilage repair systems used in the treatment of early arthritis. More complex products are currently being developed for the treatment of heart disease and other degenerative conditions.

How are tissue engineered products currently regulated in the UK?
At this time, there is no specific regulatory framework for tissue engineering and tissue engineered products (gene therapy and somatic cell therapy medicinal products fall under current medicines legislation). TEPs fall outside existing devices legislation and some TEPs also fall outside existing medicines legislation although some may fall within the definition of somatic cell therapy medicinal product.

The MHRA’s Medicines Borderline Section determines whether a particular product is medicinal or a borderline product (for example cosmetics or food supplements). Further guidance on borderline products is available within the borderline section of the website or you can contact us for further advice.