“Europe’s biotechnology sector has promising technologies to offer its citizens and the world, and it is crucial for the future of its life sciences sector that the right legal framework is created to allow these to reach the patients. Europe is already falling behind in this field and we need to act.”

--Wills Hughes-Wilson,
Chair,
EuropaBio’s Advanced Therapies Working Group

Advanced therapies - some examples

Links

To view the Regulation:
http://eur-lex.europa.eu/LexUriServ/site/en/
oj/2007/l_324/l_32420071210en01210137.pdf.

The Implementation plan: http://ec.europa.eu/enterprise/pharmaceuticals/
 advtherapies/docs/implementationplan-2007-12-11.pdf

November 2005 - the European Commission published its proposed text for a Regulation;

13 September 2006 - the ENVI Committee rejected the first Report by the European Parliament Rapporteur Miroslav Mikolasik because it contained a large number of so-called “ethical amendments”, which would have banned a range of products and technologies;

30 January 2007 - the Rapporteur’s second draft was adopted by the ENVI Committee with a convincing majority, and with none of the “ethical amendments” included;

Early 2007 - “Trialogue” negotiations started (discussions between the European Commission, the Council and the European Parliament) by the beginning of the year 2007 to explore the possibility of an early adoption;

The European Parliament‘s Plenary vote was postponed from 13 March to the end of April to give the trialogue negotiations enough time to explore an eventual agreement;

April 2007 - The trialogue negotiations failed and the plenary vote will take place in the week of the 23 April in Strasbourg.

25 April 2007 - European Parliament approves Advanced Therapies Regulation

30 December 2007 - Regulation (EC) No 1394/2007 on advanced therapy medicinal products has entered into force

Following the opinion of the European Parliament on 25 April 2007, the European Council of Ministers approved the Regulation on advanced therapies, in first-reading on 31 May 2007. The Regulation was translated into all EU official languages and on 30 October 2007 the Advanced Therapy Regulation was formally adopted by the EU Council.  The Regulation was published in the EU Official Journal on 10 December 2007 and entered into force on 30 December 2007.   Soon after the publishing of the Regulation, the DG Enterprise and Industry made public its priorities for the implementation of the Advanced Therapies Regulation. The implementation plan has been developed and agreed with the European Medicines Agency (EMEA). 

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• What are “advanced therapies”?
• Why does there need to be a European Regulation?
• How will the proposed Regulation help?
• What is the industry position?
• Where’s the controversy?
• What is the timeline of the Regulation?

• What are “advanced therapies”?

“Advanced therapies” is an umbrella term that covers the three new techniques that are revolutionising modern medicine: cell therapy, gene therapy and tissue engineering. These techniques are already producing new treatments, and in the future are likely to produce many more.

In cell therapy, new cells are introduced into tissue to treat a disease – either from the patient’s own body (autologous), from another person (allogenic) or from an animal (xenogenic). One current example is the use of human adult stem cells in treating leukaemia. Around the world, researchers have been making progress towards using stem cells to treat conditions ranging from heart disease, spinal cord injury and brain damage to muscle damage, low blood supply and even deafness and baldness.

In gene therapy, genes are introduced to replace, repair or switch off defective ones. It has been used, so far with varying degrees of success, in severe combined immunodeficiency (SCID), cystic fibrosis, muscular dystrophy and sickle-cell anaemia, among others.

Tissue engineering is aimed at replacing or repairing defective tissue, and is generally seen as relating to bone, cartilage and blood vessels such as veins and arteries. This expanding field covers the techniques of bioengineering and cell biology (and often cell therapy itself). It is already being used to repair or replace burnt skin, for example.

• Why does there need to be a European Regulation?

Patients – and companies seeking cures for them – in the different countries of the European Union face a bewildering patchwork of guidelines, regulations and procedures relating to advanced therapies. Some countries have no specific framework at all.

This diversity is failing patients in terms of safety and efficacy, quality, and availability.
Safety and efficacy. These new products are all at the leading edge of medical discovery, and there are many new challenges in judging whether they are safe to use, and whether they work as claimed – so standards need to be set and expertise needs to be highly specific. That requires bringing together the best experts from across Europe.

Quality. These new treatments are targeted at very specific processes inside and between cells in the body, and will require highly specialised manufacturing procedures to ensure quality. Again, standards need to be set and expertise needs to be highly specific.

Availability. With so many different national systems, companies making the new treatments face enormous problems in bringing them onto each national market. This leads an unfair situation where patients in some countries miss out on treatments that could save their lives. It also puts the European advanced therapy industry at a competitive disadvantage vis-à-vis the United States, whose manufacturers have a single home market to support them.

• How will the proposed Regulation help?

One procedure. The proposed Regulation will provide one single centralised procedure, run by the European Medicines Agency (EMEA), for the whole of the European Union for assessing the safety, efficacy and quality of advanced therapies and giving them marketing authorisation. While a single procedure under the EMEA already exists for products of cell and gene therapy, the Regulation will now bring tissue engineering into the system for the first time.

Specialist knowledge. The Regulation will set up a Committee for Advanced Therapies (CAT) within the EMEA to ensure the most thorough scientific evaluation possible. The CAT will be multidisciplinary, and include representatives of patients and doctors.

Monitoring. Normal medicines disappear from the body relatively quickly, but the cells, genes and tissues of advanced therapies are intended to last for many years. The Regulation will set up a “traceability” system that will track all patients treated with these advanced therapies, as well as the products themselves and their starting materials (for example, original cell lines). This system will allow regulators to see what is happening to patients once treated, even decades after the original treatment.

Availability. The centralised procedure will make it dramatically simpler and faster for companies producing advanced therapies to make their products available to patients across the European Union. There are also incentives built into Regulation to encourage small and medium-sized enterprises (SMEs) to invest in the new treatments.

• What is the industry position?

In general, the biotechnology industry welcomes the proposed Regulation. It believes that the centralised procedure through the EMEA is the best way to ensure that patients have access to high-quality, safe and effective products, and that it will help companies by providing them with universal access to the European market.

Realistically, though, this new procedure will require a transition period of five years, rather than the two years in the current proposal. And advanced therapies already authorised should continue to be available to patients during this transition period while the products are being evaluated under the procedure.

Industry welcomes the incentives for SMEs, but believes they should be extended to all innovative companies, of whatever size, to encourage investment in advanced therapies generally.

While supporting the idea of the CAT, industry is concerned that the Regulation proposes that it should only advise the EMEA’s Committee for Medicinal Products for Human Use on the scientific evaluation of new advanced therapies. It thinks there is no point having two committees doing basically the same thing, and that the CAT should decide on scientific issues, rather than merely give an opinion.

Industry is also keen to ensure that the EMEA, and specifically the CAT, is adequately funded to carry out its new duties.

• Where’s the controversy?

There are four possible flashpoints around the proposed regulation. One is neatly sidestepped. The other three could create short- or long-term issues.

Ethics…and embryonic stem cells. Some advanced therapies are and will be based on embryonic stem cell lines – and for ethical reasons some countries will not want to have products based on these available in their health systems. The Regulation basically sidesteps this issue with the “subsidiarity” principle: whatever the EMEA evaluation, it will be up to individual countries to decide whether these particular products should be placed on their own markets. But that may not satisfy some diehard critics of embryonic stem cell technology.

Combined products. Medical devices have always been covered by separate and generally simpler procedures than medicines. But the Regulation is suggesting that any products that combine devices and advanced therapies should come under the new centralised procedure. This is a potential concern for the medical devices industry, which might find its authorisation procedures more costly, complicated and time-consuming.

Hospitals. Products that are both prepared in full and used in a single hospital, in accordance with a medical prescription for an individual patient, are excluded from the scope of the proposal. There is some concern in industry, however, that this might allow an unlevel playing field to develop – especially as it might relate to large hospitals providing specialist care to large numbers of patients.

The grey areas. Some products will very clearly fall inside the category of advanced therapies, some very clearly outside – and there are bound to be number of grey areas. The Commission acknowledges this, and in response proposes a “case law” approach where companies unsure about where their products might lie can approach the CAT for a recommendation. But that approach lacks the legal certainty companies need, and could leave them in a research and legal limbo, not knowing whether proposed products fall within the Regulation, and hence not knowing what data sets will be required, for example. The solution, says industry, is to have clearer and more detailed definitions upfront of what constitutes an advanced therapy.
 

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