The European Parliament has approved the European Commission’s proposal to harmonise the law on medical treatments based on genes, cells and tissues, subject to several non-substantive amendments. The potential for using biotechnology-derived products to provide effective medical treatments not achievable by conventional medicines cannot be overlooked. The current draft Advanced Therapies Regulation covers three kinds of advanced industrially applied processes, namely gene therapy, somatic cell therapy and tissue engineering1. It strives to support the use of such new and innovative treatments by guaranteeing patient safety, facilitating market access and fostering the competitiveness of the EU pharmaceutical and biotechnology industry. But does it achieve its aim?
Safety comes first, and accordingly, any advanced therapeutic products must meet the requirements of pharmacovigiliance under the centralised authorisation procedure2. However, while there has been ample focus and investment into the development of these technologies, the area is still in its infancy and so is poorly characterised. Having this in mind, the draft regulation has called for additional measures to provide maximum patient safety by (i) pooling as much of the little information and expertise available, (ii) ensuring absolute traceability from the donor to the patients, and (iii) having a thorough post-authorisation risk management strategy. How are these requirements to be fulfilled?
(i) Getting the best expert input - Committee of Advanced Therapies
Within the European Medicines Agency (EMEA), the Committee for Medicinal Products for Human Use (CHMP) is responsible for drawing up the EMEA’s opinion on any scientific matter concerning the evaluation of medicinal products for human use. Having regard to the multidisciplinary nature of the technologies in question, a specialised Committee of Advanced Therapies (CAT) will be created. Members of CAT will include those appointed by the European Commission, some to represent clinicians and some to represent patient associations, and those associated with the CHMP, who are to come from different Member States3. The members of the CAT will be chosen for their scientific qualification or experience in respect of advanced therapy medicinal products, and further experts may join any meeting if appropriate - ensuring that the CAT is best equipped to evaluate such products using advanced technologies. CHMP will then consult the CAT on the assessment of data relating to advanced therapy medicinal products, while retaining responsibility for the final scientific opinion issued4.
(ii) Gene/cell/tissue tracking
These provisions are very extensive and stringent. The holder of the marketing authorisation for the advanced therapy medicinal product must provide a system which enables the tracing of the provenance of all the genes, cells, tissues and all substances which have come into contact with those genes, cells and/or tissues at all stages starting from the sourcing and manufacturing to eventual usage of the product. This data must be kept for a minimum of 30 years after the expiry date of the product. The institutions using it (mainly hospitals) must provide a system for patient and product traceability5.
(iii) Long term monitoring of patients
Unlike conventional pharmaceuticals, these products can stay in the body for a long time, which necessitates long-term patient follow up. Therefore, the draft regulation requires there to be a risk management system ensuring the follow up of the efficacy of the product and adverse reactions are to be detailed in the application for the marketing authorisation. If there is any particular concern, the Commission may, on the advice of EMEA, request further evaluation/studies to assess the effectiveness of such a risk management system.
Advanced therapeutic products for all EU patients
While products intended for gene and somatic cell therapy have been classified as medicinal products and regulated as such in the Community, tissue-engineered products were outside Community law. The draft regulation includes tissueengineered products allowing patients Community-wide to have access to such products.
However, according to the recital to the draft regulation, each Member State will retain the right to decide whether to allow the use of “any specific type of human cell, such as embryonic stem cells, or animal cells”6. This is rather unhappily worded as (non-human) animal cells are not human cells. According to the Commission’s explanatory memorandum to the proposed draft regulation, this is due to a lack of consensus among Member States on the use or prohibition of embryonic stem cells. If so, the recital has gone too far - it appears that each Member State may make a decision on the use of any specific type of human cell, let alone embryonic stem cells and presumably also on the use of animal cells. Varied laws on the type of cells which may be used between different Member States will be liable to create barriers between Member States.
Since several innovative small and medium-sized enterprises7 (SMEs) are in the business of developing advanced therapy products, fee incentives have been put in place to assist SMEs to compete with larger corporations. For example, SMEs will enjoy a 90 per cent reduction for fees relating to advice from EMEA on pharmacovigilance studies and risk management systems8 and where there is a particular public health interest in the Community, a 50 per cent reduction in fees pertaining to marketing authorisation9 and post-authorisation activities10.
Given that advanced therapeutic products may provide an answer for some of the most debilitating diseases, such as Parkinson’s disease, cancer and various inherited diseases, it would be tragic if access to viable advanced therapeutic products were compromised due to lack of proper safeguards for the patients and support for companies developing these products. EU-wide rules tailored for the specific needs of advanced therapeutic products were very much called for, and the draft regulation appears to render sensible measures which would help meet most of its objectives. However, as Member States have the option to decide on the sort of cells which may be used, patients of some Member States may be deprived of treatments available to patients in other Member States.
Prescribing laws for any fast progressing area is difficult and, to some extent, requires a degree of flexibility to accommodate further developments while ensuring legal certainty. The draft regulation maintains this flexibility as much as it can, for example, by providing that compliance with a number of its requirements (be it clinical trials11, or technical requirements), be determined having fully taken into account the specific nature of the products at hand. It may be that the regulation will have to be revised thoroughly in a few years time after we learn much more about the technologies underlying these products, but for now, it seems to provide a good starting point for a legislative framework.