Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Tissue engineered products – Need and requirements for an appropriate harmonised EU regulatory framework ***

Dr. Sibylle Kaiser (Abschlußjahr: 2006)

Language: English

Tissue engineering is an innovative approach in the field of regenerative medicine. Principles of life sciences and engineering are applied to create biological substitutes that are functionally, structurally and mechanically equal or better than the tissue that is to be replaced. A range of tissue engineered products (TEPs) is already on the market for the treatment of skin, cartilage and bone diseases. Products of higher complexity like blood vessels, heart valves, nerve tissues or artificial livers are in the pipeline.

TEP-sales could not fulfil high-flying market projections. Only few TEPs have reached the market during the last years and existing TEPs have not achieved broad acceptance in clinical practice. The European Commission identified the lack of a pan-European regulatory framework covering TEPs as one of the main hurdles for a rapid progression of this technology in Europe. Therefore they initiated a public consultation to stipulate the regulatory principles of such a framework and work out provisions regulating market access and post-marketing requirements.

The first approach, published 2002, favoured a self-standing regulatory framework for TEPs, separate from the medical device and medicinal product legislation. But in the course of the discussion on appropriate definition for TEPs and the scope of a TEP-regulation it became obvious that there is a broad overlap with existing legislation for tissues and cells regulated by Directive 2004/23/EC and somatic cell therapy medicinal products regulated by Directive 2001/83/EC. In order to avoid any re-drafting of already-existing and proved concepts the original proposal for a separate regulation of TEPs was absorbed by an integrated approach addressing all advanced therapies - gene therapy, somatic cell therapy and tissue engineering - in one single framework.

The new regulatory framework will come as a Regulation amending the Directive 2001/83/EC and the Regulation (EC) 726/2004. The latter one sets the framework for achieving marketing authorisation for TEPs. The previous concept of national marketing authorisation for autologous products and European marketing authorisation for allogeneic products has been abandoned in favour of a centralized procedure for all TEPs as this has already been the case for gene therapy and somatic cell therapy medicinal products. This approach takes into account that the risk potential of TEPs is not only determined by the source of the cells, but also by the manufacturing process and the performance of the finished product. Therefore all types of TEPs should be assessed and approved via the same procedure. The centralized approach should further secure availability of high level expertise for this kind of products as national expertise is rather scarce in this field. Directive 2001/83/EC will lay down the basic commitment of TEPs as a third category of advanced therapies. Annex I will have to be amended to specify technical requirements for TEPs.

The new Regulation on advanced therapy medicinal products provides a rather clear definition of TEPs by separating them from those tissues and cells that have not been substantially manipulated and that are covered by Directive 2004/23/EC. This Directive will only apply to TEPs as far as donation, procurement and testing are affected. The new Regulation does not provide a clear demarcation from somatic cell therapy products but aims on avoiding borderline products by subjecting them to the TEP provisions. Xenogeneic tissues and cells have been included into the definition for TEPs to cover also future product developments incorporating animal derived source cells.

The exclusion of advanced therapy medicinal products which are both prepared in full and used in a single hospital, in accordance with a medical prescription for an individual patient, might give rise to further discussion. Exemption of hospitals but not of SMEs from the obligation to apply for marketing authorisation for custom-made one-off products could lead to regulatory overburden of the SMEs.

The proposal for a Regulation on advanced therapy medicinal products provides legal certainty to all players in the field and secures a high level of health protection to the patients based on the applicability of proven principles of the Community legislation on medicinal products. The regulation might cause a consolidation of the tissue engineering sector that in the long run might foster competitiveness of the European market players.

Pages:49