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Regulatory framework

Regenerative Medicine (RegMed) is based on the ability to stimulate the body´s own regeneration and repair processes or to replace naturally diseased tissues by means of novel therapies. Besides conventional and biotechnological active ingredients and bio-materials, novel cell and tissue therapies have preferentially been applied. Since the end of 2008 this particular group of therapies is regulated under the term “Advanced Therapy Medicinal Products” (ATMP) in a specific EU regulation (REGULATION (EC) No 1394/2007) . In this “Lex specialis” the particularities of these class of products have been considered under the roof of the Pharmaceutical  Legislation. The motivation of the European Union to enact the new regulation was to ensure protection and safety for patients, to ensure free trade in the European Union and finally – very important for all research institutions active in this research field – not to impair the medical R&D progress . In general, this has been successful, whereby specific national exceptions  are helpful.

The basic directive for all cell and tissue products is the European Tissue Directive (DirL 2004/23/EC) (in combination with the Dir 2006/17/EC „ Procurement“ and Dir 2006/86/EC „ Processing“) Subsequent  after transposition into the German Law the conventional “Tissue preparations” have been included as medicinal products in the German Medicines Act (AMG). Their differentiation to ATMP is that in ATMPs the tissue is substantially manipulated and/or the product does not have the same function in the recipient as in the donor (“non-homologoususe”). The ATMP include gene therapy medicinal products (GT), somatic cell therapy medicinal products (SCT), and tissue engineered products (TEP), as well as “combined advanced therapy medicinal product”.

The latter contain combinations of cells/tissues and medical devices. As already mentioned, since the end of 2008 ATMPs have European wide been uniformly regulated by the REGULATION (EC) No 1394  (ATMP- Reg) Only in case of rather rare special circumstances the EU Regulation allows for special national regulations („Hospital Exemption“) which in the meantime have been defined in most member states. Unfortunately, these exceptions have not been harmonized.

The stem cell products which are predominantly applied at the RTC are ATMPs. So we have to meet the legal and the regulatory requirements of the new regulations and of the „Community code relating medicinal products for human use“ (Directive 2001/83/EC). The European Commission took into account the specifities of the novel products by means of special regulatory rules for approval, monitoring, and pharmacovigilance. This is being underlined by the fact that additional scientific and technical guidelines have been compiled and a bundling of expertise took place within the European Agency for Medicinal Products (EMA) by means of the establishment of the Committee for Advanced Therapies (CAT). Its tasks are scientific consultation, classification of products and certification of quality-related and non-clinical data. The CAT is also involved in the recommendation for approval by the EU. As biological medicinal products  the ATMP fall under the centralized authorization process by the EMA (Reg (EC) Nr. 726/2004).

The scope of the ATMP-regulation and the Community codex is is focused only on medicinal products “which are intended to be placed on the market in Member States and are either prepared industrially or manufactured by a method involving an industrial process“. For other products which do not meet these requirements the EU appealed to the Member States for the establishment of  national  authorizations.  So ATMP which are prepared on a non-routine basis (manufacturing of custom-made product for an individual patient) and which are not intended to be put on the European market (individual therapies, applications connected to interventions) fall under this „Hospital Exemption“. These ATMPs are often manufactured directly in (or for) hospitals. In Germany, this „Hospital Exemption“ - according to Article 28 of the ATMP Regulation and Article 3 of the Dir 2001/83/EC (7) – is described in the national special provisions under §4b of the German Medicines Act (AMG).

European-wide, ATMP have to be manufactured according to “Good Manufacturing Practice” (GMP)  and clinical trials according to “Good Clinical Practice”(GCP). As mentioned above, the central EU procedure is mandatory for  Marketing Authorisation. The national exemption provision – in Germany according to §4b of the AMG – requires GMP conform manufacturing procedures, too. For approval the federal authority (in Germany the Paul- Ehrlich-Institute) is responsible.
All ATMPs developed and applied at the RTC meet all legal and regulatory requirements. For this purpose a quality-assurance system has been established which guarantees our clinical work to be conducted in compliance with the principles of GCP and GMP  and our pre-/non-clinical work according to the strict requirements of „Good Laboratory Practice“(GLP).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Important EU-Regulations and Directives

  • Regulation 1394/2007/EC (ATMP-Regulation)
  • Directive 2004/23/EC: Definition of standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells
  • Directive 2006/17/EC: (implementing Directive 2004/23/EC regarding technical requirements for the donation, procurement and testing of human tissues and cells)
  • Directive 2006/86/EC: (implementing Directive 2004/23/EC regarding traceability requirements, notification of serious adverse reactions and events and certain technical requirements for the coding, processing, preservation, storage and distribution of human tissues and cells)
  • Directive 2001/83/EC: Community code relating medicinal products for human use
    + Annex I Directive 2003/63/EC
    + in addition to Annex I (regarding ATMP): Directive 2009/120/EC
  • Regulation 726/2004/EC (laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency: Regulation of central authorisation of AM)
  • Directive 2001/20/EC and Directive 2005/28/EC (GCP-Guideline: laying down principles and guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products)
  • Directive 2003/94/EC (GMP-Guideline: laying down principles and guidelines of good manufacturing practice with respect to medicinal products for human use and investigational medicinal products for human use) 

The complete European body of laws can be found under following links:
  European Agency for the Evaluation of Medicinal Products (EMA)
  Heads of Medicines agencies (HMA)

 
 

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Legal The RTC is supported by the BMBF and the State Mecklenburg-Western Pomerania using EU Structural Funds.