Gene Therapy Legislation in Europe
EU Clinical Gene Therapy Trials Legislation
The EU has several directives and guidelines for conducting clinical gene therapy trials. EU Directive 2001/83/EC provides a consolidated Community code relating to medicinal products for human use. The directive describes in great detail the considerations for conducting clinical trials without reference to specific requirements for trials involving genetically modified organisms (GMOs) as is often the case in gene therapy trials.
The EU Clinical Trials Directive 2001/20/EC establishes specific provisions regarding the conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products in particular relating to the implementation of good clinical practice. Its main purpose is to protect clinical trial subjects by establishing quality, safety and ethical criteria to be observed. In this evaluation the Ethics Committees at national level have a key role in evaluating the different aspects and providing an opinion before the trial can start. Although the Directive 2001/20/EC has led to harmonized procedures for authorizations of clinical trials in the EU member states, the detailed procedures at national level are still somewhat different.
The legislative framework for the application of genetically modified organisms (GMOs) in clinical gene therapy research is provided by several European directives and regulations. Some EU member states consider clinical trials with gene medicines as deliberate release according to Directive 2001/18/EC, while others consider them as contained use according to Directive 2009/41/EC.
Contained use is defined as any activity with GMOs for which specific containment measures are used to limit their contact with the environment. The focus of Directive 2009/41/EC is on the assessment of the biosafety level classification of the GMO and the implementation of physical, chemical and biological barriers. The risk classification has consequences for the procedure and review period of the application.
Deliberate release is defined as any activity with GMOs that is not contained use. Directive 2001/18/EC is based on a case-by-case environmental risk assessment (ERA) covering effects on human health or the environment. The ERA should be carried out in accordance with the principles set out in Annex II of this Directive. In short, the five steps involved in the ERA are i) identification of potential adverse effects, ii) estimation of the likelihood, iii) risk estimation, iv) risk management and v) assessment of the overall environmental impact. Although the approach of Directive 2009/41/EC is different from Directive 2001/18/EC, both directives aim at protecting the environment and human health and therefore require a risk assessment preceding the activity.
EU Market Authorization Procedure
The final stage in the development of a gene therapy product after conducting clinical trials is the market application. The European Medicines Agency (EMA) (formerly known as EMEA) is a European agency for the evaluation of medicinal products, including gene therapy medicinal products. The legislative framework for market authorization of human gene therapy products and other medicinal products containing or consisting of GMOs is based on Directive 2001/83/EC, Regulation (EC) No 726/2004 and Directive 2001/18/EC. If the application concerns a product that contains a GMO, the market authorisation dossier submitted directly to the EMA should also contain the environmental risk assessment in accordance with the principles set out in Annex II to Directive 2001/18/EC. Regulation (EC) 726/2004 also describes that the competent authorities of 2001/18/EC must be consulted. In addition, the regulation indicates that an application must be accompanied by a written consent to the deliberate release into the environment of GMOs for research and development purposes provided for in part B of Directive 2001/18/EC.
Thus, there is a clear connection between market authorisation of a gene therapy product and the environmental risk assessment based on Directive 2001/18/EC for clinical trials. More information regarding the placing on the market of human medicinal products can be found on the EMA website or check directly the Gene Therapy Working Party (GTWP) or the Advanced Therapies section.
