Office of Technology Assessment at the German Bundestag

Thomas Petermann • Joachim-J. Schmitt

Statutory regulation of gene therapy abroad

TAB report no. 040. Berlin 1996, 134 pages

Summary

Even the latest reports on gene therapy trials have not significantly expanded the range of known successes. However, there is evidently an increasingly turbulent course of medical research in gene therapy and a growing interest by pharmaceutical companies in developing gene therapy methods.

Despite the further development of gene therapy »tools« (e.g. new animal models for gene therapy research trials) no decisive progress has been made towards solving the familiar problems in gene therapy. It is, for example, still not possible to activate introduced genes only in predetermined organs and tissues, i.e. to ensure that the introduced gene is not introduced into other cells, such as reproductive cells. The deliberate exchange of a mutated gene for an intact one also still lacks adequate control. Ultimately, there is still no alternative in prospect for the use of viruses as gene taxis, with impossibility of entirely ruling out the associated danger that broad use of gene therapy may result in the creation of human pathological viruses.

There is accordingly unanimity among experts that gene therapy trials should only be carried out under certain safety rules. The nature and scope of these safety rules and their legislative basis are, however, matters of controversy, particularly in Germany. As far as the legal framework is concerned, one side argues that safety is adequately ensured through the network of existing regulations. The other side criticises the current situation as a tangle of legal regulations and expresses grave doubt that this takes adequate account of the specific hazards of gene therapy techniques.

In the context of this debate, the TAB commissioned a Review of statutory regulation of gene therapy abroad for selected countries, the findings of which are given in this report.

An overview of the international regulatory mechanisms shows clearly that - despite widely varying legislative approaches - the emphasis in (legislative) efforts everywhere is on patient safety and biological safety.

• Strict test criteria for pharmaceuticals (which also apply to gene therapeutic methods) are one way of limiting the risks of gene therapy. To this extent, licensing of gene therapy projects is subject to demanding requirements.
• The ethics commissions to be found in all the countries reviewed further serve the goal of maximum possible patient safety. An opinion (at least »consultative") by the ethics commissions in all the key countries (with the exception of the Italian legal system) is one element in approval and design of gene therapy trials on humans.
• Another important issue are the professional ethical regulations covering the clinical applications of gene therapy. In the overwhelming majority of regulatory systems these apply (inter alia) to:
  • adequate clinical pre-trials
  • risk-benefit reviews in the use of gene therapy techniques on humans
  • prior patient education and consent and
  • consultation with an ethical commission.
• In addition to the specific statutory regulations there are also the general statutes on civil and criminal liability which apply on a subsidiarity basis.
• Finally, it is important to stress the European dimension. The EC Order 2309/93 introduced a European minimum standard of safety for pharmaceuticals. A centralised licensing procedure is to be introduced for licensing throughout the EU of innovative and technologically sophisticated pharmaceuticals, inter alia by a new European agency.

Biological safety is ensured through various forms of legislation. All countries have a national (official) licensing authority. At EU level the Directives EEC 90/219 ("System directive") and 90/220 ("Release Directive") apply. These are also the basis for establishing a common European licensing authority responsible for biological safety in member states.

Besides the common features indicated, there are also differences, for example in terms of the statutory basis of the ethics commissions, the commission responsibilities and the binding nature of their votes.

• Under French law, there is a separate act (the »Loi Huriet") covering the duties and responsibilities of the ethics commissions. In German law the ethics commission’s powers are covered by section 40 I of the Drugs Act, in Austria by sections 30 et seq. of the Genetic Engineering Act. Italy, on the other hand, has no special regulation covering the responsibilities of the ethics commissions.
• In the USA the responsibilities of the local ethics commissions are limited to projects promoted by the National Institutes of Health, or those where individual state laws require this. The licensing procedure in the UK operates at two levels: besides local ethics commissions, the central ethics commissions must also give its approval for every gene therapy project.
• * With respect to the binding nature of their votes, some national ethics commissions have a purely advisory status, for example in France. In other countries (e.g. USA, Austria, UK, Denmark) the commission's vote is more important and can result in refusal of approval.