The European Commission proposes a Regulation for COVID-19 clinical trials conducted with medicinal products containing or consisting of GMOs

As part of the strategy to fight COVID-19, the European Commission has proposed a Regulation to facilitate the conduct of clinical trials using medicinal products containing or consisting of Genetically Modified Organisms (GMOs).

The European Commission recognises that the applicable regulatory framework in relation to GMOs is unable to adequately address the challenges created by the pandemic. While some vaccines in development contain attenuated viruses or live vectors, which may fall within the definition of a GMO, there is uncertainty on the interactions between the GMO regulatory framework and the legislation on clinical trials and medicinal products. This is further aggravated by the absence of a common approach by the EU Member States.

Background

Directive 2001/18/EC on the deliberate release of GMOs into the environment as well as Directive 2009/41/EC on the contained use of genetically modified micro-organisms (GMMs)[1] (together, the “GMO Directives”), do not foresee any specific procedures triggered in the event of a public health emergency. In contrast, Directive 2001/83/EC on the Community Code relating to medicinal products provides that EU Member States may temporarily allow the distribution of a non-authorised medicinal product in response to a suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation any of which could cause harm. Regulation 726/2004/EC provides the same exemption for medicinal products available for compassionate reasons.

The European Commission aims with this proposal to adapt the GMO regulatory framework in order to facilitate in terms of time the conduct of clinical trials in relation to medicinal products treating or preventing COVID-19 and only as long as COVID-19 is regarded as a pandemic.

No prior environmental risk assessment and/or consent

The European Commission proposes that during the COVID-19 pandemic, the requirement of a prior environmental risk assessment and/or consent, as provided by the GMO Directives, should not apply. This concerns the operations of packaging and labelling, transport, destruction, disposal, distribution, supply, administration or use of medicinal products containing or consisting of GMOs in clinical trials. However, the requirement of a prior environmental risk assessment and/or consent will have to apply to the operation of manufacturing of the relevant medicinal products.

The European Commission considers that the temporary derogation from the standard requirement will simplify the conduct of clinical trials in one or multiple EU Member States and speed up the development and marketing authorisation of COVID-19 treatments and vaccines. It highlights, nevertheless, that environmental risk assessments will have to be performed before a medicinal product becomes widely available in the EU as part of the marketing authorisation procedure.

The European Commission has proposed this Regulation as a matter of urgency and has made use of the exception provided in Article 4 of Protocol No 1 on the role of national Parliaments in the EU. This exception allows the eight-week period that must elapse between a draft legislative act being made available to national Parliaments and the date it is placed on the agenda of the Council, to be bypassed for urgent matters. Following European Commission’s proposal, the European Parliament and the Council are expected to adopt their positions very soon, according to the ordinary legislative procedure.

When do the GMO Directives apply to micro-organisms?

Awareness of the differences in how micro-organisms are regulated at an early stage of development can have a significant impact on the R&D strategy if speed is of the essence. The use of non-replicating viral vectors as candidate COVID-19 vaccines is one way to avoid falling within the definition of a GMO under the GMO Directives and thereby not being subject to the EU GMO regulatory framework, even if such vectors have been genetically modified. Organisms produced through mutagenesis are also exempt from the EU GMO regulatory framework.

Prior to the CJEU’s Confédération paysanne decision of July 2018, there was uncertainty as to whether organisms produced by directed mutagenesis techniques, using tools such as CRISPR-Cas9 to make small, precise and targeted changes to genomes, were included within the mutagenesis exemption. The CJEU confirmed that such organisms were not exempt and that the mutagenesis exemption only applies to organisms created using conventional mutagenesis techniques, such as using radiation or chemical mutagens, so long as such techniques are considered to have a long safety record. Thus, despite the end product being potentially identical, the regulatory framework for microorganisms created through directed mutagenesis techniques can differ from those created using conventional mutagenesis techniques.

[1] For the purposes of this article, the term GMO is used to refer to both GMOs and GMMs.