On 30 January 2020 the World Health Organisation (WHO) declared that the COVID-19 outbreak was a public health emergency of international concern. Subsequently, on 11 March 2020, the WHO characterised COVID-19 as a pandemic.
In the same vein, the European Union confirmed that it was facing an epidemiological situation, which was unprecedented and gave rise to serious concern. In this regard, the European Union accepted(1) that the COVID-19 pandemic was unexpected and fast-evolving. As such, it thoroughly tested the EU response capacity and the ability of public authorities at all levels to cope with the emergency. The COVID-19 pandemic was also asymmetric across the European Union in terms of incidence and impact. It affected countries and regions at different times and with varying intensity.
In March 2020, globally, Europe was the area worst affected by COVID-19 and the situation evolved rapidly. In mid-July 2020, even the three EU countries most affected by COVID-19 (ie, Italy, Spain and France), were no longer among the 10 hardest-hit countries worldwide. However, even though the pandemic slowed down consistently in the European Union from mid-May 2020 onwards, new cases and deaths are still occurring. In mid-July 2020, the cumulative number of confirmed COVID-19 cases in the European Union was approximately 1.3 million and the death toll totalled nearly 135,000. Over 69% of the COVID-19-certified deaths were in Italy, Spain and France.
As a result, the European Commission is coordinating a common EU response to the COVID-19 outbreak, taking resolute action to reinforce the EU public health sectors and mitigate the socio-economic impact in the European Union. As part of such EU response to the outbreak of COVID-19 and its consequences, the European Union has adopted a wide range of regulations in the healthcare and pharmaceutical sector, which includes measures aiming to speed up the development and the deployment of a vaccine against COVID-19 in the European Union. This article examines multicentre clinical trials with medicinal products for human use containing or consisting of genetically modified organisms (GMOs).
Multicentre clinical trials with medicinal products for human use containing or consisting of GMOs
Since COVID-19 began to spread, the majority of the world's leading pharmaceutical laboratories have begun clinical trials to find both the right vaccine and the right drug to stop it from spreading.
Nevertheless, as explained in its guidance on the management of clinical trials,(2) the European Union has acknowledged the impact of COVID-19 on the health system and broader society, and the impact that it may have on clinical trials and trial participants. Accordingly, extraordinary measures needed to be implemented and trials adjusted due to, among other things:
- trial participants being in self-isolation or quarantine;
- limited access to public places (including hospitals) due to the risk of spreading infection; and
- healthcare professionals being committed to critical tasks.
Against this background, pragmatic and harmonised actions are required to ensure the necessary flexibility and procedural simplifications needed to maintain the integrity of trials and ensure the rights, safety and wellbeing of trial participants and the safety of clinical trial staff during this global public health crisis.
Actions should be proportionate and based on:
- benefit-risk considerations; and
- contingency provisions taken nationally and locally by the authorities, with priority given to the impact on the health and safety of the trial participant.
EU regulations(3) for clinical trials set out that:
- before starting any clinical trial, laboratories must request authorisation from the competent authority of the EU member state in which the trial is to be conducted; and
- there are restrictions on the deliberate release into the environment of GMOs, requiring marketing authorisation holders to notify the competent authority of each EU member state in writing and receive its consent prior to carrying out the release.
In order to obtain the consent of the competent authority, the risks to human health and the environment associated with the release of GMOs must be assessed in each individual case. Notwithstanding the above, since clinical trials require multiple operations, including the manufacture, transport and storage of the investigational medicinal product, packaging and labelling, administration of the investigational medicinal product to trial subjects, and subsequent monitoring of the subjects, and disposal of the waste, experience shows that clinical trials containing or consisting of GMOs involve a procedure to comply with all the requirements of EU regulations that is extremely complex and may be delayed in time.
This procedure is going to become even more complicated when the clinical trials being carried out are of a multicentred nature (ie, when they are being carried out simultaneously in several EU member states), as the laboratories must submit several applications for authorisation to several competent authorities in different EU member states in parallel.
Although EU Directive 2001/18/EC on the deliberate release into the environment of GMOs and repealing EU GMO Directive 90/220/EEC sets out the requirements for laboratories for the deliberate release of GMOs, there are also national requirements and procedures for risk assessment which vary greatly depending on the EU member state to which authorisation is applied.
Over the years, there have been several attempts to streamline the process through informal coordination between the competent authorities of each EU member state; however, to date they have been unsuccessful.
Against this background, EU Regulation 2020/1043 on the conduct of clinical trials with and supply of medicinal products for human use containing or consisting of GMOs intended to treat or prevent COVID-19 aims to grant a temporary derogation from the requirements concerning a prior environmental risk assessment and consent under EU Directive 2001/18/EC and EU Directive 2009/41/EU for the duration of the COVID-19 pandemic or as long as there is a public health emergency.
In this regard, EU Regulation 2020/1043 provides that:
In this situation of public health emergency, it is of major interest for the Union that safe and efficacious medicinal products intended to treat or prevent COVID-19 can be developed and be made available within the Union as soon as possible.
To achieve the objective of making available safe and efficacious medicinal products intended to treat or prevent COVID-19, a range of measures have been taken at Union level by the European Medicines Agency (EMA) and by the network of national competent authorities to facilitate, support and speed up the development and marketing authorisation of treatments and vaccines.
To generate the robust clinical evidence necessary to support applications for marketing authorisation of medicinal products intended to treat or prevent COVID-19 multi-centre clinical trials involving several Member States will need to be conducted.
According to this background:
during the period in which the temporary derogation applies, the environmental risk assessment and consent under Directives 2001/18/EC and 2009/41/EC should not be a prerequisite for the conduct of those clinical trials.
This is to say that EU Regulation 2020/1043 aims, by virtue of the importance of ensuring a high level of human health protection, to grant a temporary derogation from the requirements for prior environmental risk assessment provided for in EU Directive 2001/18/EC and EU Directive 2009/41/EC for the duration of the COVID-19 pandemic in terms of conducting clinical trials with investigational medicinal products containing or consisting of GMOs.
However, it is important to emphasise that:
- the derogation should be limited to clinical trials with investigational medicinal products containing or consisting of GMOs intended to treat or prevent COVID-19; and
- the manufacturing of medicinal products containing or consisting of GMOs intended to treat or prevent COVID-19, including investigational medicinal products, should be excluded from the temporary derogation.
EU Regulation 2020/1043 should be limited to the situation of emergency which involves an urgent threat to human health where it is impossible to attain otherwise the objective to protect human health and does not go beyond what is necessary in order to achieve those objectives.
EU Regulation 2020/1043 aims to establish a temporary exception to the fundamental requirements provided for in the European Union's legislation on GMOs that hinder the rapid progress necessary in the current situation of crisis and thus guarantee that research carried out in parallel in the corresponding EU member states is not delayed excessively.
Endnotes
(1) "Regional health policy responses to the COVID crisis", Commission for Natural Resources, European Committee of the Regions (ISBN 978-92-895-1063-9).
(2) Guidance on the management of clinical trials during the COVID-19 (Coronavirus) pandemic, European Commission, Version 3, 28 April 2020.
(3) EU Directive 2001/83/EC on the community code relating to medicinal products for human use, EU Regulation 726/2004 setting out EU procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency and EU Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms and repealing the EU GMO Directive 90/220/EEC.
