Just as in the United States, drug approvals in the European Union typically take a long period of time and vaccines for COVID-19 are no exception. Vaccine development in the EU is still at an early stage and unfortunately there are no existing vaccines that could be repurposed to work against the new virus. Timelines for vaccine development are difficult to predict but current estimations indicate that the earliest trials won’t even begin until May 2020. What this means is that it will take several months before candidate vaccines are ready for larger clinical studies.
The normal process of drug approval in the EU looks something like this: Drug manufacturers for human and/or veterinary use conduct all of their lab tests and clinical trials, and then submit that information to the European Medicine’s Agency (EMA). The EMA then conducts a comprehensive scientific evaluation of the data. The main question they are asking themselves, which is exactly what the FDA asks during this process in the US, is “do the benefits of the drug outweigh the risk to consumers?”. If the EMA determines the answer to be “yes”, they recommend to the European Commission to approve the drug to be marketed across the EU.
In March 2020, the EMA published a “Guidance on the Management of Clinical Trials during the COVID-19 pandemic”, which outlines recommendations for sponsors on how to manage the conduct of clinical trials during this time. Sponsors and investigators need to take into account that there may be Specific national legislation and guidances already in place may take priority over or be used in conjunction with these new guidelines, but sponsors and investigators must do their due diligence to review the current laws in their region. This new document does however seek to include most of the current guidance across Member States with the aim to serve as an EU-level harmonized set of recommendations. A brief summary of the new guidance is as follows:
1. Changes to ongoing trials
- Use of tele-health by converting in-office visits to virtual appointments instead; alternately cancelling appointments that are not medically necessary or urgent
- Trials may be temporarily halted at some or all sites
- Recruitment of new trial participants will be suspended entirely, or at least slowed down
- Trial durations will be extended so that they can be completed when it is safer, after the virus is contained
- Trials could be postponed entirely, or inactive sites may be initiated
2. Risk assessment: Regarding participants enrolled in ongoing clinical trials who may be determined as being a risk group for COVID-19 or who are in trials involving therapies which may increase such risk, the potential impact of COVID-19 on these patient groups should be carefully considered when deciding to start or continue such trials.
3. Communication with authorities: Priority is given to any (new) clinical trial applications for the treatment or prevention of COVID-19 infection, and/or substantial amendment applications to existing clinical trials necessary as a result of COVID-19.
4. Changes to informed consent: Absolute priority should be given to clinical trials on treatments for COVID-19 and COVID-19-related illnesses, or trials on serious diseases with no satisfactory treatment option. In case a sponsor plans to initiate a trial aiming to test new treatments for COVID-19, advice should be sought on alternative procedures to obtain informed consent, as it is likely that the physical consent cannot leave the isolation room, and therefore is not appropriate as trial documentation.
5. Changes in the distribution of the Investigational Medicinal Products (IMP): Changes in the distribution of the IMP may be necessary to avoid unnecessary visits to sites and to provide the patients with needed treatments. Sponsors must assess the risks relating to the product and consider any alternative shipping and storage arrangements.
6. Changes to monitoring: Certain sponsor oversight responsibilities, such as monitoring and quality assurance activities need to be re-assessed and temporary, alternative proportionate mechanisms of oversight may be required. The burden of the introduction of any alternative measures for the site staff and facilities should also be considered in order to strike an acceptable balance between appropriate oversight and the capacity of and possibilities at the site.
7. Protocol deviations: A proportionate approach will be taken by the GCP inspectors when protocol deviations occur, and will be reviewed during inspections, in particular where the best interest of the participant is maintained, and the participant is not put at risk. They will however need to be assessed and reported in the clinical study report, following ICH E3.
8. Reimbursement of exceptional expenses: If, in order to implement urgent measures for the protection of participants involved in a clinical trial, expenses may arise which may be bore initially by the participants, these should typically be compensated subsequently by the sponsor via the investigator.
9. Initiation of new trials aiming to test new treatments for COVID-19: EU Member States support the submission of large, multinational trial protocols for the investigation of new treatments for COVID19. In addition, sponsors are encouraged to consider the submission of such applications for an accelerated Voluntary Harmonization Procedure3 (VHP) assessment when possible. In order to avoid or minimize delays due to the harmonized review, sponsors are recommended to prospectively contact the proposed Ref NCA to explore the feasibility of an accelerated VHP (plus) process, by an email notification.
Another important change is as of March 30th, EMA will no longer provide printed certificates for medicines but only electronically signed and authenticated certificates to maintain the Agency’s ability to provide these documents during the pandemic. The good news is that the European Medicines Agency (EMA) is now providing full fee waivers for scientific advice for potential vaccines and treatments for COVID-19. Also, developers of potential therapeutics or vaccines against COVID-19 are invited to contact the Agency as soon as possible with information about their proposed development, by emailing 2019-ncov@ema.europa.eu.
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