Each EU Health Authority has published a wide range of information regarding coronavirus, COVID-19, on their websites. In this blog we will continue to guide you through all these recommendations and measures with a focus on the European Medicines Agency (EMA), the Agency. In times like this, the Agency has a more important role than ever. Please note that new information is continually evolving therefore always check the applicable websites (EMA, Health Authority in your country, Inspectorate, etc.) if you need more information.
On March 20, 2020, the EMA has issued a Guidance document to Sponsors on how to manage clinical trials during the COVID-19 pandemic. The guidance was agreed by the Clinical Trials Expert Group (CTEG) of the European Commission, supported by EMA, the Clinical Trials Facilitation and Coordination Group (CTFG) of HMA and the GCP Inspectors’ Working Group. With this guidance, EMA is hoping to reduce the negative effects of the pandemic on current clinical trials. The document is seeking to include most of the current guidance across member states with the aim to serve as an EU-level harmonized set of recommendations. However, Sponsors are advised to also check whether there might be specific national legislation and guidance in place to complement or, in some cases, to take priority over this new guidance. But as always, subject safety prevails.
Possible changes to be applied as a result of the COVID-19 pandemic include:
Should there be events that are likely to have a serious effect on the benefit-risk balance of the trial, urging (immediate) action of the Sponsor, it is important that the Sponsor inform authorities only on the necessary changes. Please take into account the limited capacity of assessors. Sponsors should be mindful of the current pressure on the medical profession and should carefully assess the pertinence of adding new subjects to ongoing clinical trials. Absolute priority should be given to clinical trials on treatments for COVID-19 and COVID-19-related illnesses, or trials for serious diseases for which there is currently no satisfactory treatment option.
Changes in the distribution of the IMP may be necessary to remove avoidable 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.
It is essential that robust follow-up measures are planned and ready to be implemented when the situation is normalized. This should include increased on-site monitoring for a period that is sufficient to ensure the impact of the reduced monitoring could be rectified and problems resolved or properly documented for reporting in the clinical study report.
So-called remote source data verification (e.g. providing the Sponsor with copies of medical records or remote access to electronic medical records) is currently not allowed in most member states as it might infringe upon trial participants’ rights. In addition, provision of redacted/de-identified PDF files will not be acceptable as it puts disproportionate burden on site staff. Nevertheless, since the coronavirus emergency situation and containment measures are likely to last for a prolonged period, several NCAs have started to look into possible, temporary solutions related to remote access and conditions for such, providing that methods can be used that restricts access to trial participant records, in line with the principles of necessity and proportionality. This should however also be clarified with other relevant authorities in this area and is consequently not allowed unless a member state has given specific guidance allowing this.
New Treatments for COVID-19: Initiation of New Trials
The member states support the submission of large, multinational trial protocols for the investigation of new treatments for COVID-19. In addition, Sponsors are encouraged to consider the submission of such applications for an accelerated Voluntary Harmonization Procedure (VHP) assessment when possible. In order to avoid or minimize delays due to the harmonized review, the Agency is recommending that Sponsors prospectively contact the proposed Ref NCA to explore the feasibility of an accelerated VHP (plus) process. Please remember that EMA is ready to support drug developers with all available regulatory tools to advance and expedite the development of effective measures to fight and prevent the spread of COVID-19. Companies developing potential therapeutics or vaccines against COVID-19 are encouraged to contact the Agency as soon as possible with information about their proposed development, by emailing email@example.com. The Agency is also supporting EU member states by reporting any useful emerging information on investigational agents to treat or prevent COVID-19.
Additional information on fee reductions for scientific advice requests on products for the prevention and/or treatment of COVID-19 is available here.
On March 13, 2020, EMA announced that it will be providing full fee waivers for fast-track scientific advice applications from Sponsors developing potential therapeutics (to treat the disease) or vaccines (to prevent the disease) against the novel coronavirus disease (COVID-19).
Earlier last week, at least Estonia, Latvia, and the UK published guidance on clinical trial management. Their guidance was not as exhaustive as EMA’s, but very similar.
Estonia mentioned that they did not receive any request for COVID-19 therapy studies. The UK issued specifications for ventilators and coronavirus test kits to be used in UK hospitals during the coronavirus outbreak.
On March 16, 2020, AEMPS (Spanish HA) and CEIm (Ethics Committee for Drug Research) published a guide for clinical trials conducted during the COVID-19 crisis in Spain. Following the same direction, on March 17, 2020, INFARMED (Portuguese HA) and CEIC (National Ethics Committee for Clinical Research) published a similar guide in Portugal. Both guides mention that they do not supersede any EMA/EU Commission directive or instructions further published (which is the case for the EMA’s instructions published on March 20, 2020), anyway, one doesn’t disagree with the other (in fact they’re quite similar).
Swissmedic received an increasing number of questions regarding the placement of protective masks, gloves, hand sanitizer, and coronavirus tests on the market, which led them to issue an information sheet on the topic.
For those looking beyond the EU borders, it is important to stay in touch with the World Health Organization’s (WHO’s) recommendations. The WHO “R&D Blueprint” for COVID-19, initiated on January 7, 2020, will serve as the global strategy for R&D activities. Its aim is to fast-track the availability of effective tests, vaccines and medicines that can be used to save lives and avert large scale crises. As part of this, WHO is leading the global prioritization of candidate vaccines and therapeutics for development and evaluation. To support testing, WHO convened a scientific advisory group (SAG) to develop guidance on trial designs for experimental vaccines and therapeutics.
In the clinical trials register of the EU, there have already been seven EUDRA-CT protocols included. These started between the 5th and the 23rd of March and include two in the UK, one in Norway, two in France, and two that are collaborations of Germany, Spain, Italy, the Netherlands, and Sweden. The first results may be expected from mid-2020 onwards.
These studies are on different therapies, and vaccine development is still at an early stage, as there are no existing vaccines that could be repurposed to work against the novel virus. Timelines for vaccine development are difficult to predict at this point. It will take several months before candidate vaccines are ready for larger clinical studies. The first global regulatory workshop on COVID-19 vaccine development (co-chaired by FDA and EMA) was held on March 20th, 2020, focused on preclinical data requirements and the theoretical risk that vaccines against COVID-19 could enhance the disease prior to starting first-in-human clinical trials.
For companies preparing solutions for the novel coronavirus, we can help prepare emergency petitions for INDs, expedite submissions for new indications and apply for emergency use for drugs already in trials. How can we help you during this global health crisis? Please visit ProPharma Group’s global website: Novel Coronavirus Support or email your request to Info@ProPharmaGroup.com.
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