Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA issues a scientific opinion for the first medicine to treat COVID-19 in the UK

On the 26th May 2020, the MHRA gave the first positive scientific opinion under the Early Access to Medicines Scheme (EAMS) for use of Gilead’s remdesivir. This step will support the use of remdesivir in the treatment of adults and adolescents hospitalised with severe coronavirus (COVID-19) infection who meet additional clinical criteria.

https://www.gov.uk/government/news/mhra-supports-the-use-of-remdesivir-as-the-first-medicine-to-treat-covid-19-in-the-uk

MHRA guidance on coronavirus (COVID-19)

The MHRA guidance and information for industry, healthcare professionals and patients covering the coronavirus (COVID-19) outbreak was updated on 26th May 2020. Contents include regulatory flexibilities, clinical trials, inspections and good practice, medical devices, medicines and COVID-19, medical device alerts related to coronavirus (COVID-19) and fake or unlicensed medicines.

https://www.gov.uk/government/collections/mhra-guidance-on-coronavirus-covid-19

Managing clinical trials during Coronavirus (COVID-19)

On the 21st May, the MHRA published updated guidance on how investigators and sponsors should manage clinical trials during COVID-19. This guidance has been developed to assist those involved in clinical trials disrupted as a result of COVID-19. It is relevant to those involved with ongoing studies, those wishing to restart trials that have been paused or temporarily halted, and those wishing to start new studies. Contents include:

  • Managing ongoing and halted trials
  • Submitting paperwork for trials which have been halted or are proposed to be restarted
  • Providing investigational medicinal product (IMP) to trial participants
  • Accountability of Investigational Medicinal Products (IMP)
  • Remote monitoring for trials
  • Changes to the number and type of participant monitoring visits
  • ‘Dear Investigator’ Letters
  • Reporting of serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), and submission of annual safety reports (DSURs)
  • Protocol deviations and serious breaches
  • Protocol waivers
  • Urgent Safety Measures
  • Participant safety
  • Signatures
  • Help from the MHRA

https://www.gov.uk/guidance/managing-clinical-trials-during-coronavirus-covid-19

On 20th May 2020, the MHRA issued updated guidance for industry on flexible approaches to regulation they are taking during the COVID-19 outbreak. Contents include Making use of regulatory flexibilities, Clinical trials, Marketing authorisations, Pharmacovigilance, Inspections and good practice, Blood components for transfusion and Medical devices.

https://www.gov.uk/guidance/mhra-regulatory-flexibilities-resulting-from-coronavirus-covid-19#making-use-of-regulatory-flexibilities

MHRA advice for investigators and sponsors of ongoing medical devices clinical investigations and new applications was updated on the 7th May 2020.

https://www.gov.uk/guidance/medical-devices-clinical-investigations-during-the-coronavirus-covid-19-outbreak

On the 11th May 2020, the MHRA issued guidance for people who work in or run indoor labs and research facilities and similar environments.

https://www.gov.uk/guidance/working-safely-during-coronavirus-covid-19/labs-and-research-facilities

European Medicines Agency (EMA)

COVID-19: What’s new

A consolidated guidance on the COVID-19 pandemic from the European Medicines Agency (EMA), including all news and press releases has been made available on the 20th May 2020.

https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/covid-19-whats-new

Guidance on the Management of Clinical Trials during the COVID-19 (coronavirus) pandemic

For those involved in clinical trials, v3.0 of the ‘Guidance on the Management of Clinical Trials during the COVID-19 (coronavirus) pandemic’, was published 28th April 2020 which furthers the previous versions of the same with information on:

  • Distributor to trial participant IMP shipment
  • Monitoring
  • Remote source data verification (SDV)
  • Communication with authorities

Of notable interest is Annex 1 which provides detailed guidance on how the regulators expect trial participants’ rights to be protected during remote SDV.

https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/guidanceclinicaltrials_covid19_en.pdf

For veterinary medicines, guidance was provided on regulatory flexibility during the pandemic relating to marketing authorisation procedures, pharmacovigilance and good-manufacturing-practice (GMP) certificates, and inspections for veterinary medicines which was made available on 4th May 2020.

https://www.ema.europa.eu/en/news/regulatory-flexibility-ensure-availability-veterinary-medicines-during-covid-19-pandemic

Detailed pharmacovigilance guidance was also published on 4th May 2020 to provide recommendations relevant to the processing and submission of Individual Case Safety Reports (ICSRs) associated with medicinal products used for the treatment or prevention of COVID-19 infection.

https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/detailed-guidance-icsrs-context-covid-19-validity-coding-icsrs_en.pdf

EMA’s governance during COVID-19 pandemic

It was published on the 18th May 2020 that the EMA has established a dedicated task force to deal with the scientific, regulatory and operational challenges created by the COVID-19 pandemic and initiated its business continuity plan. The aim of these measures is to safeguard the Agency’s core activities related to the evaluation and supervision of medicines during the pandemic and to ringfence resources dealing with COVID-19.

On the 19th May it was published that the EMA have decided to continue holding its committee and working-party meetings virtually until the end of August 2020. Stakeholder events planned until the end of August will either be postponed or held virtually.

https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/emas-governance-during-covid-19-pandemic

The EMA and its partners in the European medicines regulatory network are addressing the Availability of medicines during COVID-19 pandemic and putting measures in place to help prevent and mitigate possible disruptions to the supply of medicines in the EU during COVID-19. Extraordinarily, EMA is acting as central coordinator in supporting Member States’ activities in this area during the pandemic.

https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/availability-medicines-during-covid-19-pandemic

Released on the 15th May 2020 were the ‘EU actions to support availability of medicines during COVID-19 pandemic – update #6’. The steering group members and the heads of the National Competent Authorities took note of the continued roll out of the i-SPOC system through which industry notifies EMA and Member States on current or anticipated shortages of medicines that are crucial in the context of the COVID-19 pandemic. Participants continued discussions on opportunities for improvement with respect to how the supply of medicines used in intensive care units (ICUs) currently matches the demand at national level, in view of the reported shortages of ICU medicines. They agreed that the development of joint principles for modelling demand at national level, and subsequent sharing of demand data by the NCAs, would be useful to ensure that the supply of ICU medicines meets the demand in the short and medium term. This could already help to prevent possible shortages of medicines during a potential second wave of COVID-19 infections in Europe.

https://www.ema.europa.eu/en/news/eu-actions-support-availability-medicines-during-covid-19-pandemic-update-6

Treatments and vaccines for COVID-19

Potential Treatments Under Investigation

The EMA has been in discussion with the developers of around 125 potential COVID-19 treatments (figure correct as of 26 May 2020). The EMA welcomes the launch of large clinical trials to test promising treatments and generate conclusive evidence on which of them work, in line the advice of its human medicines committee (CHMP).

Potential COVID-19 treatments currently undergoing clinical trials include:

  • Remdesivir (an investigational medicine);
  • Lopinavir/ritonavir (currently authorised as an anti-HIV medicine);
  • Chloroquine and hydroxychloroquine (currently authorised at national level as treatments against malaria and certain autoimmune diseases such as rheumatoid arthritis);
  • Systemic interferons, in particular interferon beta (currently authorised to treat diseases such as multiple sclerosis);
  • Monoclonal antibodies with activity against components of the immune system.
Remdesivir

On 30 April 2020, EMA’s Committee for Medicinal Products for Human Use (CHMP) started a rolling review of data on the use of remdesivir for treating COVID-19 to speed up the evaluation of a promising investigational treatment during a public health emergency. This decision followed preliminary results from a study that suggested a beneficial effect of remdesivir in the treatment of hospitalised patients with mild-to-moderate or severe COVID-19. However, EMA has not yet evaluated the full study. The CHMP will evaluate all data on remdesivir, including evidence from a recently published study from China and other clinical trials. The overall review timeline for remdesivir cannot be anticipated. However, the rolling review will allow EMA to complete the review of data significantly earlier than it would with a regular evaluation procedure, while still ensuring that a robust scientific opinion is reached.

https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines-covid-19

Update – on 26th May 2020, the MHRA published a press release giving the first positive scientific opinion under the Early Access to Medicines Scheme (EAMS) for use of Gilead’s remdesivir. This step will support the use of remdesivir in the treatment of adults and adolescents hospitalised with severe coronavirus (COVID-19) infection who meet additional clinical criteria.

https://www.gov.uk/government/news/mhra-supports-the-use-of-remdesivir-as-the-first-medicine-to-treat-covid-19-in-the-uk

Potential Vaccines Under Investigation

EMA has been in discussion with developers of a 33 potential COVID-19 vaccines (figure correct as of 14 May 2020). Vaccine development timelines are difficult to predict. Based on past experience, EMA estimates that it might take at least a year before a vaccine against COVID-19 is ready for approval and available in sufficient quantities to enable widespread use.

On the 26th May 2020, a search of EU Clinical Trials Register (EU CTR) revealed 8 ongoing vaccine trials, all with no results available. Three of the trials are ongoing in the UK (University of Oxford, Karyopharm Therapeutics Inc. and CTRG).

Ongoing Clinical Trials in the EU

Information on ongoing COVID-19 clinical trials in the European Economic Area (EEA) is available in the EU Clinical Trials Register (EU CTR).

On 26th May 2020 a search of the EU Clinical Trials Register (EU CTR) on COVID-19 found 205 ongoing trials, including a breakdown as follows:

Population/Phase No. of ongoing trials
Elderly 180
Adult 201
Minors 11
Phase 1 5
Phase 2 101
Phase 3 81

 

On the 26th May 2020, a search gave 167 results for ‘treatment’, with 32 trials ongoing in the UK. 11/32 are being conducted by the NHS.

https://www.clinicaltrialsregister.eu/ctr-search/search?query=covid-19&page=2

Notice to sponsors on validation and qualification of computerised systems used in clinical trials

Aside from COVID-19 notifications, on 7th April 2020 the EMA published a prompt to sponsors on their responsibilities regarding the validation and qualification of computer systems used in clinical trials as defined by ICH GCP E6(R2). Attention is drawn to the fact that regardless of delegation of activities, the ultimate responsibility for trial conduct remains with the Sponsor.

https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/notice-sponsors-validation-qualification-computerised-systems-used-clinical-trials_en.pdf

The US Food and Drug Administration (FDA)

COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders

FDA Guidance documents on COVID-19 can be found on this site with first entry dated 17th March 2020 and includes updates regarding drugs, biologics, medical devices, and animal and veterinary products: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders

Daily updates can be found here: https://www.fda.gov/emergency-preparedness-and-response/counterterrorism-and-emerging-threats/coronavirus-disease-2019-covid-19

The FDA has created a special emergency program for possible therapies, the Coronavirus Treatment Acceleration Program (CTAP). It uses every available method to move new treatments to patients as quickly as possible, while at the same time finding out whether they are helpful or harmful.

As of 11th May 2020, the snapshot is 144 active trials of therapeutic agents and another 457 development programs for therapeutic agents in the planning stages.

https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap

Coronavirus (COVID-19) | Drugs

The Center for Drug Evaluation and Research (CDER) is engaged in numerous activities to protect and promote public health during the COVID-19 pandemic. This site provides links to information including the Coronavirus Treatment Acceleration Program (CTAP, see below), Clinical Trial Conduct, Drug Shortages, Fraudulent Activity and Compounding; Manufacturing, Supply Chain, and Drug Inspections, and Drug Registration and Listing during the pandemic.

https://www.fda.gov/drugs/emergency-preparedness-drugs/coronavirus-covid-19-drugs

FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency

On 14th May 2020 the FDA published an update on its ‘Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency’. This is the third release on this topic and includes additional Q&A, (Q18-Q22) which cover topics such as video conferencing, post marketing studies, and Serious Adverse Event (SAE) reporting. This document builds on the initial guidance published in March 2020 and first updated (v2.0) to include Q&A on 16th April 2020.

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-public-health-emergency

COVID-19: Developing Drugs and Biological Products for Treatment or Prevention was released by the FDA on 11th May 2020 to assist sponsors in the clinical development of drugs for the treatment or prevention of COVID-19. Preventative vaccines and convalescent plasma are not within the scope of this guidance. Points of discussion include the patient population, trial design, efficacy endpoints and safety and statistical considerations. The guidance concludes with an Appendix on Examples of baseline severity categorisation.

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/covid-19-developing-drugs-and-biological-products-treatment-or-prevention

The FDA granted Emergency Use Authorization for remdesivir (Gilead Sciences Inc.) for treatment of COVID-19 on 1st May 2020. The scope of the licence includes emergency use for the treatment of hospitalized coronavirus disease (COVID-19) patients includes stipulation that it will be used only to treat adults and children with suspected or laboratory confirmed COVID-19 and severe disease defined as SpO2 ≤ 94% on room air, requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO); and is administered in an in-patient hospital setting via intravenous (IV) infusion.

https://www.fda.gov/media/137564/download

On the 8th May 2020, the FDA granted Emergency Use Authorization for the use of Fresenius Propoven 2% Emulsion (Fresenius Kabi USA, LLC) to maintain sedation via continuous infusion in patients greater than 16 years old who require mechanical ventilation in an ICU setting.

https://www.fda.gov/media/137888/download

On 12th May 2020, Moderna announced that the FDA has granted Fast Track designation for the Company’s mRNA vaccine candidate (mRNA-1273) against the novel coronavirus (SARS-CoV-2). The current Phase 2 study will evaluate the safety, reactogenicity and immunogenicity of two vaccinations of mRNA-1273 given 28 days apart. Moderna are also finalising a protocol for Phase 3 study of mRNA-1273, expected to begin in early summer of 2020.

https://investors.modernatx.com/news-releases/news-release-details/moderna-receives-fda-fast-track-designation-mrna-vaccine-mrna

 Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)

Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised) was released by the FDA on the 11th May 2020 to provide a policy to help accelerate the availability of novel coronavirus (COVID-19) tests developed by laboratories and commercial manufacturers for the duration of the public health emergency. Chapters include:

  • Laboratories Certified under Clinical Laboratory Improvement Amendments (CLIA) that Meet the CLIA Regulatory Requirements to Perform High­Complexity Testing Using Their Validated Diagnostic Tests Prior to EUA Submission
  • State Authorisation of Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High­Complexity Testing
  • Commercial Manufacturer Development and Distribution of Diagnostic Tests Prior to EUA Submission
  • Commercial Manufacturer Development and Distribution and Laboratory Development and Use of Serology Tests Prior to or Without an EUA
  • Validation Study Recommendations Based on the Technological Principles of Tests

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised

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