Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA publishes GCP inspection metrics report

On 15th February 2021, the MHRA published good clinical practice (GCP) inspection metrics report which covers the period of 1st April 2018 to 31st March 2019 and summarises results from 91 GCP Inspections conducted by the MHRA GCP Inspectorate.

The MHRA provides a summary of critical observations in the report by the category, except the results from the last three listed above (i.e., UK laboratory facilities, BE inspections, and EMA requested inspections) which were not included in this metrics report.

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Update on guidelines on managing clinical trials during Coronavirus (COVID-19)

On 17th February 2021, the MHRA updated its guidance on how investigators and sponsors should manage clinical trials during COVID-19. A section was added to on management of COVID-19 vaccine deployment for ongoing non-COVID-19 clinical trials.

Sponsors for ongoing clinical trials for indications other than treatment or prophylaxis of COVID-19 are required to evaluate the impact of the current government programme for deployment of a COVID-19 vaccine on each trial they are responsible for. Separate guidance for COVID-19 vaccine trials is being agreed with each research team.

It was highlighted that the MHRA does not state that trial participants must receive a COVID-19 vaccination as an eligibility criterion. It also does not state that if a vaccination had been required and had been justified as an eligibility criterion, that one COVID-19 vaccine would be preferred over another to take part in any clinical trial. This would be a decision for the sponsor when they design the trial, and any such position must be clearly justified.

For new trials, Sponsors are encouraged to address potential vaccination upfront in their protocol and build in appropriate flexibilities to avoid the need for substantial amendments at a later stage.

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Update on guidance on good clinical practice for clinical trials

On 16th February 2021, the MHRA updated its guidelines on how to demonstrate GCP standards are met and what to expect from an inspection. The GCP inspection dossier clinical trial spreadsheet was replaced with a new version.

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Guidance on applying human factors to medical devices

On 12th February 2021, MHRA updated guidance on the importance of applying human factors to medical devices, so they are designed and optimised to minimise patient and user safety risks. The guidance was updated to reflect the end of the transition period. The updates primarily apply to Great Britain, the changes in references to legislation and the introduction of the new UKCA mark.

It applies to the design of future products and changes in user interfaces of existing products, rather than those already on the market. It clarifies that usability engineering is an iterative process, involving design, testing and validation of design stages; it also requires attention to the post-market phase, since evidence may come to light while a device is being used in clinical practice that the design requires further improvement.

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For patients, the public and professional users: a guide to COVID-19 tests and testing kits

On 15th February 2021, guidelines were updated on the different types of tests and testing kits for COVID-19, and the specifications for manufacturers. The MHRA updated the section on lateral flow testing and added a new section on reporting issues with testing kits, in the ‘For patients, the public and professional users’ document.

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New Publications by the MHRA Inspectorate Blog

Guidance on pharmacovigilance requirements for UK authorised products from 1st January 2021

Since before the end of the transition period on 31st December 2020, the MHRA continue to update the guidance on pharmacovigilance requirements for UK marketing authorisation holders (MAH) which are set out in a revised legal framework.

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Reference Safety Information (RSI) for Clinical Trials- Part III

On 5th February 2021, the MHRA published part III of their blog on the RSI for Clinical Trials.

Since RSI blog posts part I and II were released, the MHRA GCP inspectorate has continued to see non-compliance in this key aspect of pharmacovigilance. Whilst additional guidance was released by the Heads of Medicines Agencies, Clinical Trials Facilitation, and co-ordination Group (CTFG), there are still unreported suspected unexpected serious adverse reactions and absence of adequate risk mitigation measures due to incorrect use of the RSI.

The MHRA GCP inspectorate completed a pilot of office-based inspections (OBI) focusing on clinical trials’ pharmacovigilance and the RSI. Two organisations were selected for the pilot, and critical findings were identified in both. The RSI OBIs have now been incorporated into the routine inspection programme.

In the blog post the MHRA reminds about what the RSI and what the RSI is used for, lists common findings identified during the inspections as well as provide some tips to improve compliance.

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European Medicines Agency (EMA) updates

COVID-19 Updates

On 25th February 2021, EMA issued guidance for vaccine manufacturers on Adapting COVID-19 vaccines to SARS-CoV-2 variants

EMA has issued guidance outlining the requirements for manufacturers planning to modify their COVID-19 vaccines in order to address coronavirus (SARS-CoV-2) variants.

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On 10th February 2021, EMA reported it was developing guidance on how to tackle COVID-19 variants.

The EMA is developing guidance for manufacturers planning changes to the existing COVID-19 vaccines to tackle the new virus variants, to consider options for additional testing and development of vaccines that are effective against new virus mutations, the Agency has requested all vaccine developers to investigate if their vaccine can offer protection against any new variants, i.e. those identified in the United Kingdom, South Africa, and Brazil, and submit relevant data.

The EMA will shortly publish a reflection paper that will set out the data and studies needed to support adaptations of the existing vaccines to current or future mutations of SARS-CoV-2 in the European Union (EU).

The EMA has authorised three vaccines for use in the EU: Comirnaty, COVID-19 Vaccine Moderna, and COVID-19 Vaccine AstraZeneca. There are concerns that some of these mutations could impact to different degrees the ability of the vaccines to protect against infection and disease. A reduction in protection from mild disease would however not necessarily translate into a reduction in protection from serious forms of the disease and its complications, for which more evidence needs to be collected.

In addition, the EMA is working with other regulatory authorities in the framework of the International Coalition of Medicines Regulatory Authorities (ICMRA) to determine possible changes to the composition of COVID-19 vaccines and to align a global strategy.

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On 12th February 2021, EMA published meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 8-11 February 2021

Highlights included:

  • Review of amfepramone medicines;
  • PRAC has concluded that use of Veklury is not associated with kidney problems;
  • PRAC starts new safety signal procedure with Veklury;
  • New safety information for healthcare professionals for Strimvelis, Venclyxto and Zolgensma.

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On 8th February 2021, EMA published news, that International regulators working together to enhance collaboration on COVID-19 observational research

The workshop was co-chaired by Health Canada and EMA and took place on 25th January 2021. In a dedicated COVID-19 workshop, convened under the umbrella of the ICMRA, medicine regulators from around the world emphasised the importance of international collaboration and sharing expertise and best practices on observational studies of real-world data to facilitate regulatory decision-making on COVID-19 treatments and vaccines. The full report can be found using a link below*.

The next ICMRA meeting on COVID-19 observational research is scheduled for April 2021.

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*ICMRA meeting: COVID-19 Real-World Evidence and Observational studies | International Coalition of Medicines Regulatory Authorities (ICMRA)

Latest updates from the European Commission (EC)

On 8th February 2021, the European Commission publishes updated guidance on the management of clinical trials during the COVID-19 pandemic.

The European Commission published updated guidance on the management of clinical trials during the COVID-19. Key changes from v3 (27th April 2020) are related to remote data verification.

The guidance was drafted and supported by the Clinical Trials Expert Group, EMA, the CTFG of the Heads of Medicines Agency and the GCP Inspectors Working Group coordinated by the EMA.

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Latest updates | Public Health (europa.eu)

On 17th February 2021, the European Commission proposed immediate action to prepare Europe for the increased threat of coronavirus variants.

The European Commission will establish a new biodefence plan called “HERA Incubator” to tackle short to medium-term threats and simultaneously prepare for the future by serving as the blueprint for the EU’s long-term preparedness for health emergencies. The HERA Incubator will bring together research, biotech companies, manufacturers, regulators, and public authorities to focus on rapid detection and characterisation of variants, swift adaptation of vaccines, setting up a European Clinical Trials Network, and enable the up scaling of production.

The actions announced will go hand-in-hand with global cooperation via the World Health Organisation and global initiatives on vaccines. The ground for the European Health Emergency Preparedness and Response Authority (HERA) will be prepared.

Key actions to boost preparedness, develop vaccines for the variants and increase industrial production include:

  • Detect, analyse, and assess variants;
  • Speed up regulatory approval of adapted vaccines;
  • Ramp up production of COVID-19 vaccines.

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European Commission released draft Clinical Trials Regulation (EU) No 536/2014 Questions & Answers version 3.0 document

The updated Questions & Answers document was released on 24th February 2021.

Microsoft Word – Q&A on the CTR v2.6- clean – update KB (europa.eu)

Latest updates | Public Health (europa.eu)

Food and Drug Administration (FDA) Updates

On 11th February 2021, the FDA issues 2020 Drug Safety Priorities Annual Report

The Centre for Drug Evaluation and Research (CDER) Drug Safety Priorities 2020 report details CDER’s work to manage drug safety issues through modernized safety surveillance methods and innovative responses to safety concerns.  The report highlights key safety-related milestones and accomplishments of 2020, as well as the many ways in which CDER has been involved in promoting and protecting public health during the SARS-CoV-2 COVID-19 pandemic.  The report focuses on the programs and initiatives at the core of CDER’s drug safety operations, including the FDA Adverse Event Reporting System, the Sentinel System, and the Safe Use Initiative.  It also features ongoing activities to address the national opioid crisis, work in addressing unexpected – and potentially cancer-causing – impurities in medicines, use of a broad range of communications tools and technologies such as Drug Safety Communications to transparently communicate drug safety to the public, and research being conducted CDER-wide to better understand drug safety risks.

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Update on Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency

On 27th January 2021, the FDA published the updated guidance with added content to the question-and-answer appendix.

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On 22nd February 2021, the FDA Issues Policies to Guide Medical Product Developers Addressing Virus Variants

The FDA issued guidances for medical product developers, specifically covering vaccines, diagnostics, and therapeutics products, to address the emergence and potential future emergence of variants of SARS-CoV-2, the virus that causes COVID-194:

  • The FDA updated its October 2020 guidance, Emergency Use Authorization for Vaccines to Prevent COVID-191;
  • The FDA issued a new guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests2;
  • To address the impact of emerging variants of SARS-CoV-2 on the development of monoclonal antibody products targeting the virus, the FDA has issued a new guidance, Development of Monoclonal Antibody Products Targeting SARS-CoV-2, Including Addressing the Impact of Emerging Variants, During the COVID-19 Public Health Emergency3.

1Emergency Use Authorization for Vaccines to Prevent COVID-19; Guidance for Industry (fda.gov)

2Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests – Guidance for Test Developers and Food and Drug Administration Staff (fda.gov)

3Development of Monoclonal Antibody Products Targeting SARS-CoV-2, Including Addressing the Impact of Emerging Variants During the COVID-19 Public Health Emergency (fda.gov)

4Download guidance

COVID-19 vaccines updates:

On 24th February 2021, the U.S. Food and Drug Administration said the single-dose Johnson & Johnson COVID-19 vaccine has met the requirements for emergency use authorisations, according to an analysis.

Issue Number: RN0103/01 Mar 2021

For your information, this will be the last monthly issue of Reg News. Going forward we will have weekly news summaries published on our website and LinkedIn. To subscribe, email us at info@towermains.com, with ‘Weekly Newsletter’ as the subject.