Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA draft guidance on randomised controlled trials generating real-world evidence to support regulatory decisions

A draft guidance on randomized controlled trials generating real-world evidence to support regulatory decisions was issued for the public comments on 30th October 2020 by the MHRA.

Data routinely collected while patients go about their regular lives, for example, in electronic health records and disease and patient registries, is commonly called real-world data (RWD). When such data is analysed to make inferences about the effects of different treatments, the information produced is similarly called real-world evidence. Use of pre-existing data sources has the potential for increasing the speed and reducing the cost of development programmes, which would see effective medications being approved more quickly, or even programmes which were previously thought to be unfeasible becoming feasible, with the consequent benefit to public health.

The guidance has been drafted with the input of the Commission on Human Medicines Real-World Data ad hoc group and is intended to be the first in a series of guidance documents addressing issues around using real-world evidence in support of a regulatory submission.

The comments are expected by 11th December 2020.

MHRA draft guidance on randomised controlled trials generating real-world evidence to support regulatory decisions – GOV.UK (www.gov.uk)

Consultation document: MHRA draft guidance on randomised controlled trials generating real-world evidence to support regulatory decisions – GOV.UK (www.gov.uk)

New Publications by the MHRA Inspectorate Blog

Gail Francis and Martin O’Kane published the article ‘Building resilience into clinical trial design and conduct during the pandemic’1. The article introduces a guidance on minimising disruptions to the conduct and integrity of clinical trials of medicines during COVID-19 which was published by the MHRA on 11th November 20202. This guidance follows on from that published on managing clinical trials during coronavirus (COVID-19) on 19th March 20203 and has been developed to assist those involved in running clinical trials of medicines. The aim is to avoid disruptions as a result of the continuing pandemic and will support appropriate incorporation of the available flexibilities into normal practice for the benefit of trial participants. The guidance is relevant to those involved with ongoing studies, wishing to restart trials that have been paused or temporarily halted, and those wishing to start new studies and covers the following topics:

  • Preparation and training
  • Investigational medicinal product dossiers (IMPDs)
  • Protocols
  • Risk-based approach
  • Maintaining study and data integrity
  • Adoption of data-enabled approaches to patient recruitment
  • Help from the MHRA

1Building resilience into clinical trial design and conduct during the pandemic – MHRA Inspectorate (blog.gov.uk)

2Guidance on minimising disruptions to the conduct and integrity of clinical trials of medicines during COVID-19 – GOV.UK (www.gov.uk)

3Managing clinical trials during Coronavirus (COVID-19) – GOV.UK (www.gov.uk)

MHRA post-transition period updates1

The following updates were recently published on guidance for industry and organisations to follow from 1st January 2021:

Devices

A Guidance intitled ‘Using the UKNI* marking from 1st January 2021’ was published on 30th October 2020.

*UKNI – United Kingdom, Northern Ireland region

Using the UKNI marking from 1 January 2021 – GOV.UK (www.gov.uk)

Licensing

On 27th October 2020, the MHRA added a guidance to describe the approach the MHRA intends to take to the processing of variations to marketing authorisations (MAs) from 1st January 2021.

Variations to Marketing Authorisations (MAs) from 1 January 2021 – GOV.UK (www.gov.uk)

On 23rd October 2020, the MHRA sent by email a letter providing guidance on the post-transition conversion process to the Community MA holders. The MHRA advice to email capconversion@mhra.gov.uk if the letter was not received.

Conversion of Community Marketing Authorisations (CAPs) to Great Britain Marketing Authorisations (MAs) – letter to industry – GOV.UK (www.gov.uk)

The information on renewals for MAs via unfettered access was added by the MHRA on 27th October 2020.

Renewing Marketing Authorisations for medicines from 1 January 2021 – GOV.UK (www.gov.uk)

Importing and exporting

A guidance on how the ‘Written Confirmation’ process for active substances manufactured in Great Britain (England, Wales and Scotland) will be handled from 1st January 2021 was published on 24th   November 2020.

Written Confirmations for export to EEA and Northern Ireland of Active Substances manufactured in Great Britain – GOV.UK (www.gov.uk)

Pharmacovigilance

On 27th October 2020, an update was issued on guidance on pharmacovigilance procedures from 1st January 2021: a new information was added in Section 2 around products placed on the market in Northern Ireland as well as information was clarified around Northern Ireland in sections 5.1, 5.2 and 7.

Guidance on pharmacovigilance procedures from 1 January 2021 – GOV.UK (www.gov.uk)

Few updates on guidance entitled ‘Guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF) from 1 January 2021’:

On 23rd November 2020: under ‘Submission timeframes’, an update to the XEVMPD cut-off date for the UK QPPV baseline information has been provided.

On 23rd October 2020: added new section on guidance for applicants for UK marketing authorisations from 1st January 2021.

Guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF) from 1 January 2021 – GOV.UK (www.gov.uk)

Paediatrics

New information around Northern Ireland has been added in the section on ‘General approach to UK Paediatric Investigation Plans’.

Procedures for UK Paediatric Investigation Plan (PIPs) from 1 January 2021 – GOV.UK (www.gov.uk)

1MHRA post-transition period information – GOV.UK (www.gov.uk)

Updates on the MHRA guidance on coronavirus (COVID-19)

27th November 2020: Added ‘Oxford/AstraZeneca COVID-19 vaccine: MHRA statement confirming letter received’ to the ‘Vaccines and vaccine safety’ collection.

Oxford/AstraZeneca COVID-19 vaccine: MHRA statement confirming letter received – GOV.UK (www.gov.uk)

On 23rd November 2020 the MHRA published an ‘Advice for developers of COVID-19 vaccines’. Sponsors and researchers developing COVID-19 vaccines are invited to contact the MHRA to discuss their regulatory strategy and plans for filing regulatory submissions in the UK.

Advice for developers of COVID-19 vaccines – GOV.UK (www.gov.uk)

European Medicines Agency (EMA) updates

COVID-19 Updates3

On 27th November 2020, the EMA published guidance on flexibilities to help developers of COVID-19 vaccines prepare and roll out packaging and labelling for their vaccines quickly

The guidance includes practical advice on exemptions to some requirements that are possible, while keeping in line with regulatory requirements.

Questions and answers on labelling flexibilities for COVID-19 vaccines (europa.eu)

Guidance for medicine developers and other stakeholders on COVID-19 | European Medicines Agency (europa.eu)

A statement by the International Coalition of Medicines Regulatory Authorities (ICMRA)

On 27th November 2020, the EMA has endorsed a statement by the International Coalition of Medicines Regulatory Authorities (ICMRA) that urges all stakeholders, including vaccines researchers and investigators, academia, regulators and the pharmaceutical industry, to continue COVID-19 vaccine trials beyond the time when the pre-defined cases of COVID-19 disease for final analysis in a trial have been reached. This can provide important additional and more precise information on longer-term safety and efficacy of a vaccine against COVID-19.

Global regulators urge continuation of COVID-19 vaccine trials for longer-term safety and efficacy follow-up | European Medicines Agency (europa.eu)

COVID-19: latest updates | European Medicines Agency (europa.eu)

On 27th November 2020, the EMA published guidance for developers of COVID-19 vaccines and treatments on where to find the standards and requirements related to pharmaceutical quality that are applicable in the EU

A selection of European Pharmacopoeia quality standards and accompanying guidance for vaccines and antivirals is currently available free of charge on the website of the European Directorate for the Quality of Medicines & Healthcare (EDQM) of the Council of Europe.

Specific guidance is available from EDQM on analytical strategy options for the development of COVID-19 viral vector-based vaccines. 

Scientific guidelines and other types of guidance on quality-related requirements applicable in the EU should be followed as well by medicine developers.

Guidance for medicine developers and other stakeholders on COVID-19 | European Medicines Agency (europa.eu)

The Heads of Medicines Agencies (HMA)/EMA statement on approval of vaccines

The statement was published on 20th November 2020. According to EU legislation (Regulation 726/2004) most COVID-19 vaccines fall under the scope of the centralised procedure since they are produced by biotechnological processes for which the centralised procedure is mandatory. For other types of vaccines currently under development, such as those composed of whole-inactivated virus or live attenuated virus, the EMA and the HMA network encourage marketing authorisation holders to submit their applications through the centralised procedure in order to ensure that those vaccines reach all Member States at the same time, with no unfair access in the Union.

HMA/EMA statement on approval of vaccines | European Medicines Agency (europa.eu)

Guidance for developers of potential COVID-19 vaccines

On 19th November 2020, the EMA published guidance for developers of potential COVID-19 vaccines on the clinical evidence to include in their MA application. The guidance includes a discussion on the clinical requirements for MA, clinical efficacy and safety, and post-approval follow-up for safety and efficacy.

EMA considerations on Covid-19 vaccine approval (europa.eu)

Pharmacovigilance Plan of the EU Regulatory Network for COVID-19 Vaccines document

The document was published on 13th November 20201. It provides an overview of the activities the EU regulatory network (EMA and National Competent Authorities (NCAs)) will conduct once COVID-19 vaccines are authorised. The main objectives of this plan include:

  • Active collection of data on rare potential risks;
  • Rapid detection, prioritisation and assessment of emerging safety information derived from spontaneous reporting systems, observational studies and other data sources;
  • Prompt evaluation of the impact of detected safety issues on the benefit-risk balance of the vaccines, taking into account exposure and effectiveness data;
  • Active surveillance of vulnerable populations, such as pregnant women and older vaccinees;
  • Engagement and collaboration with stakeholders including vaccinees and healthcare professionals, marketing authorisation holders (MAHs) and international partners;
  • Prompt and effective communication of new information arising from the above activities.

In addition to the Pharmacovigilance Plan, the EMA issued guidance to support pharmaceutical companies’ preparation of risk management plans for COVID-19 vaccines2.

1Pharmacovigilance Plan of the EU Regulatory Network for COVID-19 Vaccines (europa.eu)

2coreRMP19 requirements for COVID-19 vaccines (europa.eu)

3COVID-19: latest updates | European Medicines Agency (europa.eu)

International regulators and World Health Organisation (WHO) join forces to address COVID-19 challenges

The ICMRA and the WHO have joined forces to uphold and promote the most rigorous, evidence-based regulatory practices by supporting the alignment of regulatory processes across all countries. The aim is to ensure that patients have access to safe and effective medicines against COVID-19 as early as possible, while the existing rigorous scientific standards for the evaluation and safety monitoring of treatments and vaccines are maintained at all times.

International regulators and WHO join forces to address COVID-19 challenges | European Medicines Agency (europa.eu)

WHO-ICMRA joint statement on the need for improved global regulatory alignment on COVID-19 medicines and vaccines | International Coalition of Medicines Regulatory Authorities (ICMRA)

Latest updates from the European Commission (EC)

On 25th November 2020, the EC adopted a Pharmaceutical Strategy1 for Europe to ensure patients have access to innovative and affordable medicines and to support the competitiveness, innovative capacity and sustainability of the EU’s pharmaceutical industry2.

1 Click to view source

2 Click to view source

The EC plan to examine the impacts of future policy options to update the legal framework on medicines for rare diseases and paediatric medicines. EU legislation on medicines for children and rare diseases was introduced in the early 2000’s, to address the lack of medicines in this area. This initiative will explore the need for adequate measures to address a number of shortcomings in the functioning of the existing framework detected during a recent evaluation. A feedback period is 25th November 2020 – 06th January 2020.

EC Impact assessment

EC Initiatives

Eudralex Vol 10

Food and Drug Administration (FDA)

Newly issued guidance1

On 24th November 2020 the FDA issued guidance ‘Qualification Process for Drug Development Tools’

Section 3011 of the 21st Century Cures Act (Cures Act) added new section 507, Qualification of Drug Development Tools (DDTs), to the Federal Food, Drug, and Cosmetic Act (FD&C Act).

Guidance for Industry (fda.gov)

A final guidance on Guidance on Certificates of Confidentiality (CoC) for Sponsors, Sponsor-Investigators, Researchers, Industry, and Food and Drug Administration Staff was issued by the FDA on 13th November 2020

The guidance is intended to help protect the privacy of human subject research participants from whom identifiable, sensitive information is being collected or used in furtherance of the research as well as to provide information on how to request a discretionary CoC, the statutory requirements for requesting such a CoC, and the statutory responsibilities associated with possessing a CoC. Historically, a CoC generally protected a researcher from being compelled to disclose identifiable, sensitive information about the research participant, created or compiled for purposes of the human subject research. As amended, the statute broadened the protections by affirmatively prohibiting holders of CoCs from disclosing such information unless a specific exception applies.

Certificates of Confidentiality (fda.gov)

Certificates of Confidentiality | FDA

‘Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry’ was issued by the FDA on 13th November 2020

The guidance recommends approaches that sponsors of clinical trials intended to support a new drug application or a biologics license application can take to increase enrollment of underrepresented populations in their clinical trials.

Guidance for Industry (fda.gov)

On 27th October 2020, the FDA published ‘Referencing Approved Drug Products in ANDA Submissions Guidance for Industry’

The guidance is intended to provide information to potential applicants on how to identify a reference listed drug, reference standard, and the basis of submission in an abbreviated new drug application (ANDA) submission.

Referencing Approved Drug Products in ANDA Submissions Guidance for Industry | FDA

Referencing Approved Drug Products in ANDA Submissions Guidance for Industry (fda.gov)

1Search for FDA Guidance Documents | FDA

FDA COVID-19 updates:

On 20th November 2020, the FDA published new information about the vaccine development and review process

The following publications were issued by the FDA: 

The FDA published Face Masks, Including Surgical Masks, and Respirators for COVID-19

On 24th November 2020, the FDA published a comprehensive new page on FDA.gov with answers to frequently asked questions about FDA-regulated face masks (including cloth face coverings), surgical masks, and respirators (filtering facepiece respirators, such as N95 respirators) intended for a medical purpose to assist in preventing the spread of infectious materials during the COVID-19 pandemic.

Coronavirus (COVID-19) Update: November 24, 2020 | FDA

Face Masks, Including Surgical Masks, and Respirators for COVID-19 | FDA

FDA Authorizes First COVID-19 Test for Self-Testing at Home

On 17th November 2020, the FDA issued an emergency authorisation for the first COVID-19 diagnostic test for self-testing at home and that provides rapid results. The Lucira COVID-19 All-In-One Test Kit is a molecular (real-time loop mediated amplification reaction) single use test that is intended to detect the novel coronavirus SARS-CoV-2 that causes COVID-19.

Coronavirus (COVID-19) Update: FDA Authorizes First COVID-19 Test for Self-Testing at Home | FDA

FDA in brief

FDA Launches Portal for Submission of Orphan Drug Designation Requests

On 23rd November 2020 the FDA announced the availability of Orphan Drug Designation Portal. The initiative supports the development of treatments for patients with rare diseases by strengthening the information technology process within the FDA’s Office of Orphan Products Development.

FDA in Brief: FDA Launches Portal for Submission of Orphan Drug Designation Requests | FDA

The FDA’s Center for Drug Evaluation and Research (CDER) released a report titled ‘Drug Trials Snapshots Summary Report 2015-2019’

The summary report, published on 09th November 2020, aggregates demographic data from Drug Trials Snapshots (DTS) published between 2015 and 2019. The report is organized into five sections:

  1. Clinical Trials Global Report
  2. Demographics of Trial Participation
  3. S. Clinical Trial Participant Distribution by Race and Ethnicity Categories
  4. Clinical Trial Participation by Therapeutic Area
  5. Demographics of Trial Participants in Rare Diseases

2015-2019 Drug Trials Snapshots Summary Report (fda.gov)

Issue Number: RN3011/30 Nov 2020

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