Guidance for medicine developers and other stakeholders on COVID-19

EMA encourages developers of potential vaccines or treatments for COVID-19 to contact EMA as soon as possible to discuss their strategy for evidence-generation.

They should email their proposals to 2019-ncov@ema.europa.eu.

Depending on the maturity of development, EMA will set up initial discussions on suitable mechanisms to fast-track development and approval, with priority given to the most relevant proposals.

Establishing contact early in the development process is important for ensuring that developers can submit well-prepared applications and make use of the accelerated procedures EMA has put in place for COVID-19 treatments and vaccines.

Guidance is available for developers of potential COVID-19 treatments and vaccines on the rapid review procedures EMA has put in place to speed up development and approval:

• EMA initiatives for acceleration of development support and evaluation procedures for COVID-19 treatments and vaccines

These rapid procedures can accelerate every step of the regulatory pathway while ensuring that robust evidence on efficacy, safety and quality is generated to support scientific and regulatory decisions.

They are available for initial marketing authorisation applications and extension applications for authorised medicines that are being repurposed for the treatment of COVID-19.

Overview of rapid procedures

EMA is ready to apply further flexibility, where it is established that shortening of any other procedural step could have an important public-health impact in dealing with the COVID-19 pandemic.

In addition, EMA will substantially accelerate the linguistic review process for procedures related to COVID-19.

It will also keep the European Commission informed about COVID-19-related applications to help speed up decisions on authorisations.

Other development-support and early-access mechanisms

Medicine and vaccine developers may also consider other regulatory mechanisms to receive enhanced support during medicine or vaccine development, or to enable early patient access to potential treatments or vaccines, including:

• the conditional marketing authorisation route;
• the use of compassionate use programmes.

Related information materials
Visual guide: Fast-track procedures for treatments and vaccines for COVID-19

Guidance is available for developers of potential COVID-19 vaccines on the clinical evidence to include in marketing authorisation applications.

• EMA considerations on COVID-19 vaccine approval

EMA encourages developers of potential vaccines to take these considerations into account when planning their strategy for applying for marketing authorisation.

EMA and the Heads of Medicines Agencies (HMA) also encourage developers to submit applications for EU marketing authorisation via EMA. This is the case even for vaccines that do not fall under the centralised procedure’s mandatory scope.

This aims to ensure that COVID-19 vaccines reach all EU Member States at the same time.

The pharmacovigilance plan for COVID-19 vaccines set out how EMA and the national competent authorities in the EU Member States identify and evaluate any new information that arises promptly, including any safety signals that are relevant for the benefit-risk balance of these vaccine:

• Pharmacovigilance plan for COVID-19 vaccines 

Marketing authorisation applicants for COVID-19 vaccines should follow EMA's guidance on preparing risk management plans (RMPs) for COVID-19 vaccines, together with guidance on Risk management plans and Good pharmacovigilance practices, which apply to all medicines:

• Guidance on risk management plans for COVID-19 vaccines

The guidance reflects special safety monitoring measures for COVID-19 vaccines by providing considerations and requirements for several sections of the RMP. 

EMA will publish the full bofy of RMPs (plus Annex 4) for all authorised COVID-19 vaccines, in line with its exceptional transparency measures for COVID-19 medicines. 

For more information, see:

• COVID-19 vaccines: development, evaluation, approval and monitoring
• Pharmacovigilance: Overview
• Risk management plans

New: Guidance is available on flexibilities to help developers of COVID-19 vaccines prepare and roll out packaging and labelling for their vaccines quickly. It 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 COVID19 vaccines

The guidance aims to facilitate the large-scale and rapid deployment of COVID-19 vaccines within the EU.

It provides details further to the European Commission's memorandum of Understanding (MoU) with Member States on regulatory flexibility for COVID-19 vaccines.

Joint procedural information is available from EMA and the United States Food and Drug Administration (FDA) for medicine developers planning to submit a paediatric investigation plan (PIP) to EMA and an initial pediatric study plan (iPSP) to the FDA for a COVID-19 vaccine or treatment:

• FDA / EMA common commentary on submitting an initial pediatric study plan (iPSP) and paediatric investigation plan (PIP) for COVID-19 vaccines and treatments

The joint document aims to make it easier for developers to submit paediatric development plans simultaneously to the regulators, to help speed up the development and approval of COVID-19 treatments and vaccines.

EMA and the FDA are encouraging medicine developers to submit PIPs and iPSPs early.

EMA and the FDA published the joint document on 2 June 2020.

New: A selection of European Pharmacopoeia (Ph. Eur.) 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:

• EDQM: Initiatives in the context of COVID-19 vaccines and therapies
• EDQM: Pharmacopoeial texts for vaccine developers

Specific guidance is also available from EDQM on analytical strategy options for the development of COVID-19 viral vector-based vaccines. This aims to fill a gap in the guidance available on quality for these new technologies:

• EDQM: Recombinant viral vectored vaccines for human use

Medicine developers should also follow the relevant scientific guidelines and other types of guidance on quality-related requirements applicable in the EU. Click on the categories below to find links to these guidelines on this website.

EMA's Committee for Medicinal Products for Human Use (CHMP) is urging the EU research community to pritoritise large randomised controlled clinical studies as these are most likely to generate the conclusive evidence needed to enable rapid development and approval of potential COVID-19 treatments. The CHMP also emphasises the need to include all EU countries in these trials:

• CHMP statement: A call to pool EU research resources into large-scale, multi-centre, multi-arm clinical trials against COVID-19

In line with the CHMP's statement, members of EMA staff and its scientific committees provided recommendations on concrete actions that stakeholders involved in COVID-19 clinical trials should take to enable the conduct of decision-relevant clinical trials, in an article published on 15 May 2020:

• Clinical Pharmacology & Therapeutics: Clinical trials for Covid-19: can we better use the short window of opportunity?

Advice to sponsors of COVID-19 clinical trials in the EU is included in the guidance on clinical trial management during the pandemic:

• Good clinical practice: Guidance on clinical trial management during the COVID-19 pandemic

On 17 July 2020, the European Parliament and the Council of the EU adopted a Regulation on the conduct of clinical trials with treatments and vaccines against COVID-19 containing genetically modified organisms (GMOs).

The regulation aims to speed up the conduct of clinical trials by providing a temporary derogation from the mandatory environmental risk assessment for these substances during the COVID-19 pandemic. However, a COVID-19 vaccine or treatment containing GMOs would require an environmental risk assessment before it could be marketed in the EU.

EMA is currently engaging with stakeholders who can further support the conduct of COVID-19 clinical trials across Europe.

For information on ongoing COVID-19 clinical trials in the EU, see Treatments and vaccines for COVID-19: Information on ongoing clinical trials in the EU.

EMA is encouraging collaboration between researchers on high-quality, multi-centre observational studies in the context of COVID-19, and transparency about study protocols and results.

High-quality observational research of real-world data can complement the results of randomised clinical trials in providing evidence on the safety and effectiveness of vaccines and treatments for COVID-19. Such research is also critical for understanding how exposure to certain medicines can affect the risk or the severity of COVID-19.

Researchers should adhere to existing guidelines on the appropriate design and conduct of pharmacoepidemiological studies in order to generate reliable and reproducible evidence, including the Guide on methodological standards in pharmacoepidemiology developed by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP).

The foreword to revision 8 of this guide, released in July 2020, highlights the chapters that are particularly relevant to the COVID-19 pandemic and examples of good practice.

To facilitate collaboration between researchers and to help improve the size and methodological rigour of studies, ENCePP has set up a dedicated COVID-19 response group. For more information on the group's activities, see its mandate on the ENCePP website.

In addition, recommendations on conducting high-quality research during the pandemic are available in an article published by EMA staff and EU researchers on 5 May 2020:

• Pharmacoepidemiology and Drug Safety: Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic

EMA and ENCePP are encouraging researchers to register their pharmacoepidemiological studies (and make study protocols and reports public) in the European Union electronic register of post-authorisation studies (EU PAS Register). They should include ‘COVID-19’ in the study title to allow easy retrieval of their studies.

Guidance is available for clinical-trial sponsors on how they should adjust the management of clinical trials and participants during the COVID-19 pandemic. This covers concrete changes and protocol deviations for dealing with extraordinary situations, such as the need for isolating participants, limited access to public spaces and the reallocation of healthcare professionals:

• Good clinical practice: Guidance on clinical trial management during the COVID-19 pandemic

Guidance is also available on the actions that sponsors of affected clinical trials should take to help ensure the integrity of their studies and the interpretation of the study results while safeguarding the safety of trial participants as a first priority.

• Implications of coronavirus disease (COVID-19) on methodological aspects of ongoing clinical trials

EMA revised this guidance on 29 June 2020 following a four-week public consultation.

In line with this guidance, EMA will be flexible and pragmatic during the assessment of affected clinical trial data submitted to the Agency as part of marketing authorisation applications.

For inspectors, guidance on how to initiate and conduct good clinical practice inspections remotely during the pandemic is also available:

• Guidance on remote GCP inspections during the COVID-19 pandemic

Guidance is available for companies responsible for human medicines on adaptations to the regulatory framework to address challenges arising from the COVID-19 pandemic, with a particular focus on crucial medicines for use in COVID-19 patients:

• Notice to stakeholders: Questions and answers on regulatory expectations for medicinal products for human use during the COVID-19 pandemic

The guidance covers:

• marketing authorisation and regulatory procedures;
• the manufacturing and importation of active substances and finished products;
• an exceptional change management process (ECMP);
• quality variations;
• labelling and packaging requirements;
• good manufacturing practice (GMP) and good distribution practice (GDP) certificates and inspections;
• pharmacovigilance inspections, system audits and corrective and preventive actions (CAPAs);
• submitting individual case safety reports (ICSR) to EudraVigilance.

Companies should send ECMP notifications for centrally authorised products to covid-ecmp@ema.europa.eu using this template:

• Template for submission of a notification for a Covid-19 exceptional change management process (ECMP)  

Companies should note that some of the measures described in the guidance are reserved for crucial medicines used for treating COVID-19 patients.

The guidance was agreed by EMA, the European Commission, the European medicines regulatory network and endorsed by the EU Executive Steering Group on Shortages of Medicines Caused by Major Events. 

Additional guidance is available for marketing authorisation holders on submitting COVID-19-related ICSRs to EudraVigilance, including on the correct use of COVID-19-related terms of version 23.0 of the Medical Dictionary for Regulatory Activities (MedDRA):

• Detailed guidance on ICSRs in the context of COVID-19: Validity and coding of ICSRs