Guidance for medicine developers and other stakeholders on COVID-19

During the 2020-23 COVID-19 public health emergency, the European Medicines Agency (EMA) provided guidance for medicine developers and pharmaceutical companies to help speed up development and approval for COVID-19 medicines and address regulatory challenges arising from the pandemic.

The guidance in this section was intended for use during the COVID-19 public health emergency. Some of it remains relevant, either for COVID-19 medicines or if another public health emergency were to happen. Please see individual topics for more information. 

In this section

• COVID-19 guidance: research and development
• COVID-19 guidance: evaluation and marketing authorisation
• COVID-19 guidance: post-authorisation

Clinical trials affected by the pandemic

The principles in this guidance may be relevant in case another major disruption were to occur.

Guidance is available for clinical-trial sponsors on how to 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 update history

DATE	GUIDANCE ADDED
08 February 2021	Additional flexibility and clarification on the: role of centralised monitoring and central review of data collected; remote source data verification (SDV) extension to additional types of clinical trials. This aims to ensure the quality of clinical trial data and the protection of rights, safety and well-being of participants in the European Union / European Economic Area.
28 April 2020	Additional flexibility and clarification on: the distribution of medicines to trial participants. This takes into account social-distancing measures and possible limitations in trial site and hospital resources; the remote verification of source data (SDV) in the context of social distancing measures. This aims to facilitate activities that support the approval of COVID-19 and other life-saving medicines; notifying authorities of urgent actions taken to protect trial participants against an immediate hazard, or of other changes taken to support patient safety or data robustness.
27 March 2020	Safety reporting Distribution of in-vitro diagnostics Medical devices Auditing Updates in other sections, in particular on communicating with authorities, informed consent and the distribution of investigational medicines
20 March 2020	Guidance first published

Further updates are possible and likely as the pandemic develops.

Guidance is available on the actions that sponsors of affected clinical trials should take to help ensure the integrity of their studiesand 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 committed to being 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

AdoptedReference Number: EMA/INS/GCP/162006/2020Summary:

This document is intended to provide guidance on the steps to be followed during remote good clinical practice (GCP) inspections.

Regulatory expectations and flexibility (human medicines)

The regulatory flexibilities described in the guidance below are no longer granted. Those already granted, such as English-only labelling for COVID-19 vaccines, extend until the end of 2023 to ensure a smooth phase-out and avoid disruption. For more information see: Phasing out of extraordinary COVID-19 regulatory flexibilities (06/07/2023)

During the public health emergency, guidance was provided to 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

Guidance update history

DATE	GUIDANCE ADDED
June 2022	Validity of GMP and GDP certificates and time-limited manufacturing and import authorisations extended until end of 2023
30 September 2021	Validity of GMP and GDP certificates and time-limited manufacturing and import authorisations extended until end of 2022
1 July 2020	Management of corrective and preventive actions (CAPAs) Planning and conduct of pharmacovigilance system audits Pharmacovigilance inspections, including remote inspections
28 May 2020	Clarification of the exceptional change-management process in place to reduce the risk of shortages or disruption of supply of crucial medicines Further temporary flexibility on GMP and GDP inspections Inspections of plasma collection centres
20 April 2020	GMP and GDP inspections Submission of individual case safety reports (ICSRs) to EudraVigilance
10 April 2020	Guidance first published

Further updates are possible as the pandemic develops.

The guidance covered:

• 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 had to send ECMP notifications for centrally authorised products to [e-mail] using a template:

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

Summary:

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

Some of the measures described in the guidance were reserved for crucial medicines used for treating COVID-19 patients.

EMA, the European Commission and the European medicines regulatory network agreed the guidance in May 2020.

In July 2022, EMA's Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG) supported keeping these exceptional measures in place at the time.

Guidance on individual case safety reports

The principles in this guidance remain relevant in relation to COVID-19 after the public health emergency.

Guidance is available for marketing authorisation holders, sponsors, developers, applicants and national competent authorities on how to submit COVID-19-related individual case safety reports (ICSRs) to EudraVigilance.

This includes how to use COVID-19-related terms from the Medical Dictionary for Regulatory Activities (MedDRA):

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

Reference Number: EMA/174312/2020 Rev.3

EMA updated this guidance in April 2022 to provide further clarification on how to:

• recording patients' vaccine dose schedules in the ICSRs;
• indicate when a vaccine did not appear to work (‘lack of therapeutic efficacy’);
• manage cases where the recipient did not know the name of the vaccine that they received.

Stakeholders mentioned should follow the updated guidance, when submitting new cases and follow-up cases. They do not need to amend ICSRs that they have already submitted to EudraVigilance.

Regulatory expectations and flexibility (veterinary medicines)

The regulatory flexibilities described in the guidance below are no longer available. For more information, see:  Phasing out of extraordinary COVID-19 regulatory flexibilities (06/07/2023)

During the public health emergency, guidance was provided for companies responsible for veterinary medicines on adaptations to the regulatory framework to address challenges arising from the COVID-19 pandemic:

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

The guidance covered:

• marketing authorisation procedures;
• pharmacovigilance, including pharmacovilance inspections;
• good manufacturing practice (GMP) certificates and inspections;

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. 

Guidance update history

DATE	GUIDANCE ADDED
June 2022	Validity of GMP and GDP certificates and time-limited manufacturing and import authorisations extended until end of 2023
29 March 2022	Legal framework updated to reflect changes introduced by the Veterinary Medicinal Products Regulation (Regulation (EU) 2019/6)
30 September 2021	Validity of GMP and GDP certificates and time-limited manufacturing and import authorisations extended until end of 2022
30 April 2020	Guidance first published

Further updates are possible as the pandemic develops.