COVID-19 guidance: evaluation and marketing authorisation

During the COVID-19 public health emergency, the European Medicines Agency (EMA) assessed applications for COVID-19 medicines under the minimum timeframe necessary to allow for a thorough evaluation of the medicine’s benefits and risks. 

 

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. 

Rapid procedures

EMA rapid procedures helped 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 were available for initial marketing-authorisation applications for the treatment or prevention of COVID-19, as well as for applications to ‘repurpose’ medicines already authorised for other conditions, by extending their indications to include COVID-19.

PROCEDURE AND REGULATORY TOOLS	FEATURES
Rolling review	EMA's scientific committees - Committee for Medicinal Products for Human Use (CHMP) and Pharmacovigilance Risk Assessment Committee (PRAC) - review data as they become available on a rolling basis. This review is done with the support of the COVID-19 EMA pandemic Task Force (COVID-ETF). The review takes place while development is still ongoing The COVID-ETF has to agree on the start of a rolling review  Several rolling review cycles can be carried out during the evaluation of one product while data continue to emerge. The number of cycles depends on the amount to be assessed Each cycle is pre-agreed between EMA and the applicant The submission for each cycle takes place in eCTD format. In addition to the newly available data, each submission normally includes: an application form module 2 overview(s) responses to all outstanding questions from previous review cycles During the rolling review, EMA assess whether the data package is complete enough to invite the applicant to submit a formal marketing authorisation application. In these cases, EMA processes the application under a shortened timetable
Accelerated assessment	Can be considered for medicines and vaccines not undergoing a rolling review Requires a complete application to be available at the time of submission (unlike a rolling review) Review is reduced to 150 days (from 210 days) or less after validation of a complete application For more information seeAccelerated assessment
Conditional marketing authorisation	Is a regulatory tool to fast track medicines for use in emergency situations by granting a marketing authorisation as soon as sufficient data becomes available to demonstrate that the benefits outweigh the risks Ensures that the medicine is manufactured and controlled according to high pharmaceutical standards compatible with large scale commercialisation Once a it has been granted, companies must provide further data from ongoing or new studies within pre-defined deadlines to confirm that the benefits continue to outweigh the risks Is valid for one year and renewable For more information see Conditional marketing authorisation

For more information, see the guidance below. EMA may use the approaches in this document if another public health emergency were to occur: 

EMA initiatives for acceleration of development support and evaluation procedures for COVID-19 treatments and vaccines [OBSOLETE]

Reference Number: EMA/213341/2020 Rev.5

Applying for a rolling review

Applying for rolling review is a three-stage process. 

Step 1: Initiation

Applicants should email [e-mail] providing the following information:

• A justification for the assessment of the product via a rapid procedure
• Data supporting the proposed role of the product in the COVID-19 pandemic setting
• Data (including clinical data) supporting the proof of concept
• A summary of the product’s clinical development status and plans for further studies
• The status of the product's paediatric investigation plan (PIP)
• Study protocol(s)
• A high-level plan with a timetable for submitting the different rolling review data packages
• A description of the proposed manufacturing process and supply chain

Applicants can submit this information together with or following their request for eligibility to the centralised procedure. For more information, see Obtaining an EU marketing authorisation, step-by-step. 

EMA will proceed to step 2 by appointing a product team if it considers the applicant to have shown:

• pharmacological plausibility;
• sufficient evidence supporting the proof of concept, including clinical data;
• a sufficiently mature status of development;
• the strategic importance of the product in the pandemic context.

Step 2: Preliminary check of planned application's maturity and completeness

EMA appoints a product team, including a product lead, allowing it to assess the maturity and completeness of the file as part of its preliminary checks.

At this stage, EMA will require the applicant to provide additional information enabling EMA to determine:

• the availability of a clear and credible plan, including timelines, for submitting rolling review packages and a (conditional) marketing authorisation application;
• timelines for the availability of pivotal clinical data, based on the status of pivotal clinical trial(s);
• the proposed manufacturing process and supply chain;
• the proposed EU/EEA batch release site;
• whether pre-authorisation inspections are required (see Inspections: verifying compliance).

EMA will proceed to step 3 by appointing rapporteurs once these details are confirmed.

Step 3: Decision to start a rolling review

The COVID-ETF decides if the application is suitable for a rolling review and agrees a start date. 

This is based on the rapporteurs' assessment and on the EMA product team's input on whether the applicant has provided enough information for the COVID-ETF to conclude on the following:

• A confirmation of the proof of concept
• The strategic importance of the product in the pandemic context
• The applicant's expected readiness to submit a sufficiently mature and complete application for (conditional) marketing authorisation within approximately four months
• A sufficiently established manufacturing process and supply chain
• The feasibility of conducting the required inspections

Applicants can apply for a rolling review with or without having applied for scientific advice.

Applying for an accelerated assessment

See accelerated assessment for how to apply.

Applying for a conditional marketing authorisation

See conditional marketing authorisation for how to apply.

EMA applied further flexibility, where it 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 substantially accelerated the linguistic review process for procedures related to COVID-19.

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

Marketing authorisation guidance for COVID-19 vaccines

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

The principles in this guidance remain relevant for COVID-19 vaccines after the pandemic:

EMA considerations on COVID-19 vaccine approval

Adopted Reference Number: EMA/592928/2020

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.

For more information, see:

• COVID-19 vaccines: development, evaluation, approval and monitoring
• Marketing authorisation
• Conditional marketing authorisation

Labelling flexibilities for COVID-19 vaccines

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)

Guidance was provided 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, while keeping in line with regulatory requirements:

Questions and answers on labelling flexibilities for COVID-19 vaccines

Reference Number: EMA/726359/2022

The purpose of the guidance was 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.

For more information, see:

• Product-information requirements

Labelling flexibilities for COVID-19 treatments

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)

Guidance was provided on flexibilities to help developers of COVID-19 treatments prepare and roll out packaging and labelling for their treatments quickly.

It describes EMA’s criteria for deciding if a COVID-19 treatment could benefit from the same temporary labelling exemptions as COVID-19 vaccines.

Labelling flexibilities for COVID-19 therapeutics

Reference Number: EMA/35618/2021

For more information, see:

• Product-information requirements

Adapting COVID-19 vaccines to SARS-CoV-2 variants

Guidance is available for developers planning to adapt COVID-19 vaccines to address SARS-CoV-2 variants.

A reflection paper from EMA’s CHMP details the non‑clinical, clinical, quality and manufacturing data needed to support the approval of such adaptations in the EU.

CHMP expects new ‘variant’ vaccines to largely rely on the same technologies and platforms as their ‘parent’ vaccine, but with a different antigen selected to trigger the immune response. The parent would be a vaccine already approved in the EU to prevent COVID-19.

The principles in this guidance remain relevant for COVID-19 vaccines after the public health emergency:

Reflection paper on the regulatory requirements for vaccines intended to provide protection against variant strain(s) of SARS-CoV-2

Adopted Reference Number: EMA/117973/2021

Procedural guidance is also available on submitting a variation application to update the composition of an authorised COVID-19 vaccine to address SARS-CoV-2 variants. For more information:

• Post-authorisation: updating authorised COVID-19 vaccines to address SARS-CoV-2 variants