COVID-19 guidance: research and development
HumanCOVID-19Clinical trialsRegulatory and procedural guidance
During the COVID-19 public health emergency, the European Medicines Agency (EMA) provided support to medicine developers researching and developing potential COVID-19 medicines, including dedicated guidance, rapid procedures and contact points.
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.
Contact for early support (updated)
EMA encouraged developers of potential vaccines or treatments for COVID-19 to contact EMA as soon as possible to discuss their strategy for evidence-generation.
Establishing contact early in the development process was important for ensuring that developers could submit well-prepared applications and make use of the rapid procedures EMA put in place for COVID-19 treatments and vaccines.
Medicine developers needed to email their proposal with:
- a description of the candidate product and its development plan;
- a summary of available evidence supporting its potential role in the COVID-19 setting.
EMA continues to provide early support and guidance to developers of treatments and vaccines against COVID-19 outside of a declared public health emergency.
Developers may contact EMA’s ETF with queries at PHEearlyinteractions@ema.europa.eu.
For more information, see:
Rapid procedures
Depending on the maturity of development, EMA offered to set up initial discussions on suitable mechanisms to fast-track development and approval, with priority given to the most relevant proposals.
Rapid procedures, such as scientific advice, early discussions and paediatric investigation plans (PIPs), facilitated the development and timely approval of COVID-19 medicines.
Rapid procedures are only applicable during a declared public health emergency.
EMA may exceptionally accelerate procedures outside of a public health emergency, such as for the approval of strain changes for COVID-19 or flu vaccines.
| PROCEDURE | FEATURES |
|---|---|
| Rapid scientific advice |
For more information see Scientific advice and protocol assistance |
| Rapid agreement of paediatric investigation plans (PIPs) and rapid compliance check |
For more information see Paediatric investigation plans and Paediatric requirements for marketing-authorisation applications |
For more information, see the guidance below. EMA may use the approaches in this document if another public health emergency were to occur:
EMA assesses applications swiftly in most cases, within a 20-day timetable. However, it may take longer if:
• the product in question is unlikely to address an unmet medical need, based on the data available at the time of application;
• the application includes numerous queries - in such cases, EMA may need to prioritise certain questions such as those on study protocol, based on discussion with the applicant;
• EMA faces a heavy workload.
EMA considers the procedure less urgent taking into account its workload, the stage of the medicine’s development and the severity of the emergency the medicine is intended to target.
Applicants should email pheearlyinteractions@ema.europa.eu with information on the:
- candidate product;
- development status, including timelines for key studies;
- available manufacturing, pre-clinical and clinical data;
- main considerations related to the proposed scientific advice questions.
Applicants can use the CHMP protocol assistance scientific advice briefing document template as a reference when preparing their application.
Clinical trials for COVID-19 medicines
From the start of the COVID-19 pandemic, EMA's Committee for Medicinal Products for Human Use (CHMP) urged the EU research community to prioritise large randomised controlled clinical studies as these were most likely to generate the conclusive evidence needed to enable rapid development and approval of potential COVID-19 treatments. The CHMP also emphasised the need to include all EU countries in these trials:
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:
Advice to sponsors of COVID-19 clinical trials in the EU was included in the guidance on clinical trial management during the 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 aimed 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 required an environmental risk assessment before it could be marketed in the EU.
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 encouraged 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 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:
EMA and ENCePP encouraged 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.
Standards and requirements on pharmaceutical quality
A selection of European Pharmacopoeia (Ph. Eur.) quality standards and accompanying guidance for vaccines and antivirals is 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 was also provided by EDQM on analytical strategy options for the development of COVID-19 viral vector-based vaccines. This aimed to fill a gap in the guidance available on quality for these new technologies.
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.
Quality-relatedscientific guidelines are available in the following categories:
The table below contains quality-related scientific guidelines that EMA considered most relevant for COVID-19 vaccine developers.
| GUIDANCE | DESCRIPTION |
|---|---|
| Clinical trials for COVID-19 treatments and vaccines | Guidance on conducting clinical trials for COVID-19 treatments and vaccines, including a relaxation of EU requirements for clinical trials using genetically modified organisms |
| Quality of medicines: questions and answers (Q&As) | Answers to common questions raised by marketing authorisation holders and national competent authorities on matters related to the quality of medicines |
| Good manufacturing practice | The minimum standard that a medicines manufacturer must meet in their production processes. These apply to both investigational products used in clinical trials and authorised medicines |
| Nitrosamine impurities | Requirements in place to avoid the presence of nitrosamine impurities in all medicines, including vaccines |
Paediatric development plans: joint submission to EMA and FDA
Joint procedural information was provided by 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 paediatric study plan (iPSP) to the FDA for a COVID-19 vaccine or treatment:
The joint document aimed 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 encouraged medicine developers to submit PIPs and iPSPs early.
EMA and the FDA published the joint document on 2 June 2020.