European medicines regulatory network's response to public health emergencies

Expediting development and approval of safe COVID-19 vaccines and therapeutics

In 2022, two new vaccines were approved for use throughout the EU: 

• COVID-19 Vaccine Valneva is authorised to protect people from 18 to 50 years who have not been immunised before against COVID-19;
• VidPrevtyn Beta is authorised as a booster to protect adults who have received at least a primary vaccination course against COVID-19.

In 2022, adapted mRNA vaccines were developed to extend the immune response of vaccinated people against a wider range of the frequent mutations of the virus. Four bivalent vaccines, each of them targeting the original strain and a mutation of the Omicron variant, were recommended to be used in people who have received at least a primary vaccination course against COVID-19:

• Comirnaty Original/Omicron BA.1 and Comirnaty Original/Omicron BA.4-5 are adapted versions of Comirnaty containing an additional mRNA molecule with instructions for producing a protein from the Omicron BA.1 and BA.4/BA.5 subvariants of SARS-CoV-2, respectively.
• Spikevax bivalent Original/Omicron BA.1 and Spikevax bivalent Original/Omicron BA.4-5 are adapted versions of Spikevax containing an additional mRNA molecule with instructions for producing a protein from the Omicron BA.1 and BA.4/BA.5 subvariants of SARS-CoV-2, respectively.

ECDC and EMA advice on the use of COVID-19 vaccines

Throughout the year, EMA and the European Centre for Disease Prevention and Control (ECDC) gave a number of joint recommendations to provide guidance and support to Member States in the roll-out of their vaccination campaigns.

The joint statements included topics such as the use of second booster doses in the elderly and vulnerable populations and the use of Omicron-adapted COVID-19 boosters to support the planning of the autumn and winter vaccination campaigns in the EU. 

Manufacturing

EMA approved additional manufacturing capacity for COVID-19 vaccines, bringing the total of approved manufacturing sites to 68 (compared to 52 in 2021). This work ensures high-quality manufacturing processes and resulted in a steady supply of high-quality and safe vaccines.

COVID-19 therapeutics approved

Although vaccination was rolled out widely throughout the EU, there was a continued need for new and better treatments for people who contracted the disease. 

Two new treatments for COVID-19 were approved in 2022:

• Paxlovid, to treat adults with COVID-19 who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19. Paxlovid was the first antiviral treatment for COVID-19 that is taken orally and can be used in the comfort of people’s own homes. Subsequently, the use of this medicine was extended to adolescents.
• Evusheld, for the prevention of COVID-19 in adults and adolescents from 12 years of age weighing at least 40 kg before potential exposure to the SARS-CoV-2 virus. This medicine was later extended to include the treatment of adults and adolescents with COVID-19 who do not require supplemental oxygen. Updated information on the effectiveness of Evusheld and other monoclonal antibodies for COVID-19 is available in the next section.

The indication for Veklury was extended to include children at least 4 weeks old and weighing at least 3 kg with pneumonia requiring supplemental oxygen or other non-invasive ventilation at the start of treatment; and children weighing at least 40 kg who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.

Effectiveness of monoclonal antibodies against emerging strains of SARS-CoV-2

The ETF issued a warning in December 2022 to inform healthcare professionals that monoclonal antibodies that attach to the spike protein of SARS-CoV-2 may not be effective against the emerging strains of the virus and to consider alternative treatment options. These included the authorised medicines Evusheld, Regkirona, Ronapreve and Xevudy, as well as the bamlanivimab/etesevimab combination assessed under Article 5(3) of Regulation 726/2004.

Use of medicines not authorised to treat COVID-19

EMA’s ETF started a review of available data on the use of sabizabulin to treat hospitalised patients with moderate-to-severe COVID-19 who are at high risk of acute respiratory distress syndrome and death. The outcome of the review will be transmitted to CHMP in view of a possible recommendation.

The review is the first triggered under Article 18 of the new EU regulation (Reg 2022/123) that expanded the role of EMA during public health emergencies.

Safety monitoring of COVID-19 vaccines and therapeutics

The enhanced safety monitoring and supervision of all authorised COVID-19 vaccines continued throughout 2022. EMA issued monthly updates highlighting new safety signals assessed by the EMA’s safety committee (PRAC) and the related changes to the product information of these medicines.

International collaboration

EMA collaborated with international regulators from Australia, Canada, Japan, Switzerland and the World Health Organization (WHO) in the review of all COVID-19 vaccines and therapeutics under the OPEN (Opening our Procedures at EMA to Non-EU authorities) framework. Each regulatory authority conducted their own assessment in parallel with EMA’s evaluation while sharing scientific expertise and maintaining their scientific and regulatory independence.

EMA’s assessments were also used to support WHO’s Emergency Use Listing of COVID-19 vaccines, a risk-based procedure for assessing and listing vaccines to expedite their availability to people affected by a public health emergency. EMA is the regulatory authority of record for the following vaccines: Comirnaty, Vaxzevria, Jcovden, Spikevax, Nuvaxovid, VidPrevtyn, HIPRA, Valneva and Curevac.

mpox (monkeypox): the EU’s response

EMA supported the EU’s response to an atypical outbreak of mpox following reports of a number of cases in several Member States not linked to countries where the disease is endemic. The mpox outbreak was declared a Public Health Emergency of International Concern (PHEIC) by the WHO on 23 July 2022.

There was no authorised mpox vaccine in the EU when the PHEIC was declared. However, there was a smallpox vaccine, Imvanex, which had an equivalent in the US – Jynneos – that was already approved against mpox. EMA's ETF recommended – as a temporary measure – the use of the US-approved mpox vaccine Jynneos to support vaccination efforts by national authorities in the EU. In parallel, EMA also recommended an extension of the use of Imvanex to also protect adults from mpox.

The ETF also provided advice on the intradermal use of Imvanex / Jynneos against mpox based on a study of people who had received the vaccine intradermally at a lower dose as dose-sparing measure. The ETF’s advice supported the temporary use of Imvanex as an intradermal injection at a lower dose by the national authorities to protect at-risk individuals. This helped to rapidly increase the number of people who could be protected from the virus.

EMA’s ETF also interacted with developers of vaccines and therapeutics for mpox, providing scientific advice and reviewing the available scientific data on medicinal products that have the potential to address this public health emergency.

Real-world evidence (RWE) studies in public health emergencies

Building on the work in 2020 and 2021 to leverage collaborations with academics in observational research, EMA used real-world data from routine clinical practice to monitor the safety and effectiveness of COVID-19 and mpox vaccines to generate timely RWE supporting the response to both outbreaks. Building on this experience, a process for the rapid procurement of studies in emergency situations, where rapid evidence is required to support public health and regulatory actions, has been developed in line with EMA’s extended mandate (see next section).