The development of vaccines for new pathogens is a complex and laborious process that usually takes several years.
Before being authorised, a vaccine candidate must successfully complete all the phases of medicinal product development. This begins with the isolation and characterisation of the pathogen and the identification of suitable antigens. Antigens are the components of the pathogen that are intended to bring about the immune protection. This step is followed by the development of the vaccine candidate, the preclinical investigations and the clinical trials in phase 1 (immunogenicity), phase 2 (tolerability, dosage) and phase 3 (statistically significant data on safety and efficacy). In order for a vaccine to be authorised, its quality, safety and efficacy must be proven. In addition, its benefits must clearly outweigh the risks. COVID-19 vaccines are also developed and authorised in accordance with this principle.
During the pandemic, the COVID-19 vaccines were assessed in Europe via the centralised marketing authorisation procedure, which is coordinated by the European Medicines Agency (EMA). In the event of a positive assessment, the Committee for Medicinal Products for Human Use (CHMP) at the EMA issues an opinion to the European Commission with a recommendation for authorisation. The European Commission decides on the marketing authorisation of a vaccine product in Europe and thus also in Germany. After being authorised, the vaccine can be marketed in the EU Member States, including the EEA states, and can be made available to all members of the public.
The coronavirus pandemic presented the modern world with unprecedented economic, social, and health-related challenges. Vaccines were the most effective way to contain the pandemic and to protect ourselves from COVID-19. This understanding motivated all the experts involved in vaccine development to work together more closely and to make processes more efficient, without compromising on due care and diligence. This also led to significant optimisation of the process flows and time saved in development.
Vaccine developers benefit from early and ongoing scientific and regulatory advice from medicines agencies. This scientific advice is initially provided on a national level, and then in the case of advanced development on a European level. It prepares the pharmaceutical company for the regulatory requirements that will need to be observed during development, for the requirements in terms of the content of applications for the approval of clinical trials, for marketing authorisation and for batch release. It makes a smooth submission process possible without undue delays.
A rolling review procedure for marketing authorisation allows the vaccine manufacturer at an early stage – even while the clinical phase 3 trial is still ongoing – to submit individual data packages for a preliminary assessment for marketing authorisation and to answer any questions that arise during the regulatory evaluation of the application. In this way, parts of the application dossier can be checked, improved and assessed before the actual application is submitted. Once all the necessary documents for marketing authorisation have been submitted and the marketing authorisation application has been made, processing will take significantly less time. The assessment process therefore starts much earlier. The rolling review procedure precedes the marketing authorisation application with the submission of the complete data packages.
The Paul-Ehrlich-Institut has also used the rolling review procedure for the approval of clinical trials.
Clinical trials, which generally take place one after the other, are combined, e.g. phase 1 with phase 2 or phase 2 with phase 3. Organisational processes, for example the recruitment of test subjects for two phases of the clinical trial, can be bundled into one process. In addition, the necessary investigations can be combined.
In the development of a COVID-19 vaccine, scientists were able to build on preparatory research work that had already taken place into other coronaviruses and corresponding vaccine developments, e.g. the SARS coronavirus in 2003 and the MERS coronaviruses. These coronaviruses, which are similar to SARS-CoV-2, triggered the SARS epidemic in 2002/2003 and the MERS (Middle East Respiratory Syndrome) epidemic in 2012.
Updated: 19.04.2024
During the pivotal clinical trial testing the safety and efficacy of a vaccine candidate, normally phase 3 or 2/3, the study participants are assigned randomly to one of two groups. One group is vaccinated with the vaccine candidate (the “verum group”), while the control group is given a placebo or another vaccine. Care is taken to ensure that both groups have a similar composition (e.g., in terms of age, gender, etc.) and that there is a comparable risk of infection. A laboratory-confirmed symptomatic infection or illness that occurs at a specific point in time after vaccination is then recorded in both groups and the frequency is compared. A calculated efficacy of 90% means that the number of infections or illnesses that occurred in the vaccinated group within a certain time was reduced by 90% compared to a non-vaccinated control group (e.g. n = 10 vs. 100 cases with groups of the same size).
Updated: 12.08.2024
No. The mRNA booster vaccines adapted to variants of the SARS-CoV-2 coronavirus (such as Omicron) from both BioNTech/Pfizer and Moderna have received approval for a variation to the marketing authorisation of the original COVID-19 vaccine product.
Legislation (see further information) has made it possible for changes to the antigen and/or the addition of new antigens (here mRNAs) to a parental COVID-19 vaccine already authorised in the EU to take place via a variation of the original marketing authorisation so that no new authorisation is required.
However, since these changes can have an effect on aspects such as immunogenicity, approval of a type-II variation is required for vaccine adaptation. The risk-benefit assessment of the data required for approval is carried out by experts from the national medicines authorities of the EU Member States in the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The final approval of the variation is given by the European Commission.
Updated: 25.07.2024
According to current knowledge, allergy sufferers or people who have already experienced a severe allergic reaction (anaphylaxis) can be vaccinated against COVID-19 with all authorised vaccines. There is no increased risk of serious adverse effects. An exception is a pre-existing allergy to an ingredient of the specific COVID-19 vaccine or a severe intolerance reaction to previous administration of the COVID-19 vaccine. In this case, allergological clarification is recommended and it is usually possible to switch to another COVID-19 vaccine.
As a general rule, severe allergic reactions can occur in very rare cases with all vaccines. Therefore, each person should be observed for 15 minutes after vaccination so that they can receive appropriate medical treatment in the event of an allergic reaction. If the person to be vaccinated has a history of anaphylaxis or severe allergic reactions following administration of medication or other vaccines, the observation time will be increased to 30 minutes if necessary.
It is not recommended to take anti-allergic drugs before vaccination, as a possible allergic reaction could be delayed and occur outside the monitoring period of 15 or 30 minutes.
In the rare case of a severe anaphylactic reaction after the first or second dose of vaccine, a further dose should not be administered.
Updated: 23.08.2024
Monoclonal antibodies for use against the SARS-CoV-2 coronavirus are proteins of the immune system (immunoglobulins) which have been developed to specifically bind to defined surface structures of the SARS-CoV-2 coronavirus. These antibodies are directed against the surface spike protein of SARS-CoV-2.
In contrast to hyperimmune globulins, convalescent plasma and sera, monoclonal antibodies consist of identical immunoglobulin molecules with a single amino acid sequence and a single recognition domain for a specific structure (epitope) of a single specific target molecule (antigen). Monoclonal antibody medicinal products may also contain combinations of a small number of precisely specified monoclonal antibodies; this is indicated in the composition of the medicinal product.
Updated: 28.03.2024
These antibodies work by binding to the spike protein on the surface of the SARS-CoV-2 coronavirus. In this way, they block the SARS-CoV-2 viruses from binding to the receptors on the surface of human cells. As a result, the viruses cannot penetrate the cells and infect them. As viruses reproduce in cells and are released by the infected cells, the neutralisation of viral entry and infection of the cells is also associated with the prevention of viral reproduction (replication).
Updated: 28.03.2024
The short development time for the COVID-19 vaccine candidates during the pandemic was possible thanks to a number of factors:
However, as is the case for all other new vaccines and therapeutic drugs, not all potential or very rare side effects could be recorded at the time of authorisation for COVID-19 vaccines. Vaccines and all other newly authorised medicines are therefore also monitored for safety after marketing authorisation. One component of post-authorisation monitoring (surveillance) is the analysis of spontaneous reports of suspected adverse reactions or vaccination complications. Additional studies have been carried out on the COVID-19 pandemic vaccines, including active safety studies.
Updated: 11.10.2024
No.
Vaccines can contain pharmaceutical excipients that are produced by the pharmaceutical manufacturer itself or purchased from other companies. Such substances are sometimes offered as laboratory chemicals for a wide variety of applications. The manufacturer usually provides the product information on these laboratory chemicals with a warning that they are not suitable for use in humans. This can lead to the erroneous assumption that they cannot be used in humans at all.
As soon as such substances are used in medicinal products, their suitability for use in humans must be carefully examined and evaluated by the manufacturer and within the framework of the marketing authorisation, e.g. by the Paul-Ehrlich-Institut. A marketing authorisation application contains corresponding information on quality and production. The above-mentioned testing was also carried out as usual for the authorisation of mRNA vaccines.
Updated: 22.08.2024
Suspected cases of adverse events or vaccination complications that were reported to the Paul-Ehrlich-Institut on or before 31 March, 2023, as having occurred after administration of the authorised COVID-19 vaccine products were presented in periodically published safety reports along with reports on safety signals. All reported cases of suspected adverse events and vaccination complications from Germany were taken into account, regardless of how they were received – by post, email, telephone, electronically via the Paul-Ehrlich-Institut’s reporting portal www.nebenwirkungen.bund.de, via the EudraVigilance database at the European Medicines Agency (EMA) and/or via the SafeVac 2.0 app.
www.pei.de/safety-report
Online-Reporting of Side Effects - www.nebenwirkungen.bund.de
Updated: 19.04.2024
From the beginning of the vaccination campaign in Germany on 27 December, 2020, through 31 March, 2023, there were 340,282 suspected cases of adverse events and 56,432 suspected cases of serious adverse events following administration of COVID-19 vaccine products (primary or booster vaccination) reported to the Paul-Ehrlich-Institut.
Suspected case reports of adverse events and vaccination complications are reports of reactions that occurred in temporal association to vaccination and are not directly clearly attributable to other causes. When reactions that occurred after vaccination are reported as a suspected adverse event or vaccination complication, the Paul-Ehrlich-Institut examines whether such reactions could be causally related to vaccination with a specific vaccine product, specific batches of a vaccine product or vaccine products of a specific vaccine type. If necessary, the Paul-Ehrlich-Institut will take, coordinate or initiate appropriate measures to reduce risk.
Updated: 30.08.2024
Non-clinical studies of the authorised mRNA COVID-19 vaccines have produced no evidence showing that vaccination may impair female or male fertility.
Several studies on the potential toxicity to animals were carried out before human use, as is required in the EU marketing authorisation process. Potential adverse effects of repeated vaccinations on fertility, pregnancy and embryonic development were investigated in a special, very extensive study in female rats conforming to international guidelines in what is known as a DART (Developmental and Reproductive Toxicity) study. These studies show no evidence of impairment of female fertility caused by the vaccines. Furthermore,, no vaccine-related changes in female or male reproductive organs (ovaries or testes) were observed in the extensive fine-tissue (histopathological) examinations conducted in the toxicity studies with repeated administration of an increased vaccine dose ( repeat-dose toxicity study).
These data conditions ensure with the highest degree of certainty that damage to reproductive organs and impairment of reproduction in humans can be excluded within the framework of a medicinal product marketing authorisation.
The studies that have been conducted and their evaluations can be found in the published European public assessment report (EPAR) of the European Medicines Agency (EMA). The EPARs can be found in the right-hand column at www.pei.de/covid-19-vaccines. The Robert Koch-Institut reports on further studies in their report: "Does COVID-19 vaccination make men or women infertile?" (German only)
Updated: 23.08.2024
The answer is a clear no.
It has now been shown that the spike protein of the SARS-CoV-2 coronavirus, when in contact with human cells, causes the cells to fuse with neighbouring ones and partly die. Such fused cells were found in lungs of patients who had died of COVID-19.
With these findings, the question arose as to whether vaccines causing the formation of spike proteins might also cause such membrane fusions.
When the COVID-19 vaccines available in Germany (mRNA vaccines or vector vaccines) are used, a few body cells receive one batch of foreign genetic information. This information consists of mRNA (mRNA vaccines) or DNA transmitted by harmless cold viruses (vector vaccines). The genetic information is translated into protein by the affected cells. The cells generate the spike protein of the SARS-CoV-2 coronavirus. Unlike the SARS-CoV-2 coronavirus, the vaccines do not replicate, so the amount of spike protein will remain small and local. No clinical effects are to be expected because the number of cells that receive the genetic information for the formation of the spike protein via vaccination is so small.
Clinical studies in tens of thousands of vaccinated study participants have proven the safety of the vaccines. The regular public safety updates by the Paul-Ehrlich-Institut do not include any evidence of such vaccination complications either.
Membrane fusion is a natural process used by the cells to transport material such as hormones, neurotransmitters, and waste to the desired destination. Viruses also use this process to enter new cells.
Updated: 23.08.2024
The Paul-Ehrlich-Institut will deny batch release if the criteria and specifications set out in the marketing authorisation documents are not met. However, this is very rare because strict quality controls are carried out by the manufacturer during the entire production process. These controls reveal potential deficiencies at an early stage. Medicinal products that reach the manufacturer for final product testing have therefore already been intensively monitored and are very likely to meet the quality standards required in the marketing authorisation documents.
The manufacturer must prepare and submit a testing report for each batch in order to apply for batch release. If a batch of a medicinal product shows deficiencies in the context of these tests, the Paul-Ehrlich-Institut will refuse official batch release for the batch.
As a rule, a manufacturer will not even apply for batch release from the Paul-Ehrlich-Institut if it has already been determined in advance that the batch does not meet the required product specifications.
Updated: 11.11.2024
The term "Post-Vac Syndrome" is used in connection with certain symptoms observed after COVID-19 vaccination, some of which are similar to Long COVID symptoms.
Currently there is no internationally recognised, standardised case definition for Post-Vac Syndrome. In the evaluations of suspected case reports of Long COVID/Post COVID-like symptoms after COVID-19 vaccination, it was not possible to identify an increased risk of these symptoms for such reports after COVID-19 vaccinations from Germany or from the Member States of the European Economic Area (EEA) and the non-EEA countries (worldwide) in which the centrally authorised COVID-19 vaccines were administered.
The Paul-Ehrlich-Institut would like to note that in each of the evaluations, as described in the statement dated 19 May, 2023, more than 50 percent of the suspected case reports came from Germany. However, less than 50 percent of all vaccine doses administered in the countries from which suspected case reports were submitted were administered in Germany.
The Paul-Ehrlich-Institut currently has no evidence from the scientific literature that could explain the triggering factors for the development of Long COVID/Post COVID-like symptoms.
It is now known that there were also numerous asymptomatic SARS-CoV-2 infections. In such cases, the Long COVID/Post COVID-like symptoms may also be a result of the undetected infection.
Updated: 23.08.2024
Despite the risk of misinterpretations of the reported information, the Paul-Ehrlich-Institut publishes reported cases of suspected adverse events as defined in the Medicinal Products Act (Arzneimittelgesetz, AMG) and/or vaccine complications as defined in the Infection Protection Act (Infektionsschutzgesetz, IfSG) after the use of COVID-19 vaccines. This data is published on the Paul-Ehrlich-Institut’s website in consideration of the increased demand for information from some sections of the population and in favour of maximum transparency. The information is offered in a user-friendly Excel spreadsheet and supplemented with batch numbers (when available). The Paul-Ehrlich-Institut would also like to call attention to the disclaimer text displayed before the download link and to the explanations included in line one of the tables.
Data on Adverse Drug Reactions
The following text is provided by the Paul-Ehrlich-Institut to inform the interested public regarding the most important facts, along with detailed explanations, connected to the use of the published suspected adverse event reports in order to prevent misinterpretations.
Spontaneous reports are an important tool in pharmacovigilance for the detection of new safety signals, which can be investigated via such methods as more detailed analyses and comparisons with data from existing clinical studies or literature publications. Reporting a suspected adverse event has been made simple and straightforward for the reporters in order to promote the voluntary submission of reports and to enable everyone to report suspected side effects, regardless of the availability of detailed information. Reports require only the information that can be provided by the reporters without difficulty and that is absolutely necessary in the European context of medicinal product evaluation for the processing and evaluation of the report. The batch numbers are not required information.
The batch numbers have no primary significance for the routine detection of signals. The starting point for signal detection is the reactions reported for the medicinal product or the vaccine. The indication of a specific batch number is also not mandatory for submissions to the EudraVigilance database, the suspected side effect database of the European Medicines Agency (EMA), for this same reason. Information on batch numbers is not published in the EudraVigilance database.
European Database of Suspected Adverse Drug Reaction Reports
The Paul-Ehrlich-Institut has repeatedly received inquiries from the public in which the information on suspected adverse events received from the spontaneous reporting system is regarded as an appropriate means of observing batch-related frequencies of vaccine adverse events. Such a perspective can lead to the expectation that batch-related evaluations of spontaneous reports should be considered standard. However, this perspective is not expedient from a scientific point of view because suspected adverse event reports submitted via the spontaneous reporting system have various system-inherent limitations and are therefore not suitable for making concrete statements about the frequency of reactions. This data is also only one component in the evaluation of medicinal product safety. Spontaneous reporting data is supplemented by information from clinical or non-interventional studies or by information published in the literature. This data is discussed in the context of periodic safety update reports (PSURs). The pharmaceutical companies (marketing authorisation holders) must submit these reports regularly to the European Medicines Agency (EMA), and the assessment and discussion of the reports takes place within the national medicines authorities.
Suspected adverse events after vaccination or medicinal product therapy are retrospectively recorded in the spontaneous reporting system using the information available to the reporting person. The number of recorded suspected adverse events in the spontaneous reporting system is thus a subset of the totality of the actual adverse events that have occurred. The Paul-Ehrlich-Institut has no way of determining the total number of suspected cases that have occurred within the spontaneous reporting system – e.g. the number of people who have been immunised with a particular vaccine in Germany. The exact number of exposed people is also not known, which is required in addition to the exact number of adverse events to calculate a specific frequency. Therefore, the frequency of the reaction cannot simply be inferred from the number of reports. Unlike the spontaneous reporting system, this information is available in clinical studies, so is possible to calculate the frequency of an adverse event in this context.
A valid vaccine batch is only documented for a limited number of the suspected case reports that are submitted to the Paul-Ehrlich-Institut. A batch-related increase in reports cannot be identified on the basis of the information available in the suspected case reports. A scientifically-accurate extrapolation is not possible on the basis of this incomplete data.
It is not uncommon for the number of suspected case reports per batch to vary. This is partly due to the fact that batches contain very different amounts of vaccine doses. In addition, all of the vaccine doses contained in a released batch are not vaccinated exclusively in one single Member State of the European Economic Area (EEA), such as Germany.
The concern that certain batches of a COVID-19 vaccine were more likely to cause adverse events than others is altogether unjustified. The Paul-Ehrlich-Institut would like to point out as an example that none of the safety signals determined to have a connection to the administration of COVID-19 vaccines – such as thrombosis with thrombocytopenia syndrome (TTS) after administration of vector vaccines or myocarditis/pericarditis after mRNA vaccines – were found to be batch-related.
The Paul-Ehrlich-Institut publishes reports of suspected adverse events that it receives within the spontaneous reporting system, one of the building blocks of pharmacovigilance. These reports are intended to provide an early indication of possible vaccine risks. They are not confirmed adverse events. It should be noted here that reported adverse events are chronologically, but not necessarily causally, linked to vaccination. Confirmed adverse events are listed in the vaccine product information. The reactions reported to the Paul-Ehrlich-Institut are also not equivalent to vaccine damage.
According to section 24 of the Social Code (Sozialgesetzbuch, SGB) XIV, persons who have suffered damage to their health due to a prescribed or publicly recommended vaccination that exceeds the usual extent of a reaction to a vaccination or other measure of specific prophylaxis (colloquially: vaccine damage) are to receive benefits under social compensation law. The corresponding prerequisites/criteria are set out in sections 4 and 24 of the SGB XIV. In order to receive these benefits, an application for compensation must be submitted to the Social Welfare Office in the federal state in whose territory the vaccination was carried out in accordance with section 113 subsection 5 of the SGB XIV.
Section 5 of the SGB XIV regulates the degrees of damage and stipulates that temporary health conditions lasting six months or less are not to be considered as damage.
The Paul-Ehrlich-Institut is not responsible for processing applications for benefits under social compensation law.
Updated: 17.01.2025
The Paul-Ehrlich-Institut developed the SafeVac 2.0 smartphone app as part of a study for the active monitoring of the safety and tolerability of authorised COVID-19 vaccines used in Germany. The aim of the app was to rapidly obtain quantitative information on the safety profile of the COVID-19 vaccines, going beyond the marketing authorisation data. The SafeVac 2.0 app should not be confused with the established online spontaneous reporting system for the recording of suspected adverse reactions, which could be used in parallel and will continue to be available.
Users of the SafeVac 2.0 app voluntarily took part in an observational study carried out by the Paul-Ehrlich-Institut, which will ran until the end of 2023. The vaccinated persons’ agreement and consent to participate in the Paul-Ehrlich-Institut’s observational study were preconditions for using the app. Participants who registered in the app by 30 September 2022 were asked questions via the app about their current state of health at defined points in time. The recruiting phase ended on 1 October 2022. No new participants will be included in the SafeVac 2.0 survey.
The SafeVac 2.0 app survey enabled the Paul-Ehrlich-Institut to determine the frequency, severity and duration of an adverse reaction. This app not only gave the Paul-Ehrlich-Institut information on suspected adverse reactions, but also on the proportion of vaccinated persons who tolerated vaccination well.
Updated: 19.04.2024
The SafeVac 2.0 app is a further development of the SafeVac 1.0 smartphone app, which was designed in collaboration with Materna Information & Communications SE and the Helmholtz Centre for Infection Research (HZI) in Braunschweig, and was used to record adverse events after seasonal influenza vaccination. The app was commissioned by the Paul-Ehrlich-Institut and was developed as a cross-platform app for the iOS (Apple) and Android (Google) operating systems.
Updated: 18.04.2024
Individuals who had received the first COVID-19 vaccination in their primary vaccination course by 30 September 2022 had the opportunity to participate in the study. As of 1 October 2022, no new participants were allowed to register for the SafeVac 2.0 study. The tracking of the persons registered up to that point continued according to the study protocol.
The vaccinated persons’ agreement and consent to participate in the Paul-Ehrlich-Institut’s observational study were preconditions for using the SafeVac 2.0 app. Participants were asked questions via the app on seven occasions after the first vaccination and on eight occasions after the second vaccination; this took place within three weeks after the first dose and four weeks after the second dose and was designed to determine how well the vaccines are tolerated. In addition, participants were asked final questions about their state of health after six and twelve months.
The data protection concept was assessed by the Federal Commissioner for Data Protection. Steps were taken to ensure that no participant or individual smartphone could be identified at any time. On the first occasion that data was transmitted to the Paul-Ehrlich-Institut, a random number was created on the federal server and then stored in encrypted form in the participant's smartphone memory; with each new data transmission, this number was checked to ensure it was correct and then transferred with the random key to the Paul-Ehrlich-Institut in a secure connection via the federal government server.
None of this information contained any personal data and nor was it traceable by the Paul-Ehrlich-Institut. Details about the user or his/her smartphone could not be derived from the case ID.
A distinction was made in the requested information between required details and data that was not absolutely necessary. The required fields included the details on age and gender, the vaccine name and the batch number. If required information was not entered, the user received a message and was not be able to move to the other fields until these mandatory fields were completed.
The transmitted data were evaluated for the occurrence of possible adverse reactions. This included a record of how often the vaccination was well tolerated and how often adverse reactions occurred. The type, severity and time interval between vaccination and reactions were also analysed. The data after six and twelve months were evaluated with regard to the frequency of possible SARS-CoV-2 infections and the severity of possible COVID-19 illness after the vaccination.
Reports on vaccination reactions were also included in the Paul-Ehrlich-Institut’s database of adverse reactions. The Paul-Ehrlich-Institut is legally obliged to collect and evaluate all reported suspected cases of adverse reactions and to forward them to the European database of suspected adverse drug reactions.
Updated: 19.04.2024
Suspected adverse reactions to vaccination are indeed recorded via regular spontaneous reporting. What is left unknown, however, is how many reactions are not reported for various reasons. The SafeVac 2.0 study enabled the Paul-Ehrlich-Institut to make quantitative evaluations of the possible adverse reactions, since the number of participants was known and adverse reactions were documented on a daily basis. The Paul-Ehrlich-Institut did not only obtain information via the study’s SafeVac 2.0 app on suspected adverse reactions, but also on the percentage of vaccinated persons who tolerated the vaccination well.
Updated: 19.04.2024
SARS-CoV-2 antigen tests are available as self-tests (antigen tests for self-use) and as professional tests (rapid antigen tests for use by trained personnel). Both are used to quickly and easily identify people with a very high viral load and therefore also the associated potential risk of transmitting the virus to contacts.
Antigen tests are used to detect SARS-CoV-2 infections and to protect against further spread. The advantage is that the results are available quickly. The downside is that they cannot detect SARS-CoV-2 infections with the same sensitivity as polymerase chain reaction (PCR) tests. PCR tests detect SARS-CoV-2 infections even with low viral loads, but they also take significantly longer to get a result.
Updated: 30.08.2024
Combination tests that detect infections with the SARS-CoV-2 coronavirus, influenza A and influenza B viruses and, in some cases, also respiratory syncytial virus (RSV) infections must receive a CE mark from a notified body in accordance with the EU In Vitro Diagnostic Medical Device Regulation (IVDR; Regulation EU 2017/746), which has been in force since 26 May 2022. The CE mark signifies that the product conforms with the applicable requirements.
The manufacturer must submit the complete technical documentation of the IVD product to a notified body in order to obtain a CE mark. The notified body then checks whether the product meets the basic safety and performance requirements detailed in the IVDR. If the requirements have been met, the notified body will issue a CE mark. The Paul-Ehrlich-Institut is not involved in test evaluation and therefore cannot provide any information about the reliability of the tests.
Several combination tests for the detection of SARS-CoV-2 and influenza A and B viruses, and in some cases also for the detection of RSV, have been added to the EU Common List of COVID-19 rapid antigen tests – or common RAT List for short. However, the combination tests on the list are professional tests, not self-tests. A search for the term “multiplex” in the list will bring up these combination tests.
The evaluation of the performance (sensitivity, specificity) of the tests included in the Common RAT List is performed only with regard to the detection of SARS-CoV-2. However, in the context of the conformity assessment procedure, the notified body generally assesses all components of the combination tests. Therefore, it can be assumed that a combination test that has received a CE mark meets the IVDR’s safety and performance requirements for all components.
The notified body that carried out the assessment is indicated by the four-digit identification number affixed to the packaging of the test next to the CE mark. All notified bodies are listed with their identification numbers in the NANDO list.
NANDO, which stands for New Approach Notified and Designated Organisations, provides information on notified bodies that are responsible for tasks such as assessing the conformity of in vitro diagnostic medical devices in accordance with the IVDR.
Specific information on a combination test may potentially be given by the notified body which has awarded the CE mark. Contact details are available via the NANDO listing.
Updated: 11.10.2024
In accordance with the new IVD Regulation (In-vitro Diagnostic Medical Device Regulation, IVDR; Regulation (EU) 2017/746), which entered into force in the EU on 26 May 2022, new SARS-CoV-2 antigen tests may only be placed on the market after undergoing a conformity assessment procedure and receiving a CE marking by a notified body.
Information on which antigen tests have received CE marking can be found in the databases of the EU Commission (see "Further information").
The EU Commission maintains several databases on testing methods for in vitro diagnostic medical devices (IVD). These are only available in English.
You can filter the database according to different criteria. If you select "All Rapid antigen test devices with CE Marking" under "Quick searches", the list of all antigen tests (professional and self tests) with CE marking is automatically displayed.
If you want to see a list of self tests with CE marking, you can filter the results further under "Show advanced filters". A filter field opens with a drop-down menu, in which you can select "Self test" and click on the blue "Add" button. You will then be able to select the "Self test" filter by selecting "Yes" from the drop-down menu. Clicking on "Search" will apply the new filter and search the database for self tests.
Whether you are looking for professional or self tests, the results are always shown in the form of a list. The results list, in addition to applying the selected filters, specifies the manufacturer, the test name (Commercial Name), the method and the format (Manual, Near PoC, PoC, Other).
Clicking on the black arrow icon to the right of each item on the list will lead to a page with detailed information about that test, such as information on its sensitivity and specificity. Some tests are offered as both professional and self tests – this is noted on the detailed information page.
Updated: 14.10.2024
The Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines does not make any recommendations for specific products.
Updated: 14.10.2024
The EU Common List of COVID-19 Rapid Antigen Tests – Common RAT List for short – is an informational document on rapid antigen tests provided by the Health Security Committee (HSC) of the European Union.
European Commisson: Public Health - Common List of Coronavirus Rapid Antigentests (Common RAT List)11 July 2022: Information for Manufacturers and Distributors: COVID-19 Antigen TestsUpdated: 14.10.2024
The HSC's Common RAT List (list of COVID-19 rapid antigen tests for professional use) was regularly updated during the SARS-CoV-2 pandemic following discussions in the EU Health Safety Committee's COVID-19 Diagnostic Testing Technical Working Group. The EU regulation on digital COVID certificates expired on 30 June 2023. The technical working group and its activities were formally terminated at that point. The last applications for the inclusion of COVID-19 antigen tests on the list could be submitted by manufacturers until 31 March 2023.
The list of CE-marked COVID-19 antigen tests was last updated on 17 May 2023. The performance of nearly 300 COVID-19 antigen tests that met stringent criteria were reviewed in additional studies and these tests were included on the list. A document with background information on the decisions of the technical working group was also made available since the last update. This document lists the tests that have been removed or were not included at all.
Updated: 09.10.2024
Yes, a false positive is possible. Prior to marketing, the manufacturer of an antigen test must run tests to determine the specificity and sensitivity of their in vitro diagnostic device (IVD) in order to receive the required CE marking. According to the European Commission's common specifications, the specificity of SARS-CoV-2 antigen tests must be at least 98%, i.e., in 98% of the examinations of samples that do not contain SARS-CoV-2, the test must be correctly negative. The sensitivity of the SARS-CoV-2 antigen tests must be 80%, i.e., in 80% of the investigations of samples in a very high viral load range (corresponding to a CT value in the PCR of about 25 and less), the test must be positive. The common specifications were published by the European Commission in mid-2022 and apply to tests newly CE labelled under the EU IVD Regulation. Tests that received a CE marking before May 2022 may continue to be marketed until May 2025 and do not have to meet these requirements.
However, antigen tests, like all IVDs, can in rare cases react positively with some samples, even if the marker – in this case the antigen of the SARS-CoV-2 virus – is not present at all. This can occur in some tests in the range of up to two percent of results (see above information on the required specificity). In order to confirm or rule out an infection, if the test result is positive, the result can be repeated with another antigen test or a PCR test.
Updated: 14.10.2024
Yes, a false negative is possible. SARS-CoV-2 antigen tests make it possible to quickly and easily identify people with a very high viral load and therefore also identify the associated potential risk of transmitting the virus to contacts. The lower the viral load, the lower the chance of transmission to close contacts and the lower the chance that the antigen test recognises the infection, i.e., the test is positive.
Prior to marketing, the manufacturer of an antigen test must run tests to determine the specificity and sensitivity of their in vitro diagnostic device (IVD) in order to receive the required CE marking. According to the European Commission's common specifications, the specificity of SARS-CoV-2 antigen tests must be at least 98%, i.e., in 98% of the examinations of samples that do not contain SARS-CoV-2, the test must be correctly negative. However, this also means that a false positive can appear in two percent of the tests. The sensitivity of the SARS-CoV-2 antigen tests must be 80%, i.e., in 80% of the investigations of samples in a very high viral load range (corresponding to a CT value in the PCR of about 25 and less), the test must be positive. These sensitivity requirements have taken into account the fact that the antigen tests can also produce negative results for some samples, in particular those containing SARS-CoV-2 in a lower concentration. The common specifications were published by the European Commission in mid-2022 and apply to tests newly CE labelled under the EU IVD Regulation. Tests that received a CE marking before May 2022 may continue to be marketed until May 2025 and do not have to meet these requirements.
A test can also produce a false negative if the sampling was not carried out exactly according to the instructions for use and therefore there is too little viral material in the sample. In addition, the performance of the SARS-CoV-2 antigen test used plays a major role.
Updated: 14.10.2024
It can be assumed that the COVID-19 vaccination does not lead to a positive test result after antigen or PCR tests.
After an mRNA vaccination, the so-called spike protein (S protein) is formed in immune cells and other body cells. The S protein confers an immune response. Almost all antigen tests listed in the Common RAT List and used in Germany for both professional and private use are based on the detection of another protein, the nucleocapsid protein (N-protein). Therefore, since antigen tests detect a virus protein other than the protein formed by the mRNA vaccination, the vaccination will not affect the test result. The summary of product characteristics provided with the test usually indicates whether the respective test is an S-protein or an N-protein based test.
Besides, the test is performed as a nasopharyngeal or throat swab. Even if the antigen test is designed to detect the S-protein, it appears highly unlikely that a sufficient amount of S-protein will be available in the mucosa cells of the nasopharynx to be recognised by the antigen test the sensitivity of which is only limited.
The quantitative real-time PCR methods for the detection of SARS-CoV-2 mRNA are usually based on the detection of two different virus genes (dual target principle: e. g. envelope [E] plus N2; N1 plus N2; orf1a/b plus E). Interference with a previously performed vaccination with SARS-CoV-2-mRNA, which codes for the S protein can be ruled out if this type of PCR test is used.
Updated: 09.10.2024
Yes. In order for an antigen test to be as conclusive as possible, the tester must precisely follow the instructions on how to collect the sample and perform the test.
Errors in sampling are a source of error that should not be underestimated in self-use antigen tests (self-tests).
These errors include: the length of time the swab is rotated during sampling (smear), the length of time and process of soaking the sample in the buffer, the number of drops to be applied, and the duration of the exposure time. Also, when reading the test result, the control band should be clearly visible. The band is also sometimes difficult to see when the result is positive. Even a faint test band that appears within the time specified in the instructions is to be regarded as SARS-CoV-2 positive.
Updated: 11.10.2024
Targeted evaluations by the Paul-Ehrlich-Institut through the end of May 2022 revealed no evidence that the detection of the Omicron variant is impaired by SARS-CoV-2 antigen tests. In addition, a query by the Paul-Ehrlich-Institut and the Federal Institute for Drugs and Medical Devices (BfArM) with the corresponding IVD manufacturers showed that most antigen tests use specific target sequences (epitopes) for the detection of the N protein, which are not affected by Omicron variant mutations.
This information on Omicron was presented in the Paul-Ehrlich-Institut tables as well as in the lists for self-tests and professional tests for the relevant tests ("Omicron detection according to the bridging test: Yes").
The Paul-Ehrlich-Institut offers archive versions of the SARS-CoV-2 antigen test lists for documentation purposes. These lists were discontinued pursuant to the amendment of the TestV dated 29 June 2022.
Archived Version of the Minimum Criteria for SARS-CoV-2 Antigen Tests Pursuant to Section 1 Paragraph 1 Sentence 1 of the TestV: Rapid antigen tests
PDF Document: Archived version of the "Comparative Evaluation of the Sensitivity of SARS-CoV-2 Rapid Antigen Tests" (Status: 30 May 2022)
Excel Table: Archived version of the "Comparative Evaluation of the Sensitivity of SARS-CoV-2 Rapid Antigen Tests" (Status: 30 May 2022)
Excel Table: Archived version of the BfArM list pursuant to the TestV - Antigen Tests for Self-Use (Status: 24 June 2022) (German only)
Excel Table: Archived version of the BfArM list pursuant to the TestV - Antigen Tests for Professional Use (Status: 24 June 2022) (German only)
Updated: 14.10.2024
If you notice that a test kit looks significantly different (discoloration, etc.) or doesn't work normally, this could indicate a quality defect. If you suspect a test kit has a quality defect, you can report it to the manufacturer. The manufacturer can then investigate the report and take any measures that may be necessary, such as recalling the product.
As a test user, you can also report possible quality defects to the Paul-Ehrlich-Institut. Please use the Paul-Ehrlich-Institut's online reporting form ("Incident report form for users and operators as well as for patients or their relatives in accordance with Section 3 or Section 4 of the MPAMIV", available in German only) to file an incident report. Any reports submitted via the Federal Institute for Drugs and Medical Devices (BfArM) online form are forwarded by the BfArM to the Paul-Ehrlich-Institut.
In accordance with EU Regulation 2017/746 (IVDR), in vitro diagnostic medical devices (IVD), including coronavirus (SARS-Coronavirus-2) antigen tests, fall within the remit of the Paul-Ehrlich-Institut. The Paul-Ehrlich-Institut is the competent higher federal authority for centralised report collection and risk assessment. The Institute records, examines and evaluates reported incidents. If reports concerning a particular COVID-19 antigen test accumulate, the Paul-Ehrlich-Institut contacts the manufacturer and asks them for a statement. As part of the risk assessment process, the Paul-Ehrlich-Institut can ask the manufacturer to take corrective or preventive measures.
Please note that the Paul-Ehrlich-Institut only contacts test users who report an incident if further information for the evaluation of an incident report is required. For organisational reasons, no acknowledgements of receipt will be sent.
Updated: 14.10.2024
