From Development to Application
The Paul Ehrlich Institute consistently applies its scientific and regulatory expertise to the entire life cycle of vaccines and biomedicines against COVID-19.
Scientific advice accelerates development
In 2020, with its scientific and regulatory advice, the Paul-Ehrlich-Institut intensively supported the development of vaccines and biomedicines for the prevention and treatment of COVID-19 – from the first promising results in the laboratory, via the transition to clinical trials, through to marketing authorisation. The Innovation Office coordinated 61 instances of scientific advice on a national level. The experts from the various sections and units carried out 29 instances of scientific advices on the behalf of the European Medicines Agency (EMA). A new feature is the pilot scheme for of bi-national advice pilot together with agencies from other European countries. There were 21 of these in 2020, with nine of them being for medicinal products against COVID-19.
Clinical trials: a prerequisite for marketing authorisation
In 2020, 29 clinical trials of vaccines and biomedicines for the prevention and treatment of COVID-19 commenced in Germany – each of which had been previously verified and approved by the Paul-Ehrlich-Institut. The Clinical Trials unit approved the first clinical trial of convalescent plasma in April 2020; by the end of the year it had approved seven. From the start there was also a focus on monoclonal antibodies (mAbs): both proven and newly developed mAbs for treating COVID-19 were tested in clinical trials, as well as cocktails of several mAbs. Eight clinical trials of mAbs commenced in 2020. The vaccines also picked up speed: the Paul-Ehrlich-Institut approved the first clinical trial of a COVID-19 vaccine in April 2020; by the end of 2020, twelve had been approved.
Marketing authorisation: as fast as possible, but safe
At the end of 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the first vaccine from BioNTech as first COVID-19 vaccine for marketing authorisation; the European Commission issued the authorisation on the same day. In early 2021, this was followed by the authorisation of a second mRNA vaccine from Moderna and a vector vaccine from AstraZeneca. The Paul-Ehrlich-Institut worked intensively on these marketing authorisations – as a co-rapporteur for the European marketing authorisation of the mRNA vaccine from Moderna, but also as a commenting member state in all cases. Three rolling reviews – the successive evaluation of marketing authorisation documents for COVID-19 vaccines – commenced in 2020. For monoclonal antibodies, the experts at the Paul-Ehrlich-Institut played the lead role in nine European marketing authorisations.
Shift work for batch release testing
The first batches of the COVID-19 vaccine had already been tested and were ready for use when the European Commission issued the first marketing authorisation on 28 December 2020. For this purpose, experts from the Paul-Ehrlich-Institut had developed, installed and certified test methods at an early stage. New test methods for testing the innovative mRNA vaccines presented a challenge. In this context, the combination of research and regulation expertise at the Paul-Ehrlich-Institut, which is almost unique in Europe, as well as its intensive integration within the network of Official Medicines Control Laboratories (OMCLs), proved to be invaluable. Immediately after the marketing authorisation, the vaccinations against COVID-19 could begin with tested batches. The Paul-Ehrlich-Institut also prepared batch testing for hyperimmune globulins – pooled plasma from people who have recovered from COVID-19. With the introduction of shift work, the sections were able to comply with social distancing rules and cope in good time with the urgent demands placed on them.
Inspections – remote and on site
The manufacture of vaccines and biomedicines against COVID-19 resulted in the rapid creation of new production capacities, and a large number of clinical tests were carried out which had to be urgently inspected on site. Strict travel restrictions, however, made necessary inspections for biomedicines difficult. The Inspection section approached the issue proactively: they played a leading role at European level in the development of uniform, harmonised procedures for remote monitoring (remote inspections / distant assessment). They identified the possibilities and limitations and developed potential solutions. In this, the inspectors and product experts were involved in 52 remote inspections for COVID-19 vaccines and other biomedicines: 35 at national level and as specialist support for federal state authorities, 17 as experts for the European Medicines Agency (EMA). A further 61 national inspections, as well as 32 on behalf of the EMA, were performed as regular on-site visits.
Safety of medicinal products – consistent monitoring
Even before the first COVID-19 vaccinations had been administered, the Pharmacovigilance I unit was preparing to closely monitor COVID-19 vaccines. It could build on the knowledge that had been gained in the clinical trials. However, it was now necessary to follow up on possible very rare side effects that could only be detected in a very large number of vaccinated individuals. Tolerability also had to be monitored in a timely manner, as a large number of people were beeing vaccinated in a short period of time. For this purpose, Pharmacovigilance developed the mobile phone app SafeVac, which regularly asks vaccinated people about their condition. Immediately after the start of vaccination, the unit published regular safety reports in which the experts evaluate the reported suspected cases and continuously review the safety profile of the COVID-19 vaccines.
Setting Standards for COVID-19 Tests
Tests must be standardised. For this purpose, globally recognised reference materials are required. The in vitro diagnostics testing laboratory (PEI-IVD) was involved in the development of an international WHO standard, established in December 2020, as well as a reference panel for anti-SARS-CoV-2 antibodies. The IVD testing laboratory also developed its own reference panel for SARS-CoV-2 antibody tests, which covers the antibody range from high to low positive, in order to be able to check the sensitivity of diagnostic antibody tests in routine use. Until December, PEI-IVD has evaluated 28 rapid antigen tests in a study, in june 2021 there were already 140. Since 11 December 2020, the tests that have received a positive assessment have been listed on the Paul-Ehrlich-Institut website.
- Essential work in Times of Pandemic
- From Development to Application
- Communication Creates Transparency
- SafeVac – Observational Study via App
- Upgrade for High-Risk Tests
- Safe Tests for Highly Dangerous Viruses
- COVID-19: Plasma from Recovered Patients
- Blood Safety Increased Further
- Data Collection for Optimising Treatments
- Alternative Tests for Animal Welfare
- Animal Welfare in Practice
- First European Marketing Authorisation
- Gene Therapy for Muscular Atrophy
- Vaccine for the Fight Against Ebola