Vaccine development and approval
Like all medicines, vaccines are developed, tested and licensed in accordance with current regulatory guidelines and legal requirements, taking into account scientific guidelines. The goal is to provide a high-quality, effective and, above all, safe vaccine.
The development and research of a vaccine candidate in the laboratory takes about two to five years. First, the pathogen is analyzed and it is tested to which components of the virus the human immune system reacts and can build up protection (antibodies). This is followed by vaccine development and small-scale manufacturing for further vaccine testing in animals and humans.
In preclinical vaccine development, cell culture (in vitro, e.g., using human immune cells) and animal (in vivo) testing are used to test the immunogenicity (ability of the antigen to trigger immunization), efficacy and safety of the vaccine. Only after extensive testing and proof that the vaccine can be produced to a good quality and meet all the high requirements is the vaccine tested in clinical trials on voluntary study participants who have been informed of all possible risks. This also takes about two to five years.
The competent national authorities and ethics committees ensure that all studies are scientifically sound and ethically correct. Clinical trials prior to vaccine approval can be divided into three phases.
Phase I: As a rule, between 20 and 100 healthy volunteers are involved in order to test whether the vaccine elicits the expected reactions (immunogenicity) on the basis of laboratory tests. Primarily, however, safety and tolerability are tested here.
Phase II: Studies on several hundred volunteers will provide information on the best possible vaccine dosage for optimal protection, the side effect profile and the number of vaccinations needed for the best possible vaccination schedule.
Phase III: The final phase tests the vaccine in several thousand (in the case of COVID-19 vaccines, several 10,000) volunteers in the target population. It shows how effective the vaccine is in protecting against the disease compared to a control group (e.g. placebo) and what side effects, if any, may occur and with what frequency.
An official approval procedure is generally a prerequisite for a vaccine to be launched on the market. Approval means: testing of a vaccine for quality, efficacy and safety based on the data submitted by the applicant. In the EU, the approval process for COVID-19 vaccines is coordinated by the European Medicines Agency (EMA). National medicines authorities are involved in the technical review process.
The applicant submits marketing authorization dossiers for regulatory review according to clearly defined guidelines. These include regulatory information, manufacturing data, preclinical and clinical data, current literature, and information on planned long-term monitoring after approval. In addition to the vaccine antigen, the "actual active ingredient," all other ingredients of a vaccine are also evaluated. The European Pharmacopoeia, which has the character of law, defines these ingredients including their permissible limits.
A vaccine is approved if the risk-benefit ratio is positive, i.e. the benefits outweigh any risks. The "standard" approval process itself can take up to two years.
If the vaccine meets all scientific and regulatory requirements and its benefits outweigh its risks, the EMA's expert panel (consisting of representatives from the EU member states plus Norway and Iceland) issues a recommendation for approval of the vaccine to the European Commission, which then grants approval. This is valid for all EU countries; national approval is no longer required.
In addition, in Austria a batch release by an officially appointed medicines control laboratory is required (OMCL - Offical Medicines Control Laboratory of AGES). A batch is a quantity of a vaccine produced in the course of a uniform manufacturing process. Any medicines control laboratory in the EU or the European Economic Area (EEA) and Switzerland can perform batch release for vaccines if it meets the legal requirements. The release certificates must then be recognized throughout the EU or EEA and Switzerland. Manufacturers can decide for themselves to which drug control laboratory they submit their vaccine for batch release.
The development and approval process of COVID-19 vaccines is proceeding at an accelerated pace due to the severe impact of this pandemic. Extensive existing knowledge about coronaviruses and vaccine development is being incorporated.
To accelerate development, companies and research institutions are deploying significantly more human and financial resources in a shorter time than traditional development processes. Where possible, while complying with strict safety regulations, study phases are also conducted in parallel. In addition, manufacturers are expanding their production facilities at a much earlier stage of vaccine development than usual, so that large quantities of vaccine are available quickly after approval.
In addition, the European Medicines Agency (EMA) offers accelerated scientific advice to vaccine developers to drive development in a targeted and focused way.
Some vaccines against COVID-19 are being developed using new technologies that are expected to increase the quantities and speed of production compared to other methods of vaccine production. One of these new approaches is based on so-called messenger RNA (mRNA). In this approach, a small portion of the virus's "blueprint," which consists of RNA (ribonucleic acid), is produced in the laboratory and added to the vaccine. With this blueprint, cells of the human body can produce part of the virus - a so-called surface protein - which, unlike the virus, cannot cause infection and therefore cannot cause the resulting Covid-19 disease. The immune system recognizes this surface protein as foreign and produces defensive substances. When a vaccinated person becomes infected with COVID-19, the immune system is already prepared and can fight the pathogen much better. The mRNA in the vaccine is degraded by the body in a short time, which also ends the production of the surface protein. The mRNA cannot have any effect on the human genome, which consists of DNA. The two cannot combine and, moreover, the mRNA only reaches the cell area outside the nucleus where the DNA is located.
Accelerated approval procedure
The sooner a safe and effective COVID-19 vaccine is available, the sooner more serious effects of the current pandemic can be prevented. However, the benefits of a vaccine to protect against COVID-19 must far outweigh potential risks and side effects. The approval process ensures this - even at an accelerated pace - based on independent scientific assessments by the drug regulatory agency. In addition, close monitoring continues after vaccine approval.
In the case of COVID-19 vaccines, the quality, nature and scope of the regulatory review process is the same as or different from the "conventional" approval process. However, this will be accelerated in time with the following three measures to make much needed vaccines available.
1) Accelerated approval procedure
The maximum time frame for a standard approval procedure is 210 days, during which the approval authority actively works on the assessment of the submitted data. For the accelerated procedure, the maximum is 150 days. The assessment proceeds in the same steps and with the same quality, but the teams of the authorities use considerably more resources in a shorter time.
2) Rolling Review
In the case of promising vaccine candidates, the regulatory authorities can already begin to review existing data packages in parallel with the ongoing development. The subsequent "actual approval process" can then take less time, as large parts of the data have already been reviewed in detail.
3) Conditional Marketing Authorisation
This special form of "ordinary marketing authorization" can only be chosen for medicinal products for which there is an urgent need due to an emergency situation that cannot currently be met - this is fulfilled for the current Covid 19 pandemic. The applicant must first submit sufficient data to demonstrate the quality, safety, and efficacy of the vaccine and allow for a risk-benefit assessment. Certain data and information, to be precisely defined at the time of approval, must be submitted for peer review after approval has been granted. This is done with strict conditions and specifications as to when the outstanding information must be submitted to the authorities.
The conditional approval is valid for one year and can be extended if necessary. As soon as all conditions and requirements have been met, the conditional approval can be converted into a "standard" approval.
Regardless of which options are used to accelerate the procedure, the benefit-risk assessment by the EMA's panel of experts determines whether or not approval can be recommended. If there is a positive assessment and thus a recommendation for approval, the European Commission will issue the approval notification.
Vaccine safety after approval
Vaccines are continuously monitored not only before and during approval, but also as long as they are on the market. Pharmacovigilance is understood to mean a variety of methods and activities that are intended, among other things, to enable side effects to be detected, evaluated, understood and further prevented.
Part of pharmacovigilance is the reporting obligation of health care professionals in connection with the use of vaccines. It exists for human medicines for suspected adverse reactions and also for failure to achieve expected efficacy. However, not only healthcare professionals, but also patients and their relatives can report suspected adverse reactions. Reports must be submitted electronically or in writing to the Federal Office for Safety in Health Care (BASG).
All reports of suspected adverse reactions are collected throughout the EU. The analysis of all these data makes it possible to identify a possible new risk at national and European level (signal detection), to examine it closely and thus to contribute to greater drug safety for all patients. If a signal is detected, it is evaluated in the European context in the so-called PRAC (Pharmacovigilance Risk Assessment Committee) of the EMA. Depending on the outcome of the assessment, measures are taken such as the inclusion of new warnings in the product information or, in extreme cases, even the revocation of a vaccine's marketing authorization.
Vaccine information from the BASG
Last updated: 22.01.2022