Vaccine development is a long and expensive process usually taking up to 10 to 15 years of research and development before entering the market. With the global COVID-19 pandemic a 10-15-year timeline could not be accepted. According to World Health Organization there are currently 51 clinical phase and over 160 preclinical phase candidate vaccines in the pipeline. From these, Pfizer and BioNTech BNT162b2 and Moderna Biotech Spain S.L. mRNA1273 vaccines are already waiting for marketing authorization assumed to be finalized by the end of December 2020. In the U.K. Pfizer and BioNTech BNT162b2 vaccine was granted an emergency-use authorization in the beginning of December 2020 and vaccinations will begin shortly. How was it possible to do all of this in just 10 months? Is it even possible to develop a safe and effective vaccine within this timeline?
Fast-tracked vaccine development is the result of many factors in addition to the preexisting vaccine development and production technologies: The cause of the disease became known early on and the genetic code was shared among the researchers. There is good knowledge about messenger RNA (mRNA) technology—messenger RNA techniques have been used in molecular biological studies for decades albeit using this technology in vaccines is completely new. Lastly, the broad network of experts as well as the support of COVID-19 European Medicine Agency pandemic task force team combined with close cooperation with the regulatory authorities is also an important factor.
Traditionally, viruses have been grown in cell cultures or in eggs from where viruses have been purified, isolated and attenuated for use in vaccines. For example, the swine flu vaccine Pandemrix® was manufactured this way. Unfortunately, Pandemrix® vaccine included a core protein that was not found in the other similar swine flu vaccines and this caused narcolepsy in some of the genetically susceptible individuals. In current influenza vaccines, the core protein is different. It should be noted that swine flu vaccines were released to the market already after phase II clinical trials—not after phase III.
Pfizer and BioNTech BNT162b2 and Moderna Biotech Spain S.L. mRNA1273 vaccines are using mRNA technology. In this technology, viruses are not grown. The virus’s membrane protein, so-called spike protein´s, building instructions are packed as mRNA to nanostructured lipid carriers (fat particles), which carry the building instructions into the human cells. In the cell, by using its own machinery a protein is produced from the mRNA instructions. The protein induces an immune reaction in the body and creates a memory for possible future encounters with the virus. This creates immune protection against the virus. If the mRNA is not used for the production of the protein, it will be degraded. By using this technology mRNA vaccine can be manufactured in a week whereas the old technique took up to months.
To speed up market entry, the vaccine development was accelerated. In the accelerated pathway, the three different phases of the clinical research (phase I, II, and III) are carried out simultaneously providing still the same number of subjects to be tested as in traditional development. To date, almost 44,000 people have participated in the phase III clinical trial of the BNT162b2 vaccine and 30,000 people have participated in the same phase clinical trial for the mRNA1273 vaccine.
During the clinical trials vaccine manufacturers have been providing the regulatory authorities with research data as soon as it has been completed, allowing the use of rolling assessment for the European Medicines Agency and enabling accelerated evaluation and approval process for the vaccines. Even after marketing authorization is granted vaccine manufacturers will be obliged to send the authorities monthly safety reports as well as to conduct ongoing research to continue the vaccine safety and effectiveness studies.
Could rolling assessment and an accelerated approval process be used in the approval of pharmaceuticals in the future too? This is a discussion we should continue.
Writer: Milla Alkio M.Sc. (Cell and Molecular Biology), MD (Medical Doctor) student