Breaking through the COVID vaccine jargon
Over the last few months, the debate over the COVID vaccine has generated more heat than light. Terms like Phase-1, Phase-2, Phase-3, pre-clinical trials, human trials, FDA approvals and vaccine efficacy are as esoteric as they are intimidating. Currently, Johnson & Johnson, Pfizer plus BionTech, AstraZeneca plus Oxford and Moderna are the four names that are in the COVID vaccine race. All are in the Phase-3 of clinical trials, so let us understand what it means and how soon the COVID vaccine becomes a reality? Here is a quick primer.
Stage 1: Pre-Clinical Stage: How will the vaccine build immunity?
All vaccines are aimed at building immunity towards a particular strain of virus or bacteria. It is like your body has immunity up to a point to cold, fever and other regular ailments. Technically speaking, this stage will focus on finding the right antigens. What exactly are antigens? These antigens are foreign substances that trigger an immune reaction in your body. An antigen can be natural or synthetic and requires in-depth research.
This is the stage at which the company identifies the vaccine candidate after a thorough evaluation of several alternative candidates. The vaccine candidate is chosen based on the best immune response and also the best evidence of protection. In the case of COVID, most of the top pharma companies already had tested antigens for Ebola, HIV, and SARS, which made the task simpler and quicker. At this pre-clinical stage the research team zeroes in on the antigen or protein that best stimulates the immune system to react and get rid of the novel Coronavirus.
Stage 2: Testing the vaccine candidate for safety and dosage (Phase-1 and 2A)
With the vaccine candidate tested theoretically in the laboratory, the next stage is limited sample test.
- It begins with Phase-1 testing. In this phase, the vaccine candidate is tested in a small group of adults and the sample size ranges between 20 and 80. The idea is to evaluate the safety of the vaccine candidate and measure the immune response generated.
- In Phase-2A the research team determines the most effective dosage and expands safety measures. At this stage expected reactions to the vaccine are studied including adverse reactions. For COVID; Phase-1 and 2A were combined to compress launch time.
- The next stage is the Phase-2B or Phase-3, in which the pool of people receiving the vaccine increases. We look at this stage in greater detail.
This stage is about determining how effective the vaccine is? At this stage of the clinical trial, more volunteers receive the vaccine to study its effectiveness. This stage can stretch across different regions and thousands of persons. Normally, Phase 3 testing is done by dividing the sample into 2 groups. Half the group is assigned to receive the vaccine and the other half receives a placebo. They are all followed up closely for a sustained period to see if they develop COVID-19 symptoms. Normally, if reactions are adverse and serious, the regulator instructs to stop trials till technical changes are made.
This is where all the large pharma company vaccine candidates are right now. At this stage, the vaccine effectiveness is measured in percentage terms and then gradually expanded to a larger sample size to see if vaccine effectiveness ratio is sustained.
Stage 4: Regulatory approvals to market around the world
This will come only after Stage-3 is satisfactorily completed. Once Phase-3 Trials are successful, the vaccine manufacturer submits an application to regulators (USFDA or EC ), where the clinical trial data is reviewed to satisfy on vaccine safety and effectiveness. FDA approval also requires that the manufacturer exhibits consistent manufacturing process, ability to scale in consecutive batches and consistently induce the same immunity in people. The manufacturing of the vaccine starts only after this point.
Stage 5: Satisfying that the vaccine will be perennially safe
Regulatory agencies across the world don’t stop after approving the manufacture of the vaccine. Even after the vaccine is approved, regulators like USFDA continuously monitor production, inspect facilities and keep testing the vaccines for potency, safety and purity.
Pharmaceutical companies in association with the WHO have worked against time to try and deliver the vaccine ahead of time. The real test will be getting the Phase-3 through a larger sample and actual launch. WHO expects the vaccine launch in the second half of 2021!