For decades, vaccine development has occupied a significant position in medical research, owing to its effectiveness against diseases. Today, hundreds of companies manufacture vaccines, and the business has rapidly grown. Millions of people have been receiving vaccines for decades. Like all medicine, vaccines undergo rigorous and extensive testing to ensure safety and effectiveness before their release.
Each vaccine must undergo different phases of development, during which they are screened and evaluated to find the right antigens to boost immunity. No humans are tested in the preclinical stage; rather, animals are tested for safety against potential disease. If an immune response is triggered in animals, a vaccine is tested on a trial basis in humans in five phases.
Since the dramatic spread of the new coronavirus last year, efforts have been made to clinically develop a COVID-19 vaccine. Following are the four phases of vaccine development:
Preclinical stage
The first phase of vaccine development comprises intensive research to identify foreign agents or antigens that trigger an immune reaction in the body. This process is often extensive and can take up to four years.
In January 2020, Janssen Pharmaceuticals began investigating candidates for a potential SARS-CoV-2 vaccine. By March 30, the company was able to announce that a lead candidate had been identified.
“Usually, you look at several different vaccine candidates and ultimately choose the one that has the best immune response and evidence of protection,” said Macaya Douoguih, head of clinical development and medical affairs at Janssen Vaccines. This work generally lasts one to two years.
“Our investigational vaccine produces an antigen, or protein, which should cause the body’s immune system to react and get rid of the novel coronavirus,” said Dirk Redlich, head of chemistry, manufacturing and controls development and clinical trial material manufacturing at Janssen Vaccines.
Phases 1 and 2
In phase 1, vaccine testing is done on 20-80 people to measure immune response. In phase 2a, the most effective dose is discovered to increase immunity. Any side effects of the vaccine, like headache, swelling, muscle pain and mild fever, are also observed. After several months of these phases, phase 2b and 3 trials begin targeting more people. Janssen combined phases 1 and 2 trials into Phase 1/2a for its investigational SARS-CoV-2 vaccine.
Phase 3
In this phase, Janssen scientists administer the SARS-CoV-2 vaccine to thousands of COVID-19-vulnerable people. Before vaccination, they are tested for SARS-CoV-2 virus, and then are given a placebo as well as the vaccine.
“It may be that some people do go on to develop COVID-19 even after having been vaccinated, but they may have substantially milder symptoms than those who develop COVID-19 in a control group,” Ms Douoguih said. Janssen hopes to get results in this phase in a year with trials on almost 60,000 people.
Regulatory approval
Manufacturers ask for permission from the European Commission or the US Food and Drug Administration (FDA), and clinical data is continuously reviewed for safety. For FDA approval, “among the things we have to show is that the manufacturing process is consistent and that we can produce consecutive batches of vaccine that induce the same immunity in people,” Ms Douoguih said. After approval, the vaccine is manufactured.
Phase 4
The last phase involves the regulation of vaccine production and manufacturing facilities. Its potency and safety are monitored continuously by the FDA, which also monitors any adverse effects of the vaccine. The end result: A potentially life-saving vaccine for COVID-19 that’s “been developed in months,” Redlich said. “But there is an urgent medical need for us to do this, and do it safely.”
On the successful vaccine trials, Pfizer’s chair and CEO said in a media release, “Today is a great day for science and humanity. The first set of results from our Phase 3 COVID-19 vaccine trial provides the initial evidence of our vaccine’s ability to prevent COVID-19.” Tal Zaks, chief medical officer of US biotechnology company Moderna, said, “This interim Phase 1 data suggests that our COVID-19 vaccine candidate, mRNA-1273, can generate durable neutralising antibodies across all age groups, including in older and elderly adults.
This gives us further optimism to expect that the high level of efficacy recently demonstrated by the vaccine to prevent COVID-19 disease will be durable.”
Vaccine storage and handling
Vaccine effectiveness and success are also measured by its storage and handling. Temperature plays a crucial role. If any vaccine is exposed to a higher or lower temperatures than those recommended, it can have health implications and reduce potency. Most vaccines must be kept cold, as temperature fluctuations can damage them, especially inactivated vaccines.
For Moderna’s vaccine, temperatures of -25C to -15C are recommended. Long exposure to multiple temperatures can have adverse side effects.
For Pfizer’s vaccine, temperatures of -80C to -60C are required. Any error, mismanagement or carelessness in storage can cost companies thousands of dollars.
Developing countries face more significant financial losses. Bill Gates, co-chair of the Bill & Melinda Gates Foundation, is quoted in an interview in the Financial Times as saying, “The price needs three tiers, where rich countries are paying back a lot of the fixed costs, middle-income countries are paying back some of the fixed costs, and poorer countries are paying a true marginal cost.”
Mismanagement can also harm patients and lead to loss of life. Not vaccinating is better than administering mishandled vaccines.
Only good vaccine management ensures adequate immunisation. From manufacturing to administration, the vaccine must be stored properly and kept in a temperature-controlled environment during transportation.
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