Vaccines are biological formulations that provide immunity against a disease. It can take anywhere between 1 year to 10-15 years to develop a vaccine to combat a disease.
Recently, the World Health Organization estimated that it would take a minimum of 18 months to develop and release a vaccine against the novel coronavirus. For many of us in lockdown, facing anxieties over an uncertain future, vaccines seem to be a shining beacon of hope.
However, this 18-month period itself is a fast-track compared to the standard procedure and vaccine development of the past.
A normal vaccine formulation can take anywhere between 10-15 years, or sometimes more. This time allows researchers to fully understand the disease, its pathogen, and ensure that the vaccines against the disease are safe. To understand this further, let’s look at the steps it takes to create a new vaccine against a disease.
There are a few steps to the process of making a vaccine:
- Basic research and the exploratory phase
- Pre-clinical phase
- Clinical phase
- Distribution to Markets
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In a war, an opponent must understand their enemy before meeting them on the battlefield. Similarly, scientists must understand a disease and its pathogen before attacking it.
Researchers study the pathogen’s basic biology: its genome, proteins and enzymes, its shape, structure and size, its reproduction pattern, how it causes the disease, and the immune response against the disease to uncover different strategies to fight back against it.
It is difficult to estimate how long basic research will take to yield answers. Different diseases behave differently in the body; some diseases provide easier answers than others. Basic research provides the backbone for what can be considered the first effort into creating a vaccine formulation.
The Exploratory Phase
After scientists have an understanding of the pathogen, they move on to targeting the pathogen’s Achilles’ heel. They decide which vaccine strategies (live, attenuated or subunit vaccines, for example) are best suited to arm the immunity-generating substance against the disease.
Researchers identify different antigenic molecules that induce an immune response against the disease, and pick the best-suited preliminary formulations.
Most of the work here is trial and error and experimentation. This all takes time and some degree of luck to come up with a formulation that has a chance of working in humans.
This phase usually lasts for 2 to 4 years.
Animal Models And Cell Cultures
Before moving on to humans, the formulation is tested on animals to check for safety and efficacy. Animal models and cell cultures mimic the human system. Once inside a living system, the vaccine might not work as intended, so animal models provide crucial information on how the human system might react to the vaccine.
Cell cultures are a more ethical way to detect how vaccines work, and provide insight on the cellular and molecular changes that the vaccine might cause.
The pre-clinical phase can take anywhere from 1-2 years.
Around this time, a company might also take a little “breather”, slowing its pace to analyze data on the formulation, and outline any possible improvements or risks the vaccine might have before proceeding to the next step.
Clinical trials are where many vaccines get denied formal approval. Just because a vaccine formulation works in animal models does not guarantee that it will work in humans.
To move on to the clinical trial phase, manufacturers—usually private pharmacological or biotechnology companies that specialize in vaccine development—will have to get approval from the appropriate governmental body first.
In the United States, the Food and Drug Administration overlooks all approval for applications of Investigative New Drugs (IND). Similar procedures are in place all over the world.
Clinical Trials Happen In Three Rounds
The three clinical trials are set apart by two features—sample size and whether a placebo is used. The sample size matters, since a larger sample means more robust data and more reliable results. Using a placebo in a vaccine helps ascertain whether the vaccine works significantly better than either a normal salt or sugar solution, or better than a past vaccine.
Phase I of clinical trials consists of a small group of volunteers, no more than a 100. In this phase, researchers closely monitor the vaccine’s safety. They check whether the vaccine causes any harmful side effects, allergies, or other adverse reactions. This is a crucial step and often a hurdle that many formulations do not pass. Vaccine safety is of the utmost importance, since it is technically a disease agent and is composed of foreign matter being injected into the body.
Many formulations go back to the drawing board based on data from Phase 1 trials to improve the formulation in safety.
If the vaccine passes Phase I, it moves on to phase II, consisting of a larger volunteer group, where the vaccine’s efficacy in humans is compared to a placebo, a formulation either of simple saline, a sugar solution or an existing vaccine.
Phase III is the final phase, wherein the vaccine is subjected to the “real” threat. Here, the pool of volunteers is the largest, in the thousands, and every parameter of the vaccine like safety and efficacy are checked again across this larger data set.
These trials must be double-blind in nature, especially Phase III. In double-blind trials, neither the administrator nor the patient are aware of whether they are dealing with a placebo or the test vaccine. The double-blind method is designed to eliminate human bias as much as possible, allowing the raw data to speak for itself. They are the gold standard in the world of drug testing.
These phases often have sub-phases where sample sizes might differ. In these clinical trials, information on how long it takes for the vaccine to provide immunity after the vaccine is administered, how long immunity against the diseases lasts (only for a few months, or for several years), etc. All these phases together can take more than 5 years to complete.
Moving To The Market
After the stages outlined above, companies will now rush to get their vaccines licensed and acquire its patents. These procedures can take several months to review, negotiate and authorize. Beyond this, manufacturing and production must also be streamlined.
This timeline is an estimation. Vaccine development can take more than 15 years, in some cases. For example, a vaccine against human papilloma virus went into the transition between the pre-clinical to clinical phase in 1993 and took another 9 years to move forward again.
On the flip side, vaccines for influenza can be made in about 6 months. Influenza viruses mutate at a rapid rate, requiring a new vaccine against new strains to be created every year. Whenever a new strain is identified, manufacturers move quickly to make a new vaccine against it. This is possible due to basic research and data collected over decades, which gives researchers a reliable skeleton to work with.
Organizations are fervently trying to create a vaccine against diseases like HIV and malaria, but a successful formulation has yet to be discovered. These diseases have been researched since the 20th century, and have caused the deaths of millions around the world.
The process of science may be streamlined so that it is achievable to create new drugs and vaccines in a systematic manner. Yet science is also performed by humans and our still-evolving technology. Sometimes it takes years for a newer technology to open doors that make it possible to more rapidly create a vaccine against a disease.
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References (click to expand)
- Buckland, B. C. (2005, April). The process development challenge for a new vaccine. Nature Medicine. Springer Science and Business Media LLC.
- Vaccine Testing and Approval Process | CDC. The Centers for Disease Control and Prevention
- (2013) Pandemic influenza vaccine manufacturing process and timeline. The World Health Organization
- Fast Track | FDA. The United States Food and Drug Administration