If a vaccine trial is successful
If a vaccine trial is successful, an approval phase kicks in. It’s a stringent review process, involving a panel of experts who will check every part of the trial and the documentation. Image Credit: Gulf News Archives

DUBAI: Let’s say 'Vaccine A' has been found safe and effective against COVID-19. And, following human trials, it’s been approved today. Do we all get it tomorrow?

The answer is most probably "No". Unless you're one of the trial volunteers, in which case, you've had it already.

But at least for now, with Vaccine A, let’s say the three stages of clinical tests are completed, and that’s awesome. Let's all be grateful to the numerous scientists and thousands of volunteers who took a huge risk with their lives, by taking an unproven shot.

Time to celebrate? Perhaps. But not too soon.

There’s a danger: A jab that works only marginally may get approved and then get hyper-promoted, discouraging dozens of vaccine developers from continuing with their work.

A volunteer receives an injection from a medical worker during the country's first human clinical trial for a potential vaccine against the novel coronavirus, at the Baragwanath hospital in Soweto, South Africa, on June 24, 2020.
A volunteer receives an injection from a medical worker during the country's first human clinical trial for a potential vaccine against the novel coronavirus, at the Baragwanath hospital in Soweto, South Africa, on June 24, 2020. Image Credit: Reuters

Before a new approved COVID-19 vaccine even hits your arm, a lot of things need to happen. How a licensed shot will be produced, scaled up and distributed, will be the next big hurdles.

Q: A faster approval journey for a new COVID-19 shot?

Yes. All eyes are trained on this one thing — a vaccine that is both effective and safe. And fast.

Still, each candidate vaccine must go through rigorous tests. It’s an elaborate, methodical (and costly) process involving lab work, then animal and human trials. This typically lasts several years. Even then, there’s no guarantee it would work.

Now, it is being shortened — from several years to possibly just months, due to the dire need for a COVID-19 shot around the world.

Q: What is the approval process like?

If clinical trials are successful, the approval phase kicks in. It’s a stringent review, involving a panel of experts who will check every part of the trial and the documentation.

The three-phase trials is actually part of a much bigger process, which involves six-phases. In general, these are the steps in vaccine development:

  • (1) Exploratory stage
  • (2) Pre-clinical stage (animal trials)
  • (3) Clinical development (human trials)
  • (4) Regulatory review and approval
  • (5) Manufacturing
  • (6) Quality control

How a vaccine is developed:

Vaccine development process Phase I II III
Image Credit: Gulf News / FDA

World Health Organisation (WHO) has also published vaccine regulation guidelines. They cover clinical evaluation and regulation of vaccines, and good manufacturing practices for biological products, among others.

Q: Why is  a review by independent experts important?

An independent review process is designed to allow both science and reason — balancing the benefits against the risks — to decide on the merrits of a vaccine candidate(s).

Q: Who conducts the review and evaluation of vaccines?

In the United States, Food and Drug Administration (FDA) conducts the process through its 15-member panel, called the Vaccines and Related Biological Products Advisory Committee (VRBPAC), which reviews and evaluates trial data.

The review focuses on the following: Safety, effectiveness and appropriate use of vaccines and related biological products intended for use in the prevention, treatment or diagnosis of human diseases.

Q: Who are the committee members and what is their authority?

Committee members vote, including the chairperson.

Members and the chairperson are selected from among authorities knowledgeable in the fields of immunology, molecular biology, rDNA, virology; bacteriology, epidemiology or biostatistics, vaccine policy, vaccine safety science, federal immunisation activities, vaccine development -- including translational and clinical evaluation programmes -- allergy, preventive medicine, infectious diseases, paediatrics, microbiology and biochemistry.

Q: Which agency is responsible for regulating vaccines?

In the US, the Center for Biologics Evaluation and Research (CBER), under the FDA, is responsible for regulating vaccines. CBER is one of the six main centres under FDA, which is a part of the US Department of Health and Human Services (HHS).

CBER is responsible for assuring the safety, purity, potency and effectiveness of biologics and related products (such as vaccines, live biotherapeutics (probiotics), blood products, cell, tissue and gene therapies).

Most countries have their own vaccine regulators, generally based on WHO guidelines.

Q: What is the vaccine licence application process?

The sponsor of a new vaccine follows an approval process, which typically includes the following:

  • A) An Investigational New Drug application
  • B) Pre-licensure vaccine clinical trials
  • C) A Biologics License Application (BLA)
  • D) Inspection of the manufacturing facility
  • E) Presentation of findings to FDA’s Vaccines and Related Biological Products Advisory CommitteeExternal (VRBPAC)

Q: How do we ensure no shortcuts are done in vaccine production that could jeopardise public health?

A vaccine production facility must always obtain a licence. Monitoring of the vaccine and of production activities remains as long as the manufacturer holds a licence for the vaccine product. This includes periodic facility inspections.

Regulators can require a manufacturer to submit the results of their own tests for potency, safety and purity for each vaccine lot. In the US, FDA may also require each manufacturer to submit samples of each vaccine lot for testing.

Q: What is the manufacturing, inspection process?

Once a Biologics Licence Application (BLA) is approved, the manufacturing facility also undergoes a pre-approval inspection, during which, production of the vaccine, as it is in progress, is examined in detail.

Following FDA's review of a licence application for a new indication, the sponsor and the FDA may present their findings to FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC).

This non-FDA expert committee (scientists, physicians, biostatisticians and a consumer representative) provides advice to the agency regarding the safety and efficacy of the vaccine for the proposed indication.

Image Credit: Gulf News / FDA

Q: What about labelling?

Adequate product labelling is a must. This will allow health-care providers to understand the vaccine's proper use, including its potential benefits and risks. The labels must also communicate with patients and parents, and to safely deliver the vaccine to the public. The product labelling must undergo a "usability" test.

On May 26, 2020, US-based biotechnology company Novavax said they have started enrolling participants in Australia for a clinical trial of its coronavirus vaccine candidate, NVX-CoV2373. Preliminary results from the Phase 1 portion of the trial are expected this month (July 2020).

Q: After production, do vaccines undergo checks?

Yes. Checks on the production process of vaccines post-approval will continue. The FDA will oversee the manufacturing processes after approval, to ensure continuing safety.

After licensing, monitoring of the product and of production activities, including periodic facility inspections, continue.

Q: Is approval a guarantee that the vaccine will work as intended, without adverse side effects?

No. Until a vaccine is given to the general population, all potential adverse effects cannot be anticipated.

Therefore, many vaccines undergo Phase IV studies.

These are formal, on-going studies on a vaccine after it is approved, licensed and released in the market.

To report adverse side effects, the FDA has introduced the Vaccine Adverse Event Reporting System (VAERS) to identify problems after marketing and public use begins.

Q: A vaccine is approved today, will I get it tomorrow?

Again, realistically, the answer is "no". But the answer depends on where you are in the world. Watch out for our next vaccine explainer.

Sources: FDA, CBER