Vaccine Development

Now that you have a grasp of the science of vaccines, what about the regulation of vaccines?  How are they tested? Approved? What is the difference between an Emergency Use Authorization and FDA Approval? Read on!

Vaccine Development: The Stages 

Exploratory Stage:

Scientist identify natural or synthetic antigens such as virus like particles, weakened viruses, or bacteria. For years, scientists  have been researching coronaviruses and already knew that the spike protein was the best candidate for any vaccine development. 

Pre-Clinical Stage:

Tissue culture, cell culture and animal studies are done to assess safety and whether there is an immune response.  Using tissue culture of human cells, they can get an idea of  cell response, and maybe a bit about dosing. Might do some challenge studies with animals, ie give an animal the virus and then the vaccine and see if it works. Many vaccines fail at this stage.

These two stages were already mostly done by January 2020 when we knew we had a pandemic.  For example, mRNA vaccines had been researched since the early 2000's, and viral vectored vaccines since 2014.  Coronaviruses are a well-studied group, and they already knew the spike protein was the best target. 

Investigation of a New Drug application to FDA.

Once approved, vaccine is subject to 3 phases.  It can take a long time to get the paperwork done for this application. These phases are very expensive to do, so normally pharmaceutical companies will wait and see if each phase works before going on to the next. They don't want to invest any more money than they need to, if the vaccine turns out to be a dud. 

The FDA handled this paperwork VERY quickly! 

Phase I:

There are 20-80 subjects who must volunteer. There is strict enforcement of informed consent - to verify that the volunteers understand all the risks. This phase is  non-blinded- ie patients and doctors know who is in the placebo group and who is getting the vaccine. This will  test safety and the type and amount of immune response.  It is  hard to get enough volunteers for this stage

Phase II:

There are usually several 100 volunteers. There is randomized, placement in the  placebo vs. vaccine group. This stage studies safety, immune response , dosing, schedule, method of delivery

Phase III:

There are tens of thousands of volunteers who are placed randomly in placebo or vaccine trials. This is double blinded (neither the patient nor doctor know who is in which treatment). They are examining safety, side effects (low frequency events), vaccine efficacy. Does it prevent disease? Prevent infection? Produce antibodies, etc?

• • • A large number of people wanted to volunteer for these trials because they wanted to do something to help with the pandemic. That made these stage go much faster than normal. Instead of taking 6 months to get enough volunteers, they had their cohorts within weeks or a month. 
    • Normally vaccine development is a hurry up and wait situation. Lots of down time between each phase while the pharmaceutical company decides if it is worth the financial investment.  
    • Because many governments around the world (US, UK, European Union, Russia, China) paid companies to do the work NO MATTER if they companies were successful or not, companies started the planning for each Phase, before the previous one was done. This meant there was no lag time between phases (which can be years in some cases!).

Submit to FDA for Emergency Use Authorization- when there is a public health emergency 

When there is a public health emergency ( ex: Covid-19 or Ebola), the  results from each Phase are submitted to the FDA. The FDA decides if they can go ahead and manufacture the product (authorizes the product). In an EUA, the FDA allows the company to begin manufacturing before the trials are done. This means that the company might be out a lot (A LOT) of money if the trials don't pan out.  There were at least 10 different vaccines for Covid-19 that turned out to not offer protection. Those companies had invested a lot of money in the process but wouldn't have had a product to sell. In this case, many governments were backing the investment so they weren't financially harmed.  But we needed lots of companies trying to make vaccines, so at least one or two of them would work out. 

Submit for FDA Approval 

The difference between an EUA and normal FDA approval is the timing.  FDA makes its decisions based on its analysis of the benefits and risks for the intended population who will receive the vaccine, as well as the disease(s) to be prevented.  A typical FDA team is comprised of: physicians, chemists, statisticians, pharmacologists/toxicologists, microbiologists, experts in postmarketing safety, clinical study site inspectors, manufacturing and facility inspectors, and labeling and communications experts.

Tracking Side Effects Once a Vaccine is Administered

The Vaccine Adverse Event Reporting System (VAERS) is a national vaccine safety surveillance program co-sponsored by the Food and Drug Administration (FDA) and the CDC. VAERS collects and analyzes information from reports of adverse events (side effects) that occur after the administration of US licensed vaccines. Reports are welcome from all concerned individuals: patients, parents, healthcare providers, pharmacists, and vaccine manufacturers. To submit a report, use VAERS’ reporting pageexternal icon.

Other Countries

Other countries have their own version of the FDA and they use the same basic type of process as above for testing vaccines. Many countries will use the FDA approval as a stand in for their own approval process. In other words, if the FDA has approved a vaccine, then the vaccine is accepted by the UK or Slovenia, etc. 

And Vaccine Trials

See the captioned version of 'Vaccine Clinical Trials 101' video

Now take a mini-quiz on this material so that you are ready for class.