Hello. This is doctor Russell Kohl, chief medical officer at TMF Health Quality Institute, with an updated COVID Medical Minute for you. The date of this one is August 30, 2021, and probably the biggest story in the last week has been the FDA approval of the Pfizer-COVID-19 vaccine on August 23. So, I’ve received a lot of questions about, so what does FDA approval actually mean, and why is there still an emergency use authorization. So, just wanted to take a few minutes to focus in on those questions for folks. So, to answer the second question first, so what does it mean that it is approved but there is still an emergency use authorization? Well, we’ll go through the approval process. What the COVID vaccine from Pfizer BioNTech was actually approved for is the two dose series against COVID-19 in individuals who are 16 years of age and older. That’s what the actual FDA approval was for. Now, we have been using it for a variety of other things, including a third dose in those who are immunocompromised, and being able to use it in individuals down to the age of 12, those sorts of items. At this time there is not enough post-marketing studies to be able to grant full FDA approval for those. So, in those populations of 12-15 year olds, and in the third does use for the immunocompromised, that can still occur, but that is not an FDA-approved use, that is still under an emergency use authorization. So, what’s the process for FDA approval? So, there’s actually a four-phase process that goes into place an order for a drug to receive an FDA approval. And that’s accomplished by the FDA Center for Drug Evaluation and Research, or CDER. So, there’s obviously the pre-clinical aspects. This is when they are just doing the initial developments of the drug, doing animal testing and those. At the conclusion of that, they file what’s called an investigational new drug application to the FDA, and includes all of that information. Now, historically, the fastest vaccine ever created was the mumps vaccine, which back in 1967 took four years to develop. The difference is, the messenger RNA technique, lets us use a standard vaccine delivery mechanism to actually deliver a new vaccine against a different pathogen. So, in this case, a lot of the pre work around the drug development, animal testing and those sorts of things have already been accomplished. Some of it going back for years, so that moved us into a phase one step on August 12 of 2020. Now, they did combine the phase one and phase two studies. The difference is, the phase one study is a very, very small group, 20 to 80 people, which is looking for healthy volunteers, and they are looking purely for side effects. They are looking for just side effects and any information about metabolization and excretion of the vaccine. Now the phase two actually goes up and starts to look at effectiveness. This is a phase that would have hundreds of folks in it to determine whether or not does this drug actually work with regards to preventing the disease that it is supposed to. So, this is a controlled trial so it is a randomized, placebo controlled study that looks for the efficacy of the vaccine. Now remember, this is still a relatively small study, so the idea that we would be able to wait and see who gets COVID and who doesn’t in the trial isn’t really a realistic expectation based upon just simply the number of people involved. And so, in those trials, what the definition of effectiveness was, was looking at whether or not your body created a CD4 T cell response against the virus. So, could you actually develop the antibodies needed to keep the virus from replicating? So, with success in their phase one and phase two trials, they moved to phase three. Phase three is typically thousands of people where you are looking overall at safety and effectiveness, different populations and different dosages, what happens with it in a much more real world environment. The Pfizer phase three study started on July 27 of 2020 and ultimately had 43,661 participants enrolled at over 150 clinical trial sites in the U.S., Germany, Turkey, South Africa, Brazil and Argentina. So, it was a pretty wide-reaching and diverse study that was accomplished. Six months later, the FDA actually granted the emergency use authorization for Pfizer in December. So, the question becomes, so what’s the difference between the emergency use authorization and the approval process, because ordinarily after phase three comes phase four, which is where it comes out to the market and we are able to do post-marketing evaluation, look at how it is performing in the real world. Well, the part that most people forget about is the new drug application process. And so this is actually looking at how should it be labeled, what should the instructions say specifically, is the application filled out correctly, and most importantly, they actually have to physically inspect every facility where the vaccine would be manufactured. Given the circumstances of the pandemic, the FDA decided they would go ahead and move forward with the emergency use authorization, which let the drug be widely used starting in December of 2020, while they completed that ongoing NDA review. So, with that NDA being completely finished by July of 2021, August 23 they proceeded with the FDA approval, which moves us into phase four. Phase four is the post-marketing phase of drug approval. Fortunately, due to the widespread use of VERS, and a pretty significant reporting system, we probably have more post-marketing information on the COVID vaccine than we do on any other drug at its release. That will be ongoing monitoring and something that is open to the public that you can always take a look at what are we finding about post-approval issues with the vaccine. So, hopefully that helps you understand the process a little bit more of just what it means to be FDA approved. It is a rather long process, and, as I mentioned earlier, we still have the emergency use authorization for a couple of the uses, specifically those in kids 12 to 15, and a third does in the immunocompromised, which should give you some degree of additional comfort recognizing that it is only when we have the adequate data to prove safety and effectiveness that we are able to move all the way to FDA approval, which is what we have achieved for the general population. So, with that being said, feel free to reach out if you have any ongoing questions or comments. Happy to hear those. And until then, keep up the good fight, and keep making the world a better place.