In North America, and maybe the entire English-speaking world, we have a term: “Snake Oil Salesman” – someone who is selling a miracle cure (“Snake oil”) with so many claims but is completely ineffective. In the early 1900’s this was incredibly common. Traveling salesmen traveled the countryside, selling cures to unsuspecting people then leaving town before their customers learned that it was useless, or worse. I always think of this music video when I think about those people:

But they weren’t as charming as Michael Jackson and Paul McCartney, or as innocent. Some ingredients were just not sensible. Cures for colicky babies might contain alcohol, morphine or opium. It worked for sure, but at what cost?

It wasn’t just snake oil salesman in carts making mistakes. In 1901, much of the diphtheria antitoxin was made using horse serum. One horse, Jim, in St. Louis, Missouri was one of the “donors”. Unfortunately at one point he caught tetanus and the antitoxin was responsible for the deaths of thirteen children. In 1902, The Biologics Control Act was passed giving the government control over processes used to make biological products.

In 1905, a book by Upton Sinclair called The Jungle came out, exposing the meat packing Industry, making it illegal to sell adulterated food or drugs. (Yes, it’s only been illegal for a little over 100 years). It also regulated label claims. No longer could you legally sell a “cure-all” with no proof that it did what it said. Soon after, in 1906, the US Food and Drug Administration (FDA) was created.

In the 1930’s, another tragedy involving the use of a dangerous solvent in an oral suspension of sulfanilomide resulted in the death of 107 people. This was only the most extreme of examples, though. Some products caused mercury poisoning, a contraceptive was sold that, if improperly inserted could puncture the uterus, eyelash dyes were sold that caused blindness. In response the Federal Food, Drug and Cosmetic act of 1938 was passed. This set of laws required that not only did we have to prove our drugs’ effectiveness, they had to be safe as well. Looking back, this is yet another of those laws that was introduced shockingly late in the game.

While technologies have changed and laws have, over the years, been refined, the mandate since then has been that drugs, including vaccines, must be safe and effective.

But what does this mean? How do we ensure this? And who gets to make the judgement as to whether or not it’s true?

From the beginning, drugs must be clinically proven to be safe and effective with properly designed studies with statistically significant sample sizes. Data must be gathered and processed in a methodical way with oversight. Then, when compiled, the volumes of data are given to FDA and other regulatory bodies for review to determine if the data really supports the safety and efficacy claims.

Coronavirus-related information: Several things feed into how quickly a clinical trial can be completed and approval gained. Here are a few of them:

• Participant availability: Many drugs are extremely targeted – one particular type of cancer, one neurological disorder, a rare blood disease. The more rare or specialized the condition, the more challenging it may be to find a statistically significant pool of people to participate in the trial. Gathering data to support a company’s claims could take a significant amount of time. In the case of COVID-19, whether we are talking about therapeutics to treat the condition or vaccines to prevent it, we were in the position of having no shortage of people to participate.
• Money: As we all know, most of those working to develop drugs are doing it directly or indirectly for profit. They could be corporate supported grants or companies themselves. For-profit companies have to choose how much to support a clinical trial. Do you have a small trial with a few people working on it or do you create a large trial with many people supporting it? In the case of COVID-19, there was a great deal of money available from governments and other sources and a potentially good profit to be earned. Budget, which is often a barrier in drug development was not.
  • It is worth noting that this played a large part in the R&D leading up to the vaccine discoveries as well. Companies are always very careful where they direct their money, but again, money was much less of an obstacle in this case. Combine this with some of the other research already done relating to the 2003 SARS outbreak, a very similar virus, and you can see how things sped up rapidly.
• Regulatory Review: You will be glad to know that a clinical submission to FDA and other regulatory bodies is an enormous set of documents full of technical reports, patient profiles and history, raw data, and statistical analysis. This is not just binders but whole shelves full of data to be carefully reviewed. In the normal workflow, this document is compiled and sent to the agencies for review. Then, depending on their queue, they will get to it when they can and then spend a long time reviewing it. The COVID vaccine timeline would not allow for this as lives were literally being lost every day that it took to review this. As a result,, COVID-related submissions were prioritized over others. Now those packages were being brought to the front of the line. Not only that, the agencies were no longer waiting for the final package to be assembled and sent. As data was obtained and summarized it was sent. Therefore the reviews could be current. Instead of waiting weeks or longer for a review to complete after the end of the trial, the timeline could be significantly compressed, all without sacrificing the quality of the review.

But this is just the beginning. The regulations continue throughout the entire production process and in the upcoming entries we’ll talk about the rules that govern the people, equipment, and buildings in which the drugs themselves are made.