Though the federal government has had an interest in vetting the safety of agricultural products since 1848, the Food and Drug Administration (FDA) as we know it didn’t come into being until 1930. The essence of the agency came into effect in 1906 with the passage of the Pure Food and Drugs Act. What led President Theodore Roosevelt to sign the Pure Food and Drugs Act, and how does the FDA exert its regulatory powers to apply strict scrutiny to the numerous products under its purview?
The origins of the FDA
Motivations for the regulation of food
Following the Industrial Revolution of the late 1800s, more and more Americans began clustering in urban centers. With that transition, Americans became less capable of growing and creating their own foods and goods and instead grew increasingly reliant on manufactured versions of the same.
The centralization of these industries led to greater efficiency in terms of production, but there were tradeoffs. A grassroots campaign, the Pure Foods Movement, began to materialize in the 1870s with the backing of the U.S. Department of Agriculture’s chief chemist, Harvey W. Wiley, and local women’s clubs like the Ladies Health Protective Association. In 1906, Upton Sinclair’s The Jungle—a mortifying expose on working conditions in a Chicago meatpacking plant—let slip that processed meat was often rotten or tainted with rats that had slipped into the machinery, often laced with rat poison themselves.
Examples of early banned products and additives in foods
In the early 20th century, it was common practice to add a variety of adulterants to products like milk in order to improve appearance and shelf life. To investigate the damaging effects of these additives, Wiley lobbied Congress to fund a series of trials requiring 12 healthy male volunteers to eat nothing but predetermined meals, three times a day, for one year. Alongside the meals, the volunteers were required to consume a sample of the current additive of interest. Through this process, Wiley’s Poison Squad determined that a variety of additives to food products could indeed cause health issues.
The first additive targeted by Wiley, borax—now a common household cleaner and laundry detergent booster—had long been used as an adulterant that interacted with animal proteins in a way that improved the appearance of freshness. Through the controlled experiments of the Poison Squad, it was shown that borax caused a variety of ailments, including headache, digestive pain, and poor taste in the food it was mixed with.
Another additive targeted by Wiley was formaldehyde, the chief component of embalming fluid, and it was added to milk as a preservative. In a 1907 report prepared by the Assistant Commissioner of the Illinois State Pure Food Commission, 30-35% of milk was in substandard condition, with much of it containing formaldehyde. Modern issues with formaldehyde persist, including its usage in popular keratin treatments like the Brazilian blowout.
Used at the time to brighten the green color of canned peas, copper sulfate is now known to cause nausea, vomiting, and severe damage to blood, liver, and kidney cells, as well as damaging other bodily tissues. Death from extreme doses wasn’t out of the question.
Motivations for the regulation of drugs
Though the 1906 Food and Drugs Act empowers the federal government to regulate foods, subsequent events would demonstrate that the government lacked the authority to effectively solve the issues. In 1911, the Supreme Court case U.S. v. Johnson determined that companies only had a legal obligation to accurately label the contents of their products, but bore no responsibility when it came to making claims about the potential benefits of the product.
The 1912 Sherley Amendment attempted to close this loophole by prohibiting false therapeutic claims that could defraud consumers, but enforcement proved difficult. It wasn’t until 1937 when demand for a liquid version of the medicine sulfanilamide, a treatment for streptococcal infections, led to the deaths of 107 people. Formulated with the toxic ingredient diethylene glycol in order to create the liquid Elixir Sulfanilamide, the S.E. Massengill Co. only evaluated the new liquid product for aesthetic qualities like flavor and fragrance—but not for toxicity.
It was assumed that the backlash from selling toxic goods would deter corporations from cutting corners in such a way, and thus it wasn’t illegal to sell a toxic compound as part of a drug formulation. The sulfanilamide disaster changed that, and in 1938, the Food, Drug, and Cosmetic Act was passed by Congress and signed into law by President Franklin D. Roosevelt in order to increase the FDA’s purview when it came to monitoring the safety of consumer products. False therapeutic claims were reined in, safe limits for toxic compounds were set, and abuses in food quality were addressed by requiring inspections and enabling legal injunctions.
Steps of the FDA Approval Process
Now that we’ve delved into the historical motivations behind the FDA, let’s revisit how the FDA ensures that our foods, cosmetics, and drugs are safe enough for mass consumption.
There are four formal steps to the FDA approval process for a new drug. In a future post, we will walk you through how an interested party might explore the possibility of identifying a new therapeutic compound and performing the necessary tests to vet the potential drug for use in clinical trials. Let’s walk through the steps that occur once the FDA has given the greenlight for clinical trials in human subjects.
If the potential therapeutic has made it this far, it will now undergo separate phases in human subjects in order to support its candidacy for approval and general use by the public.
The emphasis of Phase I clinical trials is to determine the safety of the therapeutic in human subjects, as well as to lock in a meaningful yet tolerated dosage. The phase often involves up to 100 healthy subjects and lasts up to one year, with the studies being conducted over several months.
The emphasis of Phase II clinical trials is to determine the efficacy of the therapeutic in human subjects while also looking for the emergence of meaningful side effects. This phase involves around 200 human subjects and uses control subjects—receiving placebos—in order to determine a meaningful comparison between the drug and the placebo. Studies in this phase last from months to years, while the phase itself can last up to two years.
If a potential therapeutic makes it through Phases I & II, then it enters Phase III clinical trials. This phase investigates the drug in a few thousand subjects over the course of 1-4 years, with the goal of the phase being to solidify the overall benefit of the drug compared to placebo over a sustained period of time.
At this final stage of the FDA approval process, the company in question submits a New Drug Application, or a request to market a drug for a specific indication. This indication could be something like treatment for a particular disease, or to address a certain condition. In the case of hair loss, only two compounds, minoxidil and finasteride, have received FDA approval to treat that particular condition.
Once the application has been submitted, the FDA has 60 days to decide whether to file the application or to assign it for further review. The FDA takes into consideration the submitted data from all clinical and preclinical trials, the methods of manufacturing the compound, and the proposed labeling of the drug for the conditions it aims to treat. In some cases—like we witnessed with the vaccines for COVID-19—this may or may not involve the recommendation of a special advisory committee, which may or may not expedite the process if extraordinary circumstances warrant that it do so.
At the end of the process, the FDA either issues a letter of approval or a complete response with further instructions.
What happens after the FDA approval process?
In certain cases, the company that’s successfully submitted the New Drug Application may seek to conduct additional post-approval studies, part of what’s commonly known as Phase IV of the clinical trials. These trials seek to confirm the safety profile that was elucidated during the prior stages of review by using additional subjects, increasing the confidence that rare side effects will be detected. It also confirms the comparative effectiveness of the treatment against any alternatives. Part of this additional screening can be carried out using MedWatch, a system that receives voluntary reports of problems from clinicians in the day-to-day of prescribing the therapeutic to their patients. In this way, the company can expand its pool of data and increase its confidence in the results of its development.
Why is it important to understand the FDA approval process when it comes to hair loss treatments?
As we’ve mentioned before, when it comes to hair loss, there are only two treatments that are currently approved by the FDA: minoxidil and finasteride. Both of these products were originally developed for other indications—in the case of minoxidil, ulcers and hypotension, and in the case of finasteride, treatment for an enlarged prostate. Because of the extreme costs and labor involved in bringing a new drug to market, repurposing an old one on the basis of data that emerges during the clinical trials for a new indication can be financially advantageous: The discovery and preclinical data still has validity, and the investment can contribute to a new treatment so the prior work isn’t wasted.
Part of the consideration for bringing a new product to the market involves a type of calculus that aims to evaluate whether the investments in research and development can be recouped by sales. What is the size of the target market? How much does it cost to manufacture the therapeutic, and how much can be charged for it? Will those potential profits represent a worthwhile investment?
Many companies, either due to a lack of resources to take the risk or due to an evaluation that the formal approval process isn’t worth the cost, choose instead to market their product directly to consumers as a supplement. This means that certain claims—like claiming that the supplement directly treats or solves a condition or disease—cannot be made, but it remains a possibility that such strong claims aren’t needed to persuade consumers to purchase the product.
Are FDA-approved products more effective than those that are not?
Not necessarily. FDA approval implies efficacy, but given a level playing field, it remains a strong possibility that products that either await approval or have yet to be submitted for consideration could be equally as effective as those that have already been subject to the strict scrutiny of the FDA.
Products that have garnered the seal of approval by the FDA should certainly be trusted as known quantities—this is the advantage of scientific rigor and centralized government agencies that can make these determinations on our behalf. However, there exist other options that could be viable solutions to your issues, including hair loss, alopecia, and other conditions. Without the scrutiny of the FDA, it does mean that you as a consumer bear the burden of scrutiny and skepticism when it comes to determining safety, efficacy, and whether the potential benefits associated with the product outweigh the costs.
If you’d like to know more about the implications of the FDA approval process, read on for our follow-up in the series!