While several minor developments occurred between 1938 and 1962, the next significant milestone in drug regulation was in 1962. Once again, a tragedy caused by drugs motivated the American government to strengthen the FDA. Thalidomide, marketed as a sleeping pill and a treatment for morning sickness, had an unexpected side effect that resulted in the birth of thousands of malformed babies across Europe. Thankfully, FDA Medical Officer Frances Kelsey had blocked thalidomide from being sold on American markets. Kelsey’s decision to bar thalidomide garnered public support and interest for stronger drug regulation. Congress took advantage of the political momentum to pass the Kefauver-Harris Drug Amendments to the FD&C Act. This legislation required pharmaceutical companies to not only prove safety but also effectiveness of their medicine. Significantly, the Kefauver-Harris Drug Amendments were a foundation for extensive clinical trials of medicines, which, of course, is a cornerstone of modern pharmaceutical development. Throughout the 1960s, government contractors retroactively tested drugs approved between 1938 and 1962 to ensure their effectiveness as well as their safety, further reinforcing the emphasis that the FDA now placed on drug efficacy.[17]
Additionally, the 1962 legislation shifted the regulation of drug advertising from the Federal Trade Commission to the FDA, requiring that companies submit a marketing application for approval. Three years later, in 1965, Congress passed the Drug Abuse Control Amendments, which gave the FDA more regulatory control over amphetamines, barbiturates, hallucinogens, and other drugs that could potentially be abused. This function would, by the end of the decade, be moved to another agency that ultimately became the Drug Enforcement Administration.[18]
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Throughout the 1960s, 70s, and 80s, Congress continued passing legislation that improved labels of foods, drugs, cosmetics, and medical devices. In 1967, the government enacted the Fair Packaging and Labeling Act (FPLA), requiring all consumer products in interstate commerce to be “honestly and informatively labeled,” clarifying what is inside the box or bottle of the product. The basic requirements of the FPLA include a statement that identifies the product, the name and location of the manufacturer, and the net weight, measure, or count of the product inside.[19] A bag of Doritos, for example, will note on the bottom front that they are “Tortilla Chips” and list a net weight, and Frito-Lay’s location will be listed on the back, right beneath the ingredients. Every household consumer product has the same information somewhere on the label, allowing people who purchase these products to be informed of what exactly they are buying.
In 1970, the FDA required oral contraceptives to have information about the pill’s benefits and risks within the package. This was significant, since, before 1970, patients received all drug information from either the prescribing doctor or the pharmacist who gave them the medicine. Patient package inserts, as such, meant that the customers taking the drug directly were made aware of the potential side effects, health risks, and other information about the medicine. With the birth control pill’s surging popularity during this period and evidence that women were not fully told the potential side effects of the contraceptive, the FDA announced that they would require the pill’s manufacturers to place the insert in every package of pills. This insert, written by the FDA to be understandable by every layperson, allowed women to make informed choices about whether they wanted to take the drug. A series of controversies followed this requirement, both against (from the medical and pharmaceutical industries) and for (from feminist groups) the insert. Ultimately, the FDA decided to compromise on a shorter package insert, which gave a brief overview of the pill’s major health risks and advised women who wanted more information about the pill to ask their doctor for a longer and more comprehensive booklet written by the American Medical Association, the FDA, and the American College of Obstetricians and Gynecologists. While this compromise was not the most satisfactory in terms of informing patients of all potential health risks of a medicine (indeed, a comprehensive package insert was not required in oral contraceptives until 1978), it regardless set an important precedent for future consumer information regulations that fully informed patients about the health risks of medicines.[20]
In 1982 and 1983, responding once more to tragedy, Congress and the FDA increased anti-tampering regulations. After seven people in Chicago died after taking Tylenol laced with cyanide, the FDA issued Tamper-Resistant Packaging Requirements in 1982. These requirements were then codified by Congress and signed into law by President Ronald Reagan in October 1983. The Federal Anti-Tampering Act made it a crime to tamper with packaged consumer products; per FDA regulations, tamper-resistant packages had to have at least one indicator or barrier to visually signal to consumers that the product was altered.[21] For example, many bottles of common over-the-counter medicine such as Advil and Claritin have foil seals and cotton balls, a two-layer series of indicators that the product inside was not altered between production and the consumer opening the product.
In 1984, the Drug Price Competition and Patent Term Restoration Act became law, which expanded the number of drugs that could be approved by an abbreviated new drug application (ANDA). This allowed generic drugs to be sold more easily, requiring tests to show that the drugs had the same therapeutic effect as the brand name medicine rather than the expensive clinical safety and effectiveness trials of the brand name manufacturers. These tests had to prove that the active ingredient entered the bloodstream over the same amount of time and the same extent as the brand-name drug, showing that the generics were just as safe and effective without having to repeat the thorough trials that the name brand already had. This enabled generics to be more commonplace, which in turn helped consumers purchase important drugs like ibuprofen (Advil) or acetaminophen (Tylenol) more affordably.[22]
In 1992, Congress passed the Prescription Drug User Free Act (PDUFA). This act allowed the FDA to collect fees from drug companies, essentially creating a tax to increase FDA resources and expedite drug review times. The PDUFA increased FDA staff by 60%, enabling life-saving medicines to be approved much more quickly. This legislation had to be reauthorized every five years; President Joe Biden signed the latest reauthorization on September 30, 2022, ensuring that PDUFA would remain until its next renewal in September 2027.[23]
Perhaps the most significant major legislation regulating medicine was the FDA Modernization Act (FDAMA) of 1997. This law, designed to serve as an update to the 1938 legislation, enacted a sweeping number of changes across the food and drug regulatory industry. In addition to renewing the PDUFA for the first time, this bill codified a number of FDA regulations and practices that further accelerated review of new medications, increased patient access to experimental drugs and medical devices, and made an expanded database on clinical trial results so that patients were more informed. Furthermore, if a manufacturer planned to discontinue a medicine that patients depended on to stay alive or healthy, they would be given advanced notice so that they could find an alternative with their physician.[24]
The FDAMA also allowed drug companies to share peer-reviewed journal articles about off-label uses of their products. This was on the provision that the company filed another application to establish the safety and effectiveness of this use within a certain timeframe, effectively submitting it for FDA approval. Off-label uses are when a doctor prescribes a drug for use different from the FDA-approved drug to treat a medical condition. This can range anywhere from prescribing a different amount from the recommended dosage on the bottle to using the medicine for a disease it is not approved to treat, such as a chemotherapy approved to treat one type of cancer but prescribed to treat another.[25] The FDAMA changes meant that doctors were more informed about these off-label uses, potentially allowing them to prescribe drugs that could save lives based on scientific research rather than the often-longer FDA approval process.
The FDAMA was the last major milestone in drug regulation to date. While the W. Bush and Obama administrations did pass legislation related to the FDA, notably bioterrorism preparedness regulation after 9/11, and the Food Safety Modernization Act of 2011, the regulation of medicine has mostly remained the same since 1997. In May 2018, President Donald Trump signed Right to Try Legislation, which amended Federal law to allow certain experimental and unapproved drugs that passed the basic levels of FDA safety testing to be administered to terminally ill patients. These patients had to be unable to participate in clinical trials and tried all other approved treatment options.[26] With this law, Americans facing death from terminal illness are now able to try one last medicine or treatment before succumbing to their disease or conditions.
On December 29, 2022, Biden signed the FDA Modernization Act 2.0 into law. The FDAMA 2.0 is a bipartisan amendment to the FD&C Act that authorizes alternatives to animal testing in their safety and effectiveness trials. Instead, the law allows for nonclinical tests conducted using modern technology to limit the cruelty of animal testing. While it does not completely eliminate animal tests, the FDAMA 2.0 hopefully marks the beginning of the end of animal testing, allowing for more modern regulations that maintain the high safety and effectiveness standards set by the FDA while preventing the suffering of biological test subjects.[27] It remains to be seen whether Congress and the President enact more laws to reduce or phase out animal testing.
The FDA has come a long way since Harvey Wiley’s “Poison Squad.” Even though it isn’t the most prominent federal agency, it is one of the most significant in ensuring that Americans remain healthy. Without the many landmark drug regulations, the state of American medicine would be as it was in the turn of the century: a veritable wild west without any true safety precautions.