The U.S. Food and Drug Administration (FDA) plays a critical role in protecting public health by ensuring that drugs, medical devices, and biologics are safe and effective. However, some FDA approvals have sparked debate, drawing attention from the media, lawmakers, patient advocacy groups, and industry. These controversies often stem from questions about the strength of the evidence, the approval pathway used, or the balance between patient access and safety.
This article explores a few of the most discussed FDA approvals in history and the lessons they offer for future regulatory decision-making.
1. Aduhelm (Aducanumab) for Alzheimer’s Disease – 2021
In June 2021, the FDA granted accelerated approval to Aduhelm, a drug developed by Biogen for Alzheimer’s disease. The decision came even though clinical trials had produced conflicting results. An advisory committee overwhelmingly voted against recommending approval, citing insufficient evidence that the drug could slow cognitive decline. The FDA approved Aduhelm based on its ability to reduce amyloid plaques in the brain, a biomarker associated with Alzheimer’s, rather than clear evidence of clinical benefit. The decision triggered resignations from three advisory committee members and widespread debate about the use of surrogate endpoints in drug approval.
Key takeaway: Accelerated approval can expand patient access to potentially beneficial treatments, but it also raises concerns when long-term clinical outcomes remain uncertain.
2. Vioxx (Rofecoxib) – 1999
Vioxx, a painkiller from Merck, was approved by the FDA in 1999 as a safer alternative to traditional nonsteroidal anti-inflammatory drugs (NSAIDs) for arthritis and acute pain. However, within a few years, evidence emerged linking Vioxx to increased risks of heart attacks and strokes. In 2004, Merck voluntarily withdrew the drug from the market. The controversy centered on how early the cardiovascular risks were known and whether the FDA had acted quickly enough to protect public health.
Key takeaway: Post-market surveillance is critical, as some safety issues may only emerge after a drug is widely used.
3. Plan B One-Step – 1999–2013
The emergency contraceptive Plan B faced a long and contentious approval process. Initially approved by the FDA in 1999 as a prescription-only medication, it took more than a decade of legal battles, political pressure, and scientific review before it became available over the counter without age restrictions in 2013. The drawn-out timeline was due less to questions of safety or efficacy, and more to political and moral debates about access to emergency contraception.
Key takeaway: Regulatory decisions can be influenced by societal and political factors, even when scientific evidence is clear.
4. OxyContin – 1995
OxyContin, an opioid painkiller manufactured by Purdue Pharma, was approved in 1995. The original labeling suggested that the drug’s controlled-release formulation made it less addictive than other opioids, a claim that was later found to be misleading. The widespread prescribing of OxyContin contributed to the opioid crisis, leading to lawsuits, billions in settlements, and changes in opioid prescribing guidelines.
Key takeaway: Labeling claims can have profound public health consequences, underscoring the need for rigorous review of marketing materials.
Lessons for the Future
These cases illustrate the delicate balance the FDA must strike between granting timely access to innovative therapies and ensuring those products are safe and effective. While controversial approvals can open new treatment options, they can also lead to public mistrust if perceived as premature or influenced by non-scientific factors.
Greater transparency in the decision-making process, robust post-market monitoring, and clear communication with the public are key to maintaining confidence in the regulatory system.
About EMMA International
EMMA International is a global consulting firm specializing in quality, regulatory, and compliance services for the life sciences industry. We support companies in navigating complex FDA requirements, from premarket submissions to post-market surveillance, ensuring products meet the highest standards of safety and effectiveness.
For more information on how EMMA International can assist, visit www.emmainternational.com. Contact EMMA International at (248) 987-4497 or by email at info@emmainternational.com to learn more.
References
Carome, M. (2021). FDA’s controversial approval of Aduhelm. BMJ, 374, n1681. https://doi.org/10.1136/bmj.n1681
U.S. Food and Drug Administration. (2023). Postmarket drug safety information for patients and providers. https://www.fda.gov/drugs/drug-safety-and-availability/postmarket-drug-safety-information-patients-and-providers
