The U.S. Food and Drug Administration's job is to regulate drugs and medical devices. However, just because a drug or device is FDA-approved does not mean it is safe.
The FDA is the government agency responsible for reviewing, approving and regulating medical products, including pharmaceutical drugs and medical devices. It also regulates various other products, including food, cosmetics, veterinary drugs, radiation-emitting products, biological products and tobacco.
Protecting public health is a key priority of the FDA, and for good reason. Tens of millions of Americans rely on prescription and over-the-counter drugs to stay healthy, with as many as 3 billion prescriptions written each year. Safety concerns prompt the FDA to pull one to two drugs and six to eight medical devices from the market annually.
All medications and medical devices come with inherent risks, but it is the FDA’s duty to address serious risks that can be avoided and managed. Before any drug or medical device can gain approval to be sold in the United States, it must first meet the FDA’s regulatory standards. The FDA reviews the safety and effectiveness of medical products not only before they are approved, but also after they are sold to consumers and used.
But FDA approval does not necessarily mean that a product is safe, or that its effectiveness has been confirmed in a clinical trial. The FDA clears some medical products as long as the manufacturer can prove they are substantially similar to a product already on the market.
Even with a system in place to ensure a new product’s safety and minimize its risks, unexpected complications can arise. If adverse event reports or post-marketing surveillance indicate that a medical product is causing preventable injuries to consumers, the FDA can coordinate with the product’s manufacturer to issue a recall.
FDA Funding and Other Controversies
For decades, critics of the FDA have argued that the agency is more concerned with keeping the pharmaceutical industry happy than protecting the public from dangerous drugs and medical devices. At the heart of this stance is the source of the agency’s funding.
Prior to 1992, the U.S. Treasury provided review funding for the FDA. This changed, however, when industry-wide pressure for faster review and approval of medical products convinced Congress to pass the Prescription Drug User Fee Act (PDUFA). This law requires pharmaceutical firms to pay fees to accelerate the FDA’s review of new drugs and devices they plan to introduce to the market.
User fees accounted for only 7 percent of the costs related to the drug review process in 1993. The influence of user fees grew year after year since then, surging to 60 percent of drug review costs by 2009. In the FDA’s budget proposal for 2014, the agency requested $4.9 billion, with 94 percent of funding coming from industry user fees.
With a vast majority of review funding coming directly from the firms seeking approval, many are concerned there is an unhealthy relationship between the government and the pharmaceutical industry. According to Sidney Wolfe, M.D., co-founder of Public Citizen’s Health Research Group, the relationship has motivated the FDA to rapidly approve drugs that should not have made the cut.
Faulty Review Procedures
The FDA employs controversial methods for approving drugs and medical devices such as fast track programs and the 510(k) premarket clearance process. For example, FDA scientists complained about faulty review procedures that approved medical imaging devices for mammograms and colonoscopies that may expose patients to dangerous radiation.
The scientists called it “a substantial and specific danger to public safety.” And the FDA reacted by “spying” on their communications. In 2010, the FDA secretly gathered more than 80,000 computer documents from employees, the New York Times reported.
The agency used spy software to capture computer key strokes, personal emails and even followed messages line by line that scientists sent to Congressional officials, journalists and others.
According to the agency, it was an effort to stop the spread of negative and defamatory information about the agency.
Employees Pressured to Approve Devices
Some workers in the medical device review department of the U.S. Food and Drug Administration (FDA) say they feel pressured to approve devices that they are not sure are safe, according to a new survey reported in the Minneapolis Star Tribune.
Almost 1,000 FDA employees — 17 percent of the total solicited — took the survey. Of those, 158 survey participants worked in the center for devices. About 25 percent said they felt pressured to approve products “despite reservations about the safety, efficacy or quality of the product.”
The Vioxx Scandal
One oft-cited example of poor FDA safety oversight involved Vioxx, a non-steroidal anti-inflammatory drug (NSAID) linked to a five-fold increased risk for heart attack and stroke. Merck & Co., the drug’s manufacturer, voluntarily recalled Vioxx in 2004 amid serious safety concerns.
In 2000, one year after the FDA approved the drug, a clinical trial identified numerous heart risks associated with the drug, but Merck downplayed Vioxx’s dangers. In a congressional investigation into how Merck and the FDA handled the Vioxx recall, documents revealed that Merck knew about the severe health complications but heavily marketed the drug anyway. The company is accused of instructing its sales force to avoid discussing the trial with doctors while stressing that the drug in fact protects the heart.
Further investigation revealed that the FDA may have acted unethically as well. David Graham, an FDA researcher, testified that the agency subjected him to ostracism, veiled threats and intimidation when he attempted to publish findings that linked Vioxx to 27,000 heart attacks or sudden deaths from 1999 to 2003. In emails Graham produced, his superiors suggested that he water down the study’s conclusions.
FDA Approval Process
To investigate the safety of a new drug or medical device, the FDA typically performs a thorough review of the product’s clinical trial data, which may include laboratory, animal and human tests. The agency must conclude that the benefits of the product outweigh its risks before it can be sold. It is also the FDA’s duty to ensure that prescription drugs meet federal standards for production, advertising, accurate labeling and post-market surveillance.
Process for Drug Approval
Over the past decade, the FDA has approved more than 300 new drugs. The agency approved 39 novel medicines in 2012 alone, including 13 cancer treatments and 13 “orphan drugs” used to treat rare diseases. Some of these medications were approved in less than four months.
A division of the FDA called the Center for Drug Evaluation and Research (CDER) regulates the development of new drugs, a process that typically takes between eight and 10 years. A major goal of drug development is to identify potentially harmful interactions it may have with other drugs, and if so, determine if further safety monitoring is needed to minimize risks.
Once a drug manufacturer can demonstrate a drug’s safety in pre-clinical animal studies, it submits an Investigational New Drug (IND) application to the FDA. The drug then goes through four phases of human testing that evaluate its method of action, proper dosage and safety.
Phase I studies usually involve a small number of healthy patients. In phase II studies, which involve patients with the target disease, researchers identify the most effective dosage while minimizing toxicity. Once a drug makes it through phase III, which tests its effectiveness on a large number of patients, the manufacturer can submit a formal request to market the drug in the United States, known as a New Drug Application (NDA).
Next, CDER reviews the NDA and previous trials to decide whether to approve or reject the drug. In some cases, the FDA requires the manufacturer to conduct a phase IV post-marketing study to address potential concerns over its safety, effectiveness or cost.
Process for Medical Device Approval
The Center for Devices and Radiological Health (CDRH), another branch of the FDA, approves all medical devices sold in the United States. It also oversees how the devices are manufactured and monitors their safety.
Medical devices come in one of three categories that indicate the level of risk they present to patients. Compared with high-risk devices that pose a serious risk for injury or death, the approval and regulation of low-risk devices is far less stringent. All devices, however, must be registered with the FDA and meet the agency’s regulations for branding and quality.
Class I devices, such as tongue depressors, arm slings and bandages, present minimal risk to patients. Class II devices pose a higher risk and include hearing aids, surgical instruments and syringes. Devices with the greatest potential to injure patients belong to class III, and include heart valves, pacemakers and metal-on-metal hip implants.
Many class I and some class II devices must meet certain standards, but do not require extensive FDA review before they can be marketed to consumers. Higher-risk devices, however, are approved through one of two more rigorous pathways.
High-risk devices are typically subject to the FDA’s strictest review, the premarket approval (PMA) process. In the PMA process, a device manufacturer must provide ample proof, usually backed by clinical evidence, that its product is safe and effective.
Some medical devices sold in the United States are not considered FDA-approved, but are said to be cleared by the FDA through a process known as premarket notification or 510(k), which refers to a section of the Federal Food, Drug and Cosmetic Act. Under 510(k), a manufacturer can market a medical device after proving it is substantially similar to an FDA-approved device that has been proven to be safe and effective. To gain clearance, the new device must work the same as its approved counterpart.
This regulatory pathway is not intended to evaluate a product’s safety or effectiveness, however, and has allowed a staggering number of unsafe devices to reach the market and harm consumers. The FDA cleared high-risk metal-on-metal hip implants by 510(k) approval without performing any testing of clinical performance.
Numerous metal-on-metal hip designs, such as DePuy Orthopaedics’ ASR XL Acetabular Cup System, were later found to shed metal particles that caused severe health complications in patients, which often caused devices to fail long before their intended lifespan. The FDA now requires these products to be approved through the PMA process.
The FDA’s work isn’t done once a drug or medical device is approved for use and marketed to patients. The agency continues its responsibility to protect consumers by enforcing a variety of post-approval regulations.
Some of the agency’s most important post-market duties include monitoring patient experiences with medical products and quickly responding to any unexpected safety concerns. The American health care system faces at least 1.5 million reports of preventable adverse drug events per year, according to the Institute of Medicine. Further, doctors and patients submit several hundred thousand reports of confirmed or possible serious injuries and deaths related to medical devices annually.
In addition to managing reports of complications, the FDA also monitors the integrity of drugs and medical devices during their transition from production to use. The agency regulates how medical products are manufactured, stored and transported to doctors and patients.
Federal regulations require manufacturers to update product labels as soon as there is reasonable evidence of an association with a serious health hazard, even if there is no concrete proof. Unanticipated drug reactions are reported through the FDA’s Adverse Events Reporting System (AERS), and a similar reporting system exists for medical devices called the Medical Device Reporting (MDR) system.
When new information surfaces about a medical product’s safety or effectiveness, it is the FDA’s duty to issue an update to patients, doctors, pharmacists and the public about any future actions. If additional surveillance, studies or labeling changes are required, the FDA oversees these tasks.
If post-market surveillance uncovers serious prescription drug side effects or a medical device with an unacceptably high rate of failure, the FDA can initiate a product recall to minimize the risk these dangerous products pose to patients. The agency can also request a recall if a company violates any of the laws. The majority of companies willingly comply with medical product recalls, but the FDA has the authority to seek legal action against manufacturers if necessary.
To ensure that a recalled medical product is either corrected or removed from the market, the FDA cooperates with its manufacturer and other stakeholders, and each of these parties serve important roles in the process. The FDA generally oversees how the recall is managed, but it is the manufacturer’s primary responsibility to recall the product.
Upon initiating a recall, the FDA performs a health hazard assessment to determine the size and scope of the problem, among other factors. Next, the agency assigns a classification to the recall that reflects the product’s relative risk to consumers.
|Recalls are divided into one of three categories:|
|Class I (high risk) – These are the most serious recalls, initiated when there is a reasonable probability that use of the product will cause serious health complications or death.|
|Class II (moderate risk) – Class II recalls are less serious, and are initiated when serious adverse health consequences are remote, temporary or reversible.|
|Class III (low risk) – These are the least serious recalls for situations where the product is not likely to cause adverse health complications.|
Once the recall is classified, the FDA communicates the class information to the manufacturer in writing. The letter also provides instructions on how the manufacturer should contact physicians and patients to make sure the recall notification is received and carried out. Lastly, the FDA reviews the actions to confirm that the manufacturer and other firms involved in the recall perform all the required steps properly.
FDA Unique Device Identification (UDI) System
In July 2013, the FDA proposed that each medical device would carry a unique numeric or alphanumeric code called a unique device identification number. The UDI will link to the model and a production identifier that would have current manufacturing information. Personal information about the patient is not a part of the UDI. The FDA recommended that the system be phased in starting with the highest-risk devices, and that low-risk and over-the-counter (OTC) devices be exempt. The UDIs will help the FDA track adverse events caused by certain devices.
Class II and III devices — these include most implants such as hip and knee replacements — are supposed to include permanent markings on devices and their packaging by September 2018.
Timeline of FDA Milestones
|Year||Description of Key Event in FDA Development|
|1862||President Lincoln appoints a chemist, Charles M. Wetherill, to serve in the newly-established Department of Agriculture. This leads to the creation of the Bureau of Chemistry, predecessor to the Food and Drug Administration.|
|1906||Congress passes the Food and Drugs Act, which prohibits misbranded drugs, food and drinks in interstate commerce.|
|1914||The Harrison Narcotic Act requires prescriptions for products containing certain amounts of narcotics. It also increases recordkeeping for doctors who provide narcotics.|
|1927||The Bureau of Chemistry is divided into two entities: the Food, Drug and Insecticide Administration and the Bureau of Chemistry and Soils.|
|1930||An agricultural appropriations act shortens the name of the Food, Drug and Insecticide Administration to the Food and Drug Administration (FDA).|
|1930||Congress passes the Federal Food, Drug and Cosmetic (FDC )Act, establishing a new system of drug regulation that requires premarket safety testing for drugs.|
|1966||The Fair Packaging and Labeling Act requires honest labeling for food, drugs, cosmetics and medical devices, with provisions enforced by the FDA.|
|1970||The FDA requires the first patient package insert for oral contraceptives, informing patients of specific risks and benefits.|
|1972||The Over-the-Counter Drug Review process is established to improve the safety, effectiveness and accurate labeling of drugs sold without a prescription.|
|1976||The Medical Device Amendments passes, allowing the FDA to ensure the safety of medical devices and diagnostic products. Some products require FDA pre-market approval, while others must pass pre-marketing performance standards.|
|1988||The Food and Drug Administration Act officially establishes the FDA as an agency of the Department of Health and Human Services.|
|1990||The Safe Medical Devices Act passes, requiring hospitals and other facilities that use medical devices to report to the FDA any devices that may have contributed to the injury, serious illness or death of a patient. The act also requires manufacturers to conduct post-marketing surveillance on high-risk implanted devices and authorizes the FDA to order medical device recalls.|
|1992||Congress passes the Prescription Drug User Fee Act, which allows the FDA to collect fees from drug manufacturers to fund the approval of new drugs.|
|1993||Several adverse event reporting systems are combined to form MedWatch, a system for the voluntary reporting of medical product complications by health professionals.|
|1997||The Food and Drug Administration Modernization Act introduces the most dramatic reform to FDA policy since the FDC Act of 1938. It includes measures to accelerate medical device reviews and regulates advertising of unapproved uses for approved drugs and devices.|
|2005||The FDA announces the formation of the Drug Safety Board. The board includes representatives from the National Institutes of Health, the Veterans Administration and FDA staff, who advise the FDA on drug safety issues and communication with patients and health care providers.|