Why Was My Medicine Recalled?

Pharmaceutical safety expert Paul Beninger explains what goes on when a manufacturer pulls a drug from the shelves
Pills and open pill bottle on wooden background. Recent recalls of Zantac and other medications have left consumers concerned about the safety of the drugs they take.
“The manufacturer may discover potential contamination, defects or other problems in the packaging, or other evidence that the drug is out of its manufacturing specification,” said Paul Beninger. Photo: ingimage
December 2, 2019

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When drug recalls appear in the news, they often incite concern and confusion among consumers. What does a recall mean? Why is the product being recalled now?

While it may seem that there has been a recent spate of drug recalls in the United States—including Zantac, a generic for Xanax, and medications for high blood pressure and allergies—recalls are actually relatively common. According to the Food and Drug Administration, there were 126 drug recalls in 2018 alone.

The FDA may request a manufacturer issue a recall when a product isn’t meeting its manufacturing specifications—the package labels are in the wrong language, the number of pills in a blister pack is wrong, or a foreign substance is detected, for example. This differs from a product withdrawal, which permanently removes the drug from the market because new information shows that it is more harmful to patients than it is beneficial.

So, how do the FDA and pharmaceutical companies determine when a medication should be recalled? Where does this information come from, and what are the processes in place to ensure that medications on the market are safe to use?

Paul Beninger, an associate professor in the Department of Public Health and Community Medicine at Tufts School of Medicine, studies regulatory science, drug and vaccine safety, and pharmacovigilance. Prior to Tufts, Beninger, who has an M.D. and an M.B.A., worked at the FDA and in the pharmaceutical sector in several different capacities, including pharmacovigilance.  

Tufts Now spoke with Beninger to find out more about how drugs are monitored after they have been put on the market and what to make of what’s in the news.

Tufts Now: Can you briefly explain what pharmacovigilance is, and why it is so important in ensuring the safety of drugs on the market?

Paul Beninger: Pharmacovigilance, commonly referred to as drug safety, is the process of collecting, monitoring, evaluating, and then communicating information about medications in order to understand and prevent drug-related problems. For pharmaceutical companies, this means establishing a safety profile of a drug during the product development phase prior to requesting FDA approval to market the product.

After approval, the company must monitor the drug’s use and assess any reports that suggest an association with adverse events, with an eye to making changes in the label, as necessary. In 2009, for example, the FDA requested the addition of a black-box warning—its most serious warning— to the labels of Botox and similar medications to warn of potentially life-threatening complications. The move came after reports of deaths and hospitalizations of people who received large doses of botulinum products or did not use the products for approved uses.

To identify when something might be wrong with an approved medication, pharmaceutical companies and the FDA review internal and external sources of information about the product. They use periodic laboratory analyses, updates on ingredients, and information from regulatory agencies in other countries. They also draw on experiences reported by health-care providers and patients, which is why it’s important for patients to report any adverse events to their doctor, pharmacy, or directly to the FDA.

What has been happening with the drug recalls we’ve been reading about?

A drug can be recalled for a number of reasons. During routine checks of product lots, the manufacturer may discover potential contamination, defects or other problems in the packaging, or other evidence that the drug is out of its manufacturing specification. For example, it could be that the product in tablet or capsule formulation is taking longer to dissolve in standardized tests, or the liquid starts to discolor because of a breakdown of one of the stability-requiring chemicals.

In the case of the Zantac recall this September, low levels of N-nitrosodimethylamine, or NDMA, an environmental contaminant found in water and foods, was detected in certain lots. When there are recalls, it’s important to note that the company identifies the specific numbers of the lots being recalled. 

How has monitoring in the U.S. changed over the last sixty years?

The thalidomide tragedy in Europe in the late 1950s and early 1960s was a key moment in pharmacovigilance. The drug was marketed as a mild sleeping pill purported to be safe even for pregnant women—it was even available without a prescription in some European countries. But despite intense pressure from Richardson Merrell, the manufacturer of thalidomide, Frances Kelsey, a seasoned medical officer at the FDA at the time, did not recommend approval of the drug in the United States, citing inadequate evidence of safety. By 1961, between five and ten thousand babies whose mothers had taken the drug were born with malformed or shortened limbs worldwide. By 1962, nearly every country that had sold thalidomide had banned it.

In response to the tragedy, Congress passed the Drug Efficacy Amendments, also known as the Kefauver-Harris Amendments, to the Federal Food, Drug, and Cosmetic Act in 1962. They required manufacturers to provide substantial scientific evidence in support of the safety and efficacy of medications prior to marketing approval. The statute also established a new requirement for reporting of adverse events by the manufacturer to the FDA.

Prior to the early 1990s, drug safety laws passed by Congress were almost always in response to a disaster. It was only with the Prescription Drug User Fee Act of 1992 that Congress shifted to a proactive approach. The act allows the FDA to collect fees from companies when they submit applications to study new human drug and biological products or seek authorization to market these products. This enables the FDA to acquire the necessary resources to review these materials in a timely way. The act must be reauthorized every five years, a process that includes assessing the FDA’s review performance and planning for the next cycle.

Nako Kobayashi and Lisa LaPoint can be reached at nako.kobayashi@tufts.edu and lisa.lapoint@tufts.edu.