Generic Drug Quality Questioned in NYT Article
For the second time in a week, FDA finds itself defending its medical product oversight after a New York Times opinion piece questions the safety and quality of the products. Last week, the paper’s editorial board published a scathing critique of medical device regulatory oversight, urging FDA to abolish the 510(k) clearance process and fix other device regulatory loopholes amid growing reports of devices that were allowed on the market for decades without proper vetting (see earlier story).
This week it is generic drug manufacturing, and FDA’s role in inspecting the overseas plants where most of these products are made. A 5/12 Times opinion piece by investigative journalist Katherine Eban cites former agency inspector Peter Baker and the problems he documented at foreign drug manufacturing establishments over more than five years of audits. The article mirrors similar criticisms from a 5/10 CBS News report about allegations of widespread fraud associated with generic drugs made overseas and imported to the U.S.
Eban reports former inspector Baker’s uncovering of fraud or deceptive practices in almost four-fifths of the drug plants he inspected. “Some of the plants used hidden laboratories, secretly repeated tests and altered results to produce fake data that fundamentally misrepresented drug quality, then submitted that data to regulators,” Eban writes. “In some instances, deceptions and other practices have contributed to generic drugs with toxic impurities, unapproved ingredients and dangerous particulates reaching American patients. Some doctors have struggled to stabilize patients who became sicker after they were switched from a brand-name to a generic, or between generic versions. A low-cost drug is not a bargain if it doesn’t work.
“My reporting on the generic drug industry over the last decade,” Eban continues, “led me to four continents, and into the overseas plants where America’s generic drugs are made. Interviews with more than 240 people, including numerous whistleblowers, helped expose what was going on behind the boardroom doors at generic-drug companies. Some companies have encouraged data fraud as the most profitable path to securing approvals from regulators, and have used deceit to hold the FDA’s investigators at bay.”
Eban also touches on problems with preannounced inspections at overseas plants because the resulting audits are mostly staged. “With advance notice and low-cost labor, the plants can make anything look like anything,” she writes. “You give them a weekend, they’ll put up a building,” as one FDA investigator put it... And there was an additional negative consequence to the FDA’s system of advanced notice. With the companies serving as travel agents, FDA investigators spoke of inappropriate perks: hotel upgrades, for which the investigators would never see a bill; golf outings, massages, and trips to the Taj Mahal. The result was what some FDA employees referred to as ‘regulatory tourism.’ The FDA said in response that ‘any allegations of improper conduct by FDA personnel are investigated.’”
In a 5/13 online post, CDER director Janet Woodcock responds that a multidisciplinary team reviews safety and quality concerns when they arise. “For adverse events," she writes, "this includes other reports of adverse events, controlled clinical trials and epidemiologic studies, electronic health care databases, estimates of drug usage and adverse drug experience reporting rates, estimates of background rates of the adverse events, the pharmacology of the drug in relation to the identified safety concern, and other relevant information.
“For potential quality problems,” Woodcock continues, “a multidisciplinary team will also review manufacturing and past inspection data, and the FDA may conduct product testing and perform additional inspections of manufacturing facilities. The FDA may take regulatory action(s) to improve product safety and protect the public health, including a ban on importation, enforcement actions, updating a product's patient and doctor information, restricting use of the drug, communicating new safety information to the public, or, in rare cases, removing a drug from the market.”
Additionally, Woodcock says that to improve drug quality, FDA is “leading efforts to help industry develop cutting-edge manufacturing technologies --- such as continuous manufacturing --- and working to ensure the agency’s efforts to regulate these processes are not burdensome. As a result, companies are starting to use advanced technologies that not only increase manufacturing efficiency and decrease cost, but also make medicines of more reliable quality.”
Despite these efforts, Woodcock acknowledges there will always be “bad actors that fail to meet our exacting standards.” She says that over the past four years, CDER’s Office of Compliance has substantially increased its Warning Letters to drug manufacturers. For example, she says the agency in 2018 issued nearly five times as many Warning Letters as it did in 2015.