The last setback for the Johnson & Johnson COVID-19 vaccine was ordered by the U.S. Food and Drug Administration on June 11, 2021 to discard 60 million doses that do not meet quality and safety guidelines. A Baltimore manufacturing plant run by Emergent BioSolutions had been producing COVID-19 vaccines for both J&J and AstraZeneca and inadvertently mixed ingredients from both companies.
The FDA regularly inspects manufacturing facilities to ensure that medications are complied with strict quality standards. These standards are vital to protect patients from poorly dosed, contaminated, or ineffective medications.
But in recent years, tens of millions of doses of prescription and over-the-counter medications have failed in FDA quality expectations. This includes the ongoing 2018 recovery of thousands of batches of popular medications for blood pressure, diabetes and acid reflux containing the probable carcinogen NDMA.
In perspective, the number of individual prescription and over-the-counter tablets and capsules entering the United States each year is counted in trillions.
Manufacturers may back down as the pandemic continues to inspect the burner. Like a pharmacist i doctor research team drugs, device i dietary supplement safety, we are concerned about the current level of manufacturing supervision in the US and abroad. To protect consumers, the FDA must find a balance between the rapid exit of the life-saving drug market and the strict assurance of its safety.
FDA overseas oversight fell under the radar
In the last 30 years, American pharmaceutical companies have been fired tens of thousands of American manufacturing workers and they moved their drug manufacturing abroad. The main reasons for this outsourcing they include cheaper labor, looser environmental regulations, and less supervision. Meanwhile, pharmaceutical companies in India and China captured one higher share of the US generic drug market. As of May 2020, 74% of facilities manufacturing active ingredients and 54% of manufacturing finished medicines for the United States were located abroad.
Until 2007, the FDA focused almost entirely on inspecting U.S.-based manufacturing plants to determine the quality of drugs. Foreign plants, on the other hand, were of the honor system: the FDA relied on its own internally generated paperwork as proof of compliance.
The madness of this system came to light in 2004, when a the complainant alerted the FDA that Ranbaxy Corp., one of the world’s largest generic pharmaceutical companies, was manufacturing its drug test reports. Ranbaxy finally paid for one Fine of 500 million US dollars in 2013 to consciously produce low quality drugs for the US market from his first FDA approval in 1998.
The review of the drug inspection from 2007 to 2019
Following Ranbaxy’s failure, the FDA stepped up overseas manufacturing inspections 333 in 2007 a 966 in 2019. The proportion of foreign manufacturing plants that had never had an FDA inspection it fell from 64% in 2010 to 16% in 2019. Of these, the FDA also found it 37% did not need inspection because they either stopped working, no longer supplied drugs to the U.S. or, first, sold drugs to the U.S..
As inspections increased, so did the number of serious drug safety issues. Dozens of Indian manufactures they were banned from sending drugs to the U.S. after the FDA discovered they were manipulating and omitting quality test results and had unhealthy production conditions. Similar results resulted from inspections of Chinese manufacturing facilities, including the company behind numerous companies. recalls blood pressure medications in 2019.
Decreased oversight at U.S. manufacturing facilities
One of the reasons the FDA had less oversight of overseas facilities was limited funding. Before 2012 Amendment of the rate of consumers of generic drugs, the FDA was funded primarily by user fees of manufacturers of pharmaceuticals, vaccines and medical devices. The amendment imposed a $ 15,000 surcharge at each foreign manufacturing plant to cover the additional costs of conducting on-site inspections abroad.
Despite increased inspection funding, the FDA remained stalled by one inability to fill job vacancies both for U.S.-based and overseas inspectors. These vacancies are especially common in India and China, where 33% and 30% of jobs available as an inspector abroad respectively, they remained unfilled based on the most recent data available in November 2019.
In 2012 FDA Safety and Innovation Act it removed the legal obligation to inspect U.S. manufacturing facilities every two years. This was in part so that the FDA could transfer its national workforce to foreign inspections and ensure that all facilities in the world meet the same objective criteria. National inspections later decreased from 1,122 in 2007 to only 698 in 2019. The FDA currently inspects domestic and foreign manufacturing facilities every five years, or more often when serious problems are identified. While the decline in national inspections may have given the FDA more bandwidth for outside oversight, this may also have pressured FDA officials to look into quality issues.
For example, the U.S. Office of Special Advisers discovered in March 2021 that FDA administrators had it minimized the complainants ’concerns on serious quality issues at U.S. vaccine manufacturing facilities from 2017 to 2018.
Similarly, a FDA 2020 inspection had already identified numerous installation and manufacturing issues at Baltimore’s Emerging BioSolution facilities. If these findings had been addressed immediately, cross-contamination with Johnson & Johnson’s COVID-19 vaccine would have been less likely. But none of these problems were considered serious enough to stop production. Instead, they were allowed to settle gradually as production continued.
How has COVID-19 affected foreign inspections?
The gap between domestic and foreign inspections has widened over the COVID-19 pandemic. Because international travel closed after March 2020, the FDA conducted only three overseas inspections and 52 in the US
The effects of the pandemic on inspections can be long-lasting. From 2020, 13% of foreign manufacturers they have never had an inspection since they did business with the US Another 17% have not been inspected for more than five years. With current staffing levels, it will probably take a long time to correct the backlog.
What does it all mean for consumers?
Until the FDA has enough staff to conduct rigorous on-site inspections, consumers don’t have many options. Because many states allow or calls for automatic substitution of products that the FDA considers bioequivalent, consumers have a limited ability to specify which version of the manufacturer they want to receive at the pharmacy counter.
American consumers can have much more confidence that the pharmaceuticals they receive today are of higher quality than those of the early 2000s. But the loss of tens of millions of doses of COVID-19 vaccine due to poor manufacturing supervision underscores the value of prospective inspections and the risks involved in reducing national inspections.
Adrian V. Hernandez, Associate Professor of Comparative Effectiveness and Results Research, University of Connecticut i C. Michael White, Distinguished Professor and Head of the Pharmacy Internship Department, University of Connecticut