New report highlights weak FDA oversight of foreign firms making medications for US market

News brief

Drugs on assembly line — Gumpanat / iStock

The US Food and Drug Administration (FDA) continues to struggle in overseeing more than 4,800 foreign drug manufacturers supplying medications for the US market, although it has taken action to improve its drug-safety oversight, the Government Accountability Office (GAO) told the House of Representatives' Subcommittee on Oversight and Investigations yesterday.

"We have identified long-standing weaknesses in FDA's ability to oversee this manufacturing, an issue highlighted in our High-Risk Series since 2009," Mary Denigen-Macauley, PhD, director of GAO's healthcare team, testified.

As of 2022, 58% of makers of drugs bound for the US market were located overseas, the GAO noted.

FDA working on implementing recommendations

In 2019, the FDA performed a record number of inspections of manufacturers in India and China, but the agency postponed most inspections after the COVID-19 pandemic began in 2020, according to the GAO. During this period, the FDA relied on remote inspections, document reviews, and reports from foreign regulators. But by 2022, a backlog had grown of manufacturers never inspected or not inspected within 5 years.

"While domestic inspections have almost always been unannounced, FDA's practice of generally preannouncing foreign inspections up to 12 weeks in advance may have given establishments the opportunity to fix problems before the inspection.

Denigen-Macauley said that foreign inspections have always been problematic and that the FDA lacks enough staff specializing in foreign inspections.

"While domestic inspections have almost always been unannounced, FDA's practice of generally preannouncing foreign inspections up to 12 weeks in advance may have given establishments the opportunity to fix problems before the inspection," she said. "FDA has relied on translators provided by the foreign establishments being inspected, which investigators told us can raise questions about the accuracy of information FDA investigators collect."

The FDA has agreed with and taken steps in response to GAO recommendations to evaluate remote inspection processes, create a plan to address the inspection backlog, implement pilot programs evaluating the effect of performing unannounced inspections and employing independent translators, and develop strategies to increase its foreign inspection workforce, the GAO said.

Denigen-Macauley said the GAO will continue to monitor the FDA's foreign drug inspection program and will reports its findings.

COVID-19 vaccines in pregnancy found safe for infants

News brief

Stephanie Soucheray, MA

A new study of almost 200,000 newborns in Sweden and Norway shows that maternal receipt of the COVID-19 vaccine during pregnancy poses no risk to infants, and instead prevents babies from suffering serious complications.

Moreover, the mortality rate for babies born to mothers who were vaccinated during pregnancy was half the rate of those whose mothers were unvaccinated. The study appeared yesterday in JAMA. The authors caution, however, that they were unable to explain why the mortality risk was so reduced among infants whose mothers were vaccinated.

"A direct vaccine effect is unlikely," said Mikael Norman, PhD, first author of the study in a press release from the Karolinska Institutet in Stockholm, Sweden, where he practices. "Previous studies have shown that the vaccine does not cross the placenta and that it cannot be found in umbilical cord blood…No matter how we look at it, the finding remains and therefore, we cannot say what the lower risk of death among infants of vaccinated women relates to."

The study included national birth registry data from births from gestational week 22 and onwards after COVID-19 vaccines were available in both countries. Babies included in the study were born from June 2021 to January 2023.

Half the risk of infant death

In total, 48% of mothers had been vaccinated with one or more doses of an mRNA vaccine against COVID-19 in pregnancies of 196,470 newborns.

In addition to lower mortality rates by a half, infants born to vaccinated mothers had lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1,000; adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.61 to 0.99), and hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73; 95% CI, 0.55 to 0.96).

There were no cases of myocarditis or thrombocytopenia seen in the study, as well as no increased risk for respiratory distress syndrome or necrotizing enterocolitis.

These findings may provide reassurance to public health authorities, clinicians, pregnant individuals, and their families.

"These findings may provide reassurance to public health authorities, clinicians, pregnant individuals, and their families that infants are not at higher risk of adverse events due to COVID-19 vaccination during pregnancy," the authors concluded.

New rapid gonorrhea test shows promise in South African study

News brief

Chris Dall, MA

Gonorrhea bacteria — Dr_Microbe / iStock

A novel, low-cost, rapid point-of-care test for gonorrhea met sensitivity and specificity requirements in symptomatic male and female patients in South Africa, a team of US, South African, and Swiss researchers reported yesterday in The Lancet.

In a cross-sectional study conducted at clinics in South Africa, researchers evaluated the performance of the novel Neisseria gonorrhoeae lateral flow assay (NG-LFA) in men with urethral discharge and women with vaginal discharge. While molecular tests are widely used to diagnose gonorrhea and other sexually transmitted infections in high-resource settings, the cost and lack of laboratory access available make them not feasible for lower-resource settings. And without access to affordable diagnostic tests, men and women with symptoms of gonorrhea in the settings are typically treated with an empiric combinations of antibiotics.

To meet the requirements of the World Health Organization and the Foundation for Innovative Diagnostics, NG-LFA needs to cost less than $3 and demonstrate a minimum turnaround time of less than 30 minutes, a sensitivity of higher than 80%, and specificity greater than 95%. The optimum requirement was a turnaround time of 20 minutes or faster, sensitivity of at least 90%, and specificity greater than 98%.

The researchers tested specimens from 400 patients with both NG-LFA and the Xpert CT/NG polymerase chain reaction (PCR) assay, and conducted N gonorrhoeae multi-antigen sequence typing (NG-MAST) on all positive specimens.

High accuracy, rapid detection

NG-LFA sensitivity was 96.1% in urine specimens and 91.7% in vaginal swab specimens, and specificity was 97.2% in urine specimens and 96.3% in vaginal specimens. In 156 LFA-positive specimens, NG-MAST showed 93 different sequence types. The turnaround time met the minimum requirements.

"This study demonstrates that the novel NG-LFA was highly accurate for the rapid detection of N gonorrhoeae in symptomatic male and female patients at the primary health-care level in South Africa," the study authors wrote.

They add that with its ease of use, accuracy, and low cost, NG-LFA should provide a "major step forward" in optimizing syndromic management of gonorrhea and reducing unnecessary antibiotic use in low- and middle-income countries.

Bivalent COVID vaccine shows 54% protection in school-age kids

News brief

Lisa Schnirring

Data from three prospective US cohort studies suggest that bivalent (two-strain) mRNA COVID-19 vaccines were 54% effective against lab-confirmed COVID infection and 49.4% protective against symptomatic disease in school-aged children, researchers from the US Centers for Disease Control and Prevention (CDC) and collaborators from several states reported yesterday.

Study regularly tracked nasal swab results

The group's goal was to flesh out limited data about the effectiveness of the vaccines in children and adolescents, and the authors noted that previous studies were limited by their small sample sizes. For the new analysis, the investigators included data from three earlier studies that included nearly 3,000 participants from six diverse sites. The team published its findings yesterday in JAMA.

adolescent vaccination — VCU Capital News Service, Art Writ / Flickr cc

From September 4, 2022, to January 21, 2023, participants ages 5 to 17 years completed regular surveys, submitted self-collected nasal swabs, and sent more nasal swabs when they had symptoms. The Omicron variant was dominant over that period.

Of the 2,959 participants, 25.4% had received the bivalent COVID vaccine. Over the study period, 426 children (14.4%) had lab-confirmed infections, of whom 383 were unvaccinated or had received only the monovalent (single-strain) vaccine. Median observation time was 276 days for kids who had received only the monovalent vaccine and 50 days for those who had gotten the bivalent version.

Findings underscore vaccine recommendations

The researchers didn’t find any differences within age-groups, and they didn't see any waning in protectiveness after the bivalent vaccine, though they said there might not have been enough time for assessment. They noted the findings were consistent with limited earlier data on the bivalent vaccine in kids and teens.

"These data demonstrate the benefit of COVID-19 vaccine in children and adolescents," the group wrote. "All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations."