Tens of millions of J&J COVID-19 shots sit at Baltimore factory -sources

 An estimated 30 million to 50 million doses of Johnson & Johnson’s COVID-19 vaccine made early this year sits idle in Emergent BioSolutions Inc’s plant in Baltimore awaiting a green light from U.S. regulators to ship, two sources familiar with the matter said.

Emergent, a contract drug manufacturer, is waiting for the U.S. Food and Drug Administration to approve release of those doses. The agency must still inspect and authorize the plant before Emergent can ship newly manufactured drug substance, one of the sources said.

The exact number of doses sitting idle cannot be determined, the source said, because Emergent only makes raw vaccine substance and does not fill vials with finished product.

The FDA in April halted operations at Emergent’s production facility after J&J’s vaccine was found to be contaminated with material from AstraZeneca’s COVID-19 shots, which were also being manufactured there at the time.

The contamination ruined about 15 million J&J doses and set back its U.S. vaccine rollout by weeks.

Material manufactured for the J&J vaccine at the Baltimore plant prior to the April shutdown and awaiting FDA approval could be enough to produce as many as 50 million shots, the two sources said. They asked not to be named because they were not authorized to speak publicly on the issue.

Of the 100 million doses worth of vaccine material Emergent described in an April Congressional hearing as being sidelined, the FDA has so far cleared nine batches of J&J’s vaccine and three batches of AstraZeneca’s. It has not disclosed how many doses were in those batches.

Emergent in late July said it would resume production of J&J’s vaccine at the plant following additional FDA reviews, but has not provided updates on production or timing of potential shipments.

Emergent has begun making new vaccine substance, but the FDA has yet to provide guidance on when it plans to inspect the Baltimore facility, one of the sources said.

The FDA said in a statement that it conducted a limited inspection of Emergent’s facility in July to confirm it had conducted corrective actions following the April production pause. A previous inspection had turned up a raft of sanitary, safety and bad manufacturing practice issues at the plant.

The agency said it has not yet authorized the facility to ship doses and continues to review batches made prior to the production halt. It has based its batch approvals on reviews of facility records and quality testing conducted by the manufacturer.

The FDA typically waits for a drug manufacturing facility to produce multiple batches of its product before conducting an inspection, according to a former FDA official who asked not to be named because she was not authorized to speak with the media.

Following the Emergent plant shutdown, J&J lowered its production target for 2021 to between 500 million and 600 million doses from around 1 billion. It expects to be able to make 1 billion doses annually starting next year

J&J has not specified whether it needs Emergent to restart production to hit its 2022 target. It has another manufacturing facility in Leiden, Netherlands, and production agreements with other contract manufacturers, including Catalent Inc and India’s Biological E.

The United States contracted with J&J for 100 million shots in 2020 and ordered an additional 100 million in March.

Last week, the FDA authorized J&J’s vaccine as a booster for people who are already vaccinated but desire additional protection against COVID-19, including anyone over age 18 who originally received the company’s single-dose shot.

Use of J&J’s vaccine fell sharply in the United States after it was linked to a rare but potentially lethal blood clotting disorder. 

https://financialpost.com/pmn/business-pmn/tens-of-millions-of-jj-covid-19-shots-sit-at-baltimore-factory-sources

Antidepressant found to reduce COVID-19 hospitalization

 An affordable antidepressant has been found in a clinical trial to reduce the risk of hospitalization in high-risk adults with recently diagnosed COVID-19, according to a study published in The Lancet Global Health.

The drug, known as fluvoxamine, is a selective serotonin reuptake inhibitor (SSRI) commonly used in the treatment of depression, anxiety, obsessive-compulsive disorder and other mood disorders. Its low price makes it a desirable treatment option for less wealthy nations, the researchers wrote.

Researchers began looking into the drug during the height of the pandemic because of the antidepressant's ability to reduce inflammation, according to The New York Times. The researchers thus hypothesized that the drug may allow the body to quell an overwhelming response to a COVID-19 infection. 

Other studies have come out in the past months on fluvoxamine that also showed promising results; however, no study has been as large as the one published Wednesday, according to the Times.

The study consisted of about 1,500 Brazilian adults, half of whom were given the antidepressant and half of whom were given a placebo. The study found that the drug reduced the need for hospitalization or medical observation by about one-third.

A portion of patients struggled to tolerate the SSRI — which commonly has side effects such as nausea, weight gain, sleep disturbances, sexual dysfunction and diarrhea — and stopped taking it, according to the Times. 

However, the benefits were highest among those who continued taking the drug under a doctor's direction. In that group, hospitalization risk fell by two-thirds, and only one patient died while taking fluvoxamine, compared with 12 who died while on the placebo. 

U.S. News & World Report reported that the results have been shared with the U.S. National Institutes of Health, which publishes treatment guidelines, and that they are hoping for a recommendation from the World Health Organization (WHO). 

“If WHO recommends this, you will see it widely taken up,” said study co-author Edward Mills of McMaster University, according to U.S. News & World Report, which noted its affordability compared with antibody IV treatments that cost about $2,000 and Merck's antiviral pill against COVID-19 that is set to be about $700.

"We hope it will lead to a lot of lives saved," McMaster said.

https://thehill.com/regulation/healthcare/578843-antidepressant-found-to-reduce-covid-19-hospitalizations-study

1% of adults say they've left job due to vaccine mandate: KFF poll

 One percent of all adults in a Kaiser Family Foundation poll said they’ve left a job due to COVID-19 vaccine requirements as more workplaces institute mandates. 

The KFF Vaccine Monitor for October released on Thursday determined that out of unvaccinated adults, just 5 percent left their jobs because of the requirements, “despite widespread news reports” of workplace vaccine mandates driving resignations. 

Republicans are twice as likely as Democrats to report knowing someone who left their job due to a vaccine mandate, with almost a quarter of all adults saying they know someone who's quit.

A quarter of workers reported their employers instituted a COVID-19 vaccine mandate — an increase of 16 percentage points since June. 

About a fifth of respondents said they want a workplace vaccine requirement, while about half said they do not want a mandate, including majorities of Republicans and unvaccinated workers. 

The vaccine requirements come as the Biden administration moved forward with its plan to institute a vaccine-or-test mandate for all employers with at least 100 employees. 

Almost half of unvaccinated workers, 46 percent, said under that type of mandate, they would opt for weekly testing. Eleven percent said they’d most likely get the vaccine while 37 percent, representing 1 percent of all adults, said they would leave their job. 

But without the weekly testing option, a majority of unvaccinated workers at 72 percent said they would quit their jobs, representing 9 percent of all adults. Seventeen percent said they would get the vaccine in that situation, amounting to 2 percent of all adults. 

Sixty percent of unvaccinated employees said they’d apply for an exemption if their workplace instituted a vaccine mandate.

Overall, the vaccination rate remained the same as in September with 72 percent of respondents saying they have gotten the vaccine, matching the leveling off of the country’s vaccination rate. 

The KFF Vaccine Monitor surveyed 1,519 adults Oct. 14-24. The margin of error overall was 3 percentage points and 6 percentage points among the unvaccinated.

Several companies across the country have instituted these controversial mandates, including United Airlines, which said 99 percent of its workforce got vaccinated by the deadline last month, leaving almost 600 workers to face termination. 

Tyson Foods achieved a vaccinated rate of more than 96 percent days before its Monday deadline, the company announced earlier this week. 

Biden administration officials have consistently praised mandates as effective in boosting the vaccination rate, citing earlier this month that businesses and organizations that implemented vaccine requirements saw an at least 20 percent increase in vaccinations. 

But opponents consider the vaccine mandates as government overreach and a violation of their constitutional rights.

Concerns over mandates fueling resignations have also sparked anxiety that such requirements could exacerbate the shortage of workers in several industries.

https://thehill.com/policy/healthcare/578748-one-percent-of-adults-say-theyve-left-job-due-to-vaccine-mandate-kff-poll

ALS, dementia attacked by RNA-hunting compound that recruits cell's own virus fighter

 One of the most commonly inherited forms of ALS and frontotemporal dementia is referred to as C9 ALS/FTD, so named for the repeated section of DNA on chromosome 9 that causes it. A collaboration led by scientists at Scripps Research in Florida has successfully treated the genetic disease in mice, with a potential drug molecule engineered in the lab of chemist Matthew Disney, Ph.D. The compound works in a new way, by directing the cell's own immune machinery to degrade and eliminate the disease-causing RNA.

The team's study is published Wednesday in the journal Science Translational Medicine. Collaborators include Leonard Petrucelli, Ph.D., of the Mayo Clinic in Jacksonville, and Jeffrey Rothstein, MD, Ph.D., of Johns Hopkins University in Baltimore.

Also known as Lou Gehrig's disease, ALS causes progressive loss of motor neurons, the elongated nerve cells that connect muscles to the central nervous system. As motor neurons die, paralysis, muscle loss, swallowing and eventually, breathing difficulties develop, leading ultimately to death. Scientists are learning that ALS has multiple causes, some of them sporadic, and some inherited or familial.

Frontotemporal dementia similarly has both familial and sporadic causes. It involves progressive damage to neurons in the brain's frontal and temporal lobes. Symptoms may include difficulty walking or odd behavioral and emotional states. Like ALS, frontotemporal dementia has no cure.

One disease, many symptoms

While people with FTD appear outwardly to have a completely different illness than people with ALS, those whose condition is caused by the C9 genetic repeat have the same disease. Manifestations differ according to cell types affected. The more times the sequence repeats, the earlier and more severe the disease symptoms.

The disease-causing mutations involve repeats of the nucleotides guanine and cytosine, specifically repeats of GGGGCC segments on chromosome 9, open reading frame 72. The number of disease-causing repeats can range from around 60 into the thousands. People who inherit the diseased gene can develop ALS, FTD or both. Studies have estimated that around 1 in 5 people diagnosed with familial ALS, and around 1 in 10 people with familial FTD carry the C9 mutations. The average age of symptom onset is 58.

"This is a disease that runs in families. Based on the number of repeats, doctors can assess whether a patient would be affected with the disease. So, you know before a patient has symptoms that they have a high likelihood of developing it, and yet there is no treatment," Disney says. "That makes it even more imperative to develop strategies to that could create a medicine."

A team effort

To assess the effectiveness of their compounds, the team needed both diagnostic biomarkers and patient-derived neurons displaying the C9 mutations. The Petrucelli group at Mayo Clinic has extensively studied C9 ALS/FTD and developed the diagnostic biomarkers. The Rothstein group at Johns Hopkins treats and researches ALS and provided stem cells, which the Disney Lab then brought forward into neurons that displayed the diseased array of GGGGCC repeats.

In their research, Disney's team designed a compound that targeted the RNA involved in transcribing the gene causing the disease. The compound causes an interaction between the RNA and pathways that a cell uses to eliminate RNAs. The compound eliminated 70 percent of the toxic protein fragments from mice bread to have the disease, and removed most hallmarks of the disease from the patient-derived nerve cells.

A single injection in the mice showed benefit through the entire length of the study period, which was six weeks, says Jessica Bush, a graduate student at Scripps Research's Skaggs Institute for Chemical Biology, who was the paper's first author.

"I think that it's so exciting that we can look at a disease like ALS, and by taking a different approach or new perspective, we can open the door to a whole new world of possibilities, and start down the road toward therapies," Bush says.

Basic science behind the discovery

Disney designed the compound by applying nearly 15 years of his group's research on finding druggable structures on RNA, a notoriously changeable and transient molecule, and building a library of compounds able to bind those druggable structures.

The successful compound works by binding tightly to the disease-causing RNA in multiple places, while also attracting an enzyme that eliminates RNAs. Nature apparently created the degrading enzyme to defend cells from viral infection and provide quality control for protein production.

"We co-opt a natural process to eliminate disease-causing RNA," Disney says. "A full analysis of the RNAs in the cells treated with the compound showed it was very specific and selective."

Moving the technology forward to where it can be tested in humans requires a large amount of additional tests and refinements, a process that may take several years, Disney adds.

"These studies, we hope, will advance new ways of targeting the RNA that causes ALS as well as other diseases," he says. "There is a possibility here to eventually treat these patients before they develop symptoms, but it will be a long road before reaching the clinic."

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Explore further

Genetic cause of ALS and frontotemporal dementia blocked by RNA-binding compound

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More information: Jessica A. Bush et al, Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G 4 C 2 ) repeat expansion in vitro and in vivo ALS models, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abd5991

https://medicalxpress.com/news/2021-10-als-dementia-rna-hunting-compound-cell.html

FDA strengthens safety requirements for breast implants

 The Food and Drug Administration (FDA) announced Wednesday it will take several steps to strengthen safety requirements for breast implants, including requiring manufacturers and plastic surgeons to warn patients of the risks before they undergo surgery.

The new agency order also places new restrictions on how breast implants can be sold and distributed in an effort to ensure that patients considering breast implants can make informed decisions about devices.

The FDA is also approving new labeling for all legally marketed breast implants. It includes a boxed warning, a patient decision checklist and screening recommendations for women who receive silicone gel-filled breast implants.

Additionally, the agency is updating information on the status of breast implant manufacturer post-approval studies, according to its statement on Wednesday.

“Protecting patients’ health when they are treated with a medical device is our most important priority,” Binita Ashar, the director of the Office of Surgical and Infection Control Devices in the Center for Devices and Radiological Health, said in the statement. 

“In recent years, the FDA has sought more ways to increase patients’ access to clear and understandable information about the benefits and risks of breast implants. By strengthening the safety requirements for manufacturers, the FDA is working to close information gaps for anyone who may be considering breast implant surgery,” she continued. 

“As the FDA continues to evaluate the overall effects of breast implants in patients, today’s actions help ensure that all patients receive the information they need to make well-informed decisions affecting their long-term, personal health,” she added.

The new requirements come after tens of thousands of women have spent years complaining of experiencing symptoms following their breast implant surgeries, including brain fog, fatigue and other health issues often known as “breast implant illness,” The Washington Post reported. 

Some patients have even been linked to a rare and potentially fatal form of cancer. The FDA has documented that 573 cases of that cancer worldwide and 33 resulting deaths. 

Amid those ongoing complaints, advocates have long fought for a more consistent process so that patients considering breast implants can be better informed, according to the Post.

Regulators recommended in 2020 that manufacturers put an enclosed warning in a black box on the label to list possible complications associated with breast implants. 

The guidance also recommended medical officials use a patient checklist to guide customers through potential hazards.

https://thehill.com/policy/healthcare/public-global-health/578811-fda-strengthens-safety-requirements-for-breast

Industrial plastics found in some fast food

 A new study found small amounts of chemicals known as phthalates in food samples from fast food chains such as McDonald's, Pizza Hut, and Chipotle, reports the Washington Post. 

Researchers from George Washington University purchased 64 fast food items in San Antonio, Texas from national chains reports the Post. Their study, published Tuesday, identified chemicals in a majority of the samples they collected.

Phthalates have been linked to health problems in some studies, such as endocrine system issues, fertility issues, and a potential increase for learning, attention, and behavioral disorders in children.

Phthalates are used to make plastics soft and, according to the Centers for Disease Control (CDC), people can be exposed to them through food and drinks, breathing particles or when children crawl around in dust or dirt and put their hands in the mouths.  

These chemicals, according to the CDC, have affected some animals' reproductive systems, however, human health effects from exposures to a low amount of phthalates is not as clear. 

According to the Post, the Food and Drug Administration, which regulates food safety, has no legal parameters for phthalate concentrations in food. However, the Post notes that the FDA put out a statement that it will be reviewing the George Washington study as part of a body of scientific evidence. 

“Although the FDA has high safety standards, as new scientific information becomes available, we reevaluate our safety assessments,” said an FDA spokesperson to the Washington Post. 

The Hill reached out for comment from the six restaurants in the study, which also included Burger King, Domino's and Taco Bell.

https://thehill.com/business-a-lobbying/business-a-lobbying/578756-industrial-plastics-found-in-some-fast-food

Cigarette sales increased in 2020 for first time in two decades

 The Federal Trade Commission (FTC) reported Tuesday that cigarette sales increased in 2020 for the first time in 20 years. 

The FTC, which issued its 2020 Cigarette Report, stated that 203.7 billion cigarettes were sold by major manufacturers in the U.S. in 2020 compared to 202.9 billion the year prior, noting it represented a .4 percent increase between the years. Still, those numbers are a far cry from the FTC’s record of the number of cigarettes sold by major manufacturers — a whopping 636.5 billion in 1981.

The FTC also noted that advertising and “promotional expenditures” for cigarettes between 2019 and 2020 increased. Last year, $7.84 billion was spent on advertising and promotional expenses compared to $7.62 billion in 2019. 

The report said that the majority of this money was spent giving cigarette dealers price discounts in an effort to make cigarettes less expensive. The FTC said that roughly 77 percent of advertising and promotional expenses were geared toward the price discounts, or $6.07 billion.

The parent companies of cigarette manufacturers including Altria Group, Inc., ITG Holdings USA Inc., Reynolds American, Inc. and Vector Group Ltd. all reported their company information to the FTC. 

The agency said it did not report on data related to heated, non-combusted cigarettes — which are different from e-cigarettes — “because only one company sold such products in 2019 and 2020 and when only one company reports in a category, the Commission does not report such information in order to avoid potential disclosure” of company information.

Meanwhile, the FTC noted in their their Smokeless Tobacco report that the number of pounds of smokeless tobacco had increased between 2019 and 2020. In 2019, close to 126 million pounds of tobacco had been sold compared to 126.8 million pounds sold in 2020.

Sales in 2019 were at around $4.5 billion compared to $4.8 billion the following year.

https://thehill.com/business-a-lobbying/business-a-lobbying/578808-cigarette-sales-increased-in-2020-for-first-time-in