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Sunday, February 9, 2020

FDA Laboratory analysis of metformin products

FDA continues to investigate the presence of the N-Nitrosodimethylamine (NDMA) impurity in metformin approved for sale in the U.S. Metformin is a prescription drug used to control high blood sugar in patients with type 2 diabetes. FDA has identified low levels of NDMA in some samples of metformin drug products but has not identified NDMA in metformin active pharmaceutical ingredient (API). To date, no sample of metformin that FDA has tested exceeds the acceptable daily intake for NDMA.
FDA is posting its laboratory results in the table below showing NDMA levels in metformin products it tested. Some metformin drug products tested showed no detectable levels of NDMA, while others showed low levels of NDMA. The methods FDA used in the laboratory testing will be posted in the near future. FDA is also collaborating with international regulators to share testing results for metformin.
For reference, consuming up to the acceptable daily intake limit, 0.096 micrograms (96 nanograms), of NDMA per day is considered reasonably safe for human ingestion based on lifetime exposure. NDMA may increase the risk of cancer if people are exposed to it above the acceptable level and over a long period of time, but a person taking a drug that contains NDMA at-or-below the acceptable daily intake limit every day for 70 years is not expected to have an increased risk of cancer.
To date, FDA has not recommended metformin recalls in the U.S.

NDMA ESTIMATED RISK

FDA has determined that the levels of NDMA in metformin products range from not detectable to low levels, similar to the levels you would expect to be exposed to if you ate foods like grilled or smoked meats.
Company Product Lots Tested NDMA level (micrograms-mcg/tablet)
Heritage Rx Metformin 1000mg IR* 4521603A not detected
Ingenus Pharmaceuticals Rx Metformin 1000mg ER** 19088003 not detected
Actavis Rx Metformin 1000mg ER 1358454A, 1358453A, 1358452A 0.01-0.02
Actavis Rx Metformin 500mg ER 1358450A, 1358451A, 1358449A 0.01
Sun Pharma Rx Metformin 1000mg ER GKU0762, GKU0763, GKU0764 not detected
Sun Pharma Rx Metformin 500mg ER GKU06060 not detected
Westminster Pharmaceuticals Rx Metformin 1000mg IR D107031 not detected
Heritage Rx Metformin 1000mg IR 4521611A not detected
Aurobindo Rx Metformin 1000mg IR MTSC19039-A not detected
Major Pharmaceuticals Rx Metformin 1000mg IR M02599D not detected
*Immediate release
** Extended release

Related Information

https://www.fda.gov/drugs/drug-safety-and-availability/laboratory-tests-metformin

Novel Coronavirus Vaccine Development Still on Track

Early steps in the development of a vaccine for the novel coronavirus have gone as planned, the head of the National Institute of Allergy and Infectious Diseases (NIAID) said on Friday.
“There have been no glitches so far,” said NIAID Director Anthony Fauci, MD, discussing a messenger RNA platform for producing viral antigens being developed by the National Institutes of Health in partnership with biotech company Moderna.
Fauci said during a press briefing with members of President Trump’s Coronavirus Task Force that immunogenicity had been established in mouse models, supplies of the drug were being developed, and barring any unexpected glitches “we will be in people in a phase I trial within the next 2.5 months.”
The Task Force offered assurance that things were largely status quo in the U.S., where the virus — known as 2019-nCoV — is still a low-level threat and is being contained with aggressive measures, including 14-day quarantines for some 800 passengers that have been evacuated from the Wuhan area.
The official U.S. case count stands at 12, though reports have surfaced that 11 Americans are among dozens diagnosed with the virus aboard a cruise ship off the coast of Japan.
CDC Director Robert Redfield, MD, said the agency had already screened 17,000 passengers coming in from flights from China, including an estimated 4,000 today. Worldwide, 31,530 cases have been reported, along with 638 deaths, the vast majority in Hubei province in China.
During the briefing, FDA Commissioner Stephen Hahn, MD, said that so far the medical supply chain — which relies heavily on drugs and other goods produced in China — had been unaffected by the outbreak, but that could change.
“FDA is closely monitoring the situation,” said Hahn. “At this moment, we have received no reports from manufacturers about disruptions to the medical product supply chain. Obviously the situation is fluid, and we’ll do everything we can to continue to monitor this and act accordingly.”
In the U.S., the CDC has already started sending out coronavirus diagnostic kits to certified laboratories across the country and Fauci suggested that point-of-care antibody tests would be an important next step in order to perform broad sero-surveillance screening and better determine the scope of the outbreak.
The World Health Organization reported on Friday that among 17,000 cases of the novel coronavirus, 82% were mild, 15% severe, and 3% critical.
New data also emerged detailing the risk for hospital-acquired with the novel coronavirus and the demands on intensive care units (ICUs) at the epicenter of the outbreak.
The single-center series in JAMA included 138 consecutive patients hospitalized at Zhongnan Hospital of Wuhan University with confirmed cases of the novel coronavirus from Jan. 1 to Jan. 28.
Among these patients (median age 56, men 54.3%), 26.1% ended up in the ICU, and hospital-acquired infection was presumed to be the source of infection in 41.3% (40 healthcare workers and 17 hospitalized patients), reported Zhiyong Peng, MD, of the Zhongnan Hospital of Wuhan University, and colleagues.
Most (88.9%) were treated with antiviral therapy, at least 64.4% received antibacterials, and a little less than half received glucocorticoid therapy (44.9%). Complications leading to ICU transfer included acute respiratory distress syndrome, arrhythmia, and shock. Patients landing in the ICU tended to be older (median 66 vs 51 years), have dyspnea (63.9% vs 19.6%) or anorexia (66.7% vs 30.4%), and a higher proportion had underlying comorbidities (72.2% vs 37.3%).
The study noted that all patients showed “bilateral patchy shadows or ground glass opacity in the lungs” on CT scans.
In all, six of the 138 patients died (4.3%). Median duration of hospital stay among the 47 discharged patients was 10 days. The remaining 85 patients were still hospitalized as of Feb. 3.
Study authors reported no conflicts of interest.

Many State Medicaid Programs Flop for Lung Cancer Screening

When it comes to screening Medicaid patients for lung cancer, states need to do a better job, a report found.
“Lung cancer screening using low-dose computed tomography is recognized by the U.S. Preventive Services Task Force (USPSTF) with a Grade B rating, and therefore is a covered health benefit for Medicare and commercial insurance beneficiaries; it is not mandated for Medicaid,” noted the report commissioned by the LUNGevity Foundation, a Chicago-based group aimed at improving lung cancer survival rates. “Unfortunately, almost one-third of states do not cover lung cancer screening.”
When compared by region, screening rates were better for Northeastern states; 91% covered the screening, compared with Southern states, where only 50% covered it, according to the report, which was written by the consulting firm ADVI using publicly sourced data. A total of 66% of Midwestern states covered it, as did 61% of Western states.
Byron Crowe, MD, associate medical director at Solera Health, a Denver digital health company that creates programs to address chronic disease and social determinants of health, said it was “very exciting” to see that 66% of state Medicaid plans were covering the screening even thought they weren’t obliged to. “We’re optimistic about the other 33%” also deciding to cover it eventually, said Crowe, who spoke during a phone interview with a public relations person present. “We think coverage of these preventive services is a huge benefit to patients and should be something states embrace.” Crowe noted that more and more states have begun covering diabetes prevention programs, “and we’re hopeful more states will adopt coverage for other Grade A and B recommendations that aren’t now covered.”
The report also examined rates of coverage for lung cancer biomarker testing. “Last year, Medicare issued a National Coverage Decision (NCD) validating the clinical utility of NGS [next generation sequencing] panels for somatic mutation analysis in advanced malignancies (including lung cancer) and establishing coverage and payment for FDA-approved panels,” the authors noted. “Many, although not all, commercial insurers cover these panels as a medical benefit in lung cancer. Medicaid, however, is not bound by either Medicare NCDs or a commercial payer policy.” Overall, “we found that the vast majority of states did not have an explicit coverage policy for comprehensive biomarker testing, but that about 40% did provide coverage (as evidenced by paid claims) as a medical benefit.”
Finally, the authors looked at how many states covered the routine costs of clinical trials — procedures and services needed during the trial, excluding the drugs themselves — for experimental treatments for lung cancer and other diseases. They found that 24% of state Medicaid plans provided this coverage.
The report also graded individual states on five factors, giving them one point for each:
  • Medicaid program covers lung cancer screening
  • Medicaid fee-for-service program covers comprehensive biomarker testing
  • Is a Medicaid expansion state
  • Lung cancer incidence is less than the national average; currently lung cancer represents 13% of all cancers diagnosed nationwide
  • State’s 5-year lung cancer survival rate is higher than the national average of 21.7%
The four states receiving an “A” grade — with 5 points — were Maryland, Minnesota, Oregon, and Washington; those with “F” grades — 0 or 1 point — included Alabama, Arkansas, Georgia, Idaho, Kansas, Kentucky, Louisiana, Mississippi, Missouri, Nebraska, North Carolina, Oklahoma, South Carolina, and Tennessee.
“We recognize there is a lot of work to do,” the authors wrote, adding that their report “establishes a baseline to measure improvements (or lack thereof) in how lung cancer care is delivered, and to identify pain points and opportunities in the system that we can address to improve patient access to better care, including precision medicine treatments.”
https://www.medpagetoday.com/hematologyoncology/lungcancer/84779

China to help key industries to return to work as soon as possible – CCTV

China’s cabinet says workers in key industries must be helped to return to work as soon as possible in order to resume the production of vital food and medical supplies disrupted by the coronavirus outbreak, state broadcaster CCTV said on Sunday.

The State Council’s special coronavirus group ordered railways, airlines and other public transport to take a coordinated approach and minimise the risk of transmitting disease. It will also expand the coverage and speed of screening procedures.
It also said workers should return in “batches” and not all at once in order to reduce infection risks.

https://www.marketscreener.com/news/China-to-help-key-industries-to-return-to-work-as-soon-as-possible-CCTV–29967689/?countview=0

Coronavirus death toll tops SARS as China goes back to work

Factories in China will slowly begin getting back online tomorrow following an extended Lunar New Year break that saw two-thirds of China’s economy stay closed last week.
Meanwhile, the death toll from the new coronavirus outbreak has now surpassed that of the SARS epidemic nearly two decades ago, as the number of fatalities from the virus topped 800.
China’s National Health Commission has also confirmed 2,656 new coronavirus cases, bringing the total to 37,198. SARS infected 8,098 people during its outbreak.
https://seekingalpha.com/news/3539872-coronavirus-death-toll-tops-sars-china-goes-back-to-work

Saturday, February 8, 2020

China scrambles to keep cities in virus lockdown fed

The manager of the Wushang Mart in Wuhan, the locked-down city at the heart of China’s virus outbreak, says its shelves are loaded with 50% more vegetables and other food than usual to reassure jittery customers.
Communist leaders are trying to keep food flowing to crowded Chinese cities despite anti-disease controls and to quell fears of possible shortages and following panic buying after most access to Wuhan was cut off Jan. 23.
Employees at the Wushang Mart wear masks and protective suits. Customers wash their hands with disinfectant and are checked for the virus’s telltake fever, said the manager, who would give only her surname, Lu.
“It is normal for people to worry about supply, but we explain there will be enough,” Lu said by phone.
Food stocks in supermarkets ran low shortly after Beijing imposed travel curbs and extended the Lunar New Year holiday to keep factories, offices and other businesses closed and the public at home in an attempt to prevent the virus from spreading.
That also kept trucks off the road, disrupting supplies of food to markets, feed to farmers and poultry to slaughterhouses. As the shutdown of Wuhan expanded to cover cities with a total of 60 million people, villagers set up their own roadblocks to keep outsiders and possible infection away.
This week, a Cabinet official acknowledged vegetable supplies were uneven and some “daily necessities” were sold out.
“These problems are being coordinated and resolved,” Lian Weiliang, deputy chairman of the National Development and Reform Commission, said at a Feb. 3 news conference in Beijing.
Later that day, state TV announced the ruling Communist Party order local authorities nationwide to “ensure the supply of daily necessities” including vegetables, meat, eggs, milk and grain.
The following day, the Agriculture Ministry told officials to unblock transportation and “ensure normal operation” of livestock and feed production. Unauthorized roadblocks were banned.
Merchants were warned earlier against hoarding and price-gouging. The Shanghai city government said it fined a supermarket 2 million yuan ($270,000) for raising the price of cabbage by 400%.
To reassure the public, state media are filled with photos of boxes stuffed with eggplants, cauliflower and other vegetables being loaded onto trucks for delivery to markets.
Party leaders in Shenzhen, a city of 15 million people adjacent to Hong Kong that is a center for finance and technology, sent officials to rural Yunnan province in the southwest to make sure vegetable shipments resumed quickly after the holiday, the Shenzhen News Net reported.
China already was struggling with surging food prices due to an outbreak of African swine fever that began in 2018. Millions of pigs died or were destroyed, disrupting supplies of pork, the country’s staple meat.
The price of pork doubled in December from a year earlier, pushing up overall food costs by double digits. The government has released pork from stockpiles but industry analysts say prices and the size of Chinese pig herds are unlikely to return to normal until at least next year.
In quarantined areas, trucks with government permits are allowed through roadblocks every day to bring in food. Soldiers from the ruling party’s military wing, the People’s Liberation Army, have taken over delivery of medical supplies.
Some trucking companies are shorthanded because drivers who returned to their hometowns for Lunar New Year are stranded there by the suspension of bus and train links in some areas.
“We have eight trucks and three of them are operating now,” said an employee of a vegetable delivery company in the eastern city of Nanjing. She would give only her surname, Yao.
The Wushang Mart cut its daily opening hours from 13 to seven and put the whole staff to work in one shift, said Lu, the manager. That includes unloading 1,000-kilogram (2,000-pound) truckloads of green beans, spinach, potatoes and other vegetables.
“The stock we have now is 50% more than normal,” Lu said.
Even getting out to shop is a challenge in some cities that are under almost total quarantine.
Only one member of each household is allowed out each day to shop for food in Hangzhou, an industrial metropolis of 10 million people southwest of Shanghai, and in Huanggang, a city of 1 million near Wuhan.
Millions of households are relying instead on online grocery shopping, already a booming Chinese consumer trend.
JD.com, Alibaba Group and smaller rivals say they are delivering meat, vegetables and other supplies in locked-down cities. Employees have been given masks, goggles, protective clothing, disinfectant and other supplies.
JD.com, the country’s biggest online direct retailer, said its sales of fresh food in Wuhan were up 280% from a year ago in the week ending Feb. 2. Nationwide, it says sales of beef, pork and eggs were up 400%. The company said it sold 1.8 million bottles of disinfectant.
In Nanjing, an outlet of the Huarun supermarket chain is stocking more than usual “to make sure people have enough to eat,” said an employee who answered the phone there. He refused to give his name.
“There were some people who tried to buy a lot, but they no longer do it after seeing the abundant supply,” said the employee.
https://medicalxpress.com/news/2020-02-china-scrambles-cities-virus-lockdown.html

WHO: Number of coronavirus cases ‘stabilizing’ in China

The number of cases of the deadly novel coronavirus being reported on a daily basis in China is “stabilising”, the World Health Organization said on Saturday.
The UN health agency said this was “good news” but cautioned that it was too early to make any predictions about whether the virus might have peaked.
“There has been a stabilisation in the number of cases reported from Hubei,” Michael Ryan, head of WHO’s Health Emergencies Programme, said at a briefing in Geneva.
The central Chinese province of Hubei has been at the epicentre of the virus outbreak and has been placed under lockdown by the authorities in an effort to contain the virus.
“We’re in a four-day stable period where the number of reported cases hasn’t advanced. That’s good news and may reflect the impact of the control measures that have been put in place,” Ryan said.
But he added that it was “very early to make any predictions”.
WHO chief Tedros Adhanom Ghebreyesus said the trend was “not really accelerating” but also called for “caution”.
The coronavirus has infected more than 34,500 people and killed more than 700.
Tedros warned against misinformation about the virus, saying it made the work of healthcare staff harder.
“We’re not just battling the virus, we’re also battling the trolls and conspiracy theorists that push misinformation and undermine the outbreak response,” he said.
Asked about a planned WHO-led international mission to China, he also said a list of names had been submitted to Chinese authorities and the team leader would be travelling there on Monday or Tuesday.
“The rest of the experts will also follow after that,” he said.
Asked if the mission would include members of the US Centers for Disease Control and Prevention (CDC), he said: “I hope so”.
China has been critical of measures taken by the United States in response to the and has so far rejected an offer of assistance from the CDC.
https://medicalxpress.com/news/2020-02-coronavirus-case-stabilising.html