A study demonstrated Wellmune® may protect intestinal barrier function in adults when faced with stress.

The Council for Responsible Nutrition announced the launch of a consumer education initiative designed to raise awareness of Selective Androgen Receptor Modulators, a dangerous class of ingredients.

Obese mice with unhealthy lifestyles gain significantly less weight and avoid type 2 diabetes when they receive bacteriophages from the faeces of a lean mouse, according to a new University of Copenhagen study.

Ministers in charge of small and medium enterprises (SMEs) in the APEC region issued a statement following their meeting in Concepcion, Chile, on 5-6 September 2019.

Last month, I scheduled one-on-one discussions with our most experienced GCP auditors to ask each of them the same question: What surprises you most about the audits you conduct?

I guess you could say that I was the one who was surprised. I’m not sure exactly what I was expecting to hear, but I thought my teammates were going to talk about things that were new. Instead, I heard a lot more about things that have been around for a long time. To a person, my colleagues said they were surprised to be observing some of the same audit findings they were observing 30 years ago...which *is* surprising when you consider most of them were mere children at the time. ;-)  It seems we have some stubbornly persistent quality and compliance issues in the biopharma industry that decades of neither experience nor technology have seemed to remedy. And the problems are not just persistent; they’re interrelated.



Standard Operating Procedures (SOPs)
It’s quite common for auditors to encounter sponsors, CROs, and sites that lack an adequate set of SOPs to describe local procedures. There are several reasons for this. Sometimes it’s a lack of resources. Sometimes smaller, established organizations believe writing it all down is unnecessary, as “people know their jobs.” Sometimes newer companies are simply unaware that written procedures are required for particular operations. But when procedures are not documented, organizations are unable to demonstrate GCP compliance, cannot ensure that activities are performed correctly or consistently, and have difficulty training new staff members. (We’ll come back to training in a bit.)

Frequently missing from a good working set of SOPs are procedures for Disaster Recovery, Handling of Suspected Fraud, and Management of Regulatory Inspections. These SOPs are not used for day-to-day operations, so perhaps that’s why they don’t garner as much attention. Nevertheless, the inability to recover from a disaster, protect the organization from fraud allegations, or pass a regulatory inspection can sink a company.

A fourth SOP that is commonly absent from the set is the document that describes how to write, approve, distribute, revise, and retire SOPs. Also frequently missing from a working set of SOPs is our next topic: Training.

Training
Training can be expensive and time-consuming, and companies increasingly have to do more with less. In-person training has largely been replaced by computer-based systems, on-site training has given way to distance learning, and mentoring has gone the way of the dodo.

The good news is that study sites typically adhere to formal GCP training requirements. What’s often missing, though, is the training that connects GCP concepts to everyday activities. A trainee might correctly answer a multiple-choice question about audit trails, but without that “last mile” of coaching, use Wite-Out to correct a source document error. This is where SOPs come in. When training is conducted using well-written SOPs, it can help bridge the gap between standard GCP training and specific site operations.

It is not uncommon for study-specific training to be lacking in CROs – protocol training, device training, computer systems user training. As part of their vendor oversight procedures (also an SOP!), sponsors should be making sure that CRO staff is adequately trained. 

Trial Master Files (TMFs)
Whether paper or electronic, it’s common for TMF documents to be missing or expired. Replacements for these documents can usually be produced and filed at the time of the audit. Misfiled documents are another matter; they are already there but cannot easily be found. Locating and refiling them essentially doubles the time and cost of the original effort. For example, documents from multiple labs, such as certificates, credentials, vendor audit results, etc., are often mistakenly commingled. Documents must be sorted and refiled so that each facility listed on the 1572 has its own file or electronic folder.


Another very common mistake is treating every document on letterhead as if it’s general correspondence. Search for the word “letter” in the DIA Reference Model and you can see how many opportunities exist for misclassifying correspondence. For example, an IND safety report sent by the sponsor on letterhead should be filed under “Notification of Safety Information,” Section 8.3.18 in ICH E6(R2), not “Relevant Communications,” Section 8.3.11. In an eTMF, an IRB approval letter belongs in 04.01.02, its designated DIA Reference Model position, not 04.04.01, which is reserved for general communication.

The root cause of these misfilings? The filer does not know enough about the filing structure of the TMF and often is not familiar enough with clinical research to know the purpose of each document and where it belongs. The corrective action? Training. Training on the TMF plan, the TMF Management SOP, ICH GCP, and study operations in general.

Technology to the Rescue?
No doubt, CTMSs, eTMFs, eCRFs, ePRO, and other systems have improved clinical operations and reduced error. However, three decades of technological advances have done little to address the most common quality and compliance issues encountered by GCP auditors – and by extension regulators. Some might find that discouraging, but isn’t it also a little satisfying that the solution to our most persistent problems comes down to human communication?

______________________________________________________________________
A version of this article originally appeared in InSite, the Journal of the Society for Clinical Research Sites.

Wednesday’s initial public offering for Cambridge-based Ra Pharmaceuticals marked the ninth biotech startup to go public this year, tying the number in 2013 but still less than either of the two years since. Ra (Nasdaq: RARX), which has 40 employees in one of the former Pfizer buildings in Alewife, ended up with the third-largest IPO size for any Massachusetts-based biotech in 2016, with a total of $92 million raised from the sale of 7 million shares for $13 each. That’s more than the $86 million…

Third Rock Ventures, the Boston-based venture capital firm behind some of the Bay State’s most prominent biotechs, has reclaimed its title as the biggest life science-focused VC firm in the state with a new $616 million round, and has also named its first female partner in eight years. With the announcement of its Fund IV today — its largest ever — the firm now has raised $1.9 billion in the nine years since it was formed. That eclipses its rival across the Charles River, Flagship Ventures,…

Pfizer partners with Valneva to progress Phase II-stage vaccine candidate for Lyme disease.

by Abrahm Lustgarten

The scientists who study how diseases emerge in a changing environment knew this moment was coming. Climate change is making outbreaks of disease more common and more dangerous.

Over the past few decades, the number of emerging infectious diseases that spread to people — especially coronaviruses and other respiratory illnesses believed to have come from bats and birds — has skyrocketed. A new emerging disease surfaces five times a year. One study estimates that more than 3,200 strains of coronaviruses already exist among bats, awaiting an opportunity to jump to people.

The diseases may have always been there, buried deep in wild and remote places out of reach of people. But until now, the planet’s natural defense systems were better at fighting them off.

Today, climate warming is demolishing those defense systems, driving a catastrophic loss in biodiversity that, when coupled with reckless deforestation and aggressive conversion of wildland for economic development, pushes farms and people closer to the wild and opens the gates for the spread of disease.

Aaron Bernstein, the interim director for the C-Change Center for Climate, Health and the Global Environment at Harvard University’s T.H. Chan School of Public Health, said that ignoring how climate and rapid land development were putting disease-carrying animals in a squeeze was akin to playing Russian roulette.

“Nature is trying to tell us something,” Bernstein said.

Scientists have not suggested that climate played any direct role in causing the current COVID-19 outbreak. Though the virus is believed to have originated with the horseshoe bat, part of a genus that’s been roaming the forests of the planet for 40 million years and thrives in the remote jungles of south China, even that remains uncertain.

Scientists have, however, been studying the coronaviruses of southern China for years and warning that swift climate and environmental change there — in both loss of biodiversity and encroachment by civilization — was going to help new viruses jump to people.

There are three ways climate influences emerging diseases. Roughly 60% of new pathogens come from animals — including those pressured by diversity loss — and roughly one-third of those can be directly attributed to changes in human land use, meaning deforestation, the introduction of farming, development or resource extraction in otherwise natural settings. Vector-borne diseases — those carried by insects like mosquitoes and ticks and transferred in the blood of infected people — are also on the rise as warming weather and erratic precipitation vastly expand the geographic regions vulnerable to contagion. Climate is even bringing old viruses back from the dead, thawing zombie contagions like the anthrax released from a frozen reindeer in 2016, which can come down from the arctic and haunt us from the past.

Thus the COVID-19 pandemic, even as it unfolds in the form of an urgent crisis, is offering a larger lesson. It is demonstrating in real time the enormous and undeniable power that nature has over civilization and even over its politics. That alone may make the pandemic prologue for more far-reaching and disruptive changes to come. But it also makes clear that climate policy today is indivisible from efforts to prevent new infectious outbreaks, or, as Bernstein put it, the notion that climate and health and environmental policy might not be related is “a ​dangerous delusion.”

---

The warming of the climate is one of the principal drivers of the greatest — and fastest — loss of species diversity in the history of the planet, as shifting climate patterns force species to change habitats, push them into new regions or threaten their food and water supplies. What’s known as biodiversity is critical because the natural variety of plants and animals lends each species greater resiliency against threat and together offers a delicately balanced safety net for natural systems. As diversity wanes, the balance is upset, and remaining species are both more vulnerable to human influences and, according to a landmark 2010 study in the journal Nature, more likely to pass along powerful pathogens.

The casualties are amplified by civilization’s relentless push into forests and wild areas on the hunt for timber, cropland and other natural resources. Epidemiologists tracking the root of disease in South Asia have learned that even incremental and seemingly manageable injuries to local environments — say, the construction of a livestock farm adjacent to stressed natural forest — can add up to outsized consequences.

Around the world, according to the World Resources Institute, only 15% of the planet’s forests remain intact. The rest have been cut down, degraded or fragmented to the point that they disrupt the natural ecosystems that depend on them. As the forests die, and grasslands and wetlands are also destroyed, biodiversity sharply decreases further. The United Nations warns that the number of species on the planet has already dropped by 20% and that more than a million animal and plant species now face extinction.

Losing species has, in certain cases, translated directly to a rise in infectious disease.

Americans have been experiencing this phenomenon directly in recent years as migratory birds have become less diverse and the threat posed by West Nile encephalitis has spread. It turns out that the birds that host the disease happen to also be the tough ones that prevail amid a thinned population. Those survivors have supported higher infection rates in mosquitoes and more spread to people.

Similarly, a study published last month in the journal Proceedings of the Royal Society B found that as larger mammals suffer declines at the hands of hunters or loggers or shifting climate patterns, smaller species, including bats, rats and other rodents, are thriving, either because they are more resilient to the degraded environment or they are able to live better among people.

It is these small animals, the ones that manage to find food in garbage cans or build nests in the eaves of buildings, that are proving most adaptable to human interference and also happen to spread disease. Rodents alone accounted for more than 60% of all the diseases transmitted from animals to people, the researchers found.

Warmer temperatures and higher rainfall associated with climate change — coupled with the loss of predators — are bound to make the rodent problem worse, with calamitous implications. In 1999, for example, parts of Panama saw three times as much rainfall as usual. The rat population exploded, researchers found. And so did the viruses rats carry, along with the chances those viruses would jump to people. That same year, a fatal lung disease transmitted through the saliva, feces and urine of rats and mice called hantavirus pulmonary syndrome emerged in Panama for the first time, according to a report in the journal Emerging Infectious Diseases.

As much as weather changes can drive changes in species, so does altering the landscape for new farms and new cities. In fact, researchers attribute a full 30% of emerging contagion to what they call “land use change.” Nothing drives land use shifts more than conversion for farmland and feedstock — a result of the push to feed the planet’s 7.8 billion people. As the global population surges to 10 billion over the next 35 years, and the capacity to farm food is stressed further again by the warming climate, the demand for land will only get more intense. Already, more than one-third of the planet’s land surface, and three-quarters of all of its fresh water, go toward the cultivation of crops and raising of livestock. These are the places where infectious diseases spread most often.

Take, for example, the 1999 Nipah outbreak in Malaysia — the true-life subject matter adapted for the film “Contagion.” Rapid clearcutting of the forests there to make way for palm plantations drove fruit bats to the edge of the trees. (Separate research also suggests that climate changes are shifting fruit bats’ food supply.) They found places to roost, as it happens, alongside a hog farm. As the bats gorged themselves on fruit, they dropped pieces of food from the branches, along with their urine, into the pigsties, where at least one pig is believed to have eaten some. When the pig was slaughtered and brought to market, an outbreak is believed to have been spread by the man who handled the meat. More than 100 people died.

The U.S. Centers for Disease Control and Prevention says that fully three-quarters of all new viruses have emerged from animals. Even the 2014 Ebola outbreak in West Africa is believed to have begun when a boy dug into a tree stump that happened to be the roost of bats carrying the virus.

As Christine Johnson, the associate director of the One Health Institute, an interdisciplinary epidemiological program at the University of California, Davis, puts it, global health policymakers have a responsibility to understand how climate, habitat and land use changes lead to disease. Almost every major epidemic we know of over the past couple of decades — SARS, COVID-19, Ebola and Nipah virus — jumped to people from wildlife enduring extreme climate and habitat strain, and still, “we’re naive to them,” she said. “That puts us in a dangerous place.”

---

Once new diseases are let loose in our environment, changing temperatures and precipitation are also changing how those diseases spread — and not for the better. Warming climates increase the range within which a disease can find a home, especially those transmitted by “vectors,” mosquitoes and ticks that carry a pathogen from its primary host to its new victim.

A 2008 study in the journal Nature found nearly one-third of emerging infectious diseases over the past 10 years were vector-borne, and that the jumps matched unusual changes in the climate. Especially in cases where insects like infection-bearing mosquitoes are chasing warmer temperatures, the study said, “climate change may drive the emergence of diseases.”

Ticks and mosquitoes now thrive in places they’d never ventured before. As tropical species move northward, they are bringing dangerous pathogens with them. The Zika virus or Chikungunya, a mosquito-spread virus that manifests in intense joint pain, were once unseen in the United States, but both were transmitted locally, not brought home by travelers, in southern Texas and Florida in recent years.

Soon, they’ll be spreading further northward. According to a 2019 study in the journal PLOS Neglected Tropical Diseases, by 2050, disease-carrying mosquitoes will ultimately reach 500 million more people than they do today, including some 55 million more Americans. In 2013, dengue fever — an affliction affecting nearly 400 million people a year, but normally associated with the poorest regions of Africa — was transmitted locally in New York for the first time.

“The long-term risk from dengue may be much higher than COVID,” said Scott Weaver, the director of the Institute for Human Infections and Immunity at the University of Texas Medical Branch in Galveston. “It’s a disease of poor countries, so it doesn’t get the attention it deserves.”

The chain of events that ultimately leads to a pandemic can be long and subtle, steered by shifts in the ecosystem. The 1999 West Nile outbreak in the U.S., for example, came after climate-driven droughts dried up streams and rivers, leaving pools of stagnant water where mosquitoes bred unhindered. It turns out the loss of water also killed off their predators — dragonflies and frogs that depend on large watering holes were gone.

Coronaviruses like COVID-19 aren’t likely to be carried by insects — they don’t leave enough infected virus cells in the blood. But one in five other viruses transmitted from animals to people are vector-borne, said U.C. Davis’ Johnson, meaning it’s only a matter of time before other exotic animal-driven pathogens are driven from the forests of the global tropics to the United States or Canada or Europe because of the warming climate. “Climate is going to shift vulnerability to that,” Johnson said, “and I think some of these regions are not prepared.”

The changing climate won’t just affect how the diseases move about the planet, it will also shape how easily we get sick. According to a 2013 study in the journal PLOS Currents Influenza, warm winters were predictors of the most severe flu seasons in the following year. The brief respite in year one, it turns out, relaxed people’s natural defenses and reduced “herd immunity,” setting conditions for the virus to rage back with a vengeance.

Even harsh swings from hot to cold, or sudden storms — exactly the kinds of climate-induced patterns we’re already seeing — make people more likely to get sick. A study in the journal Environmental Research Letters linked the brutal 2017-18 flu season — which killed 79,000 people — to erratic temperature swings and extreme weather that winter, the same period in which a spate of floods and hurricanes devastated much of the country. If the climate crisis continues on its current trajectory, the authors wrote, respiratory infections like the flu will sharply increase. The chance of a flu epidemic in America’s most populated cities will increase by as much as 50% this century, and flu-related deaths in Europe could also jump by 50%.

“We’re on a very dangerous path right now,” said the University of Texas’ Weaver. Slow action on climate has made dramatic warming and large-scale environmental changes inevitable, he said, “and I think that increases in disease are going to come along with it.”

---

Twelve months before the first COVID-19 case was diagnosed, a group of epidemiologists working with a U.S. Agency for International Development project called PREDICT, or Pandemic Influenza and other Emerging Threats, was deep in the remote leafy jungle of southern China’s Yunnan province hunting for what it believed to be one of the greatest dangers to civilization: a wellspring of emerging viruses.

A decade of study there had identified a pattern of obscure illnesses affecting remote villagers who used bat guano as fertilizer and sometimes for medicine. Scientists traced dozens of unnamed, emerging viruses to caves inhabited by horseshoe bats. Any one of them might have triggered a global pandemic killing a million people. But luck — and mostly luck alone — had so far kept the viruses from leaping out of those remote communities and into the mainstream population.

The luck is likely to run out, as Yunnan is undergoing enormous change. Quaint subsistence farm plots were overtaken by hastily erected apartment towers and high-speed rail lines, as the province endured dizzying development fueled by decades of Chinese economic expansion. Cities’ footprints swelled, pushing back the forests. More people moved into rural places and the wildlife trade, common to such frontier regions, thrived. With every new person and every felled tree, the bats’ habitat shrank, putting the viruses they carried on a collision course with humanity. By late 2018, epidemiologists there were bracing for what they call “spillover,” or the failure to keep a virus locally contained as it jumped from the bats and villages of Yunnan into the wider world.

In late 2018, the Trump administration, as part of a sweeping effort to bring U.S. programs in China to a halt, abruptly shut down the research — and its efforts to intercept the spread of a new novel coronavirus along with it. “We got a cease and desist,” said Dennis Carroll, who founded the PREDICT program and has been instrumental in global work to address the risks from emerging viruses. By late 2019, USAID had cut the program’s global funding.

USAID did not respond to a detailed list of questions from ProPublica.

The loss is immense. The researchers believed they were on the cusp of a breakthrough, racing to sequence the genes of the coronaviruses they’d extracted from the horseshoe bat and to begin work on vaccines. They’d campaigned for years for policymakers to fully consider what they’d learned about how land development and climate changes were driving the spread of disease, and they thought their research could literally provide governments a map to the hot spots most likely to spawn the next pandemic. They also hoped the genetic material they’d collected could lead to a vaccine not just for one lethal variation of COVID, but perhaps — like a missile defense shield for the biosphere — to address a whole family of viruses at once. (In fact, the gene work they were able to complete was used to test the efficacy of remdesivir, an experimental drug that early clinical trial data shows can help COVID-19 patients.)

Carroll said knowledge of the virus genomes had the potential “to totally transform how we think about future biomedical interventions before there’s an emergence.” His goal was to not just react to a pandemic, but to change the very definition of preparedness.

If PREDICT’s efforts in China had the remote potential to fend off the current COVID pandemic, though, it also offered an opportunity to study how climate and land development were driving disease.

But there has been little appetite for that inquiry among policymakers. PREDICT’s staff and advisers have pushed the U.S. government to consider how welding public health policy with environmental and climate science could help stem the spread of contagions. Climate change was featured in presentations that PREDICT staff made to Congress, according to U.C. Davis’ Johnson, who is now also the director of PREDICT, which received a temporary funding extension this spring. And until 2016, leadership of New York-based EcoHealth Alliance, the research group working under PREDICT funding in Yunnan, was invited several times to the White House to advise on global health policy.

Since Donald Trump was elected, the group hasn’t been invited back.

“It’s falling on deaf ears,” said Peter Daszak, EcoHealth Alliance’s president.

A White House spokesperson did not respond to an emailed request for comment.

What Daszak really wants — in addition to restored funding to continue his work — is the public and leaders to understand that it’s human behavior driving the rise in disease, just as it drives the climate crisis. In China’s forests, he looks past the destruction of trees and asks why they are being cut in the first place, and who is paying the cost. Metals for iPhones and palm oil for processed foods are among the products that come straight out of South Asian and African emerging disease hot spots.

“We turn a blind eye to the fact that our behavior is driving this,” he said. “We get cheap goods through Walmart, and then we pay for it forever through the rise in pandemics. It’s upside down.”

---

NHS England has advised pharmacies to risk assess staff who may be particularly vulnerable to COVID-19, including those from a black, Asian or minority ethnic background.

To read the whole article click on the headline

March 4, 2020 — The U.S. Supreme Court delivered a surprise on March 2 when it announced it will hear a challenge to the constitutionality of the Affordable Care Act (ACA) next term, leap-frogging over the process that was playing out in lower courts. Oral arguments have not yet been scheduled, but are likely to […]

Come on in, the water’s warm. After billions already raised by VC firms since the advent of the pandemic for life science companies, Oberland Capital has tossed more than $1 billion into the pot.

Eli Lilly has teamed with China’s Junshi Biosciences in the U.S., marking the company's second COVID-19 pact to develop neutralizing antibodies against the virus. It promises to be a faster approach than designing a new small-molecule drug would be, but getting from idea to an effective product may not be so simple.

A recent study looking at the effects of caffeine on brief, high intensity exercise found the substance improved performance, regardless of genetic variations in how subjects metabolized caffeine.

Combining exercise with a bacterial strain isolated from an Olympic weightlifting gold medalist may synergistically increase endurance compared to training or the probiotic alone, suggests data from a mouse study.

Alternative title: Pitching a VC on Disruption of Blood Testing You may have seen some recent editorials about the necessary frequency of blood tests for healthy individuals, many of them prompted by a series of tweets from Mark Cuban: Although there are certainly potential dangers in expecting any and all test results to be immediately

Norwegian Cruise Line says it's in danger of going out of business. Maybe that's not the worst thing for an industry of floating petri dishes.

Doctors have recently identified a condition called pediatric inflammatory multi-system syndrome among children who have tested positive for antibodies against COVID-19.

Many countries saw the coronavirus as a "rich man's disease" imported by overseas travelers. It has since hit marginalized groups the hardest.

In the past week, Orange County has announced 21 deaths linked to COVID-19, pushing the total since the pandemic began to 71.

Check important government schemes launched by the Ministry of Health & Family Welfare which are important to study for the UPSC (IAS) Prelims 2020 exam.

Stormbreaker Venture, an edtech accelerator, is a common investor in both the companies.

The post Thai Digest: Edtech startups Vonder, Conicle raise early-stage funding appeared first on DealStreetAsia.

In 2018, Funtap had raised $300,000 in a seed funding round from Korean investor Soulbei.

The post Vietnamese game publisher Funtap raises Series A round led by Makers Fund appeared first on DealStreetAsia.

It plans to use the funds to hire new talent, develop its product and technology further and scale up its lending volumes.

The post Indian fintech startup NIRA raises $2.1m in pre-series A funding appeared first on DealStreetAsia.

The company said the latest round was led by existing investor Sequoia Capital.

The post Fintech startup Robinhood raises fresh funds at $8.3b valuation appeared first on DealStreetAsia.

Ninja Van becomes one of the few startups to score new funding since Covid-19 chilled deal activity.

The post Singapore’s Ninja Van raises $279m after pandemic drives e-commerce surge appeared first on DealStreetAsia.

Sydney-based document design company Qwilr has raised $7.25-million Series A led by AirTree Ventures.

The post Australia Digest: Qwilr raises $7.25m; PieLAB invests in :Different appeared first on DealStreetAsia.

Dakota will also establish “Myanmar’s first-ever cyber training centre."

The post Asia Digest: Dakota Ventures to invest $1m in Myanmar; Vietnam’s FoodHub raises funding appeared first on DealStreetAsia.

Exfinity Ventures and IAN Fund led the funding in Vernacular.ai.

The post India Deal Monitor: Vernacular.ai raises $5.1m in Series A round and more updates appeared first on DealStreetAsia.

Tencent, which first invested in Enflame's pre-Series A round in July 2018, also topped up.

The post Tencent-backed Chinese AI startup Enflame raises nearly $100m Series B funding appeared first on DealStreetAsia.