Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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States are panic buying powerful deep freezers to store the COVID vaccine at -94F

after Pfizer announced their trial had been successful


11/13/20


https://www.dailymail.co.uk/news/articl ... rries.html


Pfizer's coronavirus vaccine requires ultra-cold temperatures for storage and has led to hospitals, states and cities across the country panic-buying freezers
The scramble comes amid news from the drug giant that the new vaccine requires storage at temperatures of minus 94 degrees Fahrenheit
Usually, vaccines are required to be stored at minus 36-46 degrees Fahrenheit
CDC has said first vaccine doses will likely be shipped out in limited quantities and used right away, negating the need for such powerful freezers
Early clinical trials found the Pfizer vaccine to be 90% effective against the coronavirus in early clinical trials .

U.S. states, cities, and hospitals are scrambling to buy ultra-cold freezers that can safely store Pfizer Inc's COVID-19 vaccine, ignoring advice from the U.S. Centers for Disease Control and Prevention (CDC) to hold off.

The push reveals a lack of infrastructure to support a super cold vaccine campaign, including equipment to store millions of doses of Pfizer's vaccine at temperatures of minus 70 degrees Celsius (minus 94°F), significantly below the standard for vaccines of 2-8 degrees Celsius (36-46°F).

Some specialty freezer makers warn of months-long waits for units.

It also marks widespread wariness of the advice from the CDC, which on August 26 urged healthcare providers not to purchase ultra low temperature (ULT) freezers, saying it was working on solutions for Pfizer's 'very complex storage and handling requirements.'

A CDC spokeswoman on Thursday said the agency expects the first vaccine doses will be in limited quantities and rapidly deployed, reducing the need to store them in specialized freezers.

But the news on Monday that initial results from a pivotal trial of the vaccine developed by Pfizer and German partner BioNTech showed it to be more than 90% effective has turned attention to eventual shipping and storage logistics.

That has thrown a spotlight on makers of the niche freezers, including Thermo Fisher Scientific Inc, Luxembourg's B Medical Systems, Helmer Scientific and Stirling Ultracold, who are adding labor and expanding capacity.

'I would estimate that a third of states are purchasing ultra cold storage equipment,' said Claire Hannan, executive director of the Association of Immunization Managers, a nonprofit representing state and local public health officials who handle vaccines.

The specialized freezers required by Pfizer's vaccine can cost $5,000 to $15,000.

Moderna Inc is close to releasing efficacy results for its similar vaccine, which requires an easier to accommodate storage temperature of minus 20 degrees Celsius (minus 4°F).

At least half a dozen states, including California, Rhode Island and New Mexico, said in published comments to the CDC that they expect to face challenges due to limited supplies of ULT freezers. A similar number told Reuters or said in public filings that they are purchasing units in anticipation of the vaccine rollout.

Kentucky Governor Andy Beshear on Thursday called for federal funding for cold storage and said he hopes other vaccines with less onerous storage requirements get approved.

Earlier this year, due to lack of a coordinated federal response to the pandemic, states were forced to compete against each other for everything from protective N95 masks for healthcare workers to ventilators and testing equipment.

While demand for ULT freezers is climbing, it has not entered the early pandemic's ventilator panic phase where 'we had lead times of 18 months,' said Rebecca Gayden, who oversees sourcing of freezers and other capital equipment at Vizient, a purchasing group used by more than 5,000 not-for-profit health systems and affiliates.

Northwell Health, New York state's largest hospital system, said it has leased around 20 ultra cold freezers for the Pfizer vaccine, and that manufacturers now had waiting lists.

Thermo Fisher said it built up inventory ahead of demand, and is unaffected by capacity crunches.

Some smaller manufacturers, however, acknowledged issues due to the surge in demand. Indiana-based Helmer Scientific said production of new orders has pushed into next year.

Ohio's Stirling Ultracold, which sold a 6,000-dose portable, cooler-sized ULT to North Dakota as well as large freezers for United Parcel Service Inc's freezer farms, said delivery waits could now extend up to two months.

George Gerhardt, emergency preparedness program representative for North Dakota, where the virus is now running rampant, said his state started shopping for freezers this summer. 'If we wait till the last day, everybody's going to want one,' Gerhardt said at the time, before purchasing 10 ULT units.

The Wyoming Department of Health was not so lucky. Its ULT freezer is on 'back order' until late December, said public information officer Kim Deti.

Cities and states are searching university labs, hospitals and other facilities for available ULT freezer space.

Philadelphia is spending about $19,000 on two B Medical freezers scheduled to be installed later this month, and is working with local healthcare systems to secure additional capacity.

Pfizer's vaccine could get regulatory approval within weeks with distribution to begin almost immediately.

It will be transported in dry ice-filled, suitcase-sized containers that can only be opened twice a day and last a maximum of two weeks. Dry ice has also been offered as a potential solution for nations without access to ULT storage in vaccination centers.

'Waste is a major concern,' said Soumi Saha, vice president of advocacy at Premier Inc, which coordinates purchases for thousands of U.S. hospitals and health systems.

'Do you turn a patient away because you can't open it a third time that day?'
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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New Timestrip indicators to support the use of promising coronavirus vaccines

11/16/20


https://www.news-medical.net/news/20201 ... cines.aspx


Timestrip®, the developer of smart indicator technology, has moved fast to develop a range of products that support use of the coronavirus vaccines now promising to become available. Special liquid indicators have been created by Timestrip which can travel with the frozen vaccine supplies as they move from manufacture to the point of care, ensuring that any temperature breach can be identified.

As one or more vaccines are planned for distribution, attention is focusing on the ultra-cold chain, as Covid-19 vaccines may need to be stored and transported at temperatures as low as -70 C. Any breach of the specified temperature conditions is revealed by the new Timestrip smart labels with a clear irreversible indication.

After thawing, vaccines must be used quickly, usually within a few days, and Timestrip indicators are also available to monitor this critical period and alert medical staff to time expired product.

Antiviral treatments such as Gilead’s VEKLURY® product have also to be kept cool, and then after dilution, can be stored for between one and two days - depending on the storage temperature - prior to administration. Timestrip indicators are available to monitor these conditions and automatically adjust the time to expiry as conditions change.

Other applications now being made available include a range of indicators for virus specimens as they are sent for laboratory testing. The Virus Specimen Transport (VST) series of indicators includes a time / temperature indicator (TTI) that mirrors the response of the virus specimens, and can alert healthcare organisations to compromised samples.

In yet another initiative, Timestrip has introduced ‘Rapid Diagnostics 15’, a short term time indicator designed for use with the new rapid turnaround lateral flow test kits now being rolled out more widely.

" As market leaders in the time and temperate indicator sector, we must play our part and support the great work being carried out during the pandemic. We are working to develop cost effective, bespoke solutions to support the regulatory bodies in their efforts to deliver product safely through the cold and ultra-cold supply chains."

- Nora Murphy, Commercial Director of Timestrip
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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A Possible Covid Vaccine Means It's Time to Fix Cold Chains

The global immunization effort could offer a once-in-a-lifetime opportunity to create sustainable and resilient distribution systems.

11/11/20


https://www.wired.com/story/a-possible- ... ld-chains/


Efforts to find a lasting solution to the Covid-19 pandemic have been primarily focused on developing, testing, and manufacturing at scale an effective vaccine. But little attention has been given to the requirements for distributing that vaccine rapidly at scale. That changed this week, when the first Covid-19 vaccine candidate announced to be effective, from Pfizer-BioNTech, confirmed that it requires two doses and cold storage at –94 degrees Fahrenheit, or –70 degrees Celsius.

To protect both efficacy and safety, most vaccines need to be maintained at a specific temperature in a seamless unbroken cold-chain from the manufacturer to the point of use. Normally, it’s around 35.6 to 46.4 degrees Fahrenheit (2 to 8 degrees Celsius). But at the drastically cold temperatures this Covid-19 vaccine requires, distribution will be challenging even in the advanced economies of the Global North. The chronic absence of suitable equipment capacity, even for the manufacture of dry-ice, also means this vaccines could not currently be readily supplied at scale in Africa, South America, and Asia, where billions of people will need to be immunized.

Maintaining vaccines continuously at their required temperature is already one of the biggest challenges developing countries face with routine immunization, and this will only be exacerbated with the introduction of a new vaccine. It is estimated that we lose upwards of 25 percent of all vaccines along the way from a lack of robust cold-chains in which to move them. In some countries, only 10 percent of health centers have a proper, working vaccine fridge.

The success of Covid-19 immunization will depend on delivering temperature-controlled vaccines to every community, village, and settlement in the world. But in the Global South, a large proportion of the population lives in rural, remote, difficult to access areas. Much of the routine immunization services there are provided via outreach; essentially a health worker traveling on a bike, by foot, or in a car uses an insulated vaccine carrier with ice packs to keep the vaccine cool. Geographical barriers, difficult terrain, and poor infrastructure—such as a lack of transportation and bad road conditions—already place burdens on health care workers and reduces the ability to deliver frequent immunization sessions.

The volume and speed that a global Covid-19 vaccination will require—never before seen—will necessitate an entirely new fast-track approach. Along with the provision of additional hardware from warehouses to vehicles to fridges to insulated carriers or back-packs, we must not underestimate the impact that a shortage of qualified engineers, technicians, and mechanics, and inadequate skills training across the range of cold chain technology, will have on distribution. Long response times to equipment malfunction could potentially increase the proportion of broken cold chain equipment at any point, and result in wasted vaccines.

To add to our challenges, while the cold chain is an integral part of achieving immunization targets, it comes with an environmental cost. Including both energy emissions (indirect emissions) and leaks of highly potent HFC refrigerant gases (direct emissions), one estimate suggests that cold chains already represent 3.5 percent of greenhouse gas (GHG) emissions in developed economies. Recent estimates also indicate that the health care sector is responsible for approximately 5 percent of GHG emissions.

Many health facilities in developing countries suffer from lack of reliable electricity and often rely on polluting diesel generators for powering fridges and other cold chain equipment. Likewise, current refrigerated units in vans in the cold chain run on diesel and use high-GWP refrigerants, contributing further to emissions.

But turn the challenges on their head and, given that most of the technologies deployed today will still be in operation for years to come, the Covid-19 global immunization effort could offer us a once-in-a lifetime opportunity to create sustainable and resilient health cold-chain systems, including for ultra-low temperatures. At a minimum, it is an imperative that the new cold chain capacity is not based on environmentally harmful technologies that hinder the world’s ability to meet emissions targets. Better yet, we should go further and leapfrog to new strategies.

Drones are already proving their value for rapid delivery of pharmaceutical products in rural locations. Combined with new mobile rechargeable micro-chillers, these offer new integrated logistics solutions for the cold-chain—far faster and clean than road-based trucks. Off-grid mobile cold-rooms could enable more cost-efficient campaign approaches and have the ability to be repurposed for a long-term life. We also have the chance to embed real-time data capability across the system to ensure vaccine quality and chain of custody from point of manufacture through to point of delivery and help manage risks and breakages in the system along the way.

In the short-term, it will be the poorer nations that will face the most significant challenges to distributing Covid-19 vaccines. Access to sustainable cooling will become a serious issue of equity that underpins fair access to immunization. As governments and NGOs develop distribution plans, cold chains must guarantee the health response, but should also draw on the most sustainable solutions to build long-term resilience and contribute to green recovery worldwide. All opportunities for incorporating efficient, clean cooling technologies and approaches into equipment procurements, optimization strategies, and delivery plans must be considered and, as much as possible, taken. This will impact the health of the whole world for decades to come; let’s take the opportunity to deliver lasting positive legacy for future generations.
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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Why a strong cold chain is more critical than ever to defeat COVID-19

Published on 24 April 2020


https://www.bmedicalsystems.com/2020/04 ... -covid-19/#


History has proven the power of vaccines. Today, immunization against potential pandemics reaches more than 80% of children worldwide and saves 2 million to 3 million lives each year, thanks to national governments and the work of transnational organizations such as UNICEF, Gavi, Médecins Sans Frontières, the World Health Organization, and the Bill & Melinda Gates Foundation. The eventual discovery of a COVID-19 vaccine will undoubtedly arm the world with a powerful tool to defeat the virus.

However, history has also shown us that a vaccine in itself is not a panacea. Its development will be the beginning of a long fight against a virus that has spread at a breakneck speed across more than 150 countries. To win the fight, we will need to immunize 60% to 70% of all individuals. This will not only require massive manufacturing and logistic capabilities but also strong cold-chain systems.

As most are temperature sensitive, their transport and storage require constant refrigeration along the entire supply-chain. Solutions to transport and store vaccines in tropical weather conditions have existed since 1979. New innovative technologies and advanced features have emerged since then. There exist today vaccine refrigerators resistant to abrupt voltage spikes and cold chain equipment powered by solar panels.

Despite these technological innovations, vaccines are still wasted today because of temperature control and related logistics. The problem is that many health centers in low- and middle-income countries don’t have adequate vaccine cold-chain systems.

While the world is waiting for a vaccine, it is high time to think ahead and join forces in arming the most vulnerable countries with the reliable cold chain equipment they will need to bring the pandemic under control.
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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Vaccine storage issues could leave 3B people without access

October 25, 2020


https://apnews.com/article/virus-outbre ... adb1c14168


GAMPELA, Burkina Faso (AP) — The chain breaks here, in a tiny medical clinic in Burkina Faso that went nearly a year without a working refrigerator.

From factory to syringe, the world’s most promising coronavirus vaccine candidates need non-stop sterile refrigeration to stay potent and safe. But despite enormous strides in equipping developing countries to maintain the vaccine “cold chain,” nearly 3 billion of the world’s 7.8 billion people live where temperature-controlled storage is insufficient for an immunization campaign to bring COVID-19 under control.

The result: Poor people around the world who were among the hardest hit by the virus pandemic are also likely to be the last to recover from it.

The vaccine cold chain hurdle is just the latest disparity of the pandemic
weighted against the poor, who more often live and work in crowded conditions that allow the virus to spread, have little access to medical oxygen that is vital to COVID-19 treatment, and whose health systems lack labs, supplies or technicians to carry out large-scale testing.

Maintaining the cold chain for coronavirus vaccines won’t be easy even in the richest of countries, especially when it comes to those that require ultracold temperatures of around minus 70 degrees Celsius (minus 94 F). Investment in infrastructure and cooling technology lags behind the high-speed leap that vaccine development has taken this year due to the virus.

With the pandemic now in its eighth month, logistics experts warn that vast parts of the world lack the refrigeration to administer an effective vaccination program. This includes most of Central Asia, much of India and southeast Asia, Latin America except for the largest countries, and all but a tiny corner of Africa.

The medical clinic outside Burkina Faso’s capital, a dirt-streaked building that serves a population of 11,000, is a microcosm of the obstacles.
More on COVID-19:

After its refrigerator broke last fall, the clinic could no longer keep vaccines against tetanus, yellow fever, tuberculosis and other common diseases on site, nurse Julienne Zoungrana said. Staff instead used motorbikes to fetch vials in insulated carriers from a hospital in Ouagadougou, making a 40-minute round-trip drive on a narrow road that varies between dirt, gravel and pavement.

A mother of two who visits the Gampela clinic says she thinks a coronavirus inoculation program will be challenging in her part of the world. Adama Tapsoba, 24, walks four hours under scorching sun to get her baby his routine immunizations and often waits hours more to see a doctor. A week earlier, her 5-month-old son had missed a scheduled shot because Tapsoba’s daughter was sick and she could only bring one child on foot.

“It will be hard to get a (COVID-19) vaccine,” Tapsoba said, bouncing her 5-month-old son on her lap outside the clinic. “People will have to wait at the hospital, and they might leave without getting it.”

To uphold the cold chain in developing nations, international organizations have overseen the installation of tens of thousands of solar-powered vaccine refrigerators.
Keeping vaccines at stable temperatures from the time they are made until they are given to patients also requires mobile refrigeration, reliable electricity, sound roads and, above all, advance planning.

For poor countries like Burkina Faso, the best chance of receiving a coronavirus vaccine is through the Covax initiative, led by the World Health Organization and the Gavi vaccine alliance. The goal of Covax is to place orders for multiple promising vaccine candidates and to allocate the successful ones equitably.

The United Nations’ children’s agency, UNICEF, began laying the global distribution groundwork months ago, in Copenhagen. At the world’s largest humanitarian aid warehouse, logistics staff are trying to foresee shortages by learning from the past, especially the spring chaos surrounding global shortages of masks and other protective gear that were commandeered off airport tarmacs or stolen and traded on the black market.

Currently, 42 coronavirus vaccine candidates are in clinical trials and another 151 are in pre-clinical evaluation, according to WHO. The ones most likely to end up in the Covax mix must be stored at 2 to 8 degrees Celsius (26-46 F).

A Pfizer candidate is among the ones in advanced testing requiring storage at ultracold temperatures. The company, which has designed a special carrying case for its vaccine, has expressed interest in Covax and signed contracts with the United States, Europe and Japan.

Medical freezers that go down to minus 70 degrees Celsius are rare even in U.S. and European hospitals. Many experts believe the West African countries that suffered through a 2014-16 Ebola outbreak may be the best positioned, because a vaccine against that virus also requires ultracold storage.

For more than two-thirds of the world, however, the advanced technology is nowhere on the horizon, according to a study by German logistics company DHL. Meanwhile, billions of people are in countries that don’t have the necessary infrastructure to maintain the cold chain for either existing vaccines or more conventional coronavirus candidates, the study said.

Opportunities for vaccines to be lost expand the farther a vaccine travels. DHL estimated that 15,000 cargo flights would be required to vaccinate the entire planet against COVID-19, stretching global capacity for aircraft and potentially supplies of materials such as dry ice.

“We need to find a bridge” for every gap in the cold chain, DHL chief commercial officer Katja Busch said. “We’re talking about investments ... as a society, this is something we have to do.”

Gavi and UNICEF worked before the pandemic to supply much of Africa and Asia with refrigeration for vaccines, fitting out 40,000 facilities since 2017. UNICEF is now offering governments a checklist of what they will need to maintain a vaccine supply chain and asking them to develop a plan.

“The governments are in charge of what needs to happen in the end,” said Benjamin Schreiber, who is among the directors of UNICEF’s vaccination program.

Cracks in the global cold chain start once vaccines leave the factory. Container ships are not equipped to refrigerate pharmaceutical products with a limited shelf life. Shipping vaccines by air costs a lot more, and air cargo traffic is only now rebounding from pandemic-related border closures.

Even when flights are cold and frequent enough, air freight carries other potential hazards. WHO estimates that as much as half of vaccines globally are lost to wastage, sometimes due to heat exposure or vials breaking while in transit. With coronavirus vaccines, which will be one of the world’s most sought-after products, theft is also a danger.

“They can’t be left on a tarmac and fought over because they would actually be spoiled and they would have no value — or worse still, people would still be trying to distribute them,” said Glyn Hughes, the global head of cargo for the International Air Transport Association.

Tinglong Dai, a Johns Hopkins University researcher who specializes in health care logistics, said creativity will be needed to keep the cold chain intact while coronavirus vaccines are distributed on a global scale. Gavi and UNICEF have experimented with delivering vaccines by drone. Indian officials have floated the idea of setting aside part of the country’s vast food storage network for the coronavirus vaccines.

“If people can figure out how to transport ice cream, they can transport vaccines,” Dai said.

Temperature-sensitive labels that change color when a vaccine is exposed to heat too long and no longer safe to use, and live delivery tracking to ensure vaccines reach their destinations as intended also have allowed for progress in delivering safe shots.

Yet chances for something to go wrong multiply on the ground as vaccines are prepped to leave national depots. Since the cold chain is so fragile, logistics planning is crucial; syringes and disposal boxes must be available as soon as vaccine shipments arrive.

By the end of the year, UNICEF expects to have 520 million syringes pre-positioned for coronavirus vaccines in the developing world and maps of where the refrigeration needs are greatest “to ensure that these supplies arrive in countries by the time the vaccines do,” Executive Director Henrietta Fore said.

The last vaccine requiring cold storage that India’s national program adopted was for rotavirus, a stomach bug that typically affects babies and young children. Dr. Gagandeep Kang, who led the research for that vaccine, estimated that India has about 30% less storage capacity than it would need for a coronavirus vaccine.

In countries such as India and Burkina Faso, a lack of public transportation presents another obstacle to getting citizens inoculated before vaccines go bad.

Dr. Aquinas Edassery, who runs two clinics in one of India’s poorest and least developed regions, said patients must walk for hours to receive health care. The trip on a single road that winds 86 kilometers (53 miles) over steep hills and washes out for months at a time will pose an insurmountable barrier for many residents of the eastern district of Rayagada, Edassery said.

As with most logistics, the last kilometer (mile) is the hardest part of delivering a coronavirus vaccine to the people who need it. In Latin America, perhaps nowhere more than Venezuela provides a glimpse into how the vaccine cold chain could go dramatically off course.

When a blackout last year left much of the nation in the dark for a week, doctors in several parts of Venezuela reported losing stocks of vaccines. The country’s largest children’s hospital had to discard thousands of doses of vaccines for illnesses like diphtheria, according to Dr. Huníades Urbina, head of the Venezuelan Society of Childcare and Pediatrics.

“We won’t be able to halt either the coronavirus or measles,” Urbina said.

Preserving the cold chain has only grown more difficult since then. Gas shortages limit the ability to move vaccines quickly from one part of Venezuela to another. Dry ice to keep vaccines cool during transport is harder to find. And after years of economic decline, there also are fewer doctors and other professionals trained to keep the chain intact.

“I’m not optimistic on how the vaccine would be distributed in the inner states because there is no infrastructure of any kind to guarantee delivery — or if it gets delivered, guarantees the adequate preservation under cold conditions,” Dr. Alberto Paniz-Mondolfi, a Venezuelan pathologist, said.

Venezuela presents an extreme example, but a coronavirus vaccine also is likely to test parts of Latin America with more robust health care systems. In Peru, private businesses that typically transport fish and beef have offered their trucks, though it remains unclear whether the Health Ministry will accept.

Back in Burkina Faso, vaccination days became an ordeal at the Gampela clinic when the refrigerator went out, said Zoungrana, the nurse. Staff members on hospital courier runs must buy fuel they often can’t afford and make a second trip to and from the capital to return any unused doses.

“We’re suffering,” said Zoungrana, who was run off the road on her motorbike just a few weeks ago.

Days after journalists from The Associated Press visited the clinic this month, a long-awaited solar refrigerator arrived. With technicians in short supply, the clinic was waiting to be sure the appliance would function properly before stocking it with vaccines.

Nationwide, Burkina Faso is about 1,000 clinical refrigerators short, and less than 40% of the health facilities that conduct vaccinations have reliable fridges, national vaccination director Issa Ouedraogo said.

Multi-dose vials — the equivalent of bulk storage for vaccines — can drastically reduce global transportation costs. But once a vial is opened, its shelf life counts down even faster; if too few people show up for their jabs in time, whatever remains in the larger vials must be discarded.

“It’s really upsetting to have wastage like that. It’ll result in loss of lives and pain and suffering. It’s a waste of resources, ” said University of Massachusetts at Amherst professor Anna Nagurney, who studies supply chain logistics.

For now, UNICEF is betting on 20-dose vials of coronavirus vaccine and hoping that the amount wasted will stay below 3% for closed vials and 15% for open multi-dose vials that do not get used up, according to Michelle Siedel, one of the U.N. agency’s cold chain experts.

If Burkina Faso were given 1 million doses of a coronavirus vaccine today, the country wouldn’t be able to handle it, Jean-Claude Mubalama, UNICEF’s head of health and nutrition for the African nation.

“If we had to vaccinate against the coronavirus now, at this moment, it would be impossible,” he said.
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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The secret weapon for distributing a potential covid-19 vaccine

The history of cattle breeding in the Midwest may save lives now

November 12, 2020 at 3:00 a.m. PST


https://www.washingtonpost.com/outlook/ ... 9-vaccine/


On Monday, the pharmaceutical company Pfizer announced early data that showed a vaccine it has been developing in partnership with the German drug manufacturer BioNTech was more than 90 percent effective in preventing covid-19. This level of efficacy amazed researchers, including those at my own institution, Yale School of Medicine, who agreed that if the data holds (it has not yet been peer reviewed), then this vaccine would be poised to dramatically curtail the impact of the virus.


This news made headlines, along with Joe Biden’s and Kamala D. Harris’s rollout of a covid-19 task force composed of biomedical experts, suggesting even as the number of daily new infections reached an all-time high in the U.S., a cure was in sight. But, storing and distributing a vaccine — especially the potential Pfizer vaccine, which must be frozen until use at -70°C, around the temperature of dry ice — poses a significant challenge.

Rural cattle breeders offer a solution. In the 1950s, during the Cold War, they played a major role in developing and scaling up the technology to circulate biological materials globally at temperatures as low as -196°C, that of liquid nitrogen. In what is known as the “cold chain,” these supply networks made it possible to ship temperature-sensitive agricultural and medical products within and beyond the United States.

In other words, practices honed in the American heartland helped make cold-dependent therapeutics feasible — from organ transplantation to blood banking, artificial insemination to vaccine development and distribution. The history of how cattle breeders developed and supported a worldwide cold chain demonstrates that problems of global public health require attention to technology transfer between industrial sectors, such as agriculture and biomedicine, as well as between nations.

One of the most influential early players in this network was American Breeders Service (ABS). Founded in 1949 in Madison, Wis., by entrepreneur Rockefeller “Rock” Prentice, the company also sponsored the American Foundation for the Study of Genetics, a not-for-profit corporation devoted to the science of animal breeding. The ability to freeze bull semen contributed to an intensification of reproduction, making it possible to get thousands rather than dozens of calves from each sire.

Within four years of its founding, ABS had recruited experts in the emerging field of cryobiology, known as the “science of frosty life,” to demonstrate the potential of using cold storage to manipulate the breeding process. In 1953, it celebrated the success of their experiments in artificial insemination using frozen bull semen with the birth of a calf they named “Frosty,” and a promotional film declaring this to be “Progress, progress the American way!”

The next step was to hone the ability to keep sperm cold as it traveled between the lab and various farms. The need to improve mobile cold storage — a crucial link in the cold chain — had become imperative. Traditional kerosene gas refrigerators — which were quickly becoming obsolete — were portable, albeit cumbersome. Liquid nitrogen presented a new possibility. It was inert and nonflammable, making it safe for the materials it kept frozen as well as the field technicians transporting them.

Working together with engineers at the Linde cryobiology lab near Buffalo, ABS developed a mobile cold-storage canister that combined both a new insulation material and a vacuum to support liquid nitrogen. The biologics contained inside could be maintained for up to two weeks, enabling it to be “transported from farm to farm as the local inseminator made his rounds.”

Though ABS had invested heavily in the development of this technology, it did not seek a patent, allowing competitors to gain access. Prentice recognized that making their equipment freely available would accelerate broader innovation necessary to extend the cold chain globally. The result was a transformation in both the cattle breeding and liquid nitrogen industries.

By the 1970s, the liquid nitrogen-based distribution system developed by ABS had been endorsed by the World Health Organization (WHO), which was deeply invested in developing systems of blood-based epidemiological surveillance of infectious diseases. While this required accumulating and freezing blood samples from people living all over the world, existing modes of cold storage were either too expensive — in the case of dry ice and freeze drying — or unreliable — in the case of wet ice.

Liquid nitrogen circumvented these problems
. The container ABS had built was adapted for use in shipping biologics other than sperm. In one pilot project conducted by the WHO, the “refrigerator-transporter” was filled with liquid nitrogen in Europe and then sent to Lagos, Nigeria, where it was transported to more remote rural areas where human blood samples were being collected before being shipped back to Europe. The whole process took two weeks and represented a dramatic strengthening of the cold chain for public health.

A cattle breeding company — in partnership with corporations interested in the production of low temperature gases — had become the source for knowledge on practical considerations of working with cryopreserved materials, as well as suppliers of equipment to those wishing to preserve and transport other kinds of biological materials on an industrial scale.

The connection between vaccination demands and agriculture is not new. In fact, the word vaccination comes from the Latin for cow. The first vaccines were developed on dairy farms in the late 18th century, inoculating humans with cowpox as a means of preventing the spread of smallpox.

It would take until 1980 for smallpox to be declared eradicated. Part of what made the mass distribution of smallpox vaccine possible is that it was heat stable, meaning that it did not need to be refrigerated.

In the age of covid-19, the history of cattle breeding in the Midwest provides insights about the challenges and possibilities involved with the distribution of Pfizer’s potential vaccine, whether it ultimately uses liquid nitrogen or another mode of cold storage. In fact, how agricultural workers and engineers partnered with public health officials the world over at mid-century, during times of geopolitical strife, provides precisely the kind of unexpected object lessons necessary for surviving the present.
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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Today’s pharma cold chain is going cryogenic

Updated: September 29, 2020


https://www.pharmaceuticalcommerce.com/ ... cryogenic/

Both COVID-19 vaccine delivery and the growth of cellular/genetic therapies call for lower storage and shipping temperatures


Providers of temperature-controlled packaging, storage, and shipping capabilities for the biopharmaceutical industry are about to face their potentially finest moment. Though they are used to navigating a uniquely complex supply chain, today’s demands—framed by a worldwide pandemic—are unprecedented, and will require next-level support across critical functions such as logistics planning and data monitoring, analysis, and communications.

“Between the pressure to develop and commercialize a COVID-19 vaccine, the continued global demand for seasonal flu vaccines, and efforts to advance many promising cell and gene therapies (CGTs), it’s clear that companies throughout the pharmaceutical cold-chain infrastructure are juggling multiple priorities—all of them critical to lifesaving efforts,” says Vivian Berni, director of product management for Sonoco ThermoSafe, also noting existing responsibilities in managing the usual volume of temperature-sensitive therapies and vaccines already on the market.

Rather than relying solely on express deliveries made directly from the manufacturer to the point of care, the pharmaceutical cold chain typically involves multiple players, working in close coordination, to execute a number of handoffs. Pharmaceutical shipments are moved from the manufacturing site, through storage depots, trucks, planes, and ships, to reach the ultimate destination, usually a hospital, clinic, or pharmacy. As pharma companies entrust their cargo to others, there is very little room for error in each of these segmented journeys.

“The COVID-19 pandemic has created new logistical challenges and new country-specific regulations,” says Nick Porter, senior vice president of global commercial at World Courier, a part of AmerisourceBergen. “This has reinforced the importance of partnering with a specialty logistics provider that has a global network and a team that can mobilize contingency plans quickly, if needed, to identify an alternative route or to communicate with local officials.”

With multiple stakeholders involved in cold-chain shipments—and numerous touch points along the way—no single party has ultimate control over the integrity of the shipment, notes Dharmesh Chauhan, sales director at Softbox, a provider of temperature-control packaging systems and thermal covers for the life sciences industry. “This raises the stakes for all companies involved,” he says.

AmerisourceBergen, to better support customers, recently integrated World Courier, a global logistics provider, and Integrated Commercialization Solutions (ICS), a third-party logistics (3PL) company—creating a single specialty logistics partner. According to executives, its cryogenic supply chain includes vapor-charged cryogenic storage systems and temperature-controlled packaging solutions that enable product transport from manufacturer location to its 3PL storage facility and then to each point of care.

Reducing the number of handoffs can help eliminate potential weak points in the cold chain, says Wes Wheeler, president of UPS Healthcare. To that end, he expects to see more stringent standards and regulations—and increasingly optimized supply chain practices—installed to ensure quality management systems are standardized for high-value biopharma products such as CGTs and immunotherapies.

Rising to the challenge


Today, the stakes are higher than ever in the pharma cold chain—at all ends of the spectrum. Large-scale-wise, the cold chain industry is bracing for the arrival of the first of several COVID-19 vaccines resulting from the US’s Operation Warp Speed initiative and parallel efforts elsewhere in the world. Once approved, billions of doses of a new COVID-19 vaccine will need to be delivered to patients across the globe—quite literally on a moment’s notice.

Meanwhile, smaller in scope, the complex cold-chain requirements associated with managing shipments of ultrasmall volumes of temperature-sensitive CGTs are creating new demands, as the pipeline for these advanced therapies continues to grow. Under a typical CGT scenario, a single vial of biological materials (blood or tissue) must be extracted from the patient, and then safeguarded through its journey. That involves transfer from the clinical setting to a laboratory, where the sample is manipulated biochemically or genetically, and then sent back to the clinic for infusion.

While losses associated with temperature excursions during cold-chain storage and transportation efforts remain a hidden cost of doing business—in terms of spoiled product, excess inventory, and delayed deliveries—today’s cold-chain suppliers are also expanding their arsenal of data-collection tools, and leaning more heavily on the use of telemetry, advanced monitoring systems, and sophisticated data-driven modeling tools, to reduce the frequency and likelihood of preventable delays and temperature excursions.

“There is continued focus on controlling the total cost of cold-chain supply logistics, which, as a rule of thumb, account for roughly 5–10% of the total cost of biologic therapies and vaccines,” says Richard Ettl, CEO of SkyCell AG, noting that if there is a temperature excursion, the product cannot be released to patients—instead, a replacement pallet must be shipped immediately. “This makes a real difference when we’re talking about pallets of vaccines that may be valued at $500,000 each,” he adds.

While today’s new shipping and data-management devices are providing real-time visibility into the status and condition of a shipment, it is critical that these tools are able to be reprogrammed on the fly to better ward off potential obstacles, contends Mark Sawicki, PhD, chief commercial officer, Cryoport. He says such capabilities are in the process of being established through augmented GPS using Bluetooth, WiFi, Internet of things (IoT) technology, next-generation data loggers, enhanced software management services, geofencing capabilities, and expanded use of radio-frequency identification. Sawicki adds that the eventual rollout of 5G-enabled sensors should help to open up access to larger amounts of location and temperature data.

David Goldberg, CEO of DHL Global Forwarding in the US, believes industry investment in rapid digitization of supply-chain data analytics has been solid, and sees a concerted effort among shippers to use passive cold-chain packaging to augment active packaging options. “Improved data analytics allow for near-real-time mode optimization, and more effective use of ocean versus air freight,” he says.

Market dynamics


Under the cold-chain umbrella, the “refrigerated” category (2 to 8°C) is by far the largest category by value. However, among today’s newer CGT offerings, other novel biologic therapies, and several of the COVID-19 vaccine candidates currently in clinical trials, there is increasing demand for maintaining product at “deep frozen” temperatures (on the order of -40 to -80°C), and “cryogenic” (requiring liquid nitrogen; -160 to -180°C).

As of early 2020, annual global sales of biologics and vaccines—which require strict temperature control—exceeded $340 billion. Amid the continued growth of these markets, cold-chain logistics account for nearly 18% of all biopharma logistics spending, according to the 2020 Biopharma Cold Chain Sourcebook published by Pharmaceutical Commerce.

On the R&D side, cold-chain providers routinely support thousands of clinical trials, delivering temperature-sensitive drugs to study sites and laboratories around the globe. The 2020 market size for this sector is valued at about $3.8 billion, according to the Sourcebook, and the continued expansion of clinical trials logistics is projected to grow at a rate of about 3% per year, to about $4.2 billion by 2024.

Overall, global pharmaceutical sales are expected reach $1.58 trillion by 2024, according to IQVIA Institute projections released in March. By 2024, experts predict five of the top 10 best-sellers will be drugs requiring 2–8°C cold-chain storage and handling.

In 2019, FDA’s Center for Biologic Evaluation and Research (CBER), which handles the review of vaccines and blood products, approved 22 licenses for new biologic products, 21 of which require cold-chain handling, the Sourcebook reports. (In 2018, 20 such products were approved, 16 requiring cold-chain handling).

“Cost-reduction efforts go beyond just the cost of the packaging and freight but require an assessment of the costs of inventory and labor to complete the pack-out of temperature-controlled products as well,” says Ron Haub, segment director/general manager, Sonoco ThermoSafe. “Working closely with our clients, we try to identify ways to help them open up warehouse space, by holding temperature-controlled inventory and providing it on a just-in-time basis.” Haub notes that the expanded use of preconditioned shippers can also help to reduce the amount of refrigerator/freezer space required, and that preconditioned shippers are more simple to pack, reducing what he says is usually a 10-plus-step process to just two or three steps, saving time and labor.

Tighter process integration can also yield benefits. For example, SkyCell says it was able to create a direct savings of $120 million for one of the world’s top vaccine producers. “Before, the client had almost 30 different solutions in operation to handle its cold-chain distribution and management operations,” says Ettl. “We standardized and streamlined the overall approach to provide near-real-time IoT insights that let us pivot to redirect shipments more quickly.”

The elephant in the room

As the world awaits anxiously for the first approved COVID-19 vaccine(s), one perhaps underappreciated element of the overall challenge is whether the existing cold-chain infrastructure will be able to manage the distribution of unprecedented volumes of the vaccine, to every corner of the globe, nearly concurrently.

While specific details related to temperature, shipping, and dosing requirements for those vaccines that will end up in mass distribution are not yet known, billions of the first-approved vaccines will be quickly thrust into the supply chain to meet enormous, pent-up global demand. Stakeholders interviewed for this article described this looming challenge as “historic in scope…utterly unprecedented…a mammoth challenge… truly awe-inspiring…by far, one of the largest challenges we have faced in our lifetime.”

“Many of these investigational COVID-19 vaccines are expected to be in a frozen format, but this is not typical for many of the biologic drug products in the supply chain today (which require refrigerated but not cryogenic temperatures),” says Adam Tetz, director of worldwide marketing for Pelican BioThermal. “Once approved, the new COVID-19 vaccines will be manufactured at a rate of millions of doses per week and will need immediate worldwide distribution, so we are going to see a critical crunch, in terms of the existing cold-chain capacity worldwide.”

Patrick Schafer, CEO of CSafe Global, a provider of cold-chain shipping solutions, notes that COVID is the first pandemic the modern cold chain has had to manage. While global demand will be significant, ongoing demand for other pharmaceuticals will not wane simply because a COVID-19 vaccine is ready to ship, he stresses. “This effort will require coordination on a scale we’ve never seen,” says Schafer.

“The market is not currently prepared to handle the way the expected COVID-19 vaccine will need to be distributed, so there is a lot of concurrent activity around building up the basic systems and adding capacity to the system,” adds Sawicki. “One silver lining, though, is that this is also creating a lot of business opportunity for many companies in this space.”

To get a sense of the scale and the capacity gap the industry is facing, consider, in 2020, an estimated 194 million to 198 million doses of the seasonal flu vaccine will be transported (up from 175 million doses in 2019), according to the CDC, notes Angela Kerr, VP of product and program management at SpotSee.

According to Ettl, the industry moves about one million pallets of cold-chain pharmaceutical and life sciences products by air every year. He says if a single-dose COVID-19 vaccine is approved, there could be an additional 160,000 pallets entering the supply chain annually. If two doses are required, demand could grow to a half million additional pallets each year. “We need to work closely together to collaborate—even if we are competitors—because this unprecedented, high-stakes challenge will be too big for any one player to manage alone,” says Ettl.

Key challenges, Tetz adds, include developing plans to convert passenger planes to cargo planes to enable more cargo capacity, and establishing deep-freeze/blast-freezer farms at major distribution points worldwide.

On the shipping front, after a 35-year hiatus, American Airlines announced in August that it had expanded its cargo-only service. Starting this month, the company began offering 1,000 regular cargo-only flights, serving 32 destinations worldwide, on top of 1,200 regular passenger flights that also offer partial cargo service. Schafer points out it’s not just a matter of having enough active air cargo containers, but providing containers that can maintain a potentially wide temperature range for extended durations of time. This will be particularly crucial for vaccines shipped to new or remote locations far from a major port city.

“Trying to envision the distribution needs for the COVID-19 vaccine is creating a very fluid and dynamic situation,” says Thomas Heinzen, vice president of corporate development for Cryoport, which is supporting logistics for eight COVID-19 vaccines and/or therapies currently in clinical trials. “All sorts of different methods of distribution are being explored, and the fact that multiple vaccines could be approved, each with different dosage and temperature requirements during storage, distribution, and administration, just adds to the overall complexity.”

To prepare for the significant capacity surge, several companies are in the process of building giant freezer farms. For example, UPS Healthcare is currently installing two such units in Louisville, Kentucky and the Netherlands (both near global UPS air hubs) comprised of hundreds of -80°C freezers. “Each of these will be capable of scaling up to 300 freezers and each freezer will be capable of storing 40,000 to 50,000 individual vials of vaccine,” says Wheeler. “We are also moving the same freezers in key clinical trial locations in South America, Germany, and the UK, and we are discussing humanitarian efforts as well.” UPS Healthcare’s clinical subsidiary Marken is working with several biopharma companies and their partners on COVID-19 vaccine and treatment development efforts.

Similarly, in July, DHL opened a $1.6-million, 20,000 square-foot cold-storage facility in Indianapolis, which houses three temperature-controlled chambers with variable temperature options, and FedEx revealed this summer that it would be adding 10 freezer facilities, with more expected to follow, to meet the coming demand.

Last month, the US Department of Health and Human Services (HHS) and Department of Defense (DoD), in support of Operation Warp Speed, tapped McKesson Corporation as a central distributor for future COVID-19 vaccines and related supplies.

Meanwhile, producers of specialized cold-chain packaging are also ramping up production. For example, Tetz says Pelican BioThermal is “pre-buying” supplies and components and has three global manufacturing centers it can use to manufacture product quickly to meet anticipated demand. “We are also actively converting our main products to provide a dry ice capacity and looking at adapting our dry ice parcel shippers, expanding the range of sizes to handle a wide array of payload volumes,” he adds.

Vaccines in development based on mRNA (using RNA-containing vectors) are particularly promising, but pose considerable cold-chain challenges. Chauhan, of Softbox, notes that while these vaccines enable rapid development, low-cost manufacturing, and large-scale production, they may require ultra-low-temperature distribution levels (around -80°C) to keep the mRNA proteins viable prior to administration. “The current global supply chain is not fully geared up to handle this,” he says.

Adding to the challenge, Kerr points out, will be the need for any type of vaccine approved for the novel coronavirus to reach many developing nations concurrently, where gaps in existing infrastructures will create additional “last-mile” obstacles. On top of those, Sawicki notes that particularly in remote regions and developing nations, there may not be freezers to maintain adequate storage temperatures at the point of care.

Sonoco ThermoSafe, Haub says, is in the process of examining how its 30-plus manufacturing locations can be optimized, and are adding tooling and potential machine capacity as needed. The company hopes to secure offsite storage locations to build inventories of shippers and refrigerants.

CGT: Small parcels, little risk tolerance

COVID-19 may be grabbing the headlines, but cold-chain and logistics challenges associated with safeguarding CGTs and tissue-engineered products are testing the industry’s capabilities as well. Emerging in recent years, CGTs, also called “vein-to-vein” therapies, are durable, curative-type treatments often targeting life-threatening and debilitating genetic disorders and rare diseases.

Typically involving the production of a customized treatment for each patient, the specialized, closed-loop supply chain requirements associated with a CGT create unique challenges. Opportunities for delivery delays and temperature excursions along all the steps in the segmented journey can create potentially damaging financial and clinical risk.

Heinzen, who notes that his company (Cryoport) has supported four marketed CGTs and six more expected to file for regulatory approval by the end of the year, says cold-chain issues are particularly challenging for allogeneic CGT products, as they must be transported to multiple locations, and warehoused or stored until they are infused into one or more patients. On the plus side, according to Schafer, studies have indicated that a single donor set could be used to create therapeutic doses for more than 200 patients. This means multiple doses could be moved in one thermal shipper, significantly reducing costs to the manufacturer and ultimately the patient, he says.

Nevertheless, the specialized nature of CGTs “create more cold-chain complexity than ever, particularly in terms of organizational structure, business processes, digital capabilities, and risk tolerance,” says Berni.

Adding further complexity are other variables associated with CGTs, such as shock and orientation of the sample, which needs to be monitored in near real-time, notes Sanjay Srivastava, PhD, managing director for cell and gene, life sciences, Accenture. “The industry is evolving but currently has limited experience and capabilities to incorporate these types of sensors in the supply chain to manage the deluge of anticipated CGT shipments,” he says.

The steady growth of the CGT sector is expected to continue. According to the Alliance for Regenerative Medicine (ARM), as of June 2020, there are 1,078 clinical trials underway for these types of treatments (394 in Phase I, 587 in Phase II, and 97 in Phase III), with novel efforts aimed at oncology; musculoskeletal, endocrine, and metabolic disorders; immunology and inflammation; lymphatic disease; and respiratory disorders; among other conditions. Strong financing in the CGT space also bodes well for sustained growth. Between January and June 2020, CGT developers raised $10.7 billion in financing from IPOs, venture capital, and other funding sources—a 120% increase from the first half of 2019, according to ARM. The FDA anticipates it will approve between 10 to 20 CGTs each year by 2024.

Amid the CGT explosion, Srivastava points to the need for logistics providers to run a just-in-time supply chain to facilitate cell transfer operations and deliver raw materials to manufacturers and final product to hospitals. Accenture advocates using the supply chain control tower approach, which can provide greater visibility by generating alerts about expected shortfalls and/or delays in production at suppliers and contract manufacturers and then sequence the impact these events will have. “The goal is to help logistics providers move from just providing reactive fixes to creating synchronized, event-driven value networks,” says Srivastava.

As the number of CGTs (and their volume in the supply chain) continues to grow, Albert Cooksey, senior vice president, client relations, at ICS, says the company is anticipating heightened demand for cryogenic storage systems, as well as dry shippers that can maintain internal temperatures between -150°C and -180°C for an extended period of time. To grow its cryogenic storage infrastructure and enable clients to scale their specialty products “from many to millions,” Cooksey says ICS has recently “more than doubled its refrigeration storage (2 to 8°C) and added liquid nitrogen cryogenic storage capacity (to enable -180°C).”

Dave Murphy, executive vice president, Quick Specialized Healthcare Logistics, a unit of Kuehne+Nagel and provider of transportation and logistics solutions related to the transport of live cells, says “as more CGTs are approved, their chain-of-custody requirements and volume demands increase substantially, so scalability is key—whether managing deliveries across a country or around the world.”

To that end, Berni believes service providers in the cold-chain space should reassess and redesign their IT infrastructures to “break free from silos and build bridges” in connecting data across logistics and packaging systems to enable synchronized operations.

To support ongoing capacity expansion in the CGT space, six branches of Marken have recently become Cell and Gene Therapy Centers of Excellence, and a central, dedicated CGT control center has been established at Marken headquarters in North Carolina. “These branches are supported by the industry’s largest network of liquid nitrogen (LN2) filling stations, allowing the company to maintain cryogenic supply chains that operate around the world,” says Wheeler. “We are able to support the cryogenic transportation (at -150°C) of CGT products using Marken’s LN2 shipping fleet, which is serviced at 14 geographically distributed locations.”

In August, Cryoport made two strategic acquisitions to expand its footprint in the CGT market—acquiring CryoPDP, a Paris-based provider of containers, packaging, logistics, courier services, and clinical trials support, which operates 22 facilities in 12 countries; and MVE Biological Solutions, the life sciences business of Chart Industries. MVE makes vacuum insulated products and cryogenic freezer systems. It has three manufacturing sites—two in the US and one in China.

Data is king

Perhaps nowhere in the pharma supply chain is real-time data more important than in the realm of cold-chain packaging, transportation, storage, and logistics. The goal is to allow all stakeholders to react quickly, before things go wrong, and enable a data-driven forensic review of events after the fact.

“Smart monitoring” solutions that can track internal temperature, light, pressure, humidity, and tilt—providing real-time visibility and proof of shipment stability—allow teams to mobilize quickly, according to Porter.

For example, a recent shipment using World Courier and ICS’s Cocoon packaging tool was able to maintain its internal temperature throughout a two-week delivery from Austria to Iraq, he says, which included 10 days of storage in uncontrolled warehouse temperatures.

Since 2013, SkyCell has amassed more than two billion data points about cold-chain pharma activities, says Ettl, which enables the company to identify specific risks, make the most appropriate adjustments, and improve outcomes. “This allows us to go from ‘just a gut feeling’ to data-driven efforts to optimize the supply chain in a more agile and effective way,” explains Ettl. “It’s not enough to know after the fact that something did not work. It’s far more important to use advanced IoT capabilities to not only react to losses from temperature excursions, but to create opportunities to prevent them from occurring in the first place.”

Experts believe advanced machine learning-based algorithms are already showing great promise, “with the most significant gains being made to inform advanced scheduling systems by finding patterns in track-and-trace data captured using IoT-enabled sensors and using the derived insights to quickly detect patterns and problems,” says Sawicki.

“With these capabilities, you can use past performance and variables to continually suggest more efficient routes,” adds Berni.

Richard Wood, technical director at Softbox, says the industry is experiencing a strong shift toward the use of real-time monitoring in combination with new methods for big-data analytics and predicative simulation software to mitigate risk. “We have seen examples where enhanced visibility has saved millions of pounds of pharmaceutical products from potentially damaging temperature excursions,” he says.

Later this year, according to Schafer, CSafe Global will be launching a new telemetry technology to expand its monitoring and reporting capabilities.

“When you collect the appropriate data and exploit it, you can use the data-driven insights to select the optimum routings, carriers, and packaging solutions to meet the customers’ quality, service, and cost expectations and drive continuous service improvement,” adds Jon Chapman, vice president, pharma healthcare, at Kuehne + Nagel.

COVID-19-sparked challenges present an opportunity for the integration of blockchain technology for temperature monitoring. “Blockchain is expected to fundamentally alter the future of cold supply chain, as that would enable end-to-end traceability of temperature-controlled therapies and vaccines, and the ability to provide an audit trail of environmental condition monitoring,” says Berni. “Importantly, blockchain can help to identify which segments of the journey were in control of the shipment when any temperature excursion or damage occurred.

In July, SonocoThermoSafe joined forces with IBM to create PharmaPortal, a vendor-neutral blockchain platform for use by pharmaceutical manufacturers and carriers. The tool “intends to record a single version of the truth on all events generated on a package’s journey,” adds Berni.
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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Temperature concerns could slow the rollout of new coronavirus vaccines

11/16/20


https://www.sciencemag.org/news/2020/11 ... s-vaccines


Today’s dramatic news that Moderna’s COVID-19 vaccine might work as well as one made by Pfizer and BioNTech means the world could have two powerful weapons to fight the COVID-19 pandemic. Now, the next hot vaccine topic is, well, heat. Both vaccines use a novel technology—strands of messenger RNA (mRNA), held within lipid particles—that is vulnerable to degradation at room temperature and requires doses to be frozen for transportation, then thawed for use.

That’s where the Moderna vaccine may have an edge: Unlike Pfizer’s and BioNTech’s offering, it does not have to be stored at –70°C, but can tolerate a much warmer –20°C, which is standard for most hospital and pharmacy freezers. That difference means Moderna’s vaccine should be easier to distribute and store, particularly in the rural United States and developing countries that lack ultracold freezers. Moderna says years of development work enabled its vaccine to be stored at higher temperatures, but last week another mRNA vaccine company announced it is testing a COVID-19 vaccine that early studies suggest can survive at the even warmer temperatures of 2°C to 8°C found in refrigerators.

Many types of vaccines must be stored and transported frozen, via a cold supply chain. Public health officials have even found ways to keep a vaccine ultracold, between –60°C to –80°C, in places like sub-Saharan Africa. There, for the past 5 years, a high-tech thermos called Arktek has helped distribute Ebola vaccines that must be kept ultracold. “In all likelihood, we’ll need a wide range of supply chain tools” to distribute COVID-19 vaccines, says Daniel Lieberman, a mechanical engineer with Global Health Labs in Seattle, a nonprofit created by the Bill & Melinda Gates Foundation, which funded Arktek’s development, and by a venture capital firm started by Bill Gates. Still, relying on an ultracold chain is expensive, and in some places it may make more sense to distribute a vaccine that can tolerate warmer temperatures even if it’s less effective.

Both the Moderna and Pfizer/BioNTech vaccines give the body’s cells an mRNA template for making the spike protein of SARS-CoV-2, the virus that causes COVID-19. The protein then moves to the cell’s surface and triggers an immune response. This mRNA is relatively fragile compared with the proteins or protein fragments that often make up conventional vaccines, and it cleaves easily at room temperature, says Alana Gerhardt, who studies vaccine product development at the nonprofit Infectious Disease Research Institute (IDRI) in Seattle. Also, enzymes called ribonucleases that chew up mRNAs “are everywhere, even in the controlled environment of the lab,” from sources such as lab workers’ breath and skin, Gerhardt says.

The companies give the mRNA some protection during production and storage by inserting it into a carrier, a fatlike substance called a lipid nanoparticle. The lipid also shields the mRNA from enzymes in the blood once it has been injected. But the nanoparticle is deliberately designed to slowly degrade, so it won’t build up in the liver and cause harm, says Massachusetts Institute of Technology geneticist and chemical engineer Daniel Anderson.

Although the companies’ exact formulations are proprietary, Pfizer and BioNTech have so far said their vaccine has to be kept ultracold. But Barney Graham, a vaccine researcher at the U.S. National Institute of Allergy and Infectious Diseases who designed the mRNA used by both Moderna and Pfizer/BioNTech, says the temperature requirements are actually unclear. Pfizer and BioNtech started with –70°C when they first asked regulators to test their vaccine in humans, and Graham says the companies might ultimately be able to document that the mRNA survives warmer temperatures.

In the meantime, at sites in Kalamazoo, Michigan, and Puurs, Belgium, Pfizer will pack shipments of 200 to 1000 vials each containing five doses in insulated boxes with thermal sensors on dry ice to provide the necessary chill. Pharmacies and doctor’s offices that lack $15,000 ultracold freezers can store it in the thermal box for about 2 weeks by refilling the dry ice every 5 days; once removed, the vaccine can be refrigerated for 5 days. Moderna’s vaccine, however, is stable for 6 months at –20°C, or in a standard freezer, and the company announced today its product can be kept at normal refrigerator temperatures for up to 30 days, longer than the 7 days initially expected.

The German company CureVac is lagging behind in the mRNA COVID-19 vaccine race, but announced last week that its candidate is stable for 3 months at 5°C. Unlike the Moderna and Pfizer/BioNTech vaccines, CureVac’s mRNA does not have a modification to one of its four building blocks, a nucleoside called uridine, which the company says allows it to pack more tightly inside the nanoparticle. “Our hypothesis is that the more compact the mRNA is, the less susceptible it is to degradation,” CureVac spokesperson Sarah Fakih says. The company expects to launch a 30,000-person trial to test the vaccine’s efficacy by the end of this year.

Even a vaccine shipped and stored at –20°C, like Moderna’s, poses challenges in developing countries, where electricity for freezers can be unreliable and dry ice scarce. But frozen vaccines don’t have to be a deal breaker, as shown by the Ebola vaccine, which has been shipped in Arktek containers to different sites in the Democratic Republic of the Congo to vaccinate about 400,000 people. Ultracold freezers in large cities were still needed to store the vaccine before it was distributed and to chill the cold packs used to keep Arkteks cooled, notes Prashant Yadav of the Center for Global Development. That meant there remained a requirement for reliable electricity with backup sources. “The key thing is to have a cold chain primary storage point,” Yadav says.

The Arkteks are expensive—about $2000 each—but they’re reusable and can keep vaccines and dry ice or alcohol or salt-based cold packs chilled for much longer than an insulated box, Lieberman notes. “I see the Arktek being valuable anywhere where you want the vaccines to stay cold for days or weeks without a freezer,” Lieberman says. The Gates Foundation’s global delivery program is readying to ramp up production of the Arktek by the Chinese company that makes it, if needed for COVID-19 vaccines, Global Health Labs says.

Another option is to freeze-dry the mRNA vaccines; they would then be reconstituted with water at the delivery point. (Other vaccines already do this.) Pfizer says it is working on a such a powderized form of its vaccine. Regulators would likely require evidence to show the reconstituted vaccine works as well as the liquid vaccine, says IDRI’s Corey Casper.

Several other COVID-19 vaccines now in efficacy trials won’t require freezer storage either. If they work as well as the mRNA vaccines, there will be no need for a –20°C or –70°C cold chain in resource-restrained settings, Yadav says. But if these vaccines aren’t as effective—say only 70%, compared with 90% for an mRNA vaccine—Yadav says that might tip the scale toward deploying mRNA vaccines, despite the costs and challenges.
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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Why dry ice could be critical to coronavirus vaccine distribution

11/17/20


https://www.wkrn.com/community/health/c ... tribution/



(NewsNation Now) — There was good news Monday on the coronavirus vaccine development front as Moderna announced their vaccine is nearly 95% effective.

But there is still so much not known about how the vaccines will make it to every corner of America, and the world.

Airlines say travel restrictions could delay the rollout. The International Air Transport Association says border closures and fewer passenger flights could be big problems.

“With the decrease in passenger service, most people don’t realize how much cargo the passenger carriers move…it’s an enormous amount. All of that cargo has to find a new way to move point to point,” said Derry Huff with Amerijet International.

Only 28% of the air cargo industry feels well prepared for vaccine distribution, according to a survey by the International Air Cargo Association.

They say the main risks of transporting the COVID-19 vaccine are lack of adequate infrastructure, costs, unexpected delays, and temperature excursions — deviations from the labeled storage temperature.

Dry ice will be used to keep the vaccine cold while it is moved in some circumstances.

The Moderna vaccine has to be stored between 36 and 46 degrees Fahrenheit for up to 30 days, then -4 degrees for up to six months. And the Pfizer vaccine must be kept much, much colder at -94 degrees Fahrenheit.

There is concern about a dry ice shortage because so much will be needed.

“Everyone is trying to get ready, but no one knows for sure how much or how many pounds they are going to need. Right now it is like a big question mark about how we are going to handle this situation,” said Gio Escobar with Sub Zero Dry ICE.

And once the vaccine is shipped, there are more unanswered questions about how doctors’ offices will store it.

“This temperature…we might have to get a new refrigerator. I might have to figure out if my electric supply can handle a surge of energy for something like that. Not every practice is going to have the capability to be able to help out with distributing the vaccine,” said Chyrsa Charno with Acute Kinds Urgent Care in New York.

CVS signed a contract with the Centers for Disease Control and Prevention to distribute the vaccine at 10,000 of its locations. First priority will be for health care workers and people over the age of 65.
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Re: Cold Chain - States are panic buying powerful deep freezers to store the COVID vaccine at -94F

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The world's now scrambling for dry ice. It's just one headache in getting coronavirus vaccines where they need to go

11/21/20


https://www.cnn.com/2020/11/21/world/co ... index.html


Vaccines like to be kept cool, none more so than the Pfizer candidate for Covid-19, which has to be deep-frozen. And that's going to be an issue for developing countries -- and for rural areas in the developed world.
The "cold chain" is just one of the challenges in distributing vaccines worldwide.
There are plenty of others: decisions about priority populations and databases to keep track of who's received what vaccine, where and when. Additionally, different vaccines may have more or less efficacy with different population groups; and governments will need PR campaigns to persuade people that vaccines are safe.
But the logistics of transporting and storing vaccines -- getting them from the factory gate to the patient's arm -- are critical. And as most vaccines are likely to require two doses, the whole chain needs must be repeated within weeks.

Unique challenges

The Pfizer-BioNTech vaccine needs to be kept at around -70 degrees Celsius (-94 degrees Fahrenheit) while it's transported. That's 50 degrees Celsius colder than any other vaccine currently used.
Moderna says its vaccine can be kept in freezers typically available in pharmacies, and in a refrigerator for 30 days. But there are likely to be fewer doses of the Moderna vaccine than of the Pfizer's available over the next year.
Phase 3 trials have shown both vaccines to be around 95% effective but the results haven't yet been reviewed by regulators.
On Wednesday, the CEO of BioNTech, the German biotech company partnering with Pfizer, acknowledged the issue of temperature control.

"We are working on formulation which could allow us to ship the vaccine even maybe at room temperature," Ugur Sahin told CNN. "We believe that in the second half of 2021 we will have come up with a formulation which is comparable to any other type of vaccine."
But in the meantime US Health and Human Services Secretary Alex Azar believes the Moderna candidate is "more flexible" for settings like a local pharmacist. Pfizer's, he said Monday, would be better suited to "big institutional vaccination, say a whole hospital setting, several nursing homes at once."
Pfizer plans to ship up to 1.3 billion doses next year, requiring a lot of dry ice (carbon dioxide in solid form at around -78 degrees Celsius), and a lot of isothermic boxes. The boxes will hold up to 975 vials (4,875 doses) and can be refilled with dry ice for up to 15 days of storage.
Pfizer is testing the supply chain in four US states. Its CEO, Albert Bourla, said Wednesday he has "zero concerns" about the cold chain requirements.
But shipping such a vaccine can pose big challenges. Dr. Jarbas Barbosa, assistant director of the Pan American Health Organization, told CNN that "the rural and the urban areas in any country in the world are not ready to manage this vaccine today."
"So, who is prepared in the world? No one."

One issue is the availability of dry ice.

The Compressed Gas Association says carbon dioxide production capacity in the US and Canada is about 30,000 tons a day and is confident its members can meet demand for dry ice. It says that vaccine supply-chain officials believe less than 5% of dry ice production will be needed to support ultra-cold storage of Covid-19 vaccines in the United States and Canada.

Others in the industry expect bottlenecks. Several dry ice producers in the US told CNN they've already had offers for their entire output. Buddy Collen at Reliant and Pacific Dry Ice told online publication GasWorld: "We are in scramble mode trying to manipulate our production plants."
Sam Rushing, president of Florida-based Advanced Cryogenics, told CNN there are already regional shortages in the US.
The main problem, Rushing says, is fewer vehicles on the road during the pandemic, meaning lower production of ethanol, from which carbon dioxide is a byproduct. European ethanol production has also fallen sharply this year.

US officials are confident enough dry ice will be available. Paul Ostrowski, director of supply, production and distribution for Operation Warp Speed, told CNN last week that courier UPS had pledged to "provide dry ice reshipments throughout all of America upon demand."
But Rushing cautions that dry ice is not very user-friendly and can be hazardous if stored improperly, especially in a confined space. The Federal Aviation Administration classifies it as hazardous cargo.
Peter Gerber, CEO of Lufthansa Cargo, told CNN that the need for dry ice "clearly reduces also the transport capacity because if you have to load more ice you can't load so much vaccine. And of course the procedures have to be very special in order to ensure that it always has this degree of coldness."
US courier DHL is adapting distribution plans according to each vaccine's specifications. David Goldberg, CEO of Global Forwarding US for the company, says "there's a restriction on the amount of dry ice used on an aircraft -- typically 500-1,000 kilos depending on a number of factors."

Once they arrive, Pfizer vials can be stored at between 2 and 8 degrees Celsius for up to five days before deteriorating. Pfizer says it has developed a "just-in-time system which will ship the frozen vials direct to the point of vaccination." It will also monitor the temperature of every box being shipped.
Julie Swann, an expert in supply chains at North Carolina State University, says that large hospital systems, which often have ultra-cool freezers, may have a role as distribution hubs. But not all US states have them; Hawaii said last week none of its hospitals had such freezers.
Breaking down shipments of a frozen vaccine for rural areas or small groups of essential workers -- without compromising their temperature -- will be another headache, Swann said.
When a vaccine needs to be used within a few days, providers will need to ensure they are ready. "You can't just wait to see who shows up," Swann told CNN. "And we don't really have good data yet defining where and who the priority populations are."

The more links in the supply chain, the more risk that the vaccine's temperature will be compromised. Last month the US Centers for Disease Control and Prevention advised states they "should limit transport of frozen or ultra-cold vaccine products."
Prashant Yadav, a supply chain expert and senior fellow at the Center for Global Development, said: "It's a question of how soon can we start thinking about multiple packaging formats."

Beyond the US

If getting a frozen vaccine to tens of millions of people is a challenge in the US, it's a far greater problem for poorer countries.
Transport links are slower and medical facilities less equipped in the developing world. CO2 production is scarce, and the cost and hazards of shipping huge amounts of dry ice are also a hurdle, Yadav says.
David Gitlin, the CEO of refrigeration specialists Carrier, told CNN last week: "When you look at places like Africa and India, they just don't have the cold chain infrastructure. The United States spends 300 times more per capita on cold chain than India."
Peru is one of many countries that have ordered the Pfizer vaccine. In the capital, Lima, where large volumes can be administered quickly, it should be effective, says Dr Germán Málaga, one of a team working on Peru's vaccine options. But while there are probably 30 ultra-cold freezers in Lima "for the other 20 million Peruvians including in the Andes and the rainforest there are none."

"For the rest of the country we could use vaccines like the Chinese one that requires from 2 to 8 degrees which is more manageable," Málaga said.
"It's about cost-effectiveness, which is not just about the vaccine but the whole process of vaccinating," said Yadav. But if Pfizer's candidate proves to be the most effective, demand for ultra-cold freezers would be overwhelming.
Barbosa says the Pan American Health Organization is urging member states not to spend huge sums on preparing for one vaccine but join a multilateral facility called COVAX -- essentially a clearing house for buying vaccines run by the World Health Organization.
Beyond the cold chain, there are other logistical hurdles.
A massive airlift will be required to get vaccines where they need to go. Pfizer, which has production lines in Europe and the US, says it expects an average of 20 daily cargo flights worldwide.
DHL expects that 15 million cooling boxes will need to be delivered on 15,000 flights over the next two years. David Golberg told CNN the company has established a high quality cold-chain network and is adding flights between China, Europe and the US.

Many countries can call on existing programs as models. Peru's national vaccination program reaches about 75% of its population, Málaga said.
India's polio vaccination program is ubiquitous -- covering more than 90% of children by this year, according to Gagandeep Kang of the Wellcome Trust Research Laboratory at the Christian Medical College in Vellore.

"For polio programs, we have used boats and mules and enterprising health staff," said Kang. But such programs are designed for less than a tenth of the population, and Covid-19 vaccines will need to focus on different groups, she said.
India will need "a series of waves each addressing a different group as vaccine become available," she told CNN.
"We will need to see performance characteristics of other vaccines, and their delivery requirements before making a call on what to go with," said Kang, who is also a member of the World Health Organization's Global Advisory Committee on Vaccine Safety.
In such a dynamic situation, record-keeping becomes critical. Dr. Anna Blakney, who is working on a vaccine being developed by Imperial College London, said there is no centralized infrastructure in the US for monitoring who is getting what and when, which she describes as a "really critical issue."

Yadav says that even when the vaccine reaches its destination there will need to be some flexibility to allow people to get their second dose in a different location if desired. And that demands reliable databases.
Barbosa said that beyond the supply chain, governments "must have a good communications strategy to overcome public skepticism and conspiracy theories about vaccines."
Blakney agrees. "This process [of vaccine development] has been so fast that it's not surprising people are skeptical as they read about safety and possible side-effects," she said. Blakney is part of an international effort launched by research scientists to reassure people via social media about the safety and efficacy of COVID-19 vaccines.

Finding enough dry ice is just one in a sequence of challenges to get the world vaccinated against Covid-19.
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