health

Vaccine makers face biggest medical manufacturing challenge in history

9 Comments
By Julie Steenhuysen and Kate Kelland

Developing a COVID-19 vaccine in record time will be tough. Producing enough to end the pandemic will be the biggest medical manufacturing feat in history.

That work is underway.

From deploying experts amid global travel restrictions to managing extreme storage conditions, and even inventing new kinds of vials and syringes for billions of doses, the path is strewn with formidable hurdles, according to Reuters interviews with more than a dozen vaccine developers and their backers.

Any hitch in an untested supply chain - which could stretch from Pune in India to England's Oxford and Baltimore in the United States - could torpedo or delay the complex process.

Col Nelson Michael, director of the U.S. Army's Center for Infectious Disease Research who is working on the government's "Warp Speed" project to deliver a vaccine at scale by January, said companies usually have years to figure this stuff out.

"Now, they have weeks," he said.

Much of the world's attention is focused on the scientific race to develop a vaccine. But behind the scenes, experts are facing a stark reality: we may simply not have enough capacity to make, package and distribute billions of doses all at once.

Companies and governments are racing to scale-up machinery to address a critical shortage in automated filling and finishing capacity - the final step in the manufacturing process of putting the vaccine into vials or syringes, sealing them and packaging them up for shipping.

"This is the biggest logistical challenge the world has ever faced," said Toby Peters, an engineering and technology expert at Britain's Birmingham university. "We could be looking at vaccinating 60% of the population."

Several developers, including frontrunner Moderna, are experimenting with new ways to mitigate the extreme cold storage demands of their vaccines, which at present need to be kept at minus 80 degrees Celsius (-112 Fahrenheit).

SiO2 Materials Science is working on producing vials that won't shatter at super-cold temperatures.

Travel restrictions, meanwhile, are posing more prosaic problems; Johnson & Johnson, which plans to start clinical trials this summer, has struggled to send its vaccine experts to oversee the launch of production sites, for example.

'NEVER BEFORE IN HISTORY'

By setting up massive clinical trials involving 10,000 to 30,000 volunteers per vaccine, scientists hope to get an answer on whether a vaccine works as early as this October. But even if they succeed, manufacturing in bulk, getting regulators to sign off and packaging billions of doses is a monumental challenge.

Seth Berkley, chief executive of the GAVI vaccines alliance, said in reality, the world is unlikely to go straight from having zero vaccines to having enough doses for everyone.

"It's likely to be a tailored approach to start with," he said in an interview. "We're looking to have something like one to two billion doses of vaccine in the first year, spread out over the world population."

J&J has partnered with the U.S. government on a $1 billion investment to speed development and production of its vaccine, even before it's proven to work. It has contracted Emergent Biosolutions and Catalent to manufacture in bulk in the United States. Catalent will also do some fill-and-finish work.

"Never in history has so much vaccine been developed at the same time - so that capacity doesn't exist," said Paul Stoffels, J&J's chief scientific officer, who sees filling capacity as the main limiting factor.

Emergent's manufacturing plant in Bayview, Maryland, can accommodate four vaccines in parallel using different manufacturing platforms and equipment.

Funded by the government in 2012, the plant includes single-use disposable bioreactor equipment featuring plastic bags rather than stainless steel fermentation equipment, which makes it easier to switch from one vaccine to another.

This month, the company received an additional $628 million to make those four suites available to support any candidate the government selects, CEO Bob Kramer told Reuters.

As well as working with J&J, New Jersey-based Catalent signed a deal with British drugmaker AstraZeneca last week to provide vial-filling and packaging services at its plant in Anagni, Italy. It aims to handle hundreds of millions of doses, starting as early as August 2020 and possibly running through until March 2022.

It has ordered high-speed vial-filling equipment to boost output at its Indiana plant, where it is also hiring an additional 300 workers.

Michael Riley, Catalent's North American president for biologics, told Reuters his biggest challenge was trying to compress work that normally takes years into months.

Adding to the challenge is that glass vials are in short supply.

To save glass, companies plan to use larger vials of five to 20 doses - but this raises new problems, such as potential waste, if not all the doses are used before the vaccine spoils.

"The downside is that after a healthcare practitioner opens a vial, they need to then vaccinate 20 people in a short, 24-hour time," said Prashant Yadav, a global healthcare supply-chain expert at the Center for Global Development in Washington.

As part of the same drive, the U.S. Department of Health and Human Services and the Department of Defense have awarded ApiJect Systems up to $138 million to upgrade its facilities to be able to make up to 100 million plastic pre-filled syringes by the end of this year, and as many as 600 million in 2021.

The company plans to use a technology called Blow-Fill-Seal, where syringes are blown out of plastic, filled with vaccine and sealed in seconds. This will need Food and Drug Administration approval, CEO Jay Walker told Reuters.

BREAKING COLD CHAIN

SiO2 Materials Science is, meanwhile, ramping up capacity of plastic vials with a glass lining, which are more stable at ultra-low temperatures.

"You can bring us down to minus 196 Celsius, which none of the vaccines need," Chief Business Officer Lawrence Ganti said."You can throw it against the wall and it doesn't break. Our founder has done that. He's thrown frozen vials at me."

The company expects to boost production from the current 5-10 million vials a year to 120 million within three-and-a-half months, he told Reuters.

Once packaged, many vaccines need to be kept cold - and some leading contenders made from genetic material such as messenger RNA need to be kept very cold - presenting another challenge that may limit access.

"People who work with mRNA store it at minus 80 degrees centigrade, which is not something you're gonna find in most pharmacies or doctor's offices," said Dr. Paul Offit, director of the Vaccine Education Center at Children's Hospital of Philadelphia and co-inventor of the rotavirus vaccine.

Peters of Birmingham university has been gathering data from poorer regions of Africa and Asia, and said breaks in the temperature-controlled supply chain - "cold chain" - are already frequent.

In some places, it is common to lose 25% or more of vaccines because of broken cold chains, he told Reuters.

"So if you're looking to manufacture four billion, and you reckon you're going to lose 25%, then you have to manufacture five billion," he said. "It's all the elements to move it from the point of manufacture to the point of aggregation, right down to the health centres and then out to the community."

QUARANTINE QUAGMIRE

Companies developing mRNA vaccines, including Moderna and Translate Bio, which is partnering with Sanofi, are working to make candidates stable at higher temperatures.

Ron Renaud, CEO of Translate Bio, said he was confident this would happen "within a short amount of time".

Colleen Hussey, a Moderna spokeswoman, said: "We are getting more confident that we could run our supply chain at -20C, which is an easier storage condition than deep freezing," she said.

Moderna plans to add a small period of time in which the vaccine can be stored at normal fridge temperatures of 2 to 8 degrees Celsius in doctors' offices or clinics.

"We will know more in the next 2-3 months," she said.

The pandemic is also presenting obstacles of a less technical nature.

Catalent, which has some 30 plants globally, has had to write special permission slips in eight languages explaining that their workers are considered essential.

J&J is having trouble getting experienced personnel to far-flung labs to oversee the transfer of technology to contract manufacturers because they're subject to 14-day quarantines.

"It is absolutely a factor," said Stoffels. "If you have to send your people to the middle of India to get to filling capacity, that's not easy at the moment."

© Thomson Reuters 2020.

©2020 GPlusMedia Inc.

9 Comments
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This is serious stuff. In the age of Amazon same-day shipping, people kind of take logistics for granted. But this shouldn't be overlooked at all, and now is the time to start getting ready so when [if] the vaccine is available, everyone will be ready to hit the ground running.

Don't forget, there is also a worldwide shortage of air cargo, driving up prices and causing delays. This will also need to be considered as well.

1 ( +1 / -0 )

Avoid it will be the real trick.

-4 ( +1 / -5 )

The push is on. Ramp up fear of a devastating second wave (tick). wave, have a public begging for a vaccine so they can return to a semblance of normal (tick) and give it to them, safe or otherwise. Problem, reaction, solution.

What happens to skeptics, those of us who won’t drink the kool aid, even though the virus is far less dangerous to most of us than we’re being told by governments and the mainstream media? No travel “privileges? Points knocked off our social credit score? Frozen bank accounts?

Humans have consistently shown over thousands of years how horrible they can be to each other, and we haven’t come that far. Just look at what China does to dissidents, and fools like Victorian premier Daniel Andrews want to team up with them on the BRI!

-3 ( +2 / -5 )

The world needs to work and pull together for a change. The price of the vaccine must make it available to all.

2 ( +2 / -0 )

People should find out for themselves what actually goes into making these vaccines before deciding whether or not to put it in their bodies

-2 ( +1 / -3 )

Avoid it will be the real trick.

Not at all, if the first candidates are successful that means no special dificulties were found so plenty of options will soon be available. Or you can do as the antivaxxers do with reality and just reject it.

The push is on. Ramp up fear of a devastating second wave (tick). wave, have a public begging for a vaccine so they can return to a semblance of normal (tick) and give it to them, safe or otherwise. Problem, reaction, solution.

Fear is justified seeing how it can be objectively proved that the first one had a terrible cost in many countries. The public begs for things that have been proved safe and effective for centuries, there is nothing wrong with that either. And no, vaccines have to be proven safe by detailed and complicated tests before going into the market. Contrary to the imaginations of people that know nothing about it.

What happens to skeptics, those of us who won’t drink the kool aid,

Skeptics? the same as always, information is available and the worries subdued by objective scientific data. Deniers? well those people take pride in rejecting all science and evidence and prefer to live in fantasy so no amount of proof is ever going to change their minds, it is fortunate deniers are just a tiny spec in comparison with the number of rational intelligent people.

even though the virus is far less dangerous to most of us than we’re being told by governments and the mainstream media?

Or more dangerous, after all you offer no proof for that and the numbers by dozens of countries in the planet are much more reliable than unfounded opinions.

And do you know what is less dangerous than the pandemic? every single vaccine available today in the world.

No travel “privileges? Points knocked off our social credit score? Frozen bank accounts?

Fortunately most of the world do not live in North Korea or China or any or any other totalitarian state so those imaginary fears do not apply for most people.

People should find out for themselves what actually goes into making these vaccines before deciding whether or not to put it in their bodies

Yeah, sure, like millions of doctors, nurses, researchers, safety officials, etc. etc. that know perfectly well and still use them for themselves and their families because they understand the science much better than people that get scared by scientific names.

2 ( +3 / -1 )

Virusrex, you really don't like people questioning the official narrative, do you?

And no, vaccines have to be proven safe by detailed and complicated tests before going into the market. Contrary to the imaginations of people that know nothing about it.

There have been loads of complaints and court cases about dangerous vaccines that were released onto the market even though they have show to be unsafe in practice. The HPV vaccine Gardasil is one such recent example, and there are still court cases going on about that one. Often, the drug companies will settle out of court and pay a fine instead of risking negative publicity through lengthy court battles. Don't say it doesn't happen.

As I've said to you before, I'm not against the principle of vaccines, but I am wary of what is in many of them and the influence that pharmacy companies have on governments to get them approve before they are safe.

Yeah, sure, like millions of doctors, nurses, researchers, safety officials, etc. etc. that know perfectly well and still use them for themselves and their families because they understand the science much better than people that get scared by scientific names.

The appeal to authority is a waste of time. There are also plenty of doctors and nurses who don't believe everything they're fed either, and do their own research into the benefits and costs of various medicines. Look it up for yourself. I'm not saying that all vaccines and other medicines are bad - there's and enormous number of safe and beneficial ones. But that doesn't discount the fact that there are unsafe ones around - you need to consider them on a case-by-case basis.

I'm concerned about the political angle here because there is so much about this crisis that doesn't add up - from the original Chinese lies and obfuscations to mixed messages about testing rates, symptomatic and asymptomatic numbers of infected people, this new normal they keep banging on about.

If you're confident that COVID -19 vaccines are safe, fine, I'm not stopping you from getting one.

-3 ( +0 / -3 )

Virusrex, you really don't like people questioning the official narrative, do you?

Questioning is perfectly fine, making mistaken assumptions and repeating misinformation knowingly is nothing like questioning.

There have been loads of complaints and court cases about dangerous vaccines that were released onto the market even though they have show to be unsafe in practice

Nothing is perfect in this world, but if vaccines are much more safer than not vaccinating then this is perfectly fine, you can choose the least safe option (not vaccinating) what you cannot do is say this is logical or rational, because it is not.

Also, complains and court cases are free to make, but if damage is not proved that is no argument to say the vaccines are faulty, no single vaccine now in use has been proved unsafe, not a single one.

The HPV vaccine Gardasil is one such recent example

And its a very good example, because it has been found to prevent literally thousands of deaths from cancer and also to be perfectly safe, with irrational fears promoted by antivaxxers already proven to be false. Being vaccinated with Gardasil increase no known risk, for anything, and prevents importantly the risk of developing a lethal form of cancer.

Often, the drug companies will settle out of court and pay a fine instead of risking negative publicity through lengthy court battles. Don't say it doesn't happen.

Unfortunately demonstrating that people have irrational beliefs have a cost, and the cost is paid in public health perception and lives lost. NO fines are paid, because nothing wrong is being done, but settlements can be done because paying irrational people for unrelated tragedies is much better than demonstrating the vaccine is not at fault but at the cost of being perceived as against people in a sad situation, which would make vaccines suspected (without justification).

I'm not saying that all vaccines and other medicines are bad - there's and enormous number of safe and beneficial ones. But that doesn't discount the fact that there are unsafe ones around - you need to consider them on a case-by-case basis.

And that is exactly what the professionals in epidemiology, public health, statistics, etc. etc. do for a living, with extremely sophisticated methods to detect even faint hints of danger, and guess what? they all agree that every available vaccine is safe, at least compared with not vaccinating.

Considering them case-by-case is the miminum done, you are saying nothing that is nor routinely done by people with much higher preparation about the topic.

I'm concerned about the political angle here because there is so much about this crisis that doesn't add up - from the original Chinese lies and obfuscations to mixed messages about testing rates,

Then investigate and address those concerns, there is no need to imagine further conspiracies that involve every single health professional in the world that actually vaccinate themselves and their families. There is enough to worry without having to complicate things with things that are realistically speaking impossible to be happening.

this new normal they keep banging on about.

Its common for people to try and be in denial of what they don't like, that does not change the fact that objective and scientific data proves that there is no likely control of the pandemic without either very strong social distancing measures or wide immunity. For obvious reasons people will prever to be immune than stopping the economy and live perpetually behind a surgical mask, its human nature.

If you're confident that COVID -19 vaccines are safe, fine, I'm not stopping you from getting one.

There is not a single COVID-19 vaccine yet, there are only candidates and safety is being examined now, so nobody can say they are already safe. What can be said is that vaccines in general are safe and effective and the system in place to evaluate this is perfectly acceptable even if not perfect. Only irrational people expect everything that is not absolutely perfect to be automatically discarded as useless.

Your opinion about vaccines is your own, but if runs contrary to evidence then it can be discarded by others without problem, at least until you don't get more and better evidence that supports it. Nobody can make you vaccinate, but if not vaccinating makes it so you cannot do things because you would be infringing on the rights of others to be safe then the scientific evidence is what will help deciding who is right.

2 ( +3 / -1 )

@kyronstavic

There have been loads of complaints and court cases about dangerous vaccines that were released onto the market even though they have show to be unsafe in practice. The HPV vaccine Gardasil is one such recent example, and there are still court cases going on about that one. Often, the drug companies will settle out of court and pay a fine instead of risking negative publicity through lengthy court battles. Don't say it doesn't happen.

Sounds like you've mangled some half-remembered information that you never actually understood in the first place.

"Loads of complaints" is meaningless. Antivaccine groups complain about literally everything to do with vaccines literally all the time. Antivaxers are even vocal in JT threads. Their sources, when they trouble to give them at all, are invariably rubbish, and so are their complaints.

Often, the drug companies will settle out of court and pay a fine instead of risking negative publicity through lengthy court battles. Don't say it doesn't happen.

In the United States, vaccine manufacturers (and crucially, claimants) are protected from lengthy court battles by the National Vaccine Injury Compensation Program. They needn't settle out of court, either, because compensation is paid out of a fund, which is financed by a tax on all vaccines. The court itself is the US Court of Federal Claims. There is no jury, and cases are heard on a no-fault basis. In other words, the claim itself is examined, and a decision is reached on whether to award compensation, but that's as far as it goes. Compensation does not indicate, and the court does not determine, either scientifically or legally, that the vaccine in question has injured the claimant. The system is imperfect, but serves a purpose, which is to keep manufacturers producing vaccines instead of dumping them altogether, and to quickly handle cases (along with any payment of compensation). It also prevents those large manufacturers using their money, resources, and disproportionate power to put pressure on an individual family and its legal team - which is precisely what can happen in the mainstream US legal system.

The cases (complaint and ruling) are required to be made public, minus details removed for privacy purposes, and can be accessed online. Try it.

So there's no actual way to prevent publicity, and settlement is not out of court.

@virusrex

Questioning is perfectly fine.

Frequently it isn't. The question has to be asked in good faith. "Just asking questions" is the classic defence of the conspiracy theorist, but also the classic demonstration of why not all questioning methods are perfectly fine, and why conspiracy theorists are irritating douchebags.

They use questions as a disruptive tactic; as a means of innuendo; they ask questions they don't want an answer to; they ask questions they're incapable of understanding the answer to; or they simply ask questions that are stupid beyond belief. There are many environments and situations where this is entirely unsuitable, and taking the time to provide answers is impractical.

0 ( +0 / -0 )

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