Vaccine makers face biggest medical manufacturing feat in history

CHICAGO / LONDON (Reuters) – Developing a COVID-19 vaccine in record time will be difficult. Producing enough to end the pandemic will be the greatest 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 types of vials and syringes for billions of doses, the road is fraught with formidable obstacles, according to Reuters interviews with more than a dozen vaccine developers and their sponsors.

Any snag in an unproven supply chain, which could stretch from Pune in India to Oxford in England and Baltimore in the United States, could torpedo or delay the complex process.

Col. Nelson Michael, director of the US Army’s Infectious Diseases Research Center. USA Who is working on the government’s “Deformation Speed” project to deliver a large-scale vaccine in January, said companies generally have years to figure this out.

“They have weeks now.”

Much of the world’s attention is focused on the scientific race to develop a vaccine. But behind the scenes, experts face a stark reality: We simply may not have enough capacity to manufacture, package, and distribute billions of doses at once.

Companies and governments are competing to scale machinery to address a critical shortage in automated filling and finishing capacity – the final step in the manufacturing process of placing the vaccine in vials or syringes, sealing and packaging them for shipment.

“This is the biggest logistical challenge the world has ever faced,” said Toby Peters, an engineering and technology expert at the British University of Birmingham. “We may be looking to vaccinate 60% of the population.”

Various developers, including Moderna’s favorite (MRNA.O), are experimenting with new ways to mitigate the extreme cold storage demands of their vaccines, which currently must be kept below 80 degrees Celsius (-112 Fahrenheit).

SiO2 Materials Science is working on the production of vials that do not break at very cold temperatures.

Meanwhile, travel restrictions pose more prosaic problems; Johnson and Johnson (JNJ.N), 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 IN HISTORY’

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

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

“It is probably a personalized approach to start with,” he said in an interview. “We are looking to have between one and two billion doses of vaccine in the first year, spread across the world population.”

J&J has partnered with the United States government on a $ 1 billion investment to accelerate the development and production of its vaccine, even before it is proven to work. It has contracted Biosolutions Emergentes and Catalent to manufacture in bulk in the United States. Catalent will also do a fill and finish job.

“Never in history has so much vaccine been developed at the same time, so there is no such capacity,” said Paul Stoffels, chief scientific officer at J&J, who sees fill capacity as the main limiting factor.

Popup (EBS.N), the manufacturing facility in Bayview, Maryland, can accommodate four vaccines in parallel using different manufacturing platforms and equipment.

Funded by the government in 2012, the plant includes disposable single-use bioreactor kits with plastic bags instead of stainless steel fermentation kits, making it easy 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.

BLOW-FILL-SEAL-REPEAT

In addition to working with J&J, New Jersey-based Catalent (CTLT.N) signed an agreement with the British pharmacist AstraZeneca (AZN.L) last week to provide bottle filling and packaging services at its plant in Anagni, Italy. Their goal is to handle hundreds of millions of doses, starting in August 2020 and possibly through March 2022.

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

Michael Riley, North American president of organic products for Catalent, told Reuters his biggest challenge was trying to compress the work that normally takes years or months.

In addition to the challenge is that glass vials are scarce.

To save glass, companies plan to use larger vials of five to 20 doses, but this poses new problems, such as possible waste, if not all doses are used before the vaccine breaks down.

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

As part of the same campaign, the US Department of Health and Human Services. USA And the Department of Defense has awarded ApiJect Systems up to $ 138 million to upgrade its facilities to be able to produce up to 100 million pre-filled plastic syringes by the end of this year, and up to 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 approval from the Food and Drug Administration, CEO Jay Walker told Reuters.

BREAK THE COLD CHAIN

Meanwhile, SiO2 Materials Science is increasing the capacity of glass-lined plastic vials, which are more stable at ultra-low temperatures.

“It can bring us down to minus 196 degrees Celsius, which neither vaccine needs,” said Chief Commercial Officer Lawrence Ganti. “You can throw it against the wall and it doesn’t break. Our founder has done it. He threw frozen vials at me.

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

Once packaged, many vaccines must be kept cold, and some of the top contenders made of genetic material such as messenger RNA must be kept very cold, presenting another challenge that may limit access.

“People who work with mRNA store it at minus 80 degrees Celsius, which is not something you will find in most pharmacies or doctors’ offices,” said Dr. Paul Offit, director of the Center for Vaccine Education at the Hospital of Philly children and company. -inventor of rotavirus vaccine.

Peters, from the University of Birmingham, has been collecting data from the poorest regions of Africa and Asia, saying that interruptions in the temperature-controlled supply chain (“cold chain”) are already frequent.

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

“So if you are looking to make four billion, and you think you are going to lose 25%, then you have to make five billion,” he said. “They are all the elements to move it from the manufacturing point to the aggregation point, to the health centers and then to the community.”

QUAGANTINE QUARANTINE

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

Ron Renaud, CEO of Translate Bio, said he was confident that this would happen “in a short period of time.”

Colleen Hussey, a spokeswoman for Moderna, said: “We are increasingly confident that we could run our supply chain at -20 ° C, which is an easier storage condition than freezing,” he said.

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

“We will know more in the next 2-3 months,” he said.

The pandemic also presents obstacles of a less technical nature.

Catalent, which has some 30 plants worldwide, has had to write special permits in eight languages ​​to explain that its workers are considered essential.

J&J is having trouble taking experienced staff to remote labs to oversee the transfer of technology to contract manufacturers because they are subject to 14-day quarantines.

“It is absolutely a factor,” Stoffels said. “If you have to send your people to central India to reach filling capacity, that is not easy at the moment.”