DEVELOPING the covid-19 vaccine in record time is a difficult task, and producing it in quantities sufficient to stop a pandemic is the largest medical manufacturing venture in history.
Vaccine production is already underway, writes Reuters, and lists some of the challenges that experts will have to solve along the way.
How to hire experts at a time when the world is facing global travel constraints, how to deal with extreme storage conditions and how to invent new types of ampoules and needles for billions of doses – in short, the vaccine development path is fraught with obstacles, writes Reuters. more than a dozen people developing vaccines.
Any supply chain disruption the world has never seen or tested before – and it could stretch from Pune in India to Oxford in England and Baltimore in the United States, could undermine or delay a complex process.
Colonel Nelson Michael, director of the U.S. Military Center for Infectious Disease Research, which is collaborating with the government’s Warp Speed project to deliver the vaccine the world now needs by January, says companies typically have years at their disposal.
“And now we have weeks,” Michael says.
Experts faced with a painful reality say they simply do not have enough capacity to produce, package and distribute billions of doses of vaccine at once.
Businesses and governments will need to address a critical shortcoming in the automated process of filling and finalizing products – packaging in ampoules or injections, sealing and packaging for delivery.
“This is the biggest logistical challenge the world is facing,” says Toby Peters, an engineering and technology expert at the British University of Birmingham.
“It looks like we’re going to need to vaccinate 60 percent of the population,” he said.
Several manufacturers, a favorite of which is the American biotechnology company Moderna, are experimenting with several ways to address the requirements of providing extremely cold conditions for vaccine storage – according to current knowledge at minus 80 degrees Celsius.
Furthermore, SiO2 Materials Science is working on the production of ampoules that will not crack at super-icy temperatures.
Travel restrictions, on the other hand, are a more prosaic problem: Johnson & Johnson, which plans to begin clinical trials this summer, is struggling to send its vaccine development experts abroad to oversee, say, the construction of production facilities.
‘For the first time in history’
With mass clinical trials involving 10,000 to 30,000 volunteers per vaccine, the scientists hope to get an answer to the question of whether the vaccine can be effective as early as October. And even to succeed in doing so, to produce a vaccine, get regulatory approvals and pack billions of doses is a monumental challenge.
Seth Berkley, CEO of the GAVI Vaccine Association, finds it unrealistic to expect the world to start from scratch and have enough doses of vaccine for everyone at once.
“It is more likely to start with a specific approach,” he explained in an interview. “We think we would have one to two billion doses of vaccine in the first year that would be distributed to the world’s population.”
J&J has entered into a billion-dollar deal with the U.S. government to accelerate vaccine development and production, even before it is confirmed as effective. He hired Emergent Biosolutions and Catalent to produce vaccines wholesale in the United States. Catalent should also work on filling doses.
“Never in history have so many vaccines been developed at the same time,” says Paul Stoffels, head of scientific development at J&J.
As with J&J, Catalent of New Jersey signed an agreement with British drugmaker AstraZeneca last week for a production plant for filling ampoules and packaging at a plant in Anagni, Italy. The goal is to produce hundreds of millions of doses, starting in August 2020 until probably March 2022.
Michael Riley, president of Catalent’s biology department for North America, told Reuters that the biggest challenge for them now is how to squeeze into months the work that has otherwise been done for years.
In addition, there is a shortage of glass ampoules.
To save glass, companies plan to use larger ampoules of five to 20 doses – but this again presents a new problem, such as a potential loss if all doses are not consumed before the vaccine breaks down.
“When a medical worker opens an ampoule, he has to vaccinate 20 people in a short period of time, in 24 hours,” says Prashant Yadav, an expert at the Center for Global Development in Washington.
The U.S. Department of Health and Human Services and the Department of Defense have set aside $ 138 million for ApiJect Systems to improve capacity to produce 100 million plastic pre-filled injections by the end of the year, and about $ 600 million for 2021.
The company plans to use Blow-Fill-Seal technology, which means that in a few seconds the injections are inflated from plastic, then filled with vaccine and then sealed. This will require the approval of the Food and Drug Administration.
Breaking the ice chain
SiO2 Materials Science, meanwhile, is increasing the capacity to develop plastic ampoules with an inner glass coating that are more stable at ultra-low temperatures.
“You can put them at minus 196 degrees Celsius, but that’s not necessary for any vaccine,” says business manager Lawrence Ganti, and continues, “You can throw them in the wall and they won’t break.”
The company hopes to increase production from the current 5 to 10 million a year to 120 million within three and a half months, he explained to Reuters.
Once packaged, many vaccines must be stored in the cold, and some made from genetic material such as RNA must be stored at a very cold temperature – which is an added challenge.
“People who work with RNA have to keep it at minus 80 degrees, and that’s not something that will be provided in pharmacies or surgeries,” says Dr. Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and one of the inventors of the rotavirus vaccine.
Peters of the University of Birmingham collects data from poor regions of Africa and Asia and says violations of temperature conditions are common.
In some places, up to 25 percent or more of the vaccine is usually lost due to ice chain violations, he explained. “So if you’re planning to produce four billion, and you estimate you’re going to lose 25 percent, you’re going to have to produce five billion.”
Companies developing the RNA vaccine, including Moderna and Translate Bio in partnership with Sanofi, are working to develop the vaccine stable at higher temperatures.
Ron Renaud, CEO at Translate Bio, believes “it will happen very soon”.
Colleen Hussey, a spokeswoman for Moderna, announces “We increasingly believe that we will be able to run our supply chain at -20 degrees Celsius, which is a much easier way to store than deep-freezing.”
Modern plans to soon develop a vaccine that can be stored at a normal refrigerator temperature of 2 to 8 degrees Celsius in surgeries or clinics.
“We’ll know that in the next 2 to 3 months,” Hussey says.
But the pandemic brings with it other obstacles that are not just technical in nature.
Catalent has about 30 factories in the world and has to write important explanations for its workers in eight languages.
J&J finds it difficult to find experienced staff in remote laboratories to monitor technology transfer because the coronavirus commits to a 14-day quarantine.
“Absolutely that’s a factor you have to consider,” says Stoffels of J&J. “If you have to send people to India it’s not easy at the moment.”