Daunting task of distribution exposed as it emerges some vaccines must be 'deep frozen' at -70C

Two of the world’s leading Covid-19 vaccine contenders may have to be stored at temperatures as low as -70C, it has emerged.

The super-cooling requirements for the leading US and German contenders will add another layer of complexity to the already daunting task of distributing the vaccines, even if phase three trials prove successful. 

Most other leading candidates, including from Oxford/AstraZeneca and Johnson and Johnson, also need to be kept cool, but there are hopes that these protein-based jabs will need to be refrigerated at between two and eight degrees, rather than frozen. 

Both Pfizer and Moderna are developing mRNA vaccines, with data signalling that they will need to be transported and stored at ultracold temperatures of minus 70 and minus 24 degrees respectively to ensure their chemical structures remain stable. 

If the vaccines become too warm for too long at any point along the “cold chain” – the journey from the point of manufacturing to injection – they may be rendered ineffective. 

“I can't emphasise enough the complexity of maintaining an absolute temperature from the depo to the distribution centre to the airplane to the delivery truck to the surgery and the refrigerator in the doctors,” said Nick Jackson, head of programmes and innovative technologies at the Coalition for Epidemic Preparedness Innovations (Cepi). 

“It’s incredibly difficult even on a good day with vaccines that are refrigerated. But the challenges are made harder as you begin to lower the temperature requirements,” he added.

Growing concerns around distribution come as the stakes in vaccine development continue to rise and target dates for final stage clinical trials draw nearer. As pressure mounts, so do political tensions.

Donald Trump recently intimated he would try and shortcut regulatory hurdles to licence products ahead of the US election on November 3 and, in Britain, the Prime Minister has hinted at a special fast track licencing process.

These moves have spooked big pharma, which is worried about a consumer backlash.

In an unprecedented move on Tuesday, nine leading vaccine developers – including Pfizer, Moderna, GlaxoSmithKline and AstraZeneca, manufactures of the Oxford vaccine – issued a public pledge promising not to seek government approval of any vaccine without extensive safety and effectiveness data. 

“We believe this pledge will help ensure public confidence in the rigorous scientific and regulatory process by which Covid-19 vaccines are evaluated and may ultimately be approved,” the letter read.

Of the nine major pharmaceutical companies involved in the pledge, only Pfizer has indicated that large scale, phase three trial results could be available by October – but this is in no way certain. 

Elsewhere, Chinese firm SinoVac reported on Monday that its coronavirus vaccine appears to be safe in older people in mid-stage trials – some of the first results to be reported in the key risk group of over 60s.

Though the vaccine generated a slightly weaker immune response compared to younger adults, hundreds of thousands of Chinese have been given the two experimental Covid-19 vaccines under an emergency scheme without a single case of infection, a top official within the state-owned vaccine developer has claimed.

But although the vaccine race so far has focused on safety and efficacy data, the spotlight is increasingly on the enormous complexities around manufacturing and distribution. These issues demonstrate that access to a vaccine will trickle through the population and a successful vaccine alone will not be a “silver bullet” to end the pandemic. 

“We must temper this optimism, this talk of the perfect vaccine “just around the corner” or the idea that it will be a complete and immediate solution,” Sir Jeremy Farrar, director of Wellcome, said on Sunday. 

According to a white paper from logistics firm DHL and consultancy Mckinsey, at least two thirds of the global population is unlikely to have easy access to any coronavirus jab that needs to be maintained at sub-zero temperatures. 

This is not unprecedented – the chickenpox vaccine is stored at between minus 15 and minus 50 degrees celsius in the US. Similarly the oral polio vaccine has to be maintained at minus 20 while the Ebola jab, which 300,000 people received during the outbreak in the eastern regions of the Democratic Republic of Congo, is kept at minus 60.

But Katja Busch, DHL’s chief commercial officer, told The Telegraph that while the firm has previously transported ‘deep frozen’ goods, including animal vaccines, she is unaware of distributing a human vaccine globally at below minus 70 degrees. 

“It’s doable with a special package and dry ice,” Mrs Busch said. “Such a package will last for three to four days, depending on the temperature it is stored at and on the outside temperature, then you have to re ice it. But the biggest question is what happens at the final mile, once the package has been dropped off.”

Developed countries will not be immune from these challenges – hospitals and pharmacies often do not have the specialised freezers needed to store these ultra-cool immunisations before they are given to patients. 

It is possible that later iterations of the mRNA vaccines will not require such super-cool conditions – but given the breakneck speed of development, this data on the stability of the vaccine’s chemical structure is not yet widely available. 

However Moderna, who originally cited minus 70 as the temperature required within the cold chain, has already revised that figure to minus 24. 

And Pfizer has announced that it will provide a bespoke ‘dry ice pack’ system for its vaccine candidate under development with BioNTech. 

The packaging will be able to maintain minus 70 degrees to 10 days before vaccines require re-icing. But there is a catch: the ice will need to be replenished within 24 hours of receipt at hospitals and clinics, while the jabs will no longer work after 24 hours of refrigeration or two hours of thawing. 

Coordinating the supply chain to ensure that these vaccines not only remain cold, but arrive within a time window to use them, is a daunting, costly task – especially when so many vaccines will need to be distributed at once. 

However there are hopes that the majority of vaccine candidates will not need to be frozen, but can instead be stored and distributed in refrigerators at between two and eight degrees. 

Protein-based immunisations, from groups including Oxford/AstraZeneca and Johnson and Johnson, are targeting this temperature range. Based on previous vaccines this is realistic, said Cepi’s Dr Jackson, but “they need to generate the data to allow that claim to be on the vaccine label”. 

Any vaccine which falls between two and eight degrees is standard and can easily be absorbed into existing vaccination programmes, Gian Gandhi, Unicef’s chief of market shaping and supplier financing, told The Telegraph. 

The biggest complication could be delivering the full vaccine course, he added. 

“Most manufacturers have indicated that they're targeting a two dose schedule for the vaccine. 

“All of that is important because it is going to make administration more difficult, irrespective of whether we're talking about the US, the UK or a developing country, because you need people to come back for their second dose or their booster and [you need to make] sure the cold chain infrastructure is sufficient to store double doses,” Mr Gandhi said.

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