From fridge to freezer

posted on 4th March 2021
From fridge to freezer

Covid-19 has seen stakeholders throughout the pharma cool chain make rapid changes to how they maintain the temperature and stability of life-saving vaccine products, reports Roger Hailey

From fridge to freezer, Covid-19 vaccines have brought a sudden chill to the temperature ranges of pharmaceutical cool-chains.

Traditional pharma supply chains set at 2-8°C are now adapting to the Moderna and Pfizer-BioNTech vaccines, which require product temperatures of -20°C and -70°C, respectively, to be maintained during transport.

While airlines prepare to, and in some cases begin to, provide the necessary air freight capacity for a global vaccine airlift, the suppliers of specialist cool chain equipment – either Unit Load Devices (ULDs), palletised containers or individual packaging – are swinging into action.
They already work with the major manufacturers of life-saving pharma but now have to adjust to the extreme low temperatures that some vaccines demand in transit.

When Covid struck last year, cool chain equipment provider SkyCell began developing an ultra-low temperature container, the 1500DF, based on an existing platform but using innovations in material science to distribute the energy within the container.

Dry ice limits
Ultra-cold dry ice has strict limits on its use on aircraft due to sublimation, the process through which it turns from a solid into gaseous CO2, which can be dangerous in a confined area, and so innovative thinking was needed.

SkyCell chief executive Richard Ettl says: “The goal is to use as little dry ice as possible.” The new container uses 100 kg of dry ice – less than half that required before – which will maintain -70°C for up to 120 hours and has already undergone test flights with partner airlines.

The 1500DF has a double door system and filtering to prevent warmer air coming in when the container is opened.

The container has a drawer system which allows dry ice bricks to be refilled within minutes.

The container can be trucked to a vaccination centre and used as a temporary storage and does not need electric cabling. You also get more vials of vaccine per flight.

Adds Ettl: “You can load 50 containers per B777 freighter, with 30,000 vials in each container, meaning about 1.5m vials per flight. Each vial contains 5 shots, so in total per flight there are 7.5 million shots.”

Healthcare packaging provider Sonoco ThermoSafe is in production mode for its Pegasus ULD that will launch in second quarter 2021. It is the first passive bulk temperature-controlled container approved unit load device for pharma use, which can speed through ground handling and customs processes without delay.

Passive vs active containers
Bourji Mourad, director for global logistics and partner management at Sonoco ThermoSafe – Leasing Services, explains: “It is a passive container, eliminating the risk of mechanical failure, but the high-tech insulation and phase-change material (PCM) cover provides more than 120 hours of qualified performance at 2-8C. Engineered with composite materials, the Pegasus ULD offers a lighter solution that is substantially more damage-resistant than traditional metal containers.

“Additionally, Pegasus contains a fully integrated, FAA approved telemetry system which provides real-time, cloud-based data on payload, ambient temperature and other key environmental factors.”

Deep frozen vaccines are important, but only a small part of the story. Niklas Adamsson, chief operating officer at Envirotainer, an active temperature-controlled container supplier, told an Aviation Week vaccine webinar: “Everybody is discussing (maintaining temperatures using) dry ice at -70°C or -20°C, but that is only 10% of volume,” adding that the majority of contracted vaccines, such as that from AstraZeneca, will have product temperature requirements in the 2-8°C range.
Dr Joachim Kuhn, chief executive and founder at thermal container and box supplier va-Q-tec – whose vaccine customers include Moderna and Pfizer BioNTech – separates the cool chain into three steps. “One step is the continental long-haul flights from the factory to the distribution centres, and then you have a second level with regional distribution. Then there is the third level, the last mile to hospitals or people’s homes,” he notes.

“Our entire fleet of containers and boxes is completely applicable to all sub-zero temperatures, so we can handle 2-8°C and 15-25°C, no problem; but our entire container fleet can also do sub-zero temperatures, whether it is -20°C, -40°C or -70°C.”

He adds: “We offer a flexible door-to-door solution: our containers are not ULDs, which is why they can easily leave the airport and be transported from there directly to its destination without the need for power recharging or re-icing.”

Temperature battery
For low and ultra-low temperature ranges until -60°C, va-Q-tec does not use dry ice in its packaging but instead a temperature battery (using phase change materials – ‘PCMs’) which stores the thermal energy. At even lower temperatures, the company also uses small amounts of dry ice – but far less than in solutions from other manufacturers due to the excellent insulation of the thermal boxes and containers.

Says Dr Kuhn: “Currently, we are even developing a -70°C dry-ice-free PCM – a game changer in our industry. We store energy at a given temperature very efficiently. The temperature-prepared batteries are placed in the highly insulated container prior to delivery to the customer, to exhibit the required temperature upon arrival at the customer’s site. He puts the pharma into this pre-tempered box and the desired temperature is kept automatically for five days or longer.”

Meanwhile, Lufthansa Cargo-owned ULD management company Jettainer has launched cool&fly – a unique management service for temperature-controlled containers, delivered by a dedicated team of experts based in the Middle East, to manage “a limited resource” during the vaccine airlift: temperature-controlled ULDs such as those provided by CSafe and Envirotainer.

Thorsten Riekert, chief sales officer at Jettainer, explains: “Our cool competence centre in Abu Dhabi is specialised in the management of cool ULDs and so we serve the full range of customers from order management to final delivery. We are fully connected to the suppliers and then monitor the handling, and the positioning until the ULD is returned to the supplier.”

At present the deep frozen vaccines are mainly shipped in refrigerated packages, which in turn can be transported in standard ULDs. However, shipments using cool containers are expected to increase in the coming weeks and months. Riekert says that the cool&fly temperature bandwidth will range from -20°C to those of normal pharma supply chains.

‘Pop-up’ cargo airlines
The March 2020 start of an air freight surge to carry personal protective equipment (PPE), and now a similar rush for Covid vaccines and test kits, has seen start-up cargo airlines “popping up” for two reasons, says Riekert.

“There is money in the cargo business right now and they are also able to close the gap and keep supply chains running to participate in vaccine distribution,” he notes. “Airlines which have not been involved in the cargo business before are setting up operations, for example some low-cost carriers.”

These new customers exemplify the ramp up of additional air freight capacity for the vaccines and the demand for suitable cool chain packaging and expertise.

SkyCell was historically focused on 2-8°C and 15-25°C, but three years ago entered the vaccines market and now provides container and packaging solutions for 90% of the vaccines distributed globally by Japanese life sciences giant TSK.

Says Ettl: “We learnt a lot about vaccines,” and one lesson was how to reposition containers in order to maximise utilisation of the equipment. “We learned with TSK how best do it, so we worked closely with the freight forwarders, DHL and Kuehne + Nagel.

“For example, when it is a full charter flight, there are certain pros and cons; but the good thing about a charter is that you know there is a deadline, and that really focuses everybody to deliver on time.

“And sometimes it means less product is available, but you know that it will go out the door and it has the advantage of bringing the containers back into the system.”

Rapid changes
Covid has seen vaccine manufacturers, packing suppliers, airlines, freight forwarders and all the stakeholders in the pharma cool chain make rapid changes to how they work to maintain the stability of established pharma for cancer drugs and other illnesses alongside growing vaccine demand. All stakeholders agree that it is possible to handle both without disruption to either.

One question is whether there be a post-pandemic change in pharma supply chains of the future, on the basis that new vaccines will be needed annually at global scale to tackle regular mutations in the Covid virus.

Says Mourad: “I have been involved in cold chains for almost 40 years and they have kept growing because people are living longer, and they need new medicines. You have viruses such as SARS and then the flu vaccine which has to be changed every year.”

The supply chain providers would like longer and better forecasting from pharma companies about the timing and amount of vaccine consignments, although that is not always practical. Mourad notes: “It is continually the situation with pharma companies in terms of production and a vaccine having to pass quality control before a manufacturer can release a product. It is always a dream of any packaging solutions company and the airlines to have an earlier forecast about the kind of product they will be handling and the equipment they will need so they can allocate the resources.

Last-minute requirement
“There will be challenges, but industry cooperation is pretty good when it comes to a last-minute requirement in deciding which packaging solutions or airline to use on certain trade lanes.”

He adds: “Covid is going to be with us some time and we will need two doses for vaccinating over 8 billion people, which will take a long period and air freight capacity. Hopefully we are not talking about a variant mutation and even another vaccine.”

Ettl of SkyCell believes that centralised manufacturing of complex vaccines will be kept to a few locations, but there will be an increase in so-called fill-finish sites at a regional level where bulk consignments will be put into glass vials for onward localised distribution.
“That is definitely a possible scenario and there are very good reasons why pharmaceutical companies have very few production spots and also back-up sites with similar capabilities,” Ettl adds.

“I think the raw materials and ingredients that make a vaccine will still be produced in a very few locations but then transported in bulk to fill-finish sites for the final process at the right dosage for vials or syringes.”

Dr Kuhn of va-Q-tec believes that using dry ice is “completely obsolete”, not only for the 2-8°C pharma cool-chains, with new technology replacing that need in the near future. He agrees that there will be a greater centralisation of both the key vaccine ingredients and manufacture, again seeing the development of more fill-finish sites, due partly to better efficiencies in the cool chain.

Manufacturing location factors
“I think it will change because we need to consider whether the manufacture should all happen in one place, making the supply chain safer and not so intercontinental,” he notes.

“Many manufacturers have separate factories because of tax advantages. A good example is Puerto Rico. Do you really need a pharmaceutical factory in Puerto Rico, with all the hurricanes and relatively few people living there?

“If I was a government buying vaccines for my country, I would want them produced at least on the same continent.”

Riekert of Jettainer believes that the international community, especially in Europe, has experienced a steep learning curve in the production of vaccines and their distribution at scale through global supply chains.

“We need to keep the supply chain running and in terms of technologically, we will probably see ULDs that can manage those -70° temperature ranges, something we do not have right now.

“But what we will also see is how we cope in the future with vaccine logistics in Asia or in Africa and this needs to be implemented. There will be changes in the pharma supply chain and even closer cooperation. The whole globe has got smaller.”