Mission critical

posted on 1st December 2020
Mission critical

The success and efficacy of the first Covid-19 vaccines has heightened the focus on the massive and challenging air logistics operation that will be needed to effectively distribute them on a global, population-wide scale. Will Waters reports

News in recent weeks of the apparent success and efficacy of the first Covid-19 vaccines in late-stage clinical trials has been warmly welcomed around the world and has heightened the focus on the logistics operation that will be needed to effectively distribute it on a global, population-wide scale.
Countless freight and logistics companies have described the project as “the biggest ever logistics challenge”. And although there are reported to be 11 vaccines currently in ‘phase 3’ trials and more than 100 other candidate vaccines, requiring a variety of distribution conditions, the expectation that one of the first vaccines likely to be available at scale, the Pfizer-BioNTech vaccine, will need to be maintained at a product temperature of around -70°C has highlighted the extent and complexity of that logistics challenge.

Logistics has again been a subject for mainstream discussion amid speculation about whether pharma supply chains are ready to transport the vaccines in the vast quantities needed at ultra-low temperatures, or even in 2-8°C supply chains. Although many within the sector have been working for weeks or months on solutions, questions have persisted about the available capacity of aircraft, warehousing, packaging, dry ice, and last-mile delivery systems, along with the ability to coordinate and maintain the integrity of the vaccine – whether that requires maintenance of deep-frozen or 2-8°C supply chains.

Logistics preparations
Robert Coyle, SVP for Pharma Services at global forwarding and logistics group Kuehne + Nagel (KN), says life-science logistics specialists such as KN are involved regularly in vaccine logistics operations that involve maintaining products at ultra-deep-frozen temperatures.

“We handle these types of situations in this pharma healthcare space every day where we are shipping goods around the world at deep-frozen-temperatures, -20°C temperatures, and 2-8°C, and normal general cargo,” he explains. For KN, that is through the group’s pharma healthcare division within KN and an acquisition it made in December 2018 in the business QuickSTAT, which manages a lot of shipments at ultra-low temperatures, for example during clinical trials.

“So, we do support, for example, several companies in the flu vaccine”, a process that involves “different time periods, seasonality in the northern hemisphere, southern hemisphere, where the demand goes up and down and you have different temperature requirements”, Coyle explains.

Clinical trials
In clinical trials, you may have 40,000 or 60,000 participants where you might be handling deep frozen, notes Coyle. “So, what’s different as we look forward is really the scale of this effort – the estimated number of doses between 11 and 15 billion. And we’re assuming around a 12- to 18-month pandemic response before it would move into more of a commercial response.”

Scale implications
With that large-scale distribution requirement, it is fortunate that so many logistics and air freight companies have been building their pharma logistics capabilities even prior to the emergence of Covid-19, with most now accelerating that scale-up. For example, KN has been in a process since 2018 of doubling the scale of its life sciences business by 2022.

“So, in many ways we’re in a really good spot to be able to grow that,” Coyle notes. “We’ll do our part. There’s going to need to be multiple players in this supply chain to make it effective. So, the ministry of health or the distributor warehouse out to the patient, we don’t play in that space.”

Coyle, who before joining KN spent more than 20 years at one of the OEMs at GSK, explains: “In the typical vaccine supply chain, you have drug substance – which is like your active ingredient – and drug product. So, (for) all the materials that are needed to make the drug substance, we’re doing air freight, road logistics, sea logistics inbound to that drug substance facility and also providing warehousing.

From drug substance to drug product

“Then from drug substance to drug product, typically in the vaccine world that active ingredient is moving at deep frozen – because you don’t want any degradation before it becomes part of drug product. So, in all that road, logistics, air logistics, we have capability at deep frozen, -20°C; 2 to 8°C.”

Those ingredients then become finalised and stabilised in the form of a drug product, within its final packaging. Coyle says most of the Covid-19 vaccines are likely to be in a vial. And one thing that is often misunderstood is that “those vials can hold one dose, five doses, 10 doses, and up to 20 doses”, he notes.

Number of doses per pallet
“So, if we talk about 75 million doses, which would be equivalent to what they’re estimating is needed in Canada, that sounds like a lot; but when you break that down to number of pallets, the number of doses per pallet becomes a very critical number.”

That figure varies from company to company. “One company I’m thinking about does about 136,000 doses on a pallet – so that’s 551 pallets (needed to move those 75 million doses). We do 551 pallets in minutes across our supply chain,” says Coyle. “So, from a number standpoint, we feel like we have the capacity.”

Warehousing constraint

He adds: “I think the one area that is going to be probably the most constrained across the industry is warehousing space at those varying temperatures. So, we’ve had space available, but we’re also building a hub concept. We’ll have a hub in the US and in Europe that is flexible to be able to handle those temperature ranges, as the products are released and approved – so, everything from -80°C. You’ll hear some of our competitors call these ‘freezer farms’.”

Coyle continues: “We’re calling it our Covid-19 temperature pods. So, whether that be a reefer container or a refrigerator, or larger refrigeration mechanisms, our hubs are all capable of storing pallets at deep frozen, at -20°C, or the traditional 2-8°C capability.

“And our part will be from inbound, raw materials to drug substance, all the way to drug product, shipping that out into the country. And in the countries, it’s going to be handled either from the ministries of health or the governments, the military, or, in some cases, distributors – like they’ve selected in the US with McKesson.”

Final-mile distribution
A lot of logistics and air freight observers have talked about the challenge of final-mile distribution. Coyle says there are indications that a lot of that final mile will be handled by the traditional integrators or express parcel courier businesses.

KN does have a final-mile capability within QuickSTAT, including direct to patient distribution, and “we can leverage that capability as needed, in the COVID-19 response” on a limited scale. But under normal circumstances, the final-mile “from the in-market, warehouse outbound”, is not the domain of KN’s pharma healthcare division,

“We’re going to do our part – where we’re very good and have the infrastructure to support it,” Coyle says.

Nevertheless, in the context of this pandemic, he believes solutions like KN’s Covid-19 temperature pods can be part of the in-market solution. “We are getting a lot of requests from governments today,” he says, including “putting these temperature pods in conference centres, festival areas, into our existing general cargo warehouse space, so that there’s extra capacity”, including from “some countries south of the US, countries in Europe, that are all very interested in having the ability to store the different products that come in for COVID-19”.

He adds: “That capacity to store is going to be very critical, depending on how the governments set up their distribution.”

The air capacity challenge

Other challenges under discussion have included the availability of air capacity.

Veronique Dameme, Head of DB Schenker’s Global Healthcare Market Vertical, said DB Schenker had “committed very early to secure additional capacities for Covid-19 vaccine transports whenever they are needed”. This includes leveraging existing capabilities and the transfer of knowledge from other parts of the DB Schenker organisation, such as AOG or ‘control tower’ capabilities. “In general, and as it is a matter of ‘survival’ for a number of airlines, we have experienced great cooperation and flexibility from the airlines,” she highlights.

Mads Ravn, EVP and Global Head of Air Freight at forwarder DSV Panalpina, commented: “Unlike PPE and the extreme surge for air capacity in the second quarter of 2020, the COVID-19 vaccine will be produced more locally, and as such intra-regional distribution will offset much of the long-haul air cargo demand. The shipping of COVID-19 vaccine will be more complex, but we do not foresee the same capacity crunch as experienced earlier this year.”

That view is echoed by some other freight forwarders, including Neel Jones Shah, global head of air freight at Flexport. “If we take Pfizer for example, for the North American audience, the vast majority of the production will be manufactured in the US, which means they won’t need to rely on air transport but can rely on road transport,” notes Shah. “It will be much easier than air transport, because of things like dry ice limitations of aircraft – and the multitude of handoffs in air freight is complicated to coordinate, to make sure everybody is doing things in exactly the right way. When you do things by road, typically the pharmaceutical company can be much more in control of every aspect of that move.

“There will still be air transport, of course, but it won’t be to the extent where every vaccine is going to have to wind up on an aeroplane in order to get to a distribution facility.”

Dameme’s colleague at DB Schenker, SVP of Global Revenue Management Air Freight Christoph Hemmann, notes: “It appears right now that the expected (air) capacity is less of a challenge than initially considered. We expect vaccines to be produced throughout several months, which will rather lead to a continuous demand for capacity solutions instead of a large one-time wave.

“The largest challenges are expected not necessarily during the air freight transportation itself, but in the final-mile distribution. Capacity is rather critical regarding storage and last-mile solutions due to current infrastructure limitations – even in modern economies and developed countries.”

1,000 dedicated flights needed

Coyle also does not expect flight capacity to be such a major problem – particularly because of the number of passenger aircraft that are not currently flying. “We are actively having conversations with all of our relationships, to ensure that we will have enough capacity ready to go, to be able to handle this influx,” he says

He also believes initial calculations that the vaccine transport would require something like 8,000 cargo flights were an overestimate. “From our estimates, as you equate the number of doses into supply chain language – especially the products that are coming out at 2-8°C – if you look at flights needed assuming the product is a 2-8°C, and if we put 70 tonnes on a freighter, you’re talking about 1,000 flights.

“Some people have estimated a lot more, and I think those estimates come if you’re talking deep frozen, where there are limitations on dry ice capacity on a plane; or, some of those estimates were in the early days, when they didn’t realise a vial could hold more than one dose.”

Information still emerging
He continues: “As the knowledge of the pharma, healthcare and vaccine space starts to come out, and with more real end products – and understanding the amount of doses that can sit on a pallet – then you can start to equate: how is this going to work, and is logistics really going to be the bottleneck? Or is the ability to manufacture the volume going to be the bottleneck? And that’s going to be an interesting one to watch.” Coyle says you would have to go into each company to ascertain the answer to that question.

But because clinical trials that usually take several years have been accelerated so much, he says we are initially seeing some of the stability characteristics of clinical products – which can require their storage at temperatures from -196°C to -80°C, to -20°C – moving into their commercial product stages.

Product characteristics and requirements change

“We’re predicting that there’s going to be several phases of this commercial deployment and, in phase one, we’ll have a lot of these variations on the different temperatures. And as companies continue to do their storage and distribution stability testing, we may see some of the product characteristics and requirements change.”

Although the Pfizer vaccine reportedly needs to be transported and stored at a ‘product temperature’ of -70°C, several reports indicate that the shipper themselves, Pfizer, will pack its vaccine in specially designed boxes capable of independently maintaining that temperature for several days.

Product temperature vs transport temperature
Nathan De Valck, Chair of the air freight pharma quality organisation Pharma.Aero and Head of Cargo Product and Network Development at Brussels Airport Company, says: “Some of the other vaccines that are in the pipeline and being developed have higher temperatures. So, I think the Pfizer temperature is going to be the exception.”

He continues: “There will be some others that require below-zero temperatures. But some of the others being developed will be at normal vaccine temperature, between 2° and 8°C, because they’ll be more stable, because the manufacturers will take some more time to develop them, to test them, to get some more stability data. So, I think the fear we had a couple of months ago of all these billions of vaccines having to be shipped at -70°C is ungrounded.”
He adds: “I don’t want to minimise the effort; I just want to indicate that it will not be impossible for the industry.”

Product temperature vs transport temperature

Explaining the difference between product temperature and transport temperature, De Valck says: “The product temperature is the inside of the box temperature, where the vaccine sits, and the indications are that Pfizer has been developing a box where the vaccine sits inside the box, or a box within a box solution, and using dry ice it can be maintained at -70°C for several days – as long as the outside of the box transport temperature is kept up between 2° and 8°C. So that makes it manageable for our industry.”

No room for error
On the major pharma lanes, he says that 2-8°C temperature range is fairly standard. “The thing we have to take care of here is that there is no room for error,” he stresses. “We all know that in the air cargo supply chain, there are temperature deviations from time to time, because it is really difficult to maintain that. With the Covid vaccines, we will not have that manoeuvrability. These vaccines will need to be kept stable, so there cannot be variation. That, and the very big volumes, will be the big challenges.”

He continues: “No one knows exactly from where to where they wanted to be shipped. But it is clear that there will be considerable volumes by air, and that’s a challenge.

“I think the airlines and freight forwarders and airports that have been specialising in pharma transport, they will be very well-prepared. Those that were not really ready at the start of this year will have a hard time. But if we have a good starting point, for example at BRU, we are in a good position.”

Vaccine task force
And those that continue with the actions they have been taking in recent weeks, for example those participating in the BRUcargo task force, “will be even in a better place in a couple of weeks to start shipping these vaccines. It’s a matter of good preparation, aligning all the stakeholders in the cool chain, aligning the procedures, making sure there is some visibility in the process, that there is data sharing, that there is good infrastructure in place; and we’ll be up to handle it”.

De Valck adds: “I think the challenge will be harder for some airports in more remote locations in less developed places in the world with less specialised or sophisticated facilities, because the vaccine will have to travel virtually everywhere in the world. Forwarders and shippers will be looking at destinations in central Africa, for example, to look at how they will keep that transport stable at 2-8°C – and not just at the airside transport, but also the last mile. I think that is a big challenge for forwarders and shippers: to find those end-to-end solutions.”

He says these packaging solutions are being tested, so it is currently still unclear how long they will be up to keep a vaccine stable at around -70° Celsius, and the tolerance of that packaging solution to temperature changes outside of that packaging.

“I can only assume, knowing what type of technology they are using, that a small deviation of the couple of minutes a little bit outside of the temperature range will probably not have a big impact,” notes De Valck. “But if you have a shipment out on the tarmac in very high temperatures, then you would feel that would have a big impact on the product temperature.”

Moderna vaccine example
The expectation that the Pfizer vaccine temperature requirements will be the exception rather than the norm were reinforced by the findings of the Moderna vaccine trials, the second of the mRNA vaccines to announce highly promising efficacy results from its phase 3 clinical trials. Announcing the results in mid-November, Moderna president Robert Hoge said his company had been working very hard on stabilising its product, “to make it more deliverable to destination markets unable to guarantee ultra-frozen temperature storage”.
Hoge noted: “What we are able to do with the vaccine now, which is (store it for up to) six months at freezer temperatures of -20°C, and up to 30 days in a refrigerated temperature, 2-8°C, means that you can deliver this vaccine into local, in fact rural, GPs and even pharmacies. That means it needs no special infrastructure and equipment, and hopefully you are going to be able to do broad-based vaccination where people are, as opposed to bringing them into centralised vaccination clinics.”

Oxford-AstraZeneca vaccine
The preliminary results of the Oxford-AstraZeneca vaccine trials have further reinforced this expectation that the need for ultra-low deep-freeze product temperatures is likely to be the exception, not the rule. The vaccine can be stored, transported and handled at normal refrigerated conditions of 2-8°C “for at least six months and administered within existing healthcare settings”, the partners said, noting that they are “making rapid progress in manufacturing, with a capacity of up to 3 billion doses of the vaccine in 2021, on a rolling basis, pending regulatory approval”.

Professor Andrew Pollard, Chief Investigator of the Oxford Vaccine Trial, said: “We have a vaccine that is easy to distribute. It is stored at fridge temperatures, and we can get it to every corner of the world. It is already being manufactured in 10 different sites around the world to make sure that that can happen.”

Race against time
Nevertheless, the battle against Covid-19 and its devastating effects on both people and economies is to a significant extent a race against time. Therefore, despite the logistical challenges of flying and storing and distributing a vaccine that requires ultra-deep-frozen temperatures, that logistical operation is expected to still go ahead on a massive scale.

Given the challenges of last-mile delivery of a Pfizer vaccine requiring maintenance at -70°C, indications that Pfizer may use the big global express delivery integrators for much of that role seem reasonable, believes De Valck.

“Talking to be shippers personally, the reason they want to use the integrators, especially in the first phase, is simply because of the last mile, where they feel that in the current phase, a lot of freight forwarders are not capable yet of offering a fully integrated service – from factory to vaccination centre type solution.

“There is no problem airport to airport, but from the airport to vaccination centre in the specific country, that is the big issue. The integrators have their own distribution capabilities last mile in a lot of places, and they can also guarantee a certain maximum throughput time – 24 hours or 48 hours or 72 hours – which is not always the case in the more fragmented cargo supply chain.”

He adds: “I think there is also the challenge the rest of the air cargo industry has – the forwarders in this case, and the trucking companies: to make sure they have this kind of integrated service offering for vaccines where they can guarantee the last mile as well.”

Nevertheless, he believes significant volumes of the vaccines will also be handled within the normal commercial air cargo system. “There are, even today, flights being planned on normal commercial operators,” notes De Valck. “So, it will be a mix of integrators and the other commercial operators.”

Sweet spot: 2-8°C

Coyle says 2-8°C “is really our sweet spot”, although he says if a product needs to be kept deep frozen, shippers and logistics companies can create special packaging – much like Pfizer has described.

“With dry ice, that packaging would be validated for a certain period of time, and we would make sure that time is longer than the route time,” he says. And if, for some reason, the route time was longer, “then you’d have to re-ice. We’ve been doing re-icing for years – at our airports, at our cross docks, in road logistics.”

“But for products that don’t have to be kept deep frozen, we have trucks, active containers, gel-pack solutions” that can keep products “at -20°C or 2-8°C for many hours. We have passive and active solutions in air and road logistics to be able to handle that.”

He continues: “I hear a lot of people talking about the challenges; we do this day in, day out. I think the two things that have changed are that the evening news is now paying attention to everything we do, and just the size and scale.”

Less-developed countries
And there is also the fact that a majority of the world’s population is not in Europe and the US. “So, you have got to get products into Africa and Latin America and Asia,” notes Coyle. “And that’s where I think our Covid-19 temperature pod solution is really going to play a key role – where they may not have even 2-8°C capability. During this pandemic response, (organisations are) not going to have time to build a new warehouse and qualify that warehouse.”

DB Schenker’s Veronique Dameme highlights “four major challenges in transporting a Covid-19 vaccine. These are the magnitude of the task to transport several billions of doses, the demanding conditions of certain vaccines requiring ultra-deep-frozen transportation, the lack of adequate infrastructure, and the ability to even reach certain remote or hardly connected parts of the globe.”

On that final-mile distribution, her colleague Christoph Hemmann comments: “An important task will be to set up, for example, vaccination centres or drive-through vaccination programmes with external high-quality cooling solutions to extend transportation and storage time – which can also be utilised as a contingency plan in case of any process failure.”

Coordination challenge
Christopher Holmes, Managing Director for business advisory group IDC Insights Asia-Pacific – which recently produced a detailed paper on Covid-19 logistics planning – says the capability and expertise exists globally in the logistics sector, “but these need to be coordinated, with not one company or organisation undertaking or purporting to undertake the complete end-to-end distribution”.

He agrees that the biggest logistical challenges are likely to be “in the global south and essentially in-country, in the last mile, as vaccines need to be shipped to hot, far-flung locations in underdeveloped parts of countries”. That includes “storage at more remote and hard-to-reach locations”, he notes, adding: “Are we going to see governments rush to put up cold stores? I think that’s one of the things we may see.”

But he says these are not just challenges in parts of Africa and elsewhere in the global south, highlighting that there are plenty of less-well-connected parts of Asia that lack reliable electricity supplies.
Holmes believes one possible scenario will be for initial waves of vaccine deliveries to places where the logistics is more easily achievable given the temperature requirements of the first vaccines, with harder to reach locations served later via vaccines with less-demanding temperature-controlled storage requirements.

Cold-store logistics
Outlining the logistics of providing temporary cold-store facilities, KN’s Coyle says their provision could be a single solution or part of a more complex, end-to-end solution.

“We are looking at everything from locating that pod in one of our warehouses, where there is security and the people are trained. We also could put it in a place where we have to put a fence up and cameras and security guards and ensure the quality and security aspects of that temperature pod solution as well,” he adds.

Those temporary pods might be just a shipping reefer container, for example, which would have the capability of storing something down to -30°C, or -40°C. “And we are working with other vendors that have equipment that’s basically the same size as a reefer container that can refrigerate down into deep frozen as well,” Coyle adds. “We have road trailers that can do that as well. And then, obviously, 2-8°C is more plentiful, and that could be reefer-sized trailer size down to a typical US-size refrigerator.”
Some of these solutions are able to produce dry ice – which can also be reliably supplied at certain airports.

Coyle notes: “So we have 233 (pharma) operations. Of these, 95 are CEIV certified, and within that number, we’ve identified 32 airports that have full re-icing capabilities; and we are only going to use those airports for the deep-frozen products.”

Dry ice limitation
Flexport’s Neel Jones Shah has concerns that the amount of dry ice that can safely be carried on aircraft could be a significant limiting factor, given that “dry ice is the only way to keep a vaccine at -74°C”. For example, he says a typical widebody passenger aircraft such as a B777 is only allowed to carry up to about 1,100 kg of dry ice, “which means you’re only able to carry about 8 tonnes of vaccine”, he highlights.

“If there were no dry ice limitations, or if you didn’t need dry ice to keep it cold, you could carry five times that amount of vaccine on the aircraft, 40 tonnes. So, that gives you an order of magnitude, where there could be a lot of unused capacity when you’re flying an aircraft moving the vaccines around from manufacturing point to distribution point.”

He continues: “The airlines are coming back to Boeing and Airbus, asking: ‘can we raise the limitation’? And Boeing and Airbus are looking to see how much more tolerance is there to increase the amount of dry ice, so that you can carry more vaccine.”

Coyle emphasises that dry ice only needs to be used if the shipments need to be deep frozen. “So, -60C to -80C. You would not need to have dry ice for -20°C – there are gel pack solutions at that temperature. And you will not need dry ice for 2-8°C. So, you’re talking about a small number of products that need to be deep frozen.”

With even one of the mRNA leading vaccines candidates – the Moderna vaccine – qualified at -20C, Coyle is only aware of two currently that are likely to need to be deep frozen, although he notes that the number of viable candidates keeps changing. “But it’s a small number compared to the whole list of vaccines.”
His understanding is that a passenger B777 can only handle between 800kg and 1,000 kilos of dry ice, but he notes that a B747 freighter can handle up to 11,000 kilos of dry ice, with smaller aircraft able to take proportionally less.

So, he agrees “there are limits and limitations that we have to consider for dry ice”, but believes the extent of the challenge may be less than some had originally feared.

A challenge that can be met
Weighing up all of the logistical challenges against the capabilities available, all in all Coyle is confident that it is a challenge that can be met.

To put it into context, Coyle says the total volume of Covid-19 vaccines that are forecast to be needed to be shipped by air “is less than 1% of what we (as an industry) typically do for our overall air freight, and about 10% of (total global industry-wide) pharma healthcare (volumes), from 2019 numbers”.

He concludes: “This is not an instance to talk about ‘can we do it’? This is an instance to talk about how we are going to do it. And I have at my disposal pretty much every asset in this company to pull this off. So, I’m not concerned about overall capacity and commitment.”

Nevertheless, he highlights the importance of stressing to all of the manufacturers and governments that although “we live in an industry that loves perfect data, now is not the time for perfect data. Now is the time to share often and talk often. We have got to get out there and connect, because there are many players that have to come together to make this successful, to get it to every human that needs it.”