Supply chains to be tested when COVID-19 vaccine arrives

As COVID-19 vaccine candidates approach regulatory approval in the coming months, we look at the challenges facing the global distribution of any vaccine and what these mean for achieving widespread immunity.

• Vaccine production will be concentrated in North America, Europe and China, all of which have relatively robust logistics and supply chain infrastructure that will facilitate inoculation campaigns.
• The lack of data showing how individual vaccines can remain potent at various temperatures will require stringent measures to maintain ultracold temperatures throughout the supply chain.
• Insufficient infrastructure will likely preclude widespread distribution and administration of a highly temperature-sensitive vaccine across swathes of the Asia Pacific, Africa and Latin America, further delaying widespread immunity.
  
  
  

Approval approaches

Scientists globally are working to secure approval for a vaccine against COVID-19 in record time. A small number of contenders have already received approval for early or limited use. It is credible that the first vaccines could complete all clinical trials and receive full regulatory approval by the end of 2020. Attention will then shift to manufacturing, distributing and administering a vaccine on an unprecedented scale.

Unprecedented production

Ramping up production is the first of many logistical and supply chain challenges. Manufacturers have announced plans to produce hundreds of millions of doses by the end of 2020, and several billion by the end of 2021. High demand and competition for inputs and raw materials – some of which can only be sourced from China – may create shortages. Several drug makers have already warned of a potential shortage of glass vials to store doses prior to use.

Production will mostly be concentrated in a small number of advanced economies in Western Europe and North America, as well as in China and India. Few countries possess the capabilities to manufacture the active ingredients required in vaccines, especially for those that have not previously been produced at scale. There are also a limited number of countries with the requisite infrastructure to carry out the “fill and finish” stage (the process of filling vials and packaging a vaccine for distribution). This step already represents a common bottleneck in the vaccine supply chain.

Some stages of the manufacturing process are likely to be repurposed from other vaccine programmes. However, to avoid disrupting those existing programmes – and to meet the scale of demand for a COVID-19 vaccine – new production capabilities will be needed. Several governments are investing in additional manufacturing capacity before individual candidates receive regulatory approval. Under its Operation Warp Speed – an initiative to advance manufacturing capacity for a number of vaccine candidates while they are still in development – the US government in August alone signed USD 1.5bn and USD 1bn agreements respectively with two pharmaceutical companies to support the large-scale manufacture and delivery of their candidate vaccines. Days earlier, the government awarded a USD 160m contract to a biotechnology company for “fill and finish” manufacturing capacity.

Up in the air

Outbound logistics present the second major challenge. In the early months of the pandemic, surging demand for shipment of personal protective equipment (PPE) – and falling passenger numbers – led airlines to repurpose airliner cabins to carry more freight. To distribute a vaccine globally, and given the urgency of demand, air cargo will likely play a leading role, particularly over longer distances.

With the pandemic leading to a significant drop in passenger traffic since March, airlines have parked many aircraft in long-term storage, and air cargo capacity remains constrained. The World Health Organization (WHO) has reported problems in maintaining existing vaccine programmes during the pandemic, partly because of disruption to aviation.

Border processes and customs clearances will also need to be streamlined. This is especially the case as governments in their responses to COVID-19 have imposed public health measures that have created additional responsibilities and some delays for shippers at ports.

Chill factor

The characteristics of vaccines determine the conditions in which they need to be stored and transported. Vaccine stability – most importantly the ability to withstand a range of temperatures – is tested extensively for any new vaccine. Given the urgent demand for a COVID-19 vaccine, there is unlikely to be much stability data available for successful candidates. Shippers may therefore need to continuously maintain extremely cold conditions to ensure their safe delivery. Some of the vaccines that are in Phase 3, the late stages of clinical trials – particularly those using novel RNA platforms – likely need to be stored at ultracold temperatures of up to -80 degrees Celsius. Others will likely require temperatures of between 2 and 8 degrees Celsius. Which vaccines are first to secure regulatory approval will therefore determine the nature of the delivery required.

The WHO estimates that up to 50% of vaccine doses are wasted every year, often because of gaps in maintaining a constantly temperature-controlled supply chain – or “cold chain”. The speed and scale of the rollout of a COVID-19 vaccine will increase the likelihood of doses being lost or damaged.

Although the aviation sector has good experience of transporting refrigerated cargo, goods that require ultracold temperatures are much more commonly moved – at slower speed – by the maritime sector in “reefer” containers. Dry ice (a solid form of carbon dioxide, CO2) will likely provide a workaround for the aviation sector but will add weight and expense to shipments. Dry ice supply could add additional logistical bottlenecks – CO2 shortages have been reported in the US in recent months as the pandemic has led to reduced production.

Unloading and handling ultracold cargo require personnel to have specialist training, which is likely to be lacking at the required scale in most countries. Meanwhile, airport infrastructure and storage are also inadequate in most regions, particularly across Africa. In hot countries, there is naturally increased potential to break temperature-controlled conditions.

“Last mile” distribution (from a transport hub to the final destination or administration point) will present the greatest possibility of bottlenecks and breakdowns in the cold chain. In unintegrated supply chains, ensuring temperature controls becomes more difficult as cargoes are divided into smaller individually packaged lots, handled by different carriers. Hospitals, pharmacies and clinics are likely to be among the first vaccination points, though most are not equipped with ultracold freezers and so could not store the vaccine on site for more than a short time. Vaccines that require more than one dose will complicate and potentially undermine administration if viable booster shots do not arrive on time.

The haves and have nots

A large majority of the global population are unlikely to have access to a highly temperature-sensitive vaccine that needs to be stored at temperatures of up to -80 degrees Celsius. The countries with access to – or the capability to more quickly scale up – the requisite infrastructures are mostly located in Europe and North America, where most vaccine candidates are currently set to be produced. Meanwhile, large parts of Africa, Latin America and Asia are unlikely to be ready to receive such vaccines at scale without significant support from the international community.

More thermostable COVID-19 vaccines that do not need to be kept at ultracold temperatures would be rolled out much more easily, including across Asia and Latin America. However, large swathes of the global population are likely to remain hard to reach, especially in more remote regions with patchy electricity coverage and physical infrastructure, many of which are already likely to face the longest wait for a vaccine to be distributed at scale. Access to vaccines will vary significantly within individual countries and will decrease the further away local populations are from major transport hubs such as international airports.

Outlook

Many logistics and supply chain issues will likely ease over time. Further stability testing will likely mean that stringent temperature requirements for some vaccine candidates can be relaxed. More stable candidates that are easier to distribute may gain regulatory approval and will present more manageable challenges for countries unable to maintain a continuous cold chain. All the while, production capacity and efficiency are also likely to improve.

However, other challenges will persist or intensify as more vaccines are approved. The competition for raw ingredients or manufacturing capacity could create additional bottlenecks and shortages. Vaccines with different distribution and administration requirements will make it more difficult for countries to learn from each other. Meanwhile, some governments may even roll out more than one vaccine to different demographics or regions within their borders.

At a global level, differences in manufacturing, production and logistics capabilities will remain stark. Inoculation campaigns for some countries may become a question of “when”, but for others they will remain a question of “if”.