December 9, 2020 PAP-Q4-20-NI-001
As of October 7, 2020, more than 35.5 million confirmed cases of COVID-19, including more than 1 million deaths, were reported to the World Health Organization. There is a dire need for therapeutics and vaccines to fight this pandemic, and the biopharmaceutical industry has been working at a furious pace to develop effective products. Ten vaccines have entered phase III clinical trials around the globe (four in the United States), dozens more are in early clinical stages, and well over a hundred are in preclinical development.1
Once one, or more, candidate is proven to be safe and effective and granted marketing approval — most likely using emergency authorities of relevant regulatory agencies — those vaccines will need to be produced and distributed to a large percentage of the 7.8 billion people that comprise the global population. And this activity must take place without disrupting the production and distribution of existing medicines and vaccines, which will require additional manufacturing and logistics capacity.
Developing an effective vaccine is only the beginning of the challenge. The active ingredients need to be produced and then formulated into final products before being packaged for shipment. Delivery by air, which will be challenging given the shortage of air cargo capacity, can only occur through airports certified to receive pharmaceuticals, which can only handle so much product at a given time.2 The vaccines will then be transported to distributors for allocation to hospitals, pharmacies, and vaccination centers, which will need to be established.
Issues remain concerning the availability of raw materials for the production of these vaccines, including adjuvants used in their formulation, as well as glass vials and stoppers to store them and syringes to administer them.3 Enhanced security will be required to prevent theft of the valuable products, and many will also require specialized low-temperature packaging and shipping conditions.
Many companies are already tackling the production capacity issue, investing in expanded facilities and collaborating with contract manufacturers. The firms with the most advanced candidates have been proactive about securing needed raw materials and are even producing large numbers of doses before receiving approval so the vaccines can be immediately shipped once approved.
The level of distribution required is unprecedented. For instance, 174.5 million doses of flu vaccines were supplied to the U.S. market between September 2019 and February 2020.4 The U.S. government’s Operation Warp Speed hopes to distribute 300 million doses by January 2021.
Consideration of the challenges of distributing vast numbers of these new vaccines and the development of possible solutions are underway. A research project in India is seeking to engineer an efficient and sustainable delivery mechanism for the distribution of billions of doses of COVID-19 vaccines, including to low-income countries that lack robust cold chains.5
Assuring a sufficient portion of the population gets vaccinated is an enormous task. Even for efforts involving UN agencies and country networks, vaccination levels for polio and measles in some cases struggled to reach 70%.4 The level of vaccination required to beat SARS-CoV-2 is unknown, but, due to its mutability, some have suggested a level greater than 90% might be necessary. Doing so will be incredibly difficult and even more challenging if two doses of vaccine are required.
Questions about the production and delivery of vaccines for the novel coronavirus abound. The timeline to approval of the first products is just one unknown, as are how many doses will be necessary, and who will get the first vaccines that become available. Will the newer companies developing vaccines, which have never before commercialized a product, be able to access robust supply chains? How will the cold chain be maintained across all countries to ensure maximum inoculation? How can raw material shortages be addressed? Can all of these additional doses be manufactured and delivered without impacting the production of existing medicines and vaccines? More broadly, with no less than a hundred vaccines in development and no indications yet which will be successful, how can the industry adequately prepare?
McKinsey estimates that 7–9, and possibly up to 20, new COVID-19 vaccines could be approved over the next few years.6 As of early August 2020, vaccine manufacturers committed to producing 1 billion doses by the end of 2020 and 9 billion doses by the end of 2021. Some questions remain, however, regarding the data requirements of the FDA for granting emergency approval of any COVID-19 vaccines.
Once one, or more, candidate is proven to be safe and effective and granted marketing approval — most likely using emergency authorities of relevant regulatory agencies — those vaccines will need to be produced and distributed to a large percentage of the 7.8 billion people that comprise the global population.
Even if billions of doses are produced in the next several months, the shortage of packaging raw materials remains a significant issue. There has been a short supply of medical glass since the beginning of the pandemic, although Corning is currently expanding capacity for the production of vials for coronavirus vaccines.7 There is also a shortage of the sand required to make glass vials, and it has been estimated that it will take at least two years to produce enough vials for all of the needed doses.7 Access to enough stoppers for vials may also be a problem, as each vaccine may require a different type of stopper to ensure no interaction with the formulation components.
Capacity for syringes is also insufficient for the administration of COVID-19 doses. The White House anticipates needing 850 million syringes, according to one source.8 One potential solution is the use of multidose vials, which would reduce the number of vials required. The U.S. government is also relying on the use of plastic vials with a microscopic glass coating and plastic prefilled syringes produced using blow–fill–seal technology.9 The latter would not require any glass or rubber stoppers.
In the United States, the situation is complicated by confusion regarding the roles that the federal government and individual states will play in vaccine distribution and those that the military and CDC will play.8 Given the difficulties the federal government had with the distribution of remdesivir and implementation of testing programs, there is cause for concern. As early as August 2020, the National Governors Association was urging governors to prepare for all aspects of vaccine distribution within their states.
In the UK, one report estimated that roll-out of a COVID-19 vaccine could be delayed by as much as two years due to shortages of glass vials, refrigerated trucks, pallets, and PPE for medical personnel who will administer the doses.10
Assuming that the raw material challenges can be overcome, COVID-19 vaccines produced, whether in glass vials or plastic prefilled syringes, will need to move from manufacturing plants to distributors. The need for rapid deployment and the temperature-sensitive nature of most vaccines will require shipment via air at a time when air cargo capacity is already limited due to the pandemic.
The challenge is massive. DHL, working with McKinsey & Company as their analytics partner, published a white paper on delivering stable logistics for vaccines and medical goods during COVID-19 and future health crises. One key conclusion: to provide global coverage of COVID-19 vaccines for two years, up to ~200,000 pallet shipments and ~15 million deliveries in cooling boxes — as well as ~15,000 flights — will be required across the various supply chains.11 As a result of logistical faults and insufficient infrastructure, the study found that as many as 60% of the world’s population may not receive a vaccine.12
Millions of passenger flights have been grounded around the world, significantly reducing international belly cargo capacity. Some of this capacity has been regained by converting passenger aircraft to handle cargo.13 Even so, one industry expert estimates that vaccines for 1 billion people would fill 1,000 Boeing 777 freighters; Boeing has produced fewer than 200 of these aircraft since 2009.14
Not surprisingly, shipping prices have risen, not only because of capacity shortages, but also due to the uncertainty of the timing of vaccine approvals.2 In addition, several smartphone and electronics product launches are scheduled for late in 2020 and could potentially coincide with the first vaccine distribution efforts.14
Furthermore, converted passenger planes cannot be used as-is for the transport of most COVID-19 vaccines, because they will require storage at 2–8 °C or even as low as –80 °C. Transporters will need to develop methods to ensure that such low temperatures can be maintained throughout the aircraft or rely on specialized low-temperature packaging. Of course, that means sufficient quantities of this type of packaging must be available.
In early September, the International Air Transport Association (IATA) warned that the WHO, UNICEF, and Gavi have already reported severe difficulties in maintaining their planned vaccine programs during the COVID-19 crisis due, in part, to limited air connectivity. IATA’s Director General and CEO Alexandre de Juniac indicated that, even if half of the COVID-19 vaccine doses are shipped by land, “the air cargo industry will still face its largest single transport challenge ever.”15
Many countries have limited the movement of goods during the pandemic, which could also affect the ability of manufacturers to ship vaccines across borders. For drug products, some U.S. companies have been bringing products into Canada and then trucking them into the United States,2 while others have chartered private planes. These approaches will be impractical for the transport of hundreds of millions of doses of COVID-19 vaccines.
The need for transportation may be reduced with the location of multiple manufacturing plants in different regions. Shipping vaccines in bulk could bypass some of the raw material shortage issues and reduced the number of shipments required. Shipment in less-than-container-loads (LCLs) for transport by ocean may be an option for vaccines that receive approvals down the road.14 In August 2020, the International Air Cargo Association and Pharma. Aero announced plans to form a joint working group to provide air cargo guidance to the logistics industry for the transportation of COVID-19 vaccines.16
In early September, the International Air Transport Association (IATA) warned that the WHO, UNICEF, and Gavi have already reported severe difficulties in maintaining their planned vaccine programs during the COVID-19 crisis due, in part, to limited air connectivity.
In many parts of the world, large quantities of vaccines that require cold storage are lost due to the inability to keep them at low temperatures. Maintaining the cold chain requires a reliable supply of electricity and access to refrigerators and, for some vaccines, advanced freezers that can reach extremely low temperatures. The latter is lacking in many parts of the world, and particularly in developing countries. The World Health Organization estimated in 2005 that up to 50% of vaccines are wasted globally each year due to an unbroken cold chain.17 The value of these losses is estimated to be $35 billion.3
COVID-19 vaccines that require refrigeration will require a temperature-controlled management environment and must be shipped in certified shipping containers according to a number of international regulations, such as EU Good Distribution Practices, U.S. FDA and WHO regulations, and IATA’s standards for temperature-controlled sensitive products published in the Temperature Control Regulations (TCR).13 Truckers that provide refrigerated transportation for the pharma industry will need to meet the varying needs of different vaccines as well.
Companies that make temperature-controlled containers are working to boost production and precondition them in advance of the expected surge in demand. Shipping companies have also been preparing. FedEx has more than 90 cold chain facilities, including the FedEx Cold Chain Center in Memphis, boasting 20,000 ft2 of temperature-controlled storage, including separate areas for healthcare produts.18 UPS Healthcare recently brought online more than 1.5 million additional square feet of cGMP healthcare distribution space in key global markets and installed two freezer farms in Louisville, Kentucky, and Roermond-Venlo, Netherlands, for vaccine storage and distribution.19
Adequate refrigeration and freezer units, staffing, and supplies will also be required at hospitals, retail pharmacies, and pop-up vaccination sites. Even in the United States, the available cold storage capacity is estimated to be just 15%.20 Other longer-term solutions may include new technologies for stabilizing vaccines so they can be stored and shipped at room temperature, such as that offered by UK-based Stablepharma3 and researchers at the University of Bath.21 Better visibility into the supply chain would help in the short term.
Given the staggering challenges that governments around the world face in developing an effective distribution system for COVID-19 vaccines once they are approved, it isn’t surprising that politics is another piece of the puzzle that cannot be ignored.
Given the staggering challenges that governments around the world face in developing an effective distribution system for COVID-19 vaccines once they are approved, it isn’t surprising that politics is another piece of the puzzle that cannot be ignored.
The initial question to address is who will be given the vaccine first, since it will take time to produce the total number of doses required to vaccinate the entire global population.22 If some countries retain all of the doses prepared by domestic manufacturers, it will be even more difficult to achieve both efficient and fair distribution across the world.2 The charity Oxfam has warned that wealthy countries representing 13% of the world population have laid claim to more than half of the promised COVID-19 doses.23
Who should manage vaccine distribution is another question. In the United States there is a debate over whether the Centers for Disease Control and Prevention (CDC), which operates existing vaccine distribution programs, or the Department of Defense (DoD) should lead the effort. Many are concerned that military involvement will undermine public confidence, which in some areas of the country is already low with respect to the safety of vaccines in general.
In mid-September, the Trump administration — through the U.S. Department of Health and Human Services (HHS) and the DoD — released two documents that “provide a strategic distribution overview along with an interim playbook for state, tribal, territorial, and local public health programs and their partners on how to plan and operationalize a vaccination response to COVID-19 within their respective jurisdictions.”24
The approach relies on a combination of CDC Control health expertise, military logistics experience and resources, and a partnership with drug distributor McKesson Corporation25 as a centralized distributor of future COVID-19 vaccines and ancillary supplies needed to administer vaccinations.
Any groups that want to administer COVID-19 vaccines (e.g., medical offices, clinics, hospitals, pharmacies) must enroll in the U.S. COVID-19 vaccination program and sign an agreement that they have the space, equipment, and trained staff to do so.26 Doses will be requested through a state agency for each site, and the state will allocate the vaccine. The federal government is expected to send vaccine supplies first to sites that can reach the largest numbers of priority populations, and thus the CDC may override individual state allocations.
Vaccine orders will be shipped from McKesson distribution centers within 24 hours of approval, depending on supply, along with syringes and other ancillary materials required for administration.26 It is also possible that national drug companies (e.g., CVS, Walgreens) could serve as administration sites working directly with the CDC. The DoD will handle all military allocations.
The Biden campaign is developing its own strategy for COVID-19 vaccine distribution leveraging experts from the Obama administration who oversaw pandemics and readiness.27 They are speaking with contacts in U.S. health and safety agencies to monitor current activities and determine the needed solutions to overcome raw material and transport capacity shortages and manage distribution to millions of Americans.
Individual state and local public health departments will ultimately be responsible for administering vaccine doses. Having been underfunded for decades, these agencies are already overwhelmed by the challenges the pandemic itself has created, including finding sufficient treatment sites, medications, and PPE for medical care to tracking and tracing potentially exposed people as new cases continue to rise in many locations.28
Governors have been urged by the CDC to be prepared to begin administering the vaccine by November 1, which many doctors, nurses, and health officials say is not possible.28 According to Dr. Kelly Moore, associate director of immunization education at the Immunization Action Coalition, a national vaccine education and advocacy organization. “States will need more financial resources than they have now.”
The pharmaceutical supply chain extends from basic raw material manufacturers through logistics suppliers to those involved in product administration. Overcoming all of the challenges the industry faces with respect to the development, production, and distribution of COVID-19 vaccines will require extensive collaboration and flexibility.
IATA urged governments to begin careful planning with industry stakeholders to ensure full preparedness when vaccines for COVID-19 are approved and available for distribution. “We urge governments to take the lead in facilitating cooperation across the logistics chain so that the facilities, security arrangements and border processes are ready for the mammoth and complex task ahead,” Juniac said.15
The COVAX initiative is one such global collaboration.29 Gavi, the Vaccine Alliance, the Coalition for Epidemic Preparedness Innovations (CEPI), WHO, UNICEF, and PAHO Revolving Fund are working together to “guarantee rapid, fair and equitable access to COVID-19 vaccines for every country in the world, rich and poor.” UNICEF is the largest single vaccine buyer in the world (over two billion doses annually). The groups are working with manufacturers to plan vaccine handling and distribution and access to safe injection equipment.
Security concerns must also be addressed, and will require digital tracking of doses from the time they leave the factory until reaching the ultimate point of administration. Historically, vaccines have not been tracked by dose because of their low cost; that will likely have to change for COVID-19 vaccines.30
Sharing of manufacturing capacity for ultimately approved vaccines may be necessary. They must also be sufficiently flexible to meet varying levels of demand depending on the level of virus spread geographically and over time.6 Transporters must be able to handle vaccines with different cold-chain requirements. Governments must implement their own distribution programs across the “last mile.”
Contingency plans will also be needed to ensure that companies can adapt when problems arise in both manufacturing and distribution.31 In particular, companies need to be prepared to rescue vaccine shipments for which delivery is delayed or affected in some way so that temperature excursions do not occur.
Blockchain technology is attracting attention as a way for pharmaceutical companies to manage the supply chain for COVID-19 vaccines. This approach has the potential to engender confidence in the safety of vaccines beginning with raw materials and ending with doctors, nurses, and recipients.32
References
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Chen, Elaine. “Drugmakers Race to Build Covid-19 Vaccine Supply Chains.” Wall Street Journal. 30 Jul. 2020. Web.
Press, Victoria. “Programme to develop sustainable cold chain delivery for COVID-19 vaccine initiated.” European Pharmaceutical Review. 12 May 2020. Web.
Agrawal, Gaurav, Michael Conway, and Adam Sabow. “On pins and needles: Will COVID-19 vaccines ‘save the world’?” McKinsey. 29 Jul. 2020. Web.
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DOD Awards $138 Million Contract Enabling Prefilled Syringes for Future COVID-19 Vaccine. U.S. Department of Defense. 12 May 2020. Web.
Hodge, Mark. “Coronavirus vaccine mass roll-out could be delayed by TWO YEARS as UK ‘needs more storage and refrigerated lorries’.” The Sun. 28 Sep. 2020. Web.
Delivery of COVID-19 Vaccine: DHL Study Shows How Public and Private Sector Can Partner for Success. DHL. 3 Sep. 2020. Web.
Jauniskis, Pijus. “Up to 5B people may not receive COVID-19 vaccine, DHL warns.” Aerotime Hub. 3 Sep. 2020. Web.
Gruber, Andrea. “Transport of vaccines by air.” Logistics Update Africa. n.d. Web.
Knowler, Greg. “Capacity-constrained air cargo raises red flag for COVID-19 vaccine distribution.” Journal of Commerce. 24 Jul. 2020. Web.
The Time to Prepare for COVID-19 Vaccine Transport Is Now. IATA. 29 Sep. 2020. Web.
Rees, Victoria. “Joint working group to produce guidance on air cargo logistics for COVID-19 vaccines.” European Pharmaceutical Review. 12 Aug. 2020. Web.
“Monitoring vaccine wastage at the country level.” World Health Organization. May 2005. Web.
Garland, Max. “COVID-19 vaccine distribution will put FedEx’s ‘cold chain’ to the test.” Commercial Appeal. 27 Sep. 2020. Web.
Brooks, Kristin. “Pharma Supply Chain Logistics & Potential COVID-19 Vaccines.” Contract Pharma. 17 Sep. 2020. Web.
LaMotta, Lisa. “Pharma’s other challenge: COVID-19 vaccine distribution.” PriceWaterhouseCoopers. 25 Jun. 2020. Web.
Sartbaeva, Asel and Aswin Doekhie. “The Challenge of Vaccine Cold Chain Logistics: How a Chemical ‘Casing’ Could Save Lives.” Global Biodefense. 4 Sep. 2020. Web.
Spiro, Topher and Zeke Emanuel. “A Comprehensive COVID-19 Vaccine Plan.” Center for American Progress. 28 Jul. 2020. Web.
Small group of rich nations have bought up more than half the future supply of leading COVID-19 vaccine contenders. Oxfam. 17 Sep. 2020. Web.
Trump Administration Releases COVID-19 Vaccine Distribution Strategy. Department of Health and Human Services. 16 Sep. 2020. Web.
McKesson to Distribute Future COVID-19 Vaccines in Support of Operation Warp Speed. McKesson. 14 Aug. 2020. Web.
Weise, Elizabeth. “‘Mind-bogglingly complex’: Here’s what we know about how COVID-19 vaccine will be distributed when it’s approved.” USA TODAY. 8 Sep. 2020. Web.
Lee, Brandon. “Health Care Briefing: Biden Team Crafting Vaccine Logistics Plan.” Bloomberg Government. 16 Sep. 2020. Web.
Szabo, Liz. “The Overlooked Logistics of Covid-19 Vaccine Distribution.” Undark.org. 8 Sep. 2020. Web.
Cook, Emily. “UNICEF to lead Supply Chain for COVID-19 Vaccine.” Manufacturing. September 4. 2020. Web.
Mishra, Devendra. “A Moonshot is Required for COVID-19 Vaccine Distribution.” Biosupply Alliance. 3 Sep. 2020. Web.
“The Logistics of COVID-19 Vaccine Trials.” World Courier. 7 Sep. 2020. Web.
Brooks, Kristin. “Is Blockchain Key to COVID-19 Vaccine Distribution?” Contract Pharma. 5 Aug. 2020. Web.
Mr. Walker is the founder and managing director of That’s Nice LLC, a research-driven marketing agency with 20 years dedicated to life sciences. Nigel harnesses the strategic capabilities of Nice Insight, the research arm of That’s Nice, to help companies communicate science-based visions to grow their businesses. Mr. Walker earned a bachelor’s degree in graphic design with honors from London College of Communication, University of the Arts London, England.
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