4

Vaccine Distribution and Supply Chain

Though it can be a herculean and multiyear effort to develop critical medical products and bring them to market, research and development (R&D) efforts only represent a portion of the process of getting them to where they are most needed. The distribution and supply chain for vaccines, diagnostics, and other products related to pandemic emergencies is complex and multifaceted and often affects other areas either upstream or downstream without much coordination. This chapter highlights the challenges and potential opportunities relevant to supply chain issues during the pandemic, including upstream manufacturing issues and last-mile delivery needs. Many speakers pointed to the need for equity considerations across the supply chain continuum.

UPSTREAM SUPPLY CHAIN CHALLENGES AND DOWNSTREAM IMPLICATIONS

Several speakers discussed the various supply chain challenges during the coronavirus disease 2019 (COVID-19) pandemic and how they are interconnected to other sectors and impact other health areas. They commented on various short- and long-term challenges, needs to improve visibility—including data and information sharing and investments needed to reduce future supply shortages.

Short- and Long-Term Supply Challenges

Julie Swann, head of the Fitts Department of Industrial and Systems Engineering at North Carolina State University, asked panelists what sup-

ply chain challenges they expected to see in the next 6 months to 2 years. Matthew Downham, sustainable manufacturing lead for the Coalition for Epidemic Preparedness Innovations (CEPI), highlighted issues related to raw and single-use materials, such as bioreactor bags and filters. Another area will be the free flow of goods, he explained, which is more of a longer-term focus. Finally, he wanted to ensure that the available global capacity is maximized to meet the demands of pandemic vaccine supply. Rasmus Bech Hansen, chief executive officer of Airfinity, agreed with Downham’s points but added other short- and long-term challenges. First, he asked when manufacturers are going to make the shift to second-generation vaccines, as that will largely impact dose availability. Second, he noted the vaccine surpluses that some countries are beginning to have and commented on how critical it will be for the world to figure out how to redistribute and reallocate those. Not doing so would be a substantial failure on global society’s behalf, he added. Longer term, Hansen said, it comes down to global demand and knowing what global capacity is needed. Each country will need to answer this question, he explained, and some are already investing up to 3–4 doses per capita of COVID-19 vaccines in an ongoing capacity buildup through 2023. These long-term needs have to be better understood, because without such visibility on the demand side, he said, it is difficult for the supply side to follow.

The Pan American Health Organization (PAHO) has a very important role in the Americas to fight COVID-19, said Daniel Rodríguez, director of procurement and supply management at PAHO. He mentioned two PAHO mechanisms that support access to vaccines for 42 countries, protecting up to 25 million people per year: the revolving fund for access to vaccines and strategic funds. He explained that it has faced many challenges in the supply chain—of both COVID-19 vaccines and other, more routine, immunizations, but it is learning how to improve resiliency. Regarding short-term challenges, Rodríguez built on previous speaker comments highlighting vaccine access inequity, reporting that 1.4 million doses have been administered in the world thus far, but 76 percent of these were in just 10 countries; 44 percent were in high-income countries, which account for just 16 percent of the world’s population. Only 0.3 percent have been administered in the 29 lowest-income countries, with 9 percent of the world’s population. He echoed Hansen’s point about reallocation to those countries participating in COVID-19 Vaccines Global Access (COVAX), saying several countries have announced donations but hopefully more will follow. He also highlighted the long-term challenge of scaling up global supplies to support countries in achieving the necessary “herd immunity.” For the Latin American region in particular, he said it would be very important to rely less on a few outside countries that possess the manufacturing capabilities, more regional capacity is needed for both vaccine production and other health supplies.

This can promote sustainability of the supply chain for essential supplies and less dependence on other markets, which PAHO is focusing on doing, Rodríguez stated.

Improving Visibility for Needed Products

Swann commented that many of the challenges relate to having visibility on certain products and knowing what will be needed, where, and when. Downham explained that the parts used in vaccine manufacturing can number in the hundreds, and they come from all around the world, forming an incredible web of trade and distribution. A hold-up in any one area, however granular, can lead to problems in many areas. Through the COVAX supply chain manufacturing task force he is a part of, Downham said they are exploring establishing a voluntary partnership platform that can allow manufacturers and suppliers to share data and trade what they have in stock. While this sounds like an ideal scenario, he said that typically about 5 billion doses of vaccine are manufactured each year. In the past year, it increased to about 15 billion, which is a huge drain on all resources and supplies. This type of mechanism could ideally help disperse some of the critical materials to the right places.

Hansen agreed that this is an extremely complex area where no one really has full visibility. He acknowledged that the market forces have been working quite well in many areas, with almost 2 billion vaccines produced as of May 2021. The problem many companies will have is that the demand into 2022 and 2023 is not entirely clear. Longer-term visibility and greater transparency is needed to repay their massive investment. This also makes it harder for newcomer manufacturers and suppliers, because without regulatory approval or known efficacy, it is difficult to make investments well in advance. We may end up with just a few vaccines that dominate, he said. He continued that the key actors in this environment have been national governments. While they have worked to ensure supply chain and production, they have made less effort to look more comprehensively at the entire supply chain, including the 200–300 ingredients that may go into an individual vaccine and who the suppliers are. Through Airfinity and other partners, they have identified 20 of the most important ingredients, the producers, and where they are located. Hansen commented that many of these sub-suppliers are scaling very quickly, and revenue forecasts are growing, but national governments can play an important role because they have the capacity to oversee and support new factories being built to ensure the supply chain is functional.

Vaccines need syringes, said Rodríguez, and this year, PAHO procured 200 million syringes—9 times what is normally produced. Because of the demand outweighing supply, it has expanded to other sources evaluated by

PAHO technical staff. The market is still very challenging, he reported, as manufacturers will not produce in advance without a firm commitment or purchase order, and some have to fill their own national demand first. Overall, he noted the imbalance of ocean containers, increased freight costs, price inflation for raw materials, and increased costs of syringes due to the shortage—all potentially affecting products aside from COVID-19 vaccines and supplies.

Rodríguez responded with two main components to improve visibility of potential shortages. First, he highlighted the critical nature of collaboration, using the example of the United Nations Children’s Fund (UNICEF) and PAHO as the largest vaccine procurement entities in the world having collaborated for many years reassigning supply as needed on vaccines such as yellow fever. The benefits can also be seen in the COVID-19 response, where, because PAHO and other organizations are part of the United Nations (UN) supply chain system, they were able to address market failures of personal protective equipment (PPE) or diagnostics, conduct joint procurement processes, and secure the best price for member countries. Second, he also noted the long-term demand that is needed to feed the current investments and capacities the manufacturer has to consider. This is challenging because countries need to be educated on the importance of a good long-term demand plan, he said, which will be needed to avoid future shortages.

Investments to Reduce Future Shortages

Given the difficulties throughout the pandemic in terms of supply chain and visibility, Swann also asked panelists for places and areas to invest in to reduce the chance of shortages. Downham commented on the realization that people are quite dependent on a small selection of manufacturers and their geographic regions. CEPI did a mapping analysis and identified the predominance of vaccine manufacturers, particularly in North America, the European Union, and Southeast Asia. It was clear, he said, that certain regions had gaps, such as South Africa, Latin America, the Middle East—and argued for increasing the vaccine manufacturing footprint and diversifying options to better respond to vaccine requirements for epidemics and pandemics. Investors are motivated, he noted, to stimulate public- and private-sector financing to support vaccine manufacturing innovations across those geographies, especially in low- and middle-income countries (LMICs). However, it is also necessary to identify policy needs and build regulatory capabilities in these locations. Fundamental to all of this, and to building sustainable and resilient supply chains, Downham continued, is a skilled workforce in key areas, such as chemistry, manufacturing and controls, and regulatory or bio analysis. In summary, he said that there are many moving parts, but the focus is on improving or establishing vaccine manufacturing capacity and capability in regions of the world where needed.

While the COVID-19 vaccine development process has happened at an extraordinary speed, noted Hansen, a lag time of up to 2 years remains between when the virus was identified to when we might have enough vaccines for the global population. He asked if we need to always start from scratch when facing pandemics. Despite the years where we will not need vaccines, when we do, the world will need to produce some 11 billion vaccines; it is necessary to determine how this will be financed. Factories need to operate and people need to work, even in nonpandemic years. He argued that this should not be seen as a health crisis but more of a national security crisis and include some investments each year in prevention and mitigation efforts. Hansen agreed with Downham on the need to diversify manufacturing capabilities in different regions, ideally during the interepidemic period, but also cautioned that it would be very inefficient if each country tried to set up its own manufacturing sites. Despite a correlation between the fewer sites a company has and the faster it is able to scale, the threat of export controls results in many countries trying to do it themselves.

Rodríguez agreed this is a health security issue and that success requires a balance between efficient models of manufacturing and global diversification. A coordinated effort is needed on what makes sense for different countries to produce and agreement between countries to ensure free flow of materials and vaccine ingredients in a pandemic. Less than 4 percent of the medical products used during the COVID-19 response in PAHO’s region come from that region, he added, indicating a very high dependence on other markets, but member states are interested in expanding regional capacity. He outlined the building blocks the region has to make this happen, including academic institutions, existing manufacturing capacities for vaccines, robust regulatory systems, and capacities in several countries with technology transfer agreement plans. With this and the interest from several member states and other partners, things are moving forward to scale up these capabilities in the region, Rodríguez concluded.

Who Is Responsible for These Investments?

Rodríguez commented that since the pandemic, countries have been taking the opportunity to prioritize these issues and make important decisions they have not had political momentum for in the past. He said that it has been difficult for countries to make such big decisions about not relying on other markets or suppliers. Hansen added that it has mainly been national governments stepping in, often making bilateral deals with companies under the auspices of preserving and protecting national security. While countries have naturally been impacted by this crisis, he said, many multinational companies have as well, so he saw potential for an insurance risk model where companies pay into a global pool. Hansen stated that

this could generate $200 billion per year, which could be applied to ongoing capacity building, but the time for these conversations is right now. If we rely only on national governments, over the long run, it would likely leads to an underinvestment globally. He hoped to see more new kinds of public–private partnerships to help fill the gap. Downham added that CEPI has been hearing from many investment banks, development banks, and private investors about their interest in financing and supporting vaccine manufacturing capacity, particularly in LMICs. Momentum from the pandemic exists to invest and support diversification and improved capacity around the world. He cited the overall expected cost of COVID-19 to the global economy, with some values around $28 trillion by 2025, making the hypothetical annual cost of $200 billion to provide ongoing capacity seem almost small. Despite the interest, Downham noted, key questions remain around management, governance, and coordination. Regardless, he hoped for the continued momentum to channel investments in the right direction.

CONTRIBUTING TO BETTER INFORMATION SHARING

Challenges in information sharing were a key contributor to the lack of visibility across the supply chain. Rob Handfield, executive director of the Supply Chain Resource Cooperative and professor of supply chain management at North Carolina State University, explained that governments created a lot of funding for vaccine manufacturing, but it became clear that there were many upstream shortages occurring for key supply chain inputs, such as many single-use technologies, bioreactor bags, and filters. Hansen of Airfinity also highlighted the challenges of the variants of concern. Ideally, you would distribute vaccines after prevalence of a variant is established in certain countries, knowing the efficacy and how they match up, he explained, but the lack of widespread genomic surveillance creates a significant lack of data visibility on those variants and the prevalence in different countries. The second challenge Hansen alluded to was related to booster shots, because companies will soon begin to shift to producing the second generations of vaccines. He said that the existing projections for global vaccine availability assume manufacturers continue with existing production, but in reality, this is unlikely. He expected many to start shifting to second generation in fall 2021, but if it is not possible to do first- and second-generation production in parallel, this will affect global supply and take vaccines off the market. Simultaneously, certain regions will likely have surplus doses—Hansen asked about the mechanism for sharing or reselling those.

Swann reiterated Handfield’s point on the supply challenges being further back in the chain with raw materials for vaccines and ancillary products, such syringes, PPE, and diagnostic tests. We need a coordinated

global visibility of different supply chains, she said, and how other kinds of products might be affected by these surges in production. Once we start thinking about connecting data and the last mile, Swann continued, it becomes important to identify the gaps within a country or region and what the implications might be in terms of something more granular, such as booster shots for a certain variant.

Data Sharing: What to Share and Who Is Responsible

At a minimum, we need to understand the upstream throughput capacity of different manufacturers, said Handfield. Supply chain mapping can help illustrate who is in the chain, and there is also value in including Tier 1 and Tier 2 suppliers to see their level of inventory and where their bottlenecks are. Ideally, all vaccine manufacturers would share this information to collaborate and shift supply to different parties as needed. He acknowledged that this is quite theoretical, as companies generally do not like to share their suppliers or excess inventory. He described a proposal to the International Chamber of Commerce and the World Trade Organization to create a high-level visibility chart to show different parties in the supply chain and their throughput and capacity. Handfield said it would benefit everyone, and while collaboration in the pandemic has been unprecedented, more needs to be done in real time so critical decisions can be made quickly. Hansen commented that the largest manufacturers have the least incentive to share data, and hundreds of candidates are trying to enter this space but do not have the visibility of large companies, such as Pfizer and AstraZeneca. He suggested industry associations and governments could work together to mandate or incentivize collaboration of other companies—for example, to share production data, which they are not doing but could be helpful. Swann agreed that the mapping of facilities and capacity is important, but the improvements seen for the COVID-19 vaccines need to be translated to other products to be more complete and sustainable.

Swann highlighted the overlap between animal and human health, saying animal health data need to be shared in the ecosystem as well. Lots of data are publicly available, she said, but the information is disparately located and needs to be brought together in a usable way. Hansen added that it is possible to drive further transparency from the regulatory side. He suggested more frameworks like the database of clinicaltrials.gov that the world relies on, where companies are required to upload or be more proactive about sharing their research. He acknowledged the problem of companies with restrictions on data sharing, especially when publicly traded, but highlighted the anonymizing of data by independent third parties in other sectors that enables the company to share more. With blockchain and other technologies, Hansen saw many opportunities to overcome some of

these particular challenges. Handfield added the importance of regulatory agency collaboration at the global level. If those agencies could work to develop greater standards around requirements for data sharing among the European Union, the United States, Canada, and Asia, it could be quite valuable, also helping to capture data on disease hot spots and sharing that information in a format that can be used by everyone.

Predicting Changes in Production

Paula Barbosa, associate director of vaccines policy at the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), asked how to switch from current to next-generation vaccine formulations to ensure supply is adequate for various countries depending on their needs. Swann suggested building on the model for influenza, where a multilateral body discusses the most influential strains and can also include more than one strain in a given vaccine. Hansen commented that the problem with this model is that it reduces efficacy significantly: without a universal vaccine, the model relies on predicting which strains will be dominant months ahead of time. A mismatch with reality can significantly reduce effectiveness. Coronaviruses are much slower at mutating, but he emphasized the critical importance of staying above 80 percent effectiveness for the COVID-19 vaccine to avoid the prospect of localized epidemics. The mRNA platform is now developing vaccines against specific mutations that scientists have begun to predict may be most likely. While this could become very complex, Hansen saw it as a long-term goal, because maintaining the high levels of vaccine effectiveness is key to saving lives. Handfield agreed the ability to predict variants would be an excellent step forward. If the mRNA vaccine is the easiest and fastest to modify, potential technologies and options for variants can start to be outlined and produced in case they need to be rapidly scaled. Finally, Barbosa cautioned that this process will be quite chaotic if left to individual manufacturers, so a very clear signal and alignment is needed on which manufacturers produce what based on epidemiology.

LEVERAGING CURRENT PLATFORMS AND EMERGING LESSONS FOR FUTURE PLANNING

In terms of financing and investment, several lessons were highlighted from the COVID-19 experience across the world, as well as initial assumptions that were proven wrong as health care workers and researchers continued to learn more about how both the virus and populations were behaving. Nagwa Hasanin, senior advisor for health within the Supply Division at UNICEF, explained that their main goal is securing pediatric vaccinations in low-income countries, and they did not have the infrastructure to

deliver the large-scale vaccination campaigns required by COVID-19. Additionally, she noted the competing priorities of other public health issues, such as malaria, and that most health system strengthening components were not in place to be able to deliver the robust response necessary. Without access to good data, it was also difficult to identify epidemic trajectories; many across Africa had difficulty prioritizing COVID-19 with so many other disease burdens more closely affecting them. She noted it is about not only delivering the vaccine but also the governance, financing, and policy that surround pandemic preparedness and response, including access to surveillance data. Hasanin said that if a seasonal influenza platform were already established in these countries, the UNICEF Supply Division could build on it and start to roll out more quickly in a pandemic. However, the LMICs that UNICEF works in have essentially no such platform.

Ensuring a demand for the increased supply will also be important. Tapiwa Mukwashi, director of Supply Chain at Village Reach, recounted his experience in preparing for COVID-19 vaccination campaigns, saying that the general narrative was that a stampede for access was expected once vaccines were available, affecting available supply and requiring that populations be prioritized. Instead, what they saw across the Democratic Republic of the Congo, Liberia, Malawi, and Mozambique was so much vaccine hesitancy that many doses were wasted. The number being vaccinated each day is not enough to enable optimal use of the doses available. He agreed with comments on the need for planning to increase manufacturing supply but also called for creating sustained demand—echoing previous comments by Hansen.

Approaches to Building New Platforms

Hasanin outlined one of the lessons learned, saying that people cannot depend on a single platform for either vaccine or delivery. But key questions will include whether new mRNA platforms can be reproduced in low-resource settings and other delivery systems within the health system can be used to access target cohorts that need priority for certain pandemics, compared to targeting everyone for seasonal influenza.

Erin Sparrow, technical officer in vaccine product and delivery research at the World Health Organization (WHO), described the 2006 WHO Global Action Plan for Influenza Vaccines, which focused on increasing use of seasonal vaccines by increasing demand and production capacity and promoting R&D for new, better, and more broadly immunogenic vaccines. This R&D effort was heavily funded by the U.S. government to help several developing countries build influenza vaccine production from scratch, she said. Overall, the investment was about $1 billion across 14 manufacturers, including local and international investment. Only some were successful, but

she commented that many of them now have a working vaccine production facility yet are challenged by not having a market. They have the infrastructure but cannot compete in terms of price with some of the big multinational vaccine manufacturers that can produce at economies of scale. Additionally, the influenza market is quite volatile for small vaccine producers, Sparrow noted, with some that enter the market leaving just 2 years later. She agreed with Hasanin on the need for multiple platforms: having a seasonal influenza vaccine infrastructure that can be leveraged during pandemics but also pandemic platform technologies that can be switched on, such as plug-and-play mRNA technologies, to download genetic sequences and quickly be ready for clinical trials. Recalling previous comments about diversifying manufacturing, Sparrow liked the idea of regional production hubs to achieve equity in distribution while also maintaining economies of scale but noted that long-term vision and global cooperation would be required.

Mukwashi added that it takes a lot to sustain the capacity needed for production, and questions remain about whether the capacity needs to be sustained at peak levels or for how long. He also asked if this is sustainable and efficient for all locations. He gave an example of several manufacturers that had repurposed their production capabilities for PPE during the shortage at the start of the pandemic, which are now finding themselves with mountains of inventory that is not moving or selling at the price they had intended. Too much redundancy can result in excessive wastage, he said, which will make people question whether they are responding in the most appropriate way. He suggested repurposing capacity, avoiding inventing new capacity by engaging the private sector, and ensuring that legal constraints that limit the export of technology transfer are addressed, in order to strengthen regional production facilities.

Sparrow hoped that many countries realizing the economic losses from COVID-19 would consider shifting to invest more in pandemic preparedness to offset potential losses. Mukwashi agreed the pandemic has been an opportunity in multiple respects. We have seen that community health workers (CHWs), whose positions are typically undervalued, have been elevated in the public health space, he said. Governments now understand that CHWs can be a channel to reach people with trusted information about vaccines. But thinking also needs to shift to recognize that services can be provided outside of traditional health facilities. The capacity is there in communities, he stated; it has been used in past outbreaks and can be used for future influenza pandemics. CHWs offer a tremendous opportunity in resources available to government to really have an impact in communities, especially a resource that is sustainable and efficient.

As this is not just a technical challenge, Sparrow pointed out the need for multiagency leadership and investment from all countries, including LMICs. Long-term political commitment will be one of the biggest chal-

lenges, she said, as 5 years from now, COVID-19 could be easily forgotten as people have moved on from pandemic fatigue. Hasanin added that we also need to invest in and prioritize human resources and health system strengthening. We can have the best vaccine in the world, but if the health system is not able to deliver it, then we will not be able to use it, she concluded, and this important global work needs to be done before an outbreak occurs.

IMPROVING LAST-MILE DELIVERY

While upstream challenges and global coordination are incredibly important for managing supplies, ensuring that the products reach their intended destination and populations is also of critical concern. Ben Adeiza Adinoyi, head of the Health and Care Unit of the Africa Region for the International Federation of Red Cross and Red Crescent Societies, asked panelists to reflect on key challenges related to last-mile delivery over the past year. Rodrigo Cruz, executive secretary for the Ministry of Health in Brazil, spoke about its population of 210 million—most of whom are concentrated in large cities. However, the remainder are spread across rural regions that are difficult to access. While they have had access to three COVID-19 vaccines (AstraZeneca, Pfizer, and Sinovac), they have stressed their infrastructure trying to store and deploy them, doubling the number of vaccines typically being delivered in Brazil. They have a national center where all the vaccines are stored that distributes to 27 state-level centers; vaccines are sent to 273 distributing centers in different regions and municipalities and then to the end location. He noted the support they had received from PAHO, as they did not have the special freezers needed for Pfizer’s vaccine, so that option is only available in large cities because that is where they have the infrastructure. Highlighting concerns around equity, Cruz referenced the 34 Indigenous districts in Brazil, saying they were given priority when the national immunization plan was created. While they were the first to be vaccinated, the logistics were very challenging, as some villages are only accessible by boat and required extensive transport planning and quarantine by those delivering the vaccines.

Marie Mazur, managing director at Ready2Respond, explained its recent launch in early 2020, with support from WHO, the U.S. Centers for Disease Control and Prevention (U.S. CDC), Wellcome Trust, IFPMA, and other organizations to advance global pandemic preparedness. The most recent analysis from IFPMA shows that 49 percent of the world population received only 5 percent of influenza vaccine doses, she shared. Mazur also highlighted a survey in 2019 conducted to help understand why influenza vaccines are underused in LMICs and outlined several reasons, including access, supply and demand management and procurement, insufficient logistics, unreliable

cold chains, and regulatory challenges. In fact, she said, only half of more than 100 LMICs surveyed by WHO and the World Bank have the necessary cold chain infrastructure (World Bank, 2021), so focusing on building that capacity is a key area for them. Many countries also lack reliable electricity, with one-quarter of facilities in sub-Saharan Africa having no electricity, said Mazur. While the trickle of COVID-19 vaccines from COVAX has not required massive cold chain upgrades for many LMICs, Mazur said that when this volume increases, some of them will feel the crunch. She acknowledged Gavi and UNICEF purchasing thousands of off-grid-ready solar refrigerators for last-mile delivery in 50 countries, but even that will not be enough and a long-term solution is needed. The challenge of affordable, sustainable, modern energy for all is a Sustainable Development Goal, and it will require intersectoral solutions between energy and health, she said.

In addition to the challenge of cold chain capacity, Mazur also reinforced proper planning to have a robust vaccine supply and demand visibility and decision making at the country level. She emphasized Hansen’s comments on the importance of understanding what the needs are long term. For instance, she acknowledged published estimates showing several LMICs will not meet their COVID-19 vaccination targets before the end of 2023, well after many wealthier countries have immunized 60 percent of their populations. This potential extended demand is an example of barriers highlighted in their survey, which identified weak alignment between supply and demand of influenza vaccines. This misalignment can be somewhat alleviated by providing demand forecasting support to vaccine program managers so that the suppliers can plan and sustain additional capacity for these markets and other logistics partners can adjust strategies to the specific needs.

Patrick Tippoo, head of science and innovation at Biovac and executive director at the African Vaccine Manufacturing Initiative (AVMI), described the genesis of AVMI 10 years ago with the current situation in mind. Thinking about why LMICs would want vaccine production, Tippoo noted that it is easy to see that when you manufacture the product, you dictate the access. Of the 1.5 billion doses of COVID-19 vaccines, less than 2 percent has come to Africa, he said. The United States is managing to vaccinate 1.5 million people each day. Adding to one of Mazur’s comments, Tippoo explained that the situation in Africa has persisted for the last several years because of unreliable market demand. Building vaccine manufacturing and important inputs for capacity is just one side of the coin, he said. First the market certainty needs to be solved, as that will influence sustainability. Part of the challenge is that through the tremendous work of Gavi and UNICEF, around 1.5 billion doses of various vaccines come into the continent each year, but they are either partially or fully subsidized, which distorts the African market in terms of building commercial capacity. This

pandemic has catalyzed African governments, the African Union, and the Africa Centres for Disease Control and Prevention (CDC) to think differently, as the investment now to build production capacity is dwarfed by the cost of inaction in future pandemics.

Similar to points made by Tippoo and Mazur, John Nkengasong, director of the Africa CDC, shared supply chain challenges from across the African continent throughout the COVID-19 pandemic (see Box 4-1).

Leveraging Solutions to Address Multiple Problems

Given the challenges of last-mile delivery with COVID-19 vaccines, said Adinoyi, how will the solutions being offered cascade forward to other products and improve supplies across other health areas? One of the key things to notice, replied Tippoo, is that countries that have historically had capacity for years to produce routine vaccines were able to repurpose their facilities and production lines almost overnight. This ability to respond in a pandemic rests on that established capacity. Cruz added that these cascading effects to other products has been a challenge, as Brazil had started its influenza vaccination program 15 days prior, but it needs to be adjusted because it is in parallel with ongoing COVID-19 vaccinations. Brazil has two large laboratories that retrofit infrastructure for COVID-19—Butantan Institute, which also produces influenza vaccine, and Fio Cruz Institute, which makes the AstraZeneca COVID-19 vaccine. They have engaged in the technology transfer process so that FioCruz can produce enough for the Latin American demand. Although they have adapted their infrastructure and retrofitted things quickly, Cruz added, they cannot stop producing other vaccines, which is a challenge.

Mazur brought up the notion of a sustainable workforce, something that must be invested in before a pandemic. She saw seasonal influenza vaccination programs as a great exercise for all involved because they are annual, and health care workers, government, and the private sector need to come together and be ready. COVID-19 has shown the gaps in adult immunization programs in many LMICs, and influenza vaccinations would be an opportunity to address those. We know the next pandemic is maybe less than 10 years ahead, she said, so we really need to strengthen preparedness on all these elements, including investing in frontline health workers, in the interepidemic period.

Gaps in Multilateral Efforts

COVAX is one of the three pillars of the Access to COVID-19 Tools (ACT) Accelerator. Led by Gavi, CEPI, and WHO, it has the world’s largest and most diverse portfolio of COVID-19 vaccines (Berkley, 2020). “All participating countries, regardless of income levels, will have equal access to these vaccines” (Berkley, 2020). Mazur noted that COVAX is an amazing platform, one the world did not have in 2009 during the H1N1 epidemic. However, it has experienced some challenges, such as the trade constraints and halting of materials flowing across countries as governments closed their borders. Tippoo agreed that COVAX is a fantastic, innovative facility, but it is dependent on manufacturers and suppliers who can commit certain volumes up front and then deliver. This is challenging during normal times,

as things can shift to affect production, but now political decisions are also influencing whether doses are available. Tippoo called for securing more funds for vaccines within the COVAX platform, saying that not all countries initially understood how it would work, but future efforts should be smoother. Brazil did join COVAX, said Cruz, and purchased immunizations to cover 10 percent of the population. He underscored the importance of the platform but suggested it could be improved by having countries who purchased vaccines directly from the manufacturer donate to COVAX, which can then distribute more equitably worldwide.

IMPROVING EQUITY IN DELIVERY AND SUPPLY CHAIN

To improve equity, Cruz stated that all efforts need to be made to reach vulnerable populations. Brazil’s logistical challenges in accessing Indigenous populations led to several different modes of transport and certain isolation procedures. For example, those who vaccinate the villages isolate for 14 days ahead of time to avoid contamination, he said. This is important because the Indigenous populations do not have the antibodies that many in the general public do, as they have not been exposed to many diseases. Mazur added that accessing certain populations, including migrant populations, farm workers, and those who are chasing work, is very difficult. Not every country has prioritized Indigenous populations as Brazil has, so immunization policies need to be strengthened worldwide. However, even just knowing the numbers of those populations could help tremendously in planning and identifying sources of budgeting and funding.

Diversifying Manufacturing of Vaccines and Medical Products

Various speakers touched on the advantages and disadvantages of diversifying manufacturing and the need for finding a balance between efficiency and geographic access. Handfield highlighted the vaccine shortage and that global actors and decision makers need to make sure that vaccines are distributed much more quickly than they have been, to avoid the risk of variants continuing to grow and explode, he said. This would lead to a new cycle of booster shots and vaccine requirements and an even longer time line for being able to address the crisis.

Tippoo argued that not every country should produce vaccines, because of the high investment costs and the need to run on economies of scale—to make vaccines more cost effective, they need to be produced in larger volumes in large-scale facilities. He explained that it does not need to be one extreme versus another, identifying very concentrated capacities at scale in certain geographies and that regionalized capacity should be increased. What we have seen with COVID-19 and with H1N1 in 2009, said Tippoo,

is that Africa in particular was left behind. Having vaccines produced in Africa could also mitigate some issues of vaccine hesitancy for those who are skeptical of vaccines and products from outside.

Mazur highlighted another challenge with diversification and creation of new markets and facilities, saying that companies will face an issue of sustainability. When the pandemic is over, how can they cost-effectively continue the volume of manufacturing at these facilities? Even if COVID-19 becomes endemic and boosters are needed, vaccine companies will need to find other markets, which will create issues around identifying markets and segments to maintain production that is affordable.

Equitable Access and Allocation of Medical Countermeasures

One of the main challenges in equitable access and allocation is identifying key priority groups, said Adinoyi, such as frontline health workers, those with comorbidities, and those over 50 years of age. How has the population census or other data captured these people to ensure they are properly targeted? Messeret Shibeshi, medical epidemiologist at WHO African Region (WHO-AFRO), agreed that identifying these groups is not easy. While we talk of Universal Health Coverage, she said, health systems are limited, especially in African settings. Through microplanning at the local level, countries have tried to plan and identify at-risk populations, but it is difficult to scale up to the national level accurately. She explained that WHO-AFRO has been helping countries develop their national vaccination plans and trying to standardize equity by mandating inclusion and identification of key populations in host countries so they can be provided vaccine access. She said that by partnering with International Organization for Migration and the UN High Commissioner for Refugees, countries have successfully outlined key populations in their plans, but even with lessons from yellow fever and polio campaigns, actually reaching these populations remains challenging given their locations and the transport needed. Adinoyi suggested leveraging private-sector capabilities to address these logistical challenges—even small- or medium-scale enterprises in these communities—it does not need to be global multinational companies. For example, people in refugee camps use soap and other commodities that are delivered; those supply chains could be leveraged to provide medical products.

Adinoyi noted the need for more regionalized production and capacity for vaccines but also highlighted other medical products, such as PPE, ventilators, and oxygen, that are difficult to produce at local levels but still very much in demand. Local innovation, however, has led to improvised ventilators, and he argued for more investment in simple technologies that can be adapted to the local context. We need commitment from governments to promote Indigenous and local innovations to scale production to

the level that is needed for the country, Adinoyi said. Relying on importation, even for supplies such as PPE, has led to a scarcity in many places. But once local production took over and innovative materials were used for more contextually appropriate products, supplies became abundant and were accessible to most populations. For higher-level production of supplies such as vaccines, he continued, we can see how to invest in more regional hubs that can ensure availability once the market dynamics are well defined within that context. Mark McKinlay, director of the Center for Vaccine Equity at the Task Force for Global Health, added that another idea from its influenza program is pooled procurement for vaccines, which might be a possibility to increase availability of these needed products.

Navigating Vaccine Expiration Dates

Limited data initially justified the specific expiration dates with the new COVID-19 vaccines, said McKinlay, and as companies are generating additional data, they are pushing the expiration date further out. Additionally helpful is that new vaccines have been requiring merely refrigeration temperatures, compared to specialized ultra-freezers, which means that many recipients will have the right storage capacity. Shibeshi agreed that the limited data drove the 6-month expiration date, but she was hopeful that vaccines soon to be released will have a longer shelf life. WHO and COVAX partners have supported plans to closely monitor vaccines so none go to waste, but she reported ongoing issues across Africa, with many vaccines expiring throughout summer 2021: 178,000 doses have expired, with an additional 1.35 million at risk across 11 countries. Adinoyi agreed this is a critical issue that needs more attention. Adding to the challenge, the levels of hesitancy and uptake have not allowed for use of all available doses—he called for more work to address vaccine hesitancy issues and engage populations. David Kaslow, chief scientific officer at PATH, emphasized some last-mile delivery and equity issues are about not only raw materials and consumables but also evidence and information.

Overcoming Political and Technical Challenges

Highlighting the barriers of vaccine nationalism, Adinoyi argued for COVAX serving as an example of what can be done globally but advocated for it to transform beyond just COVID-19 needs into something more robust that can be leveraged in future pandemics. There is not just a technical issue but a political dimension that needs to be addressed, he said. Having a structure in place at the global level and ensuring political commitment to address the global challenges with appropriate frameworks is needed. Shibeshi questioned whether, without COVAX, African countries

would have even gotten the vaccines. Multilateral solutions are vague, she said, without specific thresholds and benchmarks holding organizations accountable, leading to continued infections in countries without concrete solutions. The longer the pandemic is, the more mutations will occur that continue to threaten all countries. While manufacturers are under extreme pressure, they could share their excess supply to potential countries with the right capabilities. For example, she said, South Africa and Tunisia can fill and finish the product in country. Other elements of technology transfer, such as technical knowledge and intellectual property, need to be invested in and executed over the long term but are very necessary.

Several speakers noted that building this technology transfer will be important as planning continues. McKinlay noted that mRNA technology is more viable now, with an mRNA vaccine for influenza expected soon. When we start building the capacity in LMICs, he said, we could use seasonal influenza as a platform to build the components and infrastructure. This way, when the next pandemic happens, it will be easier to switch over more quickly. Shibeshi added that many clinical trials for other vaccines happen in Africa, so why not production? She explained that five countries have already been identified with the potential to do quick packing and filling, so those would be a good place to start. Regardless of the facet of pandemic preparedness, concluded Adinoyi, it will be important to have ownership at the national, subnational, and community levels. If supply chain issues are going to be addressed, she stated that it is necessary to have deep involvement from the end users and beneficiaries.

REFLECTIONS TO BETTER PREPARE FOR FUTURE PANDEMICS

During his keynote remarks, Nkengasong shared reflections for the future to be better prepared for the next pandemic. First, he said, to strengthen global architecture, Africa as a region must embark on continental manufacturing of diagnostics and vaccines. Second, it is necessary to strengthen the African workforce and have a competent base of public health workers across the continent. For example, he said, they need 6,000 epidemiologists but only have about 1,800. He also called for strengthening National Public Health Institutes: essentially, each member state having its own “mini-CDC,” so they can quickly mobilize when threatened with future emergencies. Last, he advocated for building the right partnerships with the private sector as a critical element. He called for a new “public health order” that relies on science and protects science institutions from political harm. The trust capital during this pandemic has eroded more each time political dimensions are brought into the scientific community.

Panelists also made suggestions on how to improve future responses and prepare the sector to be more resilient. Hansen reinforced his earlier

points about focusing more on long-term demand and understanding what the needs will be. Only then can we better solve supply challenges, he said, as short-term supply and long-term demand are intricately linked conversations. Rodríguez and Downham highlighted the need for collaboration. Rodríguez pointed to the critical need to address equity and access to vaccines at the global level, as well as public–private partnerships at the regional level. Downham hoped for galvanized momentum behind collaborations specifically concentrating on establishing or upgrading manufacturing facilities—including building a sustainable workforce in LMICs.

Other speakers made calls for systems and methods to better address the challenges with visibility and data awareness. Handfield suggested a centralized third-party organization—whether through WHO, the International Chamber of Commerce, or even a consortium of companies—to create a visibility system to identify constraints and bottlenecks. It would also be helpful to see where companies are entering the market, facilities are being constructed, and capacity is being built. Swann added that this system would be useful for not only COVID-19 products but also others in other health and disease areas to understand the upstream and downstream cascading effects.

While many programs have historically kept influenza siloed in preparedness efforts, Sparrow called for taking a more holistic view that any kind of virus that might be primarily respiratory could be a threat of pandemic potential. We need to think about rapid platform technologies that can be leveraged very early on to get a vaccine developed and tested, she said, but the infrastructure and distribution systems need to be put in place to address issues such as cold chain capacity and vaccine hesitancy. Hasanin added that health systems are often a big gap, and while vaccines are a great solution, they are not the first but merely one of the available tools. Many LMICs are suffering from the lack of essential health services that is exacerbated during a pandemic.

Last-mile delivery of needed medical products is another important area for change. Tippoo noted the opportunity right now to change the way people think and create a new paradigm, given the level of the global challenge. Speaking on behalf of AVMI, he promised that Africa would make its contribution in terms of adding to the global supply of vaccines. Mazur agreed that Africa would be ready to provide a strong contribution for the next pandemic. But she also highlighted the visibility on the demand side and how, by improving that, the supply chain can become more resilient.

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