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The worldwide distribution of the first vaccines to fight COVID-19 comes with unique logistical challenges that will take unprecedented teamwork to carry out, said Wharton professor of operations and information management Gad Allon.
The immunization program is “probably the biggest vaccination initiative we’ve ever seen in humanity, so [it’s] definitely a major undertaking at the scale and the level of specificity needed to maintain it,” Allon said during a recent interview with the Wharton Business Daily radio show on SiriusXM. (Listen to the podcast at the top of this page.)
The first trucks to transport the vaccine in the United States rolled out of a Michigan manufacturing plant Sunday, just two days after the Food and Drug Administration gave emergency use authorization for the drug developed by Pfizer and Germany-based BioNTech. Health care workers and nursing home residents will be given the initial batch of about 3 million doses, which must be stored at subzero temperatures. Under Operation Warp Speed, the U.S. government has also purchased millions of doses of Moderna’s COVID-19 vaccine. People need two doses for protection against the virus, which has killed more than 300,000 Americans so far this year.
Allon, who is director of the Jerome Fisher Program in Management and Technology at Wharton, said limited manufacturing capacity is a top concern.
“These firms don’t have enough capacity to manufacture them. Moderna can manufacture a billion a year. Pfizer can do maybe 1.3 billion a year, and they’re already reporting that they have issues even with these,” he said.
The Right People
Part of the manufacturing challenge is maintaining the proper workforce.
“How do you make sure that people have the right knowledge? You also need people available,” Allon said. “Who wants to work on the project that you know is going to be very relevant now, but might not be relevant a year from now? It’s hard to get people with the right skills to work on that if they are not already part of Pfizer, Moderna and the like. I think it might not be all that fast to get them.”
While drugmakers have been developing the vaccine since the coronavirus first emerged, the runway for execution has been relatively short. Government funding has certainly helped speed the scientific path, but it doesn’t clear supply chain hurdles, Allon said. The temperature storage requirements alone present a significant challenge for every entity along the supply chain.
Allon disagreed with the suggestion that perhaps the military should handle vaccine distribution. He said the military excels in mobilizing a high number of people in a short time period, such as getting doses to front-line workers. But widespread immunization will require a sustained, scaled effort that the military isn’t best equipped for.
“A civilian supply chain is much more structured than the military one,” Allon said.
“Who wants to work on the project that you know is going to be very relevant now, but might not be relevant a year from now?”
Future Refinements
As the first iteration of the vaccine makes its way across the world, scientists must continue to refine the drug to ensure its efficacy and coverage. The current formulation has not been tested on those under the age of 16. More research could lead to vaccines that will not require extreme cold storage, cheaper versions or other therapeutics that can help get the pandemic under control. Meanwhile, drug manufacturers have to keep working on other medicines to combat all sorts of disabling and life-threatening conditions.
“It’s not a scientific question. It’s not just an operational question or a supply chain question. It’s really a combination of all of these together,” Allon said.
Learn more: Gad Allon teaches in Wharton Executive Education’s Designing and Managing the Agile Supply Chain for the Future, a new LIVE virtual program for executives who need a supply chain that can withstand future shocks.
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Anumakonda Jagadeesh
Excellent.
A COVID 19 vaccine is a vaccine intended to provide acquired immunity against COVID-19. Prior to the COVID-19 pandemic, work to develop a vaccine against the coronavirus diseases SARS and MERS had established knowledge about the structure and function of coronaviruses, which accelerated development during early 2020 of varied technology platforms for a COVID 19 vaccine.
As of mid-December 2020, 57 vaccine candidates were in clinical research: namely, 40 in Phase I–II trials and 17 in Phase II–III trials. No vaccine candidate had fully completed a Phase III trial or obtained licensure, as of 13 December.
In November 2020, BioNTech and Pfizer Inc, Moderna, the University of Oxford (in collaboration with AstraZeneca), and the Gamaleya Institute announced positive results from interim analyses of their Phase III vaccine trials. As of 15 December, 11 countries (the United Kingdom, Bahrain, United Arab Emirates, Canada, Saudi Arabia, the United States, Mexico, Kuwait, Singapore, Jordan, and Oman) have approved the Pfizer-BioNTech COVID-19 Vaccine for emergency use. Furthermore, Bahrain gave emergency marketing authorization for the vaccine manufactured by Sinopharm, followed by the United Arab Emirates. By 16 December, in the United Kingdom, 138,000 people had received the Pfizer-BioNTech COVID-19 vaccine during the first week of their vaccination programme.
By December, more than 10 billion vaccine doses had been preordered by countries, with about half of the doses purchased by high-income countries comprising only 14% of the world’s population. The manufacturers of three vaccines closest to global distribution – Pfizer, Moderna, and AstraZeneca – predicted a manufacturing capacity of 5.3 billion doses in 2021, which could be used to vaccinate about 3 billion people (as the vaccines require two doses for a protective effect against COVID-19). Due to the high demand of preorders in 2020–21, people in low-income developing countries may not receive vaccinations from these manufacturers until 2023 or 2024, increasing the need for the global COVAX initiative to supply vaccines equitably.
Partnerships, competition, and distribution
Large pharmaceutical companies with experience in making vaccines at scale, including Johnson & Johnson, AstraZeneca, and GlaxoSmithKline (GSK), are forming alliances with biotechnology companies, national governments, and universities to accelerate progression to an effective vaccine. To combine financial and manufacturing capabilities for a pandemic adjuvanted vaccine technology, GSK joined with Sanofi in an uncommon partnership of multinational companies to support accelerated vaccine development.
During a pandemic on the rapid timeline and scale of COVID 19 infections during 2020, international organizations like the WHO and CEPI, vaccine developers, governments, and industry are evaluating distribution of the eventual vaccine(s). Individual countries producing a vaccine may be persuaded to favor the highest bidder for manufacturing or provide first-service to their own country. Experts emphasize that licensed vaccines should be available and affordable for people at the frontline of healthcare and having the greatest need. Under their agreement with AstraZeneca, the University of Oxford vaccine development team and UK government agreed that UK citizens would not get preferential access to a new COVID 19 vaccine developed by the taxpayer-funded university, but rather consented to having a licensed vaccine distributed multinationally in cooperation with the WHO. Several companies plan to initially manufacture a vaccine at low cost, then increase costs for profitability later if annual vaccinations are needed and as countries build stock for future needs.
The WHO and CEPI are developing financial resources and guidelines for global deployment of several safe, effective COVID 19 vaccines, recognizing the need is different across countries and population segments. For example, successful COVID 19 vaccines would likely be allocated first to healthcare personnel and populations at greatest risk of severe illness and death from COVID 19 infection, such as the elderly or densely-populated impoverished people. The WHO, CEPI, and GAVI have expressed concerns that affluent countries should not receive priority access to the global supply of eventual COVID 19 vaccines, but rather protecting healthcare personnel and people at high risk of infection are needed to address public health concerns and reduce economic impact of the pandemic.
Compressed timelines
Geopolitical issues, safety concerns for vulnerable populations, and manufacturing challenges for producing billions of doses are compressing schedules to shorten the standard vaccine development timeline, in some cases combining clinical trial steps over months, a process typically conducted sequentially over years. As an example, Chinese vaccine developers and the government Chinese Center for Disease Control and Prevention began their efforts in January 2020, and by March were pursuing numerous candidates on short timelines, with the goal to showcase Chinese technology strengths over those of the United States, and to reassure the Chinese people about the quality of vaccines produced in China.
In the haste to provide a vaccine on a rapid timeline for the COVID 19 pandemic, developers and governments are accepting a high risk of “short-circuiting” the vaccine development process, with one industry executive saying: “The crisis in the world is so big that each of us will have to take maximum risk now to put this disease to a stop”. Multiple steps along the entire development path are evaluated, including the level of acceptable toxicity of the vaccine (its safety), targeting vulnerable populations, the need for vaccine efficacy breakthroughs, the duration of vaccination protection, special delivery systems (such as oral or nasal, rather than by injection), dose regimen, stability and storage characteristics, emergency use authorization before formal licensing, optimal manufacturing for scaling to billions of doses, and dissemination of the licensed vaccine. From Phase I clinical trials, 84–90% of vaccine candidates fail to make it to final approval during development, and from Phase III, 25.7% fail– the investment by a manufacturer in a vaccine candidate may exceed US$1 billion and end with millions of useless doses. In the case of COVID 19 specifically, a vaccine efficacy of 70% may be enough to stop the pandemic, but if it has only 60% efficacy, outbreaks may continue; an efficacy of less than 60% will not provide enough herd immunity to stop the spread of the virus alone.
As the pandemic expands during 2020, research at universities is obstructed by physical distancing and closing of laboratories. Globally, supplies critical to vaccine research and development are increasingly scarce due to international competition or national sequestration. Timelines for conducting clinical research – normally a sequential process requiring years – are being compressed into safety, efficacy, and dosing trials running simultaneously over months, potentially compromising safety assurance.
Licensure
A vaccine licensure occurs after the successful conclusion of the clinical trials program through Phases I–III demonstrating safety, immunogenicity at a specific dose, effectiveness at preventing infection in target populations, and enduring preventive effect. As part of a multinational licensure for a vaccine, the World Health Organization Expert Committee on Biological Standardization developed guidelines of international standards for manufacturing and quality control of vaccines, a process intended as a platform for national regulatory agencies to apply for their own licensure process. Vaccine manufacturers do not receive licensure until a complete clinical package proves the vaccine is safe and has long-term effectiveness, following scientific review by a multinational or national regulatory organization, such as the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA).
Upon developing countries adopting WHO guidelines for vaccine development and licensure, each country has its own responsibility to issue a national licensure, and to manage, deploy, and monitor the vaccine throughout its use in each nation. Building trust and acceptance of a licensed vaccine among the public is a task of communication by governments and healthcare personnel to ensure a vaccination campaign proceeds smoothly, saves lives, and enables economic recovery. When a vaccine is licensed, it will initially be in limited supply due to variable manufacturing, distribution, and logistical factors, requiring an allocation plan for the limited supply and which population segments should be prioritized to first receive the vaccine.
World Health Organization
Vaccines developed for multinational distribution via the United Nations Children’s Fund (UNICEF) require pre-qualification by WHO to ensure international standards of quality, safety, immunogenicity, and efficacy for adoption by numerous countries.
The process requires manufacturing consistency at WHO-contracted laboratories following GMP practices. When UN agencies are involved in vaccine licensure, individual nations collaborate by 1) issuing marketing authorization and a national license for the vaccine, its manufacturers, and distribution partners; and 2) conducting postmarketing surveillance, including records for adverse events after the vaccination program. WHO works with national agencies to monitor inspections of manufacturing facilities and distributors for compliance with GMP and regulatory oversight.
Some countries choose to buy vaccines licensed by reputable national organizations, such as EMA, FDA, or national agencies in other affluent countries, but such purchases typically are more expensive and may not have distribution resources suitable to local conditions in developing countries.
Australia
In October 2020, the Australian Therapeutic Goods Administration (TGA) granted provisional determinations to AstraZeneca Pty Ltd in relation to its COVID 19 vaccine, ChAdOx1-S [recombinant] and to Pfizer Australia Pty Ltd in relation to its COVID-19 vaccine, tozinameran [modRNA].
European Union
In the European Union (EU), vaccines for pandemic pathogens, such as seasonal influenza, are licensed EU-wide where all of the member states comply (“centralized”), are licensed for only some member states (“decentralized”), or are licensed on an individual national level. Generally, all EU states follow regulatory guidance and clinical programs defined by the European Committee for Medicinal Products for Human Use (CHMP), a scientific panel of the European Medicines Agency (EMA) responsible for vaccine licensure. The CHMP is supported by several expert groups who assess and monitor the progress of a vaccine before and after licensure and distribution.
In October 2020, the CHMP started ‘rolling reviews’ of the vaccines known as COVID 19 Vaccine AstraZeneca (ChAdOx1-SARS-CoV-2) and Pfizer-BioNTech COVID-19 Vaccine (BNT162b2).
In November 2020, the EMA published a safety monitoring plan and guidance on risk management planning (RMP) for COVID-19 vaccines. The plan outlines how relevant new information emerging after the authorization and uptake of COVID-19 vaccines in the pandemic situation will be collected and promptly reviewed. All RMPs for COVID-19 vaccines will be published on the EMA’s website. The EMA published guidance for developers of potential COVID-19 vaccines on the clinical evidence to include in marketing authorization applications.
In November 2020, the CHMP started a rolling review of the Moderna vaccine for COVID-19 known as mRNA-1273.
In December 2020, the EMA received application for conditional marketing authorizations (CMA) for the mRNA vaccines BNT162b2 and mRNA1273 (Moderna Covid-19 vaccine). The assessments of the vaccines are scheduled to proceed under accelerated timelines with the possibility of opinions issued within weeks.
In December 2020, the CHMP started a rolling review of the Ad26.COV2.S COVID-19 vaccine from Janssen-Cilag International N.V.
United States
Under the FDA, the process of establishing evidence for vaccine clinical safety and efficacy is the same as for the approval process for prescription drugs. If successful through the stages of clinical development, the vaccine licensing process is followed by a Biologics License Application which must provide a scientific review team (from diverse disciplines, such as physicians, statisticians, microbiologists, chemists) a comprehensive documentation for the vaccine candidate having efficacy and safety throughout its development. Also during this stage, the proposed manufacturing facility is examined by expert reviewers for GMP compliance, and the label must have compliant description to enable health care providers definition of vaccine specific use, including its possible risks, to communicate and deliver the vaccine to the public.
The Advisory Committee on Immunization Practices voted on 2 December that the first doses of the vaccine should be prioritized for health care workers and residents and staff of nursing homes. The board will make guidance who should receive the vaccine next as production increases, which will include older adults, emergency responders, teachers, and essential workers less able to socially distance, and people with comorbidities. However, states will make the final plans for prioritization, distribution, and logistics of vaccinating everyone as supply becomes available. After licensure, monitoring of the vaccine and its production, including periodic inspections for GMP compliance, continue as long as the manufacturer retains its license, which may include additional submissions to the FDA of tests for potency, safety, and purity for each vaccine manufacturing step.
Commercialization issues
By June 2020, tens of billions of dollars were invested by corporations, governments, international health organizations, and university research groups to develop dozens of vaccine candidates and prepare for global vaccination programs to immunize against COVID 19 infection. The corporate investment and need to generate value for public shareholders raised concerns about a “market-based approach” in vaccine development, costly pricing of eventual licensed vaccines, preferred access for distribution first to affluent countries, and sparse or no distribution to where the pandemic is most aggressive, as predicted for densely-populated, impoverished countries unable to afford vaccinations. The collaboration of the University of Oxford with AstraZeneca (a global pharmaceutical company based in the UK) raised concerns about price and sharing of eventual profits from international vaccine sales, arising from whether the UK government and university as public partners had commercialization rights. AstraZeneca stated that initial pricing of its vaccine would not include a profit margin for the company while the pandemic was still expanding.
In early June, AstraZeneca made a US$750 million deal allowing CEPI and GAVI to manufacture and distribute 300 million doses if its Oxford vaccine candidate proves safe and effective, reportedly increasing the company’s total production capacity to over 2 billion doses per year. Commercialization of pandemic vaccines is a high-risk business venture, potentially losing billions of dollars in development and pre-market manufacturing costs if the candidate vaccines fail to be safe and effective. The multinational pharmaceutical company Pfizer indicated it was not interested in a government partnership, which would be a “third party” slowing progress in Pfizer’s vaccine program. Further, there are concerns that rapid-development programs – like the Operation Warp Speed plan of the United States – are choosing vaccine candidates mainly for their manufacturing advantages to shorten the development timeline, rather than for the most promising vaccine technology having safety and efficacy.
Sovereignty
Favored distribution of vaccines within one or a few select countries, called “vaccine sovereignty”, is a criticism of some of the vaccine development partnerships, such as for the AstraZeneca-University of Oxford vaccine candidate, concerning whether there may be prioritized distribution first within the UK and to the “highest bidder” – the United States, which made an advance payment of US$1.2 billion to secure 300 million vaccine doses for Americans, even before the AstraZeneca-Oxford vaccine or a Sanofi vaccine is proved safe or effective. Concerns exist about whether some countries producing vaccines may impose protectionist controls by export restrictions that would stockpile a COVID 19 vaccine for their own population.
The Chinese government pledged in May that a successful Chinese vaccine would become a “global, public good”, implying enough doses would be manufactured for both national and global distribution. Unlike mRNA vaccines, which have to be stored at subzero temperatures, inactivated vaccines from Sinovac and Sinopharm require ordinary refrigeration and may have more appeal in developing countries.
In June, the Serum Institute of India (SII) – a major manufacturer of global vaccines – reached a licensing agreement with AstraZeneca to make 1 billion doses of vaccine for low-and-middle income countries; of which half of the doses would go to India. Similar preferential homeland distribution may exist if a vaccine is manufactured in Australia.
Equitable access
As many of the efforts on vaccine candidates have open-ended outcomes, including a high potential for failure during human testing, CEPI, WHO, and charitable vaccine organizations, such as the Gates Foundation and GAVI, raised over US$20 billion during the first half of 2020, to fund vaccine development and preparedness for vaccinations, particularly for children in under-developed countries. CEPI had stated that governments should ensure implementation of a globally-fair allocation system for eventual vaccines, using a coordinated system of manufacturing capacity, financing and purchasing, and indemnification from liability to offset risks taken by vaccine developers.
Having been created to monitor fair distribution of infectious disease vaccines to low- and middle-income countries, CEPI revised its equitable access policy that was published in February to apply to its COVID 19 vaccine funding: 1) “prices for vaccines will be set as low as possible for territories that are or may be affected by an outbreak of a disease for which CEPI funding was used to develop a vaccine;” 2) “information, know-how and materials related to vaccine development must be shared with (or transferred to) CEPI” so that it can assume responsibility for vaccine development if a company discontinues expenditures for a promising vaccine candidate; 3) CEPI would have access to, and possible management of, intellectual property rights (i.e., patents) for promising vaccines; 4) “CEPI would receive a share of financial benefits that might accrue from CEPI-sponsored vaccine development, to re-invest in support of its mission to provide global public health benefit”; and 5) data transparency among development partners should maintain the WHO Statement on Public Disclosure of Clinical Trial Results, and require results to be published in open-access publications. Some vaccine manufacturers opposed parts of these proposals.
International groups, such as the Centre for Artistic Activism and Universities Allied for Essential Medicines, advocate for equitable access to licensed COVID 19 vaccines. Scientists have encouraged that the WHO, CEPI, corporations, and governments collaborate to assure evidence-based allocation of eventual COVID 19 vaccines determined on infection risk, particularly urgent vaccinations provided first for healthcare workers, vulnerable populations, and children. During 2020, the WHO, GAVI, and CEPI combined resources to form COVAX – a program for coordination of global equitable access to a licensed vaccine.
Over 100 international scientists and concerned individuals (including those associated with religious organizations) have called for releasing COVID 19 vaccines to the public domain. Similar to the development of the first polio vaccine that was never patented, an effective COVID 19 vaccine would be available for production and approval by a number of countries and pharmaceutical manufacturing centers worldwide, therefore allowing for a more even and cost-effective distribution on a global scale.
Supply chain
During and after 2021, deploying a COVID-19 vaccine may require worldwide transport and tracking of 10–19 billion vial doses, an effort readily becoming the largest supply chain challenge in history. As of September 2020, supply chain and logistics experts expressed concern that international and national networks for distributing a licensed vaccine were not ready for the volume and urgency, due mainly to deterioration of resources during 2020 pandemic lockdowns and downsizing that degraded supply capabilities. Addressing the worldwide challenge faced by coordinating numerous organizations – the COVAX partnership, global pharmaceutical companies, contract vaccine manufacturers, inter- and intranational transport, storage facilities, and health organizations in individual countries – Seth Berkley, chief executive of GAVI, stated: “Delivering billions of doses of vaccine to the entire world efficiently will involve hugely complex logistical and programmatic obstacles all the way along the supply chain.”
As an example highlighting the immensity of the challenge, the International Air Transport Association stated that 8,000 Boeing 747 cargo planes – implemented with equipment for precision vaccine cold storage – would be needed to transport just one dose for people in the more than 200 countries experiencing the COVID 19 pandemic. GAVI states that “with a fast-moving pandemic, no one is safe, unless everyone is safe.”
In contrast to the multibillion-dollar investment in vaccine technologies and early-stage clinical research, the post-licensing supply chain for a vaccine has not received the same planning, coordination, security or investment. A major concern is that resources for vaccine distribution in low- to middle-income countries, particularly for vaccinating children, are inadequate or non-existent, but could be improved with cost efficiencies if procurement and distribution were centralized regionally or nationally. In September, the COVAX partnership included 172 countries coordinating plans to optimize the supply chain for a COVID 19 vaccine, and the United Nations Children’s Fund joined with COVAX to prepare the financing and supply chain for vaccinations of children in 92 developing countries.
Logistics
Logistics vaccination services assure necessary equipment, staff, and supply of licensed vaccines across international borders. Central logistics include vaccine handling and monitoring, cold chain management, and safety of distribution within the vaccination network. The purpose of the COVAX Facility is to centralize and equitably administer logistics resources among participating countries, merging manufacturing, transport, and overall supply chain infrastructure. Included are logistics tools for vaccine forecasting and needs estimation, in-country vaccine management, potential for wastage, and stock management.
Other logistics factors conducted internationally during distribution of a COVID 19 vaccine may include:
• visibility and traceability by barcodes for each vaccine vial
• sharing of supplier audits
• sharing of chain of custody for a vaccine vial from manufacturer to the individual being vaccinated
• use of vaccine temperature monitoring tools
• temperature stability testing and assurance
• new packaging and delivery technologies
• stockpiling
• coordination of supplies within each country (personal protective equipment, diluent, syringes, needles, rubber stoppers, refrigeration fuel or power sources, waste-handling, among others)
• communications technology
• environmental impacts in each country
A logistics shortage in any one step may derail the whole supply chain, according to one vaccine developer. If the vaccine supply chain fails, the economic and human costs of the pandemic may be extended for years.
Manufacturing capacity
By August 2020, when only a few vaccine candidates were in Phase III trials and were many months away from establishing safety and efficacy, numerous governments pre-ordered more than two billion doses at a cost of more than US$5 billion. Pre-orders from the UK government for 2021 were for five vaccine doses per person, a number dispiriting to organizations like the WHO and GAVI which are promoting fair and equitable access worldwide, especially for developing countries. In September, CEPI was financially supporting basic and clinical research for nine vaccine candidates, with nine more in evaluation, under financing commitments to manufacture two billion doses of three licensed vaccines by the end of 2021. Before 2022, 7–10 billion COVID 19 vaccine doses may be manufactured worldwide, but the sizable pre-orders by affluent countries – called “vaccine nationalism” – threaten vaccine availability for poorer nations.
After joining COVAX in October, China initially shared that it would produce 600 million vaccine doses before the end of 2020 and another one billion doses in 2021, although it was unsure how many would be for the country’s own population of 1.4 billion. Sinopharm said it may have the capacity to produce more than 1 billion doses in 2021, while its Dubai partner G42 Healthcare aimed to produce up to 100 million doses in 2021 focused on the middle east. Sinovac aimed to complete a second production facility by the end of 2020 to increase production of CoronaVac to 600 million doses from 300 million, while its Brazilian partner Instituto Butantan planned to produce 100 million doses and its Indonesian partner Bio Farma planned to produce up to 250 million doses of CoronaVac a year.
The Serum Institute of India plans to produce at least one billion vaccine doses, although the institute has stated that half the doses will be used in India.
AstraZeneca CEO, Pascal Soriot, stated: “The challenge is not making the vaccine itself, it’s filling vials. There just aren’t enough vials in the world.” Preparing for high demand in manufacturing vials, an American glass producer invested $163 million in July for a vial factory. Glass availability for vial manufacturing and contaminant control are issues of concern, indicating higher production costs with lower profit potential for developers amid demands for vaccines to be affordable.
Vaccines must be handled and transported using international regulations, be maintained at controlled temperatures that vary across vaccine technologies, and be used for immunization before deterioration in storage. The scale of the COVID 19 vaccine supply chain is expected to be vast to ensure delivery worldwide to vulnerable populations. Priorities for preparing facilities for such distribution include temperature-controlled facilities and equipment, optimizing infrastructure, training immunization staff, and rigorous monitoring. RFID technologies are being implemented to track and authenticate a vaccine dose from the manufacturer along the entire supply chain to the vaccination.
In September 2020, Grand River Aseptic Manufacturing agreed with Johnson & Johnson to support the manufacture of its vaccine candidate, including technology transfer and fill and finish manufacturing. In October 2020, it was announced that the Moderna vaccine candidate will be manufactured in Visp, Switzerland by its partner Lonza Group, which plans to produce the first doses in December 2020. The newly built 2,000-square-metre facility will ramp up production to 300 million doses annually. The ingredient will be shipped frozen at −70 °C to Spain’s Laboratorios Farmacéuticos Rovi SA for the final stage of manufacturing. Lonza’s site in Portsmouth, New Hampshire, aims to start making vaccine ingredients exclusively for the U.S. as early as November.
Cold chain
Vaccines (and adjuvants) are inherently unstable during temperature changes, requiring cold chain management throughout the entire supply chain, typically at temperatures of 2–8 °C (36–46 °F). Because COVID 19 vaccine technologies are varied among several novel technologies, there are new challenges for cold chain management, with some vaccines that are stable while frozen but labile to heat, while others should not be frozen at all, and some are stable across temperatures. Freezing damage and inadequate training of personnel in the local vaccination process are major concerns. If more than one COVID 19 vaccine is approved, the vaccine cold chain may have to accommodate all these temperature sensitivities across different countries with variable climate conditions and local resources for temperature maintenance. Sinopharm and Sinovac’s vaccines are examples of inactivated vaccines in Phase III testing which can be transported using existing cold chain systems at 2–8 °C (36–46 °F).
modRNA vaccine technologies in development may be more difficult to manufacture at scale and control degradation, requiring ultracold storage and transport. As examples, Moderna’s RNA vaccine candidate requires cold chain management just above freezing temperatures between 2 and 8 °C (36 and 46 °F) with limited storage duration (30 days), but the Pfizer-BioNTech RNA candidate requires storage between −80 and −60 °C (−112 and −76 °F), or colder throughout deployment until vaccination.
After a vaccine vial is punctured to administer a dose, it is viable for only six hours, then must be discarded, requiring attention to local management of cold storage and vaccination processes. Because the COVID 19 vaccine will likely be in short supply for many locations during early deployment, vaccination staff will have to avoid spoilage and waste, which typically are as much as 30% of the supply. The cold chain is further challenged by the type of local transportation for the vaccines in rural communities, such as by motorcycle or delivery drone, need for booster doses, use of diluents, and access to vulnerable populations, such as healthcare staff, children and the elderly.
Air and land transport
Coordination of international air cargo is an essential component of time- and temperature-sensitive distribution of COVID 19 vaccines, but, as of September 2020, the air freight network is not prepared for multinational deployment. “Safely delivering COVID 19 vaccines will be the mission of the century for the global air cargo industry. But it won’t happen without careful advance planning. And the time for that is now. 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,” said IATA’s Director General and CEO, Alexandre de Juniac, in September 2020.[382]
For the severe reduction in passenger air traffic during 2020, airlines downsized personnel, trimmed destination networks, and put aircraft into long-term storage. As the lead agencies for procurement and supply of the COVID-19 vaccine within the WHO COVAX Facility, GAVI and UNICEF are preparing for the largest and fastest vaccine deployment ever, necessitating international air freight collaboration, customs and border control, and possibly as many as 8,000 cargo planes to deliver just one vaccine dose to multiple countries.
Two of the first approved vaccines, Pfizer and BioNTech’s Pfizer-BioNTech COVID-19 vaccine and Moderna’s mRNA-1273, must be kept cold during transport. Keeping the temperatures sufficiently low is accomplished with specially-designed containers and dry ice, but dry ice is only allowed in limited quantities on airplanes as the gases released via sublimation may be toxic. In the United States, the Federal Aviation Administration (FAA) limits the amount of dry ice on a Boeing 777-224 to 3,000 lb (1,400 kg), but it temporarily allowed United Airlines to transport up to 15,000 lb (6,800 kg)—nearly 1 million doses—between Brussels and Chicago. The CDC has tasked McKesson with vaccine distribution in the US; the company will handle all major vaccines except Pfizer’s. American Airlines, Boeing, and Delta Airlines are also working to increase dry ice transportation capacity, and American, Delta, and United each operate their own cold storage networks in the US. FedEx and UPS have installed ultra-cold freezers at air cargo hubs in Europe and North America, and UPS can manufacture 1,200 lb (540 kg) of dry ice per hour.
Security and corruption
Medicines are the world’s largest fraud market, worth some $200 billion per year, making the widespread demand for a COVID-19 vaccine vulnerable to counterfeit, theft, scams, and cyberattacks throughout the supply chain. The vaccine has been referred to as “the most valuable asset on earth”; Interpol called it “liquid gold” and warned of an “onslaught of all types of criminal activity”. Anticorruption, transparency, and accountability safeguards are being established to reduce and eliminate corruption of COVID 19 vaccine supplies. Absence of harmonized regulatory frameworks among countries, including low technical capacity, constrained access, and ineffective capability to identify and track genuine vs. counterfeit vaccines, may be life-threatening for vaccine recipients, and would potentially perpetuate the COVID 19 pandemic. Tracking system technologies for packaging are being used by manufacturers to trace vaccine vials across the supply chain, and to use digital and biometric tools to assure security for vaccination teams. In December 2020, Interpol warned that organized crime could infiltrate the vaccine supply chain, steal product through physical means, and data theft, or even offer counterfeit vaccine kits. Further, vaccines which require constant freezing temperatures are also susceptible to sabotage.
GPS devices will be used in the United States to track the vaccines. In Colorado, the vaccine shipments will be escorted by Colorado State Patrol officers from Denver International Airport to the state’s eight distribution points; the exact plans are confidential and law enforcement will “maintain a low-key profile”.
Peripheral businesses may also be affected. An IBM security analyst told the New York Times that petrochemical companies are being targeted by hackers due to their central role in producing dry ice.
National infrastructure
The WHO has implemented an “Effective Vaccine Management” system, which includes constructing priorities to prepare national and subnational personnel and facilities for vaccine distribution, including:
• Trained staff to handle time- and temperature-sensitive vaccines
• Robust monitoring capabilities to ensure optimal vaccine storage and transport
• Temperature-controlled facilities and equipment
• Traceability
• Security
Border processes for efficient handling and customs clearance within individual countries may include:
• Facilitating flight and landing permits
• Exempting flight crews from quarantine requirements
• Facilitating flexible operations for efficient national deployment
• Granting arrival priority to maintain vaccine temperature requirements
Wikipedia
Dr.A.Jagadeesh Nellore(AP),India