Background

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a virus in the order of Nidovirales that envelop the positive RNA strand. This new strain of coronavirus, not previously identified in humans, emerged in December 2019 [1]. COVID-19 is the name given to the disease associated with the SARS-CoV-2 virus. This virus primarily targets epithelial cells in the respiratory and gastrointestinal tracts. The COVID-19 outbreak had spread in over 100 countries before it was characterized as a pandemic by the World Health Organization (WHO) on March 11, 2020. In early October 2020, the death counts due to the virus crossed over 1.04 million with 35.5 million cases reported worldwide. India alone reported 6.69 million which was the second-highest number of reported COVID-19 cases after the United States [2]. COVID-19 was first reported in China as an epidemic in December 2019, and the genetic sequence of the novel coronavirus was shared with the world in January 2020 for developing specific diagnostic and other health products including vaccines. COVID-19 is a highly contagious disease which makes the situation very challenging for the scientific and medical communities. The highly contagious nature of the virus underscores the need for widespread vaccination, once vaccines are available [1]. Since the last 11 months, life has come to a standstill, and the vaccine is, therefore, anxiously waited.

Previous studies revealed how human-to-human disease transmission can cause outbreaks and how the global risk can be increased through large-scale travel and migration [3]. The fatality rate of MERS was 35% [4]. The fatality rate of COVID-19 in India is 1.5% (1.5% of people infected with SARS-CoV-2 have a fatal outcome). Globally, this rate was 2.8% in October 2020. Countries are responding differently to COVID-19 by developing different strategies to address the pandemic. However, one preventive measure that could prove to be a permanent solution to this problem is immunization. In October, 214 countries were infected with COVID-19. Immunizing the entire population of the world needs an immense amount of resources, funding, and global cooperation.

Efforts to develop a vaccine commenced in January 2020 when the WHO along with researchers from several institutions started to develop and test vaccines, standardize assays, and regulatory approaches for innovative trial designs, and define criteria for prioritizing vaccine candidates. The WHO has pre-qualified diagnostics that are being used all over the world. WHO is also coordinating global trials to assess the safety and efficacy of therapeutics for COVID-19. The challenge is to speed up and harmonize the processes to ensure that a safe product can be brought to millions of people worldwide. In the early days of HIV treatment and the deployment of vaccines against the H1N1 outbreak in 2009, it was seen that even when tools are available, they are not equally distributed. Various networks and organizations such as the Coalition for Epidemic Preparedness Innovations (CEPI) and the International Vaccine Institute (IVI) have worked in partnership to develop new strategies for ensuring speedy progress in the development of vaccines to respond to future outbreaks of the Middle East Respiratory Syndrome (MERS), Zika, and other viruses. The objective was to ensure readiness for emergencies, prevent outbreaks due to re-emerging diseases such as poliomyelitis, and to stockpile vaccines. IVI was founded in 1997. Its first major initiative was to develop a safe, effective, and affordable cholera vaccine. This technology was transferred to India. A partnership with EuBiologics in South Korea helped to produce an optimized OCV product which was more suitable and enabled a higher volume supply and uptake [5]. That is how India expanded its vaccine-manufacturing capacity to meet international demand.

The WHO has, time and again, reviewed its role in improving global vaccine access, procurement, and immunization coverage. The international collaborating partners provide updates on the product, price, procurement, the pre-qualification for vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries [6]. India is leading vaccine manufacturing as a part of the Developing Countries Vaccine Manufacturers Network (DCVMN) (Box 1) which is a public health-driven alliance representing vaccine manufacturers from countries engaged in research, development, manufacture, and supply of vaccines for local and international use. The DCVMN-affiliated manufacturers are currently using various technology platforms for developing large-scale manufacture and supply of COVID-19 vaccines [1]. It is essential to work with international organizations such as WHO, United Nations International Children’s Emergency Fund (UNICEF), Pan American Health Organization (PAHO), CEPI, IVI, and Global Alliance for Vaccines and Immunization (GAVI) as individual countries cannot manufacture and distribute, in a reliable time frame, the huge number of doses would be needed. Furthermore, expertise to develop, test, manufacture, and distribute the vaccine is scattered around the world which makes it imperative for countries to work together and to share their expertise for delivering adequate quantities of reliable and tested vaccines to everyone (Fig. 7.1).

Fig. 7.1
figure 1

Source Compiled by Author

Timeline of major COVID vaccine development events in India.

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This COVID-19 pandemic has unknotted many of the gains that India made with vaccination campaigns for polio, cholera, measles, diphtheria, and meningitis. In 1997, with the support of IVI, India revealed its potential for manufacturing vaccines. Serum Institute of India (SII) developed the first meningitis vaccine which was pre-qualified by WHO in 2010 [7]. The world’s first typhoid conjugate vaccine (TCV) by Bharat Biotech International was launched in 2013 [8]. The multi-dose inactivated polio vaccine (IPV) from Bilthoven Biological was released in 2017. The first fully liquid hexavalent vaccine based on whole-cell pertussis was developed by Panacea Biotech of India, in the same year in 2017. The Serum Institute of India developed the first thermostable rotavirus vaccine [9]. All vaccines are pre-qualified by WHO. India is the only country in the DCVMN network that has as many as 23 pre-qualified vaccines.

In early June 2020, the WHO declared COVID-19 as a pandemic requiring a rapid response. Through direct communication with network members, online search, and an internal survey, certain indicators like engagement of developing countries vaccine manufacturer’s network members in the research and development of COVID-19 vaccines and their capacities in the manufacturing and distribution of vaccines were assessed [1]. As a result, a dedicated facility called COVID-19 Vaccine Global Access Facility (COVAX) was formed. The role of COVAX is to provide support for the procurement of vaccines through GAVI. India plays a leading role in the COVAX Advance Market Commitment (AMC), the Vaccine Alliance, and the Coalition for Epidemic Preparedness Innovations (CEPI) leading the research and development of vaccines. The WHO has also developed a framework called access to COVID-19 tools (ACT) accelerator which is the result of a global collaboration of WHO, European Commission, France, and The Bill and Melinda Gates Foundation, to accelerate the development, production, and equitable access to COVID-19 diagnostics, drugs, and vaccines [10, 11]. India is the largest producer of vaccines in the COVAX coalition.

On August 7, 2020, a National Expert Group on Vaccine Administration for COVID-19 was formed by the Cabinet Secretariat in India. Its mandate is to identify the right vaccines for use in the country, manage finances for large-scale procurement, and prioritize population groups that will receive the first vaccine doses [12]. The National Expert Group has obtained the structured plan from the states for demand and supply of the COVID-19 vaccine. The total estimated production capacity of India, led by private producers, is three billion doses per year. Indian firms have signed supply and license agreements with Novavax and production agreements with AstraZeneca for 100 million doses of their vaccine. In the run for vaccines, India has two candidate vaccines developed indigenously, COVAXIN and ZyCov-D [13]. In addition to manufacturing, reaching the coronavirus vaccine from manufacturing sites to different parts of the developing world is also an immense challenge that requires a very efficient supply chain as some vaccines require exceptional cold storage. Thus, merely manufacturing vaccines will not be enough to cover the population of India. A study conducted between 2018 and 2019 to measure the sudden increase in measles outbreaks despite safe and affordable vaccine availability showed that such outbreaks occurred because there were pockets of low coverage. Skepticism about vaccines and the highly contagious nature of the disease were other problems [14, 15]. All these challenges will inevitably need to be addressed even when a safe and efficient vaccine becomes available.

Vaccine Development

A vaccine is a biological substance that stimulates the production of antibodies and provides active immunity against infectious diseases. It is prepared from the causative agent of the disease, its products, or its synthetic substitute treated to act as an antigen without inducing disease. Vaccination is a process that aims to generate enough immune cells and antibodies specific to the disease to provide long-lasting protection against the disease. Initially, the immunoglobulin M (IgM) antibody is produced in small amounts. After a few days, the immune response begins to make an immunoglobulin G (IgG) antibody which is more specific to the microbe. An antigen, on subsequent administration, stimulates a secondary immune response which is much faster and lasts longer [16]. The different types of vaccines that are available are live attenuated, inactivated (killed antigen), sub-unit (purified antigen), and toxoids (inactivated compounds).

Scientists are also working on the next-generation vaccines such as DNA and RNA vaccines and viral vector vaccines [17] (Fig. 7.2). The characteristics of these vaccines determine how they work and how many doses are required to generate an immune response [16]. For the COVID-19 vaccine, scientists are exploring different types of vaccine approaches. As COVID-19 is a viral disease, it is very difficult to find its weak spot for developing a vaccine. Viruses also mutate making it harder for the immune system to launch a counter-attack as seen in the case of HIV/AIDS [17]. Although scientists have tried to estimate how contagious COVID-19 is, the accuracy of some diagnostic tests is still not up to the mark. Current estimates suggest that the average number of people that a contagious person can infect is one to seven. A person with measles can infect 11–16 people on average [18].

Fig. 7.2
figure 2

Source Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, and U.S Food and Drug Administration

Types of coronavirus vaccines approaches.

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Research and Development of Vaccines

Of more than 170 candidate vaccines developed by various manufacturers and academic institutions worldwide by the end of December 2020, three COVID-19 vaccines had arrived; the rest were still in different clinical trial phases [19]. Eight of the 19 members of DCVMN manufacturers developing COVID vaccines have had vaccines prequalified by WHO in the past. Every vaccine undergoes clinical trials before it is made available to the general population. Figure 7.3 shows the difference between the previous traditional timeline of ten to fifteen years that was required for vaccine development versus the COVID-19 vaccine development cycle which is completed in 12–18 months. Hatchett’s study findings were used for preparing the initial proposals for the Middle East Respiratory Syndrome (MERS), Lassa, and Nipah virus vaccines, thus justifying the proposed COVID-19 vaccine production cycle timeline. There are both rewards and risks of expediting COVID-19 testing and vaccine development, but nobody is sure of either [20].

Fig. 7.3
figure 3

Source US Government Accountability Office (GAO) analysis of GAO-20-215SP

Five phases of vaccine development from preclinical phase to approval phase.

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In India, there are currently 30 vaccine candidates in different stages of development. Out of these, two are in the most advanced stage. These are Covishield from SII and COVAXIN from the Indian Council of Medical Research (ICMR) and Bharat Bio-tech collaboration [21]. All trials are led by the ICMR and the National AIDS Research Institute (NARI) in Pune. In addition to the vaccines shown in Table 7.1, the Department of Biotechnology (DBT) and the Department of Science and Technology (DST) are supporting more than 20 vaccine candidates that are in different stages of development [12, 22]. The majority of the vaccine candidates would be available in multi-dose vials (2.5, 10, 20, and 50 doses per vial) [23]. Of these vaccine contenders, six are in the clinical trial phase. The rest are in the preclinical trial phase [24].

Table 7.1 Top eight potential COVID-19 vaccine candidates from various countries and networks
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The top contenders are the Covishield, COVAXIN, and Sputnik V. Covishield, a non-replicating adenovirus type five vector vaccine, is currently in Phase III human clinical trials in India. COVAXIN, an indigenously developed whole virion inactivated vaccine, is also in Phase III human clinical trials. Both these vaccine candidates were formally approved by the Central Drugs and Standards Committee (CDSCO) on January 3, 2021 [24, 25]. In the first week of August 2020, Sputnik V vaccine completed the Phase II trial successfully and entered Phase III. This Russian vaccine, developed by Gamaleya Research Institute, is built on a common cold virus and has shown to prod the immune system into producing antibodies. India is hosting larger human trials and will also manufacture this vaccine [26]. The Pfizer vaccine, developed by a German firm BioNTech, uses mRNA vaccine platform technology and has received two billion dollars from the US for 100 million doses [27]. Information related to potential vaccine candidates including names of the vaccines, manufacturers’ details, type of vaccines, doses of vaccines, phase of vaccine development, and the mode of administration is provided in Table 7.1.

In January 2021, the Government of the UK started a mix and match trial of Pfizer and AstraZeneca to give patients and doctors a wider choice of prevention approaches. Various other combination trials have been conducted such as the Sputnik V and AstraZeneca COVID-19 vaccine trial which is no less than a gamble and contradicts previous guidelines [28].

Figure 7.4 shows the mode of administration for candidate vaccines, which would be a concern once the vaccines are developed. Intratracheal and intranasal vaccines are easy to administer as they do not need trained health workers to administer them. The vaccines that are administered intramuscularly can increase vaccine hesitancy; the mode of administration could be a reason for lower vaccine uptake. Except for a few freeze-dried products, the majority of the vaccine are in liquid form. They have to be administered by intramuscular injection as two-dose regimens [23].

Fig. 7.4
figure 4

Source National Center for Biotechnology Information

Comparison of routes of administration of the ideal vaccines and the current COVID-19 vaccine candidates.

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Once the Phase I trial is completed, test license permission is required for manufacturing the COVID-19 vaccine for the preclinical test, examination, and analysis. This license is issued by the Central Drugs Standard Control Organization (CDSCO) in India. CDSCO has so far issued licenses to eight manufacturers in India [22]. Currently, the license is issued to the SII in Pune, Cadila Healthcare Ltd. in Ahmedabad, Bharat Biotech International Ltd. in Hyderabad, Biological E Ltd. in Hyderabad, Reliance Life Sciences Pvt Ltd. in Mumbai, Aurobindo Pharma Limited in Hyderabad, and Gennova Biopharmaceuticals Limited in Pune.

Leveraging Technology

One of the evident changes during the pandemic was that technology was leveraged which benefited the world in many ways. It allowed us to function from different regions of the world without the hassle of travel. It made work from home possible. Technology also enabled the dissemination of factual information to create awareness, and, more importantly, it provided the opportunity to make quick connections for working together during the crisis.

International bodies such as The Guardian [19], the London School of Hygiene and Tropical Medicine [29], and others have developed a ‘Vaccine Tracker,’ similar to the WHO COVID-19 infection tracker, to fast-track vaccines against COVID-19 vaccines. As India is on the forefront of vaccine manufacturing, the Indian Council of Medical Research (ICMR). India’s apex health research body has developed an online portal which provides information on COVID-19 vaccine development in India and abroad. This information is provided in several languages, in addition to English [30]. In India, the Prime Minister indicated that a digital health card program generating a Health ID, under the National Digital Health Mission (NDHM), would be deployed to ensure rapid immunization [31]. The Government of India launched a portal called CSIR Ushered Repurposed Drugs (CuRED) to provide information about tracking drugs, diagnostics, and devices as well as the current stage of clinical trials, partner institutions, and their role in the trials [32]. This signifies the interest of the Indian government in using technology for research and development of vaccines. The use of technology for vaccines is also vital for vaccine distribution and management.

India and International Alliances Fighting the Pandemic

Since as many as 214 countries are battling COVID-19, international cooperation and commitment are essential. Global leadership and dialog are needed to establish a coordinated strategy to harmonize regulatory requirements for meeting the demand. India’s support to its neighbors and to its partner countries developing COVID-19 vaccines can be gauged by its commitment and participation in the various alliances that have been formed globally. India plans to leverage domestic vaccine-manufacturing capacity and engage with all international players for the early delivery of vaccines not only in India, but also in other low- and middle-income countries [33].

India is a part of several global alliances including the COVID-19 Vaccine Global Access Facility (COVAX), ACT Accelerator, and DCVMN. COVAX, an initiative of 190 countries under the ACT accelerator, pools economic resources of its member countries to enable equitable access to the vaccine.

India has a central role in COVAX both as a mass producer of vaccines and as a regional leader. Although this engagement has been undermined by economically powerful countries such as the USA, China, and Russia, India can still use its diplomatic ties with its neighboring partners to develop manufacturing hubs that will further bring down vaccine prices and enable better local access to vaccines. India can also bring in countries that are not members of the consortium since it has the largest vaccine-manufacturing capacity of any single country [13].

Canada has reserved 350 million vaccine doses for a population of just over 38 million which equates to nine doses per person; it has a guaranteed supply from Pfizer and Moderna from the USA [34]. Australia has an agreement with AstraZeneca [13]. Currently, all these tie-ups are very unstable but can, in the future, divert a part of the already limited collective manufacturing capacity of these companies. And these tie-ups can also affect the ability of the private sector to supply vaccines [13]. As the vaccines are getting ready for rollout, 7.25 billion doses have already been pre-purchased by countries and organizations. India has ordered 500 million doses from AstraZeneca and one billion from Novovax. India has leveraged the power of its manufacturing agreements with the vaccine producers to pre-purchase 20% of the global share of vaccines. However, even this will not be sufficient to vaccinate India’s population [34].

Access to COVID-19 tools (ACT) accelerator is a ground-breaking global collaboration for accelerating the development, production, and equitable access to COVID-19 tests, treatments, and vaccines [35]. It is a framework to reduce the COVID-19 mortality rate with its investment plan which is being published by the organizations and includes the following three ‘pillars’ which show a path to accelerated development, equitable allocation, and scaled-up delivery of vaccines, therapeutics, and diagnostics.

The members of this group, committed to ensuring that all people have access to all the tools needed to battle COVID-19, work with partners to achieve this goal [36]. The goals of the three pillars are to make 500 million diagnostic tests available to low- and middle-income countries (LMICs), by mid-2021, provide 245 million courses of treatment to LMICs by mid-2021, and provide two billion vaccine doses, of which 50% will go to LMICs, by the end of 2021 [36] (Fig. 7.5).

Fig. 7.5
figure 5

Source Status Report and Plan September 2020—December 2021. World Health Organization

ACT accelerator vaccines pillar (COVAX) priorities critical path.

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Another network that India is supporting is the Developing Countries Vaccine Manufacturers Network (DCVMN) which provides a platform for organizations to come together regularly to share technical information, best practices, and prospects (Box 1). The network members have 181 vaccine projects in the research and development pipeline including vaccines against mosquito-borne diseases such as dengue, chikungunya, Zika, novel human papillomavirus, and pneumococcal conjugate vaccines. DCVMN has made progressive efforts with its members, particularly in the past five years, to contribute to reducing the burden of infectious diseases globally [37].

Box 1. Developing Countries Vaccine Manufacturers Network

The Developing Countries Vaccine Manufacturers Network (DCVMN) is a public health-driven alliance of corporate vaccine manufacturers as defined by the United Nation’s World Economic Situation and Prospect Report [38]. It is a unique international alliance of public and private organizations. It was formed in the year 2000 by ten vaccine manufacturers motivated by WHO and GAVI alliance. It aims to improve vaccine supply to developing countries where populations have been growing rapidly, the incidence of disease is high, and purchasing power is low. DCVMN is at the frontier to help solve the challenges which the emerging vaccine industry faces. The mandate of the network is to protect all people against known and emerging infectious diseases by improving the availability of high-quality vaccines globally. It recognizes the need for international scientific, technical, and economic cooperation [37]. Currently, there are 43 DCVMN members from 14 countries and territories. As of October 2019, 15 vaccine products of the member countries have been pre-qualified by the World Health Organization. In 2018, DCVMs supplied over 50% of the 2.36 billion doses of vaccines procured by UNICEF globally. These were valued at USD 1.453 billion and were GAVI-financed vaccines.

India has the highest score of pre-qualified (PQ) vaccine among all the DCVMN countries with 23 pre-qualified till December 31, 2019. Indonesia has 15 PQ vaccines [39].

While broad knowledge, research, and development are key to achieving an effective and safe vaccine, massive manufacturing requires global networks and countries around the world to support each other assuming that there is the high demand for the vaccine. To commence immunization globally and deploy available facilities, efficient and safe vaccines with efficient manufacture, distribution, and surveillance are key for saving time, resources, and most importantly, lives.

Vaccine Surveillance

The vaccine will hit in waves even after it has reached Phase IV as each candidate in the pipeline has its own timelines and distribution requirements. Therefore, governments are planning to rollout vaccines in a phased manner, targeting the most vulnerable groups early. Throughout the process, including the clinical trial phases and also when the vaccine is introduced for the general population, long-term and high-quality surveillance is needed to monitor the impact of the vaccination program and the changes in disease prevalence. Vaccine surveillance involves monitoring vaccine safety by performing high-quality safety trials, assessing the determinants of possible adverse reactions, and learning about preventable risk factors through public health surveillance [40].

Maintaining surveillance and laboratory capacity allows countries to leverage resources for monitoring other vaccine-preventable and non-preventable diseases. Maintaining diligent records of who received the vaccine, the lot number of the vaccine, number of vaccines scheduled for the next dose, and adverse effects, if any, particularly when vaccinating those with comorbid conditions, will be important to understand the impact of preexisting conditions and the effectiveness of the vaccine. Given the expedited nature of the COVID-19 vaccine trials, it will become a necessary attribute of the vaccination drive, as these vaccines are not tried on specific targets during the clinical trials [41]. Hence, a national identifier is required for COVID-19 immunization case tracking. The data collected will also be important for monitoring and responding to outbreaks and pandemics in the future. This was done in 2008 when WHO developed a network of regional surveillance and established standardized global sentinel hospital surveillance for rotavirus and invasive bacterial vaccine-preventable diseases (IBVPDs). The data collected described the disease burden for making decisions about rotavirus and pneumococcal conjugate vaccine (PCV) introduction and also showed short- and long-term impact globally, especially in regions with surveillance gaps for the rotavirus and pneumococcal conjugate vaccines. The vaccine surveillance platform data could also be used to leverage and monitor other vaccine-preventable diseases (VPDs).

The vaccine surveillance system can be helpful in many ways. To name a few, it can provide evidence for future studies, generate responses for similar outbreaks, and help to decide who should be vaccinated first—either to reduce mortality by vaccinating the elderly or to limit the spread of infection by vaccinating the working age population. It can also be helpful at the international platform. A study by GAVI in 2017 revealed that being a part of the VPD surveillance network provided benefits to countries through technical support and training in epidemiology and data management. It also provides linkages with partners, opportunities for network activities including research (e.g., the global pediatric diarrhea surveillance project), and in some cases, funding. Thus, the administration of the vaccine in a phased manner can enhance vaccine surveillance by offering continuous learning about the effectiveness and side effects of the vaccine.

Vaccine Supply, Stocking, and Financing

Government manufacturers need to ensure that there is adequate infrastructure for vaccine storage, handling, and transport even before the vaccine is ready for distribution. Vaccines are fragile and need to be stored at recommended temperatures and to be protected from light at every link in the cold chain. Vaccines exposed to temperatures outside the recommended ranges can result in reduced potency resulting in wastage of vaccines which is expensive. Therefore, with the current capacity in India of 28,932 cold chain points and 85,622 equipments, the government needs a solid action plan that involves governing bodies, manufacturers, and other stakeholders and uses the latest tested technologies and interventions.

India Action Plan

On August 15, 2020, Independence Day, the Prime Minister, while addressing the nation, announced that a blueprint for the production and distribution of the vaccine in the country was ready. Thereafter, the National Expert Group on Vaccine Administration for COVID-19, chaired by Vinod K Paul, a member of the National Institution for Transforming India (NITI) and co-chaired by the Union Health Secretary Rajesh Bhushan, was constituted [33]. In the same month, the WHO Strategic Advisory Groups of Experts on Immunization (SAGE) released a values framework for the distribution and prioritization of COVID-19 vaccination. The values framework provides guidance to policy-makers at the global, regional, and national levels, on the importance of using the best available science in epidemiology, public health, and economics while making the distribution plan. The values framework has six principles: human well-being, equal respect, global equity, national equity, reciprocity, and legitimacy. It also has twelve objectives for COVID-19 vaccine deployment [42]. The National Expert Group has developed a strategy for COVID-19 vaccine availability and delivery. The National Expert Group will take responsibility for the conceptualization and implementation of mechanisms for the creation of a digital infrastructure for inventory management and delivery mechanism of the vaccine, including tracking of the vaccination process, with particular focus on last mile delivery [12, 33].

The roles and responsibilities of the National Expert Group include

  1. 1.

    With the inputs and support of the Ministry of External Affairs (MEA), the National Expert Group facilitates Indian companies to develop vaccine candidates that they are interested in and also helps to provide relevant data to regulatory agencies [43].

  2. 2.

    The National Expert Group is responsible for keeping India on the forefront of ongoing global efforts to innovate, prepare, produce, and launch vaccine candidates to deal with the COVID-19 pandemic in India and the world [43].

  3. 3.

    The National Expert Group provides relevant testing data and helps to evaluate all vaccines.

The National Expert Group on Vaccines Administration for COVID-19 conducted a series of meetings since its inception in August 2020 to discuss broad parameters guiding the selection of COVID-19 vaccine candidates for the country and sought inputs from the Standing Technical Sub-Committee of the National Technical Advisory Group on Immunization (NTAGI). Along with NTAGI, the National Expert Group determined the procurement mechanisms for the COVID-19 vaccine and mobilized resources required for financing the vaccines [33]. The National Expert Group, along with the sub-committee of NTAGI, is responsible for preparing the guiding principles for prioritizing population groups for vaccination. India’s vaccination plan has identified approximately 30 crore (300 million people) that includes healthcare workers, the elderly, and people with comorbidities, to be vaccinated in Phase 1 and thus would require approximately 70–80 crore (700–800 million) doses for complete vaccination with the two doses and some wastage in transit [44]. The National Expert Group also ensures equitable and transparent delivery of the vaccine, addresses issues related to vaccine safety and surveillance, and coordinates both indigenous and international vaccine manufactures. It is also responsible for determining options in terms of delivery platforms, cold chain, and strategy for community involvement, by providing information and generating awareness and associated infrastructure for the rollout of the COVID-19 vaccine [12, 33]. The National Expert Group ensures that states do not procure vaccines through individual pathways. Two vaccine candidates, Covishield and COVAXIN, have been given emergency use authorization [24].

India is a member of the COVAX, ACT accelerator, DCVMN, and others fighting the pandemic. It led these groups in manufacturing vaccines, even before COVID-19 was declared a pandemic. India supports a domestic vaccine industry by setting up vaccine production facilities in other countries as well. India is exploring South Asian and African nations as destinations to create goodwill through scientific outreach. Africa accounts for only 0.1% of the world’s vaccine production even though it has a high prevalence of infectious diseases. There are other regional trading blocks like the East African Community, the South African Development Community, and the Economic Community of West African States that could be engaged for a COVID-19 vaccine and other vaccines relevant to Africa’s needs while meeting world demand [13].

The Indian government proposes to work on the following five distinct strategies for vaccine management after vaccines are manufactured:

  1. 1.

    Free distribution to immediate neighbors such as Bangladesh, Afghanistan, and other South Asian Association of Regional Cooperation (SAARC) countries.

  2. 2.

    Heavily subsidize supplies as a part of India’s international commitment for equitable distribution. Many African nations could benefit from this.

  3. 3.

    Strike market price purchased deals and provide guarantees for the supply of vaccines to countries.

  4. 4.

    Approach other countries for undertaking trials of Indian vaccines candidates.

  5. 5.

    Approach countries to co-produce Indian vaccines once approved [12].

Currently, Indian manufacturers are waiting for the government’s requirements that include initial procurement volumes, financial aid or support to scale-up manufacturing, and the stage at which the government will deliver on the commitment that it has made through the National Expert Group. The major players in India are representatives from SII, Bharat Biotech, Zydus Cadila, Gennova Biopharmaceuticals, and Biological E (BEL).

The world’s biggest COVID-19 vaccination program started in India in the month of January 2021. The program has four elements that include use of the digital platform Co-WIN, the formulation of an administration plan for vaccine logistics, cold chain management, communication and social mobilization, and recording adverse events following immunization (AEFI). Surveillance is undertaken at multiple levels [45] (Fig. 7.6).

Fig. 7.6
figure 6

Source Compiled by Author

India action plan for COVID-19 vaccine deployment.

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Logistics, Management, Distribution, and Data Management

For implementing the COVID-19 vaccination program, two mammoth tasks that cannot be ignored are putting together an efficient cold chain mechanism and a system for data management. Several United Nations organizations are procuring a large number of syringes to meet the demand. UNICEF is pre-positioning syringes and other necessary equipment and plans to procure approximately one billion syringes and safety boxes by 2021. The demand is for 620 million syringes that will be purchased for vaccinations against other diseases. GAVI and the Vaccine alliance will reimburse UNICEF for this procurement as it is a part of the COVAX facility [46]. India needs to do similar planning for the distribution of vaccines. The India Action Plan will include community cold chain networks by combining agricultural and medical cold chains wherever possible. But the biggest question is the development of vaccine presentation and packaging that optimize their affordability and programmatic ease of use in India as well as in other countries that have heavy burden of under-vaccinated people.

India will have to leverage its growing technological capabilities and tools to improve its vaccination rates and reverse the damage caused by COVID-19. India’s vaccination system, according to the Universal Immunization Program (UIP) plan for 2018–2022, is supported by more than 27,000 functional cold chain points of which only 750 (3%) are located at the district level and above. The rest are located below the district level. There are 2.5 million healthcare workers, 55,000 cold chain staff, and 76,000 freezers, refrigerators and other cold chain equipments, which are still inadequate for a population of 1.3 billion [47]. A social–ecological model-based framework, at the individual, community, and societal levels, will be needed to achieve sufficient immunization coverage [48]. To achieve this, the Indian government conducted a massive exercise to map out cold chain storage facilities across the country. To secure ‘the last mile connectivity’ and ensure that nothing goes wrong before the shot is administered, the National Expert Group has been working to pool the database of all public and private sector entities. The National Expert Group includes stakeholders who are a part of the pharmaceutical, food processing industry, the agro-businesses sectors as well as food delivery start-ups such as Swiggy and Zomato, to identify cold storages facilities such as fridges that can stock and distribute the vaccine at the taluka level [23]. To monitor the vaccine supply chain, beneficiary enrollment, and delivery system of the vaccine, Rajesh Bhushan, Health Secretary initially suggested use of Electronic Vaccine Intelligence Network (eVIN) [49]. However, a model similar to the Electronic Vaccine Intelligence Network (eVIN) was developed and deployed to distribute the COVID-19 vaccine. This is called the COVID vaccine intelligence network ‘Co-WIN’. eVIN currently monitors vaccine supplies, and the 25,000 cold chain points across the country in real-time.

eVIN has been enhanced to monitor the vaccination drive and to track the listed beneficiaries for vaccination in real time. It has been named Co-WIN. The Co-WIN app has two parts—one for the use of the beneficiary and the other is the back-end module for vaccinators [45]. The application can be downloaded free of cost. It is also used to provide a QR code generated beneficiary acknowledgment certificate. All the data from the block level is transferred in real time to the central server.

Box 2. Electronic Vaccine Intelligence Network (eVIN)

The Electronic Vaccine Intelligence Network (eVIN) is an Internet-based distribution system. It is an indigenously developed technology that digitizes vaccine stocks and monitors the temperature of the cold chain through a smartphone application. This technology was introduced to support the Universal Immunization Program. All cold chain handlers are provided smartphones with the eVIN application that allows the digitization of vaccine inventories. Every cold chain handler enters the net utilization of each vaccine at the end of every immunization day. This information is uploaded on the cloud server and can be viewed by program managers at the district, state, and national level through an online dashboard [50].

Variance in temperature during storage, handling, and transportation of the vaccine is major concern for global logistical strategies as millions of vaccine doses have to be transported from country to country and within the country itself.

The following are the elements for storage and transportation of vaccines:

  1. 1.

    Transportation vehicles fitted with freezers.

  2. 2.

    Freezers at the warehouses.

  3. 3.

    Freezers at hospitals and clinics.

  4. 4.

    Availability of dry ice, a by-product of ethanol production, can reduce the load on freezers. Ethanol production is dependent on gasoline demand which has dropped in the last eight months.

  5. 5.

    Life of the vaccine outside the freezer is also a potential challenge.

  6. 6.

    The other parts of the vaccine distribution puzzle are vials, stoppers, gauze, and alcohol swabs. These should be made available even before the vaccine reaches the public. Vaccine vials should be sterilized. They should be designed in such a way that they can withstand below-freezing temperatures. No compromise can be made in quality.

The temperature of the freezer should be between −50 and −15 °C, and the temperature of the refrigerator needs to be between 35 and 8 °C with the average temperature being 5 °C.

The ideal vaccine for a country like India and other such countries would be a ready-to-use dosage form which means that it would have a long shelf life when stored at ambient temperatures. Vaccines lose potency when exposed to higher temperatures. Re-cooling does not help especially with large numbers of doses. The vaccines currently available require refrigerated storage at +2 to +8 °C. Maintaining vaccines in a cold chain is challenging for both developed and developing countries as the cold chain alone contributes 80% of the total vaccination cost [47, 51]. The AstraZeneca-Oxford vaccine would pose less of a logistical challenge for India as it requires temperatures of +2 to +8 °C that can be achieved with most commercial freezers [13].

Apart from vaccine availability and coverage, the even bigger challenge for India is generating awareness to overcome vaccine hesitancy. The government needs to work with civil society organization (CSOs) to provide accurate information to the public about the vaccine and to burst myths and misconceptions. CSOs can reach hard-to-reach areas. They can reach mobile/migrants and people belonging to diverse cultural backgrounds with different religions, traditions, beliefs, and customs. Community participation is important for reaching higher levels of immunization. Various interventions can be adapted to countries to generate greater awareness. For example, the Core Group Polio Project in Baghpat, Bhopal, worked with local communities to create awareness on polio and other routine immunizations. As a part of this initiative, it encouraged village leaders to display messages on water tanks [52].

Funding

In order to prevent COVID-19, it is necessary to have a well-allocated budget for vaccine research, development, distribution, and administration. In early May 2020, the government proposed an allocation of Rs. 100 crores (13.67 million USD) from the PM-CARES (Prime Minister’s Citizen Assistance and Relief in Emergency Situations) and fund to support the development of the COVID-19 vaccine. This fund will support indigenous vaccines only [53]. With the vaccination cost of Rupees 450–550 (6–7 USD) per person, India has set aside Rupees 51,000 crore (7.65 billion USD) for vaccinating its 1.3 billion population [54]. The government announced a Rupees 900 crore (123.06 million USD) grant for the COVID Suraksha Mission that is to be used for vaccine development [21]. In October 2020, the Union Health Minister, Harsh Vardhan, announced that the government expects to receive 400–500 million doses of COVID-19 vaccine that would cover approximately 200–250 million people by July 2021. He also indicated that the states should plan for vaccine storage and distribution, an immensely challenging job [47].

Several international coalitions and national organizations are working to provide equitable access by making vaccines available to low-, low-middle, and middle-income countries. The costed plan presented has called for 31.3 billion USD in funding for diagnostics, therapeutics, and vaccines, of which 3.4 billion USD have been pledged so far [36]. Out of the total amount, 18.1 billion USD are needed globally for the next 18 months for two billion doses to be deployed by GAVI and CEPI by the end of 2021.

Challenges

Ethical Issues

The operational challenge is to ensure that the coverage of the vaccine is equitable [55]. Because of the pandemic, countries are suffering from economic losses that will take years to recover. There will be immense pressure on government to focus on vaccine manufacturing, distribution, and administration. This will likely result in diverting crucial, but limited, resources to the large-scale production of COVID-19 vaccines and will negatively impact the production of vaccines for other diseases. A survey conducted in June 2020 by UNICEF, GAVI, the Bloomberg School of Public Health, and other institutions found that already established vaccination programs were being interrupted in over 60 of the 85 countries surveyed as governments rushed to address COVID-19 on priority. The study underscored the need to co-opt unused capacity and set up new manufacturing facilities [13].

Another major issue is equitable access to vaccines. Several wealthy countries like the UK, EU, USA, and Japan are displaying nationalistic tendencies by pre-buying large stocks of vaccines for their people and reportedly signing deals to reserve 1.5 billion doses [56]. This may impact availability of vaccines for low- and middle-income countries.

The nation would need about Rs. 800 billion (10.9 billion USD) to procure and inoculate people living everywhere from the Himalayas to the remote Andaman & Nicobar Islands.

Adar Poonawalla, Head of the Serum Institute of India

Distribution and Administration

In addition to ethical issues, there are other challenges related to the distribution and administration of vaccines. One such challenge is the supply chain. Vaccine wastage, a very common problem, occurs during its distribution and administration. Studies conducted by WHO and UNICEF in different locations have shown a high vaccine wastage rate for various vaccines, ranging from 27 to 61% [57]. Vaccine wastage occurs during the time of administration, outreach, storage, and during the transition to vial dosage sizes. There are five to ten dose vaccine vials [58]. Regular monitoring of vaccine wastage is needed as vaccines are expensive commodities and newer vaccines are even more costly. Wastage of the COVID-19 vaccines can add to the financial burden on the country. Hence, a carefully phased administration strategy is required to avoid vaccine wastage. Other challenges are vaccine coverage, storage, and temperature fluctuations that can affect the shelf life of the vaccine.

Vaccine Hesitancy

Even if the government, international forums, and networks can manufacture the vaccine on time and in a sufficient amount, the issue of low vaccine uptake still exists. Assessing the reason for low vaccine uptake in a population and differentiating between those unvaccinated or under-vaccinated are essential. Vaccine hesitancy is a behavioral phenomenon. It is measured against the expectation of reaching a specific vaccination coverage goal. It is set on a continuum between those who accept all vaccines with no doubts, to those who completely refuse with no doubts [59]. In a survey conducted during July to September 2020 by the Massachusetts Institute of Technology (MIT) in collaboration with the John Hopkins University, Facebook in 67 countries that included India found that 10% of the total respondents refused to get vaccinated and 15% were not sure. Bangladesh showed the highest confidence in the COVID-19 vaccine [60].

The top three reasons reported by WHO and GAVI for vaccine hesitancy across all WHO regions have consistently been: (1) perception of risks and benefits, (2) lack of knowledge and awareness of vaccination and its importance, and (3) religion, culture, gender, and socioeconomic issues. Studies have found that vaccine hesitancy may be more and vaccine uptake low because of system failures such as stock-outs, limited availability of vaccination services, (time, place), and curtailment of vaccine services during conflicts and natural disasters [59]. Over the years, many reasons have been identified, but they usually boil down to two factors: confidence in the public health system and lack of awareness or misinformation about the vaccine.

People may not want to get vaccinated because they think the disease is not serious and does not warrant vaccination or they feel the vaccine is not safe. The anti-vaccine sentiment may also vary according to education levels. [61]

Prof K Srinath Reddy, President, Public Health Foundation of India

Concluding Comments

The development of vaccines for COVID-19 within 10 months has been an extraordinary achievement given that in the past it has taken 10–15 years to develop vaccines. Currently, six vaccines candidates are in different stages of development in India. Of these, two have been given emergency approval.

India is acknowledged globally to have robust capacity for manufacturing vaccines. India has formed partnership with all the key international organization that develop and distribute vaccines. India also has a long history of organizing and implementing immunization programs for vaccine-preventable diseases in pregnant women and children. However, organizing a national immunization program for preventing COVID-19 is challenging because of India’s large population and fragile health infrastructure.

State governments have developed plans for the storage and distribution of vaccines and implementation of the vaccination program. India has formulated its national action plan and rolled out its vaccination program for COVID-19 in January 2021. Currently, its vaccination program includes two vaccines: Covishield and COVAXIN. Important elements within the program are communications and advocacy to inform the people about the vaccine and its benefits and to encourage them to get vaccinated so that the problem of vaccine hesitancy, a major deterrent, can be prevented.

India and the world are at an important point in the history of the COVID-19 pandemic where the availability of the vaccine shows a ray of hope—a light at the end of a dark tunnel.