Accelerating the development of vaccine microarray patches for epidemic response and equitable immunization coverage requires investment in microarray patch manufacturing facilities

ABSTRACT

Introduction

There is a need for investment in manufacturing for vaccine microarray patches (vMAPs) to accelerate vMAP development and access. vMAPs could transform vaccines deployment and reach to everyone, everywhere.

Areas covered

We outline vMAPs’ potential benefits for epidemic preparedness and for outreach in low- and lower-middle-income countries (LMICs), share lessons learned from pandemic response, and highlight that investment in manufacturing-at-risk could accelerate vMAP development.

Expert opinion

Pilot manufacturing capabilities are needed to produce clinical trial material and enable emergency response. Funding vMAP manufacturing scale-up in parallel to clinical proof-of-concept studies could accelerate vMAP approval and availability. Incentives could mitigate the risks of establishing multi-vMAP manufacturing facilities early.

KEYWORDS:

• Microarray patches
• microneedle patches
• vaccine delivery
• pandemic preparedness
• coverage and equity
• product development
• pilot manufacturing facilities
• vaccine manufacturing
• vaccine development incentives
• De-risking strategies

1. Introduction: the unique promises of microarray patches for vaccine delivery

Microarray patches (MAPs), also known as microneedle patches, are single-dose devices used for intra- or transdermal delivery of vaccines and pharmaceuticals. MAPs consist of an array of multiple micron-sized projections, sometimes hundreds to thousands. There are different formats of MAPs, but the two important categories for vaccines are solid-coated vaccine-MAPs (vMAPs) and dissolving vMAPs. For solid-coated vMAPs, the microprojections are solid and coated with the vaccine, whereas for dissolving vMAPs, the microprojections contain the vaccine. In both cases, the vaccine is in a dry formulation. Upon application to the skin, the microprojections penetrate, and the dry vaccine is released from the coating of a solid-coated vMAP or in the case of a dissolving vMAP, the vaccine-containing microprojections themselves dissolve [1].

Representatives of the Biomedical Advanced Research and Development Authority (BARDA); Bill & Melinda Gates Foundation; Coalition for Epidemic Preparedness Innovations (CEPI); Gavi, the Vaccine Alliance; PATH; United Nations Children’s Fund (UNICEF); and the World Health Organization are pointing to the critical need to invest in pilot manufacturing facilities for vMAPs to accelerate their development and increase access to them, given their potential to rapidly deploy vaccines during an epidemic or a pandemic, and to increase the reach of vaccines within the Expanded Programme of Immunization in low- and lower-middle-income countries (LMICs) (see Table 1), to reach everyone everywhere, with a use case across high-income (HICs), middle-income (MICs), and LMICs.

Table 1. Overview of vMAPs’ potential benefits in relation to their use cases.

	Relevance of benefit to use case
Potential benefits of vMAPs	Epidemic or pandemic response	Immunization delivery in LMICs, especially for outreach
Ease of use [14,15] Since vaccine and device are integrated and there is no need for reconstitution	Delivery via pharmacies, self-administration, or by lesser-trained personnel, which could reduce disease exposure at mass immunization centers.	Delivery by lesser-trained personnel or self-administration.
Safety [38] Removal of reconstitution step and needle-free presentation prevent needlestick injury and errors in preparation	Facilitates self-administration or administration by lesser-trained personnel.	Facilitates self-administration or delivery by lesser-trained personnel. Reduces the number of adverse events following immunization as a result of incorrect reconstitution
Improved acceptability [15,38] Due to the needle-free presentation	Perception of being less painful may decrease vaccine hesitancy and increase uptake.
Potentially improved thermostability [15,38] The solid, dry presentation of vMAPs may improve thermostability	Facilitates stockpiling, storage, and transport during an epidemic or a pandemic.	Facilitates storage and delivery to the last mile.
Reduced wastage Single-dose presentation may decrease discarded vaccine doses in multidose vials	Reduced wastage would increase the number of doses available for coverage.	Less vaccine wastage would decrease missed opportunities for vaccination.
Potential for dose sparing [7] Administration by the intradermal route may increase immunogenicity of some vaccines, enabling lower-dosage immunization	Possibility to produce more doses from a given manufacturing footprint and to increase available volumes in short time span.	May contribute to reduction of total cost of delivery (per immunized child). [1]
vMAP delivery removes the need for ancillary supplies Syringes and glass vials are not required	Alleviates potential shortages during a pandemic.	Simplifies logistics for vaccine delivery. Eliminates needles and glass, which decreases immunization-related waste and need for waste management and increases ease of use.

Abbreviations: LMIC, low- and lower-middle-income country; vMAP, vaccine microarray patch.

During the response to the COVID-19 pandemic, bottlenecks occurred at different points in the vaccine supply chain. Initially, the amount of drug substance that could be manufactured was limiting [2]. Subsequently, there were shortages in primary packaging materials, such as glass vials [3], as well as in fill and finish capacity [4]. Then, distribution and delivery bottlenecks affected, and continue to affect, vaccine rollout in LMICs, including the availability of trained health-care workers [5] and ancillary supplies such as syringes [6], as well as the need to manage (ultra-) cold chain requirements.

vMAPs could, in principle, address a number of these issues and offer potentially significant benefits for epidemic and pandemic preparedness and response. Usage of vMAPs could reduce drug substance scarcity because vMAPs could reduce wastage compared with multidose presentations. vMAPs may further provide dose sparing through more efficient induction of immune responses for specific vaccines via the dermal route [7,8]. vMAPs are not dependent on traditional primary packaging components. Once dedicated vMAP manufacturing capabilities are built, they will provide an alternative strategy to produce and deploy vaccines that are distinct from and in addition to traditional fill and finish capacity, removing the need and therefore reducing the competition for ancillary supplies (such as glass vials, syringes, and sharps disposal) as well as for fill and finish manufacturing facilities. vMAPs do not need a supply of separate administration devices; thus, they are light and easy to distribute. Further, vMAPs potentially have better thermostability than traditional methods of vaccination. vMAPs require formulation of the vaccine in the dried state and dried formulations are known to stabilize vaccine candidates such as mRNA vaccines [9,10] and certain viral vector vaccines [11–13]. Their ease of use [14,15] also means that they could be delivered via pharmacies or mail and be self-administered. Therefore, they could lessen dependence on trained health-care workers and prevent disease exposure at mass immunization centers. Moreover, vMAPs may provide better acceptability by the public and health-care workers, which would overcome related vaccine hesitancy and contribute to increased coverage. In a white paper, it was estimated that, in a pandemic scenario similar to SARS-CoV-2, even if as little as 10% of the volume of bulk vaccine product were dedicated to vMAP application, disease burden could be reduced by 35% and deaths by 30% in the United States, and global economic impact could be reduced by US$500 billion over two years [16].

Similar potential benefits could also transform immunization delivery in LMICs, especially for outreach immunization. Easier administration and overcoming last-mile delivery hurdles could be of particular importance in these settings [17]. Given the substantial backsliding in immunization coverage in the wake of the Covid-19 pandemic as seen for example with MR coverage, [18] and the increase in zero dose and under-vaccinated children, [19] vMAPs could be an important tool to accelerate recovery given vMAPs’ potential to reach hard-to-reach populations.

Table 1 provides an overview of vMAPs’ potential benefits in relation to their use cases of epidemic or pandemic response versus immunization delivery in LMICs.

This paper focuses on the potential benefits of vMAPs and the need to invest in specialized manufacturing facilities to advance their development, however there are also challenges relative to the current approaches that will need to be addressed as briefly mentioned in the following section and as previously described [20].

2. Despite their potential benefits, vaccine microarray patches are still in early development and manufacturing is a key bottleneck

vMAPs have been in development for a few decades. However, only a few Phase 1 studies had been completed for vMAPs prior to 2020 [8,20,21]. The COVID-19 pandemic has catalyzed interest and investment in vMAPs, and there have been several recent developments in the vMAPs space. At the time of writing, at least two measles rubella MAPs are in Phase 1/Phase 2 trials, several COVID-19 MAPs are entering Phase 1 clinical trials, and more than 60 vMAPs are under preclinical evaluation for a variety of vaccines [21,22]. There is also renewed interest from organizations involved in pandemic preparedness and response, such as BARDA and CEPI, as well as from global health organizations involved in immunization for endemic diseases. For example, the Vaccine Innovation Prioritization Strategy partners – Gavi, the World Health Organization, UNICEF, the Bill & Melinda Gates Foundation, and PATH – have prioritized MAPs as a vaccine innovation to advance in LMICs [23,24]. Additionally, other public health organizations have prioritized a portfolio of needle-free technologies, including vMAPs.

As with any innovation in development, several hurdles need to be overcome before vMAP technology can deliver its potential benefits [25,26]. Developers and manufacturers will need to achieve new technical milestones, including significantly concentrating the bulk antigen to achieve dry formulation on a MAP to ensure delivery of a full dose and defining the manufacturing sterility requirements for regulatory approval. Critical quality attributes and associated test methods must be defined for each vMAP product, a process that is underway both by individual developers as well as in efforts to harmonize across the technology class [27,28]. Administration of a vMAP may be simpler than a needle and syringe vaccine, but it will be different from current best practices, which will require assessing acceptability among health-care workers and users and feasibility of use within immunization programs. The regulatory pathway for a combination product composed of both a vaccine and a MAP delivery device also will need to be clarified, which may not occur until an initial candidate vMAP reaches advanced development.

All the elements listed above are needed for vMAPs’ success [20]. However, arguably one of the most significant bottlenecks to bringing the first vMAPs to licensure is the lack of an established production line for producing vMAPs at commercial scale. A pilot manufacturing facility and scale-up are thus needed for vMAPs’ accelerated development and licensure.

So far, data from clinical trials with vMAPs are limited, and currently do not involve vaccine platforms that are now being developed for several endemic vaccines, in the context of the need for rapid epidemic response, such as mRNA vaccines or viral vector-based vaccines. More work is needed to show that microneedles can preserve the integrity of fragile and temperature sensitive vaccines such as mRNA vaccines [29]. Moreover, the demand for and future uptake of vMAPs are uncertain [29]. This situation is unlikely to change until proof of concept (PoC) is established across multiple vaccine targets, which will take several years. However, no vMAP will proceed beyond the end of Phase 2 without the establishment of a vMAP pilot line, i.e. that can be used as a small-scale late development stage/commercial facility for initial supply. A review of MAP production readiness across the industry found significant variation in readiness, but a number of developers are at a stage in design, materials, process control, quality management, etc. to be ready to execute a transition to pilot scale manufacturing capacity, if investment was available [30]. Proof-of-concept high-speed production equipment has been demonstrated for at least one vMAP technology even if challenges remain [31,32]. For solid-coated vMAPs, the key manufacturing challenge is ensuring the coating is on the tip of the microprojection, so that the full dose is delivered at time of vaccination, while minimizing wastage of antigen in the coating process. For dissolving vMAPs, producing molds and establishing a continuous rather than batch-based process for drying are key to ensure a robust manufacturing process. Both vMAPs need to concentrate the vaccine and maintain vaccine stability throughout the manufacturing process. Given this maturity stage, to set up a line in an existing or new facility could take from two to several years and would depend on the existing infrastructure.

3. De-risking strategies and incentive mechanisms to accelerate development and uptake: lessons learned from the COVID-19 pandemic and pandemic preparedness and response programs

While investing in manufacturing in parallel to Phase 1 and 2 studies entails some risks compared with waiting for clinical PoC, incentives and de-risking strategies could be leveraged to mobilize and de-risk the needed investments. This has been demonstrated by various examples from the COVID-19 pandemic and pandemic preparedness and response programs, as outlined below.

3.1. The COVAX mechanism used a mix of incentives to accelerate the development of COVID-19 vaccines

The most recent example is, of course, the response to the COVID-19 pandemic. Funding to manufacturing at risk was a key component in accelerating the availability of COVID-19 vaccines. The COVAX mechanism (which brings together governments, global health organizations, manufacturers, scientists, the private sector, civil society, and philanthropic organizations with the aim of providing innovative and equitable access to COVID-19 vaccines) used ‘push incentives,’ subsidizing developers and manufacturers directly for pharmaceutical research and development and manufacturing capacity while vaccine candidates were still in early development [30]. COVAX also provided ‘pull incentives,’ paying for performance via a reward price and/or delivery of products. These included the Advanced Purchase Commitment (APC), which provided individual vaccine developers and manufacturers with ‘volume guarantees’ for vaccines before they were licensed, as well as the Advance Market Commitment (AMC), a market-wide demand guarantee, available to any manufacturer, to buy an overall quantity of vaccines if and when they were ready. These mechanisms incentivized developers and manufacturers to invest in vaccine development and manufacturing at risk [31,33].

Kremer et al. [34] explored whether buyer contracting was more efficient when using APCs or a framework AMC. They found that, while a well-designed APC was more efficient for late-stage candidates, an AMC could be efficient for early-stage candidates. In this context, competition (more than three or four developers, as was the case with COVID-19 vaccines) would be needed to improve efficiency in terms of speed of entry, quality of the vaccine, and potential for price competition. Taken at face value, this finding could imply that an AMC-type pull incentive could be more appropriate for vaccine innovations in early development, such as vMAPs.

3.2. Investment in a variety of platform technologies under adaptable agreements allowed the US government to quickly pivot to the development of COVID-19 vaccines

In the United States, BARDA supports the development of medical countermeasures, such as vaccines, therapeutics, and diagnostics, against a broad range of agents, including influenza, emerging infectious diseases, and chemical, biological, radiological, and nuclear threats. BARDA prioritizes the use of flexible agreements and programs to support developers and manufacturers that broaden access to medical countermeasures, support sustainability and improvements in vaccine delivery, and ramp up production capacity.

BARDA’s COVID-19 response illustrates the impact that these investments have had over the past 15 years. For example, BARDA’s investment in a variety of platform technologies allowed the US government to quickly pivot to the development of COVID-19 vaccines. Moreover, BARDA, in collaboration with the US Department of Defense’s Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, along with others within the US government, funded COVID-19 vaccine production through their support for research, development, and procurement of multiple COVID-19 vaccines. Funding several COVID-19 vaccine candidates resulted in multiple successfully approved vaccines and widespread availability of vaccinations.

BARDA’s Division of Research, Innovation, and Ventures, in collaboration with the Influenza and Emerging Infectious Disease Division, also plays a key role in ‘seed’ funding for selected vaccine platforms, in particular needle-free vaccines, via the Beyond the Needle program. This program provides contracts to support early and preclinical work on needle-free vaccines by promising companies that are developing novel vaccine platforms for BARDA-relevant pathogens. BARDA’s multiple programs, which specialize in distinct pathogen types, all share a deep interest in vMAPs as a means of promoting rapid, efficient immunization in a wide variety of settings. Additionally, BARDA’s Beyond the Needle program and Emerging Infectious Disease Division have funded several MAP companies, some of which have transitioned to larger levels of funding support via venture capital, federal funders, and pharmaceutical companies.

These diverse investments from BARDA contribute to de-risking the development of innovative vaccines and ensure readiness and faster access to vaccines in the event of a pandemic, as demonstrated by the COVID-19 pandemic.

3.3. CEPI is proposing a 100-day mission to compress vaccine development timelines for the next pandemic through at-risk investments in a range of vaccine platform technologies

In responses to epidemics, speed is critical to limiting the impact of the outbreak both on human lives and on the economy. That is why CEPI has proposed the 100-day mission to compress vaccine development timelines to 100 days, about a third of the time that it took the world to develop a COVID-19 vaccine. In addition, manufacturing these vaccines at scale and making them equitably accessible to the people who need them are equally important to achieving the goal of reducing or even eliminating the future risk of pandemics and epidemics.

The key to rapid response is preparedness for the unknown. CEPI has invested in a range of vaccine platform technologies that target several known high-priority pathogens but can be adapted rapidly to new threats. This approach allows a large part of the development – including clinical, manufacturing, and regulatory aspects – to be performed during the interpandemic period; thus, it accelerates vaccine availability during a pandemic. Nevertheless, a certain level of risk needs to be accepted. For example, to achieve the 100-day mission, investments in manufacturing scale-up are required before clinical and regulatory success have been secured.

Applying these learnings to vMAPs, investments in the platform technology are required now in order to have an impact on the next outbreak. To mitigate risk, it is crucial for the technology and manufacturing facility to be flexible so that they can be applied to different vaccine targets and MAP platforms. Next to the pilot facility, development of the vMAP formulation and process for various vaccine technology platforms is essential. It is also important that a facility is used in between epidemics – for example, for routine vaccines – both to justify the investment and to keep the facility ready for rapid response.

The importance of geodiversified manufacturing has also become clear during the COVID-19 pandemic. In a pandemic situation, export of consumables, raw materials, and vaccine product may be restricted, so regional manufacturing is critical to ensuring access. Therefore, when investing in a technology and facility, the flexibility to scale out as well as scale up, and to rapidly establish new manufacturing sites also in lower-resource settings, are important considerations.

For certain known pathogens, the creation of a vaccine stockpile could be considered to enable immediate response to an outbreak. The stockpiled doses do not necessarily need to be of a licensed vaccine, but they should be of a quality that would allow emergency use. This requires engagement with regulators before an outbreak occurs to align on quality, testing requirements, and deployment scenarios. Because of their small size and good thermostability, vMAPs could be an ideal presentation for such a stockpile. The size, quality, and presentation of the stockpile depend on the target pathogen and its epidemiology, as well as the use case for deployment of the doses.

3.4. Approaches explored to diversify vaccine manufacturing footprint suggest ‘leapfrogging’ to new platforms

Currently, significant efforts are ongoing to establish vaccine manufacturing capacity in Africa to ensure equitable access to vaccines for the next pandemic and to vaccines in general [35]. Business models explored in this context showed that models should have high feasibility for implementing disruptive technologies to respond to the need for vaccines in case of a pandemic but also to be sustainable beyond pandemic response [36]. While not completely translatable to MAPs and other geographies, some of the characteristics of the proposed models could be relevant for a technology such as MAPs.

In the ‘platform leapfrog’ model, new manufacturers would start production of novel vaccine platforms, such as mRNA or DNA, rather than ‘traditional’ vaccines. Investing in these platforms could allow for economies of scale at much lower volumes given the smaller production footprint they require. This could apply to vMAPs should their potential to act as a platform delivery technology for various vaccine targets be realized. Another business model proposes a focus on outbreak vaccines (since some outbreak-prone diseases are historically underserved in the vaccine market), in which manufacturers may need to complement production of outbreak vaccines with routine products to ensure full use of production capacity and to improve the business case. This model may be particularly relevant for vMAPs given their potential benefits for outbreak and pandemic response. A combination of the platform leapfrog and outbreak models, which would bring together the platform potential and benefits for outbreak response, may be an interesting approach to explore for vMAPs.

All of the highlighted examples – COVID-19 vaccine development, current efforts in pandemic preparedness and response, and the expansion of vaccine manufacturing footprint – show that innovation development can be accelerated with significant at-risk investments. In addition, given MAPs’ potential to be a transformative platform technology for both epidemic preparedness and response and for increasing vaccine reach in LMICs, there is likely an opportunity to leverage some of these investments and lessons learned for innovations like vMAPs.

4. Investing in manufacturing facilities at risk could accelerate the availability of vMAPs, including during epidemics and pandemics

This article focuses on calling for investments to fund pilot-scale manufacturing for MAPs – as defined in the text box below – to demonstrate that vMAPs can be produced at scale for initial licensure and epidemic preparedness. A pilot microarray patch production line is defined, for the purpose of this discussion, as one that produces Good Manufacturing Practice–compliant vaccine microarray patches for clinical evaluation in pivotal licensure studies and potentially initial commercial supply. This production line would be a (semi) automated line with a potential annual output in the range of 10 to 15 million microarray patches per year.

Generally, potential vaccine MAP funders and vaccine developers are opting for a risk-averse, traditional step-wise approach, preferring to wait for clinical PoC data before committing to investing in manufacturing capacity. However, to accelerate vMAPs’ availability, investments to establish pilot manufacturing capabilities are required now, in parallel to Phase 1 and 2 clinical studies and thus at risk. Waiting for PoC across multiple vaccine targets will delay licensure and use by several years. The delay in vaccine licensure if there is no ‘at risk’ investment in parallel to PoC studies is based on the additional time needed to 1) develop a partnership between a vaccine manufacturer and MAP developer, 2) raise the investment for the pilot facility and phase III efficacy study, 3) construct the facility and perform scale up/engineering runs for the clinical trial material, and 4) validate the facility to produce material to include in a pivotal licensure study. Furthermore, as vMAPs have the potential to act as a platform technology for vaccine targets (i.e. a given MAP technology and manufacturing line could be applied to various vaccine targets), cost sharing to build multi-vaccine pilot facilities could be the most effective way to de-risk investment and incentivize vaccine manufacturers, and to accelerate the availability of several vMAPs.

To enable vMAPs to proceed beyond the end of Phase 2, a vMAP pilot line is required, with investments at a minimum of $20 to $50 million based on authors’ estimates, which would assist with establishing the MAP line in a pilot manufacturing facility. Cost estimate ranges for pilot and commercial MAP facilities were developed by the authors in consultation with multiple MAP companies, producers of vaccine/device combination product manufacturing equipment, and vaccine manufacturing facility construction experts. Investing in a vMAP pilot facility would catalyze the development and accelerate the availability of vMAPs by:

• Enabling the production of clinical trial material for pivotal clinical studies and potentially initial licensure.

• Establishing manufacturing PoC for vMAP production at commercial scale.

• Enabling more detailed assessments of the costs of producing vMAPs and providing input for further investment needs.

• Enabling the evaluation of the scalability of MAP technologies.

• Enabling emergency response with candidate vaccines in case of emergency use listing for high-priority vaccines.

Accelerating the development and availability of vMAPs through at-risk investments in a pilot manufacturing facility could ensure that the modality, at a minimum, will have undergone a minimum set of clinical trials ahead of the next epidemic. This means emergency use listing of the first vMAP could be available in less than five years. This facility could enable pressure testing of regulatory requirements (e.g. sterility of production), as well as production capabilities, including what is needed to ensure scale-up. Understanding production costs could also inform the ‘dual market use’ business case (HICs and LMICs use), enabling discussions on what is needed for long-term sustainability. Learnings could be extrapolated to inform equitable manufacturing practices, including technology transfers. In the event of an epidemic, this could be rapidly scaled, if needed. A multi-vaccine pilot facility could also increase flexibility, which is important given uncertainties in which pathogen may cause the next epidemic.

When PoC across multiple vaccine targets are demonstrated and/or sufficient demand materializes, it is assumed that further investments will be needed, and commercial facilities will need to scale up to have an annual output in the range of 100 million up to 300 million doses. Commercial production capacity targets were informed by the authors’ preliminary production economics analyses to assess how vMAP prices may be reduced by larger production scale, as well as preliminary demand models for various scenarios in pandemic response (unpublished data) and measles-rubella vaccination [37].

5. A cost-sharing model between global stakeholders and vMAP developers is needed now to de-risk investment in vMAPs and accelerate their development

Two pilot facility designs could accelerate timelines while de-risking investments: (i) a pilot facility that could produce one specific vMAP format for different vaccine targets, or (ii) a pilot facility that could produce different MAP formats for different vaccine targets. The high-level advantages and risks of these two options are outlined in Table 2.

Table 2. Proposed facility designs for a vMAP pilot manufacturing facility and the perceived advantages and risks for the investment required.

Proposed facility design	Assumptions	Advantages	Risks
Specific vMAP format pilot facility	Such a pilot plant would be dedicated to a specific MAP developer and its MAP format and sufficiently flexible to allow the manufacturing of MAPs for different vaccine targets, either in parallel or sequentially depending on the size of the plant.	This strategy would allow focused funding and allocation of resources and would be the lowest cost option. It also is likely to be the option to move the fastest and thus to allow the first vMAP to reach the market the fastest.	If funding were limited to support only the establishment of one MAP technology, this strategy would come with the risks inherent in having to choose a specific MAP developer before a comprehensive clinical and analytical dataset is available; while this may accelerate vMAPs to the market, the ‘first’ MAP technology may ultimately experience limited uptake in LMICs and/or may not be the best MAP in terms of product attributes or production cost.
Multi-MAP format pilot facility for high-priority vMAPs	Such a multi-MAP format pilot facility would be capable of producing different MAPs technologies (or formats) for different vaccine targets.	This strategy would enable evaluation of the scalability of different MAP technologies (or formats), as well as assessment of which MAP technologies may have the best product attributes and production cost, while potentially enabling early competition/diversification. It might be more economical as some aspects (e.g. quality management system, release assays, infrastructure) might be shared across MAPs technologies (formulation, packaging, etc.).	To increase the probability of successful commercialization, major MAP technology developers may need to align on a common facility design and specifications across several MAP designs. It is likely that this strategy would add complexity, with potential impact on time to reach the market. Feasibility may be limited for most advanced MAP technologies as it may be too late to redefine attributes to enable facility design standardization. Key aspects, such as the MAPs production lines and the nature of the input materials required for manufacture, are likely to be specific for each MAP format. For example, there will be limited overlap between the line equipment for coated MAPs versus that for dissolving MAPs.

Abbreviations: LMIC, low- and lower-middle-income country; MAP, microarray patch; vMAP, vaccine microarray patch.

As highlighted in Table 2, these two options would come with advantages and risks that will need to be further analyzed. Regardless of which design is chosen, investing now and at risk is needed to accelerate the availability of vMAPs. Recent investments of the Australian government in a pilot manufacturing plant for vMAPs shows that such investments are needed and can be done [38].

6. Conclusion

As the need increases for rapid, high-volume vaccines to emerging pathogens, alternatives to conventional needle-based vaccines to allow easier, faster, and broader rollout become high-priority public health goods. Given the substantial backsliding in immunization coverage in the wake of the Covid-19 pandemic, and the increase in zero dose and under-vaccinated children, we believe that there is an overwhelming global public health need – now more than ever – to develop innovations to prepare for and prevent against outbreaks of both endemic diseases such as measles as well as future pandemic outbreaks. vMAPs have great potential for meeting these needs; however, accelerating their availability requires immediate investment in pilot manufacturing capabilities. The current momentum around improving pandemic preparedness and response is an opportunity not to be missed. This will require innovative incentives and cost-sharing and de-risking strategies that, as demonstrated by past and current lessons learned, would be best funded and implemented through a broad collaboration of stakeholders who are active from early-stage development through procurement. This would mitigate risk and ensure an end-to-end view of the development and uptake pathway from the start. Herewith, to maximize the likelihood of success, all stakeholders – such as MAP developers, vaccine manufacturers, funders, donors, and investors – will need to join forces to invest in and accelerate vMAPs now.

7. Expert opinion

Global public health organizations and organizations involved in pandemic preparedness and response are calling for broader, intensified, and immediate collaboration among all public health actors – global public health organizations, MAP developers, vaccine manufacturers, funders, donors, and investors – to invest in and accelerate vMAPs availability.

vMAPs have the potential to transform the delivery of epidemic, pandemic, and endemic vaccines. The COVID-19 pandemic has shown that they are urgently needed to increase the reach of vaccines to everyone everywhere in a timely manner. If available, vMAPs would position the world to respond more effectively to the next pandemic and to reach global vaccination goals, including increased equity in LMICs. With the appropriate investment, the first vMAPs could be licensed by 2027. If investment in manufacturing is deferred until clinical PoC, the development of vMAPs is likely to languish for several more years, with earliest licensure not expected before the mid-2030s.

The development of vaccines in response to the COVID-19 pandemic has shown that the traditional vaccine development timelines can be dramatically shortened with political commitment, at-risk funding, and intensive collaboration between all actors. Similar strategies could result in increased capital for at-risk investment in vMAP pilot production facilities and for supporting partnerships between MAP developers, vaccine manufacturers, and contract development and manufacturing organizations. It is possible that, with investments made now, one or two pilot facilities could be established in two to three years and the first licensure studies could be initiated in 3 years. This would likely incentivize additional investments in research and development, resulting in a global research and development portfolio with multiple vMAPs in development for both epidemic and endemic vaccines.

This is the only strategy that would truly accelerate the availability of vMAPs by several years, ultimately make new tools available to decrease the impact of future epidemics or pandemics, and increase equitable coverage of vaccines in LMICs, including reaching zero-dose children.

Article highlights

• vMAPs could transform vaccine delivery for epidemic response and outreach in LMICs.

• vMAPs are not yet authorized; it is not expected that any vMAP will be approved for use without establishing a manufacturing line or facility. Investing at risk could accelerate vMAP availability.

• Pandemic preparedness and response show that de-risking strategies accelerate vaccine innovations uptake.

• Cost sharing to build multi-vMAP facilities could de-risk investments, improve sustainability, and ensure availability in epidemics situations.

• The momentum and investments in pandemic preparedness provide an opportunity to advance vMAPs through global health stakeholder collaboration.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

PATH’s contribution to this paper was funded with UK aid from the UK government through the Foreign, Commonwealth and Development Office under project 300341-112. WHO’s contribution to this manuscript was funded from the Bill and Melinda Gates Foundation under grant INV-005318. The authors alone are responsible for the views, opinions, and/or findings expressed in this article, and these do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. In particular, these views do not necessarily reflect the views of the Foreign Commonwealth and Development Office. They also should not be construed as an official US Department of Defense or Department of the Army position, policy, or decision.