A review of potential use cases for measles-rubella, measles-mumps-rubella, and typhoid-conjugate vaccines presented on microarray patches.

As an innovative vaccine delivery technology, vaccine microarray patches could have a meaningful impact on routine immunization coverage in low- and middle-income countries, and vaccine deployment during epidemics and pandemics. This review of the potential use cases for a subset of vaccine microarray patches in various stages of clinical development, including measles-rubella, measles-mumps-rubella, and typhoid conjugate, highlights the breadth of their applicability to support immunization service delivery and their potential scope of utilization within national immunization programs. Definition and assessment of the use cases for this novel vaccine presentation provide important insights for vaccine developers and policymakers into the strengths of the public health and commercial value propositions, and the preparatory requirements for public health systems for the future rollout of vaccine microarray patches. An in-depth understanding of use cases for vaccine microarray patches serves as a foundational input to overcoming the remaining technical, regulatory, and financial challenges. Additional efforts will help to realize the potential of vaccine microarray patches as part of the global effort to improve the coverage and equity of national immunization programs.

An Application of an Initial Full Value of Vaccine Assessment Methodology to Measles-Rubella MAPs for Use in Low- and Middle-Income Countries.

Measles and rubella micro-array patches (MR-MAPs) are a promising innovation to address limitations of the current needle and syringe (N&S) presentation due to their single-dose presentation, ease of use, and improved thermostability. To direct and accelerate further research and interventions, an initial full value vaccine assessment (iFVVA) was initiated prior to MR-MAPs entering phase I trials to quantify their value and identify key data gaps and challenges. The iFVVA utilized a mixed-methods approach with rapid assessment of literature, stakeholder interviews and surveys, and quantitative data analyses to (i) assess global need for improved MR vaccines and how MR-MAPs could address MR problem statements; (ii) estimate costs and benefits of MR-MAPs; (iii) identify the best pathway from development to delivery; and (iv) identify outstanding areas of need where stakeholder intervention can be helpful. These analyses found that if MR-MAPs are broadly deployed, they can potentially reach an additional 80 million children compared to the N&S presentation between 2030-2040. MR-MAPs can avert up to 37 million measles cases, 400,000 measles deaths, and 26 million disability-adjusted life years (DALYs). MR-MAPs with the most optimal product characteristics of low price, controlled temperature chain (CTC) properties, and small cold chain volumes were shown to be cost saving for routine immunization (RI) in low- and middle-income countries (LMICs) compared to N&S. Uncertainties about price and future vaccine coverage impact the potential cost-effectiveness of introducing MR-MAPs in LMICs, indicating that it could be cost-effective in 16-81% of LMICs. Furthermore, this iFVVA highlighted the importance of upfront donor investment in manufacturing set-up and clinical studies and the critical influence of an appropriate price to ensure country and manufacturer financial sustainability. To ensure that MR-MAPs achieve the greatest public health benefit, MAP developers, vaccine manufacturers, donors, financiers, and policy- and decision-makers will need close collaboration and open communications.

Exploring potential applications of measles and rubella microarray patches (MR-MAPs): use case identification.

Introduction: Innovative vaccine products will be critical in helping to address the existing implementation barriers that have prevented the achievement of the measles and rubella (MR) vaccine coverage targets. Overcoming those barriers will be necessary to achieve the "Immunization Agenda 2030" goals. Microarray patches (MAPs), an innovative needle-free delivery device currently in clinical development, can be a potential game changer in this respect and contribute to the equitable delivery of vaccines in low- and middle-income countries and pandemic preparedness and response. Developing in-depth knowledge of the most desired and impactful uses of MRMAPs can prove critical to identifying the critical attributes of the target product profile, informing policy and adoption decisions, and helping to evaluate the potential public health and economic value of this technology. The first step in this process is the definition of the potential use cases for MR-MAPs, i.e., where and how this product is most likely to be used within the immunization programme. Methods: By applying a design-based user-centric approach, we implemented a three-step process, including a desk review, a survey, and interviews, to define the most relevant use cases for MR MAPS. Results: Six use cases have been identified as relevant across all different countries and immunization programme designs and validated by experts. Discussion: The identified use cases have already informed the demand estimate for MR-MAPs and provided the foundation for developing an initial full vaccine value assessment. We believe that, in the future, they will be highly valuable in ensuring that the roll-out of this promising innovation is designed in a way that maximizes the impact, particularly in populations and countries that are most in need.

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

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.

Accelerating the Development of Measles and Rubella Microarray Patches to Eliminate Measles and Rubella: Recent Progress, Remaining Challenges.

Measles and rubella microarray patches (MR-MAPs) are critical in achieving measles and rubella eradication, a goal highly unlikely to meet with current vaccines presentations. With low commercial incentive to MAP developers, limited and uncertain funding, the need for investment in a novel manufacturing facility, and remaining questions about the source of antigen, product demand, and regulatory pathway, MR-MAPs are unlikely to be prequalified by WHO and ready for use before 2033. This article describes the current progress of MR-MAPs, highlights challenges and opportunities pertinent to MR-MAPs manufacturing, regulatory approval, creating demand, and timelines to licensure. It also describes activities that are being undertaken by multiple partners to incentivise investment in and accelerate the development of MR-MAPs.

Estimating the future global dose demand for measles-rubella microarray patches.

Background: Progress toward measles and rubella (MR) elimination has stagnated as countries are unable to reach the required 95% vaccine coverage. Microarray patches (MAPs) are anticipated to offer significant programmatic advantages to needle and syringe (N/S) presentation and increase MR vaccination coverage. A demand forecast analysis of the programmatic doses required (PDR) could accelerate MR-MAP development by informing the size and return of the investment required to manufacture MAPs. Methods: Unconstrained global MR-MAP demand for 2030-2040 was estimated for three scenarios, for groups of countries with similar characteristics (archetypes), and four types of uses of MR-MAPs (use cases). The base scenario 1 assumed that MR-MAPs would replace a share of MR doses delivered by N/S, and that MAPs can reach a proportion of previously unimmunised populations. Scenario 2 assumed that MR-MAPs would be piloted in selected countries in each region of the World Health Organization (WHO); and scenario 3 explored introduction of MR-MAPs earlier in countries with the lowest measles vaccine coverage and highest MR disease burden. We conducted sensitivity analyses to measure the impact of data uncertainty. Results: For the base scenario (1), the estimated global PDR for MR-MAPs was forecasted at 30 million doses in 2030 and increased to 220 million doses by 2040. Compared to scenario 1, scenario 2 resulted in an overall decrease in PDR of 18%, and scenario 3 resulted in a 21% increase in PDR between 2030 and 2040. Sensitivity analyses revealed that assumptions around the anticipated reach or coverage of MR-MAPs, particularly in the hard-to-reach and MOV populations, and the market penetration of MR-MAPs significantly impacted the estimated PDR. Conclusions: Significant demand is expected for MR-MAPs between 2030 and 2040, however, efforts are required to address remaining data quality, uncertainties and gaps that underpin the assumptions in this analysis.

Strategies for vaccine-product innovation: Creating an enabling environment for product development to uptake in low- and middle-income countries.

Vaccine-product innovations that address barriers to immunization are urgently needed to achieve equitable vaccine coverage, as articulated in the new Immunization Agenda 2030 and the Gavi 5.0 strategy. In 2020, the Vaccine Innovation Prioritisation Strategy (VIPS) prioritized three innovations, namely microarray patches (MAPs), heat-stable and controlled-temperature chain (CTC) enabled liquid vaccine formulations and barcodes on primary packaging. These innovations were prioritized based on the priority immunization barriers that they may help overcome in resource constrained contexts, as well as by considering their potential impact on health, coverage and equity, safety, economic costs and their technical readiness and commercial feasibility. VIPS is now working to accelerate the development and lay the foundation for future uptake of the three priority vaccine-product innovations, with the long term-goal to ensure equitable vaccine coverage and increased impact of vaccines in low- and middle- income countries. To inform our strategic planning, we analyzed four commercially available vaccine product-innovations and conducted interviews with individuals from 17 immunization organizations, and/or independent immunization experts. The findings are synthesized into an 'innovation conundrum' that describes the challenges encountered in developing vaccine-product innovations and a vaccine-product innovation 'theory of change', which highlights actions that should be undertaken in parallel to product development to incentivize sustainable investment and prepare the pathway for uptake and impact.

Vaccine innovation prioritisation strategy: Findings from three country-stakeholder consultations on vaccine product innovations.

As part of the Vaccine Innovation Prioritisation Strategy (VIPS), three immunization-stakeholder consultations were conducted between September 2018 and February 2020 to ensure that countries' needs drove the prioritization of vaccine product innovations. All consultations targeted respondents with immunization program experience. They included: (1) an online survey to identify immunization implementation barriers and desired vaccine attributes in three use settings, (2) an online survey to identify and evaluate the most important immunization challenges for ten exemplar vaccines, and (3) in-depth interviews to better understand the perceived programmatic benefits and challenges that could be addressed by nine innovations and to rank the innovations that could best address current challenges. The first consultation included responses from 442 participants in 61 countries, representing 89% of the 496 respondents who correctly completed at least one section of the online survey. For facility-based settings, missed opportunities for vaccination due to reluctance to open multidose vaccine vials was the barrier most frequently selected by respondents. In community-based (outreach) and campaign settings, limited access to immunization services due to geographic barriers was most frequently selected. Multidose presentations with preservative or single-dose presentations were most frequently selected as desired vaccine attributes for facility-based settings while improved thermostability was most frequently selected for outreach and campaign settings. The second online survey was completed by 220 respondents in 54 countries. For the exemplar vaccines, vaccine ineffectiveness or wastage due to heat or freeze exposure and missed opportunities due to multidose vial presentations were identified as the greatest vaccine-specific challenges. In-depth interviews with 84 respondents in six countries ranked microarray patches, dual-chamber delivery devices, and heat-stable/controlled temperature chain qualified liquid vaccines as the three innovations that could have the greatest impact in helping address current immunization program challenges. These findings informed the VIPS prioritization and provided broader application to designing immunization interventions to better meet country needs.

How can we evaluate the potential of innovative vaccine products and technologies in resource constrained settings? A total systems effectiveness (TSE) approach to decision-making.

Innovations in vaccine product attributes could play an important role in addressing coverage and equity (C&E) gaps, but there is currently a poor understanding of the full system impact and trade-offs associated with investing in such technologies, both from the perspective of national immunisation programmes (NIPs) and vaccine developers. Total Systems Effectiveness (TSE) was developed as an approach to evaluate vaccines with different product attributes from a systems perspective, in order to analyse and compare the value of innovative vaccine products in different settings. The TSE approach has been advanced over the years by various stakeholders including the Bill and Melinda Gates Foundation (BMGF), Gavi, PATH, UNICEF and WHO. WHO further developed the TSE approach to incorporate the country perspective into immunisation decision-making, in order for countries to evaluate innovative products for introduction and product switch decisions, and for vaccine development stakeholders to conduct their assessments of product value in line with country preferences. This paper describes the original TSE approach, development of the tool and processes for NIPs to apply the WHO TSE approach, and results from piloting in 12 countries across Africa, Asia and the Americas. The WHO TSE framework emerged from this piloting effort. The WHO TSE approach has been welcomed by NIP and vaccine development stakeholders as a useful tool to evaluate trade-offs between different products. It was emphasised that the concept of "total systems effectiveness" is likely to be context-specific and that TSE is valuable in facilitating a deliberative process to articulate NIP priorities, for decisions around product choice, and for prioritising the development of future vaccine innovations.