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.

Development of Norelgestromin Dissolving Bilayer Microarray Patches for Sustained Release of Hormonal Contraceptive.

Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors. Ex vivo assessments showed that the MAPs delivered an average of 176 ± 60.9 µg of NGMN per MAP into excised neonatal porcine skin, representing 15.3 ± 5.3% of the loaded drug. In vivo pharmacokinetic analysis in Sprague Dawley rats demonstrated a Tmax of 4 h and a Cmax of 67.4 ± 20.1 ng/mL for the MAP-treated group, compared to a Tmax of 1 h and a Cmax of 700 ± 138 ng/mL for the intramuscular (IM) injection group, with a relative bioavailability of approximately 10% for the MAPs. The MAP-treated rats maintained plasma levels sufficient for therapeutic effects for up to 7 days after a single application. These results indicate the potential of NGMN-loaded dissolving bilayer MAPs, with further development focused on extending the release duration and improving bioavailability for prolonged contraceptive effects.

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.

A Bilayer Microarray Patch (MAP) for HIV Pre-Exposure Prophylaxis: The Role of MAP Designs and Formulation Composition in Enhancing Long-Acting Drug Delivery.

Microarray patches (MAPs) have shown great potential for efficient and patient-friendly drug delivery through the skin; however, improving their delivery efficiency for long-acting drug release remains a significant challenge. This research provides an overview of novel strategies aimed at enhancing the efficiency of MAP delivery of micronized cabotegravir sodium (CAB Na) for HIV pre-exposure prophylaxis (PrEP). The refinement of microneedle design parameters, including needle length, shape, density, and arrangement, and the formulation properties, such as solubility, viscosity, polymer molecular weight, and stability, are crucial for improving penetration and release profiles. Additionally, a bilayer MAP optimization step was conducted by diluting the CAB Na polymeric mixture to localize the drug into the tips of the needles to enable rapid drug deposition into the skin following MAP application. Six MAP designs were analyzed and investigated with regard to delivery efficiency into the skin in ex vivo and in vivo studies. The improved MAP design and formulations were found to be robust and had more than 30% in vivo delivery efficiency, with plasma levels several-fold above the therapeutic concentration over a month. Repeated weekly dosing demonstrated the robustness of MAPs in delivering a consistent and sustained dose of CAB. In summary, CAB Na MAPs were able to deliver therapeutically relevant levels of drug.

Exploring user and stakeholder perspectives from South Africa and Uganda to refine microarray patch development for HIV PrEP delivery and as a multipurpose prevention technology.

BACKGROUND: Oral HIV pre-exposure prophylaxis (PrEP) is highly effective, but alternative delivery options are needed to reach more users. Microarray patches (MAPs), a novel drug-delivery system containing micron-scale projections or "microneedles" that deliver drugs via skin, are being developed to deliver long-acting HIV PrEP and as a multipurpose prevention technology to protect from HIV and unintended pregnancy. We explored whether MAP technology could meet user and health system needs in two African countries. METHODS: Researchers in South Africa and Uganda conducted 27 focus group discussions, 76 mock-use exercises, and 31 key informant interviews to explore perceptions about MAPs and specific features such as MAP size, duration of protection, delivery indicator, and health system fit. Participants included young women and men from key populations and vulnerable groups at high risk of HIV and/or unintended pregnancy, including adolescent girls and young women; female sex workers and men who have sex with these women; and men who have sex with men. In Uganda, researchers also recruited young women and men from universities and the community as vulnerable groups. Key stakeholders included health care providers, sexual and reproductive health experts, policymakers, and youth activists. Qualitative data were transcribed, translated, coded, and analyzed to explore perspectives and preferences about MAPs. Survey responses after mock-use in Uganda were tabulated to assess satisfaction with MAP features and highlight areas for additional refinement. RESULTS: All groups expressed interest in MAP technology, reporting perceived advantages over other methods. Most participants preferred the smallest MAP size for ease of use and discreetness. Some would accept a larger MAP if it provided longer protection. Most preferred a protection duration of 1 to 3 months or longer; others preferred 1-week protection. Upper arm and thigh were the most preferred application sites. Up to 30 minutes of wear time was considered acceptable; some wanted longer to ensure the drug was fully delivered. Self-administration was valued by all groups; most preferred initial training by a provider. CONCLUSIONS: Potential users and stakeholders showed strong interest in/acceptance of MAP technology, and their feedback identified key improvements for MAP design. If a MAP containing a high-potency antiretroviral or a MAP containing both an antiretroviral and hormonal contraceptive is developed, these products could improve acceptability/uptake of protection options in sub-Saharan Africa.

Assessing the risk of a clinically significant infection from a Microneedle Array Patch (MAP) product.

Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum, to facilitate delivery of active pharmaceutical ingredients to the underlying tissue. Numerous MAP products are proposed and there is significant clinical potential in priority areas such as vaccination. However, since their inception scientists have hypothesized about the risk of a clinically significant MAP-induced infection. Safety data from two major Phase 3 clinical trials involving hundreds of participants, who in total received tens of thousands of MAP applications, does not identify any clinically significant infections. However, the incumbent data set is not extensive enough to make definitive generalizable conclusions. A comprehensive assessment of the infection risk is therefore advised for MAP products, and this should be informed by clinical and pre-clinical data, theoretical analysis and informed opinions. In this article, a group of key stakeholders identify some of the key product- and patient-specific factors that may contribute to the risk of infection from a MAP product and provide expert opinions in the context of guidance from regulatory authorities. Considerations that are particularly pertinent to the MAP dosage form include the specifications of the finished product (e.g. microbial specification), it's design features, the setting for administration, the skill of the administrator, the anatomical application site, the target population and the clinical context. These factors, and others discussed in this article, provide a platform for the development of MAP risk assessments and a stimulus for early and open dialogue between developers, regulatory authorities and other key stakeholders, to expedite and promote development of safe and effective MAP products.

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.

Microarray patch for HIV prevention and as a multipurpose prevention technology to prevent HIV and unplanned pregnancy: an assessment of potential acceptability, usability, and programmatic fit in Kenya.

Background: Microarray patches (MAPs), a novel drug delivery system, are being developed for HIV pre-exposure prophylaxis (PrEP) delivery and as a multipurpose prevention technology (MPT) to protect from both HIV and unintended pregnancy. Prevention technologies must meet the needs of target audiences, be acceptable, easy to use, and fit health system requirements. Methodology: We explored perceptions about MAP technology and assessed usability, hypothetical acceptability, and potential programmatic fit of MAP prototypes using focus group discussions (FGD), usability exercises, and key informant interviews (KII) among key populations in Kiambu County, Kenya. Adolescent girls and young women (AGYW), female sex workers (FSW), and men who have sex with men (MSM) assessed the usability and acceptability of a MAP prototype. Male partners of AGYW/FSW assessed MAP acceptability as partners of likely users. We analyzed data using NVivo, applying an inductive approach. Health service providers and policymakers assessed programmatic fit. Usability exercise participants applied a no-drug, no-microneedle MAP prototype and assessed MAP features. Results: We implemented 10 FGD (4 AGYW; 2 FSW; 2 MSM; 2 male partners); 47 mock use exercises (19 AGYW; 9 FSW; 8 MSM; 11 HSP); and 6 policymaker KII. Participants reported high interest in MAPs due to discreet and easy use, long-term protection, and potential for self-administration. MAP size and duration of protection were key characteristics influencing acceptability. Most AGYW preferred the MPT MAP over an HIV PrEP-only MAP. FSW saw value in both MAP indications and voiced need for MPTs that protect from other infections. Preferred duration of protection was 1-3 months. Some participants would accept a larger MAP if it provided longer protection. Participants suggested revisions to the feedback indicator to improve confidence. Policymakers described the MPT MAP as "killing two birds with one stone," in addressing AGYW needs for both HIV protection and contraception. An MPT MAP is aligned with Kenya's policy of integrating health care programs. Conclusions: MAPs for HIV PrEP and as an MPT both were acceptable across participant groups. Some groups valued an MPT MAP over an HIV PrEP MAP. Prototype refinements will improve usability and confidence.

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.

Development and Evaluation of Dissolving Microarray Patches for Co-administered and Repeated Intradermal Delivery of Long-acting Rilpivirine and Cabotegravir Nanosuspensions for Paediatric HIV Antiretroviral Therapy.

PURPOSE: Whilst significant progress has been made to defeat HIV infection, the efficacy of antiretroviral (ARV) therapy in the paediatric population is often hindered by poor adherence. Currently, two long-acting (LA) intramuscular injectable nanosuspensions of rilpivirine (RPV) and cabotegravir (CAB) are in clinical development for paediatric populations. However, administration requires access to healthcare resources, is painful, and can result in needle-stick injuries to the end user. To overcome these barriers, this proof-of-concept study was developed to evaluate the intradermal delivery of RPV LA and CAB LA via self-disabling dissolving microarray patches (MAPs). METHODS: Dissolving MAPs of two conformations, a conventional pyramidal and a bilayer design, were formulated, with various nanosuspensions of RPV and CAB incorporated within the respective MAP matrix. MAPs were mechanically robust and were capable of penetrating ex vivo skin with intradermal ARV deposition. RESULTS: In a single-dose in vivo study in rats, all ARV MAPs demonstrated sustained release profiles, with therapeutically relevant plasma concentrations of RPV and CAB detected to at least 63 and 28 d, respectively. In a multi-dose in vivo study, repeated MAP applications at 14-d intervals maintained therapeutically relevant plasma concentrations throughout the duration of the study. CONCLUSIONS: These results illustrate the potential of the platform to repeatedly maintain plasma concentrations for RPV and CAB. As such, these MAPs could represent a viable option to improve adherence in the paediatric population, one that is capable of being painlessly administered in the comfort of the patient's own home on a biweekly or less frequent basis.

Evaluating Islatravir Administered Via Microneedle Array Patch for Long-Acting HIV Pre-exposure Prophylaxis Using Physiologically Based Pharmacokinetic Modelling.

BACKGROUND AND OBJECTIVES: Technologies for long-acting administration of antiretrovirals (ARVs) for the prevention and treatment of HIV are at the forefront of research initiatives aiming to tackle issues surrounding drug adherence with the current standard of once-daily oral administration. Islatravir (ISL) is an emerging ARV that shows promising characteristics for long-acting prevention and treatment both orally as well as through alternative routes of administration. Microneedle array patches (MAPs) are a pain-free and discreet transdermal delivery technology that offer extended-release administration of nanoparticulate drugs. This study aimed to utilise physiologically based pharmacokinetic (PBPK) modelling to predict the pharmacokinetics resulting from ISL administered via MAP and to identify key MAP characteristics required to sustain effective concentrations over extended dosing intervals. METHODS: A PBPK model describing the conversion of ISL to ISL-triphosphate (ISL-TP) and its whole-body disposition was developed and verified against observed clinical data for orally administered ISL in healthy adults. An intradermal PBPK model was integrated with the ISL PBPK model to predict the dose and nanoparticle release rate required for MAP administration strategies capable of achieving a minimum ISL-TP target concentration of 0.05 pmol/106 PBMCs over extended dosing intervals. MAP design was limited to a maximum therapeutic area of 20 cm2 with a dose loading of 4.09 mg/cm2 and a minimum duration of 3 months. Due to the lack of available clinical data, a range of nanoparticle release rates and MAP bioavailability scenarios were simulated to provide an overview of potential clinical outcomes. RESULTS: The ISL PBPK model was successfully verified, with predicted vs observed ratios falling within 0.5-2-fold. ISL MAP doses ranging from 15 to 80 mg were predicted to sustain ISL-TP concentrations above the minimum target concentration at 3, 6 and 12 months after administration. Nanoparticle release rate and MAP bioavailability were found to have a major impact on whether dosing strategies achieved the criteria. Minimum doses of 15 mg and 60 mg with a nanoparticle release rate of 0.0005 h-1 and bioavailability ranging from 25 to 100% were predicted to achieve effective ISL-TP concentrations up to 3 and 6 months, respectively. Doses of 15 mg and 30 mg with a nanoparticle release rate of 0.0005 h-1 were also able to attain the target concentration up to 6 months after MAP administration, albeit with a minimum bioavailability of 75% and 50%, respectively. Furthermore, when simulating a bioavailability of 100%, an 80 mg ISL MAP was predicted to sustain ISL-TP concentrations above the minimum target concentration up to 12 months after administration. CONCLUSIONS: The ISL PBPK model successfully predicted ISL and ISL-TP pharmacokinetics across a range of orally administered regimens. The integrated intradermal PBPK model outlined optimal MAP dose and nanoparticle release rates for effective ISL-TP concentrations up to 12 months, providing justification for further investigation of ISL as a candidate for MAP administration.

Syringes must be prioritized globally to ensure equitable access to COVID-19 and other essential vaccines and to sustain safe injection practices.

Supply of autodisable (AD) syringes has been a key component of global COVID-19 vaccination campaigns, and it is critical to maintaining safe injection practices for routine immunization as well as pandemic response. AD syringe production increased significantly in response to demand, but distribution challenges have included the need to coordinate syringes to meet the specific delivery requirements of various COVID-19 vaccines, shipping bottlenecks, and syringe export restrictions. Stockpiling syringes, ensuring standardization of future vaccine dose volumes, and geographical diversification of syringe production would improve syringe logistics in the future. Balancing syringe supply and demand and stabilizing the market over the long term is essential to ensure that the world is prepared for possible new variants of COVID-19 or a new global outbreak. This will require concerted action on the part of public, nonprofit, and private partners.

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.

Evaluating the potential cost-effectiveness of microarray patches to expand access to hepatitis B birth dose vaccination in low-and middle-income countries: A modelling study.

Timely birth dose vaccination is key for achieving elimination of hepatitis B, however, programmatic requirements for delivering current vaccine presentations to births outside of health facilities inhibits coverage within many low-and middle-income countries (LMICs). Vaccine technologies in development such as microarray patches (MAPs) could assist in overcoming these barriers, but procurement could incur higher per-dose commodity costs than current ten-dose (US$0.34) and single-dose (US$0.62) vial presentations, necessitating an evaluation of the economic value proposition for MAPs. Within 80 LMICs offering universal hepatitis B birth dose vaccination, the cost-effectiveness of using MAPs to expand coverage was evaluated using a mathematical model. We considered three potential per dose MAP prices (US$1.65, US$3.30, and US$5.00), and two potential MAP use-cases: (1) MAPs are used by lay-health workers to expand birth dose coverage outside of health facility settings, and (2) MAPs are also preferred by qualified health workers, replacing a proportion of existing coverage from vaccine vials. Analysis took the health system perspective, was costed in 2020 US$, and discounted at 3% annually. Across minimal (1% additional coverage) and maximal (10% additional and 10% replacement coverage) MAP usage scenarios, between 2.5 (interquartile range [IQR]: 1.9, 3.1) and 38 (IQR: 28,44) thousand DALYs were averted over the estimated 2020 birth cohort lifetime in 80 LMICs. Efficiency of MAPs was greatest when used to provide additional coverage (scenario 1), on average saving US$88.65 ($15.44, $171.22) per DALY averted at a price of US$5.00 per MAP. Efficiency was reduced when used to replace existing coverage (scenario 2); however, at prices up to US$5.00 per MAP, we estimate this use-case could remain cost-effective in at least 73 (91%) modelled LMICs. Our findings suggest even at higher procurement costs, MAPs are likely to represent a highly cost-effective or cost-saving mechanism to expand reach of birth dose vaccination in LMICs.

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.

Manufacturing readiness assessment for evaluation of the microneedle array patch industry: an exploration of barriers to full-scale manufacturing.

Microneedle array patch (MAP) technology is a promising new delivery technology for vaccines and pharmaceuticals, yet due to several differing and novel production methods, barriers to full-scale manufacturing exist. PATH conducted a manufacturing readiness assessment and follow-up interviews to identify both the current manufacturing readiness of the industry as well as how readiness varies by developer type and MAP type. Follow-up interviews identified barriers the industry faces in reaching full manufacturing readiness, including the perceived regulatory and investment risk of manufacturing MAPs at scale due to quality requirements and control methods, uncertain sterility requirements, lack of standard production methods (especially around dissolvable MAP drying methods), and the lack of available contract manufacturing organizations with MAP manufacturing capabilities. A Regulatory Working Group has been established to identify and address critical quality issues specific to MAP manufacturing with the aim of providing developers insight into what will be expected for MAP product approvals. Standardizing MAP production equipment and automatic, visual quality control could reduce the overall investment risk to developers and contract manufacturing organizations in pursuing pilot-scale manufacturing capabilities and ultimately lower barriers to the scale-up of full medical MAP product lines.

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.

Microarray patches: Breaking down the barriers to contraceptive care and HIV prevention for women across the globe.

Despite the existence of a variety of contraceptive products for women, as well as decades of research into the prevention and treatment of human immunodeficiency virus (HIV), there is still a globally unmet need for easily accessible, acceptable, and affordable products to protect women's sexual and reproductive health. Microarray patches (MAPs) are a novel platform being developed for the delivery of hormonal contraception and antiretroviral drugs. MAPs provide enhanced drug delivery to the systemic circulation via the transdermal route when compared to transdermal patches, oral and injectable formulations. These minimally invasive patches can be self-administered by the user, reducing the burden on health care personnel. Since MAPs represent needle-free drug delivery, no sharps waste is generated after application, thereby eliminating possible MAP reuse and risk of needle-stick injuries. This review discusses the administration of contraceptive and antiretroviral drugs using MAPs, their acceptability by end-users, and the future perspective of the field.

Fractional-dose inactivated poliovirus vaccine, India.

In 2016, the World Health Organization (WHO) announced a global shortage of inactivated poliovirus vaccine that was expected to last until 2020 at least. In response, WHO's Strategic Advisory Group of Experts on Immunization recommended that countries consider a strategic shift to fractional-dose inactivated poliovirus vaccine, which involves a new dosing schedule (i.e. administered at 6 and 14 weeks of age) and has a different mode of delivery than full-dose inactivated poliovirus vaccine (i.e. intradermal rather than intramuscular). Introduction of fractional-dosing requires careful planning and management to ensure adequate vaccine supplies, to prevent wastage, to provide training for health workers, and to ensure accurate record-keeping. In early 2016, given the global vaccine shortage and a limited supply from domestic manufacturers, India's Expert Advisory Group on polio recommended the staggered introduction of fractional-dosing. India was the first country to introduce fractional-dose inactivated poliovirus vaccine into routine immunization, initially in eight states in 2016. Following a rapid assessment of its initial implementation, fractional-dosing was extended and, by June 2017, all Indian states were covered. Here we summarize India's experience with the introduction, discuss the challenges faced and the strategies used to address them, and report on the outcomes achieved. We also describe the lessons learnt, especially managing vaccine supplies and wastage, monitoring and supervision, and training needs. As the use of fractional-dose inactivated poliovirus vaccine is dose-sparing and reduces the cost of the immunization programme, it will remain an important part of India's long-term strategy for polio vaccination.

En 2016, l'Organisation mondiale de la Santé (OMS) a annoncé une pénurie mondiale du vaccin antipoliomyélitique inactivé, prévue pour durer jusqu'à 2020 au minimum. Face à cette situation, le Groupe stratégique consultatif d'experts sur la vaccination a recommandé aux pays d'envisager un changement de stratégie afin de privilégier l'utilisation du vaccin antipoliomyélitique inactivé en doses fractionnées, ce qui implique un nouveau calendrier de vaccination (administration du vaccin à l'âge de 6 et de 14 semaines) et un mode d'administration différent de celui du vaccin antipoliomyélitique inactivé en dose complète (par voie intradermique et non pas par voie intramusculaire). L'introduction d'une vaccination en doses fractionnées exige de la rigueur en matière de planification et de gestion, afin de garantir des stocks de vaccins suffisants, d'éviter les gaspillages, de former les agents de santé et d'assurer une tenue précise des dossiers médicaux. Début 2016, du fait de la pénurie mondiale du vaccin et d'un approvisionnement limité par les fabricants nationaux, le Groupe consultatif d'experts de l'Inde sur l'éradication de la poliomyélite a recommandé d'introduire progressivement les doses fractionnées. Si bien que l'Inde est le premier pays à avoir introduit le vaccin antipoliomyélitique inactivé en doses fractionnées dans le calendrier de vaccination systématique, d'abord dans huit États en 2016. Après une rapide évaluation de cette mise en œuvre initiale, l'utilisation des doses fractionnées s'est étendue, pour finalement être effective dans tous les États indiens en juin 2017. Dans cet article, nous récapitulons l'expérience de l'Inde à ce sujet, nous évoquons les défis rencontrés et les stratégies employées pour les surmonter ainsi que les résultats obtenus. Nous décrivons également les enseignements tirés de cette expérience, notamment en matière de gestion des stocks de vaccins, de prévention des gaspillages, de suivi et de supervision, mais aussi concernant les besoins en formation. Étant donné que l'utilisation de doses fractionnées du vaccin antipoliomyélitique inactivé permet d'économiser des doses vaccinales et de réduire le coût du programme de vaccination, cela restera un élément essentiel dans la stratégie à long terme de l'Inde en matière de vaccination contre la poliomyélite.

En 2016, la Organización Mundial de la Salud (OMS) anunció una escasez mundial de vacunas inactivadas del poliovirus que se esperaba que se prolongara al menos hasta 2020. En respuesta, el Grupo de asesoramiento estratégico de expertos en inmunización de la OMS recomendó que los países consideraran la posibilidad de un cambio estratégico hacia una vacuna inactivada del poliovirus de dosis fraccionada, que incluye un nuevo esquema de dosificación (es decir, administrada a las seis y a las catorce semanas de edad) y que tiene un modo de administración diferente al de la vacuna inactivada del poliovirus de dosis completa (es decir, intradérmica y no intramuscular). La introducción de la dosis fraccionada requiere una planificación y una gestión minuciosas para garantizar el suministro adecuado de las vacunas, evitar el despilfarro, formar a los trabajadores sanitarios y garantizar el mantenimiento de registros precisos. A principios de 2016, dada la escasez mundial de vacunas y el limitado suministro de los fabricantes nacionales, el Grupo de asesoramiento experto sobre la polio de la India recomendó la introducción escalonada de dosis fraccionadas. La India fue el primer país en introducir la vacuna inactivada del poliovirus de dosis fraccionada en la inmunización sistemática, inicialmente en ocho estados en 2016. Tras una rápida evaluación de la aplicación inicial, se amplió la dosificación fraccionada y, para junio de 2017, se cubrieron todos los estados de la India. En este documento se resume la experiencia de la India con la introducción, se examinan los problemas encontrados y las estrategias utilizadas para resolverlos y se informa sobre los resultados alcanzados. También se describen las lecciones aprendidas, especialmente en lo que se refiere a la gestión de los suministros de vacunas y el desperdicio, el seguimiento y la supervisión, y las necesidades de formación. Dado que el uso de la vacuna inactivada del poliovirus de dosis fraccionada ahorra dosis y reduce el coste del programa de inmunización, seguirá siendo una parte importante de la estrategia a largo plazo de la India para la vacunación contra la polio.