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Background: Frequently, a country will procure a single vaccine vial size, but the question remains whether tailoring the use of different size vaccine vial presentations based on populations or location characteristics within a single country could provide additional benefits, such as reducing open vial wastage (OVW) or reducing missed vaccination opportunities., Methods: Using the Highly Extensible Resource for Modeling Supply Chains (HERMES) software, we built a simulation model of the Zambia routine vaccine supply chain. At baseline, we distributed 10-dose Measles-Rubella (MR) vials to all locations, and then distributed 5-dose and 1-dose MR vials to (1) all locations, (2) rural districts, (3) rural health facilities, (4) outreach sites, and (5) locations with average MR session sizes <5 and <10 children. We ran sensitivity on each scenario using MR vial opening thresholds of 0% and 50%, i.e. a healthcare worker opens an MR vaccine for any number of children (0%) or if at least half will be used (50%)., Results: Replacing 10-dose MR with 5-dose MR vials everywhere led to the largest reduction in MR OVW, saving 573,892 doses (103,161 doses with the 50% vial opening threshold) and improving MR availability by 1% (9%). This scenario, however, increased cold chain utilization and led to a 1% decrease in availability of other vaccines. Tailoring 5-dose MR vials to rural health facilities or based on average session size reduced cold transport constraints, increased total vaccine availability (+1%) and reduced total cost per dose administered (-$0.01) compared to baseline., Conclusions: In Zambia, tailoring 5-dose MR vials to rural health facilities or by average session size results in the highest total vaccine availability compared to all other scenarios (regardless of OVT policy) by reducing open vial wastage without increasing cold chain utilization., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Microneedle patch (MNP) technology is designed to simplify the process of vaccine administration; however, depending on its characteristics, MNP technology may provide additional benefits beyond the point-of-use, particularly for vaccine supply chains., Methods: Using the HERMES modeling software, we examined replacing four routine vaccines - Measles-containing vaccine (MCV), Tetanus toxoid (TT), Rotavirus (Rota) and Pentavalent (Penta) - with MNP versions in the routine vaccine supply chains of Benin, Bihar (India), and Mozambique., Results: Replacing MCV with an MNP (5 cm 3 -per-dose, 2-month thermostability, current single-dose price-per-dose) improved MCV availability by 13%, 1% and 6% in Benin, Bihar and Mozambique, respectively, and total vaccine availability by 1% in Benin and Mozambique, while increasing the total cost per dose administered by $0.07 in Benin, $0.56 in Bihar and $0.11 in Mozambique. Replacing TT with an MNP improved TT and total vaccine availability (3% and <1%) in Mozambique only, when the patch was 5 cm 3 and 2-months thermostable but increased total cost per dose administered by $0.14. Replacing Rota with an MNP (at 5-15 cm 3 -per-dose, 1-2 month thermostable) improved Rota and total vaccine availability, but only improved Rota vaccine availability in Bihar (at 5 cm 3 , 1-2 months thermostable), while decreasing total vaccine availability by 1%. Finally, replacing Penta with an MNP (at 5 cm 3 , 2-months thermostable) improved Penta vaccine availability by 1-8% and total availability by <1-9%., Conclusions: An MNP for MCV, TT, Rota, or Penta would need to have a smaller or equal volume-per-dose than existing vaccine formulations and be able to be stored outside the cold chain for a continuous period of at least two months to provide additional benefits to all three supply chains under modeled conditions., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: By pairing diluent with vaccines, dual-chamber vaccine injection devices simplify the process of reconstituting vaccines before administration and thus decrease associated open vial wastage and adverse events. However, since these devices are larger than current vaccine vials for lyophilized vaccines, manufacturers need guidance as to how the size of these devices may affect vaccine distribution and delivery., Methods: Using HERMES-generated immunization supply chain models of Benin, Bihar (India), and Mozambique, we replace the routine 10-dose measles-rubella (MR) lyophilized vaccine with single-dose MR dual-chamber injection devices, ranging the volume-per-dose (5.2-26 cm 3 ) and price-per-dose ($0.70, $1.40)., Results: At a volume-per-dose of 5.2 cm 3 , a dual-chamber injection device results in similar vaccine availability, decreased open vial wastage (OVW), and similar total cost per dose administered as compared to baseline in moderately constrained supply chains. Between volumes of 7.5 cm 3 and 26 cm 3 , these devices lead to a reduction in vaccine availability between 1% and 14% due to increases in cold chain storage utilization between 1% and 7% and increases in average peak transport utilization between 2% and 44%. At the highest volume-per-dose, 26 cm 3 , vaccine availability decreases between 9% and 14%. The total costs per dose administered varied between each scenario, as decreases in vaccine procurement costs were coupled with decreases in doses administered. However, introduction of a dual-chamber injection device only resulted in improved total cost per dose administered for Benin and Mozambique (at 5.2 cm 3 and $0.70-per-dose) when the total number of doses administered changed <1% from baseline., Conclusion: In 3 different country supply chains, a single-dose MR dual-chamber injection device would need to be no larger than 5.2 cm 3 to not significantly impair the flow of other vaccines., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable., Methods: Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable., Findings: Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1-2%., Conclusion: Our study shows the potential benefits of making any of Niger's EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world., (Copyright © 2012 Elsevier Ltd. All rights reserved.)