Transforming the vaccine supply chain in Australia: Opportunities and challenges

BackgroundAnalyzing potential benefits of thermostable vaccines delivered through Micro Array Patch (MAP) has received great attention in low and middle-income countries. The experience may or may not be the same in developed countries where the infrastructure is more developed. It is anticipated that transforming the vaccine supply chain from syringe-and-needle to thermostable MAP-delivered vaccines will result in reduced supply chain costs – including manufacturing/supply, logistics/distribution, and administration costs – as well as reduced wastes and improved safety. This paper provides an end-to-end supply chain analysis comparing the key aspects (cost, safety and environmental aspects) of the conventional syringe-and-needle vaccine supply chain with those of the MAP vaccine supply chain for influenza vaccine delivery in Australia. Directions for future research in this area will be provided.ObjectiveTo determine the potential supply chain impacts of replacing syringe-and-needle flu vaccine with MAP-enabled thermostable flu vaccine in Australia.MethodsWe analyze the current flu vaccine supply chain in Australia to identify practical limitations and opportunities for improvement. Data/information is collected through interviewing the key stakeholders across vaccine supply chain including vaccine manufacturers, logistics providers, clinics, hospitals, and pharmacies.FindingsA detailed practice-informed analysis is completed on the key operations of the flu vaccine supply chain. Barriers and limitations of the conventional flu vaccine are discussed, along with potential improvements that can be achieved through the implementation of MAP-enabled flu vaccine delivery. We discuss how technology-driven innovations can help advance vaccine supply chains, improve vaccine visibility, reduce wastes, and enable informed decision-making.ConclusionWe find that the benefits of moving from syringe-and-needle vaccines to thermostable MAP-delivered vaccines are beyond transportation and storage cost saving. Potential benefits through cost saving, waste reduction, and service level improvement are discussed along with various safety and wellbeing consequences followed by directions for future research in this area.     

On the vaccine supply chain coordination under subsidy contract

In this paper, we analyze the vaccine supply chain of child immunization program of India under stochastic production yield. We show that the wholesale price contract cannot achieve channel coordination. We propose a subsidy contract to coordinate the vaccine supply chain. A case analysis in the Indian context is presented to illustrate the impact of the proposed subsidy contract.     

Optimal planning of the COVID-19 vaccine supply chain

This work presents a novel framework to simultaneously address the optimal planning of COVID-19 vaccine supply chains and the optimal planning of daily vaccinations in the available vaccination centres. A new mixed integer linear programming (MILP) model is developed to generate optimal decisions regarding the transferred quantities between locations, the inventory profiles of central hubs and vaccination centres and the daily vaccination plans in the vaccination centres of the supply chain network. Specific COVID-19 characteristics, such as special cold storage technologies, limited shelf-life of mRNA vaccines in refrigerated conditions and demanding vaccination targets under extreme time pressure, are aptly modelled. The goal of the model is the minimization of total costs, including storage and transportation costs, costs related to fleet and staff requirements, as well as, indirect costs imposed by wasted doses. A two-step decomposition strategy based on a divide-and-conquer and an aggregation approach is proposed for the solution of large-scale problems. The applicability and efficiency of the proposed optimization-based framework is illustrated on a study case that simulates the Greek nationwide vaccination program. Finally, a rolling horizon technique is employed to reactively deal with possible disturbances in the vaccination plans. The proposed mathematical framework facilitates the decision-making process in COVID-19 vaccine supply chains into minimizing the underlying costs and the number of doses lost. As a result, the efficiency of the distribution network is improved, thus assisting the mass vaccination campaigns against COVID-19.     

Removing the regional level from the Niger vaccine supply chain

Objective

Since many of the world's vaccine supply chains contain multiple levels, the question remains of whether removing a level could bring efficiencies.

Methods

We utilized HERMES to generate a detailed discrete-event simulation model of Niger's vaccine supply chain and compared the current four-tier (central, regional, district, and integrated health center levels) with a modified three-tier structure (removing the regional level). Different scenarios explored various accompanying shipping policies and frequencies.

Findings

Removing the regional level and implementing a collection-based shipping policy from the district stores increases vaccine availability from a mean of 70–100% when districts could collect vaccines at least weekly. Alternatively, implementing a delivery-based shipping policy from the central store monthly in three-route and eight-route scenarios only increases vaccine availability to 87%. Restricting central-to district vaccine shipments to a quarterly schedule for three-route and eight-route scenarios reduces vaccine availability to 49%. The collection-based shipping policy from district stores reduces supply chain logistics cost per dose administered from US$0.14 at baseline to US$0.13 after removing the regional level.

Conclusion

Removing the regional level from Niger's vaccine supply chain can substantially improve vaccine availability as long as certain concomitant adjustments to shipping policies and frequencies are implemented.     

The benefits of redesigning Benin's vaccine supply chain

Introduction

New vaccine introductions have put strains on vaccine supply chains around the world. While increasing storage and transportation may be the most straightforward options, it is also important to consider what financial and operational benefits can be incurred. In 2012, suboptimal vaccine coverage and impending vaccine introductions prompted the Republic of Benin's Ministry of Health (MOH) to explore ways to improve their vaccine supply chain.

Methods

Working alongside the Beninese MOH, we utilized our computational model, HERMES, to explore the impact on cost and vaccine availability of three possible options: (1) consolidating the Commune level to a Health Zone level, (2) removing the Commune level completely, and (3) removing the Commune level and expanding to 12 Department Stores. We also analyzed the impact of adding shipping loops during delivery.

Results

At baseline, new vaccine introductions without any changes to the current system increased the logistics cost per dose ($0.23 to $0.26) and dropped the vaccine availability to 71%. While implementing the Commune level removal scenario had the same capital costs as implementing the Health Zone scenario, the Health Zone scenario had lower operating costs. This increased to an overall cost savings of $504,255 when implementing shipping loops.

Discussion

The best redesign option proved to be the synergistic approach of converting to the Health Zone design and using shipping loops (serving ten Health Posts/loop). While a transition to either redesign or only adding shipping loops was beneficial, implementing a redesign option and shipping loops can yield both lower capital expenditures and operating costs.     

从供应链角度评介美国国家医药品战略储备体系及其对我国的启示

目的：应用供应链管理理论分析美国国家医药品战略储备供应体系的优缺点,提出适用于我国国家应急医药品有效供应的建议。方法：通过文献研究和比较研究方法,了解美国应急医药品战略性国家储备体系的供应链模式与中国的差异性。结果：从供应链的视角,美国战略性国家储备对应急医药品主要采取＂应急包预先储备＂、＂管理型库存＂和＂合同储备＂的应急准备方式;对应急医药品的物流调运采取＂地方—州—国家＂申报审批管理和分时间段供应模式;信息流的传递,利用大型数据库、模拟软件和技术咨询响应单元的建立,实现实时交流,便于准确与及时地调运应急医药品。结论：完善我国应急医药品的供应链体系,明确供应管理的主体与职责,建立分救灾时间段的应急医药品目录和采用第四方物流供应模式,提高我国应急医药品准备的系统化、规范化和信息化水平。     

Re-designing the Mozambique vaccine supply chain to improve access to vaccines

IntroductionPopulations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the “Decade of Vaccine” may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines.MethodsWorking with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies.ResultsThe alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries.DiscussionRe-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful.     

Adventitious agents and smallpox vaccine in strategic national stockpile

In keeping with current standards, we urge that old smallpox vaccines that were made in animal skin and are still a key part of our strategic national stockpile be tested for adventitious infectious agents. The advisory especially applies to viruses that have the potential for zoonotic transmission to human vaccine recipients.     

Optimal vaccine stockpile design for an eradicated disease: Application to polio

Eradication of a disease promises significant health and financial benefits. Preserving those benefits, hopefully in perpetuity, requires preparing for the possibility that the causal agent could re-emerge (unintentionally or intentionally). In the case of a vaccine-preventable disease, creation and planning for the use of a vaccine stockpile becomes a primary concern. Doing so requires consideration of the dynamics at different levels, including the stockpile supply chain and transmission of the causal agent. This paper develops a mathematical framework for determining the optimal management of a vaccine stockpile over time. We apply the framework to the polio vaccine stockpile for the post-eradication era and present examples of solutions to one possible framing of the optimization problem. We use the framework to discuss issues relevant to the development and use of the polio vaccine stockpile, including capacity constraints, production and filling delays, risks associated with the stockpile, dynamics and uncertainty of vaccine needs, issues of funding, location, and serotype dependent behavior, and the implications of likely changes over time that might occur. This framework serves as a helpful context for discussions and analyses related to the process of designing and maintaining a stockpile for an eradicated disease.     

The impact of making vaccines thermostable in Niger's vaccine supply chain

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.     

Modeling the national pediatric vaccine stockpile: Supply shortages,health impacts and cost consequences

Pediatric vaccine stockpiles have been in place in the U.S. since 1983 to address the potential disruption in supply of routine pediatric vaccines. Increases in the number of vaccines recommended for pediatric and adolescent patients have increased the cost of stocking and maintaining the stockpile. Based on a spreadsheet-based model (VacStockpile) we developed, we estimated potential supply shortages of 14 stockpiled vaccines as of August 1, 2008 and its health and financial impacts under various shortage and stockpile scenarios. To illustrate the implications of policy options, we compared “high” to “low” stockpile scenarios. The high stockpile scenario ensures a 6-month vaccine supply to vaccinate all children according to recommended schedules. The low scenario comprised of 50% of the high scenario or existing stocks, whichever is smaller. For each vaccine, we used a weighted average of five shortage scenarios ranging from 0% to 100%, in 25% increments. Demand for each vaccine was based on current distribution or birth cohort size. The probabilities of shortages were based on number of manufacturers, market stability, history of manufacturing problems, and production complexity. CDC contract prices were used to estimate costs. Expert opinion and literature provided estimates of health impacts due to shortages. Applying the probabilities of shortages to all vaccines in a single year, the “low” scenario could cost $600 million, with 376,000 vaccine-preventable cases occurring and 1774 deaths. The “high” scenario could cost $2 billion, with an additional $1.6 billion initial stocking, and result in 7100 vaccine-preventable cases occurring and 508 deaths. Based on the assumptions in the model, there is the potential for large differences in outcomes between the scenarios although some outcomes could potentially be averted with measures such as catch-up campaigns after shortages. Using the VacStockpile policy makers can readily evaluate the implications of assumptions and decide which set of assumptions they wish to use in planning.     

Rabies DNA vaccine in the horse: strategies to improve serological responses

In order for DNA vaccines to become a practical alternative to conventional vaccines their ability to induce antibody responses in large mammals needs to be improved. We used DNA vaccination against rabies in the horse as a model to test the potential of two different strategies to enhance antibody responses in a large mammalian species.The administration of the DNA vaccine in the presence of aluminum phosphate improved both the onset and the intensity of serological responses but was not potent enough to achieve seroconversion in all vaccinated ponies. However, when the DNA vaccine was formulated with the cationic lipid DMRIE-DOPE instead of aluminum phosphate, a very strong impact on both onset and intensity of serological responses was observed. This latter strategy ensured excellent seroconversion in all vaccinated ponies after a primary course of two injections, demonstrating a clear improvement of the homogeneity of the induced responses. These data indicate that rabies DNA vaccination is feasible in horses and further suggests that properly formulated DNA vaccines can generate immune responses in large veterinary species at a level comparable to the responses achieved with conventional vaccines.     

5200例狂犬疫苗接种者免疫效果观察

目的了解国产纯化狂犬疫苗接种后的效果。方法以5 200例接种狂犬疫苗的暴露者为研究对象,每位对象取静脉血3 ml,分离血清,用酶联免疫吸附测定法（简称ELISA法）检测抗-RA。结果国产纯化狂犬疫苗全程免疫后总抗-RA阳转率为98.27%,性别间分布无差异,而年龄组间存在差异,70岁以上年龄组抗体阳性率较其他组低。使用狂犬病免疫球蛋白和狂犬疫苗联合接种者抗体阳性率为100%,未注射狂犬病免疫球蛋白组抗体阳性率为97.35%。多剂量（针次）接种组与常规接种组抗体阳性率差异有统计学意义（χ^2=26.997,P〈0.05）。结论按免疫程序及时全程注射人用纯化狂犬疫苗,可产生较为理想的保护性抗体,对疑似狂犬、流浪犬和三度咬伤者采用狂犬病免疫球蛋白和狂犬疫苗联合、早期、足量、全程、规则的免疫原则,中老年伤者增大剂量或增加接种针次,均可达到理想的预防效果。     

Evaluation of a pilot intervention to redesign the decentralised vaccine supply chain system in Nigeria

Responsibility for immunisation in Nigeria is decentralised to sub-national governments. So far, they have failed to achieve optimal coverage for their populations. We evaluated a pilot intervention implemented between 2013 and 2014 to redesign a vaccine supply chain management system in Kano, Nigeria. The intervention included financing immunisation services from a designated pool of government and donor funds, a visibility tool to track vaccine stock, and a private vendor engaged to deliver vaccines directly to health facilities. The number of local government areas within the state with adequate vaccine stock increased from 21% to 98% after 10 months. To understand how the intervention achieved this outcome, we analysed immunisation coverage for the period and interviewed 18 respondents across different levels of government. We found that the intervention worked by improving ownership and accountability for immunisation by sub-national governments and their capacity for generating resources and management (of data and the supply chain). While the intervention focused on improving immunisation coverage, we identified gaps in the demand for services. Efforts to improve immunisation coverage and vaccine supply systems should streamline decentralised structures, empower sub-national governments with financial and technical capacity, and promote strategies to improve the demand and use of services.