Objective: To evaluate the evidence describing how the controlled temperature chain approach for vaccination could lead to improved equitable immunization coverage in low- and middle-income countries.
Methods: We created a theory of change construct from the containing four domains: (i) uptake and demand for the approach; (ii) compliance and safe use of the approach; (iii) programmatic efficiency gains from the approach; and (iv) improved equitable immunization coverage. To verify and improve the theory of change, we applied a realist review method to analyse published descriptions of controlled temperature chain or closely related experiences.
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.
View Article and Find Full Text PDFAs 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.
View Article and Find Full Text PDFIntroduction: Limited information exists on health care workers' (HCWs) perceptions about use of multidose vaccine vials and their preferences about doses per container (DPC). We present findings from qualitative studies conducted in Senegal, Vietnam, and Zambia to explore HCWs' behavior regarding opening vials and their perceptions and preferences for the number of doses in vials of BCG and measles-containing vaccine (MCV). Zambia and Senegal currently offer MCV in 10-dose vials and BCG in 20-dose vials; 10-dose vials are used for both vaccines in Vietnam.
View Article and Find Full Text PDFInnovations 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.
View Article and Find Full Text PDFIntroduction: Inactivated poliovirus vaccine (IPV) shortages and evidence of improved immunogenicity of two intradermal (ID) fractional IPV (fIPV) doses compared with one full intramuscular dose led to recommendations for fIPV delivery. To provide evidence on the economics of fIPV, we estimated the cost per child vaccinated using full-dose IPV compared with fIPV in routine and campaign settings. We evaluated the impact on costs of alternative devices facilitating ID administration, vaccine vial sizes, and prices.
View Article and Find Full Text PDFIntroduction: A recent innovation in support of the final segment of the immunization supply chain is licensing certain vaccines for use in a controlled temperature chain (CTC), which allows excursions into ambient temperatures up to 40°C for a specific number of days immediately prior to administration. However, limited evidence exists on CTC economics to inform investments for labeling other eligible vaccines for CTC use. Using data collected during a MenAfriVac™ campaign in Togo, we estimated economic costs for vaccine logistics when using the CTC approach compared to full cold chain logistics (CCL) approach.
View Article and Find Full Text PDFA variety of vaccine packaging and delivery technologies may benefit the immunization supply chain. These include alternative primary packaging, such as blow-fill-seal polymer containers, and novel delivery technologies, such intradermal delivery devices, microarray patches, and sublingual formulations of vaccines, and others in development. The potential timeline to availability of these technologies varies and depends on their stage of development and the type of data necessary to achieve licensure.
View Article and Find Full Text PDFThis study attempts to capture the opinions of stakeholders working in immunization programs in low- and middle-income countries to understand how vaccine products could be improved to better meet their needs and to obtain feedback on specific vaccine product attributes including the number of doses per container and ease of preparing a dose for administration. We also reviewed how procurement decisions are made within immunization programs. Semi-structured interviews were undertaken with 158 immunization stakeholders in Brazil, China, India, Peru, the Philippines, and Tanzania.
View Article and Find Full Text PDFIntroduction: This study captures the perspectives of stakeholders at multiple levels of the vaccine supply chain regarding their assessment of challenges with storing vaccines within recommended temperature ranges and their perceptions on the benefits of having vaccines with improved stability, including the potential short-term storage and transport of vaccines in a controlled-temperature chain.
Methods: Semi-structured interviews were undertaken with 158 immunization stakeholders in six countries. Interviewees included national decision-makers and advisors involved in vaccine purchasing decisions, national Expanded Programme on Immunization managers, and health and logistics personnel at national, subnational, and health facility levels.
Having data on the costs of the immunization system can provide decision-makers with information to benchmark the costs when evaluating the impact of new technologies or programmatic innovations. This paper estimated the supply chain and immunization service delivery costs and cost per dose in selected districts in Kenya and Tanzania. We also present operational data describing the supply chain and service delivery points (SDPs).
View Article and Find Full Text PDFInadvertent vaccine freezing often occurs in the cold chain and may cause damage to freeze‑sensitive vaccines. Liquid vaccines that contain aluminum salt adjuvants are particularly vulnerable. Polyol cryoprotective excipients have been shown to prevent freeze damage to hepatitis B vaccine.
View Article and Find Full Text PDFVaccination is considered the most cost-effective approach to preventing infectious diseases, yet better formulations and delivery methods for efficient distribution and administration of vaccines are needed, especially for low-resource settings. A fast-dissolving tablet (FDT) that could be packaged in a compact stackable blister sheet is a potentially attractive option for formulating oral vaccines, since it would minimally impact the cold chain and could potentially be administered directly to patients without reconstitution. This study focused on using one component of a live attenuated trivalent vaccine under development to produce a FDT for the prevention of diarrhea induced by enterotoxigenic Escherichia coli (ETEC).
View Article and Find Full Text PDFWith the introduction of new vaccines, developing countries are facing serious challenges in their vaccine supply and logistics systems. Storage capacity bottlenecks occur at national, regional, and district levels and system inefficiencies threaten vaccine access, availability, and quality. As countries adopt newer and more expensive vaccines and attempt to reach people at different ages and in new settings, their logistics systems must be strengthened and optimized.
View Article and Find Full Text PDFNew vaccine platform and delivery technologies that can have significant positive impacts on the effectiveness, acceptability, and safety of immunizations in developing countries are increasingly available. Although donor support for vaccine technology development is strong, the uptake of proven technologies by the vaccine industry and demand for them by purchasers continues to lag. This article explains the challenges and opportunities associated with accelerating the availability of innovative and beneficial vaccine technologies to meet critical needs in resource-poor settings over the next decade.
View Article and Find Full Text PDFAll vaccines are susceptible to damage by elevated temperatures and many are also damaged by freezing. The distribution, storage, and use of vaccines therefore present challenges that could be reduced by enhanced thermostability, with resulting improvements in vaccine effectiveness. Formulation and processing technologies exist that can improve the stability of vaccines at temperature extremes, however, customization is required for individual vaccines and results are variable.
View Article and Find Full Text PDFA combination of unique stabilizers and mild spray drying process conditions was employed to produce heat-stable measles vaccine powder. Live attenuated measles vaccine from Serum Institute of India was formulated with pharmaceutically approved stabilizers, including sugars, proteins, amino acids, polymers, surfactants, and plasticizers, as well as charged ions. In addition, the effects of buffer salt and pH on the storage stability of measles virus were examined.
View Article and Find Full Text PDFCold chain requirements for vaccine storage and distribution are both economic and logistical burdens for immunization programs, especially those in lower-resource settings. Inadvertent exposure of vaccines to both heat and freezing temperatures within such cold chains are frequently occurring problems in both developing and industrialized countries. Here we report on a new hepatitis B vaccine formulation that is stable against repeated freezing at -20 degrees C and is also stable for 12 months at 37 degrees C.
View Article and Find Full Text PDFAll vaccines lose potency over time and the rate of potency loss is temperature-dependent. Therefore, cold-chain systems have been established to ensure that the potency of vaccines is maintained by storing them under refrigerated conditions (in most cases between 2 and 8 degrees C) until the point of use. This article aims to review the approaches being used to develop thermostable vaccine formulations that would be resistant to damage caused by freezing or excessive heat, and that could reduce dependence on the cold chain.
View Article and Find Full Text PDFVaccines containing aluminum salt adjuvants are prone to inactivation following exposure to freeze-thaw stress. Many are also prone to inactivation by heat. Thus, for maximum potency, these vaccines must be maintained at temperatures between 2 degrees C and 8 degrees C which requires the use of the cold chain.
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