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Vaccine temperature control failures represent a significant public and private healthcare cost. Vaccines damaged by excessive heat or freezing lose their effectiveness, putting public health at risk. Some vaccine administration programs recommend placing water bottles inside domestic refrigerators used for vaccine storage as a thermal ballast, to mitigate temperature excursion risks. However, the effect of variable thermal ballast loading on refrigerator performance has not been thoroughly quantified or documented, and generalized programmatic recommendations are subject to end-user interpretation. Here we show that a thermal ballast load comprising ten to fifteen percent of the total refrigerator storage volume provides a measurable effect on domestic refrigerator temperature stability during power outage events, maintaining vaccine temperatures between 2 °C and 8 °C for 4 to 6 hours without power. Thermal ballast usage does not reliably reduce the frequency or severity of temperature excursions caused by repeated door opening, accidental "door left open" events, or refrigerator defrost cycle activation. Use of a moderate thermal ballast load is a practical strategy for mitigating temperature excursions risks in areas with frequent or protracted power outages, but the practice has limited benefit in other adverse scenarios. Empowering providers to make informed decisions about the use of thermal ballast materials supports better, safer vaccine management., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: This study was partially funded by an Interagency Agreement with Centers for Disease Control and Prevention (CDC) and the authors’ institution. As part of this agreement, MC provides technical guidance and research support to the CDC’s Vaccines for Children program. Additionally, MC is a member of the NSF Joint Committee for Vaccine Storage, a consensus body responsible for creating and maintaining an ANSI standard for purpose-built vaccine storage equipment. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

After the 2010 earthquake, Haiti committed to introducing 4 new antigens into its routine immunization schedule, which required improving its cold chain (ie, temperature-controlled supply chain) and increasing vaccine storage capacity by installing new refrigerators. We tested the feasibility of using remote temperature monitoring devices (RTMDs) in Haiti in a sample of vaccine refrigerators fueled by solar panels, propane gas, or electricity. We analyzed data from 16 RTMDs monitoring 24 refrigerators in 15 sites from March through August 2014. Although 5 of the 16 RTMDs exhibited intermittent data gaps, we identified typical temperature patterns consistent with refrigerator door opening and closing, propane depletion, thermostat insufficiency, and overstocking. Actual start-up, annual maintenance, and annual electricity costs for using RTMDs were $686, $179, and $9 per refrigerator, respectively. In Haiti, RTMD use was feasible. RTMDs could be prioritized for use with existing refrigerators with high volumes of vaccines and new refrigerators to certify their functionality before use. Vaccine vial monitors could provide additional useful information about cumulative heat exposure and possible vaccine denaturation.

Background: Gavi recommends solar refrigerators for vaccine storage in areas with less than eight hours of electricity per day, and WHO guidelines are more conservative. The question remains: Can solar refrigerators provide value where electrical outages are less frequent?, Methods: Using a HERMES-generated computational model of the Mozambique routine immunization supply chain, we simulated the use of solar versus electric mains-powered refrigerators (hereafter referred to as "electric refrigerators") at different locations in the supply chain under various circumstances., Results: At their current price premium, the annual cost of each solar refrigerator is 132% more than each electric refrigerator at the district level and 241% more at health facilities. Solar refrigerators provided savings over electric refrigerators when one-day electrical outages occurred more than five times per year at either the district level or the health facilities, even when the electric refrigerator holdover time exceeded the duration of the outage. Two-day outages occurring more than three times per year at the district level or more than twice per year at the health facilities also caused solar refrigerators to be cost saving. Lowering the annual cost of a solar refrigerator to 75% more than an electric refrigerator allowed solar refrigerators to be cost saving at either level when one-day outages occurred more than once per year, or when two-day outages occurred more than once per year at the district level or even once per year at the health facilities., Conclusion: Our study supports WHO and Gavi guidelines. In fact, solar refrigerators may provide savings in total cost per dose administered over electrical refrigerators when electrical outages are less frequent. Our study identified the frequency and duration at which electrical outages need to occur for solar refrigerators to provide savings in total cost per dose administered over electric refrigerators at different solar refrigerator prices., (Copyright © 2017. Published by Elsevier Ltd.)

Introduction: The vaccine vial monitor (VVM) registers cumulative heat exposure on vaccines over time. As low- and lower-middle-income countries transition beyond support from the Global Alliance for Vaccines and Immunization (Gavi), they will assume full responsibility for vaccine financing and procurement. It is unclear to what extent countries transitioning out of Gavi support will continue to include VVMs on their vaccines. This paper aims to systematically review evidence on VVM availability and use in low- and middle-income countries to document factors behind global access to and country demand for VVMs. Such results could help identify actions needed to ensure continued use of VVMs in countries that transition out of Gavi support., Methods: We performed a systematic review of electronic databases, reference lists, and grey literature in English and French languages with publication dates from 2005 onwards. The studies included were analyzed for the following outcomes: (1) availability and deployment of VVM-labeled vaccines; (2) VVM practices and perceptions in the immunization system; (3) vaccine introduction and decision-making processes; (4) Gavi graduation and vaccine program sustainability., Results: The study found that VVM availability and use was affected by multiple sourcing of vaccines and the extent to which VVM was included in the vaccine specification in the tendering documents when procuring vaccines. Knowledge about VVM and its impact on the EPI program was found to be high among health workers as well as decision-makers. However, the study also found that weak capacity in key national institutions such as NRA and NPA might impact on demand for VVM. As countries take decisions regarding the adoption of new vaccines, factors such as disease burden and vaccine price may assume greater importance than vaccine characteristics and presentation. Finally, the study found that countries rely largely on the advice and recommendations from technical partners such as WHO and PAHO., Conclusion: The study concludes that global access to and country demand for VVM are dependent on policy statements and recommendations about VVM by key policy institutions such as WHO and UNICEF. The study also concludes that despite Gavi-eligible countries having access to VVM-labeled vaccines, inclusion is often below 100%. Weak institutional capacity in key national agencies such as NRA and NPA seems to be a contributing factor, while other factors include the procurement of clear national policies on the inclusion of VVM on vaccines, along with the capacity to enforce the policy. Finally, the study concludes that knowledge about VVM and its impact on vaccine program efficiency, safety, and cost is critical for transitioning countries' continuous demand for VVM., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

While a number of new vaccines have been rolled out across the developing world (with more vaccines in the pipeline), cold chain systems are struggling to efficiently support national immunization programs in ensuring the availability of safe and potent vaccines. This article reflects on the Clinton Health Access Initiative, Inc. (CHAI) experience working since 2010 with national immunization programs and partners to improve vaccines cold chains in 10 countries-Ethiopia, Nigeria, Kenya, Malawi, Tanzania, Uganda, Cameroon, Mozambique, Lesotho and India - to identify the root causes and solutions for three common issues limiting cold chain performance. Key recommendations include: Collectively, the solutions detailed in this article chart a path to substantially improving the performance of the cold chain. Combined with an enabling global and in-country environment, it is possible to eliminate cold chain issues as a substantial barrier to effective and full immunization coverage over the next few years., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: As part of its vaccine supply chain redesign efforts, Kano state now pushes vaccines directly from 6 state stores to primary health centers equipped with solar refrigerators. Our objective is to describe preliminary results from the first 20months of Kano's direct vaccine delivery operations., Methods: This is a retrospective review of Kano's direct vaccine delivery program. We analyzed trends in health facility vaccine stock levels, and examined the relationship between stock-out rates and each of cascade vaccine deliveries and timeliness of deliveries. Analysis of vaccination trends was based on administrative data from 27 sentinel health facilities. Costs for both the in-sourced and out-sourced approaches were estimated using a bottoms-up model-based approach., Results: Overall stock adequacy increased from 54% in the first delivery cycle to 68% by cycle 33. Conversely, stock-out rates decreased from 41% to 10% over the same period. Similar trends were observed in the out-sourced and in-sourced programs. Stock-out rates rose incrementally with increasing number of cascade facilities, and delays in vaccine deliveries correlated strongly with stock-out rates. Recognizing that stock availability is one of many factors contributing to vaccinations, we nonetheless compared pre- and post- direct deliveries vaccinations in sentinel facilities, and found statistically significant upward trends for 4 out of 6 antigens. 1 antigen (measles) showed an upward trend that was not statistically significant. Hepatitis b vaccinations declined during the period. Overall, there appeared to be a one-year lag between commencement of direct deliveries and the increase in number of vaccinations. Weighted average cost per delivery is US$29.8 and cost per child immunized is US$0.7 per year., Conclusion: Direct vaccine delivery to health facilities in Kano, through a streamlined architecture, has resulted in decreased stock-outs and improved stock adequacy. Concurrent operation of insourced and outsourced programs has enabled Kano build in-house logistics capabilities., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

International efforts to eradicate smallpox in the 1960s and 1970s provided the foundation for efforts to expand immunization programmes, including work to develop immunization supply chains. The need to create a reliable system to keep vaccines cold during the lengthy journey from the manufacturer to the point of use, even in remote areas, was a crucial concern during the early days of the Expanded Programme on Immunization. The vaccine cold chain was deliberately separated from other medical distribution systems to assure timely access to and control of vaccines and injection materials. The story of the early development of the vaccine cold chain shows how a number of challenges were overcome with technological and human resource solutions. For example, the lack of methods to monitor exposure of vaccines to heat during transport and storage led to many innovations, including temperature-sensitive vaccine vial monitors and better methods to record and communicate temperatures in vaccine stores. The need for appropriate equipment to store and transport vaccines in tropical developing countries led to innovations in refrigeration equipment as well as the introduction and widespread adoption of novel high performance vaccine cold-boxes and carriers. New technologies also helped to make injection safer. Underlying this work on technologies and equipment was a major effort to develop the human resources required to manage and implement the immunization supply chain. This included creating foundational policies and a management infrastructure; providing training for managers, health workers, technicians, and others. The vaccine cold chain has contributed to one of the world's public health success stories and provides three priority lessons for future: the vaccine supply chain needs to be integrated with other public health supplies, re-designed for efficiency and effectiveness and work is needed in the longer term to eliminate the need for refrigeration in the supply chain., (Copyright © 2017. Published by Elsevier Ltd.)

Vaccination rates have improved in many countries, yet immunization inequities persist within countries and the poorest communities often bear the largest burden of vaccine preventable disease. Madagascar has one of the world's largest equity gaps in immunization rates. Barriers to immunization include immunization supply chain, human resources, and service delivery to reflect the health system building blocks, which affect poor rural communities more than affluent communities. The Reaching Every District (RED) approach was revised to address barriers and bottlenecks. This approach focuses on the provision of regular services, including making cold chain functional. This report describes Madagascar's inequities in immunization, its programmatic causes and the country's plans to address barriers to immunization in the poorest regions in the country., Methods: Two cross-sectional health facility surveys conducted in November and December 2013 and in March 2015 were performed in four regions of Madagascar to quantify immunization system barriers., Findings: Of the four regions studied, 26-33% of the population live beyond 5km (km) of a health center. By 2015, acceptable (fridges stopped working for less than 6days) cold chains were found in 52-80% of health facilities. Only 10-57% of health centers had at least two qualified health workers. Between 65% and 95% of planned fixed vaccination sessions were conducted and 50-88% of planned outreach sessions were conducted. The proportion of planned outreach sessions that were conducted increased between the two surveys., Conclusion: Madagascar's immunization program faces serious challenges and those affected most are the poorest populations. Major inequities in immunization were found at the subnational level and were mainly geographic in nature. Approaches to improve immunization systems need to be equitable. This may include the replacement of supply chain equipment with those powered by sustainable energy sources, monitoring its functionality at health facility level and vaccination services in all communities., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Vaccine exposure to temperatures below recommended ranges in the cold chain may decrease vaccine potency of freeze-sensitive vaccines leading to a loss of vaccine investments and potentially places children at risk of contracting vaccine preventable illnesses. This literature review is an update to one previously published in 2007 (Matthias et al., 2007), analyzing the prevalence of vaccine exposure to temperatures below recommendations throughout various segments of the cold chain. Overall, 45 studies included in this review assess temperature monitoring, of which 29 specifically assess 'too cold' temperatures. The storage segments alone were evaluated in 41 articles, 15 articles examined the transport segment and 4 studied outreach sessions. The sample size of the studies varied, ranging from one to 103 shipments and from three to 440 storage units. Among reviewed articles, the percentage of vaccine exposure to temperatures below recommended ranges during storage was 33% in wealthier countries and 37.1% in lower income countries. Vaccine exposure to temperatures below recommended ranges occurred during shipments in 38% of studies from higher income countries and 19.3% in lower income countries. This review highlights continuing issues of vaccine exposure to temperatures below recommended ranges during various segments of the cold chain. Studies monitoring the number of events vaccines are exposed to 'too cold' temperatures as well as the duration of these events are needed. Many reviewed studies emphasize the lack of knowledge of health workers regarding freeze damage of vaccines and how this has an effect on temperature monitoring. It is important to address this issue by educating vaccinators and cold chain staff to improve temperature maintenance and supply chain management, which will facilitate the distribution of potent vaccines to children., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Insulin loses potency when stored at high temperatures. Various clay pots part-filled with water, and other evaporative cooling devices, are used in less-resourced countries when home refrigeration is unavailable. This study examined the cooling efficacy of such devices., Methods: Thirteen devices used in Sudan, Ethiopia, Tanzania, Mali, India, Pakistan and Haiti (10 clay pots, a goat skin, a vegetable gourd and a bucket filled with wet sand), and two identical commercially manufactured cooling wallets were compared. Devices were maintained according to local instructions. Internal and ambient temperature and ambient humidity were measured by electronic loggers every 5 min in Khartoum (88 h), and, for the two Malian pots, in Bamako (84 h). Cooling efficacy was assessed by average absolute temperature difference (internal vs. ambient), and % maximal possible evaporative cooling (allowing for humidity)., Results: During the study period, mean ambient temperature and humidity were 31.0°C and 32.0% in Khartoum and 32.9°C and 39.8% in Bamako. All devices reduced the temperature (P < 0.001) with a mean (sd) reduction from 2.7 ± 0.5°C to 8.3 ± 1.0°C, depending on the device. When expressed as % maximal cooling, device efficacy ranged from 20.5% to 71.3%. On cluster analysis, the most efficacious devices were the goat skin, two clay pots (from Ethiopia and Sudan) and the suspended cooling wallet., Conclusions: Low-cost devices used in less-resourced countries reduce storage temperatures. With more efficacious devices, average temperatures at or close to standard room temperature (20-25°C) can be achieved, even in hot climates. All devices are more efficacious at lower humidity. Further studies are needed on insulin stability to determine when these devices are necessary., (© 2016 Diabetes UK.)

This commentary reviews recent changes in Centers for Disease Control (CDC) vaccine storage guidelines that were developed in response to an investigative report by the Office of the Inspector General. The use of temperature data loggers with probes residing in glycol vials is advised along with storing vaccines in pharmaceutical refrigerators. These refrigerators provide good thermal distribution but can warm to 8 °C in less than one hour after the power is discontinued. Consequently, electric grid instability influences appropriate refrigerator selection and the need for power back-up. System Average Interruption Duration Index (SAIDI) values quantify this instability and can be used to formulate region-specific guidelines. A novel aftermarket refrigerator with a battery back-up power supply and microprocessor control system is also described.

Background: The challenge of keeping vaccines cold at health posts given the unreliability of power sources in many low- and middle-income countries and the expense and maintenance requirements of solar refrigerators has motivated the development of passive cold storage devices (PCDs), containers that keep vaccines cold without using an active energy source. With different PCDs under development, manufacturers, policymakers and funders need guidance on how varying different PCD characteristics may affect the devices' cost and utility., Methods: We developed an economic spreadsheet model representing the lowest two levels of a typical Expanded Program on Immunization (EPI) vaccine supply chain: a district store, the immunization locations that the district store serves, and the transport vehicles that operate between the district store and the immunization locations. The model compares the use of three vaccine storage device options [(1) portable PCDs, (2) stationary PCDs, or (3) solar refrigerators] and allows the user to vary different device (e.g., size and cost) and scenario characteristics (e.g., catchment area population size and vaccine schedule)., Results: For a sample set of select scenarios and equipment specification, we found the portable PCD to generally be better suited to populations of 5,000 or less. The stationary PCD replenished once per month can be a robust design especially with a 35L capacity and a cost of $2,500 or less. The solar device was generally a reasonable alternative for most of the scenarios explored if the cost was $2,100 or less (including installation). No one device type dominated over all explored circumstances. Therefore, the best device may vary from country-to-country and location-to-location within a country., Conclusions: This study introduces a quantitative model to help guide PCD development. Although our selected set of explored scenarios and device designs was not exhaustive, future explorations can further alter model input values to represent additional scenarios and device designs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Typically, vaccines distributed through the Expanded Program on Immunization (EPI) use a 2-8°C cold chain with 4-5 stops. The PfSPZ Vaccine comprises whole live-attenuated cryopreserved sporozoites stored in liquid nitrogen (LN(2)) vapor phase (LNVP) below -140°C and would be distributed through a LNVP cold chain. The purpose of this study was to model LNVP cold chain distribution for the cryopreserved PfSPZ Vaccine in Tanzania, estimate the costs and compare these costs to those that would be incurred in distributing a 'conventional' malaria vaccine through the EPI. Capital and recurrent costs for storage, transportation, labor, energy usage and facilities were determined for the birth cohort in Tanzania over five years. Costs were calculated using WHO/UNESCO calculators. These were applied to a 2-8°C distribution model with national, regional, district, and health facility levels, and for the cryopreserved vaccine using a 'modified hub-and-spoke' (MH-S) LNVP distribution system comprising a central national store, peripheral health facilities and an intermediate district-level transhipment stop. Estimated costs per fully immunized child (FIC) were $ 6.11 for the LNVP-distributed cryopreserved vaccine where the LN(2) is generated, and $ 6.04 with purchased LN(2) (assuming US $ 1.00/L). The FIC costs for distributing a conventional vaccine using the four level 2-8°C cold chain were $ 6.10, and with a tariff distribution system as occurs in Tanzania the FIC cost was $ 5.53. The models, therefore, predicted little difference in 5-year distribution costs between the PfSPZ Vaccine distributed through a MH-S LNVP cold chain and a conventional vaccine distributed through the more traditional EPI system. A LNVP cold chain provides additional benefits through the use of durable dry shippers because no refrigerators, freezers or refrigerated trucks are required. Thus strain at the cold chain periphery, vaccine wastage from cold chain failures and the environmental impact of distribution would all be reduced., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: There is limited epidemiological data on the performance of different refrigerator types for vaccine storage in the real world. This study aims to measure if the introduction of purpose-built vaccine refrigerators has reduced the cost of vaccine losses in South Australia., Methods: Data were taken from a register for all recorded vaccine storage cold chain events in South Australia from 2008 to 2009 and a survey of vaccine providers conducted in 2009., Results: There were 531 respondents to the survey (51% response rate). A greater proportion of cold chain breaches in purpose-built vaccine refrigerators did not lead to a loss of vaccine (10.3%) compared with the other refrigerator types. Purpose-built vaccine refrigerators had a relative risk of 3.31 (95% CI, 2.15-5.11) of a heat event (as opposed to cold event) and were more likely to have a cold chain breach from electrical failure (relative risk ratio 15.05, 95% CI 4.04-56.05) than bar refrigerators. The average cost of loss of vaccine for purpose-built vaccine refrigerators was $2,321.20, which was greater than the cost of vaccine loss from a bar refrigerator of $1,339.06 (95% CI $61.47-1,902.82)., Conclusions: Although purpose-built vaccine refrigerators were less likely to lead to vaccine loss per cold chain breach, they had a greater average cost of vaccine loss per cold chain event because they held a greater volume of vaccine. There is a need for development of Standards to guide purpose-built vaccine refrigerators manufacturing and a review of the National Vaccine Storage Guidelines to place a greater emphasis on the need for back up plans in the event of electrical failure., (© 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.)

This commentary compares Centers for Disease Control (CDC) guidelines for vaccine storage with international cold chain standards. Problems related to the use of domestic refrigerators in clinical settings are discussed. Optimal vaccine refrigerator design characteristics are summarized. The adoption of World Health Organization storage recommendations is advised.

Background: Cold chain maintenance is an essential activity to maintain the potency of vaccines and to prevent adverse events following immunization. One baseline study highlighted the unsatisfactory cold chain status in city of Kolkata in India., Objectives: To assess the changes which occurred in the cold chain status after the intervention undertaken to improve the status and also to assess the awareness of the cold chain handlers regarding cold chain maintenance., Methods: Intervention consisted of reorganization of cold chain points and training of health manpower in Kolkata Municipal area regarding immunization and cold chain following the guidelines as laid by Govt of India. Reevaluation of cold chain status was done at 20 institutions selected by stratified systematic random sampling after the intervention. The results were compared with baseline survey., Results: Significant improvement had been observed in correct placing of cold chain equipment, maintenance of stock security, orderly placing of ice packs, diluents and vaccines inside the equipment, temperature recording and maintenance. But awareness and skill of cold chain handlers regarding basics of cold chain maintenance was not satisfactory., Conclusions: The success of intervention included significant improvement of cold chain status including creation of a designated cold chain handler. The gaps lay in non-availability of non-electrical cold chain equipment and separate cold chain room, policy makers should stress. Cold chain handlers need reorientation training regarding heat & cold sensitive vaccines, preventive maintenance and correct contingency plan.

The Centers for Disease Control and Prevention reports that professionals in clinic settings may not be adequately storing and handling vaccine, leading to insufficient immunity of vaccinated individuals. Part 2 of this article provides information about the importance of adequate personnel training and program management policies and procedures needed to implement and maintain an effective vaccine cold chain program., (Copyright 2010, SLACK Incorporated.)

Purpose: Data regarding the recommended maximum duration that refrigerated medications available in hospital pharmacies may be stored safely at room temperature were collected and compiled in a tabular format., Methods: During May and June of 2006, the prescribing information for medications labeled for refrigeration as obtained from the supplier were reviewed for data addressing room-temperature storage. Telephone surveys of the products' manufacturers were conducted when this information was not available in the prescribing information. Medications were included in the review if they were labeled to be stored at 2-8 degrees C and purchased by the pharmacy department for uses indicated on the hospital formulary. Frozen antibiotics thawed in the refrigerator and extemporaneously compounded medications were excluded. Information was compiled and arranged in tabular format. The U.S. Pharmacopeia's definition of room temperature (20-25 degrees C [68-77 degrees F]) was used for this review., Results: Of the 189 medications listed in AHFS Drug Information 2006 for storage in a refrigerator, 89 were present in the pharmacy department's refrigerator. Since six manufacturers were unable to provide information for 10 medications, only 79 medications were included in the review. This table may help to avoid unnecessary drug loss and expenditures due to improper storage temperatures., Conclusion: Information regarding the room-temperature storage of 79 medications labeled for refrigerated storage was compiled.

Objective: A refrigerator-stable formulation of ProQuad has been developed to expand the utility of ProQuad to areas in which maintenance of a frozen cold chain (-15 degrees C or colder) during storage and transport may not be feasible. The objective of this study was to demonstrate that the immunogenicity and safety profiles of a refrigerator-stable formulation of ProQuad are similar to the recently licensed frozen formulation., Methods: In this double-blind, randomized, multicenter study, healthy 12- to 23-month-old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either the refrigerator-stable formulation of ProQuad (N = 1006) or the frozen formulation of ProQuad (N = 513). Patients were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination., Results: The refrigerator-stable formulation of ProQuad was generally well tolerated. The incidence of adverse experiences was similar between groups. No vaccine-related serious adverse experiences were reported. For both groups, the response rate was > or = 97.7% for measles, mumps, and rubella, and the percentage of patients with a varicella zoster virus antibody titer of > or = 5 U/mL glycoprotein antigen-based enzyme-linked immunosorbent assay after vaccination was > or = 88.8%. The geometric mean titers for all antigens were numerically slightly higher in patients who received the refrigerator-stable formulation., Conclusions: The refrigerator-stable formulation of ProQuad is generally well tolerated, highly immunogenic, and noninferior in terms of postvaccination antibody responses. This refrigerator-stable formulation may improve ease of vaccine administration, increase use of the vaccine throughout the world because of its improved storage conditions, and replace the frozen formulation of ProQuad or any dose of M-M-RII and Varivax in routine practice.

Objective: The purpose of this study was to determine (1) the rate of contamination for a normal saline solution prepared with distilled water and salt when stored at room temperature and (2) when stored under refrigerated conditions; and (3) to compare the rate of contamination for solutions prepared and stored under controlled conditions with those prepared and stored in patients' homes., Design: This quasi-experimental study examined the bacterial content of saline made with distilled water and stored at room temperature and that of saline stored in a refrigerator., Setting: A large urban home health agency was the setting for the study., Methods: Eight teaspoons of table salt were added to 1-gallon jugs of distilled water purchased from a grocery store to produce a normal saline solution. Two gallons of the prepared solution were stored at room temperature (80 degrees F) and 2 were stored in a refrigerator (48 degrees F). Cultures were taken from each of the 4 bottles of prepared solution immediately following preparation and at weekly intervals until bacterial growth occurred, or 4 weeks after preparation., Results: All tested solutions were negative for bacterial growth at baseline. Cultures of the solution stored at room temperature were positive for bacterial growth 2 weeks after preparation, whereas those stored under refrigerated conditions remained free of bacterial contamination 4 weeks after preparation. Two "patient-prepared" solutions were tested at 3 weeks, and both were negative for bacteria at that time. Three patient-prepared solutions were tested at 4 weeks, of which 2 showed no bacterial growth in 48 hours, whereas 1 revealed 600 cfu/mL of Pseudomonas species., Conclusions: The results of this small study suggest that saline solutions produced by adding table salt to distilled water will remain bacteria-free for 1 month if refrigerated. Additional studies are needed to confirm these findings.

The study aimed to demonstrate satisfactory inter-UK transit of cold storage clinical trial material. The product environment had to be maintained between 0 and 8 degrees C throughout transit until delivery. Straightforward, low cost and simplified shipping arrangements were sought that would be appropriate for small-scale Phase I clinical trial activities. A laboratory test defined an optimal three frozen gel pack configuration to maintain refrigerated environmental conditions for dummy product packs in a single type and size of insulated shipper. The internal environment was temperature monitored at 30-min intervals in all tests. Twelve Glasgow to London transits were then studied over 2 years to include all seasonal temperature variations. A configuration using three frozen gel packs and 4 h pre-chill of the transit container maintained the internal environment at 0-8 degrees C for up to 48 h during autumn, winter and spring. A modified four frozen gel pack configuration was suitable for summer transit. Thus cold shipment verification was successfully carried out for a small-scale distribution operation. It was proven that refrigerated shipping conditions could be maintained using a straightforward and cost effective 'passive' type system consisting of frozen gel packs and insulated transit containers.

Objectives: To study the practices of health personnel regarding vaccine storage and the integrity of the cold chain, during storage, in immunisation clinics., Design: A cross-sectional descriptive survey based on a postal questionnaire and an observational study of the cold chain during storage of a randomly selected sample., Setting: Colombo District., Participants: 10 health centres, 13 Colombo Municipal Council Clinics, 26 general practices receiving vaccines from health centres, 13 private hospitals and 10 state-run hospitals., Method: A pretested postal questionnaire collected information on storage conditions and compliance with EPI requirements. The sub-sample in which the temperatures were monitored consisted of 33% of the total. The study was carried out in 1995-1996, when there was an uninterrupted power supply., Outcome Measures: Responses to the postal questionnaires and the colour changes recorded in thermosensitive WHO cold chain monitors., Results: The response rate to the postal questionnaire was 87.5%. All 63 respondents stored vaccines in refrigerators worked by electricity. Information regarding refrigerators showed 46% to be less than 5 years old and 17% were more than 15 years old. 97% of refrigerators had good door seals. Regular defrosting was claimed by 79% of clinics and 81% had a named person responsible for vaccine storage. Only 57% had thermometers available and temperatures were monitored daily in only 40% of clinics. 76% of refrigerators were used for purposes other than storage of vaccines. Colour changes were noted in 2 out of 22 cold chain monitors.

Approaches to performing stability tests on formulations developed in hospitals, defined as the near-patient situation, are reviewed. Emphasis is placed on the selection and validation of storage conditions and the statistical methodology necessary to ensure confidence in the results obtained.