Elsevier

Vaccine

Volume 25, Issue 20, 16 May 2007, Pages 3980-3986
Vaccine

Freezing temperatures in the vaccine cold chain: A systematic literature review

https://doi.org/10.1016/j.vaccine.2007.02.052Get rights and content

Abstract

The dangers of accidental freezing of vaccines in the cold chain have prompted studies throughout the globe to better characterize the risk. To date, there has been no systematic review of these studies. This analysis highlights that accidental freezing is pervasive and occurs across all segments of the cold chain. Between 14% and 35% of refrigerators or transport shipments were found to have exposed vaccine to freezing temperatures, while in studies that examined all segments of distribution, between 75% and 100% of the vaccine shipments were exposed. More rigorous study designs were associated with higher levels of freeze exposure. As more expensive, freeze-sensitive vaccines are introduced into immunization schedules, freeze prevention will become increasingly critical for ensuring that the world's children are receiving fully potent vaccine.

Introduction

Vaccines are powerful public health tools that save an estimated 3 million lives each year [1]. Recognizing their importance, the global health community has prioritized the increased availability of vaccines to all the world's children. Yet this commitment has also had the effect of placing additional stress on an already fragile cold chain, the distribution network of equipment and procedures used to maintain vaccine quality from the vaccine manufacturer to the vaccine recipient.

World Health Organization (WHO) guidelines and manufacturer product inserts recommend that all vaccines except oral polio vaccine be kept at 2–8 °C during in-country distribution. However, a poorly functioning cold chain may deviate from this target range and expose vaccines to freezing temperatures. Damage from accidental freezing can result in potency loss for freeze-sensitive vaccines such as diphtheria, tetanus, pertussis, liquid Haemophilus influenzae type b (Hib), hepatitis B, and inactivated polio virus [2], [3], [4], [5], [6]. However, cold chain practices tend to prioritize protecting vaccine from heat damage, often at the risk of exposure to freezing temperatures. As a result, accidental freezing of vaccines is a largely overlooked problem, yet freeze-sensitive vaccines represented over 31% of the US$ 439 million UNICEF spent on all vaccines in 2005 [7].

Increased awareness of this danger has prompted studies of the cold chain, designed to characterize the risks of vaccine exposure to freezing temperatures. However, to date there has been no systematic review or cross-comparison of these studies. This paper attempts to review and analyze the current global data on freezing temperatures within the vaccine cold chain. The objective is to identify the settings in which freezing occurs and explore common factors among these studies and settings. It is our hope that this review will help raise further awareness of the extent to which vaccines are being exposed to freezing temperatures worldwide as well as encourage immunization program managers to design studies to investigate the state of their own cold chains and institute programmatic actions to prevent potential freeze exposure.

Section snippets

Identification of cold chain studies

To capture the broadest range of cold chain studies for inclusion within our analysis, a search for studies published between January 1985 and June 2006 was performed using four major electronic databases: PubMed, Popline, Embase, and Biosis. The term “vaccine” coupled with one of the following terms was searched in all databases: thermostability, stability, refrigerator, cold chain, storage, and temperature. In addition, we searched several public health websites for unpublished studies,

Identified studies

Of the 35 articles selected, 17 articles reported on research that was conducted in developed countries and 18 in developing countries. Each subset was then further divided into studies evaluating the temperatures of storage versus transport segments of the cold chain (Table 1). Two articles were dropped prior to the comparative analysis due to an inability to compare the reported data points on the same basis as the other studies (marked with an asterisk in Table 1). Six of the remaining 33

Analysis of key findings

  • During transport, the occurrence of freezing temperatures was found to be 16.7% in developed countries compared to 35.3% in developing countries. This difference was not significant, potentially indicating that the current transport practice common to all countries – vaccines placed with frozen ice packs inside of insulated carriers – is placing vaccines at risk, regardless of the resource setting in which it is conducted. Observations indicate that the WHO-recommended practice of

Conclusion

This analysis highlights that exposure of vaccines to freezing temperatures is pervasive, occurring in both developed- and developing-country settings, as well as within both the storage and transport segments of the cold chain. Across the four scenarios analyzed, the average proportion of exposure ranges from 14% to 35%. In the six studies that measured temperatures longitudinally through multiple sections of the cold chain, between 75% and 100% of the vaccine shipments were exposed to

Acknowledgements

These materials were developed at PATH with support from the Bill & Melinda Gates Foundation and the Bureau for Global Health, United States Agency for International Development (USAID), under the HealthTech Program, Cooperative Agreement #GPH-A-00-01-00005-00. The opinions expressed herein are those of the authors and do not necessarily reflect the views of either the Bill & Melinda Gates Foundation or USAID.

References (49)

  • UNICEF website. Available at: http://www.unicef.org/immunization/index_coverage.html; accessed January 10,...
  • WHO

    Temperature sensitivity of vaccines

    (2006)
  • UNICEF Supply Division annual report page. UNICEF website. Available at:...
  • World Bank website. Available at: http://www.worldbank.org/data/countryclass/countryclass.html; accessed July...
  • E. Cheriyan

    Monitoring the vaccine cold chain

    Arch Dis Childhood

    (1993)
  • S.L. Guthridge et al.

    Cold chain in a hot climate

    Aus NZ J Public Health

    (1997)
  • PATH, University of Melbourne. Unpublished report;...
  • Glele Kakaï CF. Study of factors influencing the quality of EPI vaccines in the health district of Natitingou [Benin]...
  • C.M. Nelson et al.

    Hepatitis B vaccine freezing in the Indonesian cold chain: evidence and solutions

    Bull World Health Organ

    (2004)
  • Village Reach, PATH. Unpublished report;...
  • Wirkas T, Toikilik S, Miller N, Morgan C, Clements CJ. A vaccine cold chain freezing study in PNG highlights technology...
  • S.A. Klotz et al.

    Hepatitis B vaccine in healthy hospital employees

    Infect Control

    (1986)
  • A.A. McLean et al.

    Hepatitis B vaccine

    Ann Intern Med

    (1982)
  • WHO

    Study protocol for temperature monitoring in the vaccine cold chain

    (2005)
  • Cited by (0)

    1

    Tel.: +1 206 285 3500; fax: +1 206 285 6619.

    2

    Tel.: +1 206 616 1203; fax: +1 206 616 4623.

    View full text