The Case for Investment in R&D for Three Immunization Technologies: Recommendations for GAVI Action

12th GAVI Board Meeting? 9-10 December 2003, Geneva, Switzerland
The Case for Investment in R&D for Three Immunization Technologies:
Recommendations for GAVI Action
This report was prepared by the GAVI Working Group to summarize and build upon the
findings of the New Technology Working Group (NTWG) and provide recommendations
to the GAVI Board for research and development (R&D) for immunization technologies.
Recommendations are provided both for development of each specific set of technologies
(nested in the three sections of the report) and for GAVI?s broader role in R&D for vaccines
and immunization.
Background
During its meeting in Stockholm in March 2002, the GAVI Board reviewed a proposal by
the R&D Task Force regarding priority technologies for improving the quality and reach of
immunization services. Three priorities for technology development were identified:
? Reduced costs and improved efficacy through elimination of the cold chain;
? Performance monitoring through detection of biomarkers of effective immunization;
and,
? Improved safety through improved management of infectious waste and/or
elimination of the use of sharps.
In each of the three areas, the R&D Task Force chose one specific technology as a
promising example for further study by the New Technology Working Group (NTWG) of
the R&D TF. These included:
1. Sugar glass stabilization for elimination of the cold chain
2. Non-invasive tetanus antitoxin tests for performance monitoring; and,
3. Defanging devices for improved safety.
The NTWG prepared a detailed scientific report on these selected technologies that was
discussed by the GAVI Working Group in June 2003. Before the presentation of these
findings to the Board, the Working Group recommended the preparation of a succinct
summary and the inclusion of additional analysis, including:
? The ?landscape? of current R&D efforts for related technologies;
? The summary of data establishing the ?public health case? and ?business case? for
investment in these technologies; and,
? Specific recommendations to the GAVI Board for action in the development of
these and other new technologies for immunization.
Section 1: Sugar Glass Stabilization
Magnitude of the Problem
All current vaccines are thermolabile, requiring continuous storage and transport in a cold
chain to ensure their potency and safety. This thermolability of vaccines, along with the
cost and fragility of the cold chain in resource-poor settings, defines a substantial set of
constraints to cost-effective immunization:
? Annualized direct costs of establishing and maintaining the logistics-intensive cold chain in the developing world, which are estimated at US $200 million 1;
? Frequent detection of breaks in the cold chain (including damage due to both heat
and freezing) and resulting spoilage of vaccine, estimated to result in costs in excess of
US $100 million per year 2;
? Further undetected failures of the cold chain (especially due to freezing, as the
vaccine vial monitors - VVMs ? that are currently in use detect only heat exposure),
resulting in an unknown reduction in efficacy of vaccines, excess morbidity and mortality
due to vaccine preventable disease, and damage to the public confidence in
immunization3;
? Additional logistical burden, costs, and compromise of safety due to the need to
reconstitute those vaccines that are lyophilized to enhance stability.
Technical Landscape
Other Candidate Technologies
Several technologies are currently employed routinely to solve the problem of thermolability,
by continuously maintaining a ?cold chain? from the moment of release of vaccine from the
manufacturer, through international transport and supply depots, to where vaccines are
administered. These include technologies for refrigeration, insulation (such as cold boxes),
and temperature monitoring (including vaccine vial monitors to detect heat-compromise).
No acceptable technology is in use to detect freeze damage. Other current and potential
candidate technologies to solve the problem of thermolability include:
Vaccine Vial Monitors (VVMs): VVMs enable the end-user of a vaccine to identify whether
any heat exposure has endangered the efficacy of the vaccine. This permits minor breaks in
the cold chain to be accommodated without undue vaccine wastage and ensures that heat-
compromised vaccine is ?flagged? to be discarded. While VVMs are not yet in universal use
for all GAVI-procured vaccines, efforts are underway to clear the last remaining barriers.
Improved Refrigeration Systems: Several improvements in refrigeration systems are slowly being
implemented as equipment ages and requires replacement. Central stores of vaccine stock
can be protected with computer-based monitoring to reduce both detected and undetected
temperature damage. Ice-lined refrigeration equipment with better temperature control is
being introduced gradually in intermediate stores to protect against accidental freezing of
vaccines. At the periphery, replacement of kerosene refrigerators with hybrid solar
equipment will result in better temperature control. These improvements will further drive
up the annual costs of refrigeration for vaccines in developing countries, already
conservatively estimated at US $200 million per year4.
Lyophilization: Lyophilization of vaccines (eg. Measles, HiB, Rotavirus, meningococcal
polysaccharide) involves immobilizing in a cake of semi-crystalline sugar (lactose or sorbitol
supplemented with mannitol, amino acids and, in older vaccines, proteins such as gelatin or
bovine serum). This confers reasonable stability (typically several weeks at ambient
temperature) and resistance to freezing but storage in the cold chain is still required.
Unfortunately as soon as vaccines are reconstituted they begin to lose activity and must be
kept cool. Vaccine not used within several hours is wasted. As mentioned above the
increased logistical and safety problems associated with vaccines that require reconstitution
make this approach problematic. Hence, although this approach could theoretically be
applied to alum-containing vaccines to render them freeze-resistant, the gain is offset by the
increased logistics.
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