Because the DoD is a recipient of funds from other organizations, notably USAID, NIAID, and the Gates Foundation, WRAIR and NMRC independently manage funds that at least triple the intramural total.
Worldwide, it was estimated that $323 million was spent on malaria research and development (including drugs, vaccines, vector control, and diagnostics) in 2004 (Malaria R&D Alliance, 2005). About one-quarter of this total (approximately $80 million) was spent on malaria vaccine research and development. Thus with a contribution of over $9 million in 2004, DoD is a significant contributor to the world’s malaria vaccine research and development effort in financial as well as scientific terms (see above).
Notwithstanding the DoD’s major financial contribution, the amount spent by MIDRP on malaria vaccine research and development falls far short of the required amount to bring even one vaccine product to licensure, which was estimated above to cost upwards of $300 million at the very least, and probably much more (see Table 2-3).
It appeared to the committee that lack of funding was dictating suboptimal decision making—for example, the selection by NMRC of only two of the CSLAM antigens rather than the full set of five for the first clinical trials of the DNA-adenovirus prime-boost approach. The committee’s opinion was that limiting the vaccine in this way was not fully capitalizing on previous research and was reducing the chances of success. There are other technical challenges, such as purification and production of large quantities of GMP proteins for clinical trials and licensure, that can also be overcome given sufficient resources and access to facilities.
The Forest Glen GMP pilot production facility is crucial to the program as it overcomes the barrier of producing sufficient material for phase 1 and phase 2 trials of certain antigens. It enables the program to produce in-house many potential antigens and constructs for screening. Currently the facility produces recombinant proteins but could produce certain other potential types of candidate vaccines. The facility time available to the malaria program is currently limited by the need to support the facility by contracting out to other groups.
At present, it is not envisaged that the Forest Glen GMP pilot production facility would produce the material for pivotal phase 3 licensure track trials of the vaccine. Careful planning and costing for the transition from in-house production to a larger-scale facility for phase 3 trials is needed. Ideally, the large-scale manufacture facility that would prepare the phase 3 material would be the site of manufacture of the vaccine postlicensure. External collaboration with industry will almost certainly be required, but such must be carefully managed to enable the DoD to achieve its primary goals.