Evaluating the value proposition for improving vaccine thermostability to increase vaccine impact in low and middle-income countries.

The need to keep vaccines cold in the face of high ambient temperatures and unreliable access to electricity is a challenge that limits vaccine coverage in low and middle-income countries (LMICs). Greater vaccine thermostability is generally touted as the obvious solution. Despite conventional wisdom, comprehensive analysis of the value proposition for increasing vaccine thermostability has been lacking. Further, while significant investments have been made in increasing vaccine thermostability in recent years, no vaccine products have been commercialized as a result. We analyzed the value proposition for increasing vaccine thermostability, grounding the analysis in specific vaccine use cases (e.g., use in routine immunization [RI] programs, or in campaigns) and in the broader context of cold chain technology and country level supply chain system design. The results were often surprising. For example, cold chain costs actually represent a relatively small fraction of total vaccine delivery system costs. Further, there are critical, vaccine use case-specific temporal thresholds that need to be overcome for significant benefits to be reaped from increasing vaccine thermostability. We present a number of recommendations deriving from this analysis that suggest a rational path toward unlocking the value (maximizing coverage, minimizing total system costs) of increased vaccine thermostability, including: (1) the full range of thermostability of existing vaccines should be defined and included in their labels; (2) for new vaccines, thermostability goals should be addressed up-front at the level of the target product profile; (3) improving cold chain infrastructure and supply chain system design is likely to have the largest impact on total system costs and coverage in the short term-and will influence the degree of thermostability required in the future; (4) in the long term, there remains value in monitoring the emergence of disruptive technologies that could remove the entire RI portfolio out of the cold chain.

Development, clinical evaluation, and post-licensure impact of RotaTeq, a pentavalent rotavirus vaccine.

Rotavirus gastroenteritis (RVGE) is the leading cause of severe diarrhea in children worldwide. This paper provides an overview of the development, clinical evaluation, and postlicensure impact of RotaTeq™(Rotavirus Vaccine, Live, Oral, Pentavalent, Merck & Co., Inc.). RotaTeq, an oral vaccine, is uniquely designed to contain five human-bovine reassortant rotavirus strains expressing the human serotypes G1, G2, G3, G4, and P1A[8], which represent the most common human rotavirus serotypes responsible for ∼85% of RVGE worldwide. The development required novel solutions for manufacturing, testing, and formulation for each of the reassortants. In one of the largest vaccine clinical trials conducted, the vaccine was shown to be well tolerated and highly efficacious against severe RVGE. Efficacy has also been demonstrated in lower-income countries. In large U.S. postlicensure studies, there have been no safety signals identified, and RotaTeq has had a significant impact on reducing RVGE and its associated medical costs since licensure in 2006.