PLoS Medicine
(Accessed 27 February 2011)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1c2a2501181c#results

Dengue Vaccines Regulatory Pathways: A Report on Two Meetings with Regulators of Developing Countries
Richard Mahoney, Liliana Chocarro, James Southern, Donald P. Francis, John Vose, Harold Margolis Policy Forum, published 22 Feb 2011
doi:10.1371/journal.pmed.1000418

Summary Points
– Because a dengue vaccine should be tetravalent in nature and provide protection against all four dengue serotypes, regulatory agencies need to address additional issues associated with multi-valent vaccines such as interference between the vaccine serotypes.

– Safety assessment needs to account for the potential risk of inducing antibody-enhanced diseases (antibody-dependent enhancement).

– Because of the varying epidemiology and disease impact in different countries and regions, dengue vaccines will likely need to be evaluated in diverse populations initially in both the Americas and the Asia Pacific region.

– Several national regulatory authorities (NRAs) in endemic developing countries are likely to be engaged in review of both applications for clinical evaluation and for marketing of vaccines and they should receive support as appropriate.

– Manufacturers can submit a dossier to the European Medicines Agency for the Evaluation of Medicinal Products (EMA) for review (Scientific Opinion). This is possible due to the introduction of Article 58 of EMA’s regulation 726/2004 (within which the example of dengue is specifically mentioned). This Opinion could facilitate the review process by NRAs in developing countries. Manufacturers may also obtain scientific advice and protocol assistance from the EMA, which may facilitate later Article 58 review.

– The Developing Countries’ Vaccine Regulators Network recommends that consideration be given to agreements for joint reviews of clinical trial applications by similarly affected NRAs and also the review of applications for licensure in order to accelerate the launch and introduction of dengue vaccines. The NRAs would need to have access to the necessary expertise to review the quality and safety aspects of the license application.

– It is critical that improved standardized tests be introduced as soon as possible for the diagnosis of early infection and for the measurement of immune protection (requiring identification of a correlate of protection). The World Health Organization (WHO), through its Expert Committee on Biological Standardization, can evaluate and standardize such tests; in addition, WHO and its Collaborating Centers may also help ensure availability of necessary standards and reagents for use in the field.