Vaccine development: monovalent OPVs
In September of 2004, the Advisory Committee on Poliomyelitis Eradication (ACPE) recommended that “in order to potentially enhance the impact of SIAs by improving immune response in vaccinated children, WHO should immediately work to accelerate the process of regulatory approval of monovalent oral polio vaccine type 1 (mOPV1), with the aim of having a product available for potential use in critical endemic areas by early 2005 as an adjunct to the existing eradication activities.”
Following this recommendation, the development of mOPV1 was launched and by the following March, Sanofi Pasteur - spearheading the development process from the industry side - had a product licensed by the French regulatory authority (AFSSAPS). As of October 2008, an additional five mOPV1 products have been developed and the total number of countries with licensures is now eight. This impressive achievement has since been mirrored by the equally rapid and successful development of monovalent OPV type 3 (mOPV3). In 2007, efforts were launched to develop and license monovalent OPV type 2 (mOPV2) for eventual use in a global polio vaccine stockpile or if appropriate, for control of poliovirus type 2 outbreaks.
The process from initial development through to licensing and eventually prequalification is complex and involves a number of key stages. First, there is the preparation stage which involves the assembly of all trivalent OPV (tOPV) prequalified manufacturers and related national regulatory authorities (NRAs), as was done in September 2004, immediately following the ACPE meeting. The purpose of such a meeting was to define the feasibility in terms of production and timelines, as well as the regulatory pathways. Subsequently, individual meetings were held in order to obtain indications of interest from the manufacturers and their respective NRAs. Throughout this process, UNICEF ensures a facilitated supply process by identifying the technical specifications for a mOPV tender. Furthermore, WHO pledged to purchase a minimum of 50 million doses.
WHO and the NRAs of all mOPV-producing countries agreed on an expedited approach to conduct a parallel review of the licensure dossier across both WHO and UNICEF (the traditional procurer of vaccines). This mechanism allowed licensure of mOPV in the country of origin within a few months of development. Licensure of mOPV was granted on the basis of historical clinical data generated in several countries between 1960 and 1980, however with the provision that clinical trials be conducted post-marketing to update this historical data. Part of the licensure requirements also stipulated that a clinical expert report be prepared. WHO therefore committed to commissioning such a report for each of the monovalent vaccines (since authored by Professor Peter Folb) and to implementing the necessary clinical trials, evaluating each monovalent vaccine in comparison to the trivalent version. The first of these trials was conducted in Cairo, Egypt, using Sanofi Pasteur’s mOPV1 in mid-2005. The results of this trial were recently published in the New England Journal of Medicine (1). Sanofi Pasteur’s mOPV1 was the first to achieve WHO pre-qualification.
This regulatory pathway is fully consistent with the provision made in the WHO prequalification procedure as described in the WHO document WHO/IVB/05.19 Procedure for assessing the acceptability, in principle, of vaccines for purchase by United Nations agencies. Since 2004, WHO has been facilitating the registration of mOPV through regular meetings with manufacturers and NRAs to accelerate the licensing process with respect to the specific regulations in place in each country.
Most countries accept UNICEF-purchased vaccine for use. However, national policies can dictate that licensure be required in a given country to allow the use of mOPV in immunization campaigns. Such has been the case, for example, in Egypt, Pakistan, and Nigeria. Manufacturers, along with WHO staff from HQ and country offices, have been collaborating closely with NRAs to facilitate the licensure of mOPVs in order to avoid any monopoly situation and to enlarge the flexibility of vaccine supply to high risk areas. As a result, at least two mOPV1 products are licensed in Pakistan, India and Nigeria and licensure of two additional products is underway. To date, mOPV1 and mOPV3 have been used in over 30 countries. To date, nearly 4.5 billion mOPV doses have been administered since development began, testament to the successful integration of this new vaccine into the polio eradication effort, as well as to an unprecedented vaccine development effort.
