Elsevier

Vaccine

Volume 21, Issue 15, 2 April 2003, Pages 1658-1664
Vaccine

Issues in selection of DTwP-based combination vaccines

https://doi.org/10.1016/S0264-410X(02)00629-1Get rights and content

Abstract

This study examines regulatory, supply, acceptance and financing issues of combinations based on diphtheria–tetanus–pertussis (whole cell) vaccines (DTwP). These combination vaccines are currently produced in Europe mostly for export. Future regulatory oversight issues could have an impact on their availability. Before use of acellular pertussis-containing vaccines, the number of doses of DTwP vaccines offered in response to United Nations agency procurement tenders far exceeded the projected demand. Current demand and supply are converging. Most of that supply comes from developing country manufacturers, a potential new source of combination vaccines as well. The expected development and use of DTwP-based combination vaccines raises antigen allocation issues that could further affect supply. These combination vaccines have strong programmatic advantages, but pose complex selection issues involving disease burden, presentation, and availability of long-term financing. Vaccine price is not the major driving factor. A model examining important selection factors for regional country groupings provides predictions that have been validated by decisions on use of DTwP-based combination vaccines. This model may be useful in providing long-term uptake projections for other combination vaccines.

Introduction

Combination vaccines, the best known of which is the traditional diphtheria–tetanus–(whole cell) pertussis (DTwP) vaccine, have been used for many years and offer several advantages, including a reduced number of injections, with a concomitant drop in syringe use and exposure to exipients, adjuvants and preservatives, and a non-disruptive way to introduce an additional antigen, such as hepatitis B (hep B) or Haemophilus influenzae type b (Hib) vaccines, into an immunization programme. Recent experience with DTwP-based combinations has attested to their enormous programmatic desirability. Despite their advantages, however, use of such combinations could limit programme flexibility and affect the supply of traditional vaccines. The purpose of this paper is to examine issues and implications surrounding the selection and use of DTwP-based combination vaccines. A summary of such vaccines currently available is given in Table 1.

The pros and cons of such combination vaccines are summarized in Table 2.

Section snippets

Regulatory issues

There are several special considerations for regulation of combination vaccines compared to a new single component vaccine. These include the need to demonstrate the safety and efficacy of each component in the combination, which may be difficult if there are no serological coordinates of immunity [1]. Furthermore, the response to each antigen in the combination may be adversely affected by interference with other components.

A special issue is the availability of continued regulatory oversight

Predictions for uptake

The available data allow the generation of a model to predict uptake of combination vaccines. This is shown in Table 4, where market characteristics are tabulated for different regions of the world and antigen uptake in the form of combination vaccines is predicted. Based on the knowledge we have to date, most of these predictions are upheld, as can be seen in Fig. 3, Fig. 4. This type of analysis can serve as a basis for long-term projections for future combination vaccines.

Lessons for the public health community

The current analysis supports strongly the concept that price alone is not the major predictor of uptake, especially for combination vaccines. Countries will pay a premium for an additional antigen in a combination only if it adds value. The value added for a particular antigen will differ across countries and regions, depending on epidemiological and other factors. The key is a real or perceived programmatic need, which can often offset vaccine price considerations. By adopting an approach

Acknowledgements

The authors would like to express their gratitude to Keeley Gyte, Gill Mayers, and the staff of the Vaccine Assessment and Monitoring Team of the WHO Department of Vaccines and Biologicals for providing the data in Fig. 3, Fig. 4, Fig. 5, and to Jay Wenger for reviewing the information therein.

References (4)

  • K.L. Goldenthal et al.

    Prelicensure evaluation of combination vaccines

    Clin. Infect. Dis.

    (2001)
  • ...
There are more references available in the full text version of this article.

Cited by (8)

  • Public vaccine manufacturing capacity in the Latin American and Caribbean region: Current status and perspectives

    2012, Biologicals
    Citation Excerpt :

    The prices of these vaccines are variable, but they are higher than 1 US$ per dose. For instance, the combined DTwP-HB-Hib vaccine was priced at 3.5 to 4 US$ per dose in 2007 [8,9]. Some vaccines belonging to this cluster are already licensed in a few developed countries, such as the septavalent pneumococcal conjugate polysaccharide vaccine, which has been available in the LAC region since 2000, and the rotavirus vaccine, which has been available since 2004.

  • Incremental system costs of introducing combined DTwP-hepatitis B-Hib vaccine into national immunization services in Ethiopia

    2009, Vaccine
    Citation Excerpt :

    The DTwP vaccine in a 10-dose vial requires approximately 3.0 cm3 per dose. Previously, the only other vaccine with those five antigens combined was a Glaxo Smith Kline produced product in which Hib was in lyophilised form in a separate vial [10]. This product is marketed in a 2-dose vial.

  • Industrial Development and Innovation: Some Lessons from Vaccine Procurement

    2006, World Development
    Citation Excerpt :

    This number has continued to increase to 58% for six vaccines, but the suppliers have dropped to 12, partly as a function of stricter guidelines (Milstien, Glass, Batson, Greco, & Berger, 2001). The international procurers have made a determined effort to correct this trend, with UNICEF alone going from no IC suppliers or 0% (1992) to 53% (2000), not including oral polio vaccine (OPV) for public-sector vaccine purchases (Milstien, Munira, & McKinney, 2003). In addition to the purchasing power of procurement (which arguably is the prime focus of the literature on global vaccine R&D management), an important industrial reason to study procurement is the sea of regulations and standards that surround vaccine development and manufacture.

View all citing articles on Scopus
View full text