Recommendations to assure the quality, safety and efficacy of DT-based combined vaccines, Annex 6, TRS No 980

Overview

Combined vaccines that allow simultaneous administration of diphtheria (D) and tetanus (T) toxoids with several other antigens have been in use since the middle of the 20th century. Some of the earliest DT-based combined vaccines included inactivated poliomyelitis vaccines (IPV) or whole-cell pertussis vaccine (wP), or both. These were followed by combinations with various acellular pertussis antigens (aP), which were used as an alternative to DTwP, and with combinations that included the addition of one or more of the Haemophilus influenzae type b (Hib) conjugates – Hib(conj) – and hepatitis B (HepB) surface antigen (HBsAg).

The WHO Requirements for diphtheria, tetanus, pertussis and combined vaccines (1) incorporated guidance on the individual components of these vaccines (e.g. diphtheria vaccine, tetanus vaccine and whole-cell pertussis vaccine). In addition, a separate section on the manufacture of combined vaccines containing more than one of the individual vaccines (e.g. DT and DTwP) was included; this guidance commences at the stage of the final bulk vaccine and considers the specifics of manufacture of the final combined product. However, the section on the requirements for combined vaccines (adsorbed) stated that no attempt had been “made to include other combinations, including those with Haemophilus influenzae and Neisseria meningitidis polysaccharides and poliomyelitis vaccines”. In addition, it is now WHO policy to include in new recommendations guidance on the nonclinical and clinical aspects of vaccine development. The 1990 WHO Requirements for diphtheria, tetanus, pertussis and combined vaccines (1) do not contain such guidance.

Full version of the WHO Technical Report Series N° 980