Supply of WHO-prequalified vaccines containing DTwP antigens manufactured by Novartis Vaccines, Germany
On 8 April 2011, WHO was informed of the voluntary suspension by GSK Biologicals (GSK) of the supply of Tritanrix-HB+Hib — a WHO-prequalified pentavalent vaccine to protect against diphtheria, tetanus, pertussis, hepatitis B and haemophilus influenzae type b (Hib), manufactured by GSK using DTwP antigens purchased from Novartis Vaccines, Germany. The suspension followed the detection of small particles of foreign material on the silicone tubing of the container of DTwP antigen supplied by Novartis Vaccines, Germany.
The D-, T-, and wP antigen concentrates produced by Novartis Vaccines, Germany were also supplied to Novartis Vaccines, Italy for formulation of the WHO-prequalified vaccine Quattvaxem (DTwP-Hib) and to Crucell, Republic of Korea for the formulation of Quinvaxem (DTwP-hepatitis B-Hib), also prequalified by WHO.
Novartis Vaccines, Germany has indicated that the root cause of the defect (related to the manufacturing conditions of the silicone tube) has been identified and preventive and corrective actions have been taken.
The European Medicines Agency, the regulatory authority of record for Tritanrix-HB+Hib and the Korean Food and Drug Administration (KFDA), the regulatory agency for Quinvaxem, have officially stated that the presence of particles identified in the silicone tubing of the container of DTwP antigen bulks does not have a negative impact on the quality, safety or efficacy of Tritanrix-HB+Hib or Quinvaxem respectively. The Agenzia Italiana del Farmaco (AIFA), the regulatory agency for Quattvaxem, is in agreement with the opinion of the European Medicines Agency on this matter.
WHO, the European Medicines Agency, and the national regulatory authorities of record for prequalification have reviewed all the assessment reports related to this issue and agree that the root cause has indeed been identified and appropriate preventive and corrective actions have been taken.
Since detection of the problem, GSK has increased visual controls such that, in the future, Tritanrix-HB+Hib will not be formulated using DTwP antigen that has been in contact with particles on the silicon tubing, should there be any. Indeed, all bottles of DTwP bulk with particles on the silicone tubing have been rejected by GSK, with none of them used for vaccine formulation. GSK has recommenced production and release of Tritanrix-HB+Hib.
Novartis Vaccines, Italy has recommenced manufacturing of Quattvaxem and is also confident that all final lots are suitable for release to the market.
In view of differences in the handling procedures for the DTwP antigens used by Crucell, GSK and Novartis Vaccines, Italy, at no time since the identification of the above-noted problem was the manufacture of Quinvaxem put on hold by Crucell. This decision was supported by the KFDA. However, as a further precautionary measure, Crucell has increased visual controls for DTwP antigen prior to the formulation of Quinvaxem.