Immunization standards

Panacea Biotec DTP-based combination and monovalent hepatitis B vaccines delisted from WHO list of prequalified vaccines

17 August 2011

Following a routine site audit conducted by a WHO team of the vaccine manufacturer, Panacea Biotec (hereafter referred to as Panacea), and the conclusions of an ad hoc committee convened by WHO, the following diphtheria-pertussis-tetanus-based combination vaccines: Easyfive (DTwP-Hep B-Hib), Ecovac4 (DTwP-Hep B), and EnivacHB (Hepatitis B); have been removed from the list of vaccines prequalified by WHO.

During the site audit, which took place from 27 June-1 July at the Lalru manufacturing site, it became clear to the WHO team that Panacea's quality systems on this site do not meet the requirements required for WHO prequalification.

Specifically, deficiencies in the quality management system found at the Lalru site relate to the manufacture of the haemophilus influenzae type b (Hib) and hepatitis B bulks used for the formulation of the DTwP-Hep B-Hib, DTwP-Hep B and hepatitis B vaccines.

The WHO team asked Panacea to put on hold shipments of the DTwP-based combination vaccines until a final decision on the acceptability for UN supply had been made by a WHO-convened ad hoc committee which would be constituted to review the findings of the audit team.

UNICEF and the Pan American Health Organization, through which prequalified vaccines are supplied to developing countries, were rapidly informed of the main conclusions of the audit team.

An ad hoc committee composed of WHO staff and experts from national regulatory authorities was convened to advise on potential changes to the prequalification status of the DTwP-based combination vaccines manufactured by Panacea; the continued acceptability of the oral polio vaccines produced by the company in a different site to that which was audited and supplied to countries either through United Nations agencies or by direct procurement; and the ongoing prequalification evaluation of the company's inactivated polio vaccine (IPV).

In accordance with the recommendations of the ad hoc committee, WHO:

  • has delisted Easyfive (DTw-Hep B-Hib), Ecovac4 (DTwP-Hep B), and EnivacHB (Hep B), from its list of prequalified vaccines;
  • recommends the continued supply of the OPV vaccines supplied by the company, given that the formulation and filling of the OPV vaccines are carried out at a New Delhi site at which there is no evidence available to WHO of inadequate quality assurance. These vaccines remain prequalified by WHO. A site audit by a WHO team of the New Delhi site is scheduled for the coming weeks; and
  • has placed the evaluation for prequalification of the IPV vaccine on hold until the quality assurance issues discovered at the company have been resolved.

The above-noted measures are proactive steps being taken because of the risk, unless corrective measures are taken, that the quality and safety of future batches of these vaccines will be compromised.

Batches of these vaccines already distributed to countries should not be recalled and should continue to be used. This is because there is no evidence of quality or safety defects with batches already distributed whereas there is a real risk, if immunization is withheld, of death or morbidity from the diseases against which the vaccines protect. The evidence includes: testing by WHO-contracted laboratories that has been performed on batches of Panacea vaccines that have been supplied through the UN system in accordance with the continuous monitoring performed by WHO on prequalified vaccines ; and review of complaints and reports of adverse events following immunization from either immunization programmes, national regulatory authorities or the manufacturer.

With regard to vaccine supply, the main concern brought about by this situation relates to sufficiency of supply of the pentavalent DTwP-Hep B-Hib vaccine. Strategies to ensure sufficient supply to meet global demand in the event of suspension of EasyFive have been under discussion between WHO and other immunization partners since the site audit.

WHO and UN procurement agencies have assessed that demand for pentavalent vaccine in 2011 can be filled by existing suppliers of prequalified pentavalent vaccine. Options to ensure sufficient supply to meet demand for pentavalent vaccine in the mid- to long term are being reviewed. Priority will be given by WHO to applications for prequalification of new pentavalent vaccines. In the short-term, more countries may need to use an alternative liquid-lyophilised pentavalent vaccine (i.e. the vaccine is in powder format and needs to be mixed with a diluent before use). Sufficiency of supply to meet demand will, in the long term, be dependent on the entry of new suppliers of quality vaccines to the market and/or countries switching to a liquid-lyophilised presentation.

WHO is committed to reassessment of the suitability of the affected products for prequalification as soon as it is appropriate to do so.