Immunization standards

Preliminary outcome of vaccine quality investigation of Quinvaxem (DTwP-hepatitis B-Hib)

10 February 2011

Key outcome

Following review of reports from Crucell N.V. and advice from the Korea Food and Drug Administration (KFDA) of the quality investigation regarding the pentavalent vaccine, Quinvaxem, WHO is assured that the problems identified in 2010 have been resolved. WHO will thus accept new lots of Quinvaxem produced by Crucell for supply through United Nations agencies, as and when they are released by the KFDA.

It is expected that release of newly-produced lots of Quinvaxem will resume during February.

Background

On 28 October 2010, Crucell N.V. (hereafter referred to as Crucell) announced a temporary hold on all shipments of its fully liquid pentavalent vaccine Quinvaxem (a WHO-prequalified vaccine) and its hepatitis B vaccine Hepavax-Gene (thiomersal-free, not prequalified by WHO). The reason for this temporary suspension was that the company suspected that the sterility of its Shingal facility in the Republic of Korea may have been compromised during recent operations. The problem was detected by the manufacturer through quality control tests that are routinely performed on each lot of vaccine.

In line with standard procedure for WHO-prequalified vaccines, a thorough review of the manufacturing process was subsequently undertaken by both Crucell and the national regulatory authority for the Republic of Korea, the Korea Food and Drug Administration (KFDA). The KFDA review included an inspection of the Shingal facility. All reports from Crucell were submitted to both the KFDA and WHO.

Conclusions and recommendations

An interim investigation report was submitted by Crucell to WHO and the KFDA on 24 November 2010. WHO concurred with the decision that lots of uncertain quality remain on temporary suspension pending completion of ongoing investigations. WHO also recommended measures that should be undertaken by Crucell to determine the root cause of the problem. Furthermore, WHO determined that lots produced prior to the break in sterility and which had not been distributed (a total of 8 million doses), met WHO requirements and could thus be used. The majority of these doses were subsequently distributed to countries through United Nations agencies and Médecins sans Frontières.

WHO received the final report from Crucell on 16 December. This indicated that indeed there had been a break in sterility due to malfunction of the filling machine following several consecutive power outages.

WHO's review of all reports from Crucell and of the KFDA advice as the national regulatory authority of record indicate that Crucell is now implementing measures for improved surveillance and maintenance of vaccine formulation and vial-filling processes, including additional training for all personnel involved in vaccine production.

The investigation observations and the corrective and preventive actions that are being taken are valid for all products produced at the Shingal site and will also be applied at the new facility (the Incheon site).

WHO is confident that Crucell is operating according to good manufacturing practices. WHO will accept new lots of Quinvaxem produced by Crucell for supply through United Nations agencies, as and when they are released by the KFDA.

With regard to lots that were placed on hold, the KFDA has determined that only lots produced from final bulk 3450171 can at this time be released, on condition that the results of quality control tests and national lot release prove satisfactory. WHO is in agreement to the supply of lots from bulk 3450171 through United Nations agencies if released by the KFDA.

It is expected that release of newly-produced lots of Quinvaxem will resume during February.

Quinvaxem vaccine remains on the list of WHO prequalified vaccines.

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