Canada: Several GlaxoSmithKline Inc. vaccines: Potential risk of underdosing (English Only)
 
Health Canada announces that there have been reports of leakage from ceramic coated tip (CCT) syringes used for several GlaxoSmithKline Inc. vaccines during vaccine preparation or administration. Although the leakage does not pose a concern for the vaccine sterility, there is a potential risk of underdosing associated with administration of a vaccine from a leaking syringe that may leave patients inadequately protected from disease after vaccination. The products affected include: BOOSTRIX, BOOSTRIX-POLIO, ENGERIX-B (Adult), HAVRIX, HAVRIX Junior, INFANRIX-IPV, INFANRIX-IPV/HIB, INFANRIX-hexa, TWINRIX and TWINRIX Junior. 

Beginning in Jul 2015, GlaxoSmithKline Biologicals SA identified an increase in the reporting rate of leakages in CCT syringes at the connection of the syringe tip and the needle hub during vaccine preparation and administration. The integrity of the leaking syringe and sterility of the contents were not compromised. A review of GlaxoSmithKline Biologicals SA pharmacovigilance data as of 14 Dec 2017 did not find evidence that the observed leakage has resulted in vaccination failure (lack of efficacy) or any other patient safety concern. In Canada, the syringe leakage rate is 3 per 100,000 syringes distributed, although the precise frequency of leakage is not known and may be higher. 

GlaxoSmithKline Inc. has implemented corrective actions with its syringe suppliers and has introduced improved syringes in its filling operations as of Jan 2018. However, both the improved and current CCT syringes will be on the market during 2019, with the proportion of potentially affected syringes progressively decreasing towards the end of 2019 by when the current syringes are expected to have been used up. 

Data relevant to the administration of lower antigen content are available for HAVRIX and ENGERIX-B. These data suggest that the administration of half the required antigen dose of HAVRIX or ENGERIX-B will not affect seroprotection or seropositivity. As the probability of a leakage resulting in patients receiving half the required dose is very low, leakage is not expected to impact seroprotection/seropositivity following vaccination. No dose-range studies are available for TWINRIX, but the immune response to the two antigens in the TWINRIX vaccine was demonstrated to be at least as good as that after vaccination with the monovalent vaccines, HAVRIX and ENGERIX-B, for which data on administration of lower antigen content are available. For the other vaccines potentially impacted by leakages, it is not possible to assess the likely impact of underdosing on seroprotection/seropositivity. However, for vaccines given in a multi-dose schedule (2-3 priming doses plus booster), it is highly unlikely that each dose will be administered with a leaking syringe. 

Regarding the potential risk of overdosing in case of revaccination, the reported adverse events after overdosage with vaccines, including INFANRIX-IPV and INFANRIX-IPV/HIB, BOOSTRIX, BOOSTRIX-POLIO and TWINRIX, were similar to those reported with the standard dose administration. 

Healthcare professionals are advised: 
- not to use the syringe when the leakage occurs during reconstitution of lyophilized vaccines. 
- when the leakage occurs during vaccine injection and the individual received less than the standard dose, the decision to revaccinate should take into account both the potential benefits and risks associated with administering a repeated dose. 

Please refer to the following website in Health Canada for details: http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/../66674a-eng.php 

In Hong Kong, according to GlaxoSmithKline Limited (GSK), the following 17 registered pharmaceutical products, namely TWINRIX JUNIOR VACCINE INJ (HK-44500), HAVRIX 720 JUNIOR VACCINE (HK-42693), INFANRIX-IPV+HIB VACCINE (HK-47367), BOOSTRIX VACCINE (HK-48297), TWINRIX ADULT VACCINE (HK-43814), PRIORIX POWDER FOR INJ VACCINE (LIVE) (HK-43861), HAVRIX 1440 VACCINE (HK-40826), INFANRIX-IPV VACCINE PREFILLED SYRINGE (HK-49556), INFANRIX HEXA VACCINE (HK-48745), BOOSTRIX POLIO VACCINE (HK-55589), PRIORIX-TETRA VACCINE (HK-57798), INFANRIX IPV-HIB VACCINE (HK-62548), BOOSTRIX POLIO VACCINE (DH PACK) (HK-62558), INFANRIX HEXA VACCINE (HK-62935), INFANRIX HEXA VACCINE (HK-64010), ENGERIX-B 20 ADULT VACCINE SUSPENSION FOR INJECTION IN PREFILLED SYRINGE 20MCG/1ML (HK-65374) and ENGERIX-B 10 JUNIOR VACCINE SUSPENSION FOR INJECTION IN PREFILLED SYRINGE 10MCG/0.5ML (HK-65375), are affected by the incident. All products are prescription-only medicines. 

So far, the Department of Health (DH) has received 4 cases of adverse drug reaction (ADR) related to Boostrix Polio, 4 cases related to Infanrix Hexa, 3 cases related to Infanrix Ipv-Hib, 1 case related to Engerix-B Adult and 2 cases related to Engerix-B Junior, but these cases were not related to leakage and underdosing. DH has not received any case of ADR related to Boostrix, Havrix, Havrix Junior, Infanrix-Ipv, Twinrix, Twinrix Junior, Priorix and Priorix-Tetra. 

In light of the above Health Canada’s announcement, DH has contacted GSK to follow up on the local impact of the incident. DH will continue to follow up with GSK for consideration of any action deemed necessary, and will remain vigilant on safety update of the products issued by other overseas drug regulatory authorities. 

Ends/Wednesday, May 2, 2018 
Issued at HKT 17:45 

  轉載自衛生署藥物辦公室網頁http://www.drugoffice.gov.hk/