Liquid pentavalent Diphtheria-Tetanus-Pertussis (whole cell)-Hepatitis B-Haemophilus influenzae type b vaccine (LPV) is presented as a suspension which needs to be shaken before use to ensure a homogenous turbid white suspension. The instructions for use state that the vaccine should be visually inspected for any foreign particulate matter and/or variation for physical aspect prior to administration. Failing that, the vials should be discarded.
The World Health Organization has been informed of a higher than normal incidence of white sticky aggregates in some batches of the pentavalent vaccine manufactured by Biological E. Limited India (hereafter referred to as Biological E.) that fail to resuspend upon shaking. Only lots of the single dose presentation have been impacted with the described defect. The same has not been reported for the 10-dose presentation.
No adverse events following immunization with the use of LPV have been reported to WHO. Recent clinical studies using this vaccine as a comparator did not raise safety or efficacy concerns. Following thorough investigation and independent testing, WHO confirms that the safety and efficacy profiles of the vaccine remain unchanged. Accordingly, revaccination is not recommended. WHO recommends continued vaccination with unaffected vials of the vaccine.
However, where a significant number of vials display this altered appearance, WHO recommends that the concerned batch(es) not be used.
Countries supplied by UN procurement agencies are advised to report visual appearance defects to the agencies and discuss options available under existing contracts if a significant number of vials in this particular lot show the altered appearance described above. WHO recommends that other vaccine purchasers, including countries that procure directly, international and non-governmental organizations, contact the vaccine manufacturer and discuss options under the terms of the supply agreement, with copies to the relevant WHO Country and/or Regional Offices for information.
Biological E. is conducting studies addressing several manufacturing parameters with the purpose of reducing the risk of formation of aggregates. For the time being, Biological E. has put on hold production and shipment of LPV single dose. Changes will be implemented in the manufacturing process prior to resumption of the supply of LPV single dose vaccine expected by Q1 2020.
Based on the risk benefit analysis performed by the WHO prequalification team, the single dose liquid pentavalent vaccine of Biological E will be maintained in the WHO list of prequalified vaccines supplied through UN procurement agencies.