BACKGROUND

2-Phenoxyethanol (2-PE) has been safely included as a preservative and/or stabilizer in more than thirty vaccine formulations at amounts ranging from 0.5 to 5 mg per dose; however, the nonclinical safety data publicly available for intramuscular (IM) or subcutaneous (SC) administration are relatively limited. Here, in addition to the available clinical and nonclinical data for 2-PE, we summarize the nonclinical safety data of experimental 13vPnC (Prev(e)nar 13) formulations with or without 2-PE.

METHODS

Two repeat-dose toxicity studies in rabbits, one for a 2-PE-free formulation of 13vPnC and the other for an MDV formulation of 13vPnC with 5 mg/dose 2-PE, were conducted as part of an overall nonclinical safety package for vaccine development. The studies were designed and conducted in compliance with the relevant guidelines and regulations.

RESULTS

In repeat-dose toxicity studies in rabbits, five IM administrations of a preservative-free 13vPnC single-dose syringe formulation or a 13vPnC multi-dose vial (MDV) formulation containing 5 mg 2-PE/0.5 mL dose were well tolerated with no systemic toxicity. Robust serotype-specific IgG antibody responses to each of the 13 pneumococcal serotypes were also confirmed for both formulations. The observations for the 13vPnC MDV including local inflammatory reaction, increases in fibrinogen, and increased splenic germinal centers were nonadverse, reversible, and consistent with findings previously observed for the IM administration of vaccines, including the 2-PE-free 13vPnC single-dose syringe formulation.

CONCLUSIONS

Together with the other available nonclinical and clinical data of 2-PE and vaccine formulations containing 2-PE and following the 3Rs principle, our risk-assessment-based recommendation is that no additional nonclinical safety studies are needed when evaluating a 2-PE-containing presentation of a previously well-characterized vaccine product if the amount of 2-PE is ≤10 mg/dose.