title: Preservative of choice for Prev(e)nar 13™ in a multi-dose formulation.
abstract: Development of a Prev(e)nar 13™ multi-dose vaccine, in support of vaccinating populations against pneumococcal disease, required the addition of a preservative to the vaccine formulation that met antimicrobial effectiveness tests based on the European Pharmacopoeia (EP) requirements, including deliberate multiple challenge studies and recommendation by the WHO Open Vial Policy. In this study, the antimicrobial effectiveness of several preservatives in Prev(e)nar 13™ formulations was evaluated. A Prev(e)nar 13™ formulation containing 2-Phenoxyethanol (2-PE) at a concentration of 5.0mg/dose was stable and met EP recommended criteria for antimicrobial effectiveness tests when the formulation was kept over a 30 month period. In contrast, a recommended dose of Thimerosal, as a comparator, or other preservatives did not meet EP antimicrobial effectiveness acceptance criteria. The rate of growth inhibition of Thimerosal compared to 2-PE on Staphylococcus aureus, a resilient organism in these tests, was significantly slower in single and multi-challenge studies. These results indicate that 2-PE provides a superior antimicrobial effectiveness over Thimerosal for this vaccine formulation.
authors.affiliation: Pfizer Vaccines Research, Pfizer Biotherapeutics Pharmaceutical Research and Development, 401 North Middletown Road, Pearl River, NY 10965, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Khandke
authors.forename: Cindy
authors.initials: C
authors.lastname: Yang
authors.forename: Ksenia
authors.initials: K
authors.lastname: Krylova
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Abbas
authors.initials: A
authors.lastname: Rashidbaigi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004356:Drug Storage; D005026:Ethylene Glycols / Q000494:pharmacology*; D006801:Humans; D022242:Pneumococcal Vaccines / Q000737:chemistry* / Q000276:immunology*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013849:Thimerosal / Q000494:pharmacology
chemical_list: C538862:13-valent pneumococcal vaccine; D000900:Anti-Bacterial Agents; D005026:Ethylene Glycols; D022242:Pneumococcal Vaccines; D011310:Preservatives, Pharmaceutical; D013849:Thimerosal; C005398:phenoxyethanol