title: Alignment of absolute and relative molecular size specifications for a polyvalent pneumococcal polysaccharide vaccine (PNEUMOVAX 23).
abstract: An approach was developed to align release and end-expiry specifications for molecular size for the polyvalent pneumococcal polysaccharide vaccine (PNEUMOVAX 23). Each of the 23 polysaccharide components of the vaccine was separately subjected to ultrasonication to produce a series of preparations of decreasing weight-average molecular mass (Mw). These size-reduced polysaccharides were analysed as monovalent solutions by high-performance size exclusion chromatography (HPSEC) with multi-angle laser light scattering (MALLS) and refractive index (RI) detection to measure their Mw. These samples were also analysed by HPSEC with rate nephelometry (RN) detection to measure their relative molecular size (r-MS). The data from the two molecular size measurements established a correlation between Mw and r-MS. For each polysaccharide component of the vaccine, this correlation permits the direct alignment of the r-MS specification in the final formulated product with the Mw specification for the monovalent polysaccharide preparation. The alignment of specifications provides a high level of assurance that the quality control of the final vaccine product is consistent with that of the polysaccharide starting materials.
authors.affiliation: Bioprocess and Bioanalytical Research, Merck Research Laboratories, P.O. Box 4, Sumneytown Pike, West Point, PA 19486, USA. john_macnair@merck.com
authors.forename: John E
authors.initials: JE
authors.lastname: MacNair
authors.forename: Tejal
authors.initials: T
authors.lastname: Desai
authors.forename: Jennifer
authors.initials: J
authors.lastname: Teyral
authors.forename: Chitrananda
authors.initials: C
authors.lastname: Abeygunawardana
authors.forename: John P
authors.initials: JP
authors.lastname: Hennessey
mesh_terms: D002845:Chromatography / Q000379:methods*; D008027:Light; D016014:Linear Models; D046911:Macromolecular Substances / Q000737:chemistry*; D008970:Molecular Weight; D009391:Nephelometry and Turbidimetry; D022242:Pneumococcal Vaccines / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D012542:Scattering, Radiation; D012703:Serotyping; D013010:Sonication; D013997:Time Factors
chemical_list: D046911:Macromolecular Substances; D022242:Pneumococcal Vaccines; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial