title: Determining trace amounts and the origin of formaldehyde impurity in Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS by improved C18-UPLC method.
abstract: The ability to accurately measure and report trace amounts of residual formaldehyde impurity in a vaccine product is not only critical in the product release but also a regulatory requirement. In many bacterial or viral vaccine manufacturing procedures, formaldehyde is used either at a live culture inactivation step or at a protein de-toxification step or at both. Reported here is a validated and improved C18-UPLC method (developed based on previously published C-8 HPLC method) to determine the traces of formaldehyde process impurity in a liquid form Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS. UPLC C-18 column and the conditions described distinctly resolved the 2,4-DNPH-HCHO adduct from the un-reacted 2,4-DNPH as detected by TUV detector at 360 nm. This method was shown to be compatible with PBS formulation and extremely sensitive (with a quantitation limit of 0.05 ppm) and aided to determine formaldehyde contamination sources by evaluating the in-process materials as a track-down analysis. Final nanogram levels of formaldehyde in the formulated single dose vialed vaccine mainly originated from the diphtheria toxoid carrier protein used in the production of the conjugate vaccine, whereas relative contribution from polysaccharide API was minimal.
authors: JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States. Electronic address: dr_seshu@jn-vaccines.org.
authors: Seshu K
authors: SK
authors: Gudlavalleti
authors: JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States.
authors: Erika N
authors: EN
authors: Crawford
authors: JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States.
authors: Nhi N
authors: NN
authors: Tran
authors: JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States.
authors: Dana J
authors: DJ
authors: Orten
authors: JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States.
authors: Jeffery D
authors: JD
authors: Harder
authors: JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States.
authors: Jeeri R
authors: JR
authors: Reddy
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004168:Diphtheria Toxoid / Q000737:chemistry* / Q000276:immunology; D022422:Diphtheria-Tetanus Vaccine / Q000737:chemistry* / Q000276:immunology; D004340:Drug Contamination; D005557:Formaldehyde / Q000737:chemistry*; D009345:Neisseria meningitidis / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000737:chemistry* / Q000276:immunology
chemical_list: D004168:Diphtheria Toxoid; D022422:Diphtheria-Tetanus Vaccine; D018074:Vaccines, Conjugate; D005557:Formaldehyde
keywords: Conjugate vaccines; Formaldehyde detection in liquid vaccines; Meningococcal vaccines; Neisseria meningitidis; Reverse phase UPLC