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.

Autor: Gudlavalleti SK; JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States. Electronic address: dr_seshu@jn-vaccines.org., Crawford EN; JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States., Tran NN; JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States., Orten DJ; JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States., Harder JD; JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States., Reddy JR; JN International Medical Corporation, 2720 N 84th Street, Omaha, NE 68134, United States.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2015 Mar 25; Vol. 107, pp. 432-6. Date of Electronic Publication: 2015 Jan 25.
DOI: 10.1016/j.jpba.2015.01.034
Abstrakt: 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.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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