title: A total organic carbon analysis method for validating cleaning between products in biopharmaceutical manufacturing.
abstract: The validation of cleaning procedures for biopharmaceutical products produced by recombinant DNA (rDNA) technology presents a diverse analytical challenge. This is because of the need for quantitation of a broad range of potential residual cellular components, including proteins, carbohydrates, and nucleic acids, as well as trace levels of detergents at various manufacturing stages. The validation of a Total Organic Carbon (TOC) analysis method for use in cleaning validation studies is presented. The method has a limit of detection of approximately 0.1 ppm, with a limit of quantitation of 0.5 ppm. TOC analysis has an accuracy of 50 to 70% or better in the 0.5- to 10-ppm range and demonstrates an overall variability of approximately 5%. The method is broadly applicable to a variety of impurities and contaminants that are likely to be encountered following the manufacture of rDNA products.
authors.affiliation: Genentech, Inc., South San Francisco, California.
authors.forename: R
authors.initials: R
authors.lastname: Baffi
authors.forename: G
authors.initials: G
authors.lastname: Dolch
authors.forename: R
authors.initials: R
authors.lastname: Garnick
authors.forename: Y F
authors.initials: YF
authors.lastname: Huang
authors.forename: B
authors.initials: B
authors.lastname: Mar
authors.forename: D
authors.initials: D
authors.lastname: Matsuhiro
authors.forename: B
authors.initials: B
authors.lastname: Niepelt
authors.forename: C
authors.initials: C
authors.lastname: Parra
authors.forename: M
authors.initials: M
authors.lastname: Stephan
mesh_terms: D001207:Asepsis / Q000592:standards*; D001688:Biological Products / Q000592:standards*; D002244:Carbon / Q000032:analysis; D004274:DNA, Recombinant; D012710:Serum Albumin, Bovine / Q000032:analysis; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000592:standards*
chemical_list: D001688:Biological Products; D004274:DNA, Recombinant; D012710:Serum Albumin, Bovine; D002244:Carbon