title: Application of a risk analysis method to different technologies for producing a monoclonal antibody employed in hepatitis B vaccine manufacturing.
abstract: CB.Hep-1 monoclonal antibody (mAb) is used for a recombinant Hepatitis B vaccine manufacturing, which is included in a worldwide vaccination program against Hepatitis B disease. The use of this mAb as immunoligand has been addressed into one of the most efficient steps of active pharmaceutical ingredient purification process. Regarding this, Quality Risk Management (QRM) provides an excellent framework for the risk management use in pharmaceutical manufacturing and quality decision-making applications. Consequently, this study sought applying a prospective risk analysis methodology Failure Mode Effects Analysis (FMEA) as QRM tool for analyzing different CB.Hep-1 mAb manufacturing technologies. As main conclusions FMEA was successfully used to assess risks associated with potential problems in CB.Hep-1 mAb manufacturing processes. The severity and occurrence of risks analysis evidenced that the percentage of very high severe risks ranged 31.0-38.7% of all risks and the huge majority of risks have a very low occurrence level (61.9-83.3%) in all assessed technologies. Finally, additive Risk Priority Number, was descending ordered as follow: transgenic plants (2636), ascites (2577), transgenic animals (2046) and hollow fiber bioreactors (1654), which also corroborated that in vitro technology, should be the technology of choice for CB.Hep-1 mAb manufacturing in terms of risks and mAb molecule quality.
authors.affiliation: Quality Assurance Direction, Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, PO Box. 6162, Havana 10600, Cuba.
authors.forename: Lorely
authors.initials: L
authors.lastname: Milá
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Valdés
authors.forename: Andrés
authors.initials: A
authors.lastname: Tamayo
authors.forename: Sigifredo
authors.initials: S
authors.lastname: Padilla
authors.forename: Williams
authors.initials: W
authors.lastname: Ferro
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000096:biosynthesis / Q000276:immunology; D001709:Biotechnology / Q000379:methods; D002846:Chromatography, Affinity; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000096:biosynthesis* / Q000276:immunology / Q000302:isolation & purification / Q000592:standards; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified; D012308:Risk Management
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines