title: Process development of a New Haemophilus influenzae type b conjugate vaccine and the use of mathematical modeling to identify process optimization possibilities.
abstract: Vaccination is one of the most successful public health interventions being a cost-effective tool in preventing deaths among young children. The earliest vaccines were developed following empirical methods, creating vaccines by trial and error. New process development tools, for example mathematical modeling, as well as new regulatory initiatives requiring better understanding of both the product and the process are being applied to well-characterized biopharmaceuticals (for example recombinant proteins). The vaccine industry is still running behind in comparison to these industries. A production process for a new Haemophilus influenzae type b (Hib) conjugate vaccine, including related quality control (QC) tests, was developed and transferred to a number of emerging vaccine manufacturers. This contributed to a sustainable global supply of affordable Hib conjugate vaccines, as illustrated by the market launch of the first Hib vaccine based on this technology in 2007 and concomitant price reduction of Hib vaccines. This paper describes the development approach followed for this Hib conjugate vaccine as well as the mathematical modeling tool applied recently in order to indicate options for further improvements of the initial Hib process. The strategy followed during the process development of this Hib conjugate vaccine was a targeted and integrated approach based on prior knowledge and experience with similar products using multi-disciplinary expertise. Mathematical modeling was used to develop a predictive model for the initial Hib process (the 'baseline' model) as well as an 'optimized' model, by proposing a number of process changes which could lead to further reduction in price. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:568-580, 2016.
authors.affiliation: Institute for Translational Vaccinology (Intravacc), P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
authors.forename: Ahd
authors.initials: A
authors.lastname: Hamidi
authors.affiliation: Institute for Translational Vaccinology (Intravacc), P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Kreeftenberg
authors.affiliation: Institute for Translational Vaccinology (Intravacc), P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: V D Pol
authors.affiliation: Dept. of Biotechnology, Delft University of Technology, The Netherlands.
authors.forename: Saroj
authors.initials: S
authors.lastname: Ghimire
authors.affiliation: Dept. of Biotechnology, Delft University of Technology, The Netherlands.
authors.forename: Luuk A M
authors.initials: LA
authors.lastname: V D Wielen
authors.affiliation: Dept. of Biotechnology, Delft University of Technology, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Ottens
mesh_terms: D016667:Bacterial Capsules / Q000276:immunology*; D018073:Haemophilus Vaccines / Q000032:analysis / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000276:immunology*; D008962:Models, Theoretical; D014611:Vaccination
chemical_list: D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine
keywords: PRP; conjugate; cost of goods; haemophilus influenzae type b vaccine; mathematical modeling; polysaccharide; process development; process optimization; targeted and integrated process development approach; technology transfer; unit operation