title: Integrated process optimization: lessons from retrovirus and virus-like particle production.
abstract: The optimization of production and purification processes is usually approached by engineers from a strictly biotechnological point of view. The present paper envisages the definition and application of an optimization model that takes into account the impact of both biological and technological issues upon the optimization protocols and strategies. For this purpose, the optimization of three analogous but different systems comprising animal cell growth and bioparticle production is presented. These systems were: human immunodeficiency 1 (HIV-1) and porcine parvovirus (PPV) virus-like particles (VLPs) produced in insect cells and retrovirus produced in mammalian cells. For the systematization of the optimization process four levels of optimization were defined-product, technology, design and integration. In this paper, the limits of each of the optimization levels defined are discussed by applying the concept to the systems described. This analysis leads to decisions regarding the production of VLPs and retrovirus as well as on the points relevant for further process development. Finally, the definition of the objective function or performance index, the possible strategies and tools for bioprocess optimization are described. Although developed from the three described processes, this approach can, based on the recent literature evidence reviewed here, be applied more universally for the process development of complex biopharmaceuticals.
authors.affiliation: IBET/ITQB, Apartado 12, P-2780 Oeiras, Portugal.
authors.forename: P E
authors.initials: PE
authors.lastname: Cruz
authors.forename: L
authors.initials: L
authors.lastname: Maranga
authors.forename: M J T
authors.initials: MJ
authors.lastname: Carrondo
mesh_terms: D000818:Animals; D019149:Bioreactors; D001709:Biotechnology / Q000379:methods*; D004356:Drug Storage / Q000379:methods; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007218:Industrial Microbiology / Q000379:methods*; D007313:Insecta; D008954:Models, Biological; D028323:Parvovirus, Porcine / Q000302:isolation & purification; D011786:Quality Control; D012190:Retroviridae / Q000302:isolation & purification*; D013552:Swine; D013597:Systems Analysis; D018511:Systems Integration; D014771:Virion / Q000302:isolation & purification*