TY - JOUR
T1 - Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: Current advances
AU - Vicente, Tiago
AU - Mota, José Paulo Barbosa
AU - Peixoto, Cristina
AU - Alves, Paula Maria
AU - Carrondo, Manuel José Teixeira
PY - 2011/1/1
Y1 - 2011/1/1
N2 - The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, "black-boxed" based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping. (C) 2011 Elsevier Inc. All rights reserved.
AB - The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, "black-boxed" based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping. (C) 2011 Elsevier Inc. All rights reserved.
KW - Analytical technologies
KW - Membrane processes
KW - Viral vector
KW - Virus-like particle
KW - Ion-exchange chromatography
KW - Mathematical model
U2 - 10.1016/j.biotechadv.2011.07.004
DO - 10.1016/j.biotechadv.2011.07.004
M3 - Article
C2 - 21784144
SN - 0734-9750
VL - 29
SP - 869
EP - 878
JO - Biotechnology Advances
JF - Biotechnology Advances
IS - 6
ER -
