A Simulation Analysis of an Influenza Vaccine Production Plant in Areas of High Humanitarian Flow. A Preliminary Study for the Region of Norte de Santander (Colombia)

The production of vaccines of biological origin presents a tremendous challenge for researchers. In this context, animal cell cultures are an excellent alternative for the isolation and production of biologicals against several viruses, since they have an affinity with viruses and a great capacity for their replicability. Different variables have been studied to know the system’s ideal parameters, allowing it to obtain profitable and competitive products. Consequently, this work focuses its efforts on evaluating an alternative for producing an anti-influenza biological from MDCK cells using SuperPro Designer v8.0 software. The process uses the DMEN culture medium supplemented with nutrients as raw material for cell development; the MDCK cells were obtained from a potential scale-up with a final working volume of 500 L, four days of residence time, inoculum volume of 10%, and continuous working mode with up to a total of 7400 h/Yr of work. The scheme has the necessary equipment for the vaccine’s production, infection, and manufacture with yields of up to 416,698 units/h. In addition, it was estimated to be economically viable to produce recombinant vaccines with competitive prices of up to 0.31 USD/unit.

[1]  Y. Valero,et al.  BEI Inactivated Vaccine Induces Innate and Adaptive Responses and Elicits Partial Protection upon Reassortant Betanodavirus Infection in Senegalese Sole , 2021, Vaccines.

[2]  J. Wood,et al.  Global production capacity of seasonal and pandemic influenza vaccines in 2019 , 2020, Vaccine.

[3]  Licelly Canizales,et al.  SuperPro Designer®, User-Oriented Software Used for Analyzing the Techno-Economic Feasibility of Electrical Energy Generation from Sugarcane Vinasse in Colombia , 2020, Processes.

[4]  Michael C. Borys,et al.  Biomanufacturing evolution from conventional to intensified processes for productivity improvement: a case study , 2020, mAbs.

[5]  C. Prieto,et al.  A simplified roller bottle platform for the production of a new generation VLPs rabies vaccine for veterinary applications. , 2019, Comparative immunology, microbiology and infectious diseases.

[6]  Manish M Patel,et al.  Polio endgame: Lessons for the global rotavirus vaccination program. , 2019, Vaccine.

[7]  J. Eiros,et al.  Cell culture-derived flu vaccine: Present and future , 2018, Human vaccines & immunotherapeutics.

[8]  R. Mills,et al.  Immunogenicity and safety of a cell culture-based quadrivalent influenza vaccine in adults: A Phase III, double-blind, multicenter, randomized, non-inferiority study , 2016, Human vaccines & immunotherapeutics.

[9]  Nico Vandaele,et al.  A review of integrated supply chain network design models: Key issues for vaccine supply chains , 2016 .

[10]  Udo Reichl,et al.  Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production , 2016, Applied Microbiology and Biotechnology.

[11]  E. Forleo-Neto,et al.  Non-inferiority of mammalian cell-derived quadrivalent subunit influenza virus vaccines compared to trivalent subunit influenza virus vaccines in healthy children: a phase III randomized, multicenter, double-blind clinical trial. , 2015, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[12]  Shawn T. Brown,et al.  Landscaping the structures of GAVI country vaccine supply chains and testing the effects of radical redesign. , 2015, Vaccine.

[13]  P. Alves,et al.  Improved virus purification processes for vaccines and gene therapy , 2015, Biotechnology and bioengineering.

[14]  Y. Genzel.  Designing cell lines for viral vaccine production: Where do we stand? , 2015, Biotechnology journal.

[15]  C. Reed,et al.  Estimating Influenza Disease Burden from Population-Based Surveillance Data in the United States , 2015, PloS one.

[16]  P. Moyle.  Progress in Vaccine Development , 2015, Current protocols in microbiology.

[17]  Li Fan,et al.  Rational design of medium supplementation strategy for improved influenza viruses production based on analyzing nutritional requirements of MDCK Cells. , 2014, Vaccine.

[18]  Alexandros Koulouris,et al.  Biopharmaceutical Process Optimization with Simulation and Scheduling Tools. , 2014, Bioengineering.

[19]  Shawn T. Brown,et al.  Correction: Augmenting Transport versus Increasing Cold Storage to Improve Vaccine Supply Chains , 2013, PLoS ONE.

[20]  Miladys Limonta,et al.  Simulation for the recovery of plasmid for a DNA vaccine , 2013 .

[21]  Vincenzo Guerriero,et al.  Power Law Distribution: Method of Multi-scale Inferential Statistics , 2012 .

[22]  T. Vesikari,et al.  Clinical efficacy of cell culture–derived and egg‐derived inactivated subunit influenza vaccines in healthy adults. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  Jonathan Liu,et al.  Production of cell culture (MDCK) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process , 2010, Biotechnology and bioengineering.

[24]  T. Heidmann,et al.  Risks linked to endogenous retroviruses for vaccine production: a general overview. , 2010, Biologicals : journal of the International Association of Biological Standardization.

[25]  D. Tabor,et al.  Cloning and assessment of tumorigenicity and oncogenicity of a Madin-Darby canine kidney (MDCK) cell line for influenza vaccine production. , 2010, Vaccine.

[26]  J. Chan,et al.  Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses. , 2009, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[27]  R. Bugarini,et al.  A novel mammalian cell-culture technique for consistent production of a well-tolerated and immunogenic trivalent subunit influenza vaccine. , 2009, Vaccine.

[28]  R. Bugarini,et al.  Safety and immunogenicity of a novel influenza subunit vaccine produced in mammalian cell culture. , 2009, The Journal of infectious diseases.

[29]  Suzanne S Farid,et al.  Process economics of industrial monoclonal antibody manufacture. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[30]  Sivakumar Kumaresan,et al.  Modelling and Optimization of Eurycoma longifolia Water Extract Production , 2006 .

[31]  T. Toner,et al.  Comparative study of influenza virus replication in Vero and MDCK cell lines. , 2004, Journal of virological methods.

[32]  Yao-ming Huang,et al.  Perfusion seed cultures improve biopharmaceutical fed‐batch production capacity and product quality , 2014, Biotechnology progress.