Regalado FI, Mora MOO, Zumalacárregui CL

Language: Spanish
References: 13
Page: 109-117
PDF size: 423.41 Kb.

ABSTRACT

Nimotuzumab (hR3) is produced at the Center of Molecular Immunology (CIM). It is obtained from the culture, fermentation, and purification in the cell line NS0/H7. This product has a high demand both domestically and internationally for the treatment of head and neck cancer. The use of adequate technologies for the large-scale production of this product following good manufacturing practices and reasonable production costs becomes a necessity to introduce this therapeutic antibody in high demand markets with high-quality requirements. The increase in dimers in the final product will affect its quality, which in turn affects the efficiency and effectiveness of the process. Production databases were used to perform principal component analysis using The Unscrambler 10.4 software. The conductivity of the adjusted product, pH at the output product in the protein column and membrane, the mass of supernatant, and of the eluate are detected as the variables with a higher influence on aggregate formation. The Pareto analysis was carried out to determine the critical parameters of the process: pH of elution and adjust buffers, and adjusted products, pH at the exit of protein column and membrane, the mass of protein in the eluate, and in the supernatant, and the conductivity of the adjusted product.

REFERENCES

1. García A. Anticuerpos monoclonales. Aspectos básicos. Neurología.2011;26(5):301-6.

2. Li F, Zhou J, Yang X, Tressel T, Lee B. Current therapeutic antibody production and process optimization. BioProcess. J. 2005;4(5):1-8.

3. Viada C, Vega AM, Robaina M, Frías A, Álvarez M, Santiesteban Y, et al. Evaluación de Nimotuzumab para el tratamiento de cáncer de cabeza y cuello: Meta-análisis de ensayos controlados. Bionatura.2020;5:1056-62. doi: 10.21931/RB/2020.05.01.8

4. Mora O. Impacto de un medio de cultivo alternativo en el proceso de purificación del Nimotuzumab [Tesis para optar por el título de Ingeniero Químico]. La Habana: Universidad Tecnológica de La Habana “José Antonio Echeverría”; 2015.

5. Courtois F, Agrawal N, Lauer T, Trut B. Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab. MAbs.2016;8:99-112.

6. González M. Is your biologic at risk for protein aggregation? Part 1 [monograph on the Internet]. Pharmaceutical Online; 2018. Disponible en: http://www. pharmaceuticalonline.com/doc/. (Consultado en línea: 15 de abril de 2019).

7. Liu B, Guo H, Xu J, Qin T, Xu L, Zhang J, et al. Acid-induced aggregation propensity of nivolumab is dependent on the Fc. MAbs.2016;8:1107-17.

8. Tharwat, A. Principal component analysis-a tutorial. Int. J. Appl. Pattern Recognit. 2016;3(3):197-240.

9. Rodríguez RH, Gozá O, Ojito E. Preliminary modeling of an industrial recombinant human erythropoietin purification process by Artificial Neural Networks. Brazi. J. Chem. Eng.2015;32(3):725-34. http://dx.doi.org/10.1590/0104-6632.20150323s00003527.

10. Gozá O, Fernández M, Rodríguez EH, Ojito E. Aplicación del Análisis de Componentes Principales en el proceso de purificación de un biofármaco. Vaccimonitor.2020;29(1):5-13. Disponible en: http://www.vaccimonitor.finlay.edu.cu/index.php/vaccimonitor/article/view/226.

11. AITECO Consultores S.L [homepage on the Internet] Granada: Herramientas de calidad. Disponible en: https://www.aiteco.com/diagrama-de-pareto/ (Consultado en línea: 14 de abril de 2020).

12. Jolliffe IT. Principal Component Analysis. Second Edition. New York: SpringerVerlag; 2002.

13. López LE, Zumalacárregui L, Pérez O. Análisis de componentes principales aplicado a la fermentación alcohólica. Revista Científica de la UCSA.2019;6(2):11-9. doi:10.18004/ucsa/2409-8752/2019.006.02.011-019.