Implementation of Quality by Design to the Development of the Production Process of the Chemotherapeutical Enzyme L- Asparaginase

• Grant number: 18/03734-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2018
• End date: February 28, 2021
• Field of knowledge: Engineering - Chemical Engineering
• Principal Investigator: Adalberto Pessoa Junior
• Grantee: Francisco Vitor Santos da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08617-7 - Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical, AP.TEM

Abstract

Acute lymphoblastic leukemia (ALL) is the most common type of childhood hematological malignancy in Brazil and L-Asparaginase (ASNase), which increases its remission rate from 30% to over 80%, is currently imported by the Federal Government at high costs, thus showing the need for a national producer. Guided by the Quality by Design (QbD) principles, this projects aims at suggesting a production process for a proteolysis resistant ASNase with low glutaminase activity (dubbed EcA II*) given that the QbD philosophy, since 2004 popularized by de FDA, is nowadays recognized as one of the best strategies for guiding the development of biossimilar products. This project will be undertaken within the frame of the thematic FAPESP project "Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical" (n°: 2013/08617-7) in cooperation with Professor Brahim Benyahia (Loughborough University, UK) and it will be divided in three parts. 1) Definition of the product based on Risk Assessment Tools; 2) Development of a robust production process based on Design of Experiments (DoE) and ab initio models; 3) Proposition of a control strategy with emphasis on Quality Assurance. It is expected that this project will be the basis of the large-scale production process, which will be commissioned by the Brazilian Health Ministry and result in the wide propagation of the QbD philosophy within the Brazilian pharmaceutical industry.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KLEINGESINDS, EDUARDO KREBS; PARIZOTTO, LETICIA DE ALMEIDA; EFFER, BRIAN; MONTEIRO, GISELE; LONG, PAUL F.; ARROYO-BERDUGO, YOANA; BEHRENDS, VOLKER; ESPOSITO, MARIA TERESA; CALLE, YOLANDA; PESSOA-JR, ADALBERTO. Downstream process and evaluation of the concomitant impact of a recombinant glycosylated L-asparaginase on leukemic cancer cells and the bone marrow tumor microenvironment. Process Biochemistry, v. 131, p. 11-pg., 2023-06-09. (19/06919-2, 13/08617-7, 15/07749-2, 18/03734-9, 17/25065-9, 17/20384-9, 18/15104-0)

BRUMANO, LARISSA PEREIRA; SANTOS DA SILVA, FRANCISCO VITOR; COSTA-SILVA, TALES ALEXANDRE; APOLINARIO, ALEXSANDRA CONCEICAO; PICADO MADALENA SANTOS, JOAO HENRIQUE; KLEINGESINDS, EDUARDO KREBS; MONTEIRO, GISELE; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; BENYAHIA, BRAHIM; PESSOA JUNIOR, ADALBERTO. Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 6, JAN 10 2019. (14/10456-4, 15/07749-2, 18/03734-9, 13/08617-7, 17/21819-9)