Quality in vaccine development: a case study of Bio-Manguinhos's non-replicating yellow fever vaccine

Introduction:Translating scientific research into products is one of the many challenges Brazil faces in strengthening its biopharmaceutical industry.In addition to funding, lack of infrastructure is one of the major barriers to product development.There are not many studies on the lack of pilot facilities in Brazil and efforts to scale up technological processes to move from preclinical to clinical stages. Objectives:In this work, we have demonstrated our commitment to quality guidelines in the R&D of an inactivated yellow fever vaccine (iYFV) and the gradual transition from bench to pilot scale production. Methodology:In 2015, the Target Product Profile, Critical Process Parameters and specifications of the production, seed batch and vaccine formulation were made.In 2017, a first revision of the QTPP was carried out together with the first version of the critical product attributes list, the risk analysis Preliminary Hazard Analysis and a Hazard and Operability Study, the latter being a risk analysis to support the commissioning of the bioreactors at the Bio-Manguinhos (BM) pilot plant.In 2018/19, a Vero cell bank produced and characterized was obtained from a supplier and transferred to BMs GMP production area.In 2019/20, the pilot scale upstream stage was achieved, under experimental conditions.At the same time, a projection of the production process of the iYFV was studied to enable the future production process at the BM facilities guiding the construction of the Control Strategy. Results:In 2022/23, an active gap analysis was carried out for the upstream process and all the theoretical knowledge of the upstream process was transferred to LABPE in BM.At the same time, a gap analysis and risk analysis study related to downstream step was initiated.In 2024, all the knowledge acquired has been consolidated to start the upstream and downstream steps.Finally, in 2025, the control strategy for upstream and downstream processes is underway, demonstrating the technological leapfrogging capacity that has been achieved. Conclusion:The sequence of steps described is the result of a combination of scientific knowledge and quality, working together.It is important to highlight that the organization and documentation of this with logical sequencing to optimize the development processes and technology transfer from bench to production scales.Aiming an increasing development efficiency and improving project accuracy, all project data has been and will be incorporated into the R&Ds Quality System, like the ongoing control strategy.The close collaboration between R&D and quality brings many benefits to the institution.