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| Author(s): |
Luciana Separovic
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2021-11-18 |
| Examining board members: |
Felipe Rebello Lourenço;
Ricardo Jorge Neves Bettencourt da Silva;
Maurício Yonamine
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| Advisor: | Felipe Rebello Lourenço |
| Abstract | |
The analytical results are the basis for decision-making in conformity assessment. However, due to the measurement uncertainty (MU), it is possible that analytical procedures do not present adequate performance for its application in conformity assessment, affecting the reliability of its results. Thus, the aim of this work was to establish procedures for performance evaluation of analytical procedures based on the MU and to use the concepts of Analytical Quality by Design (AQbD) to propose optimization strategies. Initially, the MU values of the procedures were estimated by top-down approach, based on trueness and precision data. The consumer\'s and producer\'s risks were estimated by Bayesian and frequentist approaches. Most of the evaluated procedures presented MU value above the recommended, reflecting on the risks of false decision. One of the evaluated procedures was the basis for optimization using AQbD. To this end, the MU was estimated by bottom-up approach, allowing the identification and quantification of the sources of uncertainty, which was used as a basis for the design of experiments, along with factors that influence the chromatographic responses. The regression models obtained were considered adequate and then were used to define the method operable design region by Monte Carlo method. The optimized procedure was verified for performance, showing a significant reduction in MU, risks of false decision, and relative costs of decision-making in conformity assessment. This work showed the importance of MU in the performance evaluation of analytical procedures and its impact on the risks of false decision in conformity assessment of medicines. Additionally, the proposed strategies to improve performance proved to be effective, obtaining a robust procedure with reduced MU, ensuring results with greater reliability. (AU) | |
| FAPESP's process: | 18/25734-0 - Measurement uncertainty in performance evaluation of analytical methods and improvement strategies using analytical quality by design |
| Grantee: | Luciana Separovic |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |