Thesis, FRANZEN Rachelle

Abstract

ABSTRACT Context: This work describes the BabyDetect neonatal screening genomic test for pediatric, treatable, genetic disorders. It is an in-house developed test that follows the IVDR regulations and the ISO15189-2022 standard. In such a context, any modification that could impact on the analytical performance, quality, reliability, and integrity of the results must be validated and/or revalidated. Objective: The objective was to evaluate the impact of changes made in the implementation of the BabyDetect test, notably the relocation of testing activities, the change in software for variant analysis and interpretation, and the implementation of the NGS-WES technology. Method: We conducted a risk analysis of the relocation and post-relocation phases, including risks related to activities associated with both the NGS-panel method and the NGS-WES method. This risk analysis led to validation plans. A global validation of the analytical workflow was performed by comparing results obtained after the relocation with those obtained before. The validation of the Qiagen-Franklin variant interpretation software was carried out by comparing results obtained with the Agilent-Alissa platform against those obtained with the new one. These validation plans were translated into actions that yielded results. Results: This work demonstrated that neither the relocation nor the change in variant interpretation software had a negative impact on the analytical performance of the BabyDetect NGS-panel test, nor on the bioinformatics performance. Furthermore, it offers prospects for expanding neonatal screening through the introduction of the BabyDetect NGS-WES test. Conclusion: The changes that occurred in the implementation of the BabyDetect test did not compromise the quality of the results. Therefore, the BabyDetect test can continue to be offered following the relocation of its associated testing activities. This work highlights the importance of change management in order to demonstrate the maintenance of compliance for our in-house developed tests throughout his life cycle.