目的:预测妊娠胎儿血型状态的非侵入性检测方法在处理因血型抗原不相容性而有有害后果风险的妊娠时,是有价值的临床工具。为了确保临床适用性,胎儿血型的非侵入性产前检测需要遵循严格的验证和质量保证规则.这里,我们提出了一份多国立场文件,其中就此类检测的验证和质量保证提出了具体建议,并根据欧盟法规讨论了其风险分类.
方法:我们综述了关于体外诊断(IVD)试验的一般验证和非侵入性胎儿RHD基因分型的文献。建议基于共同作者之间的讨论结果。
结果:关于欧洲议会和理事会的《体外诊断医疗器械法规2017/746》附件VIII,胎儿血型的非侵入性产前检测是D类风险设备。在我们看来,非免疫RhD阴性女性的靶向抗D预防筛查应置于C级风险下,以确保欧盟内外的高质量非侵入性胎儿血型检测,我们在分析检测限方面提出了具体的验证和质量保证建议,范围和线性,精度,鲁棒性,预分析和常规测试中控件的使用。关于免疫妇女,讨论了验证和IVD风险分类的不同要求。
结论:应遵循这些建议,以确保商业和内部测定的临床使用具有适当的测定性能和适用性。
OBJECTIVE: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations.
METHODS: We reviewed the literature covering validation for in-vitro diagnostic (IVD) assays in general and for non-invasive foetal RHD genotyping in particular. Recommendations were based on the result of discussions between co-authors.
RESULTS: In relation to Annex VIII of the In-Vitro-Diagnostic Medical Device Regulation 2017/746 of the European Parliament and the Council, assays for non-invasive prenatal testing of foetal blood groups are risk class D devices. In our opinion, screening for targeted anti-D prophylaxis for non-immunized RhD negative women should be placed under risk class C. To ensure high quality of non-invasive foetal blood group assays within and beyond the European Union, we present specific recommendations for validation and quality assurance in terms of analytical detection limit, range and linearity, precision, robustness, pre-analytics and use of controls in routine testing. With respect to immunized women, different requirements for validation and IVD risk classification are discussed.
CONCLUSIONS: These recommendations should be followed to ensure appropriate assay performance and applicability for clinical use of both commercial and in-house assays.