Best Practice of Biometrology to Support Nucleic Acids Detection of Infection Disease

Abstract

In response to the demand for metrology in the context of the SARS-CoV-2 epidemic, National Institute of Metrology (NIM), China has undertaken a series of initiatives in the field of infectious disease testing, ranging from cutting-edge research to practical application. Three reference measurement procedures (RMP) published at JCTLM specify the operating specifications for SARS-CoV-2 (open reading frame 1ab, ORF1ab and nucleocapsid protein, N and Envelope, E gene) RNA copy number concentration by reverse transcription digital PCR (RT-dPCR). Certified Reference Materials including in vitro transcribed RNA, genomic RNA and Pseudoviral RNA of SARS-CoV-2 and different variants (GBW0928 to GBW09318) have been developed and widely applied for practical application. These reference materials were widely used by more than 1000 institutes or companies, including IVD manufacturers, CDCs, clinical laboratories, universities and institutes. Especially in helping many IVD manufacturers obtain certification for their testing kits from National Medical Products Administration of China (NMPA), FDA and CE, it has played an important role in providing metrological traceability. To investigate the international comparability in nucleic acid measurement and supporting CMC claim, NIM successfully coordinated two rounds’ comparisons for SARS-CoV-2 (CCQM-P199B and CCQM-K181) with LGC, NIBSC and NIST. Furthermore, to support other NMIs in APMP region to establish the capability in measurement of SARS-CoV-2, an international training course of “Accurate Measurement of SARS-CoV-2 and Development of Nucleic Acids Reference Material” was organized by NIM incorporated with HSA, KRSISS and NIST. Additionally, three rounds of proficiency testing for SARS-CoV-2 RNA and its different variants were conducted to enhance the capacity and guarantee the consistency of testing facilities in China. In 2023-2024, NIM has provided invaluable assistance to China CDC in the ongoing monitoring of SARS-CoV-2, particularly in the detection of the virus in urban sewage. This support includes providing simulated samples of Pseudoviral virus of SARS-CoV-2, as well as enriching the virus in urban sewage and employing highly accurate measurement methods. The whole framework can be used as the best practice of biometrology to support nucleic acids detection of infection disease and get prepared for future epidemic.