Addressing the challenges of molecular diagnostics in infectious diseases by developing metrology tools in Colombia

Abstract

The COVID 19 pandemic highlighted the lack of molecular metrological tools such as reference materials, reference measurement methods as well as proficiency testing or inter-laboratory comparisons to support an effective response to the detection and diagnosis of infectious diseases. Although some international organizations developed the first measurement protocols as the Charite [1], and others, the first reference materials as the RGTM10169 developed by the National Institute of Standards and Technologies – NIST [2] rapid transfer was not easy, mainly due to restriction on international trade on the one hand, and by the availability of this kind of materials on the other. Now, four years later, there remain several challenges associated with the rapid development and provision of reference materials at the nucleic acid level, as well as interlaboratory comparisons in developing countries to support clinical laboratories, and related stakeholders In Colombia, leveraged by the national technical capacity already existing, the National Metrology Institute (INM) and the National Health Institute (INS) worked together for developing a qualitative proficiency test for the detection of SARS-CoV- 2 by Polymerase Chain Reaction PCR in 2020, using the synthetic RNA reference material (RGTM 10169) [2]. which was supported by NIST and the United Nations Industrial Development Organization – UNIDO Since then, INM and INS have developed two mores proficiency test to support and strength clinical laboratories in Colombia, in 2022 with genomic RNA from SARS-CoV-2 omicron variant and in 2024 genomic RNA of Influenza A and B was included, as SARS-CoV-2 became a respiratory control virus. These exercises have allowed the development of technical competences at different levels: i) strengthening the network of clinical laboratories to monitor and improve the quality of the molecular PCR assay methods, ii) development of reference molecular methods for detection and quantification of nucleic acid by digital PCR and iii) production and characterization of reference materials at DNA/RNA level to be used in proficiency testing exercises. In addition, coordination between different technical organizations in Colombia has been promoted to continue developing other molecular metrological tools. to respond to the needs of clinical laboratories for the surveillance of respiratory viruses of interest, the agreement between the INS and the INM foresees the development of new reference materials, including respiratory syncytial virus (RSV), adenovirus and influenza A subtypes H1 and H3, and the evaluation of different nucleic acid materials, such as genomic DNA/RNA, in vitro transcribed RNA, plasmids, among others to increase the stability of the material. In the coming years, we expect to support the development of proficiency testing programs covering other pathogens of importance in the region, as well as training programs for clinical laboratories to increase their technical competence to support different stakeholders. References [1] V. M. Corman et al., “Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR,” Eurosurveillance, vol. 25, no. 3, Jan. 2020, doi: 10.2807/1560-7917.ES.2020.25.3.2000045. [2] M. H. Cleveland et al., “Rapid production and free distribution of a synthetic RNA material to support SARS-CoV-2 molecular diagnostic testing,” Biologicals, vol. 82, p. 101680, May 2023, doi: 10.1016/J.BIOLOGICALS.2023.101680.