Current state of commercial point-of-care nucleic acid tests for infectious diseases

Abstract

The COVID-19 pandemic has put the spotlight on the urgent need for integrated nucleic acid tests (NATs) for infectious diseases, especially those that can be used near patient ("point-of-care", POC), with rapid results and low cost, but without sacrificing sensitivity or specificity of gold standard PCR tests. In the US, the Clinical Laboratory Improvement Amendments Certificate of Waiver (CLIA-waiver) is mandated by the Food and Drug Administration (FDA) and designated to any laboratory testing with high simplicity and low risk for error, suitable for application in the POC. Since the first issuance of CLIA-waiver to Abbot's ID NOW Influenza A&B in 2015, many more NAT systems have been developed, received the CLIA-waiver in the US or World Health Organization (WHO)'s pre-qualification, and deployed to the front line of infectious disease detection. This review highlights the regulatory process for FDA and WHO in evaluating these NATs and the technology innovation of existing CLIA-waived systems. Understanding the technical advancement and challenges, unmet needs, and the trends of commercialization facilitated through the regulatory processes will help pave the foundation for future development and technology transfer from research to the market place.

Figure 1.

Molecular Diagnostics as approved or cleared through the FDA regulatory pathway that are in-scope of the paper (in bold boxes)

Figure 2.

A. Roche Liat instrument with B. lab-in-a-tube sample preapration module. C. Liat tube operation steps as through each step from sample prepreation to PCR completion

Figure 3.

A. Principle of operation for NEAR, B. Abbot ID NOW operation steps including sample prepration modules

Figure 4.

A. FilmArray pouch and B. instrument

Figure 5.

Cepheid GeneXpert Xpress A. cartridge and B. reader ^,,

Figure 6.

A. Accula sample preparation cartridge including sample preapration layer (top) connected through internal capillary flow channel (not shown) to the ampfliciation layer (bottom); B. OPCRar amplification thermal cycles with reduced temperature range and rapid speed; C. OPCRar principle of operation with partial denaturation instead of full denaturation; D. the Accular cartridge and analyzer

Figure 7.

SAMBA semi-Q system. A: The self-sustained isothermal amplification method. B: the sample preparation features of SAMBA semi-Q compared with gold standard methods. C. SAMBA II instruments. D. SAMBA II cartridge. E. SAMBAII process flow including from sample-to-results ^,,,.

Figure 8.

A. The m-PIMA Analyzer, compatible with both B. Alere q HIV-1/2 Detect and C. m-PIMA HIV-1/2 VL sample preparation cartridges.^,

Figure 9.

Trend of number FDA-cleared or WHO-prequalified nucleic acid tests over time for major disease areas. Cleared NA tests continue to increase over time with a greater variety of pathogens included.