With the spread of a novel coronavirus disease COVID-19 in early 2020, dozens of nucleic acid amplification test (NAT) kits were developed in Japan and used for the diagnosis of COVID-19. Because of the urgent need to supply the kits to testing facilities, they were developed over a short time period and had to be urgently approved for use. In this study, we investigated the composition and specifications of COVID-19 diagnostic NAT kits that were approved for emergency use in Japan and the USA to see if there are any distinctive features that might be related to the urgency of development. With regard to primer design, we found that several NAT kits had adopted primers designed by public organizations such as the National Institute of Infectious Diseases in Japan and the USA Centers for Disease Control and Prevention (CDC), without designating manufacturer’s original primers. In addition, some of the NAT kits had been developed to detect a single region of the viral genome, rather than multiple regions. A comparison between the NAT kits approved in Japan and the USA, showed that a higher percentage of NAT kits had adopted newer methods for specimen processing and nucleic acid amplification in Japan than in the USA. In addition, some NAT kits developed in Japan did not use an internal standard, which is a positive control nucleotide sequence to ensure valid amplification reaction and/or RNA extraction, whereas all kits in the USA used an internal standard. Based on the results of this survey, we discuss how NAT kits should be developed for a future pandemic, as well as the points to be considered in order to ensure the reliability of NAT kits.

Purpose: Smart operating theater (SOT) systems called Smart Cyber Operating Theater (SCOT)^1） and OR.NET^2） have been developed in Japan and Germany, respectively. Guidelines for product lifecycle processes have also been issued in conjunction with those SOT systems. However, the guideline developed in Japan does not necessarily include medical device regulation in its scope. The purpose of this study was to identify what additional considerations might be necessary when medical device manufacturers develop interoperable products for incorporation into SOT systems according to the Japanese guideline.

Materials and Methods: We looked for sections or requirements related to “risk management” and “verification and validation” as comparable subjects in the guidelines “Development Guideline for System Configuration and Operation of Smart Operating Theatres 2019”^3）（ Development Guideline for SOT 2019） and “SDC（ Service-oriented Device Connectivity） Conformance Principles”^4）. Then, “risk management” was further subdivided into “responsible party” and “safety risks to be addressed”, and “verification and validation” was further subdivided into “verification and validation requirement”, “responsible party” and “lifecycle phases subject to verification and validation”.

Results: Our study indicates that the Development Guideline for SOT 2019 provides a reasonable reference for nonmedical devices, but additional considerations are needed for medical devices. These additional considerations include postmarketing surveillance and assessment of risk concerns related to essential performance of SOT elements for risk management and a structural approach and periodical testing for verification and validation. We also suggest that further consideration of suitable risk analysis methodology for SOT systems is needed for both guidelines.

Dissolution tests of spironolactone tablets were conducted by UV-visible spectrophotometry using six different polysorbate 80 (PS80) reagents purchased, which were conformed to the specification of The Japanese Pharmacopoeia. Four of six PS80 were used in the dissolution media, spironolactone could not be measured due to interference by high absorbance around 230 nm, which is derived from the used PS80 reagents.

On the other hand, the HPLC method was able to measure spironolactone in the PS80 solution used for dissolution medium without any particular interference.

Analysis of these PS80 samples by LC-PDA and LC-QTOFMS revealed that there were differences in chromatographic patterns between products, which showed high absorbance around UV 230 nm or not.

In addition, ¹H-NMR measurements demonstrated some characteristic signals in the product with high absorbance around UV230 nm.

To use PS80 a test solution for dissolution test employing UV-visible spectrophotometry as the measurement method, it was necessary to confirm PS80 have no interference at the measurement wavelength. In case any interference are observed, it may be preferable to perform dissolution tests using HPLC as the detection method.