(177 days)
Not Found
No
The device description focuses on the automated RT-PCR process and visual interpretation of results via color change. There is no mention of AI, ML, or any computational analysis of the results beyond a simple "RESULTS VALID" check and visual spot interpretation.
No.
This device is an in vitro diagnostic test designed to detect viral RNA for diagnostic purposes, not to provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is an "in vitro diagnostic test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, and influenza B RNA" and "is intended for use as an aid in the differential diagnosis".
No
The device description clearly states it is a "fully integrated, compact device containing a reverse transcription polymerase chain reaction (RT-PCR) based assay" and describes physical components and processes like lysis modules, sample preparation modules, thermal cycling, and visual color change detection. This indicates a hardware component is integral to the device's function.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Visby Medical Respiratory Health Test is an "in vitro diagnostic test".
- Device Description: The description details how the device analyzes biological specimens (nasopharyngeal and anterior nasal swabs) to detect and differentiate specific viral RNA. This process is performed outside of the body, which is the definition of "in vitro".
- Function: The device performs a laboratory-based test (RT-PCR) on a biological sample to provide diagnostic information about a patient's health status (presence of SARS-CoV-2, influenza A, or influenza B infection).
The entire document describes a product designed and intended for use in a laboratory or clinical setting to diagnose disease by testing samples taken from the human body. This aligns perfectly with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Visby Medical Respiratory Health Test is a single-use (disposable), fully integrated, automated Reverse Transcription Polymerase Chain Reaction (RT-PCR) in vitro diagnostic test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza B RNA in nasopharyngeal swab and anterior nasal swab specimens from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza B can be similar.
The Visby Medical Respiratory Health Test is intended for use as an aid in the differential diagnosis of SARS-CoV-2, influenza A, and influenza B infection if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza A, and influenza B viral RNA are generally detectable in nasopharyngeal swab and anterior nasal swab specimens during the acute phase of infection. This test is not intended to detect influenza C virus infections.
Positive results are indicative of the identified virus, but do not rule out bacterial infection or co-infection with other organisms not detected by the test. The agent(s) detected by the Visby Medical Respiratory Health Test may not be the definitive cause of disease. Negative results do not preclude SARS-CoV-2, influenza B infection. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
Product codes (comma separated list FDA assigned to the subject device)
OOF
Device Description
The Visby Medical Respiratory Health Test is a single-use (disposable), fully integrated, compact device containing a reverse transcription polymerase chain reaction (RT-PCR) based assay for qualitative detection of influenza B, and/or SARS-CoV-2 viral RNA in upper respiratory tract specimens. The device automatically performs all steps required to complete lysis, reverse transcription (RT), PCR amplification, and detection.
Specimen collected using nasopharyngeal (NP) or anterior nasal (AN) swabs (without transport media) are placed in the Visby Medical Respiratory Health Buffer and then transferred into the sample port of the device using the provided fixed volume pipette. The sample enters a lysis module and rehydrates the RT enzyme and RT primers. The mixture then moves through a sample preparation module where viruses and human cells are simultaneously lysed, and RNA is reverse transcribed. The resulting fluid (containing cDNA) is then mixed with lyophilized PCR reagents containing the DNA polymerase enzyme and PCR primers. The PCR mixture (containing cDNA template and reagents) is then thermal cycled to amplify the targets, including human beta-2 microglobulin (B2M) RNA, which serves as a process control. After PCR, the biotinylated product is hybridized to covalently bound capture probes at specific locations along a flow channel. The flow channel is configured to facilitate an enzymatic reaction that uses streptavidin bound horseradish peroxidase (HRP) and a colorimetric substrate that forms a purple precipitate. The operator observes a color change at the specific locations indicating the presence of an amplified target. Test results can be expected in approximately 30 minutes: illumination of a "DONE" status light on the front of the device and a purple color in the "RESULTS VALID" spot, indicate a successful test. A purple spot adjacent to "Flu A", "Flu B", and/or "COVID-19" signifies the presence of, influenza A, influenza B, and/or SARS-CoV-2 viral RNA.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasopharyngeal swab, anterior nasal swab
Indicated Patient Age Range
Not Found
Intended User / Care Setting
CLIA Waived settings, healthcare professionals
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Clinical Evaluation:
A total of 1,592 subjects were enrolled in the study. Ninety one (91) study specimens were excluded from the performance analysis due to of lack of a valid comparator result (n=53), lack of a valid Visby test result (n=21), the subject did not meet inclusion criteria (n=10), or for protocol deviations (n=6). One subject withdrew from the study. This left 1,501 subjects for performance analysis of the Visby Medical Respiratory Health Test.
Specimens were collected and tested between May 2022 and Feb 2024.
Subjects presenting with signs and symptoms of a viral respiratory infection were prospectively enrolled at five CLIA Waived study sites in the US including urgent care and family care clinics.
One NP or dual nostril AN swab specimen was placed directly in Visby Respiratory Health Buffer and tested with the Visby device. The samples were also tested with an FDA-cleared influenza molecular test and an FDA-EUA authorized SARS-CoV-2 RT-PCR test as a comparator.
Annotation Protocol: The comparator assays (FDA-cleared influenza molecular test and an FDA-EUA authorized SARS-CoV-2 RT-PCR test) seem to serve as the reference standard for annotation.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Evaluation (Prospective Sample Testing)
- Study type: Clinical study with prospectively collected fresh specimens, establishing clinical performance in intended use setting.
- Sample size: 1,501 subjects included in performance analysis.
- Key results:
- Influenza A (NP+AN): PPA 96.9% (95% CI: 91.3-98.9%), NPA 99.4% (95% CI: 98.8-99.7%)
- Influenza B (NP+AN): PPA 100% (95% CI: 88.7-100%), NPA 99.8% (95% CI: 99.4-99.9%)
- SARS-CoV-2 (NP+AN): PPA 97.2% (95% CI: 94.4-98.7%), NPA 99.0% (95% CI: 98.3-99.5%)
Reproducibility Study
- Study type: Reproducibility study to evaluate performance by untrained users in CLIA Waived settings.
- Sample size: A seven (7) member panel was tested. Six (6) study operators (2 operators at each site) tested the panel three (3) times each testing day, over six (6) non-consecutive days.
- Key results: High overall agreement with expected results for all panel members (e.g., 100.0% for Influenza A Moderate Positive, 94.4% for Influenza A Low Positive, 100.0% for SARS-CoV-2 Moderate Positive, 95.4% for SARS-CoV-2 Low Positive, 100.0% for Negative).
Analytical Evaluation
- Limit of Detection (LoD):
- Influenza A/H1N1 2009, Brisbane/02/18: 106 copies/swab
- Influenza A/H3N2, Kansas/14/2017: 125 copies/swab
- Influenza B/Washington/02/19: 728 copies/swab
- Influenza B/Oklahoma/10/2018: 778 copies/swab
- SARS-CoV-2 (USA-WA1/2020): 100 copies/swab
- WHO 1st International Standard for SARS-CoV-2 (NIBSC code: 20/146): 2.2 x 10^5 IU/mL of RNA in the sample tested.
- Inclusivity: All tested strains of Influenza A (10 H1N1, 13 H3N2), Influenza B (12 strains), and SARS-CoV-2 (6 strains) were successfully detected. Avian Influenza A strains (RNA only) were also tested. A/Egypt/321/2007 (H5N1) was not detected at 1500 pg/mL in 1/3 replicates, but returned positive results in 2/3 replicates. Omicron (BA.2.3) Isolate USA/MD-HP24556/2022 was detected at 6x LoD. In silico analysis confirmed ability to detect all circulating SARS-CoV-2 variants as of August 2024.
- Cross-Reactivity and Microbial Interference: No cross-reactivity or microbial interference observed with 43 tested microorganisms at specified concentrations.
- Competitive Interference: No competitive interference observed for any of the three target viruses.
- Endogenous/Exogenous Interfering Substances: None of the 17 tested substances interfered with test accuracy.
- Specimen Stability: Specimen stability in Visby Respiratory Health Buffer was demonstrated for up to 120 minutes (2 hours) at room temperature (15-30°C) and up to 48 hours (2 days) refrigerated (2-8°C).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Prospective Fresh NP and AN Swab Specimen Performance (Visby vs. Comparator Assays)
- Influenza A (NP): PPA 97.1% (85.1-99.5%), NPA 99.5% (98.7-99.8%)
- Influenza A (AN): PPA 96.8% (89.1-99.1%), NPA 99.2% (98.1-99.7%)
- Influenza A (NP+AN): PPA 96.9% (91.3-98.9%), NPA 99.4% (98.8-99.7%)
- Influenza B (NP): PPA 100% (79.6-100%), NPA 99.8% (99.1-99.9%)
- Influenza B (AN): PPA 100% (79.6-100%), NPA 99.9% (99.1-100%)
- Influenza B (NP+AN): PPA 100% (88.7-100%), NPA 99.8% (99.4-99.9%)
- SARS-CoV-2 (NP): PPA 96.3% (91.6-98.4%), NPA 99.0% (97.9-99.5%)
- SARS-CoV-2 (AN): PPA 98.3% (94.0-99.5%), NPA 99.1% (97.9-99.6%)
- SARS-CoV-2 (NP+AN): PPA 97.2% (94.4-98.7%), NPA 99.0% (98.3-99.5%)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
DiaSorin Molecular Simplexa COVID-19 & Flu A/B Direct (K220963)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3981 Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.
(a)
Identification. A device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test is an in vitro diagnostic device intended for the detection and identification of SARS-CoV-2 and other microbial agents when in a multi-target test in human clinical respiratory specimens from patients suspected of respiratory infection who are at risk for exposure or who may have been exposed to these agents. The device is intended to aid in the diagnosis of respiratory infection in conjunction with other clinical, epidemiologic, and laboratory data or other risk factors.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;
(ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies;
(iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety (
e.g., BSL 3 and BSL 3+, etc.) is available to receive and culture specimens; and(v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population (
e.g., when applicable, that device performance has not been established in individuals without signs or symptoms of respiratory infection).(vi) Limiting statements that indicate that:
(A) A negative test result does not preclude the possibility of infection;
(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens;
(D) That positive and negative predictive values are highly dependent on prevalence;
(E) Accurate results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(F) When applicable (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer-reviewed literature), that the clinical performance may be affected by testing a specific clinical subpopulation or for a specific claimed specimen type.(4) Design verification and validation must include:
(i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses.
(ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains (
e.g., regular review of published literature and periodic in silico analysis of target sequences to detect possible mismatches). All results of this protocol, including any findings, must be documented and must include any additional data analysis that is requested by FDA in response to any performance concerns identified under this section or identified by FDA during routine evaluation. Additionally, if requested by FDA, these evaluations must be submitted to FDA for FDA review within 48 hours of the request. Results that are reasonably interpreted to support the conclusion that novel respiratory pathogen strains or isolates impact the stated expected performance of the device must be sent to FDA immediately.(iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection.
(iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device (
e.g., saturation level of hybridization and maximum amplification and detection cycle number, etc.), internal and external controls, and computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported signal and result), as applicable.(v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review.
(vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter.
(6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following:
(i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation.
(ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to State or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
(iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result.
(iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated (
i.e., H1-2009 and H3), this result requires notification of appropriate local, State, or Federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A.(7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
February 19, 2025
Visby Medical, Inc. Jennifer Albrecht Director of Regulatory Affairs 3010 North First Street San Jose, California 95134
Re: K242526
Trade/Device Name: Visby Medical Respiratory Health Test Regulation Number: 21 CFR 866.3981 Regulation Name: Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test Regulatory Class: Class II Product Code: OOF Dated: August 23, 2024
Dear Jennifer Albrecht:
Received: August 26, 2024
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
1
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatory
2
assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Anna M. Mielech -S
Anna Mielech, Ph.D. Deputy Branch Chief (Acting) Viral Respiratory and HPV Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K242526
Device Name Visby Medical Respiratory Health Test
Indications for Use (Describe)
The Visby Medical Respiratory Health Test is a single-use (disposable), fully integrated, automated Reverse Transcription Polymerase Chain Reaction (RT-PCR) in vitro diagnostic test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza B RNA in nasopharyngeal swab and anterior nasal swab specimens from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza B can be similar.
The Visby Medical Respiratory Health Test is intended for use as an aid in the differential diagnosis of SARS-CoV-2, influenza A, and influenza B infection if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza A, and influenza B viral RNA are generally detectable in nasopharyngeal swab and anterior nasal swab specimens during the acute phase of infection. This test is not intended to detect influenza C virus infections.
Positive results are indicative of the identified virus, but do not rule out bacterial infection or co-infection with other organisms not detected by the test. The agent(s) detected by the Visby Medical Respiratory Health Test may not be the definitive cause of disease. Negative results do not preclude SARS-CoV-2, influenza B infection. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
| Type of Use (Select one or both, as applicable) | ||
|---|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D)☐ Over-The-Counter Use (21 CFR 801 Subpart C) | ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
- A. Submitter
B.
| Name:
Address:
Phone: | Visby Medical, Inc.
3010 N. First Street
San Jose, CA 95134
1-833-468-4729 |
|-----------------------------|--------------------------------------------------------------------------------------------------------|
| Contact: | Jennifer Albrecht |
| Date Prepared: | February 16, 2025 |
| Device | |
| Name of Device: | Visby Medical Respiratory Health Test |
| Common Name: | Same |
| Common Name: | Sams |
| Classification Name: | Multi-Target Respiratory Specimen Nucleic Acid Test
Including Sars-Cov-2 And Other Microbial Agents |
| Regulatory Classification: | Class II |
| Regulation: | 21 CFR 866.3981 |
| Primary Product Code: | QOF |
C. Predicate Device
DiaSorin Molecular Simplexa COVID-19 & Flu A/B Direct (K220963)
D. Device Description
The Visby Medical Respiratory Health Test is a single-use (disposable), fully integrated, compact device containing a reverse transcription polymerase chain reaction (RT-PCR) based assay for qualitative detection of influenza B, and/or SARS-CoV-2 viral RNA in upper respiratory tract specimens. The device automatically performs all steps required to complete lysis, reverse transcription (RT), PCR amplification, and detection.
Specimen collected using nasopharyngeal (NP) or anterior nasal (AN) swabs (without transport media) are placed in the Visby Medical Respiratory Health Buffer and then transferred into the sample port of the device using the provided fixed volume pipette. The sample enters a lysis module and rehydrates the RT enzyme and RT primers. The mixture then moves through a sample preparation module where viruses and human cells are simultaneously lysed, and RNA is reverse transcribed. The resulting fluid (containing cDNA) is then mixed with lyophilized PCR reagents containing the DNA polymerase enzyme and PCR primers. The PCR mixture (containing cDNA template and reagents) is then thermal cycled to amplify the targets, including human beta-2
5
microglobulin (B2M) RNA, which serves as a process control. After PCR, the biotinylated product is hybridized to covalently bound capture probes at specific locations along a flow channel. The flow channel is configured to facilitate an enzymatic reaction that uses streptavidin bound horseradish peroxidase (HRP) and a colorimetric substrate that forms a purple precipitate. The operator observes a color change at the specific locations indicating the presence of an amplified target. Test results can be expected in approximately 30 minutes: illumination of a "DONE" status light on the front of the device and a purple color in the "RESULTS VALID" spot, indicate a successful test. A purple spot adjacent to "Flu A", "Flu B", and/or "COVID-19" signifies the presence of, influenza A, influenza B, and/or SARS-CoV-2 viral RNA.
E. Intended Use
The Visby Medical Respiratory Health Test is a single-use (disposable), fully integrated, automated Reverse Transcription Polymerase Chain Reaction (RT-PCR) in vitro diagnostic test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, and influenza B RNA in nasopharyngeal swab and anterior nasal swab specimens from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza A, and influenza B can be similar.
The Visby Medical Respiratory Health Test is intended for use as an aid in the differential diagnosis of SARS-CoV-2, influenza A, and influenza B infection if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza A, and influenza B viral RNA are generally detectable in nasopharyngeal swab and anterior nasal swab specimens during the acute phase of infection. This test is not intended to detect influenza C virus infections.
Positive results are indicative of the presence of the identified virus, but do not rule out bacterial infection or co-infection with other organisms not detected by the test. The agent(s) detected by the Visby Medical Respiratory Health Test may not be the definitive cause of disease. Negative results do not preclude SARS-CoV-2, influenza A, or influenza B infection. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient manaqement decisions.
F. Substantial Equivalence
The Visby Medical Respiratory Health test is substantially equivalent to DiaSorin Molecular Simplexa COVID-19 & Flu A/B Direct, K220963.
The following table compares the Visby Medical Respiratory Health Test to DiaSorin Molecular Simplexa COVID-19 & Flu A/B Direct and outlines the similarities and differences between the two tests.
6
| Characteristic | Predicate Device:
DiaSorin Molecular
Simplexa COVID-19 & Flu A/B Direct
(K220963) | Subject Device:
Visby Medical
Respiratory Health
(K242526) |
|----------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulation | 21 CFR 866.3981 | Same |
| Product Code | QOF | Same |
| Device Class | Class II | Same |
| Technology/
Detection | Real-time Reverse Transcription
Polymerase Chain Reaction (RT-PCR)
system, qualitative | Same |
| Characteristic | Predicate Device:
DiaSorin Molecular
Simplexa COVID-19 & Flu A/B Direct
(K220963) | Subject Device:
Visby Medical
Respiratory Health
(K242526) |
| Intended Use | The DiaSorin Molecular Simplexa COVID-
19 & Flu A/B Direct is a real-time RT-PCR
assay intended for use on the LIAISON
MDX instrument for the in vitro qualitative
detection and differentiation of nucleic
acid from severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2),
influenza A virus and influenza B virus in
nasopharyngeal swabs (NPS) from
individuals with signs and symptoms of
respiratory tract infection.
The Simplexa COVID-19 & Flu A/B Direct
assay is intended for use as an aid in the
differential diagnosis of SARS-CoV-2,
influenza A and influenza B infection.
Negative results do not preclude SARS-
CoV-2, influenza A or influenza B
infection and should not be used as the
sole basis for patient management
decisions. Positive results do not rule out
coinfections with other organisms.
Results should be combined with clinical
observations, patient history, and
epidemiological information.
The Simplexa COVID-19 & Flu A/B Direct
assay is intended for use by qualified and
trained clinical laboratory personnel
specifically instructed and trained in the
techniques of real-time PCR and in vitro
diagnostic procedures. | The Visby Medical Respiratory Health
Test is a single-use (disposable), fully
integrated, automated Reverse
Transcription Polymerase Chain Reaction
(RT-PCR) in vitro diagnostic test intended
for the simultaneous qualitative detection
and differentiation of severe acute
respiratory syndrome coronavirus 2
(SARS-CoV-2), influenza A, and influenza
B RNA in nasopharyngeal swab and
anterior nasal swab specimens from
individuals with signs and symptoms of
respiratory tract infection. Clinical signs
and symptoms of respiratory tract
infection due to SARS-CoV-2, influenza
A, and influenza B can be similar.
The Visby Medical Respiratory Health
Test is intended for use as an aid in the
differential diagnosis of SARS-CoV-2,
influenza A, and influenza B infection if
used in conjunction with other clinical and
epidemiological information, and
laboratory findings. SARS-CoV-2,
influenza A, and influenza B viral RNA are
generally detectable in nasopharyngeal
swab and anterior nasal swab specimens
during the acute phase of infection. This
test is not intended to detect influenza C
virus infections.
Positive results are indicative of the
presence of the identified virus, but do not
rule out bacterial infection or co-infection
with other organisms not detected by the
test. The agent(s) detected by the Visby
Medical Respiratory Health Test may not
be the definitive cause of disease.
Negative results do not preclude SARS-
CoV-2, influenza A, or influenza B
infection. The results of this test should
not be used as the sole basis for
diagnosis, treatment, or other patient
management decisions. |
| Characteristic | Predicate Device:
DiaSorin Molecular
Simplexa COVID-19 & Flu A/B Direct
(K220963) | Subject Device:
Visby Medical
Respiratory Health
(K242526) |
| Indication for Use | Symptomatic patients;
Rx - For Prescription Use Only | Same |
| Assay Targets | SARS-CoV-2, influenza A virus and
influenza B virus | Same |
| Sample to answer
system | Automated | Same |
| Specimen Types | Nasopharyngeal Swab | Nasopharyngeal Swab;
Anterior Nasal Swab |
| Sample Extraction | Self-contained and automated after
specimen sample elution | Same |
| Assay Results | Qualitative | Same |
| Instrument System | LIAISON MDX | N/A, self-contained assay and instrument
system |
| Assay Controls | Internal processing control (IPC), External
controls available. | Same |
| Turn-around Time | Approximately 90 minutes to results. | Approximately 30 minutes to results. |
7
8
G. Summary of Performance Data
Clinical Evaluation
Performance characteristics of the Visby Medical Respiratory Health Test were established in a clinical study that included testing of prospectively collected fresh specimens. The objective of this study was to establish the clinical performance of the Visby Medical Respiratory Health Test for the detection and differentiation of SARS-CoV-2, influenza A, and influenza B viral RNA in clinical specimens when in the intended use setting. This study was conducted at five CLIA Waived testings in the US. All study specimens were tested with the Visby Medical Respiratory Health Test by typical CLIA Waived operators according to the Quick Reference Guide (QRG) and Instructions for Use (IFU). Specimens were collected and tested between May 2022 and Feb 2024.
Prospective Sample Testing
Subjects presenting with signs and symptoms of a viral respiratory infection were prospectively enrolled at five CLIA Waived study sites in the US including urgent care and family care clinics. One NP or dual nostril AN swab specimen was placed directly in Visby Respiratory Health Buffer and tested with the Visby device. The samples were also tested with an FDA-cleared influenza molecular test and an FDA-EUA authorized SARS-CoV-2 RT-PCR test as a comparator.
A total of 1,592 subjects were enrolled in the study. Ninety one (91) study specimens were excluded from the performance analysis due to of lack of a valid comparator result
9
(n=53), lack of a valid Visby test result (n=21), the subject did not meet inclusion criteria (n=10), or for protocol deviations (n=6). One subject withdrew from the study. This left 1,501 subjects for performance analysis of the Visby Medical Respiratory Health Test. The distribution of subjects in the performance analysis by sex and age range is presented in Table 1.
| Category | Number Evaluated (as %) |
|---|---|
| Sex | Male 573 (38.2%) |
| Female 928 (61.8%) | |
| Age | ≤ 5 years 85 (5.7%) |
| 6 - 21 years 325 (21.7%) | |
| 22 - 59 years 883 (58.8%) | |
| ≥60 years 208 (13.9%) | |
| Total | 1501 |
| Table 1. Demographic Summary - Enrollment from May 2022 to Feb 2024 | |
|---|---|
| --------------------------------------------------------------------- | -- |
A total of 1,575 Visby tests were performed on subjects that met the inclusion criteria, did not experience a protocol deviation, did not withdraw from the study. Of these 79 (5.0%) had an initial invalid test result of which 21 (1.3%) were invalid when retested. Of the 840 NP swab specimens tested, 30 (3.6%) had an initial invalid test result of which 5 (0.6%) were invalid when retested. Of the 735 AN swab specimens tested, 49 (6.7%) had an initial invalid test result of which 16 (2.2%) were invalid when retested.
The positive percentage agreement (PPA) and neqative percentage agreement (NPA) of influenza A, influenza B, and SARS-CoV-2 are shown in Table 2 below.
10
| | Specimen
Type (NP/AN) | TP | FP | TN | FN | PPA (95% CI) | NPA (95% CI) |
|-------------|--------------------------|-----|----|------|----|-----------------------|-----------------------|
| Influenza A | NP | 33 | 4a | 791 | 1c | 97.1%
(85.1-99.5%) | 99.5%
(98.7-99.8%) |
| | AN | 61 | 5b | 604 | 2d | 96.8%
(89.1-99.1%) | 99.2%
(98.1-99.7%) |
| | NP+AN | 94 | 9 | 1395 | 3 | 96.9%
(91.3-98.9%) | 99.4%
(98.8-99.7%) |
| Influenza B | NP | 15 | 2e | 812 | 0 | 100%
(79.6-100%) | 99.8%
(99.1-99.9%) |
| | AN | 15 | 1f | 656 | 0 | 100%
(79.6-100%) | 99.9%
(99.1-100%) |
| | NP+AN | 30 | 3 | 1468 | 0 | 100%
(88.7-100%) | 99.8%
(99.4-99.9%) |
| SARS-CoV-2 | NP | 130 | 7g | 687 | 5i | 96.3%
(91.6-98.4%) | 99.0%
(97.9-99.5%) |
| | AN | 116 | 5h | 549 | 2j | 98.3%
(94.0-99.5%) | 99.1%
(97.9-99.6%) |
| | NP+AN | 246 | 12 | 1236 | 7 | 97.2%
(94.4-98.7%) | 99.0%
(98.3-99.5%) |
Table 2. Prospective Fresh NP and AN Swab Specimen Performance - Enrollment from May 2022 to Feb 2024 (Visby vs. Comparator Assays)
a 3 of 4 false positive NP specimens tested positive and one tested negative with an alternate molecular assay
b 5 of 5 false positive AN specimens tested positive with an alternate molecular assay
& 1 false negative NP specimen tested positive with an alternate molecular assay
d 2 false negative AN specimen tested positive with an alternate molecular assay
e 2 of 2 false positive NP specimens tested positive with an alternate molecular assay
「 1 of 1 false positive AN specimens tested positive with an alternate molecular assay
9 5 of 7 false positive NP specimens tested positive and 2 tested negative with an alternate molecular assay
h 4 of 5 false positive AN specimens tested positive, and 1 tested negative with an alternate molecular assay
1 3 of 5 false negative NP specimens tested negative and 2 tested positive with an alternate molecular assay
İ 1 of 2 false negative AN specimen tested negative and 1 tested positive with an alternate molecular assay
Reproducibility
A study was performed to evaluate the reproducibility of the Visby Medical Respiratory Health Test when used by untrained users in CLIA Waived settings. The operators performing the testing were non-laboratorians representing healthcare professionals that may be encountered at such sites. The study evaluated a seven (7) member panel composed of NP swabs seeded with unspiked clinical matrix (negative) and NP swabs seeded with clinical matrix individually spiked with low (1x LoD) or moderate (3-5x LoD) concentrations of the three target viruses.
A total of six (6) study operators (2 operators at each site) tested the panel three (3) times each testing day, over six (6) non-consecutive days. Three reagent lots were used in the study. Each lot was used for two (2) days of testing. The composition of the panel
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members along with a summary of results (correct count / total count) and percent agreement with the expected results for each panel member is presented in Table 3 below.
| Panel Member | Site 1
% Agreement
(count) | Site 2
% Agreement
(count) | Site 3
% Agreement
(count) | Overall Agreement
% Agreement
(count) | 95% CI |
|-------------------------------------------------------------------------------------|----------------------------------|----------------------------------|----------------------------------|---------------------------------------------|--------------|
| Influenza A
Moderate Positive | 100.0%
(36/36) | 100.0%
(36/36) | 100.0%
(36/36) | 100.0%
(108/108) | 96.6%-100.0% |
| Influenza A Low
Positive | 94.4%
(34/36) | 100.0%
(36/36) a | 88.9%
(32/36) | 94.4%
(102/108) a | 88.4%-97.4% |
| Influenza B
Moderate Positive | 97.2%
(35/36) | 100.0%
(36/36) | 100.0%
(36/36) | 99.1%
(107/108) | 94.9%-99.8% |
| Influenza B Low
Positive | 97.2%
(35/36) | 100.0%
(36/36) | 91.7%
(33/36) | 96.3%
(104/108) | 90.9%-98.6% |
| SARS-CoV-2
Moderate Positive | 100.0%
(36/36) | 100.0%
(36/36) | 100.0%
(36/36) | 100.0%
(108/108) | 96.6%-100.0% |
| SARS-CoV-2 Low
Positive | 97.2%
(35/36) | 100.0%
(36/36) | 88.9%
(32/36) | 95.4%
(103/108) | 89.6%-98.0% |
| Negative | 100.0%
(36/36) | 100.0%
(36/36) | 100.0%
(36/36) | 100.0%
(108/108) | 96.6%-100.0% |
| a One sample was positive for influenza A, but unexpectedly positive for SARS-CoV-2 | | | | | |
| Table 3. Summary of Reproducibility Results with the Visby Medical Respiratory | |
|---|---|
| Health Test |
Analytical Evaluation
Limit of Detection
The limit of detection (LoD) is the lowest concentration of viral nucleic acid that is reliably detected by the Visby Respiratory Health Test. Influenza A, influenza B, and SARS-CoV-2 were tested in a range-finding study of 3-fold dilutions in neqative clinical matrix, and the lowest concentration with 100% detection was established as the estimated LoD. The estimated LoD was confirmed by testing 20 replicates, where confirmation of the LoD was achieved when at least 19 of the 20 replicates returned a positive result for the virus tested. All viruses were tested individually in single-positive samples. The LoD of the Visby Medical Respiratory Health Test for influenza B, and SARS-CoV-2 are summarized in Table 4 below.
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| Virus | LoD Concentration |
|---|---|
| Influenza A/H1N1 2009, Brisbane/02/18 | 106 copies/swab |
| 4.89 TCID50/swab | |
| Influenza A/H3N2, Kansas/14/2017 | 125 copies/swab |
| 2.01 FFUa/swab | |
| Influenza B/Washington/02/19 | 728 copies/swab |
| 9.20 TCID50/swab | |
| Influenza B/Oklahoma/10/2018 | 778 copies/swab |
| 88.37 TCID50/swab | |
| SARS-CoV-2 (USA-WA1/2020) | 100 copies/swab |
| Table 4. Limit of Detection (LoD) for the Visby Medical Respiratory Health Test |
|---|
| Analytes |
ª FFU: Fluorescent Focus Units. Titer by Fluorescent Focus Assay in MDCK-SIAT1 Cells.
WHO 1st International Standard for SARS-CoV-2
The established analytical sensitivity or LoD of the Visby Medical Respiratory Health Test when tested with the World Health Organization (WHO) 1st International Standard for SARS-CoV-2 RNA (NIBSC code: 20/146) is 2.2 x 105 IU/mL of RNA in the sample tested.
Inclusivity
The ability of the Visby Medical Respiratory Health Test to detect 10 H1N1 (pandemic 2009) strains, 13 H3N2 strains, 12 influenza B strains (5 each of Victoria and Yamagata lineages and 2 additional strains), 6 SARS-CoV-2 strains, and 6 avian influenza A strains (RNA only, representing H5N1, H7N9, and H9N2). Each virus was individually spiked into negative clinical matrix at or near 3x LoD (unless otherwise noted) and tested in triplicate. All strains were successfully detected within 3x LoD, with the exception of the Omicron (BA.2.3) Isolate USA/MD-HP24556/2022 (detected at 6x LoD) and A/Egypt/321/2007 (H5N1).
| Virus | Strain | Tested
Concentration |
|---------------------------------|-------------------------------------------------------------|-------------------------------------------------|
| Influenza A H1N1
(pdm2009) | A/Brownsville/39H/2009 | 318 copies/swab |
| | A/Hong Kong/H090-761-V1(0)/2009 | 318 copies/swab |
| | A/Netherlands/2629/2009 | 318 copies/swab |
| | A/Massachusetts/15/2013 | 318 copies/swab |
| | A/Bangladesh/3002/2015 | 318 copies/swab |
| | A/Michigan/45/2015 | 318 copies/swab |
| | A/St. Petersburg/61/2015 | 318 copies/swab |
| | A/Hawaii/66/2019 | 318 copies/swab |
| | A/Wisconsin/588/2019 | 318 copies/swab |
| | A/Indiana/02/2020 | 318 copies/swab |
| Virus | Strain | Tested
Concentration |
| Influenza A H3N2 | A/Netherlands/22/2003 | 393 copies/swab |
| | A/New York/55/2004 | 393 copies/swab |
| | A/Brisbane/10/2007 | 393 copies/swab |
| | A/Uruguay/716/2007 | 393 copies/swab |
| | A/Hong Kong/H090-756-V1(0)/2009 | 393 copies/swab |
| | A/Perth/16/2009 | 393 copies/swab |
| | A/Victoria/361/2011 | 393 copies/swab |
| | A/Texas/50/2012 | 393 copies/swab |
| | A/Switzerland/9715293/2013 | 393 copies/swab |
| | A/Alaska/232/2015 | 393 copies/swab |
| | A/California/55/2020 | 393 copies/swab |
| | A/Hong Kong/2671/2019 | 393 copies/swab |
| | A/Wisconsin/04/2018 | 393 copies/swab |
| Avian Influenza A¹ | A/duck/Hunan/795/2002 (H5N1) | 1500 pg/mL |
| | A/chicken/Yunnan/1251/2003 (H5N1) | 1500 pg/mL |
| | A/Vietnam/1194/2004 (H5N1) | 1500 pg/mL |
| | A/Egypt/321/2007 (H5N1) | Not Detected² |
| | A/Anhui/1/2013 (H7N9) | 1500 pg/mL |
| | A/chicken/Hong Kong/G9/1997 (H9N2) | 1500 pg/mL |
| Influenza B | B/Lee/1940 | 2334 copies/swab |
| | B/Maryland/1/1959 | 2334 copies/swab |
| | B/Malaysia/2506/2004 | 2184 copies/swab |
| Influenza B Victoria
Lineage | B/St. Petersburg/14/2006 | 2184 copies/swab |
| | B/Brisbane/60/2008 | 2184 copies/swab |
| | B/Nevada/03/2011 | 2184 copies/swab |
| | B/New Jersey/1/2012 | 2184 copies/swab |
| | | B/New York/1061/2004 |
| | B/Florida/4/2006 | 2334 copies/swab |
| Influenza B
Yamagata Lineage | B/Texas/06/2011 | 2334 copies/swab |
| | B/Phuket/3073/2013 | 2334 copies/swab |
| | | B/Guangdong-Liwan/1133/2014 |
| | | Alpha (B.1.1.7) England/204820464/2020 |
| | | Beta (B.1.351) South Africa/ KRISP-K005325/2020 |
| | Gamma (P.1) Japan/TY7-503/2021 | 300 copies/swab |
| SARS-CoV-2 | Delta (B.1.617.2) USA/PHC658/2021 | 300 copies/swab |
| | Β.1.1.529 BA.1 Isolate: USA/MD-HP20874/2021 | 300 copies/swab |
| | Omicron (BA.2.3) Isolate: USA/MD-HP24556/2022 | 600 copies/swab |
| | ¹ Purified RNA will be tested due to biosafety regulations. | |
Table 5. Analytical Reactivity (Inclusivity) of the Visby Respiratory Health Test
13
2 The Visby Medical Respiratory Health Test returned influenza A positive results in 2/3 replicates at 1500 pg/mL for the A/Egypt/321/2007 (H5N1) strain RNA.
In silico analysis of sequences from GISAID are conducted routinely to assess the ability of the Visby Medical Respiratory Health Test to detect the most recent COVID-19 strains. The results of these analyses of 16,852,539 total sequences, as of August 2024, show that the Visby Medical Respiratory Health Test will detect all variants in circulation.
14
Cross-Reactivity and Microbial Interference
The potential for cross-reactivity from microorganisms that may be found in an upper respiratory sample other than the target respiratory viruses (influenza A, influenza B, and SARS-CoV-2) on the performance of the Visby Medical Respiratory Health Test was evaluated. Forty-three (43) microorganisms were tested in triplicate at high concentrations (>105 units/mL for viruses and >106 units/mL for bacteria and yeast) in negative samples (negative clinical matrix). No cross-reactivity was observed with any of the organisms at the concentrations tested.
Microbial Interference was evaluated by testing the same 43 microorganisms in triplicate in negative clinical matrix in the presence of low concentrations of the target organisms (3X LoD for influenza A, influenza B, and SARS-CoV-2). No microbial interference was observed with any of the microorganisms at the concentrations tested.
Table 6. Microorganisms Evaluated for Cross-Reactivity and Microbial Interference on Visby Respiratory Health Test
| Viruses (ATCC Number) | Bacteria and Yeast (ATCC Number) |
|---|---|
| Human Coronavirus 229E (VR-740) | Bordetella parapertussis (15311) |
| Human Coronavirus OC43 (VR-1558) | Bordetella pertussis (9340) |
| Human coronavirus HKU1 (VR-3262SD) * | Candida albicans (18804) |
| Human Coronavirus NL63 (VR-3263SD) * | Chlamydia pneumoniae (53592) |
| SARS-Coronavirus (VR-3280SD) * | Corynebacterium xerosis (373) |
| MERS-Coronavirus (VR-3248SD) * | Escherichia coli (25922) |
| Adenovirus strain 1, C1 Ad 71 (VR-1) | Haemophilus influenzae (49247) |
| Adenovirus strain 7 (VR-7) | Lactobacillus brevis (14869) |
| Cytomegalovirus (VR-977) | Legionella pneumophila (33152) |
| Epstein Barr virus (B95-8, ZeptoMetrix) | Moraxella (Branhamella) catarrhalis (25238) |
| Enterovirus 68 (NR-51430, BEI) | Mycobacterium tuberculosis (25177) |
| Human metapneumovirus (hMPV) (NR-22232, BEI) | Mycoplasma genitalium (49123) |
| Human parainfluenza virus 1 (NR-48681, BEI) | Mycoplasma pneumoniae (15531) |
| Human parainfluenza virus 2 (VR-92) | Neisseria meningitidis serogroup a (13077) |
| Human parainfluenza virus 3 (VR-93) | Neisseria mucosa (19695) |
| Human parainfluenza virus 4b (NR-3238, BEI) | Pneumocystis jirovecii also called Pneumocystis carinii Delanoe and Delanoe (PRA-159) |
| Measles (VR-24) | Pseudomonas aeruginosa (0801519, ZeptoMetrix) |
| Mumps (VR-106DQ) * | Staphylococcus aureus (12600) |
| Respiratory syncytial virus (Strain B) (VR-1400) | Staphylococcus epidermidis (12228) |
| Human rhinovirus 1A (strain 2060) (VR-1559) | Streptococcus pneumoniae (49619) |
| * Purified RNA was tested for these viruses. | Streptococcus pyogenes (19615) |
| Streptococcus salivarius (9759) | |
| Pooled human nasal wash |
15
Competitive Interference
The potential for high concentrations of one target organism to interfere with detection of low concentrations of another target organism was evaluated. Influenza A, influenza B, and SARS-CoV-2 viruses were spiked into negative clinical matrix at varying concentrations and then tested in triplicate. Low concentrations were prepared at 3x LoD for the respective viruses, and high concentrations were prepared at ≥ 105 copies/swab. No competitive interference was observed for any of the three target viruses at the concentrations tested.
| Viral Targets in Sample | Detection Rate (# Positive / # Tests) | ||||
|---|---|---|---|---|---|
| Influenza A | Influenza B | SARS-CoV-2 | Influenza A | Influenza B | SARS-CoV-2 |
| High | Low | Neg | 3/3 | 3/3 | 0/3 |
| High | Neg | Low | 3/3 | 0/3 | 3/3 |
| Low | High | Neg | 3/3 | 3/3 | 0/3 |
| Neg | High | Low | 0/3 | 3/3 | 3/3 |
| Low | Neg | High | 3/3 | 0/3 | 3/3 |
| Neg | Low | High | 0/3 | 3/3 | 3/3 |
Table 7. Competitive Interference for each Target Virus
Endogenous/Exogenous Interfering Substances
Potentially interfering substances that may be found in a clinical nasal sample were evaluated to determine if they interfere with the accuracy of test results. The potential interfering substances were spiked in negative clinical matrix and tested in the presence and absence of low concentrations (3x LoD) of influenza A, influenza B, and SARS-CoV-2 viruses. All samples were tested in triplicate. As shown in Table 8 below, all of the neqative samples returned valid results that were negative for influenza B, and SARS-CoV-2. All the positive samples returned valid results that were positive for influenza A, influenza B, and SARS-CoV-2. None of the tested substances were found to interfere with test accuracy at the concentrations tested.
16
| Substance | Concentration | Negative Samples
(# Negative / # Tests) | Low Positive Samples
(3x LoD)
(# Positive / # Tests) |
|----------------------------------------------------|---------------|--------------------------------------------|------------------------------------------------------------|
| Afrin | 25% (v/v) | 3/3 | 3/3 |
| Biotin | 3.5 µg/mL | 3/3 | 3/3 |
| Flonase | 25% (v/v) | 3/3 | 3/3 |
| Fresh Whole Blood Pooled
Human Donors | 5% (v/v) | 3/3 | 3/3 |
| Human lotion | 5% (w/v) | 3/3 | 3/3 |
| Hand sanitizer | 5% (w/v) | 3/3 | 3/3 |
| Purified mucin protein | 1% (w/v) | 3/3 | 3/3 |
| Method all purpose cleaner | 5% (v/v) | 3/3 | 3/3 |
| Mupirocin | 12 mg/mL | 3/3 | 3/3 |
| Nasacort | 25% (v/v) | 3/3 | 3/3 |
| Nasal Saline Spray | 25% (v/v) | 3/3 | 3/3 |
| NeoSynephrine Cold & Sinus
Extra Strength Spray | 25% (v/v) | 3/3 | 3/3 |
| Seventh generation
disinfectant | 5% (v/v) | 3/3 | 3/3 |
| Softsoap moisturizing hand
soap | 5% (w/v) | 3/3 | 3/3 |
| Tobramycin | 2.43 mg/mL | 3/3 | 3/3 |
| Zanamivir (Relenza) | 5 mg/mL | 3/3 | 3/3 |
| Zicam Allergy Relief | 25% (v/v) | 3/3 | 3/3 |
Table 8. Potentially Interfering Substances
Specimen Stability
The stability of nasal swab specimens after elution into the Visby Respiratory Health Buffer was determined when stored at room temperature (15 - 30°C) or refrigerated (2 -8°C) conditions. Influenza A, influenza B, and SARS-CoV-2 viruses were spiked into neqative clinical matrix at 2x LoD and tested at baseline and at each storage time-point with 20 replicates. All low positive devices returned the expected triple positive results at all time-points tested. Based on the results, the following specimen stability in Visby Respiratory Health Buffer is claimed:
- Room temperature (15 30°C) storage up to 120 minutes (2 hours) ●
- Refrigerated (2 - 8°C) storage up to 48 hours (2 days)
H. Conclusions
The analytical and clinical studies have demonstrated that the Visby Medical Respiratory Health Test is substantially equivalent to the predicate device (K220963).