(521 days)
No
The description details a fully automated PCR process with colorimetric detection. There is no mention of AI/ML in the device description, intended use, or performance studies. The detection method is based on a chemical reaction and visual color change, not algorithmic interpretation.
No
The device is an in vitro diagnostic test used to detect the DNA of specific sexually transmitted infections, aiding in diagnosis rather than providing direct therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the test is "intended for use... for the rapid detection and differentiation of DNA... The test results are to aid in the diagnosis of symptomatic infections". This directly indicates its role in diagnosing medical conditions.
No
The device description clearly states that the test system includes hardware components such as the "Visby Medical Sexual Health Click device," "Visby Medical power supply," "Visby Medical Vaginal Collection kit," and "fixed-volume transfer pipettes." It describes a physical process involving sample processing, lysis, PCR, and detection via a colorimetric assay, all of which are hardware-dependent functions.
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 device is an "in vitro diagnostic test."
- Purpose: The test is designed to detect and differentiate DNA from specific pathogens in a biological sample (female vaginal swab specimens) to aid in the diagnosis of infections. This is a core function of an IVD.
- Method: The device uses Polymerase Chain Reaction (PCR), which is a common technique used in in vitro diagnostics to amplify and detect specific genetic material.
- Sample Type: It analyzes a biological specimen (vaginal swab).
- Setting: It is intended for use in point-of-care or clinical laboratory settings, which are typical environments for IVDs.
N/A
Intended Use / Indications for Use
The Visby Medical Sexual Health Click Test is a single-use (disposable), fully-integrated, automated Polymerase Chain Reaction (PCR) in vitro diagnostic test intended for use in point of-care or clinical laboratory settings for the rapid detection and differentiation of DNA from Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in self-collected female vaginal swab specimens using the Visby Medical Sexual Health Vaginal Specimen Collection Kit in a health care setting. The test results are to aid in the diagnosis of symptomatic infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.
Product codes (comma separated list FDA assigned to the subject device)
OEP, MKZ, LSL, OUY
Device Description
The test system includes the Visby Medical Sexual Health Click device, the Visby Medical power supply, the Visby Medical Vaginal Collection kit, and fixed-volume transfer pipettes. The device processes a vaginal swab sample by automatically performing all steps required to complete lysis, polymerase chain reaction, and amplicon detection.
The patient uses the Visby Medical Vaginal Collection Kit to self-collect a vaginal specimen with the provided flocked swab, and then the patient elutes the specimen into the Visby Medical Collection Media. The test operator transfers the collection media containing the patient specimen into the sample port of the device using the provided fixed-volume pipette where it rehydrates a lyophilized internal process control. The sample enters a lysis module, where the DNA of the sample and the internal process control are extracted using a combination of chemical lysis and high temperature. The extracted DNA enters a mixing chamber where it rehydrates lyophilized PCR reagents, followed by thermocycling to amplify target DNA. If present, the amplified pathogen target (CT, NG, and/or TV) and internal process control hybridize to specific probes located on a flow channel. Detection of the target-specific PCR product is accomplished via an enzyme-linked colorimetric assay using streptavidin bound horseradish peroxidase (HRP) and a colorimetric substrate that forms a purple precipitate. Test results can be expected in approximately 30 minutes: a green check mark will appear, and a purple color will appear in the "Control" spot, indicating a valid test. A purple spot adjacent to "Chlamydia," "Gonorrhoeae," and/or "Trichomonas" signifies the presence of amplified CT, NG, and/or TV DNA in the sample. Tests with invalid results due to an error (indicated by a red X status light) or failure to develop a purple spot in the "Control" spot, are retested with a new Visby device.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Female vaginal swab specimens
Indicated Patient Age Range
14 years of age and older
Intended User / Care Setting
point of-care or clinical laboratory settings / health care setting
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
A reproducibility study was performed to evaluate the reproducibility of the Visby Medical Sexual Health Click Test when used by untrained users in CLIA waived settings. The study evaluated four (4) panel members that were prepared using cultured organisms in negative clinical vaginal swab matrix, including negative (unspiked) and positive samples. A total of six (6) study operators (2 operators at each site) tested the panel three (3) times each testing day, over six (6) nonconsecutive days. Three reagent lots were used.
An additional study using low positive (spiked at ~1x LoD) and negative (unspiked) samples was performed to evaluate the repeatability of test results near the assay limit of detection when tested by untrained users in a CLIA waived setting. A total of six (6) operators (2 operators at each site) tested the panel twice a day for 5 days.
Performance characteristics were established in two multi-center CLIA Waived studies conducted at 14 clinical sites. A total of 32 untrained operators participated. 1899 subjects were initially enrolled, of which 1881 were eligible for inclusion. Of those, 1789 were included in the data analysis. The study subjects were prospectively enrolled females, 14 years of age and older, who self-collected vaginal swab specimens using the Visby Vaginal Collection Kit. The collected samples were provided to participating study operators who tested them on-site using the Visby Medical Sexual Health Click Test. The Visby Sexual Health Click Test results were compared to a composite comparator result (CCR) for CT and NG and a patient infected status algorithm (PIS) for TV. The CCR and PIS was comprised of three FDA-cleared NAAT assays. A study participant was considered infected for CT, NG, or TV if a positive result was reported from two NAAT tests. If the test results of the first two NAAT were discordant, the CCR/PIS was determined by the third NAAT.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Reproducibility Study:
Sample Size: 6 operators (2 at each of 3 sites) testing 4 panel members (CT Positive, NG Positive, TV Positive, Negative) 3 times/day for 6 nonconsecutive days. Also, 6 operators (2 at each of 3 sites) testing CT Low Positive, NG Low Positive, TV Low Positive, and Negative samples twice a day for 5 days.
Key Results:
Reproducibility (Overall Agreement % and 95% CI):
CT Positive: 100% (96.5%-100.0%)
NG Positive: 97.2% (92.0%-99.0%)
TV Positive: 100% (96.5%-100%)
Negative: 98.1% (93.5%-99.5%)
Repeatability (Overall Agreement % and 95% CI) for samples near LoD:
CT Low Positive: 100% (94.0%-100%)
NG Low Positive: 96.7% (88.6%-99.1%)
TV Low Positive: 96.7% (88.6%-99.1%)
Negative: 100% (93.8%-100%)
Clinical Performance Study:
Study Type: Two multi-center CLIA Waived studies at 14 clinical sites.
Sample Size: 1789 subjects included in data analysis.
Key Results:
Clinical Performance for CT vs. Composite Comparator Results (Overall):
PPA: 97.4% (93.5%-99.0%)
NPA: 97.8% (96.9%-98.4%)
Clinical Performance for NG vs. Composite Comparator Results (Overall):
PPA: 97.8% (88.4%-99.6%)
NPA: 99.1% (98.5%-99.4%)
Clinical Performance for TV vs. PIS (Overall):
Sensitivity: 99.3% (96.0%-99.9%)
Specificity: 96.7% (95.8%-97.5%)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
CT (Overall - vs. Composite Comparator Results):
PPA: 97.4% (93.5%-99.0%)
NPA: 97.8% (96.9%-98.4%)
TP=149, FP=36, TN=1585, FN=4
NG (Overall - vs. Composite Comparator Results):
PPA: 97.8% (88.4%-99.6%)
NPA: 99.1% (98.5%-99.4%)
TP=44, FP=16, TN=1725, FN=1
TV (Overall - vs. PIS):
Sensitivity: 99.3% (96.0%-99.9%)
Specificity: 96.7% (95.8%-97.5%)
TP=136, FP=53, TN=1575, FN=1
Predicate Device(s)
Reference Device(s)
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
§ 866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s).
(a)
Identification. A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) is an in vitro diagnostic device intended for the detection and identification of nucleic acids from non-viral microorganism(s) and their associated resistance markers in clinical specimens collected from patients suspected of sexually transmitted infections. The device is intended to aid in the diagnosis of non-viral sexually transmitted infections in conjunction with other clinical and laboratory data. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist that are not detected by the device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(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 discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate;
(iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) Limiting statements indicating 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) Reliable 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
(D) If appropriate (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type; and(v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that:
(A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present;
(B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora;
(C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and
(D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy.
(4) Design verification and validation must include:
(i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result (
e.g., how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies, including, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate.
(iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses.
(iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food & 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.
Visby Medical, Inc. Beth Lingenfelter Clinical and Regulatory Affairs 3010 N. First Street San Jose, California 95134
August 26, 2021
Re: K200748
Trade/Device Name: Visby Medical Sexual Health Click Test Regulation Number: 21 CFR 866.3393 Regulation Name: Nucleic acid detection system for non-viral microorganism(s) causing sexually transmitted infections. Regulatory Class: Class II Product Code: OEP, MKZ, LSL, OUY Dated: June 24, 2021 Received: June 25, 2021
Dear Beth Lingenfelter:
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 (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 located 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
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 (reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531 -542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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-regulatoryassistance/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.
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K200748
Device Name Visby Medical Sexual Health Click Test
Indications for Use (Describe)
The Visby Medical Sexual Health Click Test is a single-use (disposable), fully-integrated, automated Polymerase Chain Reaction (PCR) in vitro diagnostic test intended for use in point of-care or clinical laboratory settings for the rapid detection and differentiation of DNA from Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in seff-collected female vaginal swab specimens using the Visby Medical Sexual Health Vaginal Specimen Collection Kit in a health care setting. The test results are to aid in the diagnosis of symptomatic infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.
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) |
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3
510(k) Summary
According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence
A. Submitter
| Name: | Visby Medical, Inc. |
|---|---|
| Address: | 3010 N. First Street |
| San Jose, CA 95134 | |
| Phone: | (408) 650 - 8878 |
| Contact: | Beth Lingenfelter |
| Date Prepared: | August 11, 2021 |
B. Device
| Trade Name: | Visby Medical Sexual Health Click Test |
|---|---|
| Classification Name: | Nucleic acid detection system for non-viral |
| microorganism(s) causing sexually transmitted infections | |
| Regulatory Number: | 866.3393 |
| Regulatory Class: | Class II |
| Product Code: | QEP |
| Subsequent | |
| Product Codes: | MKZ, LSL, OUY |
C. Predicate Devices
The Visby Medical Sexual Health Click Test is substantially equivalent to the Cepheid Xpert® CT/NG Assay and Cepheid Xpert® TV Assay, cleared under K121710 and K151565 on December 27, 2012 and October 16, 2015, respectively.
D. Intended Use
The Visby Medical Sexual Health Click Test is a single-use (disposable), fully-integrated, automated Polymerase Chain Reaction (PCR) in vitro diagnostic test intended for use in point of-care or clinical laboratory settings for the rapid detection and differentiation of DNA from Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in self-collected female vaginal swab specimens using the Visby Medical Sexual Health Vaginal Specimen Collection Kit in a health care setting. The test results are to aid in the diagnosis of symptomatic or asymptomatic infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.
4
E. Device Description
The test system includes the Visby Medical Sexual Health Click device, the Visby Medical power supply, the Visby Medical Vaginal Collection kit, and fixed-volume transfer pipettes. The device processes a vaginal swab sample by automatically performing all steps required to complete lysis, polymerase chain reaction, and amplicon detection.
The patient uses the Visby Medical Vaginal Collection Kit to self-collect a vaginal specimen with the provided flocked swab, and then the patient elutes the specimen into the Visby Medical Collection Media. The test operator transfers the collection media containing the patient specimen into the sample port of the device using the provided fixed-volume pipette where it rehydrates a lyophilized internal process control. The sample enters a lysis module, where the DNA of the sample and the internal process control are extracted using a combination of chemical lysis and high temperature. The extracted DNA enters a mixing chamber where it rehydrates lyophilized PCR reagents, followed by thermocycling to amplify target DNA. If present, the amplified pathogen target (CT, NG, and/or TV) and internal process control hybridize to specific probes located on a flow channel. Detection of the target-specific PCR product is accomplished via an enzyme-linked colorimetric assay using streptavidin bound horseradish peroxidase (HRP) and a colorimetric substrate that forms a purple precipitate. Test results can be expected in approximately 30 minutes: a green check mark will appear, and a purple color will appear in the "Control" spot, indicating a valid test. A purple spot adjacent to "Chlamydia," "Gonorrhoeae," and/or "Trichomonas" signifies the presence of amplified CT, NG, and/or TV DNA in the sample. Tests with invalid results due to an error (indicated by a red X status light) or failure to develop a purple spot in the "Control" spot, are retested with a new Visby device.
5
F. Substantial Equivalence
The Visby Medical Sexual Health Click Test is substantially equivalent to the Cepheid Xpert CT/NG Assay and the Cepheid Xpert TV Assay, cleared under K121710 and K151565 on December 27, 2012 and October 16, 2015, respectively. Table 1 outlines the similarities and differences between the two system
| Characteristic | Visby Medical
Sexual Health Click Test
(K200748) | Predicate:
Cepheid Xpert CT/NG
Assay
(K121710) | Predicate:
Cepheid Xpert TV Assay
(K151565) |
|--------------------------|----------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------|
| Regulation | 21 CFR 866.3393 | 21 CFR 866.3390 | 21 CFR 866.3860 |
| Device Class | Class II | Class II | Class II |
| Technology/
Detection | An automated multiplex
polymerase chain reaction
with colorimetric detection | An automated multiplex real-
time polymerase chain
reaction | An automated real-time
polymerase chain reaction |
| Assay Targets | DNA from Chlamydia
trachomatis (CT), Neisseria
gonorrhoeae (NG), and
Trichomonas vaginalis (TV) | DNA from Chlamydia
trachomatis (CT) and/or
Neisseria gonorrhoeae (NG) | DNA from Trichomonas
vaginalis (TV) |
| Specimen Types | Patient-collected vaginal
swab | Urine (male and female),
endocervical swab, and
patient-collected vaginal
swab | Endocervical Swabs Female
Urine
Patient-collected vaginal
swab |
| CT Analyte Targets | CT cryptic plasmid DNA | CT genomic DNA | N/A |
| NG Analyte
Targets | NG genomic DNA | NG genomic DNA | N/A |
| TV Analyte Targets | TV genomic DNA | N/A | T. vaginalis genomic DNA |
| Assay Results | Qualitative | Qualitative | Qualitative |
| Collection Kit | Swab collection kit | Urine collection kit
Swab collection kit | Urine collection kit
Swab collection kit |
| Sample Extraction | Self-contained and
automated after specimen
sample elution | Self-contained and
automated after specimen
sample elution and two
single-dose reagent
additions. | Self-contained and
automated after specimen
sample elution and two
single-dose reagent
additions. |
| Instrument System | Visby Medical Sexual Health
Click Test | Cepheid GeneXpert
Instrument Systems | Cepheid GeneXpert
Instrument Systems |
| Turn-around Time | Approximately 30 minutes to
results. | Approximately 90 minutes to
results. | Approximately 90 minutes to
results. |
| Table 1. Comparison of the Visby Medical Sexual Health Click Test to the Predicate devices |
|---|
| --------------------------------------------------------------------------------------------- |
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visby medical
| Characteristic | Visby Medical
Sexual Health Click Test
(K200748) | Predicate:
Cepheid Xpert CT/NG
Assay
(K121710) | Predicate:
Cepheid Xpert TV Assay
(K151565) |
|--------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The Visby Medical Sexual
Health Click Test is a single-
use (disposable), fully-
integrated, automated
Polymerase Chain Reaction
(PCR) in vitro diagnostic test
intended for use in point of-
care or clinical laboratory
settings for the rapid
detection and differentiation
of DNA from Chlamydia
trachomatis, Neisseria
gonorrhoeae, and
Trichomonas vaginalis in
self-collected female vaginal
swab specimens collected in
Visby Medical Collection
Media in a health care
setting. The test results are
to aid in the diagnosis of
symptomatic or
asymptomatic infections
with Chlamydia trachomatis,
Neisseria gonorrhoeae, and
Trichomonas vaginalis. | An automated, multiplex
real-time RT-PCR assay,
performed on the GeneXpert
Instrument Systems,
intended for the in vitro
qualitative and differentiation
of genomic DNA from
Chlamydia trachomatis (CT)
and/or Neisseria
gonorrhoeae (NG) to aid in
the diagnosis of chlamydial
gonorrheal urogenital
disease. The assay may be
used to test the following
specimens from
asymptomatic and
symptomatic individuals:
female and male urine,
endocervical swab, and
patient-collected vaginal
swab (collected in a clinical
setting). | The Cepheid Xpert TV
Assay, performed on the
GeneXpert Instrument
Systems, is a qualitative in
vitro diagnostic test for the
detection of Trichomonas
vaginalis genomic DNA. The
test utilizes automated real-
time polymerase chain
reaction (PCR) to detect
Trichomonas vaginalis
genomic DNA. The Xpert TV
Assay uses female urine
specimens, endocervical
swab specimens, or patient-
collected vaginal swab
specimens (collected in a
clinical setting). The Xpert
TV Assay is intended to aid
in the diagnosis of
trichomoniasis in
symptomatic or
asymptomatic individuals. |
| Indication for Use | Asymptomatic and
symptomatic female patients | Asymptomatic and
symptomatic patients | Asymptomatic and
symptomatic patients |
| Assay Controls | Internal sample processing
control (SPC). External
controls available. | Internal sample processing
control (SPC), sample
adequacy control (SAC),
and probe check control
(PCC). External controls
available. | Internal sample processing
control (SPC), sample
adequacy control (SAC),
and probe check control
(PCC). External controls
available. |
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The Visby Medical Vaginal Specimen Collection Kit is substantially equivalent to the following predicate assays:
- Cepheid Xpert Vaginal/Endocervical Specimen Collection Kits
| Table 2. Comparison of the Visby Medical Vaqinal Specimen Collection Kit to the Predicate | ||||
|---|---|---|---|---|
| -- | -- | -- | -- | ------------------------------------------------------------------------------------------- |
| Characteristic | Visby Medical
Vaginal Specimen Collection Kit | Cepheid Xpert
Vaginal/Endocervical Specimen
Collection Kits |
|----------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Description | A single use package containing an
individually packaged sterile collection swab
(for vaginal sampling) and a Visby Medical
Collection Media tube. The collection swab
is eluted into the Collection Media tube after
swab sampling. | Contains one individually packaged sterile
large cleaning swab (for endocervical
samples) and a package containing an
individually packaged sterile collection swab
(for vaginal and endocervical sampling) and
an Xpert CT/NG Swab Transport Reagent
tube. The collection swab is placed into the
Transport Reagent Tube after swab
sampling to stabilize the nucleic acid until
sample preparation. |
G. Non-clinical Data
1. Limit of Detection
Limit of Detection (LoD) of the Visby Medical Sexual Health Click Test was determined for CT in elementary bodies per mL (EB/mL), NG in colony forming units per mL (CFU/mL), and TV in trophozoites per mL (troph/mL), from two distinct strains or serovars, seeded into negative clinical vaginal sample matrix (previously determined to be negative for CT, NG, TV). LoD is defined as the lowest concentration of organism that is reliably detected (≥ 95% of tested samples).
The LoD values for each strain were estimated by probit analysis of the results from range-finding studies. The calculated LoDs were verified by testing 20 replicates at the estimated LoD concentration and demonstrating that at least 19 out of 20 replicates were positive. The LoD for each strain is shown in Table 3.
| Organism | LoD | |||
|---|---|---|---|---|
| CT Serovar H (VR-879) | 16.0 EB/mL | |||
| CT Serovar D (VR-885) | 5.9 EB/mL | |||
| NG (ATCC 19424) | 5.7 CFU/mL | |||
| NG (ATCC 49226) | 6.2 CFU/mL | |||
| TV (ATCC 30001, metronidazole susceptible) | 1.2 troph/mL | |||
| TV (ATCC 30238, metronidazole resistant) | 0.24 troph/mL |
Table 3. LoD of CT Serovars. NG strains, and TV strains
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2. Inclusivity
The ability of the Visby Medical Sexual Health Click Test to detect a wide range of target organisms was evaluated by testing 14 serovars of CT, 30 strains of NG, and 15 strains of TV at by spiking them into negative vaginal swab matrix near the assay LoD. For CT, Serovars A, Ba, C, E, F, G, J, K, LGV1 and LGV3 were detected at 32 EB/mL, serovar LGV2 was detected 64 EB/mL and serovar I was detected at 128 EB/mL. For NG, 29 strains were detected at 12.4 cfu/mL and 1 was detected at 24.8 cfu/mL. For TV, all isolates were detected at 2.4 trophs/mL.
3. Cross Reactivity and Microbial Interference
The cross reactivity of the Visby Medical Sexual Health Click Test was evaluated by testing 144 microorganisms seeded into negative vaginal swab matrix at high concentrations (>106 genomic copies/mL for bacteria and >105 genomic copies/mL for viruses). No cross reactivity was observed with the Visby Sexual Health Click Test when testing the organisms listed in Table 4.
In addition, microbial Interference of the same 144 microorganisms on the Visby Medical Sexual Health Click Test was evaluated by testing the same microorganisms spiked into a low positive (3x LoD) sample containing CT, NG and TV. No microbial interference of these microorganisms was observed when testing high concentrations of the organisms listed in the table in a low positive sample.
Additionally, three organisms could not be obtained for direct testing (Bacterial Vaginosis Associated Bacteria 2 (BVAB-2). Meqasphaera type 1, and Dientamoeba fragilis). The sequences of these organisms were analyzed against the Visby Medical Sexual Health Click primer and amplicon sequences using basic local alignment search tool (BLAST). This in-silico analysis did not predict any cross reactivity or microbial interference.
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| Achromobacter xerosis | Cutibacterium acnes | Lactobacillus vaginalis | Pentatrichomonas hominis |
|---|---|---|---|
| Acinetobacter calcoaceticus | Deinococcus radiodurans | Lactococcus lactis | Peptostreptococcus |
| anaerobius | |||
| Acinetobacter Iwoffii | Derxia gummosa | Legionella pneumophila | Peptostreptococcus |
| productus | |||
| (Blautia producta) | |||
| Actinomyces israelii | Dientamoeba fragilis* | Listeria monocytogenes | Plesiomonas shigelloides |
| Aerococcus viridans | Eikenella corrodens | Megashaera type 1* | Prevotella bivia |
| Aeromonas hydrophila | Elizabethkingia | ||
| meningoseptica | Micrococcus luteus | Proteus mirabilis | |
| Alcaligenes faecalis | Entamoeba histolytica | Mobiluncus curtisii | Proteus vulgaris |
| Arcanobacterium pyogenes | Enterococcus faecalis | Mobiluncus mulieris | Providencia stuartii |
| Atopobium vaginae | Enterococcus faecium | Moraxella lacunata | Pseudomonas aeruginosa |
| Bacteroides fragilis | Enterobacter cloacae | Moraxella osloensis | Pseudomonas fluorescens |
| Bacteroides ureolyticus | Enterococcus raffinosus | ||
| (avium) | Moraxella (Branhamella) | ||
| catarrhalis | Pseudomonas putida | ||
| Bergeriella denitrificans | Erysipelothrix | ||
| rhusiopathiae | Morganella morganii | Rahnella aquatilis | |
| Bifidobacterium adolescentis | Escherichia coli | Mycobacterium smegmatis | Rhodospirillum rubrum |
| Bifidobacterium breve | Fusobacterium nucleatum | Mycoplasma genitalium | Saccharomyces cerevisiae |
| Bifidobacterium longum | Gardnerella vaginalis | Mycoplasma hominis | Salmonella minnesota |
| Blastocystis hominis | Gemella haemolysans | Neisseria elongata (3) | Salmonella typhimurium |
| Brevibacterium linens | Giardia intestinalis | Neisseria cinerea | Serratia marcescens |
| BV associated bacteria | |||
| (BVAB-2) * | Haemophilus ducreyi | Neisseria subflava | Staphylococcus aureus |
| Campylobacter jejuni | Haemophilus influenzae | Neisseria flavescens (2) | Staphylococcus epidermidis |
| Candida albicans | Herpes simplex virus I | Neisseria perflava | Staphylococcus |
| saprophyticus | |||
| Candida glabrata | Herpes simplex virus II | Neisseria lactamica (4) | Streptococcus agalactiae |
| Candida parapsilosis | HIV-1 (synthetic RNA) | Neisseria meningitidis | |
| serogroup A | Streptococcus bovis | ||
| Candida tropicalis | Human papilloma virus 16 | ||
| (synthetic DNA) | Neisseria meningitidis | ||
| serogroup B | Streptomyces griseinus | ||
| Chlamydophila pneumoniae | Human papilloma virus 16 | ||
| E6/E7 (Transformed cells) | Neisseria meningitidis | ||
| serogroup C (4) | Streptococcus mitis | ||
| Chlamydophila psittaci | Kingella dentrificans | Neisseria meningitidis | |
| serogroup D | Streptococcus mutans | ||
| Chlamydia trachomatis | |||
| LGVII** | Kingella kingae | Neisseria meningitidis | |
| serogroup W-135 | Streptococcus pneumoniae | ||
| Chromobacterium violaceum | Klebsiella aerogenes | Neisseria meningitidis | |
| serogroup Y | Streptococcus pyogenes | ||
| Citrobacter freundii | Klebsiella oxytoca | Neisseria polysaccharea | Streptococcus salivarius |
| Clostridium difficile | Klebsiella pneumoniae | Neisseria subflava | Streptococcus sanguinis |
| Clostridium perfringens | Lactobacillus acidophilus | Neisseria mucosa (3) | Trichomonas tenax |
| Corynebacterium genitalium | Lactobacillus brevis | Neisseria sicca (3) | Ureaplasma urealyticum |
| Corynebacterium xerosis | Lactobacillus crispatus | Pantoea agglomerans | Vibrio parahaemolyticus |
| Cryptococcus neoformans | Lactobacillus jensenii | Paracoccus denitrificans | Yersinia enterocolitica |
Table 4. Microorqanisms Evaluated for Cross-Reactivity and Microbial Interference
- These organisms were not available for direct testing and were evaluated using in-silico analysis
** This organism was correctly positive with the CT assay and negative for NG and TV
(n) number of strains tested
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4. Competitive Interference
The Visby Medical Sexual Health Click test was evaluated for performance in the case of a mixed infection (the presence of multiple target organisms). Each of the target orqanisms (CT, NG, and TV) were seeded into clinical negative vaqinal sample matrix at varying concentrations and then tested in triplicate. Low concentrations were prepared at 3x LoD for the respective organism and high concentrations were prepared at 1 x 106 units/mL. Three (3) replicates were tested for each condition. No competitive interference was observed at the levels tested for all three target organisms.
5. Interfering Substances
The performance of the Visby Medical Sexual Health Click Test in the presence of potentially interfering substances that may be found in a vaginal swab sample was evaluated. Substances were tested in positive (3x LoD) samples for CT, NG, and TV as well as samples negative for CT, NG, and TV. The following substances were tested and found not to interfere with the assay up to the concentrations shown below.
| Substances | Concentration |
|---|---|
| Abreva Cold Sore Cream | 0.25% w/v |
| Biotin | 3.5 µg/mL |
| Menstrual Blood | 10.0% v/v |
| Beta Estradiol | 0.07 mg/mL |
| Dove 0% alcohol anti-perspirant spraya | 0.19% w/v |
| Mucin (bovine) | 0.80% w/v |
| KY Jelly personal lubricant | 0.25% w/v |
| Leukocytes | 1x106 cells/mL |
| Monistat 1 | 0.25% w/v |
| Preparation H Hemorrhoidal Ointment | 0.25% w/v |
| Progesterone | 0.07 mg/mL |
| RepHresh Odor Eliminating pH Balancing Gelb | 1.25% w/v |
| Replens Long Lasting Vaginal Moisturizerc | 2.50% w/v |
| Seminal fluid | 5.00% v/v |
| Summer's Eve Povidone-Iodine Medicated Douche | 0.25% w/v |
| Summer's Eve, Cleansing Wash | 0.40% w/v |
| Vaginal anti-fungal | 0.25% w/v |
| 7-day Vaginal cream | 0.25% w/v |
| Vagisil Moisturizer | 0.25% w/v |
| Vagisil Regular Strength Anti-Itch Creme | 0.25% w/v |
| VCF Vaginal Contraceptive Gel | 0.25% w/v |
| Yeast Gard Douche Advanced | 0.25% w/v |
| Table 5. Potentially Interfering Substances | |||
|---|---|---|---|
| -- | -- | -- | --------------------------------------------- |
e 0% alcohol anti-perspirant spray may cause false positive results for CT. NG, and/or TV when present at a concentration greater than 0.19% (w/y epHresh Odor Eliminating pH Balancing Gel may cause false negative results for CT and/or NG when present at a concentration greater than 1.25% (w/) Replens Long Lasting Vaginal Moisturizer may cause invalid results when present at a concentration greater than 2.50% (w/y
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6. Reproducibility
A reproducibility study was performed to evaluate the reproducibility of the Visby Medical Sexual Health Click 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 four (4) panel members that were prepared using cultured organisms in negative clinical vaginal swab matrix. The study was performed with negative (unspiked) and positive samples. A total of six (6) study operators (2 operators at each site) tested the panel three (3) times each testing day, over six (6) nonconsecutive days. Three reagent lot were used in the study. A summary of the results (count correct / total count) and % agreement for each analysis is presented in the table below. The Visby Medical Sexual Health Click test demonstrated robust reproducibility with no significant effect observed for the components of variation evaluated (sites, days, operators, lots).
| Site 1 | Site 2 | Site 3 | Overall Agreement | ||
|---|---|---|---|---|---|
| Panel Member | % Agreement | ||||
| (count) | % Agreement | ||||
| (count) | % Agreement | ||||
| (count) | % Agreement | ||||
| (count) | 95% CI | ||||
| CT Positive | 100% | 100% | 100% | 100% | 96.5%-100.0% |
| (49.72 EB/mL) | (35/35)a | (36/36)b | (36/36)c | (107/107) | |
| NG Positive | 97.1% | 94.3% | 100% | 97.2% | 92.0%-99.0% |
| (22.68 cfu/mL) | (34/35)a | (33/35)a | (36/36) | (103/106) | |
| TV Positive | 100% | 100% | 100% | 100% | 96.5%-100% |
| (21.6 troph/mL) | (36/36) | (35/35)a | (35/35)a | (106/106) | |
| Negative | 97.2% | ||||
| (35/36)d | 100% | ||||
| (36/36) | 97.2% | ||||
| (35/36)e | 98.1% | ||||
| (106/108) | 93.5%-99.5% |
| Table 6. Summary of Reproducibility Study Results | ||
|---|---|---|
| -- | --------------------------------------------------- | -- |
One sample had invalid results and was omitted from the analysis.
b One sample was CT positive, but unexpectedly positive for NG and T.
c Two samples were CT positive, but unexpected positive f
One sample was uuestedlynesitive for
One sample was unexpectedly positive for TV
e One sample was unexpectedly positive for NG
An additional study using low positive (spiked at ~1x LoD) and negative (unspiked) samples was performed to evaluate the repeatability of test results near the assay limit of detection when tested by untrained users in a CLIA waived setting. A total of six (6) operators (2 operators at each site) tested the panel twice a day for 5 days. The composition of the panel members along with summary of results (count correct / total count) and percent agreement with the expected result for each panel member is presented in the table below. The study demonstrated that untrained users can perform the test and interpret the results accurately when testing samples with organism concentrations near the LoD.
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| Site 1 | Site 2 | Site 3 | Overall Agreement | ||
|---|---|---|---|---|---|
| Panel Member | % | ||||
| Agreement | |||||
| (count) | % | ||||
| Agreement | |||||
| (count) | % | ||||
| Agreement | |||||
| (count) | % | ||||
| Agreement | |||||
| (count) | 95% CI | ||||
| CT Low Positive | |||||
| (16.0 EB/mL) | 100% | ||||
| (20/20) | 100% | ||||
| (20/20) | 100% | ||||
| (20/20) | 100% | ||||
| (60/60) | 94.0%-100% | ||||
| NG Low Positive | |||||
| (6.2 cfu/mL) | 95.0% | ||||
| (19/20) | 95.0% | ||||
| (19/20) | 100% | ||||
| (20/20) | 96.7% | ||||
| (58/60) | 88.6%-99.1% | ||||
| TV Low Positive | |||||
| (1.2 troph/mL) | 100% | ||||
| (20/20) | 95.0% | ||||
| (19/20) | 95.0% | ||||
| (19/20) | 96.7% | ||||
| (58/60) | 88.6%-99.1% | ||||
| Negative | 100% | ||||
| (18/18)* | 100% | ||||
| (20/20) | 100% | ||||
| (20/20) | 100% | ||||
| (58/58) | 93.8%-100% |
Table 7. Summary of Study with Sample Near Assay LoD
- Two samples had invalid results and were omitted from the analysis
7. External Control Lot-to-Lot Reproducibility
Lot-to-lot reproducibility of the external controls manufactured by ZeptoMetrix Corporation (Buffalo, NY) was evaluated. Three (3) unique lots of the single-use positive control and three (3) unique lots of the single-use negative control were evaluated on five Visby Medical Sexual Health Click tests each for a total of 30 tests. 100% concordance with expected results across all lots was observed.
During the analytic studies positive and negative controls were tested on each day that testing was performed. During the clinical study and reproducibility studies, a positive and negative control was tested for each new operator, for each new lot or shipment of reagents and every 30 days. A total of 490 external controls were tested during the analytic and clinical testing. Of these 459 (93.7%, 459/490) had an initial valid result. Of the 31 external controls that required a test, 29 had the correct valid result first retest and 2 required a 2nd retest to obtain a valid result.
8. Specimen Stability
Vaginal specimen stability was evaluated for specimens collected using the Visby Medical Sexual Health collection kit. Storage was evaluated at room temperature (15-30°C), refrigerated (2-8°C), and frozen (