XPERT CT/NG

K121710 · Cepheid · LSL · Dec 27, 2012 · Microbiology

Device Facts

• Record ID: K121710
• Device Name: XPERT CT/NG
• Applicant: Cepheid
• Product Code: LSL · Microbiology
• Decision Date: Dec 27, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3390
• Device Class: Class 2

Intended Use

The Xpert® CT/NG Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro real-time PCR test for the automated detection and differentiation of genomic DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and 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® CT/NG Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve and transport patient Chlamydia trachomatis and Neisseria gonorrhoeae DNA in endocervical and vaginal specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay. The Cepheid® Xpert® CT/NG Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis and Neisseria gonorrhoeae DNA in first-catch male and female urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.

Device Story

The Xpert CT/NG Assay is an automated, qualitative in vitro diagnostic test performed on GeneXpert Instrument Systems (Dx, Infinity-48, Infinity-80). It processes urogenital specimens (urine, endocervical/vaginal swabs) to detect and differentiate Chlamydia trachomatis and Neisseria gonorrhoeae genomic DNA. The system integrates sample purification, nucleic acid amplification, and real-time PCR detection within single-use disposable cartridges. Each cartridge contains reagents for target amplification, a Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC). The instrument uses an ultrasonic horn for cell lysis, a syringe drive for fluid movement, and an I-CORE thermocycler for PCR. Results are generated in approximately 90 minutes and displayed in tabular and graphic formats. The device is used in clinical laboratories to aid in the diagnosis of chlamydial and gonorrheal urogenital disease, providing clinicians with rapid, automated results to inform patient management and treatment decisions.

Clinical Evidence

Clinical performance was evaluated in a multi-site prospective study (n=14,790 tests) comparing the Xpert CT/NG Assay to a Patient Infected Status (PIS) algorithm based on two predicate NAATs. Sensitivity for CT ranged from 96.0% to 99.5% and specificity from 99.1% to 99.8% across specimen types. Sensitivity for NG ranged from 94.4% to 100% and specificity from 99.9% to 100%. Indeterminate rate was 2.81%.

Technological Characteristics

Multiplex real-time PCR assay. Uses single-use disposable cartridges with integrated sample prep and I-CORE® thermocycler. Detects CT genomic DNA (CT1 target) and NG genomic DNA (NG2 and NG4 targets). Includes internal controls: Sample Processing Control (SPC), Sample Adequacy Control (SAC), and Probe Check Control (PCC). System includes instrument, PC, and preloaded software. Operates on GeneXpert Dx, Infinity-48, and Infinity-80 systems.

Indications for Use

Indicated for symptomatic and asymptomatic individuals, including males and females, for the detection and differentiation of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in urine, endocervical swabs, and patient-collected vaginal swabs to aid in the diagnosis of urogenital infections.

Regulatory Classification

Identification

Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identify Neisseria spp. from cultured isolates. Additionally, some of these reagents consist of Neisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence of Neisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Neisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.

Predicate Devices

• GEN-PROBE® APTIMA® Combo 2 Assay (K043224)
• Becton Dickenson ProbeTec™ ET Chlamydia trachomatis /Neisseria gonorrhoeae Amplified DNA Assay (K012351)

Submission Summary (Full Text)

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Xpert CT/NG Package Insert – IVD
Page 1 of 40

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
k121710

B. Purpose for Submission:
To obtain substantial equivalence determination for the Xpert® CT/NG Assay

C. Measurand:
Genomic DNA of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG)

D. Type of Test:
Real Time Polymerase Chain Reaction (PCR)

E. Applicant:
Cepheid

F. Proprietary and Established Names:
Xpert® CT/NG Assay

G. Regulatory Information:
1. Regulation section:
21 CFR 866.3120 Chlamydia serological reagents
21 CFR 866.3390 Neisseria spp. direct serological test reagents
21 CFR 862.2570 Instrumentation for clinical multiplex systems
2. Classification:
Class II
3. Product code:

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MKZ: DNA Probe, Nucleic Acid Amplification, Chlamydia
LSL: DNA-Reagents, Neisseria
OOI: Real Time Nucleic Acid Amplification System

4. Panel:
Microbiology 083

H. Intended Use:

1. Intended use(s):

Xpert® CT/NG Assay

The Xpert® CT/NG Assay, performed on the GeneXpert® Instrument Systems, is a qualitative *in vitro* real-time PCR test for the automated detection and differentiation of genomic DNA from *Chlamydia trachomatis* (CT) and/or *Neisseria gonorrhoeae* (NG) to aid in the diagnosis of chlamydial and 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).

Ancillary Specimen Collection Kits

Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit

The Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve and transport patient *Chlamydia trachomatis* and *Neisseria gonorrhoeae* DNA in endocervical and vaginal specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.

The Cepheid Xpert CT/NG Vaginal/Endocervical Specimen Collection Kit has only been cleared for use with the Cepheid Xpert CT/NG Assay.

Cepheid® Xpert® CT/NG Urine Specimen Collection Kit

Cepheid® Xpert® CT/NG Urine Specimen Collection Kit is designed to preserve and transport *Chlamydia trachomatis* and *Neisseria gonorrhoeae* DNA in first-catch male and female urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.

2. Indication(s) for use:

Same as the Intended Use

Xpert CT/NG– IVD, Decision Summary
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3. Special conditions for use statement(s):

Prescription Use Only

4. Special instrument requirements:

GeneXpert Instrument Systems
- GeneXpert Dx
- GeneXpert Infinity-48
- GeneXpert Infinity-80

I. Device Description:

The Xpert CT/NG Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of DNA from *Chlamydia trachomatis* (CT) and/or *Neisseria gonorrhoeae* (NG). The assay is performed on the Cepheid GeneXpert Instrument Systems. The GeneXpert Instrument Systems automate and integrate sample purification, nucleic acid amplification, and detection of the target sequences in urogenital samples using real-time PCR for gene specific sequence amplification.

The GeneXpert Instrument Systems, comprised of the GeneXpert Dx System, the GeneXpert Infinity-48 System and the GeneXpert Infinity-80 System, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing sample preparation and real-time PCR tests individually for each patient. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

The system consists of an instrument, personal computer, and preloaded software for running the tests on collected samples and viewing the results. The system is designed to minimize cross-contamination during the testing process by the use of assay specific single-use disposable cartridges that hold the PCR reagents and host the PCR process.

The Xpert CT/NG Assay includes reagents for the 5' exonuclease real-time PCR detection and differentiation of CT and NG. Reagents for the detection of a Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are also included in the cartridge. The SPC is present to control for adequate processing of the target bacteria and to monitor the presence of inhibitors in the PCR reaction. The SAC reagents detect the presence of a single copy human gene and monitor whether the specimen contains human DNA. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability. The primers and probes in the Xpert CT/NG Assay detect chromosomal sequences in the bacteria.

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The Xpert CT/NG Assay is designed for use with genital and urine specimens (first-catch male urine, female urine, endocervical specimens and vaginal swab specimens) collected in specific Urine and Endocervical /Vaginal Specimen Collection kits designed to preserve patient specimens to allow transport to the laboratory for analysis with Xpert CT/NG Assay and GeneXpert Instrument System. The specimen is briefly mixed and transferred to the sample chamber of the Xpert CT/NG cartridge using the supplied transfer pipette. The provided Binding Reagent is manually added into the designated chamber of the Xpert CT/NG cartridge. The cartridge is loaded onto the GeneXpert Instrument System platform, which performs hands-off, automated sample processing, and real-time PCR for detection of DNA. Test results are obtained in approximately 90 minutes and are displayed in tabular and graphic formats.

## J. Substantial Equivalence Information:

1. Predicate device names:

GEN-PROBE APTIMA Combo 2x Assay

Becton Dickenson ProbeTec™ ET Chlamydia trachomatis/Neisseria gonorrhoeae Amplified DNA Assay

2. Predicate 510(k) numbers:

K043224

K012351

3. Comparison with predicate:

| | Device | Predicates | |
| --- | --- | --- | --- |
| Item | Cepheid Xpert CT/NG Assay | GEN-PROBE® APTIMA Combo 2® Assay | Becton Dickenson ProbeTec™ ET Chlamydia trachomatis /Neisseria gonorrhoeae |
| Regulation | 866.3120, 866.3390 | 866.3120, 866.3390 | 866.3120, 866.3390 |
| Device Class | I, II | I, II | I, II |
| Technology / Detection | An automated multiplex real-time polymerase chain | An automated multiplex transcription-mediated amplification (TMA) | An automated multiplex strand displacement amplification (SDA) |
| Intended Use | An automated, multiplex real-time RT-PCR assay, | A target amplification nucleic acid probe test | Strand Displacement Amplification (SDA) |

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| | 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). | that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) in clinician-collected endocervical, vaginal, and male urethral swab specimens, patient-collected vaginal swab specimens*, and female and male urine specimens. The assay is also intended for use with testing of gynecological specimens collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease. *Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The | technology for the direct, qualitative detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in endocervical swabs, male urethral swabs, and in female and male urine specimens as evidence of infection with C. trachomatis, N. gonorrhoeae, or of co-infection with both C. trachomatis and N. gonorrhoeae. Specimens may be from symptomatic or asymptomatic females and males. A separate Amplification Control is an option for inhibition testing (BDProbeTec™ ET CT/GC/AC Reagent Pack). |
| --- | --- | --- | --- |
| Indication for Use | Asymptomatic and symptomatic patients | Same | Same |

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| Assay Targets | DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) | ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) | DNA from Chlamydia trachomatis (CT) and Neisseria gonorrhea (NG) |
| --- | --- | --- | --- |
| Specimen Types | Urine (male and female), endocervical swab, and patient-collected vaginal swab | Clinician-collected endocervical, vaginal, and male urethral swab specimens, patient-collected vaginal swab specimens, and female and male urine specimens | Endocervical swabs, male urethral swabs, and urine specimens for females and males |
| CT Analyte Targets | CT genomic DNA | CT ribosomal RNA | CT cryptic plasmid DNA |
| NG Analyte Targets | NG genomic DNA | NG ribosomal RNA | NG genomic DNA |
| Collection Kit | Urine collection kit Swab collection kit | Urine collection kit Swab collection kit | Urine collection kit Swab collection kit |
| Nucleic Acid Extraction | Yes | Yes | Yes |
| Sample Extraction | Self-contained and automated after specimen sample elution and two single-dose reagent additions. | Manual | Manual |
| Assay Results | Qualitative | Qualitative | Qualitative |
| Instrument System | Cepheid GeneXpert Instrument Systems | Gen-Probe Leader HC+ Luminometer and Gen-Probe Target Capture System | ProbeTec ETTM System |
| Assay Controls | Internal sample processing control (SPC), sample adequacy control (SAC), and probe check control (PCC). External controls available. | The Positive Control, CT / Negative Control, GC and the Positive Control, GC / Negative Control, CT act as controls for the target capture, amplification, and detection steps of the assay. | Amplification Control (AC) |

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Similarities and Differences between the Cepheid Collection Kits and the Predicate Collection Devices

| | Device : | Predicate: | Predicate: |
| --- | --- | --- | --- |
| Item | Cepheid Xpert CT/NG Vaginal/Endocervical Specimen Collection Kit | GEN-PROBE® APTIMA® Unisex Swab Specimen Collection kit for Endocervical and Male Urethral Swab Specimen | GEN-PROBE® APTIMA® Vaginal Swab Specimen Collection kit |
| Description | Contains an 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 a 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. | Contains an individually packaged sterile Endocervical cleaning swab and an individually-packaged sterile specimen collection swab that is placed into the Transport Tube after swab sampling and is used to stabilize the nucleic acid until sample preparation. | Contains an individually packaged sterile specimen collection swab that is placed into the Transport Tube after swab sampling and is used to stabilize the nucleic acid until sample preparation. |
| Item | Cepheid Xpert CT/NG Urine Specimen Collection Kit | GEN-PROBE® APTIMA® Urine Specimen Collection kit |
| --- | --- | --- |
| Description | Contains one individually packaged sterile disposable transfer pipette and one Xpert CT/NG Urine Transport Reagent tube. Approximately 7 mL of a first-catch urine specimen is transferred to the Urine Transport Reagent tube to preserve and transport the specimen prior to analysis with the Cepheid Xpert CT/NG Assay. | Contains a disposable transfer pipette for adding approximately 2 mL of urine to a Specimen Transport Tube containing 2.0 mL of Transport Buffer. |

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K. Standard/Guidance Document Referenced:

1. Establishing the Performance Characteristics of In Vitro Diagnostic Devices for Chlamydia trachomatis and/or Neisseria gonorrhea: Screening and Diagnostic Testing - Draft Guidance for Industry and FDA Staff, May 11, 2011.
2. CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline –Second Edition.
3. EN 13640, Stability Testing of in vitro Diagnostic Reagents, June 2002
4. ASTM D4169-05 and ASTM D4169-09, Standard Practice for Performance Testing of Shipping Containers and Systems.
5. CLSI MM3-A2, Molecular Diagnostic Methods for Infectious Disease; Approved Guideline –Second Edition
6. Nucleic Acid Based In Vitro Diagnostic Devices for Detection of Microbial Pathogens - Draft Guidance for Industry and FDA Staff, December 8, 2005.
7. Guidance for Industry and FDA Staff, Format for Traditional and Abbreviated 510(k), August 12, 2005.
8. Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems, March 10, 2005.
9. Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices - Guidance for Industry and FDA Staff, May 11, 2005.
10. Guidance for Off-the-Shelf Software Use in Medical Devices; Final, September 9, 1999.

L. Test Principle:

Detection of the amplified DNA is by fluorogenic target-specific probe hybridization followed by 5'-nuclease cleavage of the probe to release the fluorophore. The primers and probes in the Xpert CT/NG Assay are designed to amplify and detect one unique chromosomal gene sequence for Chlamydia trachomatis and two unique chromosomal gene sequences for Neisseria gonorrhoeae.

The GeneXpert Instrument Systems perform hands-off, automated sample preparation by first mixing the sample with Lysis Reagent and then taking the mixture to re-suspend the Sample Processing Control in the form of a lyophilized bead within the cartridge. Lysis of bacterial cells with Lysis Reagent is followed by mixing with Binding Reagent which allows capture of the nucleic acids on the glass fiber column. The column is then washed to remove contaminants and finally, the purified nucleic acids are eluted with an elution reagent. The nucleic acid solution is mixed with dry real-time PCR reagents and transferred into the PCR tube for real-time PCR and detection of chromosomal DNA gene sequences for Chlamydia trachomatis and/or Neisseria gonorrhoeae. During real time-PCR cycling, optical signals from five (5) sequence specific fluorescent probes within the reaction are monitored in real time. The probes correspond to the one CT and two NG targets, SAC target and the SPC target.

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# Controls:

## Internal Controls:

The Xpert CT/NG Assay includes three internal controls contained in each cartridge:

- The Probe Check Control (PCC) performs a check on the amplification portion of the assay. It controls for missing or incompletely hydrated beads of enzyme and target specific reagent. It also controls for the generated fluorescence which must meet internal acceptance criteria.
- The Sample Processing Control (SPC) contains DNA from *Bacillus globigii* and verifies the sample processing and target amplification.
- The Sample Adequacy Control (SAC) ensures that the sample contains human cells and that the cells are adequately lysed in order to extract nucleic acids.

Additionally, the GeneExpert Instrument performs a System Control Check for Temperature. This check ensures that the instrument is operating within validated heating and cooling specifications.

## External Controls:

External Controls are not included with the kit and must be obtained by the user.

## Interpretation of Results:

The results are interpolated by the GeneXpert System from measured fluorescent signals and embedded calculation algorithms. The diagnostic algorithm is based on the results for the optical curves associated with the CT and NG targets as well as the Sample Processing Control (SPC) and Sample Adequacy Control (SAC). A cycle threshold (Ct) is obtained for each curve. The values for Ct are used to determine the presence or absence of the targets being detected (CT, NG, SAC, and SPC). The optical curves for the CT and/or NG target are interpreted as positive if they satisfy fixed criteria for valid threshold fluorescence crossing. The optical curves for the CT and/or NG targets are interpreted as negative if they fail to satisfy fixed criteria for a valid threshold crossing. The following table shows the possible final test results:

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| Result Text | CT1 | NG2 | NG4 | SPC | SA |
| --- | --- | --- | --- | --- | --- |
| CT DETECTED; NG DETECTED | + | + | + | +/- | +/- |
| CT DETECTED; NG NOT DETECTED | + | + | - | +/- | +/- |
| CT DETECTED; NG NOT DETECTED | + | - | + | +/- | +/- |
| CT NOT DETECTED; NG DETECTED | - | + | + | +/- | +/- |
| CT NOT DETECTED, NG NOT DETECTED | - | - | + | +/- | +/- |
| CT NOT DETECTED, NG NOT DETECTED | - | - | - | + | + |
| INVALID | - | - | - | - | +/- |
| INVALID | - | - | - | +/- | - |

There are 3 possible outcomes that require a re-test of the specimen:

INVALID indicates that the SPC and/or the SAC failed. The sample was not properly processed, PCR was inhibited, or the sample was inadequate.

ERROR indicates that the PCC failed and the assay was aborted possibly because the reaction tube was filled improperly, a reagent probe integrity problem was detected, pressure limits were exceeded, or a valve positioning error was detected.

NO RESULT indicates that insufficient data were collected. For example, the operator stopped a test that was in progress.

A re-test is performed on the leftover sample from the CT/NG Transport Reagent tube using a new cartridge.

## M. Performance Characteristics

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility Study:

Reproducibility of the Xpert CT/NG Assay was evaluated at three sites using specimens comprised of CT and NG organisms seeded into pooled, negative male urine (urine matrix) or pooled, negative female vaginal swab samples (swab matrix). The specimens were prepared at concentration levels representing low positive (1X LoD), moderate positive (2-3X LoD), and high positive (>20X LoD) for each organism. The panel members prepared with high concentrations (>20xLoD) of one organism and low concentrations (1xLoD) of the other organism allowed for the evaluation of potential competitive inhibition of one organism by the other one.

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Negative panel members were also included, and were comprised of pooled, negative male urine and pooled, negative vaginal swab samples. A panel of 22 specimens (11 in urine matrix and 11 in swab matrix) was tested on five different days by two different operators four times per day at three sites (22 specimens x 2 operators x 5 days x 4 replicates per day x 3 sites). Three lots of Xpert CT/NG reagents were included in the study, with two lots being tested at each site. Xpert CT/NG Assays were performed according to the Xpert CT/NG Assay procedure. The rate of agreement with expected results of CT and NG for each panel member was calculated for each site. The results are presented separately for swab samples and urine samples.

Summary of Reproducibility Results for Swab Samples; Percent Agreement by Study Site

| Sample | | Site 1 (GeneXpert Dx) | Site 2 (Infinity-80) | Site 3 (Infinity-48) | % Total Agreement by Sample |
| --- | --- | --- | --- | --- | --- |
| CT >20X LoD; NG >20X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT >20X LoD; NG 1X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 87.5% (35/40) | 97.5% (39/40) | 95.0% (38/40) | 93.3% (112/120) |
| CT >20X LoD; NG neg | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT 1X LoD; NG >20X LoD | CT | 90.0% (36/40) | 97.5% (39/40) | 95.0% (38/40) | 94.2% (113/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT 1X LoD; NG 1X LoD | CT | 97.5% (39/40) | 100% (40/40) | 100% (40/40) | 99.2% (119/120) |
| | NG | 92.5% (37/40) | 90.0% (36/40) | 90.0% (36/40) | 90.8% (109/120) |
| CT 1X LoD; NG neg | CT | 97.5% (39/40) | 90.0% (36/40) | 90.0% (36/40) | 92.5% (111/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT 2-3X LoD; NG neg | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT neg; NG >20X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |

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| Sample | | Site 1 (GeneXpert Dx) | Site 2 (Infinity-80) | Site 3 (Infinity-48) | % Total Agreement by Sample |
| --- | --- | --- | --- | --- | --- |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT neg; NG 1X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100.0% (40/40) | 97.5% (39/40) | 97.5% (39/40) | 98.3% (118/120) |
| CT neg; NG 2-3X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 97.5% (39/40) | 100% (40/40) | 100% (40/40) | 99.2% (119/120) |
| CT neg; NG neg | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |

Summary of Reproducibility Results for Urine Samples; Percent Agreement by Study Site

| Sample | | Site 1 (GeneXpert Dx) | Site 2 (Infinity-80) | Site 3 (Infinity-48) | % Total Agreement by Sample |
| --- | --- | --- | --- | --- | --- |
| CT >20X LoD; NG >20X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT >20X LoD; NG 1X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 92.5% (37/40) | 97.5% (39/40) | 97.5% (39/40) | 95.8% (115/120) |
| CT >20X LoD; NG neg | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT 1X LoD; NG >20X LoD | CT | 92.5% (37/40) | 95.0% (38/40) | 90.0% (36/40) | 92.5% (111/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT 1X LoD; NG 1X LoD | CT | 95.0% (38/40) | 80.0% (32/40) | 87.5% (35/40) | 87.5% (105/120) |
| | NG | 95.0% (38/40) | 85.0% (34/40) | 87.5% (35/40) | 89.2% (107/120) |
| CT 1X LoD; NG neg | CT | 87.5% (35/40) | 97.5% (39/40) | 97.5% (39/40) | 94.2% (113/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT 2-3X LoD; NG neg | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT neg; NG >20X LoD | CT | 97.5% (39/40) | 100% (40/40) | 100% (40/40) | 99.2% (119/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT neg; | CT | 100% (40/40) | 100% (40/40) | 97.5% (39/40) | 99.2% (119/120) |

Xpert CT/NG- IVD, Decision Summary

{12}

| Sample | | Site 1
(GeneXpert Dx) | Site 2
(Infinity-80) | Site 3
(Infinity-48) | % Total Agreement by Sample |
| --- | --- | --- | --- | --- | --- |
| NG 1X LoD | NG | 100% (40/40) | 97.5% (39/40) | 100% (40/40) | 99.2% (119/120) |
| CT neg;
NG 2-3X LoD | CT | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |
| CT neg;
NG neg | CT | 100% (40/40) | 100% (40/40) | 97.5% (39/40) | 99.2% (119/120) |
| | NG | 100% (40/40) | 100% (40/40) | 100% (40/40) | 100% (120/120) |

The reproducibility of the Xpert CT/NG Assay was also evaluated in terms of the fluorescence signal expressed in Ct values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) measures between-sites, between-lots, between-days, and between-runs for each panel member, for each target detected, are presented below.

Xpert CT/NG- IVD, Decision Summary

{13}

Summary of Reproducibility data for Swab and Urine Specimens – CT1 Target

| Type | Target Conc. | | | | | Between-Site | | Between- Lot | | Between-Day | | Between-Run¹ | | Within-Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | CT (LoD) | NG (LoD) | Agree/N | Agrmt (%) | Mean Ct | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Swab | >20X | >20X | 120/120 | 100 | 20.67 | 0.21 | 1.0 | 0.11 | 0.5 | 0.11 | 0.5 | 0.00 | 0.0 | 0.29 | 1.4 | 0.39 | 1.9 |
| | >20X | 1X | 112/120 | 93.3 | 20.73 | 0.29 | 1.4 | 0.37 | 1.8 | 0.00 | 0.0 | 0.00 | 0.0 | 1.59 | 7.7 | 1.66 | 8.0 |
| | >20X | NEG | 120/120 | 100 | 20.59 | 0.00 | 0.0 | 0.21 | 1.0 | 0.06 | 0.3 | 0.08 | 0.4 | 0.26 | 1.3 | 0.35 | 1.7 |
| | 1X | >20X | 113/120 | 94.2 | 37.20 | 0.10 | 0.3 | 0.21 | 0.6 | 0.00 | 0.0 | 0.00 | 0.0 | 1.15 | 3.1 | 1.18 | 3.2 |
| | 1X | 1X | 106/120 | 88.3 | 37.04 | 0.17 | 0.5 | 0.00 | 0.0 | 0.00 | 0.0 | 0.12 | 0.3 | 1.08 | 2.9 | 1.10 | 3.0 |
| | 1X | NEG | 111/120 | 92.5 | 37.04 | 0.06 | 0.2 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.12 | 3.0 | 1.12 | 3.0 |
| | 2-3X | NEG | 120/120 | 100 | 35.63 | 0.13 | 0.4 | 0.00 | 0.0 | 0.15 | 0.4 | 0.10 | 0.3 | 0.77 | 2.2 | 0.80 | 2.3 |
| | NEG | >20X | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | 1X | 118/120 | 98.3 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | 2-3X | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Urine | >20X | >20X | 120/120 | 100 | 21.46 | 0.23 | 1.0 | 0.00 | 0.0 | 0.12 | 0.5 | 0.02 | 0.1 | 0.31 | 1.4 | 0.40 | 1.9 |
| | >20X | 1X | 115/120 | 95.8 | 21.33 | 0.13 | 0.6 | 0.05 | 0.2 | 0.13 | 0.6 | 0.00 | 0.0 | 0.43 | 2.0 | 0.47 | 2.2 |
| | >20X | NEG | 120/120 | 100 | 21.36 | 0.19 | 0.9 | 0.00 | 0.0 | 0.12 | 0.6 | 0.02 | 0.1 | 0.47 | 2.2 | 0.52 | 2.4 |
| | 1X | >20X | 111/120 | 92.5 | 37.24 | 0.36 | 1.0 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.33 | 3.6 | 1.38 | 3.7 |
| | 1X | 1X | 97/120 | 80.8 | 37.15 | 0.40 | 1.1 | 0.18 | 0.5 | 0.17 | 0.4 | 0.00 | 0.0 | 1.02 | 2.8 | 1.13 | 3.0 |
| | 1X | NEG | 113/120 | 94.2 | 37.39 | 0.10 | 0.3 | 0.32 | 0.9 | 0.00 | 0.0 | 0.00 | 0.0 | 1.38 | 3.7 | 1.42 | 3.8 |
| | 2-3X | NEG | 120/120 | 100 | 35.26 | 0.24 | 0.7 | 0.00 | 0.0 | 0.30 | 0.9 | 0.00 | 0.0 | 0.80 | 2.3 | 0.89 | 2.5 |
| | NEG | >20X | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | 1X | 118/120 | 98.3 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | 2-3X | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | NEG | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |

Agrmt=Agreement, Conc=concentration, CV=coefficient of variation, N/A=Not Applicable for negative samples, SD=standard deviation
Note: Variability from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.
¹A run is defined as the four samples per panel member run by one operator at one site on one day

Xpert CT/NG Package Insert – IVD
Page 14 of 40

{14}

Summary of Reproducibility data for Swab and Urine Specimens – NG2 Target

| Type | Target Conc. | | | | | Between-Site | | Between- Lot | | Between-Day | | Between-Run¹ | | Within-Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | CT (LoD) | NG (LoD) | Agree/N | Agrmt (%) | Mean Ct | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Swab | >20X | >20X | 120/120 | 100 | 19.65 | 0.03 | 0.1 | 0.09 | 0.4 | 0.07 | 0.3 | 0.02 | 0.1 | 0.24 | 1.2 | 0.26 | 1.3 |
| | >20X | 1X | 112/120 | 93.3 | 35.38 | 0.22 | 0.6 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.98 | 5.6 | 1.99 | 5.6 |
| | >20X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 1X | >20X | 113/120 | 94.2 | 19.69 | 0.12 | 0.6 | 0.00 | 0.0 | 0.19 | 1.0 | 0.00 | 0.0 | 0.43 | 2.2 | 0.49 | 2.5 |
| | 1X | 1X | 106/120 | 88.3 | 35.61 | 0.00 | 0.0 | 0.53 | 1.5 | 0.00 | 0.0 | 0.80 | 2.2 | 1.37 | 3.9 | 1.67 | 4.7 |
| | 1X | NEG | 111/120 | 92.5 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | >20X | 120/120 | 100 | 19.60 | 0.10 | 0.5 | 0.07 | 0.4 | 0.00 | 0.0 | 0.07 | 0.4 | 0.20 | 1.0 | 0.25 | 1.3 |
| | NEG | 1X | 118/120 | 98.3 | 35.43 | 0.39 | 1.1 | 0.00 | 0.0 | 0.04 | 0.1 | 0.22 | 0.6 | 0.94 | 2.6 | 1.04 | 2.9 |
| | NEG | 2-3X | 119/120 | 99.2 | 33.97 | 0.00 | 0.0 | 0.15 | 0.4 | 0.00 | 0.0 | 0.15 | 0.4 | 0.71 | 2.1 | 0.74 | 2.2 |
| | NEG | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Urine | >20X | >20X | 120/120 | 100 | 20.34 | 0.06 | 0.3 | 0.09 | 0.4 | 0.00 | 0.0 | 0.07 | 0.3 | 0.23 | 1.1 | 0.26 | 1.3 |
| | >20X | 1X | 115/120 | 95.8 | 35.41 | 0.00 | 0.0 | 0.00 | 0.0 | 0.19 | 0.5 | 0.30 | 0.8 | 1.15 | 3.3 | 1.20 | 3.4 |
| | >20X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 1X | >20X | 111/120 | 92.5 | 20.40 | 0.06 | 0.3 | 0.07 | 0.3 | 0.00 | 0.0 | 0.00 | 0.0 | 0.39 | 1.9 | 0.40 | 2.0 |
| | 1X | 1X | 97/120 | 80.8 | 35.57 | 0.20 | 0.6 | 0.00 | 0.0 | 0.13 | 0.4 | 0.10 | 0.3 | 1.28 | 3.6 | 1.31 | 3.7 |
| | 1X | NEG | 113/120 | 94.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | >20X | 119/120 | 99.2 | 20.39 | 0.00 | 0.0 | 0.07 | 0.4 | 0.14 | 0.7 | 0.05 | 0.3 | 0.26 | 1.3 | 0.31 | 1.5 |
| | NEG | 1X | 118/120 | 98.3 | 35.35 | 0.00 | 0.0 | 0.11 | 0.3 | 0.00 | 0.0 | 0.36 | 1.0 | 0.92 | 2.6 | 0.99 | 2.8 |
| | NEG | 2-3X | 120/120 | 100 | 33.80 | 0.00 | 0.0 | 0.18 | 0.5 | 0.00 | 0.0 | 0.00 | 0.0 | 0.54 | 1.6 | 0.57 | 1.7 |
| | NEG | NEG | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |

Agrmt=Agreement, Conc=concentration, CV=coefficient of variation, N/A=Not Applicable for negative samples, SD=standard deviation
Note: Variability from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.
¹A run is defined as the four samples per panel member run by one operator at one site on one day

Xpert CT/NG- IVD, Decision Summary
Page 15 of 40

{15}

Summary of Reproducibility data for Swab and Urine Specimens – NG4 Target

| Type | Target Conc. | | | | | Between-Site | | Between- Lot | | Between-Day | | Between-Run¹ | | Within-Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | CT (LoD) | NG (LoD) | Agree/N | Agrmt (%) | Mean Ct | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Swab | >20X | >20X | 120/120 | 100 | 19.34 | 0.00 | 0.0 | 0.12 | 0.6 | 0.11 | 0.6 | 0.00 | 0.0 | 0.39 | 2.0 | 0.42 | 2.2 |
| | >20X | 1X | 112/120 | 93.3 | 35.00 | 0.41 | 1.2 | 0.00 | 0.0 | 0.00 | 0.0 | 0.32 | 0.9 | 1.89 | 5.4 | 1.96 | 5.6 |
| | >20X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 1X | >20X | 113/120 | 94.2 | 19.41 | 0.07 | 0.4 | 0.00 | 0.0 | 0.14 | 0.7 | 0.03 | 0.2 | 0.49 | 2.5 | 0.52 | 2.7 |
| | 1X | 1X | 106/120 | 88.3 | 35.47 | 0.32 | 0.9 | 0.00 | 0.0 | 0.00 | 0.0 | 0.70 | 2.0 | 0.90 | 2.5 | 1.19 | 3.3 |
| | 1X | NEG | 111/120 | 92.5 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | >20X | 120/120 | 100 | 19.35 | 0.02 | 0.1 | 0.04 | 0.2 | 0.00 | 0.0 | 0.07 | 0.4 | 0.28 | 1.5 | 0.29 | 1.5 |
| | NEG | 1X | 118/120 | 98.3 | 35.05 | 0.00 | 0.0 | 0.16 | 0.5 | 0.00 | 0.0 | 0.00 | 0.0 | 1.00 | 2.9 | 1.01 | 2.9 |
| | NEG | 2-3X | 119/120 | 99.2 | 33.57 | 0.14 | 0.4 | 0.17 | 0.5 | 0.00 | 0.0 | 0.00 | 0.0 | 0.78 | 2.3 | 0.81 | 2.4 |
| | NEG | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Urine | >20X | >20X | 120/120 | 100 | 20.06 | 0.12 | 0.6 | 0.12 | 0.6 | 0.09 | 0.4 | 0.00 | 0.0 | 0.39 | 1.9 | 0.43 | 2.1 |
| | >20X | 1X | 115/120 | 95.8 | 35.27 | 0.17 | 0.5 | 0.13 | 0.4 | 0.00 | 0.0 | 0.00 | 0.0 | 1.04 | 2.9 | 1.06 | 3.0 |
| | >20X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 1X | >20X | 111/120 | 92.5 | 20.16 | 0.00 | 0.0 | 0.08 | 0.4 | 0.00 | 0.0 | 0.12 | 0.6 | 0.56 | 2.8 | 0.58 | 2.9 |
| | 1X | 1X | 97/120 | 80.8 | 35.25 | 0.00 | 0.0 | 0.00 | 0.0 | 0.41 | 1.2 | 0.00 | 0.0 | 1.17 | 3.3 | 1.24 | 3.5 |
| | 1X | NEG | 113/120 | 94.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | NEG | 120/120 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | >20X | 119/120 | 99.2 | 20.12 | 0.09 | 0.5 | 0.10 | 0.5 | 0.06 | 0.3 | 0.00 | 0.0 | 0.41 | 2.0 | 0.43 | 2.2 |
| | NEG | 1X | 118/120 | 98.3 | 35.05 | 0.24 | 0.7 | 0.00 | 0.0 | 0.15 | 0.4 | 0.12 | 0.4 | 1.09 | 3.1 | 1.13 | 3.2 |
| | NEG | 2-3X | 120/120 | 100 | 33.67 | 0.00 | 0.0 | 0.33 | 1.0 | 0.00 | 0.0 | 0.16 | 0.5 | 0.83 | 2.5 | 0.91 | 2.7 |
| | NEG | NEG | 119/120 | 99.2 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |

Agrmt=Agreement, Conc=concentration, CV=coefficient of variation, N/A=Not Applicable for negative samples, SD=standard deviation
Note: Variability from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.
¹A run is defined as the four samples per panel member run by one operator at one site on one day

Xpert CT/NG- IVD, Decision Summary
Page 16 of 40

{16}

Xpert CT/NG Package Insert – IVD
Page 17 of 40

# Instrument Precision Study:

An in-house precision study was conducted to compare the performance of the GeneXpert Dx and the Infinity-80 Instrument Systems using specimens comprised of CT and NG organisms seeded into negative urine simulated swab matrix. The specimens were prepared at concentration levels representing low positive (0.25-0.5X LoD), moderate positive (2-3X LoD), and high positive (>20X LoD) for each organism. Negative panel members were also included and were comprised of negative urine and negative diluent. A panel of 20 specimens (10 in urine matrix and 10 in swab matrix) was tested on 12 different days by two operators. The samples were tested in a different order throughout the study; the specimens were blinded with a Specimen ID, which was used to define the order in which the samples were tested. Each operator conducted four runs of each panel specimen per day on each of the two instrument systems (20 specimens x 4 times/ day x 12 days x 2 operators x 2 instrument systems). One lot of Xpert CT/NG Assay was used for the study. Xpert CT/NG assays were performed according to the Xpert CT/NG Assay procedure. External controls were run on each instrument by each operator on each day that samples were tested. The study challenged the Infinity-80 system by loading the test cartridges continuously by the two operators, which resulted in the worst-case scenario where the maximum number of cartridges was loaded and analyzed simultaneously. Xpert CT/NG assays were performed according to the Xpert CT/NG Assay procedure.

The rate of agreement with expected results of CT and NG for each panel member, in swab matrix, is presented below.

Summary of Instrument System Precision Results; Percent Agreement Swab Matrix

| Sample | | GeneXpert Dx | Infinity-80 | % Total Agreement by Sample |
| --- | --- | --- | --- | --- |
| CT >20X LoD; NG >20X LoD | CT | 100% (96/96) | 100% (95/95)^{a} | 100% (191/191) |
| | NG | 100% (96/96) | 100% (95/95)^{a} | 100% (191/191) |
| CT >20X LoD; NG 0.25-0.5X LoD | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| | NG | 62.5% (60/96) | 52.1% (50/96) | 57.3% (110/192) |
| CT >20X LoD; NG neg | CT | 100% (96/96) | 100% (95/95)^{b} | 100% (191/191) |
| | NG | 100% (96/96) | 100% (95/95)^{b} | 100% (191/191) |
| CT 0.25-0.5X LoD; NG >20X LoD | CT | 46.9% (45/96) | 42.7% (41/96) | 44.8% (86/192) |
| | NG | 100% | 100% (96/96) | 100% (192/192) |

{17}

The rate of agreement with expected results of CT and NG for each panel member, in urine matrix, is presented below.

Summary of Instrument System Precision Results; Percent Agreement Urine Matrix

| Sample | | GeneXpert Dx | Infinity-80 | % Total Agreement by Sample |
| --- | --- | --- | --- | --- |
| CT >20X LoD; NG >20X LoD | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| | NG | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| CT >20X LoD; NG 0.25-0.5X LoD | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |
| | NG | 46.9% (45/96) | 49.0% (47/96) | 47.9% (92/192) |
| CT >20X LoD; | CT | 100% (96/96) | 100% (96/96) | 100% (192/192) |

One sample was indeterminate after initial and retest.
One sample each of CT >20X LoD;NG neg sample and CT neg; NG 0.25-0.5X LoD resulted in ERROR on initial test and were not retested.
One sample mistakenly not tested.

{18}

The precision of the Xpert CT/NG Assay in this study was also evaluated in terms of the fluorescence signal expressed in Ct values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) between-instruments, between-days, and between-runs for each panel member, for each target detected, are presented below.

Summary of In-house Precision Data for Swab and Urine Specimens - CT1 Target

| Type | Target Conc. | | | | | Between-Instrument | | Between-Day | | Between-Run' | | Within-Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | CT (LoD) | NG (LoD) | Agree/N | Agrmt (%) | Mean Ct | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Swab | >20X | >20X | 191/191 | 100 | 23.52 | 0.05 | 0.2 | 0.02 | 0.1 | 0.00 | 0.0 | 0.25 | 1.1 | 0.26 | 1.1 |
| | >20X | 0.25-0.5X | 110/192 | 57.3 | 23.52 | 0.00 | 0.0 | 0.00 | 0.0 | 0.08 | 0.3 | 0.18 | 0.7 | 0.19 | 0.8 |
| | >20X | NEG | 191/191 | 100 | 23.55 | 0.03 | 0.1 | 0.00 | 0.0 | 0.00 | 0.0 | 0.22 | 0.9 | 0.22 | 0.9 |
| | 0.25-0.5X | >20X | 86/192 | 44.8 | 38.77 | 0.00 | 0.0 | 0.00 | 0.0 | 0.32 | 0.8 | 1.38 | 3.6 | 1.42 | 3.7 |
| | 0.25-0.5X | 0.25-0.5X | 59/192 | 30.7 | 38.46 | 0.00 | 0.0 | 0.30 | 0.8 | 0.00 | 0.0 | 1.35 | 3.5 | 1.39 | 3.6 |
| | 0.25-0.5X | NEG | 118/191 | 61.8 | 38.05 | 0.08 | 0.2 | 0.00 | 0.0 | 0.00 | 0.0 | 1.26 | 3.3 | 1.26 | 3.3 |
| | 2-3X | 2-3X | 192/192 | 100 | 31.49 | 0.04 | 0.1 | 0.00 | 0.0 | 0.06 | 0.2 | 0.24 | 0.8 | 0.25 | 0.8 |
| | NEG | >20X | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | 0.25-0.5X | 116/191 | 60.7 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | NEG | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Urine | >20X | >20X | 192/192 | 100 | 24.35 | 0.05 | 0.2 | 0.20 | 0.8 | 0.10 | 0.4 | 0.30 | 1.2 | 0.38 | 1.6 |
| | >20X | 0.25-0.5X | 92/192 | 47.9 | 24.25 | 0.00 | 0.0 | 0.06 | 0.3 | 0.00 | 0.0 | 0.62 | 2.6 | 0.62 | 2.6 |
| | >20X | NEG | 192/192 | 100 | 24.12 | 0.00 | 0.0 | 0.15 | 0.6 | 0.19 | 0.8 | 0.34 | 1.4 | 0.41 | 1.7 |
| | 0.25- | >20X | 98/192 | 51.0 | 38.33 | 0.12 | 0.3 | 0.00 | 0.0 | 0.84 | 2.2 | 1.03 | 2.7 | 1.33 | 3.5 |

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| Type | Target Conc. | | | | | Between-Instrument | | Between-Day | | Between-Run1 | | Within-Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | CT (LoD) | NG (LoD) | Agree/N | Agrmt (%) | Mean Ct | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| | 0.5X | | | | | | | | | | | | | | |
| | 0.25-0.5X | 0.25-0.5X | 48/192 | 25.0 | 38.26 | 0.00 | 0.0 | 0.00 | 0.0 | 0.56 | 1.5 | 1.05 | 2.7 | 1.19 | 3.1 |
| | 0.25-0.5X | NEG | 90/192 | 46.9 | 38.39 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.09 | 2.8 | 1.09 | 2.8 |
| | 2-3X | 2-3X | 192/192 | 100 | 31.85 | 0.00 | 0.0 | 0.11 | 0.4 | 0.18 | 0.6 | 0.32 | 1.0 | 0.39 | 1.2 |
| | NEG | >20X | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | 0.25-0.5X | 67/192 | 34.9 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | NEG | NEG | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |

Agrmt=Agreement, Conc=concentration, CV=coefficient of variation, N/A=Not Applicable for negative samples, SD=standard deviation
Note: Variability from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.
${}^{1}$ A run is defined as the four samples per panel member run by one operator at one site on one day

Summary of In-house Precision Data for Swab and Urine Specimens - NG2 Target

| Type | Target Conc. | | | | | Between-Instrument | | Between-Day | | Between-Run1 | | Within-Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | CT (LoD) | NG (LoD) | Agree/N | Agrmt (%) | Mean Ct | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Swab | >20X | >20X | 191/191 | 100 | 19.03 | 0.01 | 0.0 | 0.02 | 0.1 | 0.00 | 0.0 | 0.21 | 1.1 | 0.21 | 1.1 |
| | >20X | 0.25-0.5X | 110/192 | 57.3 | 37.63 | 0.07 | 0.2 | 0.46 | 1.2 | 0.00 | 0.0 | 1.55 | 4.1 | 1.62 | 4.3 |
| | >20X | NEG | 191/191 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 0.25-0.5X | >20X | 86/192 | 44.8 | 19.08 | 0.00 | 0.0 | 0.00 | 0.0 | 0.10 | 0.5 | 0.31 | 1.6 | 0.32 | 1.7 |
| | 0.25-0.5X | 0.25-0.5X | 59/192 | 30.7 | 36.78 | 0.00 | 0.0 | 0.24 | 0.6 | 0.00 | 0.0 | 1.47 | 4.0 | 1.49 | 4.0 |
| | 0.25-0.5X | NEG | 118/191 | 61.8 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | 2-3X | 192/192 | 100 | 31.35 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 0.33 | 1.1 | 0.33 | 1.1 |
| | NEG | >20X | 192/192 | 100 | 19.02 | 0.00 | 0.0 | 0.00 | 0.0 | 0.07 | 0.4 | 0.22 | 1.2 | 0.23 | 1.2 |
| | NEG | 0.25-0.5X | 116/191 | 60.7 | 36.77 | 0.00 | 0.0 | 0.46 | 1.2 | 0.00 | 0.0 | 1.65 | 4.5 | 1.71 | 4.7 |
| NEG | NEG | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| Urine | >20X | >20X | 192/192 | 100 | 19.85 | 0.00 | 0.0 | 0.15 | 0.7 | 0.00 | 0.0 | 0.34 | 1.7 | 0.37 | 1.8 |
| | >20X | 0.25-0.5X | 92/192 | 47.9 | 36.72 | 0.15 | 0.4 | 0.00 | 0 | 0.00 | 0.0 | 1.36 | 3.7 | 1.37 | 3.7 |
| | >20X | NEG | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 0.25-0.5X | >20X | 98/192 | 51.0 | 19.51 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.20 | 6.1 | 1.20 | 6.1 |
| | 0.25-0.5X | 0.25-0.5X | 48/192 | 25.0 | 36.38 | 0.26 | 0.7 | 0.00 | 0.0 | 1.98 | 5.5 | 1.13 | 3.1 | 2.30 | 6.3 |
| | 0.25-0.5X | NEG | 90/192 | 46.9 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | 2-3X | 192/192 | 100 | 31.53 | 0.00 | 0.0 | 0.09 | 0.3 | 0.16 | 0.5 | 0.42 | 1.3 | 0.46 | 1.4 |
| | NEG | >20X | 192/192 | 100 | 19.26 | 0.14 | 0.7 | 0.00 | 0.0 | 0.17 | 0.9 | 0.43 | 2.3 | 0.49 | 2.4 |
| | NEG | 0.25-0.5X | 67/192 | 34.9 | 36.88 | 0.00 | 0.0 | 0.31 | 0.8 | 0.00 | 0 | 1.45 | 3.9 | 1.48 | 7.5 |
| | NEG | NEG | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |

Agrmt=Agreement, Conc=concentration, CV=coefficient of variation, N/A=Not Applicable for negative samples, SD=standard deviation
Note: Variability from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.
${}^{1}$ A run is defined as the four samples per panel member run by one operator at one site on one day

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Summary of In-house Precision Data for Swab and Urine Specimens - NG4 Target

| Type | Target Conc. | | | | | Between-Instrument | | Between-Day | | Between-Run1 | | Within-Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | CT (LoD) | NG (LoD) | Agree/N | Agrmt (%) | Mean Ct | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Swab | >20X | >20X | 191/191 | 100 | 18.67 | 0.00 | 0.0 | 0.00 | 0.0 | 0.19 | 1.0 | 0.34 | 1.8 | 0.39 | 2.1 |
| | >20X | 0.25-0.5X | 110/192 | 57.3 | 36.94 | 0.49 | 1.3 | 0.00 | 0.0 | 0.10 | 0.3 | 1.63 | 4.4 | 1.71 | 4.6 |
| | >20X | NEG | 191/191 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 0.25-0.5X | >20X | 86/192 | 44.8 | 18.72 | 0.06 | 0.3 | 0.00 | 0.0 | 0.21 | 1.1 | 0.41 | 2.2 | 0.46 | 2.5 |
| | 0.25-0.5X | 0.25-0.5X | 59/192 | 30.7 | 36.57 | 0.00 | 0.0 | 0.50 | 1.4 | 0.00 | 0.0 | 1.55 | 4.3 | 1.63 | 4.5 |
| | 0.25-0.5X | NEG | 118/191 | 61.8 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | 2-3X | 192/192 | 100 | 31.06 | 0.00 | 0.0 | 0.05 | 0.2 | 0.00 | 0.0 | 0.42 | 1.4 | 0.43 | 1.4 |
| | NEG | >20X | 192/192 | 100 | 18.69 | 0.00 | 0.0 | 0.00 | 0.0 | 0.22 | 1.2 | 0.38 | 2.0 | 0.44 | 2.3 |
| | NEG | 0.25-0.5X | 116/191 | 60.7 | 36.31 | 0.08 | 0.2 | 0.13 | 0.4 | 0.00 | 0.0 | 1.24 | 3.4 | 1.25 | 3.4 |
| | NEG | NEG | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Urine | >20X | >20X | 192/192 | 100 | 19.44 | 0.01 | 0.1 | 0.10 | 0.5 | 0 | 0 | 0.45 | 2.3 | 0.46 | 2.4 |
| | >20X | 0.25-0.5X | 92/192 | 47.9 | 36.31 | 0 | 0 | 0.04 | 0.1 | 0.17 | 0.5 | 1.18 | 3.2 | 1.19 | 6.1 |
| | >20X | NEG | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 0.25-0.5X | >20X | 98/192 | 51.0 | 19.08 | 0 | 0 | 0 | 0 | 0 | 0 | 1.35 | 7.1 | 1.35 | 6.9 |
| | 0.25-0.5X | 0.25-0.5X | 48/192 | 25.0 | 36.16 | 0 | 0 | 0.24 | 0.7 | 0 | 0 | 1.98 | 5.5 | 2.00 | 10.3 |
| | 0.25-0.5X | NEG | 90/192 | 46.9 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| | 2-3X | 2-3X | 192/192 | 100 | 31.09 | 0 | 0 | 0.16 | 0.5 | 0.11 | 0.4 | 0.49 | 1.6 | 0.53 | 2.7 |
| | NEG | >20X | 192/192 | 100 | 18.80 | 0.04 | 0.2 | 0 | 0 | 0.14 | 0.7 | 0.47 | 2.5 | 0.50 | 2.6 |
| | NEG | 0.25-0.5X | 67/192 | 34.9 | 36.58 | 0.18 | 0.5 | 0 | 0 | 0.74 | 2.0 | 1.40 | 3.8 | 1.60 | 8.2 |
| | NEG | NEG | 192/192 | 100 | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |

Agrmt=Agreement, Conc=concentration, CV=coefficient of variation, N/A=Not Applicable for negative samples, SD=standard deviation
Note: Variability from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.
1A run is defined as the four samples per panel member run by one operator at one site on one

# b. Linearity/assay reportable range:

Not Applicable, The Xpert CT/NG Assay is a qualitative assay.

# c. Traceability, Stability, Expected values (controls, calibrators, or methods):

# Specimen Stability

Specimen stability studies were conducted to evaluate the length of time the claimed specimen types can be stored prior to analysis with the Xpert CT/NG Assay. This study was conducted using cultured and tittered C. trachomatis and N. gonorrhoeae cells spiked into known negative urine and swab specimens and transferred to the appropriate transport reagent tubes. The samples were stored at different temperatures and tested at various time intervals to determine the conditions under which the specimens remain stable. Replicates of three (3) were tested at each time and temperature.

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22

# Urine Specimens

## Preserved urine:

Aliquots of pooled negative urine were diluted into Xpert CT/NG Urine Transport Reagent at a ratio of 7:1 (v/v) consistent with Package Insert instructions. *C. trachomatis* LGVII (ATCC 434/VR-902B0) and *N. gonorrhoeae* (ATCC 19424) were spiked into the preserved pooled negative urines. Specimens were stored at 2°C, 15°C and 30°C and tested at several time points out to 45 days. Female urine and male urine were evaluated separately. The data supported stability of preserved female urine specimens up to 45 days when stored at refrigerator temperatures (approximately 4°C) and up to 3 days when left at room temperature. The preserved male urine was stable for 45 days when stored at temperatures from 2°C to 15°C and up to 30 days at temperatures not exceeding 30°C.

## Unpreserved urine:

Spiked unpreserved urines were stored at 4°C and at room temperature and tested at several time points out to 14 days. The data supported stability of unpreserved female and male first catch urine specimens for 1 day at room temperature and for up to 8 days when stored in a refrigerator (4°C).

# Swab Specimens

*C. trachomatis* LGVII (ATCC 434/VR-902B0) and *N. gonorrhoeae* (ATCC 49226) were spiked into preserved pooled negative endocervical swabs and pooled negative vaginal swabs. Specimens were stored at 2°C and 30°C and tested with Xpert CT/NG Assay at several time points out to 60 days. The study data indicate that endocervical and vaginal swab specimens transferred into the Xpert CT/NG Swab Transport Reagent tube (preserved endocervical/vaginal swab specimen) can be stored up to 60 days at temperatures from 2°C to 30°C prior to testing with the Xpert CT/NG Assay.

## d. Detection limit:

Studies were performed to determine the analytical limit of detection (LoD) of the Xpert CT/NG Assay with purified CT elementary bodies seeded into negative natural human pooled vaginal swab and pooled male urine matrices and NG cells seeded into negative pooled simulated swab and pooled male urine matrices.

## Limit of Detection for CT in Pooled Vaginal Swab Matrix

Elementary bodies from two CT serovars, ATCC vr885 serovar D and ATCC vr879 serovar H, were purified by centrifugation through a 30% sucrose cushion and titered by enumeration of elementary bodies using transmission electron microscopy. Each serovar was diluted into pooled negative vaginal swab matrix and tested with the Xpert CT/NG Assay. Replicates of 20 were evaluated at eight concentrations for CT

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serovar D and at seven concentrations for CT serovar H and LoDs were estimated by probit analysis. The claimed LoDs were confirmed by analyzing at least 20 replicate samples with elementary bodies diluted to the estimated LoD concentrations. For this study, the claimed LoD is defined as the lowest concentration at which 95% of at least 20 replicates are positive.

The claimed LoD for purified CT serovar D elementary bodies (EB) in vaginal swab matrix is 84 EB/mL. The claimed LoD for purified CT serovar H elementary bodies in vaginal swab matrix is 161 EB/mL (Table 13). In this study, LoDs for the remaining purified CT serovars (in EB/mL) are A (600), B (6), Ba (1900), C (34), E (6), F (202), G (96), I (21), J (150), K (117), LGV I (31), LGV II (20) and LGV III (210) EB/mL.

LoD of Two CT Serovars in Pooled Vaginal Swab Matrix

| Organism | LoD (EB/mL) |
| --- | --- |
| CT ATCC vr885 serovar D | 84 |
| CT ATCC vr879 serovar H | 161 |

## Limit of Detection for NG in Simulated Vaginal Swab Matrix

Two NG strains (ATCC 19424 and ATCC 49226) were tested. Replicates of 20 were evaluated at six concentrations. The LoD was estimated by probit analysis.

The LoD for NG, estimated by probit analysis, is 1.5 – 1.6 CFU/mL in a simulated swab matrix background (Table 14). An additional 30 NG strains were tested in a simulated matrix and the LoD was confirmed by testing replicates of three at or near the LoD.

LoD of Two NG Strains in Pooled Vaginal Swab Matrix

| Organism | LoD (CFU/mL) |
| --- | --- |
| NG ATCC19424 | 1.5 |
| NG ATCC49226 | 1.6 |

## Limit of Detection for CT in Pooled Male Urine Matrix

Purified and titered elementary bodies from two CT serovars, ATCC vr885 serovar D and ATCC vr879 serovar H, were each tested in a sample matrix of negative pooled male urine. Replicates of 20 were evaluated at eight concentrations for CT serovar D and at seven concentrations for CT serovar H and LoDs were estimated by probit analysis. The claimed LoDs were confirmed by analyzing at least 20 replicate samples with elementary bodies diluted to the estimated LoD concentrations. For this study, the claimed LoD is defined as the lowest concentration at which 95% of at least 20 replicates are positive.

The claimed LoD for purified CT serovar D elementary bodies in male urine matrix is 75 EB/mL. The claimed LoD for purified CT serovar H elementary bodies in male

23

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urine matrix is 134 EB/mL (Table 15). In this study, LoDs for the remaining purified CT serovars (in EB/mL) are A (900), B (11), Ba (3037), C (34), E (12), F (151), G (48), I (43), J (112), K (88), LGV I (31), LGV II (40) and LGV III (157).

LoD of Two CT Serovars in Pooled Male Urine Matrix

| Organism | LoD (EB/mL) |
| --- | --- |
| CT ATCC vr885 serovar D | 75 |
| CT ATCC vr879 serovar H | 134 |

## Limit of Detection for NG in Pooled Male Urine Matrix

Two NG strains, ATCC 19424 and ATCC 49226, were tested in a sample matrix of negative pooled male urine. Replicates of 20 were evaluated at six concentrations. The LoD was estimated by probit analysis.

The LoD for NG, estimated by probit analysis, is 1.2 – 2.7 CFU/mL in a male urine matrix background (Table 16). LoD for 30 additional NG strains was confirmed by testing replicates of three at or near the LoD.

LoD of Two NG Strains in Pooled Male Urine Matrix

| Organism | LoD (CFU/mL) |
| --- | --- |
| NG ATCC19424 (CFU/mL) | 2.7 |
| NG ATCC49226 (CFU/mL) | 1.2 |

## e. Inclusivity

Analytical reactivity of additional 13 serotypes and 30 additional NG strains was evaluated in the LoD studies above.

## f. Interference

The analytical performance of the assay was evaluated in the presence of potentially interfering substances that may be found in vaginal/endocervical swab and urine specimens. Potentially interfering exogenous substances were diluted into vaginal/endocervical swab simulated matrix and urine matrix containing two different mixtures of CT and NG cells. The first mixture contained CT serovar D and NG strain ATCC 49226, each at the 5x LoD concentration. The second mixture contained CT serovar H and NG strain ATCC 19424, each at the 5x LoD concentration.

The following table lists the highest concentration of each potential interferent tested, at which no assay interference was observed for samples in vaginal/endocervical matrix.

24

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Potentially Interfering Substances in Vaginal/Endocervical Matrix

| Substance | Concentration |
| --- | --- |
| Blood | 1.0% v/v |
| Mucin | 0.8% w/v |
| Seminal Fluid | 5.0% v/v |
| Hormones | 7mg/mL Progesterone + 0.07mg/mL Beta Estradiol |
| LGV II (CT EB) | 10^{6} EB/mL |
| Vagisil Anti-Itch Cream | 0.25% w/v |
| Clotrimazole Vaginal Cream | 0.25% w/v |
| Preparation H Hemorroidal Cream | 0.25% w/v |
| Miconazole 3 | 0.25% w/v |
| Monistat 1 | 0.25% w/v |
| Zovirax Cold Sore Cream | 0.25% w/v |
| Vagisil Moisturizer | 0.25% w/v |
| Vagi Gard Moisturizing Gel | 0.25% w/v |
| KY Jelly Personal Lubricant | 0.25% w/v |
| Yeast Gard Douche | 0.25% w/v |
| Delfen Vaginal Contraceptive Foam | 0.25% w/v |
| VH Essentials Povidone-Iodine Medicated Douche | 0.25% v/v |
| Leukocytes | 10^{6} cells/mL |

The following table lists the highest concentration of each potential interferent tested, at which no assay interference was observed for samples in urine matrix.

Potentially Interfering Substances in Urine Matrix

| Substance | Concentration |
| --- | --- |
| Blood | 0.3% v/v |
| Mucin | 0.2% v/v |
| Seminal Fluid | 5.0% v/v |
| Hormones | 7mg/mL Progesterone + 0.07mg/mL Beta Estradiol |
| LGV II (CT EB) | 10^{6} EB/mL |
| Leukocytes | 10^{6} cells/mL |
| Norforms Deodorant Suppositories | 0.25% w/v |
| BSA | 10mg/ml |
| Glucose | 10mg/mL |
| Bilirubin | 0.2mg/mL |
| Aspirin | 40mg/mL |
| Azithromycin | 1.8mg/mL |
| Doxycycline | 3.6 mg/mL |
| Organisms - UTI Candida albicans/ | 2.9 x 10^{4} CFU/mL |

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| Substance | Concentration |
| --- | --- |
| Staphylococcus aureus/Escherichia coli | |
| Acetaminophen | 3.2 mg/mL |
| Vagisil Feminine Powder | 0.25% w/v |
| Acidic Urine | pH 4.0 |
| Alkaline Urine | pH 9.0 |

With vaginal/endocervical specimens, assay interference may be observed in the presence of:

- Blood at a concentration greater than $1\%$ v/v;
- Mucin at a concentration greater than $0.8\%$ w/v.

With urine specimens, assay interference may be observed in the presence of:

- Blood at a concentration greater than $0.3\%$ v/v;
- Mucin at a concentration greater than $0.2\%$ w/v;
- Bilirubin at a concentration greater than $0.2\mathrm{mg / mL}$ (20 mg/dL);
Vagisil feminine powder at a concentration greater than $0.2\%$ w/v.

# g. Analytical specificity:

One hundred and one (101) different microorganisms at a concentration of at least $10^{6}$ CFU/mL or $10^{5}$ genome copies/mL were tested in replicates of three. All isolates were reported CT NOT DETECTED; NG NOT DETECTED; none of the organisms tested were detected by the Xpert CT/NG Assay. Positive and negative controls were included in the study.

Potential Cross-reacting Microorganisms in the Xpert CT/NG Assay

| Acinetobacter calcoaceticus | Herpes simplex virus I1 | Neisseria sicca (3) |
| --- | --- | --- |
| Acinetobacter Iwoffii | Herpes simplex virus II1 | Neisseria subflava (2) |
| Aerococcus viridans | Human papilloma virus1 | Paracoccus denitrificans |
| Aeromonas hydrophila | Kingella denitrificans | Peptostreptococcus anaerobius |
| Alcaligenes faecalis | Kingella kingae | Plesiomonas shigelloides |
| Arcanobacterium pyogenes | Klebsiella oxytoca | Propionibacterium acnes |
| Bacteriodes fragilis | Klebsiella pneumoniae | Proteus mirabilis |
| Bifidobacterium adolescentis | Lactobacillus acidophilus | Proteus vulgaris |
| Branhamella catarrhalis | Lactobacillus brevis | Providencia stuartii |
| Brevibacterium linens | Lactobacillus jensonii | Pseudomonas aeruginosa |
| Candida albicans | Lactobacillus lactis | Pseudomonas fluorescens |
| Candida glabrata | Legionella pneumophila | Pseudomonas putida |
| Candida parapsilosis | Leuconostoc paramensenteroides | Rahnella aquatilis |
| Candida tropicalis | Listeria monocytogenes | Saccharomyces cerevisiae |
| Chlamydia pneumoniae | Micrococcus luteus | Salmonella minnesota |
| Chlamydia trachomatis | Pseudomonas putida | Pseudomonas putida |
| Chlamydia trachomatis | Pseudomonas putida | Pseudomonas putida |
| Chlamydia trachomatis | Pseudomonas | Pseudomonas |

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| Chromobacterium violaceum | Moraxella lacunata | Salmonella typhimurium |
| --- | --- | --- |
| Citrobacter freundii | Moraxella osloensis | Serratia marcescens |
| Clostridium perfringens | Morganella morganii | Staphylococcus aureus |
| Corynebacterium genitalium | Mycobacterium smegmatis | Staphylococcus epidermidis |
| Corynebacterium xerosis | N. meningiditis | Staphylococcus saprophyticus |
| Cryptococcus neoformans | N. meningitidis Serogroup A | Streptococcus agalactiae |
| Cytomegalovirus1 | N. meningitidis Serogroup B | Streptococcus bovis |
| Eikenella corrodens | N. meningitidis Serogroup C | Streptococcus mitis |
| Entercoccus avium | N. meningitidis Serogroup D | Streptococcus mutans |
| Entercoccus faecalis | N. meningitidis Serogroup W135 | Streptococcus pneumoniae |
| Entercoccus faecium | N. meningitidis Serogroup Y | Streptococcus pyogenes |
| Enterobacter aerogenes | Neisseria cinerea | Streptococcus salivarius |
| Enterobacter cloacae | Neisseria dentrificans | Streptococcus sanguis |
| Erysipelothrix rhusiopathiae | Neisseria elongata (3) | Streptococcus griseinus |
| Escherichia coli | Neisseria flava | Vibrio parahaemolyticus |
| Elizabethkingia meningoseptica2 | Neisseria flavescens (2) | Yersinia enterocolitica |
| Fusobacterium nucleatum | Neisseria lactamica (5) | |
| Gardnerella vaginalis | Neisseria mucosa (3) | |
| Gemella haemolysans | Neisseria perflava | |
| Haemophilus influenzae | Neisseria polysaccharea | |

(n) number of strains tested
1 Tested at $1 \times 10^{5}$ genome copies/mL
2 Previously known as Flavobacterium meningosepticum

# h. Carryover/Cross-contamination

A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent carry-over contamination in negative samples run following very high positive samples in the same GeneXpert module. The study consisted of a negative sample processed in the same GeneXpert module immediately following a sample with high CT spike $(1.9 \times 10^{4} \mathrm{EB/mL})$ and a high NG spike $(5.2 \times 10^{5} \mathrm{CFU/mL})$ . Two sample types were used for this testing: a) known pooled negative urine samples; and b) known pooled negative swab samples. Each sample type was tested in each of four GeneXpert modules for a total of 44 runs for both swab and urine samples resulting in 20 positives and 24 negatives. All 40 positive samples were correctly reported as CT DETECTED; NG DETECTED. All 48 negative samples were correctly reported as CT NOT DETECTED; NG NOT DETECTED. There was no cross-contamination observed during this study.

# i. Assay cut-off:

The valid cycle threshold (Ct) range for the C. trachomatis CT1 analyte, the N. gonorrhoeae analyte 1 (NG2), the N. gonorrhoeae analyte 2 (NG4), and the Sample Adequacy Control (SAC) is 12 to 45. The valid Ct range for the Sample Processing Control (SPC) is 25 to 45. For a valid "NG DETECTED" result, Cts for both N.

{27}

gonorrhoeae analytes (NG2 and NG4) must be reported in the valid detectable range. These cutoffs maximize sensitivity without specificity falling below $98\%$ . The cutoff of 45 Cts for each target was validated in the clinical study.

# 2. Comparison studies

# a. Comparison with predicate device:

The comparison studies were conducted in a clinical study with prospectively collected samples (see the Clinical studies section below). The performance of the Xpert CT/NG assay with patient specimens was evaluated by comparison to a Patient Infected Status (PIS) algorithm based on a combination of results from two sample types (matrices) each tested by two predicate devices. A patient was considered infected (I), for CT or for NG, if at least one positive result for the respective organism was obtained from each reference assay. Any other combination of results was categorized as not infected (NI). In this study, reference testing was performed using endocervical swab specimens and urine specimens from females, and urethral swabs and urine specimens from male patients. Result obtained by Xpert CT/NG assay for each claimed specimen type (female endocervical swabs and self-collected vaginal swabs, female urine specimens and male urine specimens) was evaluated against the Patient Infected Status (PIS). One exception was made for females with positive results on both reference urine specimens and negative results on both reference swab specimens; these patients were categorized as infected (I) for urine and not infected (NI) for the swab specimens.

The table below shows the results from symptomatic and asymptomatic females designated as infected or not infected with CT based on the PIS algorithm.

Patient Infected Status - Female CT

| PISa | NAAT1 | | NAAT2 | | Xpert | | | Symptom Status | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SWa | URa | SW | UR | PC-VSa | ESa | UR | Symp | Asymp | |
| NIb | - | - | - | - | - | - | - | 1160 | 2269 | 3429 |
| NI | - | - | - | - | IND | - | - | 6 | 8 | 14 |
| NI | - | - | - | - | - | INDc | - | 6 | 16 | 22 |
| NI | - | - | - | - | - | - | IND | 5 | 6 | 11 |
| NI | - | - | - | - | + | + | - | 0 | 1 | 1 |
| NI | - | - | - | - | + | - | - | 6 | 4 | 10 |
| NI | - | - | - | - | - | + | - | 3 | 5 | 8 |
| NI | - | - | - | - | - | - | + | 1 | 0 | 1 |
| NI | - | - | - | EQd | - | - | - | 6 | 20 | 26 |
| NI | - | - | - | EQ | IND | IND | - | 1 | 0 | 1 |
| NI | - | - | EQ | - | - | - | - | 3 | 4 | 7 |
| NI | - | - | EQ | - | - | - | IND | 1 | 0 | 1 |
| NI | - | - | - | + | - | - | - | 0 | 7 | 7 |
| NI | - | - | + | - | - | - | - | 3 | 0 | 3 |

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| PISa | NAAT1 | | NAAT2 | | Xpert | | | Symptom Status | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SWa | URa | SW | UR | PC-VSa | ESa | UR | Symp | Asymp | |
| NI | - | - | + | - | - | + | - | 0 | 1 | 1 |
| NIf | - | + | - | + | + | - | + | 7 | 1 | 8 |
| NIf | - | + | - | + | + | - | - | 0 | 1 | 1 |
| NIf | - | + | - | + | - | - | + | 0 | 1 | 1 |
| NI | - | + | - | - | - | - | - | 1 | 0 | 1 |
| NI | - | + | - | - | + | - | + | 1 | 0 | 1 |
| NI | + | - | - | - | - | - | - | 4 | 8 | 12 |
| NI | + | - | - | - | + | - | - | 2 | 1 | 3 |
| NI | + | - | - | - | + | + | - | 1 | 2 | 3 |
| NI | + | - | - | - | - | + | - | 0 | 1 | 1 |
| NI | + | + | - | - | - | - | - | 1 | 0 | 1 |
| NI | + | + | - | - | - | - | + | 0 | 1 | 1 |
| NI | + | + | - | - | + | + | + | 1 | 1 | 2 |
| NI | + | + | - | - | + | - | + | 1 | 0 | 1 |
| NI | + | + | - | - | + | - | - | 1 | 0 | 1 |
| Total Non-Infected | | | | | | | | 1221 | 2358 | 3579 |
| Ie | + | + | + | + | + | + | + | 65 | 104 | 169 |
| I | + | + | + | + | IND | + | + | 0 | 1 | 1 |
| I | + | + | + | + | + | IND | + | 0 | 1 | 1 |
| I | + | + | + | + | + | + | IND | 1 | 0 | 1 |
| I | + | + | + | + | - | + | + | 0 | 1 | 1 |
| I | + | + | + | + | + | - | + | 0 | 1 | 1 |
| If | - | + | - | + | + | - | + | 7 | 1 | 8 |
| If | - | + | - | + | + | - | - | 0 | 1 | 1 |
| If | - | + | - | + | - | - | + | 0 | 1 | 1 |
| I | - | + | + | + | + | + | + | 0 | 2 | 2 |
| I | + | - | + | + | + | + | + | 1 | 0 | 1 |
| I | + | - | + | + | + | - | + | 0 | 1 | 1 |
| I | + | - | + | + | + | + | + | 1 | 0 | 1 |
| I | + | + | - | + | + | - | + | 3 | 2 | 5 |
| I | + | + | - | + | + | + | + | 4 | 2 | 6 |
| I | + | + | + | - | + | + | + | 3 | 4 | 7 |
| I | + | + | + | - | + | + | - | 1 | 1 | 2 |
| I | + | + | + | - | + | - | + | 0 | 1 | 1 |
| I | + | - | + | - | + | + | + | 1 | 0 | 1 |
| I | + | - | EQ | + | + | + | + | 0 | 1 | 1 |
| Total Infected | | | | | | | | 87 | 125 | 212 |

${}^{a}$ PIS = Patient Infected Status; SW = swab; UR = urine; PC-VS = patient-collected vaginal swab; ES = endocervical swab
${}^{\mathrm{b}}\mathrm{NI} =$ Non-infected
${}^{c}$ IND = Indeterminate - ERROR,INVALID or NO RESULT by Xpert CT/NG Assay; specimens with IND results by Xpert are not included in the performance tables for that specimen type.
${}^{d}$ EQ = Equivocal result for this individual specimen type only; PIS status determined based on remaining specimens.
${}^{\mathrm{e}}\mathrm{I} =$ Infected
These samples are infected for urine and non-infected for swabs. In this table they appear twice.

The table below shows the results from symptomatic and asymptomatic females designated as infected or not infected with NG based on the PIS algorithm.

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Patient Infected Status – Female NG

| PIS^{a} | NAAT1 | | NAAT2 | | Xpert | | | Symptom Status | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SW^{a} | UR^{a} | SW | UR | PC-VS^{a} | ES^{a} | UR | Symp | Asymp | |
| NI^{b} | - | - | - | - | - | - | - | 1229 | 2390 | 3619 |
| NI | - | - | - | - | IND^{c} | - | - | 6 | 9 | 15 |
| NI | - | - | - | - | - | IND | - | 6 | 17 | 23 |
| NI | - | - | - | - | - | - | IND | 6 | 6 | 12 |
| NI | - | - | - | - | + | - | + | 0 | 1 | 1 |
| NI | - | - | - | - | + | - | - | 1 | 0 | 1 |
| NI | - | - | EQ^{d} | - | - | - | - | 2 | 5 | 7 |
| NI | - | - | - | EQ | - | - | - | 9 | 20 | 29 |
| NI | - | - | - | + | - | - | - | 1 | 3 | 4 |
| NI | - | - | + | - | - | - | - | 7 | 4 | 11 |
| NI^{f} | - | + | - | + | + | + | + | 1 | 0 | 1 |
| NI^{f} | - | + | - | + | - | - | + | 1 | 0 | 1 |
| NI | - | - | + | + | - | - | - | 1 | 0 | 1 |
| NI | + | - | - | - | - | - | - | 1 | 1 | 2 |
| NI | - | - | EQ | - | - | - | IND | 1 | 0 | 1 |
| NI | - | - | - | EQ | - | IND | IND | 1 | 0 | 1 |
| Total Non-Infected | | | | | | | | 1273 | 2456 | 3729 |
| I^{e} | + | + | + | + | + | + | + | 19 | 19 | 38 |
| I | + | + | + | - | + | + | + | 2 | 2 | 4 |
| I | + | - | + | + | + | + | + | 1 | 1 | 2 |
| I^{f} | - | + | - | + | + | + | + | 1 | 0 | 1 |
| I^{f} | - | + | - | + | - | - | + | 1 | 0 | 1 |
| I | + | - | + | - | + | + | - | 1 | 2 | 3 |
| I | + | - | + | - | + | + | + | 1 | 0 | 1 |
| I | + | + | - | + | + | + | + | 1 | 0 | 1 |
| I | + | + | + | EQ | + | + | + | 0 | 1 | 1 |
| I | + | + | EQ | + | + | + | + | 1 | 0 | 1 |
| I | + | EQ | + | - | + | + | + | 1 | 0 | 1 |
| Total Infected | | | | | | | | 29 | 25 | 54 |

aPIS = Patient Infected Status; SW = swab; UR = urine; PC-VS = patient-collected vaginal swab; ES = endocervical swab
bNI = Non-infected
cIND = Indeterminate – ERROR, INVALID or NO RESULT by Xpert CT/NG Assay; specimens with IND results by Xpert are not included in the performance tables for that specimen type.
dEQ = Equivocal result for this individual specimen type only; PIS status determined based on remaining specimens.
fI = Infected
These samples are infected for urine and non-infected for swabs. In this table they appear twice.

The table below shows the results from symptomatic and asymptomatic males designated as infected or not infected with CT based on the PIS algorithm.

Patient Infected Status – Male CT

| PIS^{a} | NAAT1 | | NAAT2 | | GX | Symptom Status | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SW^{a} | UR^{a} | SW | UR | UR | Symp | Asymp | |
| NI^{b} | - | - | - | - | - | 568 | 2621 | 3189 |
| NI | - | - | - | EQ^{c} | - | 0 | 19 | 19 |
| NI | - | - | + | - | - | 2 | 1 | 3 |
| NI | + | - | - | - | - | 6 | 1 | 7 |

{30}

The table below shows the results from symptomatic and asymptomatic males designated as infected or not infected with NG based on the PIS algorithm.

| Patient Infected Status – Male NG | | | | | |
| --- | --- | --- | --- | --- | --- |
| PISa | NAAT1 | | NAAT2 | | GX |
| | SWa | URa | SW | UR | UR |
| NIb | - | - | - | - | - |
| NI | - | - | - | - | - |
| NI | - | - | EQc | - | 0 |
| NI | - | - | - | - | 0 |
| NI | - | - | + | - | 0 |
| NI | - | - | + | - | 0 |
| NI | - | - | + | - | 0 |
| NI | + | - | - | - | 2 |
| NI | - | EQ | - | - | 0 |
| NI | + | - | - | - | 0 |
| NI | + | - | - | - | 0 |
| Total Non-Infected | | | | | |
| Ie | + | + | + | + | + |
| I | + | + | - | + | + |
| I | + | + | - | + | + |
| I | + | + | + | - | + |
| I | + | - | + | - | + |
| I | + | + | + | - | + |

aPIS = Patient Infected Status; SW = Swab; UR = urine.
bNI = Non-infected
cEQ = Equivocal result for this individual specimen type only; PIS status determined based on remaining specimens.
dIND = Indeterminate - ERROR, INVALID or NO RESULT by Xpert CT/NG Assay; specimens with IND results by Xpert are not included in the performance tables for that specimen type.
eI = Infected

| PISa | SWa | URa | SW | UR | UR |
| --- | --- | --- | --- | --- | --- |
| NIb | - | - | - | - | - |
| NI | - | - | - | - | - |
| NI | - | - | EQc | - | 0 |
| NI | + | - | + | - | 0 |
| NI | - | - | + | - | 0 |
| NI | - | - | + | - | 0 |
| NI | + | - | - | - | 0 |
| NI | - | - | - | - | 0 |
| NI | - | - | + | - | 0 |

{31}

| PISa | NAAT1 | | NAAT2 | | GX | Symptom Status | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SWa | URa | SW | UR | UR | Symp | Asymp | |
| I | + | - | + | - | - | 0 | 1 | 1 |
| I | + | - | - | + | - | 1 | 0 | 1 |
| Total Infected | | | | | | 106 | 13 | 119 |

$^{\mathrm{a}}$ PIS = Patient Infected Status; SW = Swab; UR = urine.
$\mathrm{NI} =$ Non-infected
$^{\mathrm{c}}$ EQ = Equivocal result for this individual specimen type only; PIS status determined based on remaining specimens.
$^{\mathrm{d}}$ IND = Indeterminate - ERROR, INVALID or NO RESULT by Xpert CT/NG Assay; specimens with IND results by Xpert are not included in the performance tables for that specimen type.
$\mathrm{I} =$ Infected

# b. Matrix comparison:

Each claimed specimen type was evaluated individually against the Patient Infected Status algorithm, as presented above.

# 3. Clinical studies:

# a. Prospective Clinical Studies:

The performance of the Xpert CT/NG assay was evaluated in a multi-site investigational study comparing the Xpert CT/NG Assay on the GeneXpert instrument systems to a patient infected status algorithm (PIS) based on results from the BD ProbeTec™ ET Chlamydia trachomatis and Neisseria gonorrhoeae Amplified DNA Assays, and the Gen-Probe® APTIMA Combo 2® Assay. The study included prospectively collected male urine, male urethral swab, female urine, endocervical swab, and patient-collected vaginal swab (collected in a clinical setting) specimens. Specimens included in the study were collected at 36 geographically diverse sites (including four sites located in the United Kingdom) from consenting asymptomatic and symptomatic, sexually active males and females seen at locations including, but not limited to: OB/GYN, sexually transmitted disease (STD), teen, public health, and family planning clinics. All reference testing was conducted at one of two central testing laboratories. Collection-only sites also shipped specimens to laboratories for Xpert testing. Collection and testing sites conducted Xpert testing on site. There were 36 collection sites and 15 testing sites. Nine testing sites used the GeneXpert Dx system, five sites used the GeneXpert 16 system and one site used the Infinity 48 and the Infinity 80 systems. Site personnel performing the Xpert CT/NG Assay testing were trained prior to performing any study procedures. The training included the minimum requirements to be eligible for CLIA moderate complexity. Three external controls (commercially available), one positive for Neisseria gonorrhoeae, one positive for Chlamydia trachomatis and one negative (human cell line) control, were run each day of testing to monitor the performance of the Xpert CT/NG Assay. A total of 1525 controls were run during the study (502 negative, 525 CT positive, 498 NG negative).

The study subjects ranged from 17 to 61 years of age. Each female study participant provided three endocervical swabs, one self-collected vaginal swab (collected in a

{32}

clinical setting), and one urine specimen. Each male study participant provided one urine specimen and two urethral swabs.

Performance of the Xpert CT/NG Assay was calculated relative to the PIS for each of the three female sample types (endocervical swabs, patient-collected vaginal swabs and urine), and male urine.

## Performance with Chlamydia trachomatis

Among the 3781 females, a total of 212 female subjects were infected with CT. Symptoms were reported in 41.0% (87/212) of infected and 34.1% (1221/3579) non-infected female subjects. Among the 3444 males, 196 male subjects were infected with CT. The calculated sensitivity, specificity, and predictive values (based on the prevalence of infection observed during the study) of the Xpert CT/NG Assay for CT, compared against the PIS algorithm, are presented by gender, sample type, and symptom status in the following table.

### Xpert CT/NG Assay vs. Patient Infected Status for CT Detection

| Specimen | | Sx Status | n | TP | FP | TN | FN | Prev % | Sensitivity % (95 CI) | Specificity % (95 CI) | PPV % (95 CI) | NPV % (95 CI) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Female | PC-VS | Sym | 1294 | 79 | 20 | 1195 | 0 | 6.1 | 100 (95.4-100) | 98.4 (97.5-99.0) | 79.8 (70.5-87.2) | 100 (99.7-100) |
| | | Asym | 2472 | 121 | 11 | 2339 | 1 | 4.9 | 99.2 (95.5-100) | 99.5 (99.2-99.8) | 91.7 (85.6-95.8) | >99.9 (99.8-100) |
| | | All | 3766 | 200 | 31 | 3534 | 1 | 5.3 | 99.5 (97.3-100) | 99.1 (98.8-99.4) | 86.6 (81.5-90.7) | >99.9 (99.8-100) |
| | | | | | | | | | | | | |
| | ES | Sym | 1293 | 76 | 5 | 1209 | 3 | 6.1 | 96.2 (89.3-99.2) | 99.6 (99.0-99.9) | 93.8 (86.2-98.0) | 99.8 (99.3-99.9) |
| | | Asym | 2464 | 117 | 11 | 2331 | 5 | 5.0 | 95.9 (90.7-98.7) | 99.5 (99.2-99.8) | 91.4 (85.1-95.6) | 99.8 (99.5-99.9) |
| | | All | 3757 | 193 | 16 | 3540 | 8 | 5.4 | 96.0 (92.3-98.3) | 99.6 (99.3-99.7) | 92.3 (87.9-95.6) | 99.8 (99.6-99.9) |
| | | | | | | | | | | | | |
| | Urine | Sym | 1292 | 84 | 4 | 1203 | 1 | 6.6 | 98.8 (93.6-100) | 99.7 (99.2-99.9) | 95.5 (88.8-98.7) | 99.9 (99.5-100) |
| | | Asym | 2475 | 123 | 2 | 2347 | 3 | 5.1 | 97.6 (93.2-99.5) | 99.9 (99.7-100) | 98.4 (94.3-99.8) | 99.9 (99.6-100) |
| | | All | 3767 | 207 | 6 | 3550 | 4 | 5.6 | 98.1 (95.2-99.5) | 99.8 (99.6-99.9) | 97.2 (94.0-99.0) | 99.9 (99.7-100) |
| | | | | | | | | | | | | |
| | | | | | | | | | | | | |
| Male | Urine | Sym | 706 | 120 | 2 | 581 | 3 | 17.4 | 97.6 (93.0-99.5) | 99.7 (98.8-100) | 98.4 (94.2-…