Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on standard PCR amplification and detection methods, and there is no mention of AI or ML in the device description, intended use, or performance studies.

Therapeutic

No
Explanation: This device is an in vitro diagnostic test designed to detect the DNA of specific bacteria to aid in the diagnosis of chlamydial and gonococcal disease. It does not provide treatment or therapy.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the test is used "to aid in the diagnosis of chlamydial and gonococcal disease."

SaMD (Software as a Medical Device)

No

The device description explicitly lists multiple reagent kits and sample collection kits, which are physical components. It also describes the use of the cobas x 480 Instrument and cobas z 480 Analyzer, which are hardware instruments. While software is mentioned as integrating the processes, the device is clearly a system involving both hardware and software for sample preparation, amplification, and detection.

IVD (In Vitro Diagnostic)

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 cobas® CT/NG Test is an "in vitro nucleic acid amplification test" used "to aid in the diagnosis of chlamydial and gonococcal disease." This clearly indicates that the device is intended to be used outside of the body to analyze specimens for diagnostic purposes.
Device Description: The description details the components of the test, including reagent kits and sample collection kits, which are typical for in vitro diagnostic devices. It also describes the process of analyzing biological specimens (nucleic acid amplification and detection).
Clinical Performance Studies: The document describes clinical studies where the device was used to test human specimens (vaginal swabs, urine, etc.) and the results were compared to reference assays to evaluate its performance in diagnosing CT and NG infections. This is a standard process for validating IVD devices.
Predicate Devices: The mention of predicate devices, which are other commercially available IVD tests for CT and NG, further confirms the device's classification as an IVD.

The definition of an In Vitro Diagnostic (IVD) device is a medical device that is intended for use in vitro for the examination of specimens, including blood, tissue, and urine, derived from the human body, solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to monitor therapeutic measures. The description provided perfectly aligns with this definition.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The cobas® CT/NG Test is an in vitro nucleic acid amplification test that utilizes Polymerase Chain Reaction (PCR) and nucleic acid hybridization for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonormoeae (NG) DNA to aid in the diagnosis of chlamydial and gonococcal disease. The test may be used with vaginal swab specimens self-collected in a clinical setting and male urine from both symptomatic and asymptomatic individuals. Specimens to be tested should be collected in cobas® PCR Media.

Ancillary Collection Kits

The cobas® PCR Female Swab Sample Kit is used to collect and transport self-collected vaginal swab specimens in a clinical setting. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG Test. NOTE: This collection kit should not be used for collection of alternative gynecological specimens.

The cobas® PCR Urine Sample Kit is used to collect and transport male urine specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas® CT/NG Test. NOTE: This collection kit should not be used for collection of female urine specimens.

Product codes (comma separated list FDA assigned to the subject device)

MKZ, LSL, OOI

Device Description

The Roche Molecular Systems (RMS) cobas® CT/NG Test consists of five reagent kits:

cobas® 4800 System Sample Preparation Kit .
cobas® 4800 CT/NG Amplification/Detection Kit .
cobas® 4800 CT/NG Controls Kit .
. cobas 4800 System Wash Buffer Kit
. cobas® 4800 System Control Diluent Kit

Sample Collection Kits to be used for the cobas® CT/NG Test are:

. cobas® PCR Female Swab Sample Kit
cobas® PCR Urine Sample Kit .

The cobas® CT/NG Test for Chlamvdia trachomatis (CT) and Neisseria gonorrhoeae (NG) is based on two major processes: (1) automated sample preparation to obtain nucleic acids. including CT and NG DNA; (2) simultaneous PCR amplification of target DNA sequences using both CT and NG specific complementary primer pairs and real-time detection of cleaved fluorescent-labeled CT and NG specific oligonucleotide detection probes. Internal control, containing CT and NG DNA, is added to all samples during automated sample preparation and is amplified and detected simultaneously with each sample to monitor the entire process.

The cobas 4800 System utilizes the cobas x 480 Instrument for automated sample preparation, and the automated cobas z 480 Analyzer for automated amplification and detection. The cobas 4800 system software integrates the sample preparation with nucleic acid amplification and detection to generate test results.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Vaginal swab specimens, male urine, (for female subjects: urine, clinician- or self-collected vaginal swab, endocervical swabs, and a cervical sample; for male subjects: urethral swabs and urine specimens)

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

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 across lot, testing site, operator, run, and day for the cobas 8 CTNG Test using 2 panels prepared from swabs and urine collected in cobas PCR Media. A run for cobas® PCR Media (urine or swab) included 3 replicates of each of 5 panel members and 1 positive and 1 negative control (17 total tests). If cobas PCR Media panels were combined in a run, only 1 positive and 1 negative control were included (32 total tests). The 2 operators at each site performed 2 runs per day, for a total of 3 days of testing per operator per panel type (6 days of testing total for each panel type and reagent lot). Testing was performed with 2 reagent lots (6 days of testing per lot).

Overall. 74 runs were performed. and 72 valid runs were obtained for urine and swab panel types. The 2 invalid runs were due to instrument errors. A total of 1,080 tests were performed on the 5 panel members for each panel type in the valid runs. There was 1 invalid test result in the urine panel type, and 2 invalid test results in the swab panel type. These invalid tests were due to instrument errors.

All valid test results were included in the analyses that reported the percent agreement for CT and NG for each panel type separately. There were no false positive results for either analyte (CT and NG) for both panel types for negative panel members, thus giving negative percent agreement (NPA) of 100% for each analyte.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

The analytical sensitivity (Limit of Detection or LOD) for the cobas® CT/NG Test was determined by analyzing dilutions of quantified CT and NG cultures of CT and NG were diluted into negative vaginal swab specimen in cobas® PCR Media and negative urine specimen plus cobas® PCR Media to determine the LOD for vaginal swab and urine specimens, respectively. All levels were analyzed using the full cobas® CT/NG Test workflow across 3 unique lots of cobas® CT/NG Test reagents. This test defines LOD as the target concentration which can be detected as positive in ≥ 95% of the replicates tested with each reagent lot.

The sensitivity of the cobas CT/NG Test was determined for 14 additional CT serovars, the Swedish new variant (nvCT) strain and an additional 44 independently isolated strains of NG. Testing was done to demonstrate that these targets can be detected around the LOD levels determined during analytical sensitivity testing for the CT serovar D culture and NG strain 19424. Panels were prepared as described for the LOD study with the number of panel levels varying from 1 to 5, as required. At least 49 replicates were tested for each panel level using one lot of cobas CT/NG Test reagents.

Competitive inhibition testing: Panels were prepared by spiking CT and NG cultures into urine and vaginal specimens stabilized in cobas® PCR Media to various concentration levels to examine the potential for competitive inhibition. Panels were prepared with two strains each of CT and NG. Panels were tested in one run per day over the course of 5 days. Two replicates of each panel member were tested in every run, generating a maximum of 10 test results for each level and CT and NG strain respectively. All CT and NG hit rates were 100% for all panel levels in both matrices. Competitive inhibition was not seen in any combination of CT and NG levels in either matrix.

Analytical specificity: A panel of 184 bacteria, fungi and viruses, including those commonly found in the male/female urogenital tract, as well as representatives of N. cineria, N. flava, N. lactamica, N. perflava and N. subflava and other phylogenetically related organisms, were tested with the cobas® CT/NG Test to assess analytical specificity. The organisms were spiked at high concentrations into CT/NG negative urine specimens plus cobas PCR Media and pooled negative vaginal specimen spiked with CT and NG cultures at 3 times the limit of detection. Results indicated that none of these organisms interfered with detection of CT and NG or produced a false positive result in the CT/NG negative matrices.

Interference testing: Interference testing was performed using cobas® PCR Media plus negative urine and negative vaginal swab specimen spiked with CT and NG cultures at ~ 3 x LOD for each target. Eighteen over-the-counter (OTC) products, including contraceptive jelly, lubricants, feminine sprays, antifungal cream and anti-itch cream, as well as whole blood, cervical mucus and PBMC cells were tested for interference. Of the 18 OTC products tested, Replens® vaginal moisturizer produced invalid and/or false negative results in the cobas® PCR Media plus negative urine panel samples. No interference from Replens® vaginal moisturizer was observed with vaginal swab specimens tested. The levels of whole blood, mucus and PBMC cells shown in Table 10 represent maximum allowable concentrations which will not interfere with cobas® CT/NG Test performance.

Precision: Precision of the cobas CT/NG Test was examined in-house using a test panel composed of CT and NG cultures diluted into cobas® PCR Media and cobas® PCR Media mixed with negative urine. The precision panel was designed to include members with either CT or NG at approximately the LOD for the panel matrix, members with both CT and NG at approximately the LOD and 2.5 x LOD for the panel matrix and a negative level. Testing was done with three unique lots of cobas CT/NG Test reagents and three instruments for a total of 24 runs. All positive panel levels yielded the anticipated hit rates. All negative panel levels tested negative throughout the study.

Clinical performance: Performance characteristics of the cobas CT/NG Test were evaluated in a multi-center clinical study conducted in the United States. Specimens were collected at 12 geographically diverse sites including OB-GYN practices, public and private STD clinics, and family planning centers. A total of 2,851 evaluable male and female, symptomatic and asymptomatic subjects were enrolled. Subjects were classified as symptomatic if the subject reported symptoms indicative of CT or NG infection. Specimens collected from each female subject included urine, a clinician- or self-collected vaginal swab, endocervical swabs, and a cervical sample in PreservCyt" Solution (Hologic Corporation, Bedford MA) obtained with a spatula/cytobrush or a broom. Male subjects provided urethral swabs and urine specimens. Specimens were tested using the cobas CT/NG Test and two commercially available nucleic acid amplification tests (NAAT) for CT and NG. The NAATs were used as reference assays in the clinical study.
For each subject, a patient infected status (PIS) was determined based on the combined results from the reference assays. A subject was categorized as infected for CT or NG if a minimum of two positive results (at least one from each reference NAAT) was reported, as described in Table 14. Female subjects with positive results on both reference urine specimens and negative results on both reference endocervical swab specimens and the reference cervical sample were categorized as infected for urine and not infected for swab specimens. A subject was classified as non-infected if at least one of the reference NAATs reported negative results for all sample types.
Results from the cobas CT/NG Test were compared with the PIS for calculation of test sensitivity and specificity. A total of 21,988 CT and 21,987 NG results were analyzed by sex, sample type, and the presence of symptoms.
The overall sensitivity and specificity for CT was 95.7% and 99.7%. The overall prevalence was 9.0% for CT (6.3% in women and 16.4% in men). The overall sensitivity and specificity for NG was 99.0% and 99.9%. The overall prevalence was 3.6% for NG (1.6% in women. 9.2% in men).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Overall sensitivity and specificity for CT: 95.7% and 99.7%.
Overall prevalence for CT: 9.0% (6.3% in women and 16.4% in men).
Overall sensitivity and specificity for NG: 99.0% and 99.9%.
Overall prevalence for NG: 3.6% (1.6% in women, 9.2% in men).

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

Gen-Probe APTIMA Combo 2 Assay (K060652), BD ProbeTec Q* Chlamydia trachomatis Amplified DNA Assay (K091724), BD ProbeTec Q* Neisseria gonorrhoeae Amplified DNA Assay' (K091730), Abbott multi-Collect Specimen Collection Kit (K092704)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3120 Chlamydia serological reagents.

(a)
Identification. Chlamydia serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to chlamydia in serum. Additionally, some of these reagents consist of chlamydia antisera conjugated with a fluorescent dye used to identify chlamydia directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusChlamydia and provides epidemiological information on these diseases. Chlamydia are the causative agents of psittacosis (a form of pneumonia), lymphogranuloma venereum (a venereal disease), and trachoma (a chronic disease of the eye and eyelid).(b)
Classification. Class I (general controls).

Summary

0

Roche Molecular Systems, Inc. Pleasanton, CA 94588-2722

JAN 2 4 2012

K110923

cobas® CT/NG Test Section 5: 510(k) Summary 510(k) Summary Report

cobas® CT/NG Test 510(k) Summary

| Submitted by: | Roche Molecular Systems, Inc.
4300 Hacienda Drive
Pleasanton, CA 94588-2722
Phone Number: (925) 730-8729
Fax Number: (925) 730-8128 |
|---------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | James Bonds |
| Date of Preparation: | January 24, 2012 |
| Device Trade Name: | cobas® CT/NG Test |
| Common Name: | Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) Test |
| Type of Test: | Nucleic Acid Amplification Test, DNA, Chlamydia trachomatis (CT) and
Neisseria gonorrhoea (NG), qualitative |
| Classification Names: | Chlamydia serological reagents
Neisseria spp. Direct serological test reagents
Real Time Nucleic Acid Amplification System |
| Regulations: | 866.3120
866.3390
862.2570 |
| Product codes: | MKZ (DNA Probe, Nucleic Acid Amplification, Chlamydia)
LSL (DNA Reagents, Neisseria)
OOI (Real Time Nucleic Acid Amplification System) |
| Panel: | Microbiology |
| Predicate Devices - Assay: | Gen-Probe APTIMA Combo 2 Assay (K060652)
BD ProbeTec Q* Chlamydia trachomatis Amplified DNA Assay (K091724)
and BD ProbeTec Q* Neisseria gonorrhoeae Amplified DNA Assay'
(K091730) |
| Predicate Device - Collection
Kits | Abbott multi-Collect Specimen Collection Kit (K092704) |

510(k) Premarket Notification

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------↓ 510(k) Summary Report Page 1

」

r

1

1.			Device Description
2.	Intended Use
3.	Technological Characteristics
4.	Non-Clinical Performance Evaluation
	4.1.		Analytical Sensitivity
	4.2.		Inclusivity
	4.3.		Analytical Specificity
	4.4.		Interference
	4.5.		Precision
5.			Clinical Performance
	5.1.		Reproducibility
		5.1.1.	C. trachomatis (Table 10 and Table 11)
		5.1.2.	N. gonorrhoeae (Table 12 and Table 13)
	5.2.		Clinical Specimen Study
		5.2.1.	Study Design
		5.2.2.	Determination of Patient Infected Status
		5.2.3.	Study Results
		5.2.4.	Conclusion Drawn from Clinical Specimen Study
6.			Conclusion

List of Tables

Table 1: Comparison of the cobas® CT/NG Test with the Predicate Devices	6
Table 2: Comparison of the cobas® PCR Sample Collection Devices with the Predicate Device	7
Table 3: cobas® CT/NG Test Limit of Detection	8
Table 4: Summary of CT Serovars/Variant Inclusivity Verification Results	9
Table 5: Summary of NG Strains Inclusivity Verification Results	10
Table 6: Microorganisms Tested for Analytical Specificity
Table 7: List of Microorganisms Tested Below 1 x 106 copies/mL for Analytical Specificity 13
Table 8: Results from Endogenous Interference Testing
Table 9: In-House Precision Study Hit Rate Analysis
Table 10: C. trachomatis: Percent Agreement by Panel Member for Lot, Site/Instrument, and
Day - PCR Media/Urine
Table 11: C. trachomatis: Percent Agreement by Panel Member for Lot, Site/Instrument, and
Day - PCR Media/Swab
Table 12: N. gonorrhoeae: Percent Agreement by Panel Member for Lot, Site/Instrument, and
Day - PCR Media/Urine
Table 13: N. gonorrhoeae: Percent Agreement by Panel Member for Lot, Site/Instrument, and
Day - PCR Media/Swab
Table 14: Determination of Patient Infected Status
Table 15: CT Clinical Performance Compared with Patient Infected Status by Gender, Sample
Type, and Symptom Status
Table 16: NG Clinical Performance Compared With Patient Infected Status by Gender, Sample
Type, and Symptom Status
Table 17: CT Positive/Negative Analysis for Female Patient Infected Status
Table 18: CT Positive/Negative Analysis for Male Patient Infected Status
Table 19: NG Positive/Negative Analysis for Female Patient Infected Status
Table 20: NG Positive/Negative Analysis for Male Patient Infected Status
Table 21: Positive Predictive Value and Negative Value for Hypothetical CT
Prevalence
Table 22: Positive Predictive Value and Negative Value for Hypothetical NG
Prevalence

2

3

DEVICE DESCRIPTION 1.

The Roche Molecular Systems (RMS) cobas® CT/NG Test consists of five reagent kits:

cobas® 4800 System Sample Preparation Kit .
cobas® 4800 CT/NG Amplification/Detection Kit .
cobas® 4800 CT/NG Controls Kit .
. cobas 4800 System Wash Buffer Kit
. cobas® 4800 System Control Diluent Kit

Sample Collection Kits to be used for the cobas® CT/NG Test are:

. cobas® PCR Female Swab Sample Kit
cobas® PCR Urine Sample Kit .

The cobas® CT/NG Test for Chlamvdia trachomatis (CT) and Neisseria gonorrhoeae (NG) is based on two major processes: (1) automated sample preparation to obtain nucleic acids. including CT and NG DNA; (2) simultaneous PCR amplification of target DNA sequences using both CT and NG specific complementary primer pairs and real-time detection of cleaved fluorescent-labeled CT and NG specific oligonucleotide detection probes. Internal control, containing CT and NG DNA, is added to all samples during automated sample preparation and is amplified and detected simultaneously with each sample to monitor the entire process.

The cobas 4800 System utilizes the cobas x 480 Instrument for automated sample preparation, and the automated cobas z 480 Analyzer for automated amplification and detection. The cobas 4800 system software integrates the sample preparation with nucleic acid amplification and detection to generate test results.

4

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2. INTENDED USE

Assav

The cobas® CT/NG Test is an in vitro nucleic acid amplification test that utilizes Polymerase Chain Reaction (PCR) and nucleic acid hybridization for the qualitative detection of Chlamvdia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA to aid in the diagnosis of chlamydial and gonococcal disease. The test may be used with vaginal swab specimens self-collected in a clinical setting and male urine from both symptomatic individuals. Specimens to be tested should be collected in cobas® PCR Media.

Ancillary Collection Kits

The cobas® PCR Female Swab Sample Kit is used to collect and transport self-collected vaginal swab specimens in a clinical setting. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas® CT/NG Test. NOTE: This collection kit should not be used for collection of alternative gynecological specimens.

The cobas PCR Urine Sample Kit is used to collect and transport male urine specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for . urine specimens. Use this collection kit only with the cobas CT/NG Test. NOTE: This collection kit should not be used for collection of female urine specimens.

3. TECHNOLOGICAL CHARACTERISTICS

The primary technological characteristics and intended use of the RMS cobas® CT/NG Test are substantially equivalent to other legally marketed nucleic acid amplification tests intended for the qualitative detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).

As indicated in Table 1, the RMS cobas® CT/NG Test is substantially equivalent to significant characteristics of the identified predicate devices, the Gen-Probe APTIMA Combo 2 Assay (K060652), the BD ProbeTec Q* Chlamydia trachomatis Amplified DNA Assay (K091724) and the BD ProbeTec Q* Neisseria gonorrhoeae Amplified DNA Assay (K091730).

5

| | Submitted Device:
RMS cobas® CT/NG Test | Predicate Device:
Gen-Probe APTIMA Combo
2 Assay (K060652) | Predicate Devices:
BD ProbeTec Q CT
Amplified DNA Assay
(K091724) and BD
ProbeTec Q GC Amplified
DNA Assay (K091730) |
|------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| General
Intended Use | Qualitative in vitro diagnostic
test for the direct qualitative
detection of Chlamydia
trachomatis and/or Neisseria
gonorrhoeae in patient
specimens | same | same |
| Sample
Types | Male urine
Patient-collected vaginal
swabs | Male urine
Male urethral swabs
Female urine
Endocervical swabs
Clinician-collected vaginal
swabs
Patient-collected vaginal
swabs
Cervical specimens in
PreservCyt® media | Male urine
Male urethral swabs
Female urine
Endocervical swabs
Patient-collected vaginal
swabs
Cervical specimens in
PreservCyt® and SurePath®
media |
| Subject
Status | Asymptomatic and
symptomatic | Asymptomatic and
symptomatic | Asymptomatic and
symptomatic |
| Sample
Collection
Devices | Urine collection kit
Swab collection kit | Urine collection kit
Swab collection kit | Urine collection kit
Vaginal collection kit |
| CT Analyte
Targets | CT cryptic plasmid DNA
CT ompA gene | CT ribosomal RNA | CT cryptic plasmid DNA |
| NG Analyte
Targets | NG genomic DNA | NG ribosomal RNA | NG genomic DNA |
| Sample
Preparation
Procedure | Semi-automated | Semi-automated/automated | Manual/semi-automated |
| Amplification
Technology | Real-time PCR | Ribosomal RNA transcription
medicated amplification
(TMA) | Strand displacement DNA
amplification (SDA) |
| Detection
Chemistry | Paired reporter and
quencher fluorescence
labeled probes (TaqMan
Technology) using
fluorescence resonance
energy transfer (FRET) | Photon measurment from
selectively hybridized
chemiluninescent probes
reported as Relative Light
Units (RLU) | Fluorescent dye labeled
probes using fluorescence
resonance energy transfer
(FRET) |
| | Submitted Device:
RMS cobas® CT/NG Test | Predicate Device:
Gen-Probe APTIMA Combo
2 Assay (K060652) | Predicate Devices:
BD ProbeTec Qx CT
Amplified DNA Assay
(K091724) and BD
ProbeTec Qx GC Amplified
DNA Assay (K091730) |
| Result
Analysis | Based on PCR cycle
threshold (Ct) analysis | Determined by a cut-off
based on the total RLU and
kinetic curve type | Determined by relating
MOTA scores (signal
strength) to pre-determined
cutoff values |

Table 1: Comparison of the cobas® CT/NG Test with the Predicate Devices

.

6

As indicated in Table 2, the cobas® PCR Female Swab Sample Kit and the cobas® PCR Urine Sample Kit are substantially equivalent to those characteristics for the predicate device. The collection kits have the same basic components and intended use, and all are intended as accessories to their respective assays. Data presented in this pre-market notification further support the substantial equivalence of the subject devices to the predicate.

Table 2: Comparison of the cobas® PCR Sample Collection Devices with the Predicate Device

| | Submitted Device:
RMS cobas® PCR Female
Swab Sample Kit | Submitted Device:
RMS cobas® PCR Urine
Sample Kit | Predicate Device:
Abbott multi-Collect
Specimen Collection Kit
(K092704) |
|-------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| General
Intended Use | Collection and transport of
vaginal swab specimens
self-collected in a clinical
environment for the detection
of Chlamydia trachomatis
and Neisseria gonorrhoeae
per the instructions provided.
Not intended for home use. | Collection and transport of
urine specimens for the
detection of Chlamydia
trachomatis and Neisseria
gonorrhoeae per the
instructions provided. Not
intended for home use. | Collection and transport of
male and female, swab and
urine specimens for the
detection of Chlamydia
trachomatis and Neisseria
gonorrhoeae per instructions
provided. Not intended for
home use. |
| Sample
Types | Vaginal swab self-collected
in a clinical setting | Male urine | Male urine
Male urethral swabs
Female urine
Endocervical swabs
Vaginal swabs, clinician
collected and self-collected |

7

In summary, the intended use, technology, and functionality of the cobas® CT/NG Test as compared to the predicate devices do not raise any new types of safety or effectiveness questions and are substantially equivalent.

4. NON-CLINICAL PERFORMANCE EVALUATION

4.1. Analytical Sensitivity

The analytical sensitivity (Limit of Detection or LOD) for the cobas® CT/NG Test was determined by analyzing dilutions of quantified CT and NG cultures of CT and NG were diluted into negative vaginal swab specimen in cobas® PCR Media and negative urine specimen plus cobas® PCR Media to determine the LOD for vaginal swab and urine specimens, respectively. All levels were analyzed using the full cobas® CT/NG Test workflow across 3 unique lots of cobas® CT/NG Test reagents. This test defines LOD as the target concentration which can be detected as positive in ≥ 95% of the replicates tested with each reagent lot.

The LOD for the CT serovar D culture and NG strain 19424 in cobas® PCR Media, vaginal swab specimens stabilized in cobas® PCR Media and urine specimens diluted into cobas® PCR Média are shown in Table 3.

	C. trachomatis			N. gonorrhoeae
Specimen Types	Levels
Tested	Replicates/
Level	LOD
(IFU/mL)	Levels
Tested	Replicates/
Level	LOD
(CFU/mL)
Urine	7	192*	0.75	7	192*	2.25
Vaginal Swabs	5	192**	10.00	5	192**	100.00

Table 3: cobas® CT/NG Test Limit of Detection

*Testing included one negative level with 167-168 replicates

** Testing included one negative level with 82-84 replicates

4.2. Inclusivity

The sensitivity of the cobas CT/NG Test was determined for 14 additional CT serovars, the Swedish new variant (nvCT) strain and an additional 44 independently isolated strains of NG. Testing was done to demonstrate that these targets can be detected around the LOD levels determined during analytical sensitivity testing for the CT serovar D culture and NG strain

8

Panels were prepared as described for the LOD study with the number of panel levels varying from 1 to 5, as required. At least 49 replicates were tested for each panel level using one lot of cobas CT/NG Test reagents. Results are shown in Table 4 and Table 5. In Table 5, all NG strains with identical LOD results are presented as a group, shown in the columns labeled "Numbers of NG Strains." Since LOD evaluation was done with samples stabilized in cobas PCR Media, the LOD for untreated urine is twice the level reported in Table 4 and Table 5.

The analytical sensitivity for all 14 CT serovars plus the nvCT variant (Table 4) ranged from 0.2 IFU/mL (IFU= Inclusion Forming Units) to 5.0 IFU/mL in cobas® PCR Media and from 0.13 IFU/mL to 0.75 IFU/mL in cobas® PCR Media plus negative urine specimen. All CT serovars and the nvCT variant were tested at 10 IFU/mL only in stabilized negative vaginal specimen and all showed 100% positive hit rates at 10 IFU/mL.

The analytical sensitivity for all 44 NG strains ranged from 3.0 CFU/mL to 20 CFU/mL in cobas® PCR Media and was 3.75 CFU/mL in cobas® PCR Media plus urine specimens. All NG strains were tested at 100 CFU/mL only in stabilized negative vaginal specimen. All showed 100% hit rates at 100 CFU/mL (CFU = Colony Forming Units).

	LOD Results for C. trachomatis
Serovar Type or
Variant	Vaginal Swabs*		Urine
	IFU/mL	% Pos	IFU/mL	% Pos
A	10.0	100%	0.125	98%
B	10.0	100%	0.75	100%
Ba	10.0	100%	0.75	100%
C	10.0	100%	0.75	100%
E	10.0	100%	0.75	100%
F	10.0	100%	0.75	100%
G	10.0	100%	0.75	100%
H	10.0	100%	0.75	100%
I	10.0	100%	0.75	98%
J	10.0	100%	0.125	96%
K	10.0	100%	0.75	100%
LV Type 1	10.0	100%	0.125	100%

Table 4: Summary of CT Serovars/Variant Inclusivity Verification Results

9

LV Type 2	10.0	100%	0.125	100%
LV Type 3	10.0	100%	0.125	100%
nvCT	10.0	100%	0.75	100%

Table 5: Summary of NG Strains Inclusivity Verification Results

| Numbers of NG

Strains	LOD Urine
	CFU/mL	% Hit Rate
3	3.75	96%
4	3.75	98%
37	3.75	100%
Total = 44
Numbers of NG
Strains	LOD Vaginal Swabs*
	CFU/mL	% Hit Rate
Total = 44	100	100%

4.3. Competitive Inhibition

Panels were prepared by spiking CT and NG cultures into urine and vaginal specimens stabilized in cobas® PCR Media to various concentration levels to examine the potential for competitive inhibition. Panels were prepared with two strains each of CT and NG. Panels were tested in one run per day over the course of 5 days. Two replicates of each panel member were tested in every run, generating a maximum of 10 test results for each level and CT and NG strain respectively. Average Ct values for each of the panel levels are summarized in Tables 6 and 7. All CT and NG hit rates were 100% for all panel levels in both matrices. Competitive inhibition was not seen in any combination of CT and NG levels in either matrix.

Table 6: Competitive inhibition Study for CT and NG Cultures in Urine Stabilized in
cobas® PČR Media (Ct Values)

Panel Level		Strain 1		Strain 2
CT Level
/IFU/mL	NG Level /
(CFU/mL)	CT	NG	CT	NG
Low/2	Low/6	35.1	34.8	32.5	34.8
Low/2	Medium/
24	34.9	33.1	32.6	33.0
Medium/
8	Low/6	33.5	34.1	30.1	35.0

10

| High/

1.00E+05	Low/6	19.4	34.1	18.6
Low/2	High/
1.00E+06	35.2	17.6	32.6	17.4
High/
1.00E+05	High/
1.00E+06	19.5	18.1	18.9	17.7

Table 7: Competitive inhibition Study for CT and NG Cultures in Vaginal Swabs
Collected in cobas® PCR Media (Ct Values)

Panel Level		Strain 1		Strain 2
CT Level/
IFU/mL	NG Level /
(CFU/mL)	CT	NG	CT	NG
Low/25	Low/250	36.4	35.1	34.1	34.7
Low/25	Medium/
1000	36.2	33.2	33.7	31.8
Medium/
100	Low/250	34.5	35.1	32.2	34.4
High/
1.00E+05	Low/250	23.9	33.8	22.9	33.8
Low/25	High/
1.00E+06	35.7	22.8	33.8	22.0
High/
1.00E+05	High/
1.00E+06	23.7	23.2	21.9	22.1

4.4. Analytical Specificity

A panel of 184 bacteria, fungi and viruses, including those commonly found in the male/female urogenital tract, as well as representatives of N. cineria, N. flava, N. lactamica, N. perflava and N. subflava and other phylogenetically related organisms, were tested with the cobas® CT/NG Test to assess analytical specificity. The organisms listed in Table 6 were spiked at high concentrations (microorganisms tested below 1 x 106 copies/mL are listed in Table 9) into CT/NG negative urine specimens plus cobas PCR Media and pooled negative vaginal specimen spiked with CT and NG cultures at 3 times the limit of detection.

Results indicated that none of these organisms interfered with detection of CT and NG or produced a false positive result in the CT/NG negative matrices.

Achromobacter xerosis	Helicobacter pylori	Neisseria sicca
Acinetobacter calcoaceticus	Hepatitis B virus (HBV)	Neisseria subflava
Acinetobacter Iwoffi	Hepatitis C virus (HCV)	Neisseria subflava 6458
Acinetobacter sp. genospecies 3	Human immunodeficiency virus	Neisseria subflava 6617
Actinomyces israelii	Human papillomavirus type 16
(CaSki cells)	Neisseria subflava 6618
Actinomyces pyogenes	Human papillomavirus type 18
(HeLa cells)	Neisseria subflava 7441
Adenovirus	Herpes Simplex Virus (HSV-1)	Neisseria subflava 7452
Aerococcus viridans	Herpes Simplex Virus (HSV-2)	Neisseria weaverii
Aeromonas hydrophila	Kingella dentrificans	Pantoea agglomerans
Alcaligenes faecalis	Kingella kingae	Paracoccus denitrificans
Bacillus subtilis	Klebsiella oxytoca	Pasteurella maltocida
Bacillus thuringiensis	Klebsiella pneumoniae ss ozaenae	Pediococcus acidilactica
Bacteroides caccae	Lactobacillus acidophillus	Peptostreptococcus anaerobius
Bacteroides fragilis	Lactobacillus brevis	Peptostreptococcus asacharolyticus
Bacteroides ureolyticus	Lactobacillus crispatus	Peptostreptococcus magnus
Bifidobacterium adolescentis	Lactobacillus delbrueckii subsp.
lactis	Plesiomonas shigelloides
Bifidobacterium breve	Lactobacillus jensenii	Prevotella bivia
Bifidobacterium longum	Lactobacillus lactis lactis	Prevotella corporis
Branhamella catarrhalis	Lactobacillus oris	Prevotella intermedia
Brevibacterium linens	Lactobacillus parabuchneri	Propionibacterium acnes
Campylobacter gracilis	Lactobacillus vaginalis	Proteus mirabilis
Campylobacter jejuni	Lactococcus lactis cremoris	Proteus vulgaris
Candida albicans	Legionella bozemnii	Providencia stuartii
Candida glabrata	Legionella pneumophila	Pseudomonas aeruginosa
Candida guilliermondi	Listeria monocytogenes	Pseudomonas fluorescens
Candida krusei	Micrococcus luteus	Pseudomonas putida
Candida parapsilosis	Mobiluncus curtisii subsp. curtisii	Rahnella aquatilis
Candida tropicalis	Mobiluncus curtisii subsp. holmesii	Rhizobium radiobacter
Chlamydophila pneumoniae	Mobiluncus mulieris	Rhodospirillum rubrum
Chromobacter violaceum	Moraxella catarrhalis	Ruminococcus productus
Chryseobacterium
meningosepticum	Moraxella lacunata	Saccharomyces cerevisiae
Citrobacter braakii	Moraxella osloensis	Salmonella Choleraesuis
Citrobacter freundii	Morganella morganii	Salmonella Minnesota
Clostridium innocuum	Mycobacterium avium	Salmonella Typhimurium
Clostridium perfringens	Mycobacterium gordonae	Serratia denitrificans
Clostridium sporogenes	Mycobacterium smegmatis	Serratia marcescens
Corynebacterium genitalium	Mycoplasma genitalium	Staphylococcus aureus
Corynebacterium renale	Mycoplasma hominis	Staphylococcus epidermidis
Corynebacterium xerosis	Mycoplasma pneumoniae	Staphylococcus saprophyticus
Cryptococcus neoformans	Neisseria cinerea 832	Streptococcus agalactiae
Cytomegalovirus	Neisseria cinerea 3306	Streptococcus anginosus
Deinococcus radiodurans	Neisseria cinerea 3307	Streptococcus bovis
Deinococcus radionugnans	Neisseria cinerea 3308	Streptococcus dysgalactiae
Derxia gummosa	Neisseria cinerea 6317	Streptococcus equinis
Edwardsiella tarda	Neisseria denitrificans	Streptococcus mitis
Eikenella corrodens	Neisseria elongata ssp.
nitroreducans	Streptococcus mutans
Enterobacter aerogenes	Neisseria flava	Streptococcus pneumoniae
Enterobacter cloacae	Neisseria flavescens	Streptococcus pyogenes
Enterococcus avium	Neisseria kochi	Streptococcus salivarius
Enterococcus faecalis	Neisseria lactamica	Streptococcus sanguis
Enterococcus faecium	Neisseria meningitidis 135	Streptomyces griseinus
Epstein Barr Virus	Neisseria meningitidis Serogroup A	Treponema pallidum
Erwinia herbicola	Neisseria meningitidis Serogroup B	Trichomonas vaginalis
Erysipelothrix rhusiopathiae	Neisseria meningitidis Serogroup C	Ureaplasma urealyticum
Escherichia coli	Neisseria meningitidis Serogroup D	Veillonela parvula
Ewingella americana	Neisseria meningitidis Serogroup Y	Vibrio parahaemolyticus
Flavobacterium meningosepticum	Neisseria mucosa	Weissella paramesenteroides
Fusobacterium nucleatum	Neisseria perflava 837	Yersinia enterocolitica
Gardnerella vaginalis	Neisseria perflava 911
Gemella haemolysans	Neisseria perflava 6339
Gemella morbillorum	Neisseria perflava 6340
Haemophilus ducreyi	Neisseria perflava 6341
Haemophilus influenzae	Neisseria polysaccharea

Table 8: Microorganisms Tested for Analytical Specificity

11

12

Table 9: List of Microorganisms Tested Below 1 x 106 copies/mL for Analytical Specificity

| Microorganism Tested | Concentration Tested in Listed Matrix*
Negative Urine
Specimen plus
cobas®
PCR Media | Negative Vaginal
Specimen plus
cobas®
PCR Media |
|----------------------------------------------------|--------------------------------------------------------------------------------------------------|----------------------------------------------------------|
| Adenovirus | 8x105 copies/mL | 8x105 copies/mL |
| Chlamydophila pneumoniae | 1.1x104 copies/mL | 1.1x104 copies/mL |
| Gemella morbillorum | | 4.5 x 104 copies/mL |
| Hepatitis C virus (HCV) | 5.6 x 104 copies/mL | 5.6 x 104 copies/mL |
| Human papillomavirus (HPV) type 16
(SiHa cells) | 5x104 copies/mL | 5x104 copies/mL |
| Human papillomavirus (HPV) type 18
(HeLa cells) | 1x104 copies/mL | 1x104 copies/mL |
| Neisseria cinerea 3308 | 4x105 copies/mL | 4x105 copies/mL |
| Prevotella bivia | | 9x104 copies/mL |
| Prevotella corporis | | 1.4x105 copies/mL |
| Treponema pallidum | Not Tested | 1x105 copies/mL |
| Trichomonas vaginalis | | 6.5x105 copies/mL |

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*Gray cells indicate concentration tested was ≥ 1 x 106 copies/mL in that matrix

4.5. Interference

Interference testing was performed using cobas® PCR Media plus negative urine and negative vaginal swab specimen spiked with CT and NG cultures at ~ 3 x LOD for each target. Eighteen over-the-counter (OTC) products, including contraceptive jelly, lubricants, feminine sprays, antifungal cream and anti-itch cream, as well as whole blood, cervical mucus and PBMC cells were tested for interference. Of the 18 OTC products tested, Replens® vaginal moisturizer produced invalid and/or false negative results in the cobas® PCR Media plus negative urine panel samples. No interference from Replens® vaginal moisturizer was observed with vaginal swab specimens tested.

The levels of whole blood, mucus and PBMC cells shown in Table 10 represent maximum allowable concentrations which will not interfere with cobas® CT/NG Test performance. Concentrations in urine samples were determined using total sample volume, including stabilizing media.

	Blood (v/v)		PBMC (cells/mL)
	Conc.
Tested	Interference
Observed	Conc.
Tested	Interference
Observed	Conc.
Tested	Interference
Observed
Urine stabilized in
cobas® PCR Media	0, 0.25%,
0.35%, 0.5%,
1%, 3%	> 0.35%	0, 1.0E+05,
1.0E+06,
1.0E+07	> 1 x 105	NT	NT
Vaginal Specimen
stabilized in cobas® PCR
Media	0, 1%,
3%, 5%, 10%	None	0, 1.0E+05,
1.0E+06,
1.0E+07	> 1 x 105	Routine
level*	None

Table 10: Results from Endogenous Interference Testing

NT = Not Tested

*Routine level = Quantity of cervical mucus equivalent to amount normally removed prior to sampling

4.6. Precision

Precision of the cobas CT/NG Test was examined in-house using a test panel composed of CT and NG cultures diluted into cobas® PCR Media and cobas® PCR Media mixed with

14

negative urine. The precision panel was designed to include members with either CT or NG at approximately the LOD for the panel matrix, members with both CT and NG at approximately the LOD and 2.5 x LOD for the panel matrix and a negative level. Testing was done with three unique lots of cobas CT/NG Test reagents and three instruments for a total of 24 runs. A description of the precision panels and the study performance in % hit rate are shown in Table 11. All positive panel levels yielded the anticipated hit rates. All negative panel levels tested negative throughout the study.

| Panel
Number | Panel Matrix | Target Conc. | | N
Tested | N Pos
CT | N Pos
NG | Hit Rate | 95% CI | |
|-----------------|-----------------------------|--------------|-----------|-------------|-------------|-------------|----------|--------|-------|
| | | CT | NG | | | | | Lower | Upper |
| 1 | cobas® PCR Media | Neg | Neg | 144 | 0 | 0 | 0% | 0.0 | 2.5 |
| 2 | cobas® PCR Media | 1 X LOD | Neg | 144 | 144 | 0 | 100% | 97.5 | 100.0 |
| 3 | cobas® PCR Media | Neg | 1 X LOD | 144 | 0 | 144 | 100% | 97.5 | 100.0 |
| 4 | cobas® PCR Media | 1 X LOD | 2.5 X LOD | 144 | 144 | 144 | 100% | 97.5 | 100.0 |
| 5 | cobas® PCR Media | 2.5 X LOD | 1 X LOD | 144 | 144 | 144 | 100% | 97.5 | 100.0 |
| 1 | cobas® PCR Media +
Urine | Neg | Neg | 144 | 0 | 0 | 0% | 0.0 | 2.5 |
| 2 | cobas® PCR Media +
Urine | 1 X LOD | Neg | 144 | 144 | 0 | 100% | 97.5 | 100.0 |
| 3 | cobas® PCR Media +
Urine | Neg | 1 X LOD | 144 | 0 | 144 | 100% | 97.5 | 100.0 |
| 4 | cobas® PCR Media +
Urine | 1 X LOD | 2.5 X LOD | 144 | 144 | 144 | 100% | 97.5 | 100.0 |
| 5 | cobas® PCR Media +
Urine | 2.5 X LOD | 1 X LOD | 144 | 144 | 144 | 100% | 97.5 | 100.0 |

Table 11: In-House Precision Study Hit Rate Analysis

*99.3 Hit Rate for NG. CT Hit Rate is 100%

5. . CLINICAL PERFORMANCE

The clinical performance characteristics of the cobas® CT/NG Test were established in two multi-center clinical investigations conducted in the United States. One study evaluated the reproducibility at one internal and two external testing sites. The other study evaluated the sensitivity, specificity, and predictive values of the cobas® CT/NG Test on clinical specimens.

15

5.1. Reproducibility

A Reproducibility Study was performed across lot, testing site, operator, run, and day for the cobas 8 CTNG Test using 2 panels prepared from swabs and urine collected in cobas PCR Media. A run for cobas® PCR Media (urine or swab) included 3 replicates of each of 5 panel members and 1 positive and 1 negative control (17 total tests). If cobas PCR Media panels were combined in a run, only 1 positive and 1 negative control were included (32 total tests). The 2 operators at each site performed 2 runs per day, for a total of 3 days of testing per operator per panel type (6 days of testing total for each panel type and reagent lot). Testing was performed with 2 reagent lots (6 days of testing per lot).

Overall. 74 runs were performed. and 72 valid runs were obtained for urine and swab panel types. The 2 invalid runs were due to instrument errors. A total of 1,080 tests were performed on the 5 panel members for each panel type in the valid runs. There was 1 invalid test result in the urine panel type, and 2 invalid test results in the swab panel type. These invalid tests were due to instrument errors.

All valid test results were included in the analyses that reported the percent agreement for CT and NG for each panel type separately. There were no false positive results for either analyte (CT and NG) for both panel types for negative panel members, thus giving negative percent agreement (NPA) of 100% for each analyte.

C. trachomatis (Table 12 and Table 13) 5.1.1.

Percent agreement for the positive panel members was excellent across both panel types and panel members showing a positive percent agreement (PPA) of 100%.

Analysis of variance components of the Ct values from valid tests performed on positive panel members yielded overall CV (%) ranges from 1.1% to 1.5% for the urine panel type and 1.6% to 1.8% for the swab panel type.

Table 6: C. trachomatis: Percent Agreement by Panel Member for Lot, Site/Instrument, and Day - PCR Media/Urine

| THE COLLECTION CONTRACT CONTRACTOR COLLECTION CONTROLLERS CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRA
anel | 1 | ﻟ | 1
A 44. 44. 146-46. 44. 446
Cice Castel

Actively All American
1 40 000 0000 |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------|---|---------------------------------------------------------------------------------------------------|
| | and procession of the confinited and contract and consideration of the different | | Comments of the American Company Company Company Company Company of Children |

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.

Member	SD	CV %	Lot			Site/Instrument			Day
Negative CT, Negative NG	n/a	n/a	2	100.0	108/108	1	100.0	71/71	1	100.0	72/72
			3	100.0	107/107	2	100.0	72/72	2	100.0	71/71
						3	100.0	72/72	3	100.0	72/72
1x LOD CT, Negative NG	0.54	1.5	2	100.0	108/108	1	100.0	72/72	1	100.0	72/72
			3	100.0	108/108	2	100.0	72/72	2	100.0	72/72
						3	100.0	72/72	3	100.0	72/72
Negative CT, 1x LOD NG	n/a	n/a	2	100.0	108/108	1	100.0	72/72	1	100.0	72/72
			3	100.0	108/108	2	100.0	72/72	2	100.0	72/72
						3	100.0	72/72	3	100.0	72/72
1x LOD CT, 2.5x LOD NG	0.48	1.3	2	100.0	108/108	1	100.0	72/72	1	100.0	72/72
			3	100.0	108/108	2	100.0	72/72	2	100.0	72/72
						3	100.0	72/72	3	100.0	72/72
2.5x LOD CT, 1x LOD NG	0.40	1.1	2	100.0	108/108	1	100.0	72/72	1	100.0	72/72
			3	100.0	108/108	2	100.0	72/72	2	100.0	72/72
						3	100.0	72/72	3	100.0	72/72

For Negative samples, Percent Agreement = (number of negative results/total valid results);

For Positive samples, Percent Agreement = (number of positive results/total valid results)

17

| Panel
Member | Ct
SD | Ct
CV
% | Lot | | | Site/
Instrument | | | Day | | |
|-----------------------------|----------|---------------|-----|-------|---------|---------------------|-------|-------|-----|-------|-------|
| Negative CT,
Negative NG | n/a | n/a | 2 | 100.0 | 108/108 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 |
| | | | 3 | 100.0 | 108/108 | 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 |
| | | | | | | 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 |
| 1x LOD CT,
Negative NG | 0.61 | 1.6 | 2 | 100.0 | 107/107 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 |
| | | | 3 | 100.0 | 108/108 | 2 | 100.0 | 71/71 | 2 | 100.0 | 72/72 |
| | | | | | | 3 | 100.0 | 72/72 | 3 | 100.0 | 71/71 |
| Negative CT,
1x LOD NG | n/a | n/a | 2 | 100.0 | 108/108 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 |
| | | | 3 | 100.0 | 107/107 | 2 | 100.0 | 71/71 | 2 | 100.0 | 71/71 |
| | | | | | | 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 |
| 1x LOD CT,
2.5x LOD NG | 0.66 | 1.8 | 2 | 100.0 | 108/108 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 |
| | | | 3 | 100.0 | 108/108 | 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 |
| | | | | | | 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 |
| 2.5x LOD CT,
1x LOD NG | 0.59 | 1.6 | 2 | 100.0 | 108/108 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 |
| | | | 3 | 100.0 | 108/108 | 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 |
| | | | | | | 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 |

Table 7: C. trachomatis: Percent Agreement by Panel Member for Lot, Site/Instrument, and Day - PCR Media/Swab

For Negative samples, Percent Agreement = (number of negative results/total valid results); For Positive samples, Percent Agreement = (number of positive results/total valid results)

5.1.2. N. gonorrhoeae (Table 12 and Table 13)

Percent agreement for the positive panel members was excellent across all panel types and panel members. The lowest overall PPA was 99.52% for the "Negative CT, 1 x LOD NG" panel member for PCR Media/Urine panel type.

Analysis of variance components of the Ct values from valid tests performed on positive panel members yielded overall CV (%) ranges from 1.2% to 1.5% for the urine panel type and 1.4% to 1.9% for the swab panel type.

18

| Panel
Member | Ct
SD | Ct
CV % | Lot | | Site/Instrument | | Day | |
|-----------------------------|----------|------------|-----|------------------|-----------------|----------------|-----|----------------|
| Negative CT,
Negative NG | n/a | n/a | 2 | 100.0
108/108 | 1 | 100.0
71/71 | 1 | 100.0
72/72 |
| | | | 3 | 100.0
107/107 | 2 | 100.0
72/72 | 2 | 100.0
71/71 |
| | | | | | 3 | 100.0
72/72 | 3 | 100.0
72/72 |
| 1x LOD CT,
Negative NG | n/a | n/a | 2 | 100.0
108/108 | 1 | 100.0
72/72 | 1 | 100.0
72/72 |
| | | | 3 | 100.0
108/108 | 2 | 100.0
72/72 | 2 | 100.0
72/72 |
| | | | | | 3 | 100.0
72/72 | 3 | 100.0
72/72 |
| Negative CT,
1x LOD NG | 0.53 | 1.5 | 2 | 99.1
107/108 | 1 | 100.0
72/72 | 1 | 100.0
72/72 |
| | | | 3 | 100.0
108/108 | 2 | 100.0
72/72 | 2 | 98.6
71/72 |
| | | | | | 3 | 98.6
71/72 | 3 | 100.0
72/72 |
| 1x LOD CT,
2.5x LOD NG | 0.41 | 1.2 | 2 | 100.0
108/108 | 1 | 100.0
72/72 | 1 | 100.0
72/72 |
| | | | 3 | 100.0
108/108 | 2 | 100.0
72/72 | 2 | 100.0
72/72 |
| | | | | | 3 | 100.0
72/72 | 3 | 100.0
72/72 |
| 2.5x LOD CT,
1x LOD NG | 0.54 | 1.5 | 2 | 100.0
108/108 | 1 | 100.0
72/72 | 1 | 100.0
72/72 |
| | | | 3 | 100.0
108/108 | 2 | 100.0
72/72 | 2 | 100.0
72/72 |
| | | | | | 3 | 100.0
72/72 | 3 | 100.0
72/72 |

Table 8: N. gonorrhoeae: Percent Agreement by Panel Member for Lot, Site/Instrument, and Day - PCR Media/Urine

1 For Negative samples, Percent Agreement = (number of negative results/total valid results);

For Positive samples, Percent Agreement = (number of positive results/total valid results)

| Panel
Member | Ct
SD | Ct
CV
% | Percent Agreement ¹
Lot | | | Site/
Instrument | | | Day | | |
|-----------------------------|----------|---------------|----------------------------|-------|---------|---------------------|-------|-------|-----|-------|-------|
| Negative CT,
Negative NG | n/a | n/a | 2 | 100.0 | 108/108 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 |
| | | | 3 | 100.0 | 108/108 | 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 |
| | | | | | | 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 |
| 1x LOD CT,
Negative NG | n/a | n/a | 2 | 100.0 | 107/107 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 |
| | | | 3 | 100.0 | 108/108 | 2 | 100.0 | 71/71 | 2 | 100.0 | 72/72 |
| | | | | | | 3 | 100.0 | 72/72 | 3 | 100.0 | 71/71 |
| Negative CT,
1x LOD NG | 0.68 | 1.8 | 2 | 100.0 | 108/108 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 |
| | | | 3 | 100.0 | 107/107 | 2 | 100.0 | 71/71 | 2 | 100.0 | 71/71 |
| | | | | | | 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 |

Table 9: N. gonorrhoeae: Percent Agreement by Panel Member for Lot, Site/Instrument, and Day - PCR Media/Swab

19

| Panel
Member | Ct
SD | Ct
CV
% | Lot | | Site/
Instrument | | Day | |
|---------------------------|----------|---------------|-----|---------------|---------------------|-------------|-----|-------------|
| 1x LOD CT,
2.5x LOD NG | 0.49 | 1.4 | 2 | 100.0 108/108 | 1 | 100.0 72/72 | 1 | 100.0 72/72 |
| | | | 3 | 100.0 108/108 | 2 | 100.0 72/72 | 2 | 100.0 72/72 |
| | | | | | 3 | 100.0 72/72 | 3 | 100.0 72/72 |
| 2.5x LOD CT,
1x LOD NG | 0.71 | 1.9 | 2 | 100.0 108/108 | 1 | 100.0 72/72 | 1 | 100.0 72/72 |
| | | | 3 | 100.0 108/108 | 2 | 100.0 72/72 | 2 | 100.0 72/72 |
| | | | | | 3 | 100.0 72/72 | 3 | 100.0 72/72 |

1 For Negative samples, Percent Agreement = (number of negative results/total valid results); For Positive samples, Percent Agreement = (number of positive results/total valid results)

5.2. Clinical Specimen Study

5.2.1. Study Design

Performance characteristics of the cobas CT/NG Test were evaluated in a multi-center clinical study conducted in the United States. Specimens were collected at 12 geographically diverse sites including OB-GYN practices, public and private STD clinics, and family planning centers. A total of 2.851 evaluable male and female, symptomatic and asymptomatic subjects were enrolled. Subjects were classified as symptomatic if the subject reported symptoms indicative of CT or NG infection. Specimens collected from each female subject included urine, a clinician- or self-collected vaginal swab, endocervical swabs, and a cervical sample in PreservCyt" Solution (Hologic Corporation, Bedford MA) obtained with a spatula/cytobrush or a broom. Male subjects provided urethral swabs and urine specimens. Specimens were tested using the cobas CT/NG Test and two commercially available nucleic acid amplification tests (NAAT) for CT and NG. The NAATs were used as reference assays in the clinical study.

For females, urine specimens were collected first. If a cervical cytology test was a scheduled part of the visit, that sample was taken next, followed by a vaginal swab and then endocervical swabs. If a cervical cytology test was not a scheduled part of the visit, a vaginal swab was taken next, followed by endocervical swabs and then the cervical specimen. The order of endocervical swab collection as well as clinician- or self-collection of the vaginal swab was alternated to minimize collection bias. For males, the urethral swabs were collected first in alternating order

20

and then the urine specimen was collected. All specimens were taken and stored according to the manufacturer's instructions.

Determination of Patient Infected Status 5.2.2.

For each subject, a patient infected status (PIS) was determined based on the combined results from the reference assays. A subject was categorized as infected for CT or NG if a minimum of two positive results (at least one from each reference NAAT) was reported, as described in Table 14. Female subjects with positive results on both reference urine specimens and negative results on both reference endocervical swab specimens and the reference cervical sample were categorized as infected for urine and not infected for swab specimens. A subject was classified as non-infected if at least one of the reference NAATs reported negative results for all sample types.

| NAAT1
Urine/Endocervical or
Urethral Swab | NAAT2
Urine/Endocervical or
Urethral Swab | NAAT2
Cervical Specimen in
PreservCyt | Patient Infected Status |
|-------------------------------------------------|-------------------------------------------------|---------------------------------------------|------------------------------------------|
| +/+ | +/+ | + or - | Infected |
| +/+ | +/- or -/+ | + or - | Infected |
| +/- or -/+ | +/+ | + or - | Infected |
| +/- | -/+ | + or - | Infected |
| -/+ | +/- | + or - | Infected |
| -/+ | -/+ | + or - | Infected |
| +/- | +/- | + | Infected |
| +/- | +/- | - | Infected (Urine)
Non-Infected (Swabs) |
| +/- or -/+ | -/- | + or - | Non-Infected |
| +/+ | -/- | + or - | Non-Infected |
| -/- | +/+ | + or - | Non-Infected |
| -/- | +/- or -/+ | + or - | Non-Infected |
| -/- | -/- | + or - | Non-Infected |

Table 10: Determination of Patient Infected Status

21

If patient infected status could not be determined due to missing and/or indeterminate results from the reference tests, the subject was excluded from the analysis. PIS could not be determined for one subject.

5.2.3. Study Results

Table 15 through Table 22 summarize the data from the clinical specimen study.

Results from the cobas CT/NG Test were compared with the PIS for calculation of test sensitivity and specificity. A total of 21,988 CT and 21,987 NG results were analyzed by sex. sample type, and the presence of symptoms. The overall sensitivity and specificity for CT was 95.7% and 99.7%. The overall prevalence was 9.0% for CT (6.3% in women and 16.4% in men). The overall sensitivity and specificity for NG was 99.0% and 99.9%. The overall prevalence was 3.6% for NG (1.6% in women. 9.2% in men). Sensitivity, specificity, and prevalence for CT are presented in Table 15. Sensitivity, specificity, and prevalence for NG are presented in Table 16.

A comparison of patient infected status, test results from the reference tests and test results from the cobas CT/NG Test was performed. CT results for female subjects are presented in Table 17, and for male subjects in Table 18. NG results for female subjects are presented in Table 19. and for male subjects in Table 20.

The positive and negative predictive values (PPV and NPV) were calculated using hypothetical prevalence rates and the cobas® CT/NG Test sensitivity and specificity determined in the study. The positive and negative predictive value estimates for CT are presented in Table 21, and for NG in Table 22.

Table 11: CT Clinical Performance Compared with Patient Infected Status by Gender, Sample Type, and Symptom Status

| Sample
Typea | Symptom
Statusb | Total
(n) | SENS | 95% CI | SPEC | 95% CI | PREV
(%) | PPV
(%) | NPV
(%) |
|-----------------|--------------------|--------------|------------------|-------------------|--------------------|-------------------|-------------|------------|------------|
| Female | | | | | | | | | |
| VG | Symp | 1073 | 93.8%
(75/80) | (86.2%,
97.3%) | 99.7%
(990/993) | (99.1%,
99.9%) | 7.5 | 96.2 | 99.5 |
| | Asymp | 1010 | 94.1%
(48/51) | (84.1%,
98.0%) | 99.7%
(956/959) | (99.1%,
99.9%) | 5.0 | 94.1 | 99.7 |

22

| | Overall | 2083 | 93.9%
(123/131) | (88.4%,
96.9%) | 99.7%
(1946/1952) | (99.3%,
99.9%) | 6.3 | 95.3 | 99.6 |
|--------------|---------|------|--------------------|-------------------|----------------------|-------------------|------|------|------|
| Male | | | | | | | | | |
| | Symp | 296 | 97.3%
(72/74) | (90.7%,
99.3%) | 99.5%
(221/222) | (97.5%,
99.9%) | 25.0 | 98.6 | 99.1 |
| UR | Asymp | 472 | 98.1%
(51/52) | (89.9%,
99.7%) | 99.5%
(418/420) | (98.3%,
99.9%) | 11.0 | 96.2 | 99.8 |
| | Overall | 768 | 97.6%
(123/126) | (93.2%,
99.2%) | 99.5%
(639/642) | (98.6%,
99.8%) | 16.4 | 97.6 | 99.5 |
| All Combined | | 2851 | 95.7%
(246/257) | (92.5%,
97.6%) | 99.7%
(2585/2594) | (99.3%,
99.8%) | 9.0 | 96.5 | 99.6 |

³ VG-S = self-collected vaginal swab; UR = urine.

b Symp = symptomatic; Asymp = asymptomatic.

Note: Subjects were designated as being infected with CT if at least 2 NAATs with different target regions gave positive results for the endocervical swab (urethral swab for males) and or the urine specimen. However, females were categorized as non-infected for any swab specimen if the swab specimens and the PreserVCyt specimen (NAAT2) were negative and the urine specimens were positive. Note: Subjects with designated infection status and valid cobas CTING Test results were considered evaluable and included in this summary table.

Note: CI = (score) confidence interval; PREV = prevalence; SENS = sensitivity; SPEC = specificity;

PPV = positive predictive value; NPV = negative predictive value.

Table 12: NG Clinical Performance Compared With Patient Infected Status by
Gender, Sample Type, and Symptom Status

| Sample
Typea | Symptom
Statusb | Total
(n) | SENS | 95% CI | SPEC | 95% CI | PREV
(%) | PPV
(%) | NPV
(%) |
|-----------------|--------------------|--------------|--------------------|--------------------|-----------------------|--------------------|-------------|------------|------------|
| Female | | | | | | | | | |
| VG | Symp | 1073 | 95.7%
(22/23) | (79.0%,
99.2%) | 99.9%
(1049/1050) | (99.5%,
100.0%) | 2.1 | 95.7 | 99.9 |
| VG | Asymp | 1010 | 100.0%
(10/10) | (72.2%,
100.0%) | 100.0%
(1000/1000) | (99.6%,
100.0%) | 1.0 | 100.0 | 100.0 |
| | Overall | 2083 | 97.0%
(32/33) | (84.7%,
99.5%) | 100.0%
(2049/2050) | (99.7%,
100.0%) | 1.6 | 97.0 | 100.0 |
| Male | | | | | | | | | |
| UR | Symp | 296 | 100.0%
(64/64) | (94.3%,
100.0%) | 99.1%
(230/232) | (96.9%,
99.8%) | 21.6 | 97.0 | 100.0 |
| UR | Asymp | 472 | 100.0%
(7/7) | (64.6%,
100.0%) | 100.0%
(465/465) | (99.2%,
100.0%) | 1.5 | 100.0 | 100.0 |
| | Overall | 768 | 100.0%
(71/71) | (94.9%,
100.0%) | 99.7%
(695/697) | (99.0%,
99.9%) | 9.2 | 97.3 | 100.0 |
| All Combined | | 2851 | 99.0%
(103/104) | (94.8%,
99.8%) | 99.9%
(2744/2747) | (99.7%,
100.0%) | 3.6 | 97.2 | 100.0 |

23

1 .

|
A L MOND SHIPE & A

A & A MINNERIAL AND I
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| Sample
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Status | An and profits | A . Commend Collection Collection Collection Collection Collection Collection Concession Compressional Concession Compressional Concession Comercial Concession Compressional
SENS | A B A - A -
95%
(
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | SPEC | S
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------------------------------------------------------------------------------------------------------	---------------	------------------	----------------	---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	------	------------	----------	------	-------------

ªVG-S = self-collected vaginal swab; UR = urine.

b Symp = symptomatic; Asymp = asymptomatic.

Note: Subjects were designated as being intelled with NG if at least 2 NAATs with different target regions gave positive results for the endocervical swab (urethral swab for males) and/or the urine specimen.

Note: Subjects with designated infection status and valid cobas CT/NG Test results were considered in this summary table.

Note: CI = (score) confidence interval; PREV = prevalence; SENS = sensitivity; SPEC = specificity;

PPV = positive predictive value; NPV = negative predictive value.

24

	NAAT1		NAAT2		cobas CT/NG Test	Symptom Status
Patient Infected
Status	SW	UR	SW	UR	PC Pre	VG	Symp	Asymp	Total
Infected	+	+	+	+	+	+	61	39	100
Infected	+	-	+	-	+	+	2	4	6
Infected	+	-	+	+	+	+	5	0	5
Infected	+	+	+	+	NA	+	2	1	3
Infected	+	+	+	+	+	+	2	1	3
Infected	+	+	+	-	+	+	1	1	2
Infected	+	+	-	+	+	+	1	1	2
Infected	+	+	+	+	+	-	1	0	1
Infected	+	+	+	+	-	+	0	1	1
Infected	+	+	+	-	-	-	0	1	1
Infected	+	+	-	+	-	+	1	0	1
Infected	+	-	+	+	+	-	1	0	1
Infected	+	-	+	-	+	-	1	0	1
Infected	+	-	+	-	-	-	0	1	1
Infected	-	+	+	+	+	-	1	0	1
Infected	-	+	+	+	-	-	1	0	1
Infected	-	+	-	+	NA	-	0	1	1
Total Infected							80	51	131
Non-Infected	-	-	-	-	-	-	957	911	1868
Non-Infected	-	-	-	-	NA	-	16	24	40
Non-Infected	-	-	+	-	-	-	8	3	11
Non-Infected	NA	NA	-	-	-	-	0	9	9
Non-Infected	-	-	+	+	-	-	3	0	3
Non-Infected	-	-	-	-	+	-	0	3	3
Non-Infected	-	-	-	-	-	+	2	1	3
Non-Infected	-	+	-	+	-	-	1	1	2
Non-Infected	-	+	-	-	-	-	0	2	2
Non-Infected	-	-	NA	-	-	-	0	2	2
Non-Infected	-	NA	-	-	-	-	2	0	2
Non-Infected	NA	-	-	-	-	-	2	0	2
Non-Infected	+	-	-	-	-	-	0	1	1
Non-Infected	-	-	+	+	+	+	0	1	1
Non-Infected	-	-	+	-	+	+	0	1	1
Non-Infected	-	-	-	-	+	+	1	0	1
Non-Infected	-	-	-	NA	-	-	1	0	1
Total Non-Infected							922	959	1881

Table 13: CT Positive/Negative Analysis for Female Patient Infected Status

Symp = symptomatic; Asymp = asymptomatic.

Note: Subjects were designated as being infected with CT if at least 2 NAATs with different target regions gave positive results for the endocervical swab and/or urine specimen. However, females were categorized as non-infected for any swab specimen if the swab specimens and the PreservCyt specimen (NAAT2) were negative and the unine specimens were positive.

Note: Subjects with designated infection status and valid cobas CT/NG Test results were considered evaluable and are included in this summary table.

Note: + denotes Positive; - denotes Negative; NA indicates specimen was not obtained for test result was missing/invalid. Note: SW = endocervical swab; UR = urine; VG = vaginal swab; PC Pre = PreservCyt (pre-aliquot).

25

| Patient
Infected
Status | NAAT1 | | NAAT2 | CT/NG Test | Symptom Statusa | |-------------------------------|-- | | Infected | Infected | Infected | Infected | Infected | Infected | Infected | Infected | Infected | Total Infected | Non-Infected | Non-Infected | Non-Infected | Non-Infected | Non-Infected | Non-Infected | Non-Infected | Non-Infected | Non-Infected | Total Non-Infected | cobas
| |
-----|----|-------|----|---------------------|-----------------|-------|-------|
| SW | UR | SW | UR | UR | Symp | Asymp | Total |
| + | + | + | + | + | 67 | 43 | 110 |
| - | + | - | + | + | 3 | 3 | 6 |
| - | + | + | + | + | 0 | 3 | 3 |
| + | + | + | - | + | 1 | 1 | 2 |
| + | - | + | - | - | 0 | 1 | 1 |
| + | - | + | + | + | 0 | 1 | 1 |
| - | + | + | - | + | 1 | 0 | 1 |
| - | + | - | + | - | 1 | 0 | 1 |
| + | + | + | + | - | 1 | 0 | 1 |
| | | | | | 74 | 52 | 126 |
| - | - | - | - | - | 218 | 412 | 630 |
| - | - | + | - | - | 1 | 1 | 2 |
| - | - | - | + | - | 1 | 1 | 2 |
| - | - | + | + | - | 0 | 2 | 2 |
| - | + | - | - | - | 0 | 2 | 2 |
| - | - | - | - | + | 0 | 1 | 1 |
| - | - | + | + | + | 0 | 1 | 1 |
| + | - | - | - | - | 1 | 0 | 1 |
| + | + | - | - | + | 1 | 0 | 1 |
| | | | | | 222 | 420 | 642 |

Table 14: CT Positive/Negative Analysis for Male Patient Infected Status

4 Symp = symptomatic; Asymp = asymptomatic.

Note: Subjects were designated as being infected with CT if at least 2 NAATs with different target regions gave positive results for the urether swab and/or the urine specimen.

Note: Subjects with designated infection status and valid cobas " CT/NG Test results were considered in this summary table.

Note: + denotes Positive; - denotes Negative.

Note: SW = urethral swab; UR= urine.

Table 15: NG Positive/Negative Analysis for Female Patient Infected Status

	NAAT1		NAAT2			cobas CT/NG Test	Symptom Status
Patient Infected
Status	SW	UR	SW	UR	PC Pre	VG	Symp	Asymp	Total
Infected	+	+	+	+	+	+	16	9	25
Infected	+	-	+	-	+	+	3	0	3
Infected	-	+	+	+	+	+	1	1	2
Infected	+	+	+	+	+	-	1	0	1
Infected	+	+	+	+	-	+	1	0	1
Infected	+	+	+	-	+	+	1	0	1
Total Infected							23	10	33
Non-Infected	-	-	-	-	-	-	1017	958	1975
Non-Infected	-	-	-	-	NA	-	18	26	44
Non-Infected	NA	NA	-	-	-	-	0	9	9
Non-Infected	+	-	-	-	-	-	4	1	5
Non-Infected	-	-	-	+	-	-	2	2	4
Non-Infected	-	-	NA	-	-	-	2	2	4
Non-Infected	-	-	-	+	-	-	1	1	2
Non-Infected	-	NA	-	-	-	-	2	0	2
Non-Infected	NA	-	-	-	-	-	2	0	2

26

| Patient Infected
Status | NAAT1 | | NAAT2 | | | cobas CT/NG
Test | Symptom Statusa | | Total | |
|----------------------------|-------|----|-------|----|--------|---------------------|-----------------|-------|-------|------|
| | SW | UR | SW | UR | PC Pre | | Symp | Asymp | | |
| Non-Infected | - | + | - | - | - | - | 0 | 1 | 1 | |
| Non-Infected | - | - | - | - | - | + | 1 | 0 | 1 | |
| Non-Infected | - | - | - | NA | - | - | 1 | 0 | 1 | |
| Total Non-Infected | | | | | | | | 1050 | 1000 | 2050 |

ª Symp = symptomatic; Asymp = asymptomatic.

Note: Subjects were designated as being infected with NG if at least 2 NAATs with different target regions gave positive results for the endocervical swab and/or the urine specimen.

Note: Subjects with designated infection status and valid cobas CT/NG Test results were considered evaluable and are included in this summary table.

Note: + denotes Positive; - denotes Negative; NA indicates specimen was not obtained for test result was missing/invalid. Note: SW = endocervical swab; UR = urine; VG = vaginal swab; PC Pre = PreservCyt (pre-aliquot).

Table 16: NG Positive/Negative Analysis for Male Patient Infected Status

| Patient
Infected
Status | NAAT1 | | NAAT2 | | cobas
CT/NG Test | Symptom Statusa | | Total |
|-------------------------------|-------|----|-------|----|---------------------|-----------------|-------|-------|
| | SW | UR | SW | UR | UR | Symp | Asymp | |
| Infected | + | + | + | + | + | 63 | 7 | 70 |
| Infected | + | + | - | + | + | 1 | 0 | 1 |
| Total Infected | | | | | | 64 | 7 | 71 |
| Non-Infected | - | - | - | - | - | 227 | 464 | 691 |
| Non-Infected | - | - | - | - | + | 2 | 0 | 2 |
| Non-Infected | - | + | - | + | - | 1 | 1 | 2 |
| Non-Infected | - | - | + | - | - | 1 | 0 | 1 |
| Non-Infected | + | - | - | - | - | 1 | 0 | 1 |
| Total Non-Infected | | | | | | 232 | 465 | 697 |

4 Symp = symptomatic; Asymp = asymptomatic.

Note: Subjects were designated as bein NG if at least 2 NAATs with different target regions gave positive results for the urethral swab and/or the urine specimen.

Note: Subjects with designated infection status and valid cobas CT/NG Test results and are included in this summary table.

Note: + denotes Positive; - denotes Negative.

Note: SW = urethral swab; UR= urine.

Table 17: Positive Predictive Value and Negative Predictive Value for Hypothetical CT Prevalence

Prevalence (%)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
1	95.7	99.7	73.6	100.0
3	95.7	99.7	89.5	99.9
5	95.7	99.7	93.6	99.8
10	95.7	99.7	96.8	99.5
15	95.7	99.7	98.0	99.2
20	95.7	99.7	98.6	98.9
30	95.7	99.7	99.2	98.2
50	95.7	99.7	99.6	95.9

Cverall sensitivity and specificity were estimated by compains the cobas to patient infected status in both female and male subjects.

Note: PPV = positive predictive value; NPV = negative predictive value.

27

Prevalence (%)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
	89.0	ශිරි විශ්‍රී ලිපි	90.2	100.0
3	aalin	ਰੰਤੇ ਰੋ	96.6	100.0
5	99.0	ರಿದಿ. ರಿ	87.9	વેત્ત્વે છે. છે. છે. છે છે છે. છ
10	99.0	વેવી જેવી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આં	ಕ್ಕಿ.ರ	વેલું છે. કે
15	99.0	89.9	ਰੇਰੇ 4	99.8
20	99.0	છે. વિવેત જેવી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમ	99.6	99.8
30	99.0	ਰੇਰੇ ਰੋ	99.7	99.6
പ്പ	n bo	ag a	ag a	00 0

Table 18: Positive Predictive Value and Negative Predictive Value for 1 More +1. ~+1.

Overall sensitivity and specificity were estimated by comparing the cobas to patient infected status in both female and male subjects.

Note: PPV = positive predictive value; NPV = negative predictive value.

5.2.4. Conclusion Drawn from Clinical Specimen Study

In both symptomatic and asymptomatic patients, the cobas® CT/NG Test offers high sensitivity, specificity, and positive and negative predictive values for the direct, qualitative detection of CT and NG in male urine specimens and self-collected vaginal swabs. These results are of key importance from both diagnostic and public health perspectives.

CONCLUSION 6.

A comparison of the intended use, technological characteristics, and the results of non-clinical analytical and clinical performance studies demonstrate that the cobas® CT/NG Test is safe and effective when used in accordance with the product labeling.

28

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/28/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird symbol on the right side. To the left of the bird symbol is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion.

10903 New Hampshire Avenue Silver Spring, MD 20993

Mr. James R. Bonds Director, Regulatory Affairs Roche Molecular Systems, Inc. 4300 Hacienda Drive Pleasanton, CA 94588-0900

JAN 2 4 2012

Re: K110923 Trade Name: cobas® CT/NG Test Regulation Number: 21 CFR §866.3120 Chlamydia serological reagents Regulation Name: Regulatory Class: Class I, II Product Code: MKZ, LSL, OOI Dated: January 20, 2012 Received: January 23, 2012

Dear Mr. Bonds:

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. 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.

If your device is classified (see above) into class II (Special Controls), it may be subject to such 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.

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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a

29

legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 http://www.fda.goy/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Vag a
Sallie A. Kintner, M.S., R.D.

A. Hoivat, M Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

30

cobas® CT/NG Test Indications for Use Statement

510(k) Number (if known): Device Name: Indications for Use:

K110923 Roche cobas® CT/NG Test Assav

The cobas® CT/NG Test is an in vitro nucleic acid amplification test that utilizes Polymerase Chain Reaction (PCR) and nucleic acid hybridization for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonormoeae (NG) DNA to aid in the diagnosis of chlamydial and gonococcal disease. The test may be used with vaginal swab specimens self-collected in a clinical setting and male urine from both symptomatic and asymptomatic individuals. Specimens to be tested should be collected in cobas® PCR Media.

Ancillary Collection Kits

The cobas® PCR Female Swab Sample Kit is used to collect and transport self-collected vaginal swab specimens in a clinical setting. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG Test. NOTE: This collection kit should not be used for collection of alternative gynecological specimens.

The cobas® PCR Urine Sample Kit is used to collect and transport male urine specimens.

The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas® CT/NG Test. NOTE: This collection kit should not be used for collection of female urine specimens.

Prescription Use X (Per 21 CFR Subpart D) OR

Over-The-Counter Use (Per 21 CFR Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE — CONTINUE ON ANOTHER PAGE IF NEEDED

Concu
Jayass

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnestie Device Exaluation and Safety ·

Indications for Use Statement Page 1

510(k) K110923

Intended Use / Indications for Use

Ancillary Collection Kits

Product codes (comma separated list FDA assigned to the subject device)

Device Description

Mentions image processing

Mentions AI, DNN, or ML

Input Imaging Modality

Anatomical Site

Indicated Patient Age Range

Intended User / Care Setting

Description of the training set, sample size, data source, and annotation protocol

Description of the test set, sample size, data source, and annotation protocol

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

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).

§ 866.3120 Chlamydia serological reagents.

JAN 2 4 2012

cobas® CT/NG Test 510(k) Summary

TABLE OF CONTENTS

List of Tables

DEVICE DESCRIPTION 1.

2. INTENDED USE

Assav

Ancillary Collection Kits

3. TECHNOLOGICAL CHARACTERISTICS

Table 1: Comparison of the cobas® CT/NG Test with the Predicate Devices

4. NON-CLINICAL PERFORMANCE EVALUATION

4.1. Analytical Sensitivity

4.2. Inclusivity

4.3. Competitive Inhibition

4.4. Analytical Specificity

Table 9: List of Microorganisms Tested Below 1 x 106 copies/mL for Analytical Specificity

4.5. Interference

4.6. Precision

5. . CLINICAL PERFORMANCE

5.1. Reproducibility

C. trachomatis (Table 12 and Table 13) 5.1.1.

Table 6: C. trachomatis: Percent Agreement by Panel Member for Lot, Site/Instrument, and Day - PCR Media/Urine

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Table 7: C. trachomatis: Percent Agreement by Panel Member for Lot, Site/Instrument, and Day - PCR Media/Swab

5.1.2. N. gonorrhoeae (Table 12 and Table 13)

Table 8: N. gonorrhoeae: Percent Agreement by Panel Member for Lot, Site/Instrument, and Day - PCR Media/Urine

Table 9: N. gonorrhoeae: Percent Agreement by Panel Member for Lot, Site/Instrument, and Day - PCR Media/Swab

5.2. Clinical Specimen Study

5.2.1. Study Design

Determination of Patient Infected Status 5.2.2.

5.2.3. Study Results

Table 13: CT Positive/Negative Analysis for Female Patient Infected Status

Table 14: CT Positive/Negative Analysis for Male Patient Infected Status

Table 15: NG Positive/Negative Analysis for Female Patient Infected Status

Table 16: NG Positive/Negative Analysis for Male Patient Infected Status

Table 17: Positive Predictive Value and Negative Predictive Value for Hypothetical CT Prevalence

Table 18: Positive Predictive Value and Negative Predictive Value for 1 More +1. ~+1.

5.2.4. Conclusion Drawn from Clinical Specimen Study

CONCLUSION 6.

DEPARTMENT OF HEALTH & HUMAN SERVICES

cobas® CT/NG Test Indications for Use Statement

Ancillary Collection Kits

| THE COLLECTION CONTRACT CONTRACTOR COLLECTION CONTROLLERS CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRA
anel | 1 | ﻟ | 1
A 44. 44. 146-46. 44. 446
Cice Castel