Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes an automated PCR-based diagnostic test with a software update for workflow modification. There is no mention of AI or ML in the device description, intended use, or performance studies. The analysis focuses on analytical and clinical performance metrics typical of molecular diagnostic assays.

Therapeutic

No

This device is an in vitro diagnostic (IVD) test intended to aid in the diagnosis of chlamydial and gonococcal disease by detecting bacterial DNA, not to treat or cure these conditions.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states, "This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals." This directly indicates its purpose is to diagnose diseases.

SaMD (Software as a Medical Device)

No

The device is an in vitro diagnostic (IVD) test that includes reagent kits and relies on specific hardware systems (cobas x 480 Instrument and cobas z 480 Analyzer) for sample preparation, amplification, and detection. While it mentions a system software update, the device itself is not solely software.

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 v2.0 Test is an "in vitro nucleic acid amplification test". This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
Specimen Type: The test is designed to detect DNA in "urogenital specimens", which are specimens taken from the human body.
Purpose: The test is intended as an "aid in the diagnosis of chlamydial and gonococcal disease". This is a diagnostic purpose, which is a key function of IVDs.
Device Description: The description details the components and processes involved in performing the test on these specimens, including sample preparation, amplification, and detection.

The information provided clearly indicates that this device is intended for use outside of the body to analyze human specimens for diagnostic purposes, which is the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonormoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chiamydia trachomatis and Neisseria gonormoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas® PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt® solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals.

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

MKZ, LSL, OOI

Device Description

The changes between the previously cleared cobas® CT/NG Test (K110923) and the currently submitted cobas® CTNG v2.0 Test are limited to the modification of the sample preparation workflow which requires a system software update related to the cobas 4800 system. There are no changes for the reagents or the design between the cobas® CT/NG v2.0 Test and the cobas® CT/NG Test. The Roche Molecular Systems (RMS) cobas® CT/NG v2.0 Test consists of six reagent kits:

cobas® 4800 System Sample Preparation Kit .
cobas 4800 CT/NG v2.0 Amplification/Detection Kit .
cobas® 4800 CT/NG Controls Kit .
cobas 4800 System Wash Buffer Kit .
cobas® 4800 System Control Diluent Kit .
cobas® 4800 System Liquid Cytology Preparation Kit .

Sample Collection Kits to be used for the cobas CT/NG v2.0 Test are:

cobas® PCR Female Swab Sample Kit •
cobas® PCR Urine Sample Kit .
PreservCyt® (Hologic, Inc.) .

The cobas® CTNG v2.0 Test for Chlamydia 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 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

Urogenital specimens, male and female urine, self-collected vaginal swab specimens, clinician-collected vaginal swab specimens, endocervical swab specimens, cervical 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

Not Found

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

Clinical Performance Studies:

Study Type: Three multi-center clinical investigations conducted in the United States. One study evaluated reproducibility, and two studies evaluated sensitivity, specificity, and predictive values on clinical specimens.
Sample Size:
- Reproducibility Study: 127 runs performed in total, 900 tests on 5 panel members for each panel type.
- Clinical Specimen Study: 6,045 subjects enrolled (5,306 females and 739 males). 6,004 evaluable for CT and/or NG primary analyses (5,266 females and 738 males).
Key Results:
- Reproducibility:
  - No false positive results for CT or NG for negative panel members across all panel types, resulting in 100% Negative Percent Agreement (NPA).
  - For C. trachomatis: Total CV(%) ranged from 1.4% to 2.6%. Percent agreement for 3 X LOD CT was 100% across all 3 panel types. For 1 X LOD CT, percent agreement was 100% for urine, 96.7% for swab, and 98.9% for PreservCyt panel types.
  - For N. gonorrhoeae: Total CV(%) ranged from 1.6% to 2.6%. Percent agreement for 3 X LOD NG was 99.4% for urine panel and 100% for swab and PreservCyt panel types. For 1 X LOD NG, percent agreement was 95% for urine, 89.4% for swab, and 99.4% for PreservCyt panel types.
- Clinical Specimen Study:
  - CT Performance:
    - Sensitivity ranged from 93.7% to 98.4%.
    - Specificity ranged from 98.8% to 99.8%.
    - Performance estimates were similar between symptomatic and asymptomatic subjects.
    - Total infected females: 365. Total infected males: 122.
    - Overall CT prevalence: 6.9% in women, 16.5% in men, and 8.1% in the entire study population.
  - NG Performance:
    - Sensitivity ranged from 95.6% to 100.0%.
    - Specificity ranged from 99.1% to 100.0%.
    - Performance estimates were similar between symptomatic and asymptomatic subjects.
    - Total infected females: 92. Total infected males: 67.
    - Overall NG prevalence: 1.7% in women, 9.1% in men, and 2.6% in the entire study population.

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

Chlamydia trachomatis (CT):

Overall Sensitivity (compared with PIS): 94.1%
- Endocervical swabs: 94.9%
- Female urine specimens: 94.0%
- Male urine specimens: 98.4%
- Self-collected vaginal swabs: 97.6%
- Clinician-collected vaginal swabs: 98.2%
- PreservCyt specimens (pre-ThinPrep processing): 94.2%
- PreservCyt specimens (post-ThinPrep processing): 93.7%
Overall Specificity (compared with PIS): 99.6%
- Range: 98.8% to 99.8% in both females and males.
Hypothetical PPV for CT:
- 1% Prevalence: 69.0%
- 3% Prevalence: 87.2%
- 5% Prevalence: 92.0%
- 10% Prevalence: 96.1%
- 15% Prevalence: 97.5%
- 20% Prevalence: 98.2%
- 30% Prevalence: 98.9%
- 50% Prevalence: 99.5%
Hypothetical NPV for CT:
- 1% Prevalence: 99.9%
- 3% Prevalence: 99.8%
- 5% Prevalence: 99.7%
- 10% Prevalence: 99.3%
- 15% Prevalence: 99.0%
- 20% Prevalence: 98.5%
- 30% Prevalence: 97.5%
- 50% Prevalence: 94.4%

Neisseria gonorrhoeae (NG):

Overall Sensitivity (compared with PIS): 97.1%
- Range: 95.6% to 100.0%.
Overall Specificity (compared with PIS): 99.8%
- Range: 99.1% to 100.0% for both females and males.
Hypothetical PPV for NG:
- 1% Prevalence: 82.0%
- 3% Prevalence: 93.3%
- 5% Prevalence: 96.0%
- 10% Prevalence: 98.0%
- 15% Prevalence: 98.8%
- 20% Prevalence: 99.1%
- 30% Prevalence: 99.5%
- 50% Prevalence: 99.8%
Hypothetical NPV for NG:
- 1% Prevalence: 100.0%
- 3% Prevalence: 99.9%
- 5% Prevalence: 99.8%
- 10% Prevalence: 99.7%
- 15% Prevalence: 99.5%
- 20% Prevalence: 99.3%
- 30% Prevalence: 98.8%
- 50% Prevalence: 97.2%

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.

K110923

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

§ 866.3390

Neisseria spp. direct serological test reagents.(a)
Identification. Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identifyNeisseria spp. from cultured isolates. Additionally, some of these reagents consist ofNeisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence ofNeisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusNeisseria, 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.(b)
Classification. Class II (performance standards).

Summary

0

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

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

K 132270
DEC - 2 2013

cobas® CT/NG v2.0 Test 510(k) Summary

	Roche Molecular Systems, Inc.
	4300 Hacienda Drive
Submitted by:	Pleasanton, CA 94588-2722
Phone Number: (925) 730-8046
Fax Number: (925) 730-8128
Contact:	Wilk von Gustedt
Date of Preparation:	July 16, 2013
Device Trade Name:	cobas® CT/NG v2.0 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 Device-Assay:	cobas® CT/NG Test (K110923)
Predicate Devices-Collection Kits:	cobas® PCR Female Swab Sample Kit and the cobas® PCR Urine Sample
Kit, previously cleared with the cobas® CT/NG Test (K110923)

1

દિ

・・

1.	Device Description	5
2.	Intended Use	6
3.	Technological Characteristics	6
4.	Non-Clinical Performance Evaluation	8
	4.1. Analytical Sensitivity	8
	4.2. Inclusivity.	9
	4.3. Analytical Specificity.	11
	4.4. Interference.	14
	4.5. Precision	17
5.	Clinical Performance	20
	5.1. Reproducibility.	20
	5.1.1. C. trachomatis (Table 12, Table 13, Table 14, and Table 15).	21
	5.1.2. N. gonorrhoeae (Table 16. Table 17, Table 18, Table 19).	26
	5.2. Clinical Specimen Study	30
	5.2.1. Study Design.	30
	5.2.2. Determination of Patient Infected Status	31
	5.2.3. Study Results	32
	5.2.4. Chlamydia trachomatis (CT)	33
	5.2.5. Neisseria gonorrhoeae (NG)	39
	5.2.6. Prevalence	44
	5.2.7. Positive and Negative Predictive Value.	44
6	Conclusion	45

2

List of Tables

Table 1:	Comparison of the cobas® CT/NG v2.0 Test with the Predicate Device	7
Table 2:	cobas® CT/NG v2.0 Test Limit of Detection for CT serovar D and serovar I	9
Table 3:	cobas® CT/NG v2.0 Test Limit of Detection for NG strain 2948 (ATCC

and Strain 6693 | 9 |
| Table 4: | Summary of CT Serovars/Variant Inclusivity Verification Results. | 10 |
| Table 5: | Summary of NG Strains Inclusivity Verification Results. | 11 |
| Table 6: | Microorganisms Tested for Analytical Specificity | 12 |
| Table 7: | List of Microorganisms Tested below 1 x 10⁶ Units/mL for Analytical
Specificity. | 14 |
| Table 8: | Results from Endogenous Interference Testing for Albumin, Bilirubin,
Glucose, and pH. | 16 |
| Table 9: | Results from Endogenous Interference Testing for Whole Blood. PBMC, and
Mucus | 16 |
| Table 10: | Panel Design for In-House Precision Study | 17 |
| Table 11: | In-House Precision Study Hit Rate Analysis | 18 |
| Table 12: | C. trachomatis: Overall Mean, Standard Deviations, and Coefficients of
Variation (%) for Cycle Threshold, Estimated From Valid Samples of
Positive Sample Type Panel Members. | 22 |
| Table 13: | C. trachomatis: Percent Agreement by Panel Member Overall and for
Site/Instrument, Operator. and Day - PCR Media/Urine | 23 |
| Table 14: | C. trachomatis: Percent Agreement by Panel Member Overall and for
Site/Instrument, Operator, and Day - PCR Media/Swab | 24 |
| Table 15: | C. trachomatis: Percent Agreement by Panel Member Overall and for
Site/Instrument, Operator, and Day - PreservCyt | 25 |
| Table 16: | N. gonorrhoeae: Overall Mean. Standard Deviations, and Coefficients of
Variation (%) for Cycle Threshold, Estimated From Valid Samples of
Positive Sample Type Panel Members. | 26 |
| Table 17: | N. gonorrhoeae: Percent Agreement by Panel Member Overall and for
Site/Instrument, Operator, and Day - PCR Media/Urine | 27 |
| Table 18: | N. gonorrhoeae: Percent Agreement by Panel Member Overall and for
Site/Instrument, Operator, and Day - PCR Media/Swab | 28 |

3

| Table 19: N. gonorrhoeae: Percent Agreement by Panel Member Overall and for

Site/Instrument. Operator, and Day - PreservCyt	29
Table 20: Determination of Female Patient Infected Status.	31
Table 21: Determination of Male Patient Infected Status	32
Table 22: CT: Clinical Performance Compared With Patient Infected Status by Gender
and Sample Type, and Symptom Status.	33
Table 23: CT: Positive/Negative Analysis for Female Patient Infected Status.	35
Table 24: CT: Positive/Negative Analysis for Male Patient Infected Status	39
Table 25: NG: Clinical Performance Compared With Patient Infected Status by
Gender, Sample Type, and Symptom Status.	40
Table 26: NG: Positive/Negative Analysis for Female Patient Infected Status	42
Table 27: NG: Positive/Negative Analysis for Male Patient Infected Status.	44
Table 28: Positive Predictive Value and Negative Predictive Value for Hypothetical CT
Prevalence	45
Table 29: Positive Predictive Value and Negative Predictive Value for Hypothetical
NG Prevalence.	45

.

4

DEVICE DESCRIPTION 1.

The changes between the previously cleared cobas® CT/NG Test (K110923) and the currently submitted cobas® CTNG v2.0 Test are limited to the modification of the sample preparation workflow which requires a system software update related to the cobas 4800 system. There are no changes for the reagents or the design between the cobas® CT/NG v2.0 Test and the cobas® CT/NG Test. The Roche Molecular Systems (RMS) cobas® CT/NG v2.0 Test consists of six reagent kits:

cobas® 4800 System Sample Preparation Kit .
cobas 4800 CT/NG v2.0 Amplification/Detection Kit .
cobas® 4800 CT/NG Controls Kit .
cobas 4800 System Wash Buffer Kit .
cobas® 4800 System Control Diluent Kit .
cobas® 4800 System Liquid Cytology Preparation Kit .

Sample Collection Kits to be used for the cobas CT/NG v2.0 Test are:

cobas® PCR Female Swab Sample Kit •
cobas® PCR Urine Sample Kit .
PreservCyt® (Hologic, Inc.) .

The cobas® CTNG v2.0 Test for Chlamydia 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.

5

The cobas 4800 System utilizes the cobas x 480 Instrument for automated sample preparation, and the 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.

INTENDED USE 2.

The cobas® CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt® solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals.

The coloas® PCR Female Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with either the cobas® CT/NG Test or the cobas® CT/NG v2.0 Test.

The cobas® PCR Urine Sample Kit is used to collect and transport urine specimens. The cohuse PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with either the cobas® CT/NG Test or the cobas® CT/NG v2.0 Test.

3. TECHNOLOGICAL CHARACTERISTICS

The primary technological characteristics and intended use of the RMS cobas® CT/NG v2.0 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).

6

As indicated in Table 1, the RMS cobas® CT/NG v2.0 Test is substantially equivalent to significant characteristics of the identified predicate device, the currently cleared cobase CT/NG Test (K110923).

| | Submitted Device:
RMS cobas® CT/NG v2.0 Test | Predicate Device:
RMS cobas® CT/NG Test
(K110923) |
|---------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Qualitative in vitro diagnostic test for the
direct qualitative detection of Chlamydia
trachomatis and/or Neisseria gonorrhoeae
in patient specimens | Same |
| Sample Types | Male urine
Female urine
Endocervical swabs
Clinician-collected vaginal swabs
Patient-collected vaginal swabs
Cervical specimens in PreservCyt®
Solution | Male urine
Patient-collected vaginal swabs |
| Subject Status | Asymptomatic and symptomatic | Asymptomatic and symptomatic |
| Sample Collection Devices | Urine collection kit
Female swab collection kit | Urine collection kit
Female swab collection kit |
| CT Analyte Targets | CT cryptic plasmid DNA
CT ompA gene | CT cryptic plasmid DNA
CT ompA gene |
| NG Analyte Targets | NG genomic DNA | NG genomic DNA |
| Sample Preparation
Procedure | Semi-automated | Semi-automated |
| Amplification Technology | Real-time PCR | Real-time PCR |
| Detection Chemistry | Paired reporter and quencher
fluorescence labeled probes (TaqMan
Technology) using fluorescence
resonance energy transfer (FRET) | Paired reporter and quencher
fluorescence labeled probes (TaqMan
Technology) using fluorescence
resonance energy transfer (FRET) |
| Result Analysis | Based on PCR cycle threshold analysis | Based on PCR cycle threshold analysis |

		Table 1: Comparison of the cobas® CT/NG v2.0 Test with the Predicate Device
--	--	-----------------------------------------------------------------------------	--	--	--	--

In summary, the intended use, technology, and functionality of the cobas CT/NG v2.0 Test are substantially equivalent to the predicate device.

7

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

NON-CLINICAL PERFORMANCE EVALUATION 4.

All performance related testing summarized in this report was performed using the cobas® CT/NG v2.0 Test with the exception of the Analytical Specificity study (Section 4.3 below) which is based on the currently cleared cobas® CT/NG Test (K110923). The changes between the previously cleared cobas® CT/NG Test (K110923) and the currently submitted cobas® CT/NG v2.0 Test are limited to the modification of the sample preparation workflow which requires a system software update related to the cobas 4800 system. There are no changes for the reagents or the design between the cobas® CT/NG v2.0 Test and the cobas® CT/NG Test. Therefore it was concluded that data for the cobas® CT/NG Test can also be used to demonstrate performance of the cobas® CT/NG v2.0 Test for Analytical Specificity.

Analytical Sensitivity 4.1.

The analytical sensitivity (Limit of Detection or LOD) for the cobas 8 CTNG v2.0 Test was determined by analyzing dilutions of quantified CT and NG cultures of CT and NG were diluted into negative urine specimens stabilized in cobas PCR Media, negative endocervical swab specimen in cobas® PCR Media, negative vaginal swab specimen in col>ass® PCR Media, and negative PreservCyt® specimen to determine the LOD for each specimen tvpc. All levels for each specimen type were analyzed using the full cobas 8 CT/NG v2.0 Test workflow with 3 unique lots of cobas CT/NG v2.0 Test reagents. In the course of the study, a total of 5 unique lots of reagents were used. The LOD of the test is defined as the target concentration which can be detected as positive in ≥ 95% of the replicates tested.

The LOD for the CT serovar D and serovar 1 cultures in urine specimens stabilized in cobas PCR Media, endocervical swab specimen in cobas® PCR Media, vaginal swab specimen in cobas® PCR Media, and PreservCyt® specimen are shown in Table 2. The LOD for NG strain 2948 (ATCC 19424) and strain 6693 in urine specimens stabilized in cobas® PCR Media, cndocervical swab specimen in cobas® PCR Media, vaginal swab specimen in cobas® PCR Media. and negative PreservCvt® specimen are shown in Table 3. When analyzed separately. male and female urine results were statistically equivalent for both CT and NG cultures.

8

cobas® CT/NG v2.0 Test Limit of Detection for CT scrovar D and serovar I Table 2:

Specimen Types	C. trachomatis serovar D			C. trachomatis serovar I
	Levels
Tested*	Replicates/
Level	LOD
(EB/mL)	Levels
Tested*	Replicates/
Level**	LOD
(EB/mL)
Urine (Female)	6	60	40	6	60	10
Urine (Male)	6	60	40	6	60	20
Endocervical Swabs	6	59-60**	200	6	60	100
Vaginal Swabs	6	60	300	6	60	70
PreservCyt®	6	60	200	6	59-60**	50

Testing included one negative level with 24-48 replicates

** One replicate was not processed by the cobas® x 480 due to insufficient sample volume

cobas® CT/NG v2.0 Test Limit of Detection for NG strain 2948 (ATCC 19424) Table 3: and Strain 6693

Specimen Types	N. gonorrhoeae strain 2948			N. gonorrhoeae strain 6693
	Levels Tested*	Replicates/ Level	LOD (CFU/mL)	Levels Tested*	Replicates/ Level**	LOD (CFU/mL)
Urine (Female)	6	60	0.2	7	60	0.4
Urine (Male)	6	60	0.2	7	60	0.6
Endocervical Swabs	6	59-60**	2	6	60	2
Vaginal Swabs	6	60	3	6	60	1.5
PreservCyt®	6	60	1	6	59-60**	1

Including one negative level with 24-72 replicates

** One replicate was not processed by the cobas x 480 due to insufficient sample volume

4.2. Inclusivity

The sensitivity of the cobas CT/NG v2.0 Test was determined for 13 additional CT serovars, the Swedish variant CT strain (nvCT), and an additional 43 independently isolated strains of NG. Panels were prepared by spiking each CT culture stock into specimen type specific CT/NG negative pools to approximately 0.5 and 1.5 times the LOD of CT serovar D as determined in the LOD studies. Each NG culture was spiked into CT/NG negative pools to approximately 1.5 times the LOD of NG strain 2948 (ATCC 19424) as determined in the LOD studies. At least 20 replicates were tested for each CT and NG levels that did not produce a 95% or greater hit rate at the levels tested, a higher concentration was prepared and tested.

9

A total of 13 CT serovars and one nvCT (Swedish variant) strain were evaluated. The minimum concentration from which all of the CT serovars returned a hit rate of ≥ 95% was 60 EB/mL for urine stabilized in cobas PCR Media; 300 EB/mL for endocervical specimen in cobas PCR Media; 150 EB/mL for vaginal specimen in cobas PCR Media; and 100 EB/mL for cervical specimen collected in PreservCyt Solution (Table 4).

A total of 43 strains of NG were evaluated. The minimum concentration from which all of the . NG strains returned a hit rate of ≥ 95% was 1 CFU/mL for urine stabilized in cobas PCR Media; 10 CFU/mL for endocervical specimen in cobas PCR Media; 10 CFU/mL for vaginal specimen in cobas PCR Media; and 5 CFU/mL for cervical specimen collected in PreservCyt Solution (Table 5).

	Results for C. trachomatis
Serovar Type or
Variant	Urine		Endocervical Swabs		Vaginal Swabs		PreservCyt®
	EB/mL	% Hit Rate	EB/mL	% Hit
Rate	EB/mL	% Hit
Rate	EB/mL	% Hit
Rate
A	20	100%	100	100%	150	100%	100	100%
B	20	100%	100	100%	150	100%	100	100%
Ba	20	100%	100	100%	150	100%	100	100%
C	20	100%	100	100%	150	100%	100	100%
E	20	100%	100	100%	150	100%	100	100%
F	20	100%	100	100%	150	100%	100	100%
G	20	100%	100	95%	150	100%	100	100%
H	20	100%	100	95%	150	100%	100	100%
J	20	100%	100	100%	150	100%	100	100%
K	20	100%	100	100%	150	100%	100	100%
LV Type 1	20	100%	100	100%	150	100%	100	100%
LV Type 2	20	100%	100	100%	150	100%	100	100%
LV Type 3	20	100%	100	100%	150	100%	100	100%
nvCT	60	100%	300	100%	150	95%	100	100%

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

10

| Numbers of
NG Strains | Urine | | Numbers of
NG Strains | Endocervical Swabs | |
|--------------------------|---------------|------------|--------------------------|--------------------|------------|
| 34 | 0.3 | ≥ 95% | 39 | 3 | ≥ 95% |
| 9 | 1 | 100% | 4 | 10 | 100% |
| Total = 43 | | | Total = 43 | | |
| Numbers of | Vaginal Swabs | | Numbers of NG | PreservCyt | |
| NG Strains | CFU/mL | % Hit Rate | Strains | CFU/mL | % Hit Rate |
| 42 | 4.5 | ≥ 95% | 40 | 1.5 | 100% |
| 1 | 10 | 100% | 3 | 5 | 100% |
| Total = 43 | | | Total = 43 | | |

Summary of NG Strains Inclusivity Verification Results Table 5:

4.3. Analytical Specificity

A panel of 184 bacteria, fungi and viruses, including those commonly found in the female urogenital tract, as well as representatives of N. cineria, N. flava, N. lactamica, N. perflava and N. subflava and other phylogenetically unrelated organisms, were tested to assess analytical specificity. The organisms tested are listed in Table 6. All organisms were tested at concentrations of at least 1 x 106 Units*/mL except those organisms listed in Table 7. All organisms were spiked into CT/NG negative cobas® PCR Media, pooled negative urine stabilized in cobas " PCR Media, pooled negative vaginal specimen in cobas® PCR Media, and pooled negative PreservCyt® 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.

All bacteria were quantified as Colony Forming Units (CFU) except Chlanndophila pneumoniae as Inclusion Forming Units (IFU). Treponema pallidum and HBV were quantified as DNA copies. Adenovirus was quantified as Plaque Forming Units (PFU). CMV, EBV, HSV-1 and HSV-2 were quantified as Viral Particles (VP). HCV and HIV-1 were quantified in International Units (IU). Trichomonas vaginalis, HPV16 and HPV18 were quantified as cells/mL.

11

ﻟﺴﻤﺔ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺴﺘﻘﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ

Microorganisms Tested for Analytical Specificity Table 6:

Achromobacter xerosis	Helicobacter pylori	Neisseria sicca
Acinetobacter calcoaceticus	Hepatitis B virus (HBV)	Neisseria subflava
Acinetobacter lwoffi	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 weaveni
Aeromonas hydrophila	Kingella dentifricans	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 radiopugnans	Neisseria cinerea 3308	Streptococcus dysgalactiae
Derxia gummosa	Neisseria cinerea 6317	Streptococcus equinis
Edwardsiella tarda	Neisseria dentrificans	Streptococcus mitis
Eikenella corrodens	Neisseria elongata subsp.
niroreducans	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

12

13

		Concentration Tested in Listed Matrix*
Microorganism Tested	cobas®
PCR Media	Negative Urine
Specimen	Negative Vaginal
Specimen	Negative
PreservCyt
Specimen
Adenovirus		8x105 PFU/mL	8x105 PFU/mL	8x105 PFU/mL
Cytomegalovirus (CMV)	1x104 VP/mL
Chlamydophila pneumoniae	1x105 IFU/mL	1.1x104 IFU/mL	1.1x104 IFU/mL	1.1x104 IFU/mL
Gemella morbillorum		4.5 x 104 CFU/mL	4.5 x 104 CFU/mL	4.5 x 104 CFU/mL
Hepatitis C virus (HCV)		5.6 x 104 IU/mL	5.6 x 104 IU/mL	5.6 x 104 IU/mL
Human papillomavirus (HPV)
type 16 (SiHa cells)		1x104 cells/mL	1x104 cells/mL	1x104 cells/mL
Human papillomavirus (HPV)
type 18 (HeLa cells)		1x104 cells/mL	1x104 cells/mL	1x104 cells/mL
Neisseria cinerea 3307			4x105 CFU/mL	4x105 CFU/mL
Prevotella bivia		9x104 CFU/mL	9x104 CFU/mL	9x104 CFU/mL
Prevotella corporis			1.4x105 CFU/mL	1.4x105 CFU/mL
Treponema pallidum	Not Tested	1x105 copies/mL	1x105 copies/mL	1x105 copies/mL
Trichomonas vaginalis			6.5x105 cells/mL	6.5x105 cells/mL

Table 7: List of Microorganisms Tested below 1 x 10° Units/mL for Analytical Specificity

*Gray cells indicate concentration tested was ≥ 1 x 10° Units/mL in that matrix

4.4. Interference

Interference testing was performed using CT/NG negative urine specimen stabilized in cobass PCR Media, endocervical swab specimen in cobas® PCR Media, vaginal swab specimen in cobas® PCR Media, and PreservCyt® specimen spiked with CT and NG cultures at ~ 3 x LOD for each target. Twenty-three over-the-counter (OTC) products and prescription medications, as well as whole blood, and PBMC cells were tested for interference. Additionally, cervical mucus was tested in swabs samples, and albumin, bilirubin, glucose, and pH were tested for interference in the urine specimen type.

Of the 23 products tested, Metronidazole Vaginal Gel and Vagisil Satin produced invalid and/or false negative results in the urine panel samples. Replens® vaginal moisturizer produced invalid and/or false negative results in urine and endocervical swab panel samples. No interference from any of the other products was observed with the other sample matrices tested.

14

The levels of albumin, bilirubin, glucose, and pH shown in Table 8 and the levels of whole blood, mucus and PBMC cells shown in Table 9 represent maximum allowable concentrations which will not interfere with the cobas® CT/NG v2.0 Test performance.

15

loche Molecular Systems,
Teasanton, CA 94588-2722

cobas® CT/NG v2.0 Tes
ction 5: 510(k) Summary Repor

sults from Endogenous Interference Testing for Albumin, Bilirubin, Glucose, and Table 8:

.

Specimer	Albumin (w/v		Bilirubin (w/v
Type	Concentration
Tested	nterference
Observed	Concentration
Tested	Interference
Observed	Concentration
Fested	interference
Observer	Concentration
ested
1	Interference
Observer
Urine	0%, 1%, 2%, 5%	None	0%,0.05%,0.10%
0.25%,0.50%	None	1%
0%, 0.5%,	None	Alkaline (pH9)
Acidic (pH4)	None

lesults from Endogenous Interference Testing for Whole Blood, PBMC, and Muc Table 9:

Specimen Type	Whole Blood (v/v)		PBMC (cells/mL)		Mucus
	Concentration Tested	Interference Observed	Concentration Tested	Interference Observed	Concentration Tested	Interference Observed
Urine	0%, 0.10%, 0.25%,
0.50%, 1%	> 0.25%	0, 1.0+E05, 1.0+E06,
1.0+E07	> 1.0+E05	Not Tested	Not Tested
Endocervical Swab	0%, 3%, 5%, 10%	None	0, 1.0+E05, 1.0+E06,
1.0+E07	> 1.0+E06	Routine Level *	None
Vaginal Swab	0%, 3%, 5%, 10%	None	0, 1.0+E05, 1.0+E06,
1.0+E07	> 1.0+E06	Routine Level *	None
Cervical PreservCyt	0%, 3%, 5%, 10%	> 3%	0, 1.0+E05, 1.0+E06,
1.0+E07	None	Routine Level *	None

outine Level = Quantity of cervical mucus equivalent to amount normally removed prior to samp

16

4.5. Precision

Precision of the cobas CT/NG v2.0 Test was examined in-house using a test panel composed of CT and NG cultures diluted into pools of CT and NG negative urine specimen stabilized in cobas PCR Media, vaginal swab specimen in cobas® PCR Media, and PreservCvt® specimen. The precision panel was designed to include negative samples as well as samples with CT and/or NG concentrations at and above the LOD of the cobas® CT/NG v2.0 Test. Additionally, samples with high CT or NG titers were examined for suppression of low titer target in the adjacent channel. Testing was done with three unique lots of cobas® CT/NG v2.0 Test reagents, three instruments, over 12 days. A description of the precision panels is shown in Table 10 and the study performance in % hit rates is shown in Table 11. All positive panel levels vielded the anticipated hit rates, with the exception of panel member 3 in urine which resulted in a hit rate of 83%. All negative panel levels tested negative throughout the study.

	CT		NG
Panel Member	Level	Anticipated Hit Rate
(%)	Level	Anticipated Hit Rate
(%)
1	Negative	0	Negative	0
2	Negative	0	High Negative	20-80
3	High Negative	20-80	Negative	0
4	Low Positive	≥ 90	Low Positive	≥ 90
5	Moderate Positive	≥ 99	Low Positive	≥ 90
6	Low Positive	≥ 90	Moderate Positive	≥ 99
7	Low Positive	≥ 90	High Positive	≥ 99
8	High Positive	≥ 99	Low Positive	≥ 90
9	High Positive	≥ 99	High Positive	≥ 99

	Table 10: Panel Design for In-House Precision Study

17

cobas® CT/NG v2.0 Tess
Section 5: 510(k) Summary
510(k) Summary Repor

Roche Molecular Systems, Inc
Pleasanton, CA 94588-2722

able 11: In-House Precision Study Hit Rate Analysi

| Panel Matrix Panel
Member | CT
Mean | CT
Positive | CT
Valid | CT
% Hit
Rate | CT
95% CI | NG
Mean | NG
Positive | NG
Valid | NG
% Hit
Rate | NG
95% CI |
|--------------------------------------------|-- | Urine stabilized
in cobas® PCR
Media | 1 | N/A | 0 | | 2 | | 3 | | 4 | | 5 | | 6 | | 7 | | 8 | | 9 | Vaginal swab in
cobas® PCR
Media | 1 | N/A | | 2 | | 3 | | 4 | | 5 | | 6 | | 7 | | 8 | | 9 | Matrix Panel
Member | CT
Mean | CT
Positive | CT
Valid | CT
% Hit Rate | CT
95% CI | NG
Mean | NG
Positive | NG
Valid | NG
% Hit Rate | NG
95% CI |
| | 1 | | 2 | | 3 | | 4 | PreservCyt® | 5 | | 6 | | 7 | | 8 | | 9 | Target
-------------------------|------------|----------------|-------------|---------------------|--------------|------------|----------------|-------------|---------------------|--------------|
| 48 | 0 | 0 - 7.4% | N/A | 0 | 48 | 0 | 0 - 7.4% |
| N/A | 0 | 48 | 0 | 0 - 7.4% | 36.9 | 32 | 48 | 67 | 51.6 - 79.6% |
| 37.9 | 40 | 48 | 83 | 69.8 - 92.5% | N/A | 0 | 48 | 0 | 0 - 7.4% |
| 35.5 | 48 | 48 | 100 | 92.6 - 100% | 36.2 | 48 | 48 | 100 | 92.6 - 100% |
| 34.6 | 48 | 48 | 100 | 92.6 - 100% | 36.1 | 48 | 48 | 100 | 92.6 - 100% |
| 35.4 | 48 | 48 | 100 | 92.6 - 100% | 35.1 | 48 | 48 | 100 | 92.6 - 100% |
| 36.1 | 48 | 48 | 100 | 92.6 - 100% | 18.4 | 48 | 48 | 100 | 92.6 - 100% |
| 18.0 | 48 | 48 | 100 | 92.6 - 100% | 36.7 | 48 | 48 | 100 | 92.6 - 100% |
| 18.3 | 48 | 48 | 100 | 92.6 - 100% | 18.0 | 48 | 48 | 100 | 92.6 - 100% |
| 0 | 48 | 0 | 0 - 7.4% | N/A | 0 | 48 | 0 | 0 - 7.4% |
| N/A | 0 | 48 | 0 | 0 - 7.4% | 37.6 | 29 | 48 | 60 | 45.3 - 74.2% |
| 36.9 | 22 | 48 | 46 | 31.4 - 60.8% | N/A | 0 | 48 | 0 | 0 - 7.4% |
| 36.5 | 48 | 48 | 100 | 92.6 - 100% | 37.1 | 48 | 48 | 100 | 92.6 - 100% |
| 35.8 | 48 | 48 | 100 | 92.6 - 100% | 37.2 | 48 | 48 | 100 | 92.6 - 100% |
| 36.7 | 47 | 48 | 98 | 88.9 - 99.9% | 36.5 | 48 | 48 | 100 | 92.6 - 100% |
| 36.6 | 47 | 48 | 98 | 88.9 - 99.9% | 18.6 | 48 | 48 | 100 | 92.6 - 100% |
| 21.6 | 48 | 48 | 100 | 92.6 - 100% | 36.8 | 48 | 48 | 100 | 92.6 - 100% |
| 21.2 | 48 | 48 | 100 | 92.6 - 100% | 18.1 | 48 | 48 | 100 | 92.6 - 100% |
| Target
| N/A | 0 | 47 | 0 | 0 - 7.5% | N/A | 0 | 47 | 0 | 0 - 7.5% |
| N/A | 0 | 47 | 0 | 0 - 7.5% | 36.0 | 26 | 47 | 55 | 40.1 - 69.8% |
| 36.4 | 26 | 47 | 55 | 40.1 - 69.8% | N/A | 0 | 47 | 0 | 0 - 7.5% |
| 35.0 | 48 | 48 | 100 | 92.6 - 100% | 34.7 | 47 | 48 | 98 | 88.9 - 99.9% |
| 33.7 | 47 | 47 | 100 | 92.5 - 100% | 34.8 | 47 | 47 | 100 | 92.5 - 100% |
| 34.7 | 48 | 48 | 100 | 92.6 - 100% | 33.5 | 48 | 48 | 100 | 92.6 - 100% |
| 34.8 | 48 | 48 | 100 | 92.6 - 100% | 18.9 | 48 | 48 | 100 | 92.6 - 100% |
| 18.9 | 48 | 48 | 100 | 92.6 - 100% | 34.3 | 48 | 48 | 100 | 92.6 - 100% |
| 18.8 | 48 | 48 | 100 | 92.6 - 100% | 17.7 | 48 | 48 | 100 | 92.6 - 100% |

18

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

510(k) Premarket Notification
Print Date: November 18, 2013

19

CLINICAL PERFORMANCE 5.

The clinical performance characteristics of the cobas® CT/NG v2.0 Test were established in three multi-center clinical investigations conducted in the United States. One study evaluated the reproducibility at one internal and two external testing sites and two studies evaluated the sensitivity, specificity, and predictive values of the cobas CT/NG v2.0 Test on clinical specimens tested at 7 external testing sites.

One clinical investigation used archived endocervical specimens, self-collected and clinician collected vaginal specimens, endocervical specimens in PreservCyt Solution and male and female urine specimens, from symptomatic and asymptomatic males and females, collected during the clinical evaluation of the cobas® CT/NG Test (archived samples). A sccond investigation was performed using prospectively collected endocervical specimens, cliniciancollected vaginal specimens, female urine specimens, and cervical specimens in PrescryCvt Solution from asymptomatic women (prospective fresh samples). Specimen collection for these studies took place at 18 collection sites in the US, which included family planning and Obstetrics/Gynecology (OB/GYN) clinics, and sexually transmitted disease clinics.

Reproducibility 5.1.

A Reproducibility Study was performed across, testing site, operator, run, and day for the cobase CT/NG v2.0 Test for detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using 3 panels prepared from negative vaginal swabs collected in cobas® PCR Media, negative urine stabilized in cobas® PCR Media and negative cervical specimens collected in PreservCvt® Solution. The 5 panel members for each matrix type contained single target levels of CT and NG at 1 x LOD and 3 x LOD plus one CT/NG negative level. Testing was performed at two external sites and one in-house site. A run for cobas® PCR Media (urine and swab) included 3 replicates of each of 5 panel members and 1 negative control (32 total tests). A run for the PreservCyt® Solution panel included 3 replicates of each of 5 panel members and 1 positive and 1 negative control (17 total tests). The 2 operators at each site performed 1 run per day each, for, a total of 5 days of testing per operator per panel type (10 days of testing total for each panel type). Testing was performed with 1 reagent lot.

20

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

Overall, 127 runs were performed: 62 were for urine and swab panels (which were run together) and 65 were for PreservCyt panels. Sixty valid runs were obtained for each media type. Two failed runs occurred for the urine and swab panels, and 5 failed runs occurred for the PreservCvt panels. Failed runs were attributed to protocol deviations and instrument errors. A total of 900 tests were performed on the 5 panel members for each panel type. There was 1 invalid test result in the PreservCyt panel type, and 1 failed test result each in the swab, urine and PreservCyt panels. These failed tests were due to instrument errors.

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

C. trachomatis (Table 12, Table 13, Table 14, and Table 15) 5.1.1.

Tuble 12 below presents the total standard deviation (SD) and total percent coefficient of variation (CV [%]) for each panel type, respectively. Across all panel types, the total CV (%) ranged from 1.4% to 2.6%.

Percent agreement for the CT-positive panel members was 100% for 3 X LOD CT of all 3 panel types and also for the 1 X LOD CT of urine panel type. For the remaining 1 X LOD CT. percent agreement was 96.7% for swab and 98.9% for PreservCyt panel types. (Table 13 through Table 15.)

21

.

Table 12: C. trachomatis: Overall Mean, Standard Deviations, and Coefficients of Variation (%) for Cycle Threshold, Estimated From Valid Samples of Positive Sample Type Panel Members

			Standard Deviation [SD] and Percent Coefficient of Variation [CV(%)]
Panel
Member	n¹/
N	Mean
Ct		Within-
Run		Between-
Run		Between-
Day		Between-
Operator		Between-
Site/
Instrument		Total
			SD	CV%	SD	CV%	SD	CV%	SD	CV%	SD	CV%	SD	CV%
			PCR Media/Urine
1 X LOD CT,
Negative NG	180/
180	37.11	0.54	1.5%	0.00	0.0%	0.23	0.6%	0.13	0.4%	0.22	0.6%	0.64	1.7%
3 X LOD CT,
Negative NG	180/
180	35.77	0.38	1.1%	0.18	0.5%	0.15	0.4%	0.00	0.0%	0.21	0.6%	0.50	1.4%
			PCR Media/Swab
1 X LOD CT,
Negative NG	174/
180	36.99	0.82	2.2%	0.17	0.5%	0.00	0.0%	0.00	0.0%	0.00	0.0%	0.84	2.3%
3 X LOD CT,
Negative NG	180/
180	36.11	0.42	1.2%	0.24	0.7%	0.14	0.4%	0.14	0.4%	0.00	0.0%	0.53	1.5%
			PreservCyt Solution
1 X LOD CT,
Negative NG	177/
179	35.21	0.88	2.5%	0.00	0.0%	0.28	0.8%	0.00	0.0%	0.00	0.0%	0.93	2.6%
3 X LOD CT,
Negative NG	180/
180	33.81	0.68	2.0%	0.03	0.1%	0.18	0.5%	0.15	0.4%	0.00	0.0%	0.72	2.1%

1 n is the number of positive tests, which contribute Ct values to the analysis. N is the total number of valid tests for the panel member.

22

| Panel
Member | Ct
SD | Ct CV
% | Overall | Percent Agreement* | | | |
|-----------------------------|----------|------------|---------|--------------------|-------------------------------------------------|----------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------|
| | | | | Site / Instrument | Operator | Day | |
| 1 X LOD CT,
Negative NG | 0.64 | 1.7 | 100.0 | 180/180 | 1 100.0 60/60
2 100.0 60/60
3 100.0 60/60 | 1 100.0 30/30
2 100.0 30/30
3 100.0 30/30
4 100.0 30/30
5 100.0 30/30
6 100.0 30/30 | 1 100.0 36/36
2 100.0 36/36
3 100.0 36/36
4 100.0 36/36
5 100.0 36/36 |
| 3 X LOD CT,
Negative NG | 0.50 | 1.4 | 100.0 | 180/180 | 1 100.0 60/60
2 100.0 60/60
3 100.0 60/60 | 1 100.0 30/30
2 100.0 30/30
3 100.0 30/30
4 100.0 30/30
5 100.0 30/30
6 100.0 30/30 | 1 100.0 36/36
2 100.0 36/36
3 100.0 36/36
4 100.0 36/36
5 100.0 36/36 |
| Negative CT,
1 X LOD NG | n/a | n/a | 100.0 | 180/180 | 1 100.0 60/60
2 100.0 60/60
3 100.0 60/60 | 1 100.0 30/30
2 100.0 30/30
3 100.0 30/30
4 100.0 30/30
5 100.0 30/30
6 100.0 30/30 | 1 100.0 36/36
2 100.0 36/36
3 100.0 36/36
4 100.0 36/36
5 100.0 36/36 |
| Negative CT,
3 X LOD NG | n/a | n/a | 100.0 | 179/179 | 1 100.0 60/60
2 100.0 59/59
3 100.0 60/60 | 1 100.0 30/30
2 100.0 30/30
3 100.0 30/30
4 100.0 29/29
5 100.0 30/30
6 100.0 30/30 | 1 100.0 36/36
2 100.0 36/36
3 100.0 35/35
4 100.0 36/36
5 100.0 36/36 |
| Negative CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 100.0 60/60
2 100.0 60/60
3 100.0 60/60 | 1 100.0 30/30
2 100.0 30/30
3 100.0 30/30
4 100.0 30/30
5 100.0 30/30
6 100.0 30/30 | 1 100.0 36/36
2 100.0 36/36
3 100.0 36/36
4 100.0 36/36
5 100.0 36/36 |

Table 13: C. trachomatis: Percent Agreement by Panel Member Overall and for Site/Instrument, Operator, and Day - PCR Media/Urine

For negative samples, percent agreement = (number of negative results/total valid results) x 100;

for positive samples, percent agreement = (number of positive results/total valid results) x 100.

Ct = cycle threshold; SD = standard deviation; CV = coefficient of variation; LOD = limit of detection;

n/a = not applicable; CT = C. trachomatis; NG = N. gonorthoeae; n/a = not applicable.

23

Table 14: C. trachomatis. Percent Agreement by Panel Member Overall and for
Site/Instrument, Operator, and Day - PCR Media/Swab

| Panel
Member | Ct
SD | Ct CV
% | Overall | Site / Instrument | Operator | Day |
|-----------------------------|----------|------------|------------------|-------------------|------------------|------------------|
| 1 X LOD CT,
Negative NG | 0.84 | 2.3 | 96.7
174/180 | 1 98.3
59/60 | 1 96.7
29/30 | 1 100.0
36/36 |
| | | | | 2 95.0
57/60 | 2 100.0
30/30 | 2 97.2
35/36 |
| | | | | 3 96.7
58/60 | 3 96.7
29/30 | 3 97.2
35/36 |
| | | | | | 4 93.3
28/30 | 4 94.4
34/36 |
| | | | | | 5 96.7
29/30 | 5 94.4
34/36 |
| | | | | | 6 96.7
29/30 | |
| 3 X LOD CT,
Negative NG | 0.53 | 1.5 | 100.0
180/180 | 1 100.0
60/60 | 1 100.0
30/30 | 1 100.0
36/36 |
| | | | | 2 100.0
60/60 | 2 100.0
30/30 | 2 100.0
36/36 |
| | | | | 3 100.0
60/60 | 3 100.0
30/30 | 3 100.0
36/36 |
| | | | | | 4 100.0
30/30 | 4 100.0
36/36 |
| | | | | | 5 100.0
30/30 | 5 100.0
36/36 |
| | | | | | 6 100.0
30/30 | |
| Negative CT,
1 X LOD NG | n/a | n/a | 100.0
180/180 | 1 100.0
60/60 | 1 100.0
30/30 | 1 100.0
36/36 |
| | | | | 2 100.0
60/60 | 2 100.0
30/30 | 2 100.0
36/36 |
| | | | | 3 100.0
60/60 | 3 100.0
30/30 | 3 100.0
36/36 |
| | | | | | 4 100.0
30/30 | 4 100.0
36/36 |
| | | | | | 5 100.0
30/30 | 5 100.0
36/36 |
| | | | | | 6 100.0
30/30 | |
| Negative CT,
3 X LOD NG | n/a | n/a | 100.0
180/180 | 1 100.0
60/60 | 1 100.0
30/30 | 1 100.0
36/36 |
| | | | | 2 100.0
60/60 | 2 100.0
30/30 | 2 100.0
36/36 |
| | | | | 3 100.0
60/60 | 3 100.0
30/30 | 3 100.0
36/36 |
| | | | | | 4 100.0
30/30 | 4 100.0
36/36 |
| | | | | | 5 100.0
30/30 | 5 100.0
36/36 |
| | | | | | 6 100.0
30/30 | |
| Negative CT,
Negative NG | n/a | n/a | 99.4
178/179 | 1 100.0
60/60 | 1 100.0
30/30 | 1 100.0
36/36 |
| | | | | 2 100.0
59/59 | 2 100.0
30/30 | 2 100.0
35/35 |
| | | | | 3 98.3
59/60 | 3 100.0
29/29 | 3 97.2
35/36 |
| | | | | | 4 100.0
30/30 | 4 100.0
36/36 |
| | | | | | 5 96.7
29/30 | 5 100.0
36/36 |
| | | | | | 6 100.0
30/30 | |

For negative samples, percent agreement = (number of negative results/total valid results) x 100;

for positive samples, percent agreement = (number of positive results/total valid results) x 100.

Ct = cycle threshold; SD = standard deviation; CV = coefficient of variation; LOD = limit of delection; n/a = not applicable; CT = C. trachomatis; NG = N. gonorthoeae; n/a = not applicable.

24

| Panel
Member | Ct
SD | Ct CV
% | Overall | | Site / Instrument | | Operator | | Day | | | | |
|-----------------------------|----------|------------|---------|---------|-------------------|-------|----------|---|-------|-------|---|-------|-------|
| 1 X LOD CT,
Negative NG | 0.93 | 2.6 | 98.9 | 177/179 | 1 | 98.3 | 59/60 | 1 | 96.7 | 29/30 | 1 | 100.0 | 36/36 |
| | | | | | 2 | 98.3 | 58/59 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 100.0 | 60/60 | 3 | 96.7 | 29/30 | 3 | 97.2 | 35/36 |
| | | | | | 4 | | | 4 | 100.0 | 29/29 | 4 | 100.0 | 35/35 |
| | | | | | 5 | | | 5 | 100.0 | 30/30 | 5 | 97.2 | 35/36 |
| | | | | | 6 | | | 6 | 100.0 | 30/30 | | | |
| 3 X LOD CT,
Negative NG | 0.72 | 2.1 | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 |
| | | | | | 4 | | | 4 | 100.0 | 30/30 | 4 | 100.0 | 36/36 |
| | | | | | 5 | | | 5 | 100.0 | 30/30 | 5 | 100.0 | 36/36 |
| | | | | | 6 | | | 6 | 100.0 | 30/30 | | | |
| Negative CT,
1 X LOD NG | n/a | n/a | 100.0 | 179/179 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 35/35 |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 100.0 | 59/59 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 |
| | | | | | 4 | | | 4 | 100.0 | 30/30 | 4 | 100.0 | 36/36 |
| | | | | | 5 | | | 5 | 100.0 | 29/29 | 5 | 100.0 | 36/36 |
| | | | | | 6 | | | 6 | 100.0 | 30/30 | | | |
| Negative CT,
3 X LOD NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 |
| | | | | | 4 | | | 4 | 100.0 | 30/30 | 4 | 100.0 | 36/36 |
| | | | | | 5 | | | 5 | 100.0 | 30/30 | 5 | 100.0 | 36/36 |
| | | | | | 6 | | | 6 | 100.0 | 30/30 | | | |
| Negative CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 |
| | | | | | 4 | | | 4 | 100.0 | 30/30 | 4 | 100.0 | 36/36 |
| | | | | | 5 | | | 5 | 100.0 | 30/30 | 5 | 100.0 | 36/36 |
| | | | | | 6 | | | 6 | 100.0 | 30/30 | | | |

Table 15: C. trachomatis. Percent Agreement by Panel Member Overall and for Site/Instrument, Operator, and Day - PreservCyt

For negative samples, percent agreement = (number of negative results/total valid results) x 100; for positive samples, percent agreement = (number of positive results/total valid results) x 100.

Ct = cycle threshold; SD = standard deviation; CV = coefficient of variation; LOD = limit of detection; CT = C. trachomatis; NG = N. gonorrhoeae; n/a = not applicable.

25

N. gonorrhoeae (Table 16, Table 17, Table 18, Table 19) 5.1.2.

Table 16 below presents the total standard deviation (SD) and total percent coefficient of variation (CV [%]) for each panel type, respectively. Across all panel types, the total CV (%) ranged from 1.6% to 2.6%.

Percent agreement for the NG positive panel members was 99.4% for the 3 X LOD NG urinc panel and 100% for the 3 X LOD NG swab and PreservCyt panel types. ) For the 1 X LOD NG, percent agreement was 95% for the urine panel type, 89.4% for the swab panel type and 99.4% for the PreservCyt panel type (Table 17 through Table 19).

There were no false positive results for NG negative panel members across all 3 panel types, thus vielding an analytical specificity of 100% for each panel type.

| Panel
Member | n¹/
N | Mean
Ct | Within-
Run | | Between-
Run | | Between-
Day | | Between-
Operator | | Between-
Site/
Instrument | | Total | |
|----------------------------------------------------------------------|-------------|------------|----------------|------|-----------------|------|-----------------|------|----------------------|------|---------------------------------|------|-------|------|
| Standard Deviation [SD] and Percent Coefficient of Variation [CV(%)] | | | | | | | | | | | | | | |
| PCR Media/Urine | | | | | | | | | | | | | | |
| Negative CT,
1 X LOD NG | 171/
180 | 38.00 | 0.58 | 1.5% | 0.26 | 0.7% | 0.00 | 0.0% | 0.17 | 0.5% | 0.16 | 0.4% | 0.67 | 1.8% |
| Negative CT,
3 X LOD NG | 178/
179 | 36.93 | 0.52 | 1.4% | 0.18 | 0.5% | 0.17 | 0.5% | 0.02 | 0.1% | 0.26 | 0.7% | 0.63 | 1.7% |
| PCR Media/Swab | | | | | | | | | | | | | | |
| Negative CT,
1 X LOD NG | 161/
180 | 37.97 | 0.58 | 1.5% | 0.24 | 0.6% | 0.05 | 0.1% | 0.27 | 0.7% | 0.00 | 0.0% | 0.68 | 1.8% |
| Negative CT,
3 X LOD NG | 180/
180 | 37.31 | 0.56 | 1.5% | 0.12 | 0.3% | 0.00 | 0.0% | 0.08 | 0.2% | 0.15 | 0.4% | 0.60 | 1.6% |
| PreservCyt Solution | | | | | | | | | | | | | | |
| Negative CT,
1 X LOD NG | 178/
179 | 35.22 | 0.92 | 2.6% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.92 | 2.6% |
| Negative CT,
3 X LOD NG | 180/
180 | 33.72 | 0.70 | 2.1% | 0.19 | 0.6% | 0.00 | 0.0% | 0.21 | 0.6% | 0.10 | 0.3% | 0.76 | 2.3% |

Table 16: N. gonorrhoeae. Overall Mean, Standard Deviations, and Coefficients of Variation (%) for Cycle Threshold, Estimated From Valid Samples of Positive Sample Type Panel Members

1 n is the number of positive tests, which contribute Ct values to the total number of valid tests for the panel member.

26

Table 17: N. gonorrhocac: Percent Agreement by Panel Member Overall and for
Site/Instrument, Operator, and Day - PCR Media/Urine

| Panel
Member | Ct
SD | Ct CV
% | Percent Agreement * | | | | | | | | | | |
|-----------------------------|----------|------------|---------------------|-------------------|---|----------|-------|-------|-------|-------|-------|-------|-------|
| | | | Overall | Site / Instrument | | Operator | | | Day | | | | |
| 1 X LOD CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 |
| | | | | | | | 4 | 100.0 | 30/30 | 4 | 100.0 | 36/36 | |
| | | | | | | | 5 | 100.0 | 30/30 | 5 | 100.0 | 36/36 | |
| | | | | | | | 6 | 100.0 | 30/30 | | | | |
| 3 X LOD CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 |
| | | | | | | | 4 | 100.0 | 30/30 | 4 | 100.0 | 36/36 | |
| | | | | | | | 5 | 100.0 | 30/30 | 5 | 100.0 | 36/36 | |
| | | | | | | | 6 | 100.0 | 30/30 | | | | |
| Negative CT,
1 X LOD NG | 0.67 | 1.8 | 95.0 | 171/180 | 1 | 96.7 | 58/60 | 1 | 96.7 | 29/30 | 1 | 91.7 | 33/36 |
| | | | | | 2 | 96.7 | 58/60 | 2 | 96.7 | 29/30 | 2 | 94.4 | 34/36 |
| | | | | | 3 | 91.7 | 55/60 | 3 | 96.7 | 29/30 | 3 | 100.0 | 36/36 |
| | | | | | | | 4 | 96.7 | 29/30 | 4 | 91.7 | 33/36 | |
| | | | | | | | 5 | 96.7 | 29/30 | 5 | 97.2 | 35/36 | |
| | | | | | | | 6 | 86.7 | 26/30 | | | | |
| Negative CT,
3 X LOD NG | 0.63 | 1.7 | 99.4 | 178/179 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 |
| | | | | | 2 | 100.0 | 59/59 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 98.3 | 59/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 35/35 |
| | | | | | 4 | 100.0 | 29/29 | 4 | 100.0 | 30/30 | 4 | 100.0 | 36/36 |
| | | | | | 5 | 100.0 | 30/30 | 5 | 97.2 | 35/36 | 5 | 97.2 | 35/36 |
| | | | | | | | 6 | 96.7 | 29/30 | | | | |
| Negative CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 |
| | | | | | | | 4 | 100.0 | 30/30 | 4 | 100.0 | 36/36 | |
| | | | | | | | 5 | 100.0 | 30/30 | 5 | 100.0 | 36/36 | |
| | | | | | | | 6 | 100.0 | 30/30 | | | | |

For negative samples, percent agreement = (number of negative results) x 100; for positive samples, percent agreement = (number of positive results/total valid results) x 100.

Ct = cycle threshold; SD = standard deviation; CV = coefficient of variation; LOD = limit of detection; CT = C. trachomatis; NG = N. gonorrhoeae; n/a = not applicable.

27

1

| Panel
Member | Ct
SD | Ct CV
% | Percent Agreement | | | | | | | | | | | | |
|-----------------------------|----------|------------|-------------------|---------|-------------------|-------|-------|----------|-------|-------|-------|-------|-------|--|--|
| | | | Overall | | Site / Instrument | | | Operator | | | Day | | | | |
| 1 X LOD CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 | | |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 | | |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 | | |
| | | | | | 4 | | | 100.0 | 30/30 | 4 | 100.0 | 36/36 | | | |
| | | | | | 5 | | | 100.0 | 30/30 | 5 | 100.0 | 36/36 | | | |
| | | | | | 6 | | | 100.0 | 30/30 | | | | | | |
| 3 X LOD CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 | | |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 | | |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 | | |
| | | | | | 4 | | | 100.0 | 30/30 | 4 | 100.0 | 36/36 | | | |
| | | | | | 5 | | | 100.0 | 30/30 | 5 | 100.0 | 36/36 | | | |
| | | | | | 6 | | | 100.0 | 30/30 | | | | | | |
| Negative CT,
1 X LOD NG | 0.68 | 1.8 | 89.4 | 161/180 | 1 | 91.7 | 55/60 | 1 | 93.3 | 28/30 | 1 | 91.7 | 33/36 | | |
| | | | | | 2 | 85.0 | 51/60 | 2 | 90.0 | 27/30 | 2 | 94.4 | 34/36 | | |
| | | | | | 3 | 91.7 | 55/60 | 3 | 73.3 | 22/30 | 3 | 88.9 | 32/36 | | |
| | | | | | 4 | | | 96.7 | 29/30 | 4 | 86.1 | 31/36 | | | |
| | | | | | 5 | | | 93.3 | 28/30 | 5 | 86.1 | 31/36 | | | |
| | | | | | 6 | | | 90.0 | 27/30 | | | | | | |
| Negative CT,
3 X LOD NG | 0.60 | 1.6 | 100.0 | 180/180 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 | | |
| | | | | | 2 | 100.0 | 60/60 | 2 | 100.0 | 30/30 | 2 | 100.0 | 36/36 | | |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 30/30 | 3 | 100.0 | 36/36 | | |
| | | | | | 4 | | | 100.0 | 30/30 | 4 | 100.0 | 36/36 | | | |
| | | | | | 5 | | | 100.0 | 30/30 | 5 | 100.0 | 36/36 | | | |
| | | | | | 6 | | | 100.0 | 30/30 | | | | | | |
| Negative CT,
Negative NG | n/a | n/a | 100.0 | 179/179 | 1 | 100.0 | 60/60 | 1 | 100.0 | 30/30 | 1 | 100.0 | 36/36 | | |
| | | | | | 2 | 100.0 | 59/59 | 2 | 100.0 | 30/30 | 2 | 100.0 | 35/35 | | |
| | | | | | 3 | 100.0 | 60/60 | 3 | 100.0 | 29/29 | 3 | 100.0 | 36/36 | | |
| | | | | | 4 | | | 100.0 | 30/30 | 4 | 100.0 | 36/36 | | | |
| | | | | | 5 | | | 100.0 | 30/30 | 5 | 100.0 | 36/36 | | | |
| | | | | | 6 | | | 100.0 | 30/30 | | | | | | |

Table 18: N. gonorrhocae. Percent Agreement by Panel Member Overall and for Site/Instrument, Operator, and Day - PCR Media/Swab

For negalive samples, percent agreement = (number of negalive results) x 100; for positive samples, percent agreement = (number of positive results/total valid results) x 100.

Ct = cycle threshold; SD = standard deviation; CV = coefficient of variation; LOD = limit of detection;

CT = C. trachomatis; NG = N. gonorrhoeae; n/a = not applicable.

28

Table 19: N. gonorrhoeac. Percent Agreement by Panel Member Overall and for
Site/Instrument, Operator, and Day - PreservCyt

| Panel
Member | Ct
SD | Ct CV
% | Percent Agreement * | | | | | | | |
|-----------------------------|----------|------------|---------------------|-------------------|-------------|-------------|-------------|-------------|-------------|-------------|
| | | | Overall | Site / Instrument | | Operator | | Day | | |
| 1 X LOD CT,
Negative NG | n/a | n/a | 100.0 | 179/179 | 1 | 100.0 60/60 | 1 | 100.0 30/30 | 1 | 100.0 36/36 |
| | | | | 2 | 100.0 59/59 | 2 | 100.0 30/30 | 2 | 100.0 36/36 | |
| | | | | 3 | 100.0 60/60 | 3 | 100.0 30/30 | 3 | 100.0 36/36 | |
| | | | | | | 4 | 100.0 29/29 | 4 | 100.0 35/35 | |
| | | | | | | 5 | 100.0 30/30 | 5 | 100.0 36/36 | |
| | | | | | | 6 | 100.0 30/30 | | | |
| 3 X LOD CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 60/60 | 1 | 100.0 30/30 | 1 | 100.0 36/36 |
| | | | | 2 | 100.0 60/60 | 2 | 100.0 30/30 | 2 | 100.0 36/36 | |
| | | | | 3 | 100.0 60/60 | 3 | 100.0 30/30 | 3 | 100.0 36/36 | |
| | | | | | | 4 | 100.0 30/30 | 4 | 100.0 36/36 | |
| | | | | | | 5 | 100.0 30/30 | 5 | 100.0 36/36 | |
| | | | | | | 6 | 100.0 30/30 | | | |
| Negative CT,
1 X LOD NG | 0.92 | 2.6 | 99.4 | 178/179 | 1 | 100.0 60/60 | 1 | 100.0 30/30 | 1 | 100.0 35/35 |
| | | | | 2 | 98.3 59/60 | 2 | 100.0 30/30 | 2 | 97.2 35/36 | |
| | | | | 3 | 100.0 59/59 | 3 | 96.7 29/30 | 3 | 100.0 36/36 | |
| | | | | | | 4 | 100.0 30/30 | 4 | 100.0 36/36 | |
| | | | | | | 5 | 100.0 29/29 | 5 | 100.0 36/36 | |
| | | | | | | 6 | 100.0 30/30 | | | |
| Negative CT,
3 X LOD NG | 0.76 | 2.3 | 100.0 | 180/180 | 1 | 100.0 60/60 | 1 | 100.0 30/30 | 1 | 100.0 36/36 |
| | | | | 2 | 100.0 60/60 | 2 | 100.0 30/30 | 2 | 100.0 36/36 | |
| | | | | 3 | 100.0 60/60 | 3 | 100.0 30/30 | 3 | 100.0 36/36 | |
| | | | | | | 4 | 100.0 30/30 | 4 | 100.0 36/36 | |
| | | | | | | 5 | 100.0 30/30 | 5 | 100.0 36/36 | |
| | | | | | | 6 | 100.0 30/30 | | | |
| Negative CT,
Negative NG | n/a | n/a | 100.0 | 180/180 | 1 | 100.0 60/60 | 1 | 100.0 30/30 | 1 | 100.0 36/36 |
| | | | | 2 | 100.0 60/60 | 2 | 100.0 30/30 | 2 | 100.0 36/36 | |
| | | | | 3 | 100.0 60/60 | 3 | 100.0 30/30 | 3 | 100.0 36/36 | |
| | | | | | | 4 | 100.0 30/30 | 4 | 100.0 36/36 | |
| | | | | | | 5 | 100.0 30/30 | 5 | 100.0 36/36 | |
| | | | | | | 6 | 100.0 30/30 | | | |

For negative samples, percent agreement = (number of negative results/total valid results) x 100;

for positive samples, percent agreement = (number of positive results/total valid results) x 100.

Ct = cycle threshold; SD = standard deviation; CV = coefficient of variation; LOD = limit of detection; CT = C. trachonia(is; NG = N. gonorrhoeae; n/a = not applicable.

29

5.2. Clinical Specimen Study

5.2.1. Study Design

The clinical performance characteristics of the cobas® CT/NG v2.0 Test were evaluated in two multi-center clinical studies conducted in the United States. One clinical investigation used archived endocervical specimens, self-collected and clinician collected vaginal specimens, endocervical specimens in PreservCyt Solution and male urine specimens, from symptomatic and asymptomatic males and females, collected during the clinical evaluation of the cobas® CT/NG Test (archived samples). A second investigation was performed using prospectively collected endocervical specimens, clinician-collected vaginal specimens, female urine specimens, and cervical specimens in PreservCyt Solution from asymptomatic women (prospective fresh samples). Specimen collection for these studies took place at 18 collection sites in the US, which included family planning and Obstetrics/Gynecology (OB/GYN) clinics. and sexually transmitted disease clinics.

At collection sites, each female subject provided a urine specimen, a self-collected or cliniciancollected vaginal swab specimen. a clinician-collected endocervical swab specimen. and a cervical specimen in PreservCyt® solution obtained with a spatula/cytobrush or a broom. For determination of Patient Infected Status (PIS) an aliquot of each urine, aliquots of each cervical specimen in PreservCyt solution, and an additional endocervical specimen, were collected in the appropriate transport media for two commercially available nucleic acid amplification tests (NAAT). For females, urine specimens were collected first. If a cervical cvtology test was a scheduled part of the visit, that sample was taken next, followed by a vaginal 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 an endocervical swab and then the cervical specimen. The order of endocervical swab collection as well as clinician- or self-collection of the vaginal swabs was alternated to minimize collection bias.

Male subjects provided a urine specimen in cobas® PCR media and for the determination of PIS, urine and urethral swab specimens in collection media from two commercially available NAAT. For males, the urethral swabs were collected first in alternating order and then the urine specimen was collected.

30

5.2.2. Determination of Patient Infected Status

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 20 and Table 22. For CT only, 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. 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 was determined for all evaluable subjects enrolled in the study.

| NAAT1
Urine/Endocervical | NAAT2
Urine/Endocervical | NAAT2
Cervical Specimen
in PreservCyt | Patient Infected Status |
|-----------------------------|-----------------------------|---------------------------------------------|-----------------------------------------------------------------------------------|
| +/+ | +/+ | + or - | Infected |
| +/+ | +/- or -/+ | + or - | Infected |
| +/- or -/+ | +/+ | + or - | Infected |
| +/- | -/+ | + or - | Infected |
| -/+ | +/- | + or - | Infected |
| -/+ | -/+ | + or - | Infected |
| +/- | +/- | + | Infected |
| +/- | +/- | | CT: Infected (Urine)
Non-Infected (Swabs)
NG: Infected
(Urine and Swabs) |
| +/- or -/+ | -/- | + or - | Non-Infected |
| +/+ | -/- | + or - | Non-Infected |
| -/- | +/+ | + or - | Non-Infected |
| -/- | +/- or -/+ | + or - | Non-Infected |
| -/- | -/- | + or - | Non-Infected |

	Table 20: Determination of Female Patient Infected Status
--	-----------------------------------------------------------	--	--	--	--

31

| NAAT 1
Urethral Swab/Urine | NAAT 2
Urethral Swab/Urine | Patient Infected Status
(PIS) |
|-------------------------------|-------------------------------|----------------------------------|
| +/+ | +/+ | Infected |
| +/+ | +/- or -/+ | Infected |
| +/- or -/+ | +/+ | Infected |
| +/- | -/+ | Infected |
| -/+ | +/- | Infected |
| -/+ | -/+ | Infected |
| +/- | +/- | Infected |
| +/- or -/+ | -/- | Non-Infected |
| +/+ | -/- | Non-Infected |
| -/- | +/+ | Non-Infected |
| -/- | +/- or -/+ | Non-Infected |
| -/- | -/- | Non-Infected |

Table 21: Determination of Male Patient Infected Status

5.2.3. Study Results

Results from the cobas " CT/NG v2.0 Test were compared with the PIS for calculation of test sensitivity and specificity. Of the 6,045 subjects enrolled (5,306 females and 739 males), 10 were excluded from the analyses because they did not meet study entry criteria or because they withdrew consent; 31 were considered non-evaluable and were excluded from all statistical analyses because of errors in specimen collection, transport, and storage; unknown PIS for both CT and NG; or invalid cobas® CTNG v2.0 Test results after initial testing and/or retesting. Therefore, of 6,035 eligible subjects enrolled, 6,004 (99.5%) were evaluable for CT and/or NG primary analyses (5,266 females and 738 males).

Results obtained from 1,011 prospective female asymptomatic subjects were analyzed combined with results obtained in the re-testing of all available samples (archived specimens) collected in the previous clinical study (4,255 females and 738 males).

In the clinical study, there was 1/385 (0.3%) invalid runs and 15/385 (3.9%) failed runs due to instrument error. Of the 26,283 specimens tested with the cobas® CT/NG v2.0 Test, 0.28% and 0.23% were initially invalid for CT and NG respectively and 1.38% initially had failed results for

32

both CT and NG. Following retesting up to two more times. 0.10% and 0.13% had final results of failed for both CT and NG. Table 22 through Table 29 summarize the data from the clinical specimen studies.

Chlamydia trachomatis (CT) 5.2.4.

Sensitivity, specificity, and predictive values of the cobas® CT/NG v2.0 Test for CT as defined by PIS are presented by gender, sample type, and symptom status in Table 22. Overall Sensitivity ranged from 93.7% to 98.4%. The sensitivity for CT was 94.9%, 94.0%, 98.4%, 97.6%, 98.2%, 94.2%, and 93.7% for endocervical swabs, female urine specimens, male urine specimens, self-collected vaginal swabs, clinician-collected vaginal swabs, and PreservCyt specimens (pre- and post-ThinPrep processing), respectively. Overall specificity ranged from 98.8% to 99.8% in both females and males. Performance estimates for CT detection were similar between symptomatic and asymptomatic subjects.

| Sample
Typeᵃ | Symptom
Statusᵇ | Total
(n) | SENS | 95% CI | SPEC | 95% CI | PREV
(%) | PPV
(%) | NPV
(%) |
|-----------------|--------------------|--------------|--------------------|--------------------|----------------------|-------------------|-------------|------------|------------|
| Female | | | | | | | | | |
| SW | Sympᶜ | 1932 | 94.7%
(144/152) | (90.0%,
97.3%) | 99.3%
(1767/1780) | (98.8%,
99.6%) | 7.9 | 91.7 | 99.5 |
| | Asympᵈ | 994 | 95.3%
(81/85) | (88.5%,
98.2%) | 99.6%
(905/909) | (98.9%,
99.8%) | 8.6 | 95.3 | 99.6 |
| | Overall | 2926 | 94.9%
(225/237) | (91.4%,
97.1%) | 99.4%
(2672/2689) | (99.0%,
99.6%) | 8.1 | 93.0 | 99.6 |
| UR | Sympᶜ | 1937 | 94.4%
(151/160) | (89.7%,
97.0%) | 99.7%
(1771/1777) | (99.3%,
99.8%) | 8.3 | 96.2 | 99.5 |
| | Asympᵈ | 1008 | 93.3%
(84/90) | (86.2%,
96.9%) | 99.5%
(913/918) | (98.7%,
99.8%) | 8.9 | 94.4 | 99.3 |
| | Overall | 2945 | 94.0%
(235/250) | (90.3%,
96.3%) | 99.6%
(2684/2695) | (99.3%,
99.8%) | 8.5 | 95.5 | 99.4 |
| VG-C | Sympᶜ | 899 | 96.2%
(76/79) | (89.4%,
98.7%) | 98.8%
(810/820) | (97.8%,
99.3%) | 8.8 | 88.4 | 99.6 |
| | Asympᵈ | 1003 | 100.0%
(89/89) | (95.9%,
100.0%) | 99.5%
(909/914) | (98.7%,
99.8%) | 8.9 | 94.7 | 100.0 |
| | Overall | 1902 | 98.2%
(165/168) | (94.9%,
99.4%) | 99.1%
(1719/1734) | (98.6%,
99.5%) | 8.8 | 91.7 | 99.8 |

Table 22: CT: Clinical Performance Compared With Patient Infected Status by Gender and Sample Type, and Symptom Status

33

| Sample
Typea | Symptom
Statusb | Total
(n) | SENS | 95% CI | SPEC | 95% CI | PREV
(%) | PPV
(%) | NPV
(%) |
|-----------------|--------------------|--------------|--------------------|-------------------|----------------------|-------------------|-------------|------------|------------|
| VG-S | Sympc | 1041 | 98.7%
(76/77) | (93.0%,
99.8%) | 99.2%
(956/964) | (98.4%,
99.6%) | 7.4 | 90.5 | 99.9 |
| | Asympc | 996 | 96.0%
(48/50) | (86.5%,
98.9%) | 99.4%
(940/946) | (98.6%,
99.7%) | 5.0 | 88.9 | 99.8 |
| | Overall | 2037 | 97.6%
(124/127) | (93.3%,
99.2%) | 99.3%
(1896/1910) | (98.8%,
99.6%) | 6.2 | 89.9 | 99.8 |
| PC Pre | Sympc | 1935 | 94.1%
(143/152) | (89.1%,
96.9%) | 99.7%
(1778/1783) | (99.3%,
99.9%) | 7.9 | 96.6 | 99.5 |
| | Asympd | 1002 | 94.3%
(83/88) | (87.4%,
97.5%) | 99.8%
(912/914) | (99.2%,
99.9%) | 8.8 | 97.6 | 99.5 |
| | Overall | 2937 | 94.2%
(226/240) | (90.4%,
96.5%) | 99.7%
(2690/2697) | (99.5%,
99.9%) | 8.2 | 97.0 | 99.5 |
| PC Post | Sympc | 1871 | 93.9%
(139/148) | (88.8%,
96.8%) | 99.5%
(1715/1723) | (99.1%,
99.8%) | 7.9 | 94.6 | 99.5 |
| | Asympd | 1007 | 93.3%
(83/89) | (86.1%,
96.9%) | 99.5%
(913/918) | (98.7%,
99.8%) | 8.8 | 94.3 | 99.3 |
| | Overall | 2878 | 93.7%
(222/237) | (89.8%,
96.1%) | 99.5%
(2628/2641) | (99.2%,
99.7%) | 8.2 | 94.5 | 99.4 |
| UR | Male | | | | | | | | |
| | Sympc | 278 | 98.6%
(69/70) | (92.3%,
99.7%) | 99.0%
(206/208) | (96.6%,
99.7%) | 25.2 | 97.2 | 99.5 |
| | Asympc | 460 | 98.1%
(51/52) | (89.9%,
99.7%) | 99.3%
(405/408) | (97.9%,
99.7%) | 11.3 | 94.4 | 99.8 |
| | Overall | 738 | 98.4%
(120/122) | (94.2%,
99.5%) | 99.2%
(611/616) | (98.1%,
99.7%) | 16.5 | 96.0 | 99.7 |

ª SW = endocervical swab, UR = urine, VG-C = clinician-collected vaginal swab, VG-S = self-collected vaginal swab, PC Pre = PreservCyt (pre-aliquot), PC Post = PreservCyt (post-aliquot).

b Symp = symptomatic, Asymp = asymptomatic.

cobas® CT/NG v2.0 Test results from archived specimens.

a cobas® CT/NG v2.0 Test results from prospectively collected specimens.

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

Note: Subjects with designated infection status and valid cobas CT/NG v2.0 Test results are 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.

For archived specimens from female asymptomatic patients, sensitivity for CT was

91.2% (93/102), 92.9% (104/112), 94.4% (51/54), 88.6% (93/105), and 87.5% (91/104),

respectively for endocervical swabs, female urine specimens, clinician-collected vaginal swabs,

and PreservCyt specimens (pre- and post-ThinPrep processing), with specificity for CT of

99.9% (2,076/2,078), 99.8% (2,065/2,070), 99.9% (1,183/1,184), 99.6% (2,085/2,094), and

99.7% (1,881/1,886) respectively for these sample types.

34

Table 23 and Table 24 summarize the results from symptomatic and asymptomatic subjects designated as infected or non-infected with CT (females and males, respectively) according to the PIS algorithm. A total of 365 females and 122 males were infected with CT. Symptoms were reported in 44.4% (162/365) of infected and 37.0% (1,814/4,900) of non-infected women. Similarly, symptoms were reported in 57.4% (70/122) of infected and 33.8% (208/616) of non-infected men. Overall, the CT prevalence was 6.9% (365/5,265), 16.5% (122/738), and 8.1% (487/6,003) in women, men, and the entire study population, respectively.

| Patient
Infected

Status	NAAT1ª		NAAT2ª		cobas CT/NG v2.0 Test			Symptom Statusb		Total
	SW	UR	SW	UR	PC Pre	SW	UR	VG	PC Pre	PC Post	Symp	Asymp
Infected	+	+	+	+	+	+	+	+	+	+	113	144	257
Infected	+	+	+	+	+	NA	+	+	+	+	3	7	10
Infected	+	+	+	+	+	+	-	+	+	+	3	2	5
Infected	+	+	+	+	-	+	+	-	+	+	2	3	5
Infected	+	+	+	+	+	+	+	+	+	NA	3	1	4
Infected	+	+	+	+	+	+	+	+	+	+	2	2	4
Infected	+	+	+	+	+	+	+	+	+	+	4	0	4
Infected	+	+	+	+	+	+	+	+	+	+	2	1	3
Infected	+	-	+	+	+	+	+	+	+	+	1	2	3
Infected	+	+	+	+	+	+	+	+	+	+	1	1	2
Infected	+	+	+	+	+	+	+	+	NA	NA	1	1	2
Infected	+	+	+	+	+	+	+	+	+	+	1	1	2
Infected	+	+	+	+	+	NA	+	NA	+	+	0	2	2
Infected	+	+	+	+	NA	+	+	+	NA	NA	1	1	2
Infected	+	-	+	+	+	+	-	-	+	-	0	2	2
Infected	-	+	+	+	+	+	+	+	+	+	0	2	2
Infected	-	+	+	+	+	-	+	+	-	-	1	1	2
Infected	-	+	+	+	+	-	+	+	-	-	2	0	2
Infected	+	+	-	+	+	-	+	+	-	-	1	1	2
Infected	+	+	+	+	+	+	+	+	NA	+	0	1	1
Infected	+	+	+	+	+	+	+	NA	+	+	1	0	1
Infected	+	+	+	+	+	+	+	+	+	-	0	1	1
Infected	+	+	+	+	+	+	NA	+	+	+	1	0	1
Infected	+	+	+	+	+	-	+	+	+	+	1	0	1
Infected	+	+	+	+	+	-	+	+	+	-	0	1	1
Infected	+	+	+	+	+	+	+	+	-	-	0	1	1
Infected	+	+	+	+	-	+	+	+	+	+	0	1	1
Infected	+	+	+	+	NA	NA	+	+	NA	NA	1	0	1
Infected	+	+	-	+	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	+	+	+	+	+	+	1	0	1
Patient
Infected
Status	NAAT1a		NAAT2a		cobas CT/NG v2.0 Test					Symptom Statusb		Total
	SW	UR	SW	UR	PC Pre	SW	UR	VG	PC Pre	PC Post	Symp	Asymp
Infected	+	+	-	+	+	-	+	+	+	-	0	1	1
Infected	+	+	-	+	+	-	+	+	+	-	0	1	1
Infected	+	+	-	+	+	+	+	+	+	NA	1	0	1
Infected	+	+	NA	+	NA	NA	NA	NA	NA	+	0	1	1
Infected	+	+	+	-	+	+	+	+	NA	+	1	0	1
Infected	+	+	+	+	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	+	+	+	+	+	-	0	1	1
Infected	+	+	+	+	+	NA	+	+	+	-	0	1	1
Infected	+	+	+	+	+	+	+	+	+	-	0	1	1
Infected	+	+	+	+	+	NA	+	+	+	NA	0	1	1
Infected	+	+	+	NA	+	+	+	+	+	+	1	0	1
Infected	+	+	+	+	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	+	+	+	+	+	NA	1	0	1
Infected	+	+	+	+	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	+	NA	+	+	+	+	1	0	1
Infected	+	+	+	+	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	+	+	+	+	+	+	1	0	1
Infected	+	+	+	+	+	NA	+	+	+	+	0	1	1
Infected	+	+	+	+	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	+	+	+	+	+	+	1	0	1
Infected	+	+	+	+	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	+	NA	+	+	+	+	0	1	1
Infected	+	+	NA	+	+	+	+	+	+	+	0	1	1
Infected	+	+	NA	+	NA	NA	NA	NA	NA	+	1	0	1
Infected	+	+	+	+	+	+	+	+	+	+	1	0	1
Infected	-	+	+	+	+	+	+	+	+	+	1	0	1
Infected	-	+	+	+	+	+	+	+	+	+	0	1	1
Infected	-	+	+	+	+	+	+	+	+	+	1	0	1
Infected	-	+	+	+	+	+	+	+	+	-	0	1	1
Infected	-	+	+	+	+	-	+	+	+	-	1	0	1
Infected	-	+	-	+	+	+	+	+	+	-	0	1	1
Infected	-	+	+	+	+	+	+	+	+	+	1	0	1
Infected	-	+	+	+	+	+	+	+	+	+	1	0	1
Infected	-	+	+	+	+	+	+	+	+	+	0	1	1
Infected	-	+	+	+	+	+	+	+	+	+	1	0	1
Infected	-	+	+	+	NA	+	+	+	NA	NA	0	1	1
Infected	-	+	NA	+	+	+	+	+	+	-	0	1	1
Infected	-	+	+	+	+	-	+	+	-	-	0	1	1
Total Infected											162	203	365
Patient
Infected
Status	NAAT1a		NAAT2a			cobas CT/NG v2.0 Test					Symptom Statusb
	SW	UR	SW	UR	PC Pre	SW	UR	VG	PC Pre	PC Post	Symp	Asymp	Total
Non-Infected	-	-	-	-	-	-	-	-	-	-	1575	2561	4136
Non-Infected	-	-	-	-	-	-	-	-	NA	-	57	178	235
Non-Infected	-	-	-	-	-	NA	-	-	-	-	27	30	57
Non-Infected	-	-	-	-	-	-	-	NA	-	-	26	27	53
Non-Infected	-	-	-	-	-	-	NA	-	-	-	23	26	49
Non-Infected	-	-	-	-	NA	-	-	-	NA	NA	17	28	45
Non-Infected	-	-	-	-	-	-	NA	-	NA	-	3	37	40
Non-Infected	-	-	-	-	-	-	NA	-	-	NA	5	32	37
Non-Infected	-	-	-	-	-	-	-	-	NA	NA	10	18	28
Non-Infected	-	-	-	-	-	NA	NA	-	-	-	1	18	19
Non-Infected	NA	NA	-	-	-	NA	-	-	-	-	0	16	16
Non-Infected	-	-	-	-	-	NA	-	NA	-	-	2	13	15
Non-Infected	-	-	+	-	-	-	-	-	-	-	8	6	14
Non-Infected	-	-	-	-	-	NA	-	-	-	NA	1	12	13
Non-Infected	-	-	-	-	-	-	-	+	-	-	7	5	12
Non-Infected	-	-	-	-	-	-	+	-	-	-	4	7	11
Non-Infected	-	-	-	-	-	NA	NA	-	-	NA	1	9	10
Non-Infected	NA	-	-	-	-	-	-	-	-	-	3	7	10
Non-Infected	-	-	-	-	-	+	-	-	-	-	7	2	9
Non-Infected	+	-	-	-	-	-	-	-	-	-	2	5	7
Non-Infected	-	+	-	-	-	-	-	-	-	-	4	3	7
Non-Infected	-	-	-	-	-	-	-	-	+	-	1	6	7
Non-Infected	-	-	-	-	+	-	-	-	-	-	1	5	6
Non-Infected	-	-	-	-	-	NA	NA	NA	-	-	3	3	6
Non-Infected	-	-	-	-	-	-	-	-	+	-	2	3	5
Non-Infected	-	+	-	-	-	-	-	-	-	-	0	4	4
Non-Infected	-	-	-	-	-	-	NA	-	NA	NA	1	2	3
Non-Infected	-	-	NA	-	-	-	-	-	-	-	2	1	3
Non-Infected	-	-	-	-	+	-	-	-	+	-	0	2	2
Non-Infected	-	-	NA	-	-	-	-	-	-	-	0	2	2
Non-Infected	-	NA	-	-	-	-	-	-	-	-	1	1	2
Non-Infected	NA	NA	-	-	-	NA	-	-	NA	-	0	2	2
Non-Infected	+	+	-	-	-	+	-	+	-	+	1	0	1
Non-Infected	+	-	-	-	+	+	-	+	+	+	1	0	1
Non-Infected	+	-	-	-	+	-	-	+	+	+	1	0	1
Non-Infected	+	-	-	-	-	+	-	+	-	-	0	1	1
Non-Infected	+	-	-	-	-	+	-	-	-	-	1	0	1
Non-Infected	-	+	-	-	-	-	NA	-	-	-	1	0	1
Non-Infected	-	-	+	+	+	+	+	+	+	+	0	1	1
Non-Infected	-	-	+	+	-	+	+	+	-	-	1	0	1
Non-Infected	-	-	+	+	-	-	-	+	-	-	1	0	1
Non-Infected	-	-	+	+	-	-	-	-	+	-	0	1	1
Non-Infected	-	-	-	+	+	-	+	+	+	-	0	1	1
Non-Infected	-	-	-	+	-	-	+	-	-	-	1	0	1
Patient
Infected
Status	NAAT1a		NAAT2a			cobas CT/NG v2.0 Test				Symptom Statusb		Total
	SW	UR	SW	UR	PC Pre	SW	UR	VG	PC Pre	PC Post	Symp	Asymp
Non-Infected	-	-	+	-	+	-	-	+	+	+	0	1	1
Non-Infected	-	-	+	-	-	-	-	+	-	-	1	0	1
Non-Infected	-	-	+	-	-	-	-	NA	NA	+	1	0	1
Non-Infected	-	-	+	-	-	+	-	-	-	+	1	0	1
Non-Infected	-	-	-	-	+	-	-	-	-	NA	0	1	1
Non-Infected	-	-	-	-	+	-	-	NA	-	-	0	1	1
Non-Infected	-	-	-	-	+	+	+	-	-	-	0	1	1
Non-Infected	-	-	-	-	-	+	+	+	-	-	1	0	1
Non-Infected	-	-	-	-	-	-	-	+	+	+	0	1	1
Non-Infected	-	-	-	-	-	-	-	+	-	NA	1	0	1
Non-Infected	-	-	-	-	-	-	-	NA	+	NA	0	1	1
Non-Infected	-	-	-	-	-	-	-	NA	-	NA	0	1	1
Non-Infected	-	-	-	-	-	-	NA	NA	+	NA	0	1	1
Non-Infected	-	-	-	-	-	NA	NA	NA	-	-	0	1	1
Non-Infected	-	-	-	-	-	NA	NA	NA	NA	NA	1	0	1
Non-Infected	-	-	-	-	-	NA	NA	-	NA	NA	0	1	1
Non-Infected	-	-	-	-	-	NA	NA	NA	-	NA	1	0	1
Non-Infected	-	-	-	-	-	NA	NA	NA	NA	NA	1	0	1
Non-Infected	-	-	NA	NA	NA	NA	NA	NA	-	NA	1	0	1
Non-Infected	-	NA	-	-	-	-	-	-	-	NA	1	0	1
Non-Infected	NA	NA	-	-	-	-	-	-	-	-	0	1	1
Total Non-Infected											1814	3086	4900

Table 23: CT, Positive/Negative Analysis for Female Patient Infected Status

35

. " .

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

cobas® CT/NG v2.0 Test Section 5: 510(k) Summary 510(k) Summary Report

36

.

37

9 NAAT1 and NAAT2 = Commercially available CT/NG NAAT assays.

b Symp = symptomatic, Asymp = asymptomatic.

Note: Subjects are designated as being infected with CT if at least 2 predicate NAATs with different target regions give positive results in the endocervical swab and/or the urine specimen. However, females are 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 CT/NG v2.0 Test results are considered evaluable and included in this summary table.

Note: + denotes Positive; - denotes Negative; NA indicates specimen was not obtained or available for testing.

Note: SW = endocervical swab, UR = urine, VG = vaginal swab, PC Pre = PreservCyt (pre-aliquot), PC Post = PreservCyt (post-aliquot).

38

| Patient
Infected
Status | NAAT1a | | NAAT2a | | cobas
CT/NG
v2.0 Test
UR | Symptom Statusb | | Total |
|-------------------------------|--------|----|--------|----|-----------------------------------|-----------------|-------|-------|
| | SW | UR | SW | UR | UR | Symp | Asymp | |
| Infected | + | + | + | + | + | 64 | 43 | 107 |
| Infected | - | + | - | + | + | 3 | 3 | 6 |
| Infected | - | + | + | + | + | 0 | 3 | 3 |
| Infected | + | + | + | + | + | 1 | 1 | 2 |
| Infected | + | - | + | - | - | 0 | 1 | 1 |
| Infected | + | - | + | + | + | 0 | 1 | 1 |
| Infected | - | + | + | - | + | 1 | 0 | 1 |
| Infected | - | + | - | + | - | 1 | 0 | 1 |
| Total Infected | | | | | | 70 | 52 | 122 |
| Non-Infected | - | - | - | - | - | 203 | 399 | 602 |
| Non-Infected | - | - | - | - | + | 1 | 2 | 3 |
| Non-Infected | - | - | + | - | - | 1 | 1 | 2 |
| Non-Infected | - | - | - | + | - | 1 | 1 | 2 |
| Non-Infected | - | - | + | + | - | 0 | 2 | 2 |
| Non-Infected | - | - | - | + | - | 0 | 2 | 2 |
| Non-Infected | - | - | + | + | + | 0 | 1 | 1 |
| Non-Infected | + | - | - | - | - | 1 | 0 | 1 |
| Non-Infected | + | + | - | - | + | 1 | 0 | 1 |
| Total Non-Infected | | | | | | 208 | 408 | 616 |

Table 24: CT, Positive/Negative Analysis for Male Patient Infected Status

4 NAAT1 and NAAT2 = Commercially available CT/NG NAAT assays.

b Symp = symptomatic, Asymp = asymptomatic.

Note: Subjects are designated as being infected with CT if at least 2 predicate NAATs with different target regions give positive results in the urethral swab and/or the urine specimen.

Note: Subjects with designated infection status and valid cobas CT/NG v2.0 Test results are considered evaluable and included in this summary table.

Note: + denotes Positive; - denotes Negative.

Note: SW = urethral swab, UR= urine.

5.2.5. Neisseria gonorrhoeae (NG)

Sensitivity, specificity, and predictive values of the cobas® CTNG v2.0 Test for NG as defined by PIS are shown by gender, sample type, and symptom status in Table 25. Overall sensitivity ranged from 95.6% to 100.0%. Overall specificity ranged from 99.1% to 100.0% for both females and males. Performance estimates for NG detection were similar between symptomatic and asymptomatic subjects.

39

Table 25: 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 | | | | | | | | | |
| | Sympc | 1930 | 95.2%
(40/42) | (84.2%,
98.7%) | 99.9%
(1886/1888) | (99.6%,
100.0%) | 2.2 | 95.2 | 99.9 |
| SW | Asympd | 3174 | 97.9%
(46/47) | (88.9%,
99.6%) | 99.9%
(3124/3127) | (99.7%,
100.0%) | 1.5 | 93.9 | 100.0 |
| | Overall | 5104 | 96.6%
(86/89) | (90.6%,
98.8%) | 99.9%
(5010/5015) | (99.8%,
100.0%) | 1.7 | 94.5 | 99.9 |
| | Sympc | 1937 | 90.5%
(38/42) | (77.9%,
96.2%) | 99.7%
(1890/1895) | (99.4%,
99.9%) | 2.2 | 88.4 | 99.8 |
| UR | Asympd | 3190 | 100.0%
(48/48) | (92.6%,
100.0%) | 99.6%
(3130/3142) | (99.3%,
99.8%) | 1.5 | 80.0 | 100.0 |
| | Overall | 5127 | 95.6%
(86/90) | (89.1%,
98.3%) | 99.7%
(5020/5037) | (99.5%,
99.8%) | 1.8 | 83.5 | 99.9 |
| | Sympc | 898 | 100.0%
(21/21) | (84.5%,
100.0%) | 99.7%
(874/877) | (99.0%,
99.9%) | 2.3 | 87.5 | 100.0 |
| VG-C | Asympd | 2240 | 100.0%
(37/37) | (90.6%,
100.0%) | 99.7%
(2197/2203) | (99.4%,
99.9%) | 1.7 | 86.0 | 100.0 |
| | Overall | 3138 | 100.0%
(58/58) | (93.8%,
100.0%) | 99.7%
(3071/3080) | (99.4%,
99.8%) | 1.8 | 86.6 | 100.0 |
| | Sympc | 1041 | 95.2%
(20/21) | (77.3%,
99.2%) | 100.0%
(1020/1020) | (99.6%,
100.0%) | 2.0 | 100.0 | 99.9 |
| VG-S | Asympd | 996 | 100.0%
(9/9) | (70.1%,
100.0%) | 100.0%
(987/987) | (99.6%,
100.0%) | 0.9 | 100.0 | 100.0 |
| | Overall | 2037 | 96.7%
(29/30) | (83.3%,
99.4%) | 100.0%
(2007/2007) | (99.8%,
100.0%) | 1.5 | 100.0 | 100.0 |
| | Sympc | 1935 | 100.0%
(43/43) | (91.8%,
100.0%) | 99.9%
(1890/1892) | (99.6%,
100.0%) | 2.2 | 95.6 | 100.0 |
| PC Pre | Asympd | 3196 | 93.9%
(46/49) | (83.5%,
97.9%) | 99.8%
(3142/3147) | (99.6%,
99.9%) | 1.5 | 90.2 | 99.9 |
| | Overall | 5131 | 96.7%
(89/92) | (90.8%,
98.9%) | 99.9%
(5032/5039) | (99.7%,
99.9%) | 1.8 | 92.7 | 99.9 |
| | Sympc | 1872 | 95.3%
(41/43) | (84.5%,
98.7%) | 99.8%
(1825/1829) | (99.4%,
99.9%) | 2.3 | 91.1 | 99.9 |
| PC Post | Asympd | 2996 | 95.8%
(46/48) | (86.0%,
98.8%) | 99.7%
(2940/2948) | (99.5%,
99.9%) | 1.6 | 85.2 | 99.9 |
| | Overall | 4868 | 95.6%
(87/91) | (89.2%,
98.3%) | 99.7%
(4765/4777) | (99.6%,
99.9%) | 1.9 | 87.9 | 99.9 |
| Sample
Typea | Symptom
Statusb | Total
(n) | SENS | 95% CI | SPEC | 95% CI | PREV
(%) | PPV
(%) | NPV
(%) |
| Male | | | | | | | | | |
| UR | Sympc | 278 | 100.0%
(60/60) | (94.0%,
100.0%) | 99.1%
(216/218) | (96.7%,
99.7%) | 21.6 | 96.8 | 100.0 |
| | Asympc | 460 | 100.0%
(7/7) | (64.6%,
100.0%) | 99.3%
(450/453) | (98.1%,
99.8%) | 1.5 | 70.0 | 100.0 |
| | Overall | 738 | 100.0%
(67/67) | (94.6%,
100.0%) | 99.3%
(666/671) | (98.3%,
99.7%) | 9.1 | 93.1 | 100.0 |

40

ª SW = endocervical swab, UR = urine, VG-C = clinician-collected vaginal swab, VG-S = self-collected vaginal swab, PC Pre = PreservCyt (pre-aliquot), PC Post = PreservCyt (post-aliquot).

6 Symp = symptomatic, Asymp = asymptomatic.

cobas CT/NG v2.0 Test results from archived specimens.

d cobas® CT/NG v2.0 Test results from archived and prospectively collected specimens.

Note: Subjects are designated as being infected with NG if at least 2 predicate NAATs with different target regions qive positive results in the endocervical swab (urethral swab for males) and/or the urine specimen

Note: Subjects with designated infection status and valid cobas CT/NG v2.0 Test results are considered evaluable and included in this summary table.

Note: CI = (score) confidence interval, PREV = prevalence, SENS = sensitivity, SPEC = specificity, PPV = posilive predictive value, NPV = negative predictive value.

Table 26 and Table 27 summarize the results from symptomatic and asymptomatic subjects designated as infected or non-infected with NG (females and males, respectively) according to the PIS algorithm.

A total of 92 females and 67 males were infected with NG. Symptoms were reported in 46.7% (43/92) of infected and 37.4% (1,932/5,171) of non-infected women. Similarly, symptoms were reported in 89.6% (60/67) of infected and 32.5% (218/671) of non-infected men. Overall, the NG prevalence was 1.7% (92/5,263), 9.1% (67/738), and 2.6% (159/6,001), respectively, in women, men, and the entire study population.

41

ﻨ

Patient		NAAT1ª		NAAT2ª					cobas CT/NG v2.0 Test			Symptom Status®
Infected
Status	SW	UR	ટેખ	UR	PC
Pre	SW	UR	VG	PC
Pre	PC
Post	Symp	Asymp	Total
Infected	+	+	+	+	+	+	+	+	+	+	29	37	રહ
Infected	+	+	+	+	+	+	+	NA	+	+	1	2	3
Infected	+	+	+	-	+	+	+	+	+	+	1	2	3
Infected	+	-	+		+	+	-	+	+	+	3	0	3
Infected	+	+	+	+	+	NA	+	+	+	+	1	1	2
Infected	+	+	+	+	1	+	+	+	+	+	0	2	2
Infected	+	+	+	+	+	+	+	+	+	1	1	0	1
Infected	+	+	+	+	+	+	+	+	-		0	1	1
Infected	+	+	+	+	+	+	+		+	+	1	0	1
Infected	+	+	+	+	+	+	-	+	+	+	1	0	1
Infected	+	+	+	+	+	+	NA	+	+	+	1	0	1
Infected	+	+	+	+	+	NA	NA	NA	+	+	0	1	1
Infected	+	+	+	+	-		+	+	+	-	1	0	1
Infected	+	י	+	-	+	+	+	+	+	+	1	0	1
Infected	+	-	+	-	-	+	+	+	+	+	1	0	1
Infected	-	+	+	+	+	+	+	+	+	+	0	1	1
Infected	-	+	+	+	+	+	+	+	-	NA	0	1	1
Infected	"	+	+	+	+	"	+	+	+	+	1	0	1
Infected	-	+	+	+	+	1	+	+	l	-	0	1	1
Total Infected											43	49	ರಿ 2
Non-Infected			-	-	l	-	1	1		-	1704	2709	4413
Non-Infected	-	-	-	-		י	し	-	-	NA	62	177	239
Non-Infected	-	-	-	-	-	NA	-	-	-	-	30	રૂદ	રિક
Non-Infected	•		-	•		-	-	NA	ー	•	26	29	રેર
Non-Infected	-	-	-	י	-	•	NA	-	-	-	24	25	49
Non-Infected			し	・	NA	ー	"	"	NA	NA	18	30	ਕ 8
Non-Infected	-	-	"	す	-	-		-	NA	-	7	37	44
Non-Infected	-	-	-	ー		"	NA	-	-	NA	3	38	4 1
Non-Infected	し	l	-	-	1				NA	NA	10	19	29
Non-Infected			"	-	-	NA	NA	"		י	1	18	19
Non-Infected	-	-	-	-		NA	-	NA			2	15	17
Non-Infected	NA	NA	-	-		NA	-	-			0	16	16
Non-Infected				t	-	•	+	-	ﮯ	-	5	9	14
Non-Infected		-	-	-	-	NA	י		-	NA	1	12	13
Non-Infected	+	-	l	-	-			-	-	-	5	ರಿ	11
Non-Infected	-	-	・	-	-	NA	NA	-	-	NA	1	9	10
Non-Infected	NA	-	-	-	-	(	י		-	l	3	7	10
Non-Infected	-	+	-	ー	-		"		-	-	0	9	g
Non-Infected	-	-	-	-	-		-	-	지	+	3	4	7
Non-Infected		-	t	-	・	NA	NA	NA	-	-	3	2	5
Non-Infected	-		-	+	-				-	1	2	2	4
Patient
Infected
Status	NAAT1a		NAAT2a		cobas CT/NG v2.0 Test					Symptom Statusb		Total
	SW	UR	SW	UR	SW	UR	VG	PC Pre	PC Post	Symp	Asymp
Non-Infected	-	-	-	-	-	-	-	+	-	-	2	2	4
Non-Infected	-	-	-	NA	-	-	-	-	-	-	2	2	4
Non-Infected	-	-	-	+	-	-	-	-	-	-	1	2	3
Non-Infected	-	-	-	-	-	-	-	+	-	-	1	2	3
Non-Infected	-	-	-	-	-	-	NA	-	NA	NA	1	2	3
Non-Infected	-	-	-	NA	-	-	-	-	-	-	2	1	3
Non-Infected	-	+	-	-	-	-	-	-	-	-	1	1	2
Non-Infected	-	-	-	-	-	-	-	-	+	+	0	2	2
Non-Infected	-	-	-	-	-	-	-	NA	-	NA	0	2	2
Non-Infected	-	-	-	-	-	-	NA	NA	-	-	1	1	2
Non-Infected	-	NA	-	-	-	-	-	-	-	-	1	1	2
Non-Infected	NA	NA	-	-	-	NA	-	-	NA	-	0	2	2
Non-Infected	+	+	+	+	+	+	+	+	+	+	0	1	1
Non-Infected	+	+	+	NA	+	+	+	+	+	+	0	1	1
Non-Infected	+	+	-	-	-	-	-	-	-	-	0	1	1
Non-Infected	+	-	-	-	-	+	NA	-	-	-	0	1	1
Non-Infected	-	+	-	-	-	-	-	-	NA	-	0	1	1
Non-Infected	-	-	+	-	-	-	-	-	+	-	0	1	1
Non-Infected	-	-	-	-	+	-	-	-	-	NA	1	0	1
Non-Infected	-	-	-	-	-	+	-	-	-	NA	0	1	1
Non-Infected	-	-	-	-	-	+	NA	-	NA	NA	1	0	1
Non-Infected	-	-	-	-	-	-	+	-	NA	-	0	1	1
Non-Infected	-	-	-	-	-	-	-	-	NA	+	1	0	1
Non-Infected	-	-	NA	-	-	NA	NA	-	+	+	1	0	1
Non-Infected	-	-	NA	NA	-	NA	-	NA	NA	NA	1	0	1
Non-Infected	-	-	NA	NA	-	NA	NA	-	NA	-	0	1	1
Non-Infected	-	-	NA	NA	-	NA	NA	NA	NA	NA	1	0	1
Non-Infected	-	-	NA	NA	NA	NA	NA	NA	-	NA	1	0	1
Non-Infected	-	-	NA	NA	NA	NA	NA	NA	NA	NA	1	0	1
Non-Infected	-	NA	NA	NA	NA	NA	NA	NA	-	NA	1	0	1
Non-Infected	NA	NA	-	-	-	-	-	-	NA	-	0	1	1
Non-Infected	NA	NA	NA	NA	-	-	-	-	1	-	0	1	1
Total Non-Infected											1932	3239	5171

Table 26: NG, Positive/Negative Analysis for Female Patient Infected Status

42

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

、 , . .

cobas® CT/NG v2.0 Test Section 5: 510(k) Summary 510(k) Summary Report

.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

a NAAT1 and NAAT2 = Commercially available CT/NG NAAT assays.

6 Symp = symptomatic, Asymp = asymptomatic.

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

Note: Subjects with designated infection status and valid cobas CT/NG v2.0 Test results are considered evaluable and included in this summary table.

Note: + denotes Positive; - denotes Negative; NA indicates specimen was not obtained or available for testing.

Note: SW = endocervical swab, UR = urine, VG = vaginal swab, PC Pre = PreservCyt (pre-aliquot), PC Post = PreservCyt (post-aliquot).

43

| Patient
Infected
Status | NAAT1a | | NAAT2a | | cobas
CT/NG
2.0 Test | Symptom Statusb | | Total |
|-------------------------------|--------|----|--------|----|----------------------------|-----------------|-------|-------|
| | SW | UR | SW | UR | UR | Symp | Asymp | |
| Infected | + | + | + | + | + | 59 | 7 | 66 |
| Infected | + | + | - | + | + | 1 | 0 | 1 |
| Total Infected | | | | | | 60 | 7 | 67 |
| Non-Infected | - | - | - | - | - | 213 | 449 | 662 |
| Non-Infected | - | - | - | - | + | 2 | 3 | 5 |
| Non-Infected | - | + | - | - | - | 1 | 1 | 2 |
| Non-Infected | - | - | + | - | - | 1 | 0 | 1 |
| Non-Infected | + | - | - | - | - | 1 | 0 | 1 |
| Total Non-Infected | | | | | | 218 | 453 | 671 |

Table 27: NG, Positive/Negative Analysis for Male Patient Infected Status

9 NAAT1 and NAAT2 = Commercially available CT/NG NAAT assays.

b Symp = symptomatic, Asymp = asymptomatic.

Note: Subjects are designated as being infected with NG if at least 2 predicate NAATs with different target regions give positive results in the urethral swab and/or the urine specimen.

Note: Subjects with designated infection status and valid cobas CT/NG v2.0 Test results are considered evaluable and included in this summary table.

Note: + denotes Positive; - denotes Negative.

Note: SW = urethral swab, UR= urine.

5.2.6. Prevalence

The prevalence of CT and NG in patient populations depends upon a variety of factors including age, gender, the presence of symptoms, clinic type, and test method. The prevalence of CT observed with the cobas® CT/NG v2.0 Test during a multi-center clinical trial ranged from 5.0% to 8.9% in females , and from 11.3% to 25.2% in males (Table 22); the prevalence of NG ranged from 0.9% to 2.3% in females, and from 1.5% to 21.6% in males (Table 25).

5.2.7. Positive and Negative Predictive Value

Hypothetical positive and negative predictive values (PPV & NPV) derived from discase prevalence of I to 50% for the cobas® CT/NG v2.0 Test are shown in Table 28 and Table 29, The overall sensitivity and specificity (compared with PIS) were 94.1% and 99.6%, respectively, for CT; and 97.1% and 99.8%, respectively, for NG.

44

Table 28: Positive Predictive Value and Negative Predictive Value for Hypothetical CT Prevalence

Prevalence (%)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
1	94.1	99.6	69.0	99.9
3	94.1	99.6	87.2	99.8
5	94.1	99.6	92.0	99.7
10	94.1	99.6	96.1	99.3
15	94.1	99.6	97.5	99.0
20	94.1	99.6	98.2	98.5
30	94.1	99.6	98.9	97.5
50	94.1	99.6	99.5	94.4

Overall sensitivity and specificity were estimated by comparing the cobas CT/NG v2.0 Test results to patient infected status across all sample types in both female and male subjects.

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

Table 29: Positive Predictive Value and Negative Predictive Value for Hypothetical NG Prevalence

Prevalence (%)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
1	97.1	99.8	82.0	100.0
3	97.1	99.8	93.3	99.9
5	97.1	99.8	96.0	99.8
10	97.1	99.8	98.0	99.7
15	97.1	99.8	98.8	99.5
20	97.1	99.8	99.1	99.3
30	97.1	99.8	99.5	98.8
50	97.1	99.8	99.8	97.2

Overall sensitivity and specificity were estimated by companing the cobas CT/NG v2.0 Test results to patient infected status across all sample types in both female and male subjects.

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

6. CONCLUSION

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 v2.0 Test is substantially equivalent to the predicate device.

45

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/45/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the graphic.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 2, 2013

ROCHE MOLECULAR SYSTEMS, INC. C/O DR. WILK VON GUSTEDT 4300 HACIENDA DRIVE PLEASANTON CA 94588-2722

Re: K132270

Trade/Device Name: cobas® CT/NG v2.0 Test Regulation Number: 21 CFR 866.3390 Regulation Name: Neisseria spp. direct serological test reagents Regulatory Class: II Product Code: LSL, MKZ, OOI Dated: November 8, 2013 Received: November 12, 2013

Dear Dr. von Gustedt:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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 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.

46

Page 2-Dr. von Gustedt

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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.gov/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/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Sally AsHojvat -S

Sally Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

47

INDICATIONS FOR USE

510(k) Number: K132270

Device Name: Roche cobas® CT/NG v2.0 Test

Indications For Use: The cobas CT/NG v2.0 Test is an automated, in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonormoeae (NG) DNA in urogenital specimens. The Test utilizes the Polymerase Chain Reaction (PCR) for the detection of Chiamydia trachomatis and Neisseria gonormoeae DNA in male and female urine, self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical swab specimens, all collected in cobas® PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt® solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals.

Ancillary Collection Kits

The cobas® PCR Female Swab Sample Kit is used to collect and transport endocervical transport and storage medium for gynecological specimens. Use this collection kit only with either the cobas® CT/NG Test or the cobas CT/NG v2.0 Test.

The cobas® PCR Urine Sample Kit is used to collect and transport 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 either the cobas® CT/NG Test or the cobas® CT/NG v2.0 Test.

Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (Part 21 CFR 801 Subpart C)

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Concurrence of Center for Devices and Radiological Health (CDRH)

Tamara V 2013.12.09

Intended Use / Indications for Use

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).

§ 866.3390

cobas® CT/NG v2.0 Test 510(k) Summary

TABLE OF CONTENTS

List of Tables

DEVICE DESCRIPTION 1.

INTENDED USE 2.

3. TECHNOLOGICAL CHARACTERISTICS

NON-CLINICAL PERFORMANCE EVALUATION 4.

Analytical Sensitivity 4.1.

cobas® CT/NG v2.0 Test Limit of Detection for CT scrovar D and serovar I Table 2:

cobas® CT/NG v2.0 Test Limit of Detection for NG strain 2948 (ATCC 19424) Table 3: and Strain 6693

4.2. Inclusivity

Summary of NG Strains Inclusivity Verification Results Table 5:

4.3. Analytical Specificity

Microorganisms Tested for Analytical Specificity Table 6:

Table 7: List of Microorganisms Tested below 1 x 10° Units/mL for Analytical Specificity

4.4. Interference

lesults from Endogenous Interference Testing for Whole Blood, PBMC, and Muc Table 9:

4.5. Precision

CLINICAL PERFORMANCE 5.

Reproducibility 5.1.

Table 12: C. trachomatis: Overall Mean, Standard Deviations, and Coefficients of Variation (%) for Cycle Threshold, Estimated From Valid Samples of Positive Sample Type Panel Members

Table 13: C. trachomatis: Percent Agreement by Panel Member Overall and for Site/Instrument, Operator, and Day - PCR Media/Urine

Table 15: C. trachomatis. Percent Agreement by Panel Member Overall and for Site/Instrument, Operator, and Day - PreservCyt

N. gonorrhoeae (Table 16, Table 17, Table 18, Table 19) 5.1.2.

Table 18: N. gonorrhocae. Percent Agreement by Panel Member Overall and for Site/Instrument, Operator, and Day - PCR Media/Swab

5.2. Clinical Specimen Study

5.2.1. Study Design

5.2.2. Determination of Patient Infected Status

Table 21: Determination of Male Patient Infected Status

5.2.3. Study Results

Chlamydia trachomatis (CT) 5.2.4.

Table 24: CT, Positive/Negative Analysis for Male Patient Infected Status

5.2.5. Neisseria gonorrhoeae (NG)

Table 25: NG: Clinical Performance Compared With Patient Infected Status by Gender, Sample Type, and Symptom Status

Table 26: NG, Positive/Negative Analysis for Female Patient Infected Status

Table 27: NG, Positive/Negative Analysis for Male Patient Infected Status

5.2.6. Prevalence

5.2.7. Positive and Negative Predictive Value

Table 28: Positive Predictive Value and Negative Predictive Value for Hypothetical CT Prevalence

Table 29: Positive Predictive Value and Negative Predictive Value for Hypothetical NG Prevalence

6. CONCLUSION

DEPARTMENT OF HEALTH & HUMAN SERVICES

Sally AsHojvat -S

INDICATIONS FOR USE

510(k) Number: K132270

Device Name: Roche cobas® CT/NG v2.0 Test

Ancillary Collection Kits

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