cobas® CT/NG v2.0 Test

K163184 · Roche Molecular Systems, Inc. · LSL · Feb 9, 2017 · Microbiology

Device Facts

• Record ID: K163184
• Device Name: cobas® CT/NG v2.0 Test
• Applicant: Roche Molecular Systems, Inc.
• Product Code: LSL · Microbiology
• Decision Date: Feb 9, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3390
• Device Class: Class 2

Intended 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 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. Ancillary Collection Kits: The cobas® PCR Media Dual 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 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 the cobas® CT/NG v2.0 Test.

Device Story

Modified ancillary specimen collection kit for cobas® CT/NG v2.0 Test; replaces spun bud swab with flocked bud swab for endocervical collection. Kit includes collection medium tube (guanidine hydrochloride/Tris-HCl buffer) and two swabs (one flocked, one woven). Flocked swab collects endocervical specimens; woven swab cleans mucus. Vaginal specimens use woven swab. Specimens transported in cobas® PCR Media to stabilize DNA. System uses real-time PCR on cobas® 4800 System to detect CT/NG DNA. Healthcare providers use results to diagnose chlamydial and gonococcal infections. Benefits include improved specimen collection and continued diagnostic accuracy for STI testing.

Clinical Evidence

Prospective clinical study of 1,949 women. Comparison of flocked vs. woven swabs for endocervical specimen collection. CT PPA: 94.3% (95% CI: 88.63%-97.19%); NPA: 99.7% (95% CI: 99.36%-99.88%). NG PPA: 86.96% (95% CI: 67.87%-95.46%); NPA: 99.95% (95% CI: 99.71%-99.92%). Student's t-test showed no significant difference (p=0.92 for CT, p=0.84 for NG). Analytical dilution sensitivity study confirmed flocked swab performance is equivalent or superior to woven swab.

Technological Characteristics

Collection kit includes polyester flocked/woven swabs, polystyrene shafts, and 4.3 mL cobas® PCR Media (≤40% w/w guanidine hydrochloride/Tris-HCl buffer). Sterilization via ethylene oxide. Operates with cobas® 4800 System for real-time PCR amplification. Designed for endocervical/vaginal specimen transport and stabilization.

Indications for Use

Indicated for use as an aid in the diagnosis of chlamydial and gonococcal disease in symptomatic and asymptomatic individuals. Prescription use only.

Regulatory Classification

Identification

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

Predicate Devices

• cobas® CT/NG v2.0 assay (K132270)
• cobas® PCR Female Swab Sample Kit (K132270)
• cobas® PCR Urine Sample Kit (K132270)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K163184

B. Purpose for Submission:
This submission is for a modification to the ancillary specimen collection kit used with the cobas® CT/NG v2.0 Test (K132270). The modification consists of changing the endocervical collection swab from a spun (woven) bud to a flocked bud. The swab used for the collection of vaginal specimens, as previously cleared as an ancillary collection kit to the above two assays, remains unchanged. The modified collection kit will be marketed under the name cobas® PCR Media Dual Swab Sample Kit and the original cobas® PCR Female Swab Sample Kit will be gradually phased out.

The cobas® CT/NG v2.0 Test remains unchanged.

C. Measurand:
Chlamydia trachomatis DNA and Neisseria gonorrhoeae DNA

D. Type of Test:
Qualitative in vitro diagnostic assay that utilizes amplification of target DNA by real-time Polymerase Chain Reaction.

E. Applicant:
Roche Molecular Systems, Inc.
4300 Hacienda Drive
Pleasanton, CA, 94588-2722
Phone number: 925-730-8237
Fax number: 925-730-8128

F. Proprietary and Established Names:
cobas® CT/NG v2.0 Test

Ancillary collection kits:
cobas® PCR Media Dual Swab Sample Kit
cobas® PCR Urine Sample Kit

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G. Regulatory Information:

1. Regulation section:
21 CFR 866.3390 Neisseria spp. direct serological test reagents
21 CFR 866.3120 Chlamydia serological reagents

2. Classification:
Class II

3. Product code(s):
LSL, MKZ, OOI

4. Panel:
Microbiology (83)

H. Intended Use:

1. Intended use(s):

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.

Ancillary Collection Kits:

The cobas® PCR Media Dual 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 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 the cobas® CT/NG v2.0 Test.

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2. Indication(s) for use:

For use as an aid in the diagnosis of chlamydial and gonococcal disease in symptomatic and asymptomatic individuals.

3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

cobas® 4800 System.

I. Device Description:

The full description of the device may be found under K132270.

This document is limited to the modified ancillary collection kit which is the subject of this submission.

The modified Swab Sample kit, the cobas® PCR Media Dual Swab Sample Kit, is comprised of a collection medium tube and a packet containing two sterile swabs and may be used to collect endocervical or vaginal specimens.

Collection Kit Composition:

- cobas® PCR Media Dual Swab Sample Kit: 1 spun (woven) bud swab (polyester) and 1 flocked bud swab (polyester)
- cobas® PCR Media 1 x 4.3 mL
- ≤40% (w/w) Guanidine hydrochloride Tris-HCl buffer

Collection of endocervical specimens:

The flocked swab is used to collect the endocervical specimen. The woven swab is intended to remove excess mucus from the cervical and surrounding mucosa prior to the collection of endocervical specimen and is discarded after cleaning.

Collection of vaginal specimens:

The woven swab is used to collect vaginal specimens (the flocked swab is discarded).

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J. Substantial Equivalence Information:

1. Predicate device name(s):
cobas® CT/NG v2.0 assay,
cobas® PCR Female Swab Sample Kit (for endocervical and vaginal swabs)
cobas® PCR Urine Sample Kit

2. Predicate 510(k) number(s):
K132270

3. Comparison with predicate:
Comparison of Similarities and Differences with the Predicate Device

| Item | Device | Predicate Device |
| --- | --- | --- |
| | cobas® CT/NG v2.0 Test (K163184) | cobas® CT/NG v2.0 Test (K132270) |
| Similarities | | |
| Intended Use Assay | 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 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. |

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| Item | Device | Predicate Device |
| --- | --- | --- |
| | cobas® CT/NG v2.0 Test
(K163184) | cobas® CT/NG v2.0 Test
(K132270) |
| Intended Use Ancillary Collection Kits | The cobas® PCR Media Dual 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 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 the cobas® CT/NG v2.0 Test. | The cobas® 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 **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. |
| Sample Type | Endocervical and vaginal Specimens | Same |
| PCR Media | ≤40% (w/w) Guanidine hydrochloride Tris-HCl buffer | Same |
| PCR Media Volume | 4.3mL | Same |
| Swab Count | 2 | Same |
| Sterilization Method | Ethylene Oxide | Same |
| Fiber Composition | Polyester | Same |
| Shaft Composition | Polystyrene | Same |
| Swab Vendor | Puritan | Same |
| | Differences | |
| Swab Type | 1 Spun Bud and 1 Flocked Bud | 2 Spun Buds |
| Bud Size | 5.6 mm Diameter (Spun)
2.9 mm Diameter (Flocked) | 5.6 mm Diameter |
| Tube | 15.8 mm Diameter | 16.5 mm Diameter |
| Closure | 19.7 mm Outer Diameter | 19.3 mm Outer Diameter |
| Tube and Closure Vendor | Thermo-Fisher | Sarstedt |

K. Standard/Guidance Document Referenced (if applicable):

Not applicable

L. Test Principle:

The test principle for the cobas® CT/NG v2.0 Test is described in detail under the K132270.

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The swab sample collection kit, which is the subject of this submission, is designed to preserve the integrity of the Chlamydia trachomatis and Neisseria gonorrhoeae DNA in gynecological specimens collected from female patients.

Cells in the collected specimens are lysed in the collection device by the chaotropic agent in the cobas® PCR Media. The guanidine hydrochloride denatures all proteins in the sample, preventing any enzymatic degradation of the nucleic acid in the sample.

## M. Performance Characteristics (if/when applicable):

The performance characteristics of the cobas® CT/NG v2.0 Test were established under K132270; please refer to that file for the associated data.

A risk analysis was performed to evaluate the modification made to the collection kit and its impact on the performance of the cobas® CT/NG v2.0 Test. The FMEA identified one significant risk from the change from a spun swab to a flocked swab. The risk identified was a risk of a false negative result if the collected swab sample did not contain enough cells due to the design change from spun to flocked.

Two analytical studies using clinical samples were performed to demonstrate that the flocked swab was substantially equivalent to the spun swab for the endocervical specimens.

### 1. Analytical performance:

#### a. Dilution Sensitivity Study:

This study’s purpose was to demonstrate that clinical samples co-collected with Puritan woven swab and Puritan flocked swab have similar detection levels in serial dilutions using clinical matrix. This study was performed using the cobas® CT/NG v2.0 according to the instructions for use.

**Method:** Ten pairs of co-collected clinical specimens were selected based on positivity for CT or NG and Ct values within 1 Ct of each other, based on testing with the cobas® CT/NG v2.0 assay. See Table 1 below for the obtained specimen Ct values. Two negative background matrix pools were prepared from previously tested negative specimens. One negative pool was made for each swab type. Each swab of the ten positive pairs of co-collected specimens was diluted in the appropriate negative matrix pool. A minimum of eight dilution levels were made for each specimen and swab type.

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Table 1. Comparison of Detection Levels Between Flocked and Spun Swabs

| Specimen ID | | cobas® 4800 | | |
| --- | --- | --- | --- | --- |
| | CT or NG | Flocked Swab (CI) | Woven Swab (CI) | Difference |
| 1107 | CT | 30.0 | 30.4 | 0.4 |
| 1412 | CT | 32.0 | 32.2 | 0.2 |
| 7740 | CT | 31.4 | 31.7 | 0.3 |
| 123 | CT | 31.3 | 30.6 | 0.7 |
| 252 | CT | 33.5 | 33.7 | 0.2 |
| 185 | NG | 29.6 | 29.0 | 0.6 |
| 1006 | NG | 30.4 | 31.4 | 1.0* |
| 1070 | NG | 30.7 | 30.6 | 0.1 |
| 1490 | NG | 29.5 | 29.9 | 0.4 |
| 1552 | NG | 32.2 | 32.5 | 0.3 |

*this specimen exhibited one cycle (Ct value) difference suggesting approximately 2 fold N. gonorrhoeae DNA concentration difference even before dilution series were prepared. The specimen was included in the study despite being exactly at the borderline of inclusion/exclusion criteria.

Results: Each dilution was tested with the cobas® CT/NG v2.0 assay in triplicate. The first dilution where 2 out of 3 replicates were negative was considered the dilution limit. The limit for each dilution of each swab sample was recorded in Table 2 below. The new flocked swab performed equally or better than the original woven swab in detecting CT or NG. One sample, 1006, had disparate dilution limits for each swab type, however the newer swab type (flocked swab) performed better than the original woven swab. No demonstrated negative impact was observed when using a flocked swab as compared to a woven swab. Equivalence was defined as both swabs having a dilution limit within one dilution of each other.

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Table 2. Dilution Limit for Each Sample and Swab Type

| Sample ID | Dilution Limit (≥2/3 negative results) | | Equivalency Criteria Met? |
| --- | --- | --- | --- |
| | Flocked Swab | Woven Swab | |
| 1107 (CT) | 1:8192 | 1:4096 | Yes |
| 1412 (CT) | 1:1024 | 1:512 | Yes |
| 77400 (CT) | 1:2048 | 1:1024 | Yes |
| 123 (CT) | 1:1024 | 1:512 | Yes |
| 252 (CT) | 1:64 | 1:128 | Yes |
| 185 (NG) | 1:4096 | 1:8192 | Yes |
| 1006 (NG) | 1:4096 | 1:512 | * |
| 1070 (NG) | 1:4096 | 1:4096 | Yes |
| 1490 (NG) | 1:32768 | 1:32768 | Yes |
| 1552 (NG) | 1:512 | 1:256 | Yes |

*Sample 1006 exhibited negatives at more than one dilution level which was not unexpected considering that the starting concentration of $N$ .gonorrhoeae DNA was already 2 fold different even before the dilution series were prepared. More importantly, signal loss was observed at a higher dilution in the specimen collected with proposed flocked swab device suggesting that this swab had no negative impact on the results.

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b. Method comparison with predicate device:

A swab comparison study was performed to demonstrate that the flocked swab has equivalent performance to the woven swab when used with the cobas® CT/NG v2.0 Test in a clinical environment. One woven and one flocked swab were prospectively collected from 1,949 women who came in to the clinical facility for STI testing. The swab type collected first was alternated between the two swab types.

The comparison of the two swab types is presented as Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) between results obtained with the flocked swab vs. the woven swab for positive and negative patients. Table 3 (CT) and Table 4 (NG) below show the results of this study.

Table 3. Swab Comparison Detecting Chlamydia trachomatis
| CT | Woven + | Woven - |
| --- | --- | --- |
| Flocked + | 115 | 5 |
| Flocked - | 7 | 1822 |

PPA: 94.3% (95%CI : 88.63%-97.19%)
NPA: 99.7% (95%CI : 99.36%-99.88%)

Table 4. Swab Comparison Detecting Neisseria gonorrhoeae
| NG | Woven + | Woven - |
| --- | --- | --- |
| Flocked + | 20 | 1 |
| Flocked - | 3 | 1925 |

PPA: 86.96% (95%CI : 67.87%-95.46%)
NPA: 99.95% (95%CI : 99.71%-99.92%)

All discordant samples were at or near the limit of detection with a Ct value above 35, except for one Chlamydia trachomatis positive specimen which was positive in the flocked swab only with a Ct value of 25.

The performance of the two Puritan swabs (woven and flocked) used for collection of endocervical specimens for testing on the cobas® 4800 platform with CT/NG v2.0 are not significantly different. A Student's t-test was performed on the data resulting in a p-value of 0.92 for Chlamydia trachomatis and 0.84 for Neisseria gonorrhoeae demonstrating no significant difference between the swab types. Although the PPA point estimate for Chlamydia trachomatis results (94.3%) and Neisseria gonorrhoeae (86.96%) were below the desirable 95% goal, the data provided do not raise concerns with the use of the flocked swab instead of the woven swab for the collection of endocervical specimens and support a substantially equivalent decision.

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2. Clinical Studies:

The analytical studies listed above were conducted using clinical specimens collected prospectively from 1,949 women who came in to the clinical facility for STI testing.

N. Instrument Name:

cobas® 4800 System

O. Other Supportive Instrument Performance Characteristics Data Not Covered in the "Performance Characteristics" Section Above:

N/A

P. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

Q. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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