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

The cobas® CT/NG Tests for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are 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® CT/NG Tests utilize the cobas® 4800 System for automated sample preparation and automated amplification and detection. The cobas® 4800 system software integrates the sample preparation with nucleic acid amplification and detection to generate test results.

This platform consists of modular hardware components that are linked by a dedicated network. The major hardware components of the cobas 4800 system are shown in Figure 1:

• cobas x 480 instrument (for automatic sample preparation) .
• cobas z 480 analyzer (for automatic amplification and detection using real-time PCR) t
• Control Unit with cobas® 4800 software .
• Assay reagents .
• (Optional) Communication through a firewall with a Laboratory Information System . (LIS) and/or intranet for LIS and/or telecommunications

This 510(k) submission (K140887) describes software system changes to the cobas® CT/NG v2.0 Test (K132270) and the cobas® CT/NG Test (K110923). The primary purpose of this submission is to demonstrate that migrating these tests to the new cobas® 4800 system software version 2.1 does not adversely affect their performance.

Here's a breakdown of the acceptance criteria and the supporting study:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criterion for this submission is demonstrating that the migration of the cobas® CT/NG Tests to software version 2.1 does not impact the analytical sensitivity (Limit of Detection) of the assays, maintaining equivalence to the predicate devices. This is shown by the overlapping 95% confidence intervals for the Limit of Detection (LOD) between the previous software versions and the new software version 2.1.

Study Proving the Device Meets Acceptance Criteria

The study described is primarily a technical performance verification / regression testing study focused on demonstrating the non-inferiority of the device's analytical sensitivity after the software upgrade.

• Study Name: CT/NG Test Technical Performance Verification (Limit of Detection regression testing)

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Test Set: For Limit of Detection (LOD) testing, a total of 10 runs were performed, generating up to 90 replicates for each of six levels for each test (cobas® CT/NG Test for SR1.1 vs SR2.1, and cobas® CT/NG v2.0 Test for SR1.2 vs SR2.1).
• Data Provenance: The document implies that this was prospective testing conducted by Roche Molecular Systems (RMS) in Pleasanton, California for system-level verification and at Roche Diagnostics Ltd. (RDI, Rotkreuz, Switzerland) for component and unit-level testing. The data is from internal studies conducted by the manufacturer. Specific country of origin for the samples is not explicitly stated, but the testing sites are in the US (California) and Switzerland.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

N/A. This was an analytical performance study (Limit of Detection) assessing the instrument's ability to detect specific analytes at low concentrations. It does not involve human interpretation or a "ground truth" derived from expert consensus on clinical cases. The "ground truth" in this context would be the spiked concentrations of CT and NG, and the device's ability to consistently detect them.

4. Adjudication Method for the Test Set

N/A. As this is an analytical performance study, a clinical adjudication method is not applicable. The device's output (positive/negative detection based on PCR cycle threshold analysis) is compared against pre-defined expected outcomes for spiked concentrations.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

No. A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This submission focuses on the analytical performance of an in vitro diagnostic device, specifically verifying that software changes do not alter its established Limit of Detection. MRMC studies are typically used for imaging devices where human readers interpret results, often with and without AI assistance, to measure diagnostic accuracy and reader improvement.

6. Standalone (Algorithm Only) Performance Study

Yes, in essence. The Limit of Detection (LOD) regression testing specifically evaluates the performance of the algorithm and instrument system itself (the combined cobas® 4800 System and the CT/NG Tests with the new software) by measuring its ability to detect specific concentrations of CT and NG. While not explicitly termed a "standalone" study in the context of clinical diagnostic accuracy, it represents the algorithm's performance without human intervention in the interpretation of the raw signal data, as the software processes raw fluorescence data using data analysis algorithms and determines validity and outputs results (Section {6}).

7. Type of Ground Truth Used

The ground truth used was analytically prepared samples with known concentrations of Chlamydia trachomatis (EB/mL) and Neisseria gonorrhoeae (CFU/mL). These samples were spiked at various levels around the expected Limit of Detection. This allowed for the determination of the LOD using Probit analysis.

8. Sample Size for the Training Set

The document does not specify a separate training set sample size. This submission is for a software update to an already cleared device. The focus is on verifying that the changes do not degrade the performance of the established algorithms. Therefore, it's more about re-validation and regression testing rather than developing a new algorithm requiring a distinct training set. The algorithms themselves would have been "trained" during the development of the original predicate devices (K132270 and K110923).

9. How the Ground Truth for the Training Set Was Established

As no new algorithm requiring a specific training set is discussed or implied in this submission, the establishment of ground truth for a training set is not applicable. The underlying algorithms for the CT/NG tests were already established and validated in the predicate submissions; this submission verifies their performance is unchanged after a software update to the platform.

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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.

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.

Here's a breakdown of the acceptance criteria and study details for the cobas® CT/NG v2.0 Test, based on the provided 510(k) summary:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the reported performance metrics, primarily sensitivity and specificity, at various specimen types and symptom statuses. The device generally aims for high sensitivity and specificity.

Chlamydia trachomatis (CT) Clinical Performance

Neisseria gonorrhoeae (NG) Clinical Performance

2. Sample Size for the Test Set and Data Provenance

• Total Evaluable Subjects: 6,004 (5,266 females and 738 males)

• Female Test Set Sub-samples:

  • Endocervical Swabs (SW): 2926 (1932 symptomatic, 994 asymptomatic)
  • Urine (UR): 2945 (1937 symptomatic, 1008 asymptomatic)
  • Clinician-collected Vaginal Swabs (VG-C): 1902 (899 symptomatic, 1003 asymptomatic)
  • Self-collected Vaginal Swabs (VG-S): 2037 (1041 symptomatic, 996 asymptomatic)
  • PreservCyt (PC Pre): 2937 (1935 symptomatic, 1002 asymptomatic)
  • PreservCyt (PC Post): 2878 (1871 symptomatic, 1007 asymptomatic)

• Male Test Set Sub-samples:

  • Urine (UR): 738 (278 symptomatic, 460 asymptomatic)

• Data Provenance: The studies were multi-center clinical investigations conducted in the United States.

  • One clinical investigation used archived samples (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) from the previous cobas® CT/NG Test evaluation.
  • A second investigation used prospectively collected fresh samples (endocervical specimens, clinician-collected vaginal specimens, female urine specimens, and cervical specimens in PreservCyt Solution from asymptomatic women).
  • Specimen collection took place at 18 collection sites in the US, including family planning, Obstetrics/Gynecology (OB/GYN) clinics, and sexually transmitted disease clinics.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not explicitly state the number of "experts" or their qualifications. The ground truth ("Patient Infected Status" - PIS) was established using a combination of results from two commercially available nucleic acid amplification tests (NAATs) (NAAT1 and NAAT2). These reference NAATs are implicitly considered the "expert" or gold standard. The qualifications of personnel performing these reference NAATs are not specified.

4. Adjudication Method for the Test Set

The adjudication method for establishing Patient Infected Status (PIS) was based on a "2+1" or consensus approach using two reference NAATs.

• 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.
• 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.
• Subjects were excluded if PIS could not be determined due to missing/indeterminate results from reference tests.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study focuses on the standalone performance of the device (a diagnostic test kit), not on human reader performance with or without AI assistance. Therefore, there is no effect size of human readers improving with AI.

6. If a Standalone Study was done

Yes, a standalone performance study (algorithm only without human-in-the-loop performance) was done. The entire clinical performance section (Section 5) evaluates the cobas® CT/NG v2.0 Test directly against the established Patient Infected Status (PIS), which is derived from other NAATs, representing the algorithm's performance.

7. The Type of Ground Truth Used

The ground truth used was expert consensus (proxy by reference assays), specifically the Patient Infected Status (PIS), determined by the concordance of results from two commercially available predicate/reference Nucleic Acid Amplification Tests (NAATs).

8. The Sample Size for the Training Set

The document does not explicitly state a separate sample size for a training set. The language used ("clinical investigations") suggests that the samples described in Section 5.2 are primarily for performance evaluation and not necessarily a distinct, partitioned training set as might be found in machine learning contexts. However, the study does mention using archived samples from a previous clinical study of the cobas® CT/NG Test (K110923) combined with prospectively collected fresh samples for the current evaluation. It's possible the archived data contributed to various stages of development or internal validation, but a formal "training set" for the v2.0 device as a distinct phase with specified numbers is not detailed in this summary.

9. How the Ground Truth for the Training Set was Established

As a distinct "training set" is not explicitly defined, the method for establishing its ground truth is also not detailed. However, it's reasonable to infer that any data used in the development or internal validation phases would have relied on similar or equivalent methods for ground truth determination, likely involving comparison to established reference methods or culture, as is standard for diagnostic assay development. The summary focuses on the clinical performance evaluation of the final device using the PIS as described in point 4.

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