(28 days)
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.
| Acceptance Criterion (Implicit) | Reported Device Performance |
|---|---|
| For cobas® CT/NG v2.0 Test: The Limit of Detection (LOD) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) with Software Release 2.1 (SR2.1) must demonstrate equivalence to the LOD with Software Release 1.2 (SR1.2), as indicated by overlapping 95% confidence intervals. | cobas® CT/NG v2.0 Test (SR1.2 vs. SR2.1): |
| CT (EB/mL): | |
| SR1.2 LOD: 16.5 (95% CI: 13.2 - 22.8) | |
| SR2.1 LOD: 16.5 (95% CI: 13.1 - 23.4) | |
| NG (CFU/mL): | |
| SR1.2 LOD: 0.08 (95% CI: 0.07 - 0.11) | |
| SR2.1 LOD: 0.10 (95% CI: 0.08 - 0.13) | |
| Performance meets criterion: The 95% confidence intervals for both CT and NG overlap between SR1.2 and SR2.1, indicating equivalent levels of sensitivity. | |
| For cobas® CT/NG Test: The Limit of Detection (LOD) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) with Software Release 2.1 (SR2.1) must demonstrate equivalence to the LOD with Software Release 1.1 (SR1.1), as indicated by overlapping 95% confidence intervals. | cobas® CT/NG Test (SR1.1 vs. SR2.1): |
| CT (EB/mL): | |
| SR1.1 LOD: 24.7 (95% CI: 20.4 - 36.6) | |
| SR2.1 LOD: 22.4 (95% CI: 19.3 - 32.1) | |
| NG (CFU/mL): | |
| SR1.1 LOD: 0.17 (95% CI: 0.13 - 0.24) | |
| SR2.1 LOD: 0.13 (95% CI: 0.11 - 0.18) | |
| Performance meets criterion: The 95% confidence intervals for both CT and NG overlap between SR1.1 and SR2.1, indicating equivalent levels of sensitivity. | |
| General Non-Interference: The software changes, including the User Defined Workflow (UDF) feature, must not interfere with the performance or integrity of the cobas® 4800 IVD workflows and results for the CT/NG Tests. | UDF Non-Interference with IVD: |
| Testing concluded that the UDF software does not interfere with the co-installed cobas® 4800 IVD system. Regardless of UDF installation, "the cobas® 4800 IVD system meets its intended use requirements for running the HPV and CT/NG Tests." | |
| Performance meets criterion. | |
| No Impact on Assay Functional Processing Steps: The various software improvements and changes (e.g., Integrated Work Order Editor, Integrated CT/NG Workflow Selection, Tip Tracking and Counting, Early Specimen Removal, Flexible Run Sizes, Result View and Report Layout Improvements, Recovery Workflow, Generic Calculation Engine, LIS Improvements) must not affect the sample preparation process, PCR cycling profile, or data analysis. | Verification, Validation, and Regression Testing: |
| "Testing has shown that these changes do not impact the sample preparation process, PCR cycling profile, or data analysis of the CT/NG tests that were consolidated onto the version 2.1 platform." Specific sections (1.4-1.13) detail why each change does not affect assay performance. The "Generic Calculation Engine" section explicitly states: "The same data analysis algorithms, algorithm parameters, and final results determination tables were retained for each migrated test. Results outputs were verified to be the same before and after migration." | |
| Performance meets criterion. | |
| Acceptable Risk Level: All identified risks, after mitigation, must be acceptable for the intended use of the system and tests. | Risk Assessment: |
| Final risk assessments for the cobas® 4800 system and CT/NG tests, performed after hazard analysis and risk mitigations, "identified no intolerable risks. The overall level of risk associated with each instrument, software or component was determined to be acceptable for its intended use in the cobas® 4800 system." (Specifically, all "Red" risks were eliminated, and remaining risks were "Green" or "Yellow" with documentation for acceptance). | |
| Performance meets criterion. |
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.
§ 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).