(179 days)
The BD CTGCTV2 assay incorporates automated DNA extraction and real-time polymerase chain reaction (PCR) for the direct, qualitative detection of DNA from:
- Chlamydia trachomatis (CT)
- Neisseria gonorrhoeae (GC)
- Trichomonas vaginalis (TV)
The assay may be used for detection of CT, GC and/or TV DNA in patient- or clinician-collected vaginal swab specimens (in a clinical setting) and male and female urine specimens. The assay may also be used for the detection of CT and GC DNA in endocervical swab and Liquid-Based Cytology (LBC) specimens in ThinPrep® PreservCyt® Solution using an aliquot that is removed prior to processing for the ThinPrep® Pap test. The assay may also be used for the detection of CT and GC DNA in clinician-collected rectal and oropharyngeal swab specimens.
The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of chlamydial, gonococcal, and/or trichomoniasis urogenital disease and chlamydial and gonococcal extragenital infection.
The BD CTGCTV2 assay is available for use with the BD MAX™ System (urogenital specimens) or the BD COR™ System (urogenital and extragenital specimens), as described above.
The BD CTGCTV2 assay, performed on the BD COR™ System (hereafter referred to as BD CTGCTV2), is designed for use with the applicable BD Molecular specimen collection and transport devices for male and female urine, rectal swabs, oropharyngeal swabs, vaginal swabs, endocervical swabs, and LBC specimens (PreservCyt®). Specimens are collected and transported to the testing laboratory using their respective transport devices under conditions of time and temperature that have been determined to maintain the integrity of the target nucleic acids.
The BD COR™ MX Instrument, when combined with the BD COR™ PX Instrument, is to be used for automated sample preparation, extraction, and purification of nucleic acids from multiple specimen types, as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR for simultaneous and differential detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.
The BD CTGCTV2 assay extraction reagents are dried in 96-well microtiter plates that contain binding magnetic affinity beads and Sample Processing Control (SPC). Each tube is capable of binding and eluting sample nucleic acids. The SPC monitors the integrity of the reagents and the process steps involved in DNA extraction, amplification and detection, as well as for the presence of potential assay inhibitors.
The BD CTGCTV2 assay liquid reagent plate includes Wash, Elution and Neutralization buffers. The beads (described above), together with the bound nucleic acids, are washed and the nucleic acids are eluted by a combination of heat and pH. When performed on BD COR™ System, there is an additional buffer to rehydrate the dried extraction mix. Eluted DNA is neutralized and transferred to the Amplification reagent (described below) to rehydrate the PCR reagents. After reconstitution, the BD COR™ System dispenses a fixed volume of PCR-ready solution containing extracted nucleic acids into the BD PCR Cartridge. Microvalves in the BD PCR Cartridge are sealed by the system prior to initiating PCR in order to contain the amplification mixture and thus prevent evaporation and contamination.
The BD CTGCTV2 assay is comprised of two targets for Chlamydia trachomatis (detected on the same optical channel), two targets for Neisseria gonorrhoeae (detected on two different optical channels) and one target for Trichomonas vaginalis (detected on one optical channel). Only one Chlamydia trachomatis target is required to be positive in order to report a positive result. Both Neisseria gonorrhoeae targets are required to be positive in order to report a positive result.
The amplified DNA targets are detected using hydrolysis (TaqMan®) probes, labeled at one end with a fluorescent reporter dye (fluorophore), and at the other end, with a quencher moiety. Probes labeled with different fluorophores are used to detect the target analytes in different optical channels of the BD COR™ System. When the probes are in their native state, the fluorescence of the fluorophore is quenched due to its proximity to the quencher. However, in the presence of target DNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5'-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the DNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The BD COR™ System monitors these signals at each cycle of the PCR and interprets the data at the end of the reaction to provide qualitative test results for each analyte (i.e., positive or negative).
The provided FDA 510(k) clearance letter and summary for the BD CTGCTV2 assay detail its performance in detecting Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in extragenital specimens (rectal and oropharyngeal swabs).
Here's an analysis based on your request:
Acceptance Criteria and Reported Device Performance
The acceptance criteria for the BD CTGCTV2 assay are implicitly demonstrated through its clinical performance results, where the assay's sensitivity (Positive Percent Agreement - PPA) and specificity (Negative Percent Agreement - NPA) for extragenital specimens are compared against a Composite Comparator Algorithm (CCA). The FDA's clearance indicates that these performance metrics met the necessary standards for substantial equivalence.
Table of Acceptance Criteria and Reported Device Performance:
While explicit numerical acceptance criteria (e.g., "PPA must be >= X%") are not directly stated in the provided text, the reported performance measures are the ones that met the FDA's requirements for clearance.
| Metric | Target/Condition (Implicit Acceptance Criteria) | Reported Device Performance (BD CTGCTV2) |
|---|---|---|
| Chlamydia trachomatis (CT) - Oropharyngeal | ||
| Sensitivity (PPA) | Sufficiently high for diagnostic use | 100% (86.2–100% CI) |
| Specificity (NPA) | Sufficiently high for diagnostic use | 99.8% (99.5–99.9% CI) |
| Neisseria gonorrhoeae (GC) - Oropharyngeal | ||
| Sensitivity (PPA) | Sufficiently high for diagnostic use | 92.8% (85.8–96.5% CI) |
| Specificity (NPA) | Sufficiently high for diagnostic use | 99.5% (99.1–99.7% CI) |
| Chlamydia trachomatis (CT) - Rectal | ||
| Sensitivity (PPA) | Sufficiently high for diagnostic use | 97.7% (93.5–99.2% CI) |
| Specificity (NPA) | Sufficiently high for diagnostic use | 99.4% (99.0–99.7% CI) |
| Neisseria gonorrhoeae (GC) - Rectal | ||
| Sensitivity (PPA) | Sufficiently high for diagnostic use | 95.8% (89.7–98.4% CI) |
| Specificity (NPA) | Sufficiently high for diagnostic use | 99.8% (99.5–99.9% CI) |
| Non-Reportable Rate (Total CT and GC) | Reasonably low for clinical utility (e.g., |
§ 866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s).
(a)
Identification. A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) is an in vitro diagnostic device intended for the detection and identification of nucleic acids from non-viral microorganism(s) and their associated resistance markers in clinical specimens collected from patients suspected of sexually transmitted infections. The device is intended to aid in the diagnosis of non-viral sexually transmitted infections in conjunction with other clinical and laboratory data. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist that are not detected by the device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;
(ii) Detailed discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate;
(iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) Limiting statements indicating that:
(A) A negative test result does not preclude the possibility of infection;
(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) Reliable results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(D) If appropriate (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type; and(v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that:
(A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present;
(B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora;
(C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and
(D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy.
(4) Design verification and validation must include:
(i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result (
e.g., how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies, including, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate.
(iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses.
(iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.