(68 days)
The GEN-PROBE APTIMA® Assay for Chlamydia trachomatis is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) to aid in the diagnosis of chlamydial urogenital disease using the TIGRIS® DTS® Automated Analyzer or semiautomated instrumentation as specified. The assay may be used to test the following specimens from symptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens and female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens, patient-collected vaginal swab specimens, and female and male urine specimens. The assay is also intended for use with the testing of gynecological specimens, from both symptomatic and asymptomatic patients collected in the PreservCyt® Solution and processed with the Cytyc ThinPrep® 2000 System.
Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE®APTIMA® Assay for Chlamydia trachomatis with the testing of gynecological specimens collected in the PreservCyt® Solution and processed with the Cytyc ThinPrep® 2000 System, for use on the TIGRIS® DTS® System. The ancillary kit for this application is commercially available as the GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for ruse regarding decontamination and specimen processing procedures. The APTIMA Transfer Kit may only be used in conjunction with the APTIMA Assays.
Acceptance Criteria and Device Performance for APTIMA® Assay for Chlamydia trachomatis
The APTIMA® Assay for Chlamydia trachomatis (CT) on the TIGRIS® DTS® System extends the clinical performance claims for testing gynecological specimens collected in PreservCyt® Solution and processed with the Cytyc ThinPrep® 2000 System. The study aimed to demonstrate equivalent performance between the previously validated DTS Systems and the TIGRIS DTS System.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity | Detection of Chlamydia trachomatis rRNA at 1 Inclusion Forming Unit (IFU) / assay (5 fg of total CT rRNA) in post-processed PreservCyt liquid Pap specimens should show high percent positivity. | 100% positive results (60/60 replicates) with a 95% Confidence Interval of (95.1 - 100) at 1 IFU (5 fg)/assay. This demonstrates robust analytical sensitivity. |
| Analytical Specificity | Diverse culture isolates, especially those phylogenetically related to C. trachomatis, and those known to cross-react in other amplification assays, should produce negative results when tested in PreservCyt liquid Pap media and Swab Transport Media (STM) on the TIGRIS DTS System. | All 24 culture isolates (including Neisseria species and Chlamydia pneumoniae/psittaci, some known to cross-react in other assays) produced negative results on the TIGRIS DTS System when tested in PreservCyt liquid Pap media. This indicates good analytical specificity and minimal cross-reactivity. |
| Specimen-Caused Inhibition | The frequency of inhibition in negative clinical post-processed PreservCyt liquid Pap specimens, when spiked with CT rRNA at the limit of detection, should be minimal or absent. | 0% inhibition (0/239 specimens) was detected in post-processed PreservCyt liquid Pap specimens. All 239 spiked negative specimens yielded CT positive results, indicating no inhibition. |
| Interference by Whole Blood | The presence of whole blood (up to 10% v/v) in PreservCyt liquid Pap specimens should not interfere with background signals in negative samples or with the recovery of a positive signal in CT-spiked samples. | PreservCyt liquid Pap specimens with up to 10% (v/v) blood yielded background signals below the assay cut-off for unspiked samples. For spiked samples, the presence of up to 10% (v/v) blood did not interfere with the recovery of a positive signal. |
| Clinical Performance Equivalence (Clinical Specimen Study) | Performance of the ACT Assay on the TIGRIS System should be equivalent to performance on the DTS Systems in PreservCyt specimens, demonstrated by high percent agreement (overall, positive, and negative) for both symptomatic and asymptomatic individuals. | Agreement between TIGRIS and DTS Systems was 100% (116/116) across all symptomatic (81 subjects) and asymptomatic (35 subjects) female subjects. Specifically: |
- Positive % Agreement: 100% (94.4-100% CI)
- Negative % Agreement: 100% (93.2-100% CI)
- Overall % Agreement: 100% (96.9-100% CI) |
| Clinical Performance Equivalence (Clinical Panel Study) | The ACT Assay on the TIGRIS System should show 100% agreement with expected CT results for panel members with varying CT rRNA concentrations (including 0 fg/assay and various positive concentrations) in PreservCyt liquid Pap specimens, and demonstrate equivalence to the DTS Systems. | The percent agreement for each level of rRNA in PreservCyt liquid Pap specimens with the expected CT results for both the TIGRIS System and the DTS Systems was 100% for all panel members. The overall % agreement between TIGRIS and DTS was 100% (97.2-100% CI). |
2. Sample Sizes and Data Provenance
- Analytical Sensitivity: 60 replicates of C. trachomatis rRNA spiked into post-processed PreservCyt liquid Pap specimen pool.
- Analytical Specificity: 24 culture isolates tested.
- Specimen-Caused Inhibition: 239 negative clinical post-processed PreservCyt liquid Pap specimens.
- Interference by Whole Blood: Clinical post-processed PreservCyt liquid Pap specimen pools, tested with 0% and 10% whole blood, both unspiked and spiked with CT rRNA.
- Clinical Specimen Study: 116 PreservCyt specimens from female subjects (81 symptomatic, 35 asymptomatic).
- Clinical Panel Study: 5 panel members, including a negative control and 4 positive concentrations of CT rRNA, prepared by spiking. Total of 132 replicates (12 for negative, 30 for each positive concentration).
Data Provenance: The report indicates a "prospective, multi-center clinical study" was conducted for the clinical performance data. Patient enrollment occurred at "family planning, OB/GYN, public health, and STD clinics." This suggests the clinical data is prospective and collected from various clinical sites. The country of origin is not explicitly stated but implied to be the USA given the FDA 510(k) submission.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state the "number of experts" or their specific "qualifications" used to establish ground truth in the traditional sense of expert review for image interpretation or diagnosis.
- For the Clinical Specimen Study, specimens were first screened using "FDA-cleared applications of the APTIMA COMBO 2 (AC2) Assay." The results from this FDA-cleared assay served as the reference standard (ground truth proxy) for comparing the DTS Systems and TIGRIS System results.
- For the Clinical Panel Study, negative PreservCyt specimens were pooled and confirmed negative by testing with the ACT Assay on the DTS Systems. Then, CT ribosomal RNA (rRNA) was spiked at known concentrations to create panel members. The "expected CT results" based on the known spiked concentrations served as the ground truth.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method like 2+1 or 3+1. For the clinical specimen study, the "ground truth" was established by prior testing with an "FDA-cleared" assay (APTIMA COMBO 2 Assay), implying it was considered a reliable reference. Discrepancies, if any, between the test systems (TIGRIS vs. DTS) were analyzed for percent agreement, rather than adjudicated by independent readers. "Specimens with final invalid or equivocal screening results were not selected for testing," suggesting a pre-screening step to ensure data quality.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was performed as this is an in vitro diagnostic (IVD) assay detection system, not an imaging device requiring human reader interpretation. The study compares the performance of two automated systems (TIGRIS DTS System vs. DTS Systems) for detecting Chlamydia trachomatis. There is no human-in-the-loop component for which an improvement effect size with AI assistance would be relevant.
6. Standalone Performance Study
Yes, a standalone performance study was done for the algorithm (the APTIMA Assay on the TIGRIS DTS System). The entire document describes the analytical and clinical performance of the device on its own, comparing it against a reference standard or a previously cleared device. The "overall % agreement" in the clinical studies directly reflects the standalone performance of the TIGRIS DTS System relative to the DTS system and the expected results.
7. Type of Ground Truth Used
- Analytical Studies (Sensitivity, Specificity, Inhibition, Interference): Ground truth was established by known concentrations of C. trachomatis rRNA or culture isolates, or by the absence of target/interfering substance in controlled laboratory settings.
- Clinical Specimen Study: Ground truth was established by results from a previously FDA-cleared assay (APTIMA COMBO 2 Assay), acting as the reference standard.
- Clinical Panel Study: Ground truth was established by known spiked concentrations of CT ribosomal RNA (rRNA) into confirmed negative PreservCyt specimens.
8. Sample Size for the Training Set
The document describes an analytical validation and clinical performance study for a diagnostic assay, not a machine learning or AI algorithm in the context of a "training set." Therefore, a "training set" as understood in AI/ML development is not applicable here. The assays are based on target amplification nucleic acid probe technology.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, there is no explicit "training set" as this is not an AI/ML device that requires machine learning for its core function. The assay's parameters and cut-offs would have been established during earlier development and validation phases (not detailed in this 510(k) summary), likely using characterized positive and negative samples, similar to the "panel" approach seen in the clinical panel study.
§ 866.3120 Chlamydia serological reagents.
(a)
Identification. Chlamydia serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to chlamydia in serum. Additionally, some of these reagents consist of chlamydia antisera conjugated with a fluorescent dye used to identify chlamydia directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusChlamydia and provides epidemiological information on these diseases. Chlamydia are the causative agents of psittacosis (a form of pneumonia), lymphogranuloma venereum (a venereal disease), and trachoma (a chronic disease of the eye and eyelid).(b)
Classification. Class I (general controls).