(210 days)
The Alinity m STI Assay is an in vitro polymerase chain reaction (PCR) assay for use with the automated Alinity m System for the direct, qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis (CT), DNA from Neisseria gonorrhoeae (NG), ribosomal RNA from Trichomonas vaginalis (TV), and ribosomal RNA from Mycoplasma genitalium (MG), to aid in the diagnosis of disease(s) caused by infection from these organisms. The assay may be used to test the following specimens from symptomatic and asymptomatic individuals for the following analytes:
- . CT: vaginal swabs (clinician-collected and self-collected in a clinical setting). endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, female urine, male urine, oropharyngeal swabs, and rectal swabs
- . NG: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, female urine, male urine, oropharyngeal swabs, and rectal swabs
- . TV: vaginal swabs (clinician-collected and self-collected in a clinical setting). endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, female urine, and male urine
- . MG: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, and male urine
A vaginal swab (self-collected or clinician-collected) is the preferred specimen type for MG testing in females due to the higher clinical sensitivity compared to endocervical swabs. If endocervical swab specimens test negative, testing with a vaginal swab may be indicated if M. genitalium infection is suspected.
The Alinity m STI Assay utilizes real time PCR to amplify and detect Chlamydia trachomatis (CT) ribosomal RNA sequences, Neisseria gonorrhoeae (NG) genomic DNA sequences, Trichomonas vaginalis (TV) ribosomal RNA sequences, Mycoplasma genitalium (MG) ribosomal RNA sequences, and human genomic DNA sequences that have been extracted from endocervical swab specimens, vaginal swab specimens, oropharyngeal swab specimens, rectal swab specimens, male and female urine specimens, and gynecological specimens preserved in PreservCyt Solution. Endocervical swab, vaginal swab, oropharyngeal swab, rectal swab, and urine specimens are collected with the Alinity m multi-Collect Specimen Transport Kit. PreservCyt specimens are transferred to a transport tube for processing on the Alinity m System.
This device is similar to the predicate device originally cleared (K202977). It does not introduce any changes to the Alinity m STI Assay reagents, sample processing, assay procedure, and data reduction. This device is updating the previous FDA-cleared Intended Use (K202977) to include claims for the following specimens for the following analytes:
- CT: Gynecological specimens in ThinPrep PreservCyt Solution, female urine .
- NG: Female urine
Two studies were initiated to support these claims (refer to Section 1.7.2.) This supplemental data was used with data previously obtained from the Alinity m STI Assay clinical testing studies submitted in K202977.
The steps of the Alinity m STI Assay consist of sample preparation. RT-PCR assembly, amplification/detection, and result calculation and reporting. All stages of the Alinity m STI Assay procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random-access analyzer that can perform the Alinity m STI Assay in parallel with other Alinity m assays on the same instrument.
The Alinity m STI Assay is an in vitro diagnostic device for the qualitative detection and differentiation of nucleic acids from Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG) in various human specimen types. The device operates on the automated Alinity m System and utilizes real-time Polymerase Chain Reaction (PCR) technology. This submission primarily focuses on supporting expanded claims for specific analytes and specimen types: CT in gynecological specimens in ThinPrep PreservCyt Solution and female urine, and NG in female urine.
Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" for the clinical performance in terms of specific thresholds (e.g., minimum PPA/NPA). Instead, it presents the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) values with 95% Confidence Intervals (CI) as the primary performance metrics, demonstrating the device's accuracy against a Composite Comparator Algorithm (CCA).
| Analyte | Specimen Type | Symptom Status | N (Analyzed) | Alinity m STI PPA (95% CI) | Alinity m STI NPA (95% CI) |
|---|---|---|---|---|---|
| CT | Female Urine | Symptomatic | 714 | 95.9 (86.3, 98.9) | 99.8 (99.2, 100.0) |
| CT | Female Urine | Asymptomatic | 2071 | 97.0 (92.6, 98.8) | 99.8 (99.5, 99.9) |
| CT | Female Urine | All | 2785 | 96.7 (93.0, 98.5) | 99.8 (99.6, 99.9) |
| NG | Female Urine | Symptomatic | 714 | 100.0 (79.6, 100.0) | 100.0 (99.5, 100.0) |
| NG | Female Urine | Asymptomatic | 2070 | 97.1 (85.1, 99.5) | 99.9 (99.6, 100.0) |
| NG | Female Urine | All | 2784 | 98.0 (89.3, 99.6) | 99.9 (99.7, 100.0) |
| CT | PreservCyt | Symptomatic | 953 | 98.5 (92.0, 99.7) | 99.9 (99.4, 100.0) |
| CT | PreservCyt | Asymptomatic | 986 | 98.1 (90.1, 99.7) | 99.4 (98.6, 99.7) |
| CT | PreservCyt | All | 1939 | 98.3 (94.1, 99.5) | 99.6 (99.2, 99.8) |
Note: The table is constructed based on the "specimen-specific positive and negative agreement" data. The document does not provide specific acceptance thresholds, but the presented performance metrics are high, demonstrating the device's effectiveness.
2. Sample Size Used for the Test Set and Data Provenance:
- CT and NG in Female Urine:
- Sample Size: A total of 2,798 female subjects were enrolled. 2,785 CT results and 2,784 NG results were used in the analysis after exclusions due to missing/indeterminate CCA results.
- Data Provenance: The study was a multicenter clinical study conducted in the United States. Subjects provided urine specimens. The data includes both symptomatic and asymptomatic individuals.
- CT in PreservCyt Specimens:
- Sample Size: 1,939 specimens from a multicenter clinical study were included in the analysis.
- Data Provenance: The study was a multicenter clinical study conducted in the United States. Female subjects provided gynecological specimens collected in PreservCyt Solution.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
The ground truth was established using a clinical comparator method, not individual experts.
- Ground Truth Method: A Composite Comparator Algorithm (CCA) was used.
- Details: For each subject, a CCA was determined for each analyte based on the combined results from commercially available nucleic acid amplification tests (NAATs).
- For the female urine study (CT and NG), comparator assays included 3 commercially available NAATs. Specimens were initially tested with 2 NAATs. If they disagreed or a result was missing/indeterminate, a third tiebreaker NAAT was used.
- For the PreservCyt study (CT), specimens were tested with up to 3 comparator NAATs. Similar to the urine study, specimens were initially tested with 2 NAATs, and a third was used as a tiebreaker if needed.
- Qualifications of Experts: The document does not mention the use of human experts or their qualifications for establishing ground truth. The ground truth is effectively an "expert panel of assays" (the comparator NAATs).
4. Adjudication Method for the Test Set:
- Method: A 2+1 adjudication method was employed for establishing the Composite Comparator Algorithm (CCA).
- Description: Specimens were initially tested with two comparator NAATs.
- If the two initial NAATs agreed (both positive or both negative), that result formed the CCA.
- If the two initial NAATs disagreed, or if one result was missing or indeterminate, a third "tiebreaker" NAAT was used to resolve the discrepancy and establish the CCA.
- A subject was categorized as "Positive" if at least 2 comparator assay results were positive and "Negative" if at least 2 comparator assay results were negative.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:
No, an MRMC comparative effectiveness study was not done. The Alinity m STI Assay is an in vitro diagnostic device (IVD) that provides a qualitative result directly. Its performance is compared against a composite reference standard (CCA) derived from other NAATs, not against human readers. Therefore, the concept of human readers improving with AI assistance is not applicable in this context.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:
Yes, a standalone performance study was done. The reported performance metrics (PPA and NPA) reflect the accuracy of the Alinity m STI Assay (algorithm and reagents performed on the automated Alinity m System) operating independently against the established ground truth (CCA). The device provides a direct, qualitative result without human interpretation of the algorithm's output for diagnosis.
7. The Type of Ground Truth Used:
The ground truth used was a Composite Comparator Algorithm (CCA), which is an expert consensus based on multiple FDA-cleared nucleic acid amplification tests (NAATs). These NAATs are considered the gold standard for detecting these pathogens. The CCA essentially serves as the "best available truth" when a true clinical outcome or pathological confirmation for all cases is not feasible or practical in a large-scale clinical trial.
8. The Sample Size for the Training Set:
The document does not explicitly describe a separate "training set" for the Alinity m STI Assay in the context of this 510(k) submission. This is typical for IVD devices, where the assay's design, reagent formulation, and analytical parameters are developed through internal R&D, rather than a machine learning training paradigm with a distinct training dataset for an "algorithm." The clinical studies mentioned (both the original K202977 studies and the supplemental studies) serve as validation/test sets to demonstrate the performance of the already developed assay.
9. How the Ground Truth for the Training Set Was Established:
Since a distinct "training set" in the machine learning sense is not described, the question of how its ground truth was established is not directly applicable. The Alinity m STI Assay's underlying technology (real-time PCR) and design would have been established and optimized based on known genetic sequences, analytical performance studies (e.g., analytical sensitivity, specificity), and prior knowledge of the target organisms, where ground truth sources for these developmental phases would likely include:
- Well-characterized isolates/strains: Known positive and negative biological samples.
- Synthetic nucleic acid targets: Designed to validate primer and probe performance.
- Spiked matrix samples: To assess analytical performance in relevant specimen types.
These developmental activities would precede the clinical validation studies that are the focus of this 510(k) submission.
§ 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.