(56 days)
The binx health io CT/NG Assay, when tested using the binx health io Instrument, is a fully automated, rapid, qualitative test intended for use in point-of-care or clinical laboratory settings for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA by polymerase chain reaction. The binx health io CT/NG Assay is intended for use with female vaginal swab specimens, collected either by a clinician or self-collected by a patient in a clinical setting, or male urine specimens, as an aid in the diagnosis of symptomatic or asymptomatic Chlamydia trachomatis and/or Neisseria gonorrhoeae infection. For a symptomatic male patient with a chlamydia negative test result, further testing with a laboratory-based molecular test is recommended.
The binx health io CT/NG Assay System (the "binx io System", "binx io CT/NG Assay" or "the System") is a rapid qualitative in vitro diagnostic system consisting of the following:
- The binx io Instrument for running the Cartridge (the "Instrument")
- The binx io CT/NG Cartridge (the "CT/NG Cartridge", "Cartridge" or "Cartridges"), that contains all the necessary reagents to perform the binx io CT/NG Assay (the "Assay") on the binx io Instrument
- A single-use, fixed-volume transfer pipet (packaged with the Cartridge) for transferring the sample to the Cartridge
- A Male Urine Collection Kit consisting of sample Collection tube containing preservation medium and a transfer pipet (the "Male Urine Collection Kit")
All reagents are contained in the Cartridge as a combination of liquid reagents in blister packs and dried reagents. The Instrument is a small, desk top, fully-integrated instrument that uses air pressure to open and close valves on the binx io CT/NG Cartridge which, in turn, controls the movement of solutions within the Cartridge; the Instrument takes full control of the Cartridges once they are inserted, and no further user interaction is required. The operation of the Instrument is designed to be simple and intuitive; a user follows simple instructions on the graphical user interface (GUI) screen to load the Cartridge onto the Instrument with no further interaction required.
The Male Urine Collection Kit consists of a tube containing a small volume of preservative medium and a Urine Transfer Pipet. To obtain a sample suitable for use on the CT/NG Cartridge, a 20-30 mL first-catch urine sample is collected by a patient in a suitable sterile vessel. The Urine Transfer Pipet provided with the Male Urine Collection Kit is used to transfer a sufficient volume of urine (nominally 4 mL in 2x 2 mL steps) into the collection tube such that the total volume falls between the two indicated lines on the collection tube.
Once a sample has been correctly collected, the required sample volume (0.5 mL) is transferred from the sample collection tube to the Cartridge using the Sample Transfer Pipet provided with the Cartridge. The Cartridge has a visual sample addition indicator window which turns from light to dark to show the user that a sample has been added to the Cartridge.
The Cartridge has three main Assay steps: sample preparation to isolate and purify target DNA; ultra-rapid polymerase chain reaction (PCR), which amplifies specific regions of DNA from the target organisms; and a proprietary electrochemical detection method to identify the presence of amplified DNA.
When the specimen is added to the Cartridge, it is automatically mixed with a lysis solution to disrupt the cells present and release DNA which also rehydrates the Internal Process Control (IPC) sample. DNA extraction takes place and the eluted DNA is transferred to a homogenization chamber.
The DNA in solution is transferred into two separate amplification chambers and reconstitutes the dried PCR reagents as it enters the chambers which are located over the Instrumentcontrolled PCR heater. Ultra-rapid PCR is carried out using sequence-specific primers for CT, NG (two separate genomic targets) and the IPC.
Following amplification, the amplified target DNA is transferred from each PCR chamber into two separate detection chambers (four detection chambers in total) which contain a carbonbased screen-printed electrode. When the target is present and amplified, the target-specific probes and amplicon hybridize. The electrochemical labels are cleaved using a double-strand specific exonuclease. The cleaved electrochemical label diffuses to the electrode surface generating an electrical current that can be measured at a distinct voltage in nano Amps (nA) for each electrochemical label used.
The presence of a measurable peak to a fixed cut-off parameter for each target returns a qualitative result without the need for any user interpretation or calculations.
The binx health io CT/NG Assay and System is a fully-automated, rapid, qualitative test for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) DNA. The following information details its acceptance criteria and the study that demonstrated its performance.
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria | Reported Device Performance (Male Urine) - Total |
|---|---|---|
| Chlamydia trachomatis (CT) | ||
| Sensitivity | Not explicitly stated, implied to be high for regulatory clearance | 92.5% (95% CI: 86.4% - 96.0%) |
| Specificity | Not explicitly stated, implied to be high for regulatory clearance | 99.3% (95% CI: 98.4% - 99.7%) |
| Neisseria gonorrhoeae (NG) | ||
| Sensitivity | Not explicitly stated, implied to be high for regulatory clearance | 97.3% (95% CI: 90.7% - 99.3%) |
| Specificity | Not explicitly stated, implied to be high for regulatory clearance | 100.0% (95% CI: 99.5% - 100.0%) |
Note: The document provides confidence intervals for sensitivity and specificity, indicating high performance was expected for regulatory approval.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 922 fully evaluable male urine specimens.
- Data Provenance: Prospective, multi-center study conducted at nine investigational sites throughout the U.S.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number or specific qualifications of experts used for establishing ground truth for the test set. However, the ground truth (Composite Infected Status - CIS) was established using a concordance of three legally marketed predicate devices, run on validated laboratory systems. These predicate devices are themselves validated diagnostic tools, implying a high level of accuracy typically overseen by qualified laboratory personnel.
4. Adjudication Method for the Test Set
The adjudication method used to establish the Composite Infected Status (CIS) for the test set was defined as follows:
- A patient was considered infected if at least two out of the three reference tests were positive.
- A patient was considered not infected if at least two out of the three reference tests were negative.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. The study evaluated the standalone performance of the binx io CT/NG Assay against a Composite Infected Status derived from multiple reference NAATs, rather than assessing human reader improvement with AI assistance.
6. Standalone Performance Study
Yes, a standalone performance study was conducted. The clinical performance data presented (sensitivity and specificity) are for the binx io CT/NG Assay and System operating independently, without a human-in-the-loop for interpretive decisions, other than initial sample collection and loading. The system provides qualitative results (e.g., "CT Detected") without user interpretation.
7. Type of Ground Truth Used
The type of ground truth used was a Composite Infected Status (CIS). This CIS was established by comparing the results of the binx io CT/NG Assay to three legally marketed and clinically validated reference nucleic acid amplification tests (NAATs):
- Hologic Aptima Combo 2 (AC2) Chlamydia/Gonorrhea Assay run on Panther
- BD ProbeTec Chlamydia trachomatis (CT) Q* and BD ProbeTec Neisseria gonorrhoeae (GC) Q* assays run on the Viper XTR™
- Roche cobas CT/NG v2.0 test run on the cobas 4800 System
8. Sample Size for the Training Set
The document does not explicitly provide the sample size for a separate "training set" in the context of clinical performance evaluation. The clinical study described is a prospective validation study against a defined ground truth for market clearance purposes. Analytical studies (e.g., LoD, inclusivity, exclusivity) generally use controlled laboratory samples for method development and validation, which can be considered analogous to "training" or "development" data in an algorithm context, but a distinct clinical training set size is not reported.
9. How the Ground Truth for the Training Set Was Established
Given that a specific clinical "training set" with established ground truth is not detailed, the ground truth for the analytical performance studies (which would inform development) was established through controlled laboratory methods. For example:
- Limit of Detection (LoD): Determined using cellular CT and NG material with quantified genome equivalents (GE/mL).
- Analytical Reactivity (Inclusivity/Exclusivity): Evaluated against known concentrations of various CT serovars, NG strains, and panels of potentially cross-reactive microorganisms or human genomic DNA. These "ground truths" are based on the known identity and concentration of the spiked organisms or substances.
§ 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.