FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

The BD ProbeTec Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay, when tested with either the BD Viper™ System in Extracted Mode or the BD Viper™ LT System, uses Strand Displacement Amplification technology for the direct, qualitative detection of Neisseria gonorrhoeae DNA in clinician-collected female endocervical and male urethral swab specimens, patient-collected vaginal swab specimens (in a clinical setting), and male and female urine specimens (both UPT and Neat). The assay is also intended for use with gynecological specimens collected in BD SurePath™ Preservative Fluid or PreservCyt™ Solution using an aliquot that is removed prior to processing for either the BD SurePath or ThinPrep™ Pap test. The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of gonococcal urogenital disease.

Device Description

The BD ProbeTec GCO Assay is based on the simultaneous amplification and detection of target DNA using amplification primers and a fluorescently-labeled detector probe The reagents for strand displacement amplification (SDA) are dried in two separate disposable microwells: the Priming Microwell contains the amplification primers, fluorescently-labeled detector probe, nucleotides and other reagents necessary for amplification, while the Amplification Microwell contains the two enzymes (a DNA polymerase and a restriction endonuclease) that are required for SDA. In alignment with the FDA Guidance Document, "Assay Migration Studies for In Vitro Diagnostic Devices, Guidance for Industry and FDA Staff", April 25, 2013 the BD ProbeTec GCQ Assay is being migrated from the existing BD Viper System operating in extracted mode (Viper XTR) to the new BD Viper LT System.

The BD Viper LT System is a table-top instrument that is designed to be fully contained on a standard laboratory bench-top. The system performs automated extraction of nucleic acids from multiple specimen types in addition to amplification and detection of target nucleic acid sequences when utilized with legally marketed in vitro diagnostic assays.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay on the BD Viper LT System, based on the provided text:

Acceptance Criteria and Device Performance

The general acceptance criteria for this type of diagnostic device is that the performance on the new system (BD Viper LT) should be substantially equivalent to the predicate device (BD Viper System in Extracted Mode), which implies comparable Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA). While explicit numerical acceptance criteria for PPA and NPA are not stated in the document, the clinical study results are presented to demonstrate this equivalence. The analytical performance (system contamination rate and reproducibility) also contributes to the overall equivalence determination.

Acceptance Criteria Category	Reported Device Performance
Clinical Performance	Positive Percent Agreement (PPA):

Female (All specimen types): 97.9% (320/327) with 95% CI (95.1%, 100.0%)
Male (Q*UPT): 100.0% (120/120)
Overall (All): 98.4% (440/447) with 95% CI (96.4%, 100.0%)

Negative Percent Agreement (NPA):

Female (All specimen types): 98.8% (934/945) with 95% CI (97.9%, 99.6%)
Male (Q*UPT): 99.5% (218/219) with 95% CI (98.6%, 100.0%)
Overall (All): 99.0% (1152/1164) with 95% CI (98.1%, 99.6%) |
| Analytical Performance | System Contamination Rate:
Q* Swab Diluent: 0.32% (2/630)
LBC Specimen Matrix: 0.0% (0/630)

Reproducibility (Overall for various specimen types and panels):

LBC: % Correct between 20.8% (High Negative) and 100.0% (Negative, Low Positive, Moderate Positive)
Swab: % Correct between 13.5% (High Negative) and 100.0% (Negative, Low Positive, Moderate Positive)
UPT: % Correct between 18.8% (High Negative) and 100.0% (Negative, Low Positive, Moderate Positive)
Overall %CVs range from 9.1% to 433.8% (for negative/high negative where the mean is very low and thus %CV can be high) for quantitation, but 100% agreement for positive controls. |

Study Details

Sample size used for the test set and the data provenance:
- Clinical Performance Test Set:
  - Female subjects: 617 compliant subjects
  - Male subjects: 167 compliant subjects
  - Total Clinical Samples: A total of 327 positive and 945 negative results for females across various specimen types were evaluated on the BD Viper LT system. For males, 120 positive and 219 negative results were evaluated for Q*UPT.
  - Data Provenance: The specimens were collected prospectively from individuals attending OB/GYN, sexually transmitted disease (STD), and family planning clinics at four geographically diverse clinical sites in North America. These were then assembled into comparison panels at BD and shipped to test sites.
- Analytical Performance Test Set:
  - System Contamination: 630 Negative samples (Q* Swab Diluent or LBC Specimen Matrix) and 630 Positive samples (spike GC at 10^3 CT EB/mL) per matrix type (Q* Swab Diluent, LBC Specimen Matrix). Tested on three BD Viper LT Systems.
  - Reproducibility: 3 levels of CT and GC organisms (and negative controls) seeded into LBC specimen matrix, vaginal matrix in Q* Swab Diluent, and urine specimen matrix. Two operators per site ran one panel each day for 8 days, totaling 16 runs. Each run consisted of 8 LBC, 8 swab, and 8 UPT panel members. This means for each panel type (LBC, Swab, UPT) and each level (Negative, High Negative, Low Positive, Moderate Positive), there were 96 replicates (3 sites * 2 operators * 8 days * 2 replicates per panel member or 3 sites * 16 runs * 2 replicates per panel member).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The ground truth for the clinical performance study was established by the BD Viper System in extracted mode reference results (the predicate device). It's not explicitly stated that human experts were involved in establishing the ground truth for each individual case in the test set. Instead, the predicate device itself served as the reference standard for comparison. The document does not specify the number or qualifications of experts directly used to establish this "ground truth" beyond relying on the previously cleared predicate device.
Adjudication method for the test set:
The document states: "Each comparison panel consisted of randomly chosen positive and negative specimens (based on BD Viper System in extracted mode reference results). The positive and negative specimens were randomized within the panel, and labeled such that the instrument user was blinded to the specimen results." This implies that the results from the BD Viper LT System were compared against the established reference results from the predicate BD Viper System. There is no mention of a human expert adjudication method (e.g., 2+1, 3+1) for discordant results between the new device and the predicate device. The comparison appears to be direct.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a molecular diagnostic assay (NAAT) for the detection of Neisseria gonorrhoeae DNA, not an imaging device requiring human reader interpretation. Therefore, the concept of "human readers improving with AI vs without AI assistance" is not applicable in this context. The assay provides a qualitative "positive" or "negative" result.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
Yes, the device's performance is standalone. The BD ProbeTec GCQ Assay on the BD Viper LT System is an automated instrument that performs nucleic acid extraction, amplification, and detection. It provides a qualitative result ("positive" or "negative") directly. Human involvement is in specimen collection, loading the samples, and interpreting the final automated result from the instrument, but not in the analytical process of generating the result itself. The clinical performance study directly compares the results of this automated system to the predicate automated system.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
The ground truth for the clinical performance comparison was the results from the predicate device: the BD ProbeTec GCQ Assay on the BD Viper System in Extracted Mode. This type of ground truth is often referred to as a "reference method" or "comparator method" in device migration studies. While the predicate device itself would have initially been cleared against a gold standard (e.g., culture or a combination of clinical outcomes and other diagnostic tests), for this 510(k) submission, the predicate device serves as the established "truth" for demonstrating substantial equivalence of the new system for the same assay.
The sample size for the training set:
The document does not explicitly state the sample size used for a "training set." This submission focuses on the migration of an existing assay formulation to a new instrument system. The assay formulation itself has "not changed." Therefore, it is implied that the assay was developed and "trained" (in a molecular biology sense, not necessarily machine learning) prior to this study on the new platform. The data provided are for analytical verification and a clinical comparison study.
How the ground truth for the training set was established:
As there is no distinct "training set" described in the context of machine learning, the concept of establishing ground truth for it is not applicable here. The assay formulation itself was developed based on established molecular biology principles for detecting Neisseria gonorrhoeae DNA. The ground truth for the predicate device (K081825) would have been established through its own clinical trials, likely using culture as a primary reference standard, possibly augmented by discrepant analysis with other methods. For this K140448 submission, the primary ground truth for comparison is the performance of the predicate device itself.

Summary

Regulation Number and Section

§ 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).