(28 days)
Aptima BV Assay: The Aptima BV Assay is an in vitro nucleic acid amplification test that utilizes real time Transcription-Mediated Amplification (TMA) technology for detection and quantitation of ribosomal RNA from bacterial vaginosis (BV), including Lactobacillus (L. gasseri, L. crispatus, and L. jenseni), Gardnerella vaginalis), and Atopobium vaginae (A. vaginae). The assay reports a qualitative result for BV and does not report results for individual organisms. The assay is intended to aid in the diagnosis of BV on the automated Panther System using clinician-collected and patient-collected vaginal swab specimens from females with a clinical presentation consistent with vaginitis and/or vaginosis.
Aptima CV/TV Assay: The Aptima CV/TV Assay is an in vitro nucleic acid amplification of RNA from microorganisms associated with vulvovaginal candidiasis and trichomoniasis. The assay utilizes real time Transcription-Mediated Amplification (TMA) technology to detect and qualitatively report results for the following organisms: Candida species group (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis), Candida glabrata (C. glabrata), Trichomonas vaginalis (TV). The assay differentiates between C. glabrata and the Candida species group (C spp) by targeting the RNA component of RNAse P ribonucleoprotein; the assay does not differentiate among C spp. For TV, the assay targets ribosomal RNA (rRNA) and differentiates the results for C. glabrata and C spp. The assy is intended to aid in the diagnosis of vulvovaginal candidiasis and trichomoniasis on the automated Panther System using clinician-collected and patientcollected vaginal swab specimens from females with a clinical presentation consistent with vagintis.
Aptima BV Assay: Like the Aptima BV assay 100 test kit, the Aptima BV assay 250 test kit is an in vitro nucleic acid amplification test for the detection and quantitation of rRNA from bacteria associated with bacterial vaginosis in women with a clinical presentation consistent with vaginitis/vaginosis. The Aptima BV assay utilizes the automated Panther system to provide qualitative results to aid in the diagnosis of bacterial vaginosis.
Aptima CV/TV Assay: Like the Aptima CV/TV assay 100 test kit, the Aptima CV/TV assay 250 test kit is an in vitro nucleic acid amplification test for the detection and quantitation of RNA from microorganisms associated with vaginitis, trichomoniasis, and vulvovaginitis, in women with a clinical presentation consistent with vaginitis, trichomoniasis, and vulvovaginitis. The Aptima CV/TV assay utilizes the automated Panther system to provide qualitative results to aid in the diagnosis of vulvovaginal candidiasis and trichomoniasis.
The provided document, a 510(k) summary for the Hologic Aptima BV Assay and Aptima CV/TV Assay, describes the device's technical specifications and a general statement regarding performance data for substantial equivalence. However, it does not contain the detailed acceptance criteria and a comprehensive study report with specific performance metrics (like sensitivity, specificity, PPV, NPV against a clinical gold standard) that would typically be expected for demonstrating a device meets acceptance criteria in a clinical validation context.
Specifically, the document focuses on demonstrating substantial equivalence of a new kit configuration (250 tests) to an already cleared kit configuration (100 tests) by showing similar analytical performance, particularly Limit of Detection (LoD). It does not present a de novo clinical study with pre-defined acceptance criteria for diagnostic accuracy against a true clinical ground truth.
Therefore, many of the requested items (e.g., number of experts, adjudication method, MRMC studies, training set details) are not applicable or not provided in this specific type of submission, which is for a modification to an already cleared device, not a novel device requiring full clinical validation from scratch.
Here's an attempt to answer the questions based only on the provided text:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly present a table of acceptance criteria and reported device performance in terms of diagnostic accuracy (e.g., sensitivity, specificity) against a clinical reference for the 250-test kit. Instead, it asserts equivalence by confirming L.O.D. for the new kit configuration.
The primary acceptance criteria for the new 250-test kit configuration, as implied by the performance data section, is that it must meet the established Limit of Detection (LoD) of the previously cleared 100-test kit configuration.
Aptima BV Assay (250 Test Kit):
| Acceptance Criteria (LoD of 100-Test Kit) | Reported Performance (LoD Confirmation for 250-Test Kit) |
|---|---|
| L. crispatus (LC): 143 CFU/mL | LC: 143 CFU/mL |
| L. gasseri (LG): 2,207 CFU/mL | LG: 2,207 CFU/mL |
| L. jenseni (LJ): 10 CFU/mL | LJ: 10 CFU/mL |
| A. vaginae (AV) C95: 5.10 log CFU/mL | AV C95: 5.10 log CFU/mL (128,397 CFU/mL) |
| G. vaginalis (GV) C95: 4.86 log CFU/mL | GV C95: 4.86 log CFU/mL (72,836 CFU/mL) |
Aptima CV/TV Assay (250 Test Kit):
| Acceptance Criteria (LoD of 100-Test Kit) | Reported Performance (LoD Confirmation for 250-Test Kit) |
|---|---|
| C. albicans C95 (LoD): 4439 CFU/mL | C. albicans C95 (LoD): 4439 CFU/mL |
| C. parapsilosis C95 (LoD): 9416 CFU/mL | C. parapsilosis C95 (LoD): 9416 CFU/mL |
| C. tropicalis C95 (LoD): 811 CFU/mL | C. tropicalis C95 (LoD): 811 CFU/mL |
| C. dubliniensis C95 (LoD): 1176 CFU/mL | C. dubliniensis C95 (LoD): 1176 CFU/mL |
| C. glabrata LoD: 41 CFU/mL | C. glabrata LoD: 41 CFU/mL |
| T. vaginalis LoD: 0.0024 cells/mL | T. vaginalis LoD: 0.0024 cells/mL |
The conclusion states: "The performance study results demonstrate that the Aptima BV assay 250 Test Kit on the Panther system performs comparably to the predicate device that is currently marketed for the same intended use." and "The Aptima BV 100 Test Kit LoD was confirmed in the Aptima BV 250 Test Kit configuration." (Similar statements are made for the CV/TV assay).
2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size: For the LoD confirmation study for both assays, at least 20 replicates per concentration, per reagent lot, using three lots were tested. This totals to at least 60 replicates per strain (for BV) or per organism (for CV/TV).
- Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. It describes analytical sensitivity studies using prepared dilutions of cell lysates/suspensions. For the CV/TV assay, the use of "Natural Vaginal Swab Matrix (NVSM)" and "Simulated Vaginal Swab Matrix (SVSM)" is mentioned for dilutions.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This information is not provided and is not applicable to the type of analytical study performed. The LoD confirmation uses known concentrations of target organisms, not clinical samples requiring expert interpretation for ground truth.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not provided and is not applicable to an analytical LoD confirmation study.
5. 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
This information is not provided and is not applicable. The device is a diagnostic assay (in vitro nucleic acid amplification test), not an AI-assisted imaging device that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
The device itself is a standalone diagnostic assay (an in vitro nucleic acid amplification test) run on an automated system (Panther system). Its performance (LoD) was confirmed without human interpretation of raw signals, as the Panther system software interprets the amplification signal emergence times to generate results.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth used for this specific study (LoD confirmation) was known concentrations of purified target organisms/cell lysates. This is an analytical ground truth, not a clinical ground truth derived from expert consensus, pathology, or outcomes data.
8. The sample size for the training set
This information is not provided and is not applicable. This is not an AI/ML device that requires a training set in the conventional sense. The "training" for the assay involves internal optimization and validation during development, but the document does not detail these earlier stages.
9. How the ground truth for the training set was established
This information is not provided and is not applicable, as it's not an AI/ML device with a distinct training set and ground truth establishment methodology in the context of this submission.
§ 866.3975 Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis.
(a)
Identification. A device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis is a qualitative in vitro diagnostic device intended for the detection of microbial nucleic acid sequences in vaginal specimens collected from patients with signs and symptoms of vaginitis or bacterial vaginosis. This device is intended to aid in the diagnosis of vaginitis or bacterial vaginosis when used in conjunction with clinical signs and symptoms and other laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) Documentation with a detailed device description of device components; ancillary reagents required but not provided; and explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
(ii) Documentation with information that demonstrates the performance characteristics of the device, including:
(A) Limit of Detection;
(B) Precision (reproductivity);
(C) Analytical specificity;
(D) Analytical reactivity (inclusivity);
(E) Specimen stability; and
(F) Effects of interfering substances.
(iii) Detailed documentation from a prospective clinical study. As appropriate to the intended use, the prospective clinical study must be performed on an appropriate study population, including women of various ages and ethnicities. The prospective clinical study must compare the device performance to results obtained from well-accepted comparator methods.
(iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed explanation of the interpretation of results and acceptance criteria;
(ii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, clinical performance stratified by patient demographics such as race, ethnicity, age, and pregnancy status.
(iii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, a summary of device results in an asymptomatic population with demographic characteristics appropriate to the intended use population.
(iv) For devices with an intended use that includes detection of either Candida species or bacteria associated with bacterial vaginosis, a limitation that
Candida species and bacterial compositions associated with bacterial vaginosis can be present as part of normal vaginal flora and results should be considered in conjunction with available clinical information.