The BD Vaginal Panel is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and/or Trichomonas vaginalis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• · Bacterial vaginosis (BV) markers (Individual markers are not reported)
  • o Lactobacillus spp. (L. crispatus and L. jensenii)
  • o Gardnerella vaginalis
  • o Atopobium vaginae
  • o Bacterial Vaginosis Associated Bacteria-2 (BVAB-2)
  • o Megasphaera-1
• · Vulvovaginal candidiasis (VVC) markers (Markers are reported in the following groups)

o Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)

• o Candida glabrata
• o Candida krusei
• · Trichomonas vaginalis (TV)

The assay may be used to detect DNA associated with BV, VVC, and TV, or a subset of these conditions per clinician order, in vaginal swab specimens collected from patients who are symptomatic for vaginitis/vaginosis. The BD Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.

The BD Vaginal Panel is available for use with the BD MAX™ System or the BD COR™ System.

The BD MAX™ Vaginal Panel performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacterial vaginosis (qualitative results reported based on detection and of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and/or Trichomonas vaginalis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• · Bacterial vaginosis markers (Individual markers not reported)
  • o Lactobacillus spp. (L. crispatus and L. jensenii)
  • o Gardnerella vaginalis
  • o Atopobium vaginae
  • o Bacterial Vaginosis Associated Bacteria-2 (BVAB-2)
  • o Megasphaera-1
• · Vulvovaginal candidiasis (VVC) markers (markers are reported in the following groups)
  • o Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C.dubliniensis)
  • o Candida glabrata
  • o Candida krusei
• • Trichomonas vaginalis (TV)

The assay may be used to detect BV, VVC, and/or TV, or a subset of these conditions per clinician order, in vaginal swab specimens collected from patients who are symptomatic for vaginitis/vaginosis. The BD MAX™ Vaginal is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.

The BD Vaginal Panel is an automated, qualitative in vitro diagnostic test for bacterial vaginosis markers. Candida species associated with vulyovaginal candidiasis, and Trichomonas vaginalis. From a single specimen, a vaginal swab collected from a patient who is symptomatic for vaginitis or vaginosis, the test provides qualitative (positive) results for the presence of the following conditions and/or organisms:

• Bacterial vaginosis (based on detection of Lactobacillus spp. (L. crispatus and L. . jensenii), Gardnerella vaginalis, Atopobium vaginae, Bacterial Vaginosis Associated Bacteria-2, and Megasphaera-1)
• Candida spp. (C. albicans, c. tropicalis, C. parapsilosis, and C. dubliniensis) .
• Candida glabrata ●
• Candida krusei ●
• Trichomonas vaginalis ●

The BD Vaginal Panel is available for use with the BD MAX™ System or the BD COR™ System under the trade names BD MAX™ Vaginal Panel and BD Vaginal Panel, respectively. The assay previously provided results for all five targets for every specimen run, regardless of whether the ordering clinician desires evaluation of all reported conditions. After clearance of this 510(k) submission, BD will release updates to the BD MAX™ and BD COR ™ software to allow users the versatility to mask results, per specimen, based on the order received from the clinician. This change allows a laboratory to use the BD Vaginal Panel to test a specimen for an individual target group (BV, VVC, or TV) or any two of the three targeted conditions, in addition to the current configuration that reports all three conditions simultaneously.

The provided text describes a 510(k) premarket notification for the BD Vaginal Panel, an in vitro diagnostic test. While the document details the device's intended use, technological principles, and comparison to a predicate device, it does not contain specific acceptance criteria and detailed study results in the format usually provided for device performance evaluation against such criteria. Instead, it states that "The clinical utility of the Vaginal Panel is unchanged from the clinical utility described in DEN160001" and that enabling a subset of results to be masked "has no clinical impact," implying that performance data was previously established and still applies.

Therefore, I cannot extract a table of acceptance criteria and reported device performance from the provided text, nor can I provide specific details on sample sizes, ground truth establishment, or expert involvement for the test set.

However, I can describe the basis for the claim of continued performance and what typically would be found in a complete submission to address these points.

Based on the provided text, here's what can be inferred and what information is missing:

Inferred Information Regarding Acceptance Criteria and Study to Prove Device Meets Them:

The core of the argument for "acceptance" in this submission (K243725) is that the changes to the BD Vaginal Panel (specifically, the ability to mask results for certain conditions based on clinician order) do not impact the analytical or clinical performance that was already established for the predicate device (BD Vaginal Panel, referenced by DEN160001, K191957, K201017, K223653).

The text states:

• "The clinical utility of the Vaginal Panel is unchanged from the clinical utility described in DEN160001."
• "BD has determined that introducing the capability to order a subset of the conditions evaluated by the Vaginal Panel while masking the results for those conditions that are not ordered has no clinical impact."
• "Enabling the assay to report results for only a subset of the conditions does not change the specimen type, the test conditions, or the logic that is used to determine whether a specimen is positive or negative for the associated condition: conditions that are not ordered are simply not reported to the user."
• "Therefore, analytical and clinical performance of the assays is not impacted."

This implies that the previous submissions (DEN160001, K191957, K201017, K223653) would contain the detailed study data that established the acceptance criteria and demonstrated the device's performance against them. The current submission is a modification where the manufacturer asserts that the modification does not alter the already proven performance.

Unavailable Information from the Provided Text:

Since this submission argues "no impact" on performance rather than providing new performance data, the following specific details are not present in the provided document:

1. A table of acceptance criteria and the reported device performance: This information would be in the predicate device's summary (e.g., DEN160001). The current submission leverages the established performance.
2. Sample sizes used for the test set and the data provenance: Not provided for this submission's changes, as it relies on previous data.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not provided for this submission's changes.
4. Adjudication method for the test set: Not provided for this submission's changes.
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 is a molecular diagnostic test, not an AI-assisted diagnostic imaging device. Therefore, an MRMC study is not relevant here.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: The device is described as an "automated qualitative in vitro diagnostic test," meaning its performance is its standalone performance without continuous human interpretation of raw data. The "human-in-the-loop" aspect here is the clinician receiving the final positive/negative result. The change highlighted in this 510(k) is masking results, not altering the fundamental detection algorithm.
7. The type of ground truth used: Not explicitly stated for this submission's changes, but for molecular diagnostics, ground truth typically involves a combination of clinical diagnosis, other laboratory methods (e.g., microscopy, culture, or other validated molecular assays), and sometimes expert clinical assessment.
8. The sample size for the training set: Not applicable as this is not an AI/ML device that requires a separate "training set" in that context. The "training" in molecular diagnostics refers to assay development and optimization, which isn't sample-size driven in the same way.
9. How the ground truth for the training set was established: See point 8.

Summary of what is present in the document relevant to the assertion of continued performance:

The basis of acceptance for this 510(k) submission (K243725) is that the modifications to the BD Vaginal Panel (specifically, the software update to allow result masking) do not compromise the established performance of the predicate device. The detailed performance data, acceptance criteria, study designs, and ground truth methodologies would be found in the original and subsequent predicate device submissions (DEN160001, K191957, K201017, K223653). The current submission serves to inform the FDA that a software change introducing result masking does not require new efficacy studies because it does not alter the underlying test's analytical or clinical capability to detect the specified targets.

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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):

Aptima CV/TV Assay (250 Test Kit):

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.

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The Xpert® Xpress MVP test, performed on the GeneXpert® Xpress System, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• Organisms associated with bacterial vaginosis (detected organisms not reported individually) .
  • Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226) O
  • Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) O
  • Megasphaera-1 O
• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated) .
• Candida glabrata/Candida krusei (species not differentiated) ●
• . Trichomonas vaginalis

The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.

The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. In the CLIA-waived environment, the Xpert Xpress MVP test is performed on the GeneXpert® Xpress System.

The latest Hub configuration of the GeneXpert Xpress System consists of a GeneXpert IV instrument that executes sample preparation, nucleic acid amplification and real-time fluorescent signal detection for the tests, and a GeneXpert Hub with preloaded GeneXpert Xpress software for running the tests and viewing the test results. The GeneXpert Hub accessory integrates the computer, touchscreen monitor and barcode scanner. Each of the GeneXpert modules in the GeneXpert IV instrument can perform independent sample preparation and testing.

The Xpert Xpress MVP test is a PCR-based Nucleic Acid Amplification Test. Each test requires the use of a single-use disposable GeneXpert cartridge that contains all necessary reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge serving as internal controls. The SPC is present to control for adequate sample processing, to monitor PCR conditions, the presence of potential inhibitor(s) and possible reagent degradation. The PCC verifies reagent rehydration. PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability. Because the cartridges are self-contained, the risk of cross- contamination between samples is minimized.

The Xpert Xpress MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The ancillary specimen collection kit for use with the Xpert Xpress MVP test is the Xpert Swab Specimen Collection Kit. The swab and the transport reagent included in the Xpert Swab Specimen Collection Kit are designed to collect and preserve patient specimens to allow transport to the testing site prior to analysis with the Xpert Xpress MVP test.

Here's a summary of the acceptance criteria and study details for the Cepheid Xpert Xpress MVP device based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a numerical, threshold-based format. Instead, it presents the clinical performance results (PPA/NPA, Sensitivity/Specificity) for the Xpert Xpress MVP test. The implication is that these reported performance metrics meet internal or regulatory acceptance thresholds for substantial equivalence.

*Target includes C. albicans, C. tropicalis, C. parapsilosis, and C. dubliniensis

2. Sample Size for the Test Set and Data Provenance:

• Sample Size:
  • Clinical Study: 1,275 female patients (18 to ≥50 years of age, plus two patients 14-17 years old). A total of 2,544 vaginal swabs were tested (likely one clinician-collected and one self-collected per patient).
• Data Provenance: Retrospective and prospective. The clinical study was conducted at 9 geographically diverse sites in the U.S.

3. Number of Experts Used to Establish Ground Truth and Qualifications:

The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical study. It refers to "reference/comparator methods" for ground truth.

4. Adjudication Method for the Test Set:

• For BV, Candida group, Candida glab-krus, and TV, the performance was determined relative to specific reference/comparator methods (see point 7).
• For discrepant results, "investigation of discrepant results was performed by testing specimens with another FDA-cleared NAAT." This indicates a form of discrepancy resolution rather than a multi-expert adjudication on all cases. The exact adjudication method (e.g., 2+1, 3+1) for discrepant cases is not detailed, but it involves re-testing with an FDA-cleared NAAT.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

No MRMC comparative effectiveness study was mentioned. The device is an in vitro diagnostic test, which typically does not involve human readers interpreting images or data to the same extent as AI-assisted diagnostic tools. Performance is typically compared against reference methods.

6. Standalone (Algorithm Only) Performance:

Yes, the entire clinical study and analytical studies described are standalone performance evaluations of the Xpert Xpress MVP device (an automated qualitative in vitro diagnostic test) without human-in-the-loop assistance in its diagnostic output. Its output is a qualitative detection result (Positive/Negative/Not Detected).

7. Type of Ground Truth Used:

• Bacterial Vaginosis (BV): An FDA-cleared nucleic acid amplification test (NAAT).
• Candida group (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis): Yeast culture followed by mass spectrometry for species identification.
• Candida glabrata/Candida krusei: Yeast culture followed by mass spectrometry for species identification.
• Trichomonas vaginalis (TV): A patient infected status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture.
• Discrepant Results: Re-tested with another FDA-cleared NAAT.

8. Sample Size for the Training Set:

The document does not explicitly mention a "training set" in the context of machine learning model development. This device is a PCR-based NAAT, not an AI/ML-driven diagnostic. Therefore, the concept of a training set for an algorithm is not directly applicable in the same way as for an image-based AI device. Analytical studies (e.g., Limit of Detection, Analytical Reactivity, Analytical Specificity) and reproducibility studies served to characterize the device's performance chemically and biologically.

9. How the Ground Truth for the Training Set Was Established:

As noted above, the device is a PCR-based NAAT, not an AI/ML system, so a "training set" for an algorithm in the traditional sense is not discussed. The development and optimization of the assay's chemical and molecular components would have been guided by fundamental scientific principles and laboratory testing, rather than an algorithmic training process using labeled data. Benchmarking for analytical characteristics (like LoD) would involve preparing samples with known concentrations of organisms.

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The BD Vaginal Panel is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginosis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• · Bacterial vaginosis markers (Individual markers not reported) Lactobacillus spp. (L. crispatus and L. jensenii) Gardnerella vaginalis Atopobium vaginae Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) Megasphaera-1
• · Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)
• · Candida glabrata
• Candida krusei
• Trichomonas vaginalis

The BD Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.

The BD Vaginal Panel is available for use with the BD MAX™ System or the BD COR™ System.

As with the existing BD Vaginal Panel for use with the BD MAX™ System (K201017), the BD COR™ PX/MX (BD COR) high throughput system conducts sample extraction steps to isolate and concentrate DNA which is then amplified to detect specific sequences for diagnostic purposes.

The BD COR™ System is designed to allow the user to place clinical specimens directly into designated transport racks to be loaded into the System. Once the specimens are loaded, the System will perform the necessary pre-analytical steps such as vortexing, aliquoting into a molecular tube with the correct diluent, sorting/grouping of the secondary samples for testing by assay, pre-warming and cooling of the sample (where required), and transport of the sample into a molecular analyzer, where extraction, amplification and detection will take place.

Additionally, the steps of ordering tests on the instrument for specific samples will be managed directly by the user interaction with the Laboratory Information System (LIS), which communicates drectly with the instrument.

Once the clinical specimens are received in the laboratory and loaded into the transport racks, the user will not be required to directly handle the specimen again reporting and removal from the system.

The BD Vaginal Panel is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginosis.

The study aimed to demonstrate the equivalence of the BD Vaginal Panel on the BD COR™ System to its performance on the BD MAX™ System, which is the legally marketed predicate device.

1. Table of Acceptance Criteria and Reported Device Performance:

2. Sample sizes used for the test set and the data provenance:

   • Precision Study: Panel members (spiked in simulated vaginal matrix) were tested in 12 days, 2 runs/day, 2 replicates/panel, for a total of 48 runs. This resulted in varying numbers for total N for each target and level (e.g., 288 for BV True Negative, 48 for Candida Low Positive, etc.; see Table 3 for details). Data provenance is internal laboratory testing.
   • Reproducibility Study: Similar panel members to the precision study. Tested at 3 sites (2 external, 1 internal) over 8 days, with 2 operators performing 2 runs on alternate days, for a total of 48 runs. This resulted in varying numbers for total N for each target, level, and site (e.g., 192 for BV True Negative per site, 32 for BV High Negative per site; see Table 6 for details). Data provenance is internal and external laboratory testing.
   • Analytical Sensitivity Confirmation Study: 20 panels of Vaginosis and/or Vaginitis targets at varying concentration levels (1.99x LoD, 5x LoD, C5) with 48 replicates each. Samples were prepared by spiking organisms into simulated vaginal matrix. Data provenance is internal laboratory testing.
   • Cross-Contamination Study: 543 negative samples (interspersed with high positive samples). Data provenance is internal laboratory testing.
   • Clinical Agreement Study: 700 panel members. These included:
     • Clinical vaginal specimens from internal collections.
     • Pooled previously collected clinical specimens.
     • High positive clinical specimens spiked.
     • Contrived samples created by spiking organisms into negative vaginal matrix or simulated vaginal matrix.
     • BV Contrived panel members prepared with different BV marker combinations using simulated vaginal matrix.
     • BV Natural samples derived from Cgroup, TV, and negative vaginitis panel members in natural vaginal matrix.
     • Data provenance is a mix of internal collections and contrived samples.

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):

   The document does not mention the use of experts or their qualifications for establishing ground truth. For the analytical studies (precision, reproducibility, analytical sensitivity, cross-contamination), ground truth was established by spiking known concentrations of target organisms/DNA into simulated or negative matrices. For the clinical agreement study, "BD MAX™ results served as the reference" meaning the predicate device's results were used as the comparator, not human expert consensus.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

   For the clinical agreement study, the positive or negative status of a panel member using the BD MAX™ System (the reference) was defined by ">2 out of 3 evaluable results obtained on the BD MAX™". This suggests a form of 3-reader consensus (with the BD MAX™ itself acting as a 'reader' in triplicate, or at least three independent runs determining the status). Equivocal BD MAX™ comparator results were defined as "one positive, one negative, and one non-evaluable result from the BD MAX™." No human adjudication is mentioned.

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:

   No MRMC comparative effectiveness study was done or reported in this document. The device is an automated in vitro diagnostic test (nucleic acid amplification test) and does not involve human readers interpreting images or other data with or without AI assistance. The comparison is between two automated systems (BD COR™ vs. BD MAX™).

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

   Yes, the entire study focuses on the standalone performance of the BD Vaginal Panel on the BD COR™ System. The device is an automated diagnostic test, meaning it operates "algorithm only" without human-in-the-loop performance for result generation. The human role is in sample loading and result interpretation (based on the device's output), not in forming the initial diagnostic call.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • Analytical Studies (Precision, Reproducibility, Analytical Sensitivity, Cross-Contamination): Laboratory-contrived ground truth through spiking known concentrations of target organisms/DNA into simulated vaginal matrix or negative matrix.
   • Clinical Agreement Study: The results from the predicate device (BD MAX™ System) were used as the reference ("ground truth") for comparison. For panel member status, a consensus method of ">2 out of 3 evaluable results obtained on the BD MAX™" was used.

8. The sample size for the training set:

   The document does not explicitly mention a "training set" in the context of machine learning or AI algorithm development. The BD Vaginal Panel is a PCR-based assay. The performance studies described are for analytical and clinical validation of the device, not for training a new algorithm. The development of the assay (e.g., probe design, primer selection) would have involved extensive R&D, but the concept of a "training set" as typically used in AI/ML is not applicable here.

9. How the ground truth for the training set was established:

   As a PCR-based diagnostic, it's not an AI system that relies on a "training set" in the conventional sense to learn to make predictions. The "ground truth" for developing such an assay typically relies on purified nucleic acid from known organisms, synthetic controls, and well-characterized clinical samples to ensure the primers and probes are specific and sensitive for the intended targets. The document does not describe the specific methods for establishing ground truth during the assay development phase.

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The Xpert® Xpress MVP test, performed on the GeneXpert® Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV). Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• . Organisms associated with bacterial vaginosis (detected organisms not reported individually)
  • o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)
  • Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) O
  • o Megasphaera-1
• . Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)
• Candida glabrata/Candida krusei (species not differentiated)
• . Trichomonas vaginalis

The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.

The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis. Candida species associated with vulyovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. The Xpert Xpress MVP test is performed on GeneXpert Instrument Systems. The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of the target sequences in simple or complex samples using real-time PCR assays. The systems consist of an instrument, computer, and preloaded software for running tests and viewing the results. The systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The Xpert Xpress MVP test includes reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis from vaginal swab samples. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert System instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The swab transport reagent included in the Xpert Swab Specimen Collection Kit is designed to collect and preserve patient specimens to allow transport to the laboratory prior to analysis with the Xpert Xpress MVP test.

Here's a breakdown of the acceptance criteria and study details for the Cepheid Xpert Xpress MVP device, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on demonstrating equivalence between a "new design" and an "original design" of the Xpert Xpress MVP, rather than establishing de novo acceptance criteria against a clinical reference standard in this specific submission. The acceptance criteria for the analytical sensitivity equivalency study were defined internally for comparison between the two designs:

1. Both original and new design report 19/20 or 20/20 POSITIVE/DETECTED results at LoD/Near Cut-off concentrations.
2. Statistical analysis (two-sample t-test) comparing mean Ct values shows no statistically significant difference (p-value > 0.05) with a marginal difference of 1.0 Ct value. | Met:

• All targets (Atopobium vaginae, Megasphaera-1, BVAB2, Candida albicans, Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei, Trichomonas vaginalis) consistently showed 19/20 or 20/20 positive/detected results at LoD.
• All BV targets showed 19/20 or 20/20 positive/detected (BV positive) results at near cut-off concentrations.
• For all targets and conditions (SVM/VS matrix), the difference in mean Cts between the two designs was within 1.0 Ct, and the t-test p-values were consistently > 0.05 (most were >0.9), indicating no statistically significant difference in analytical sensitivity. |
  | Clinical Specimen Equivalency (PPA/NPA) | The PPA (Positive Percent Agreement) and NPA (Negative Percent Agreement) of the new design relative to the original design for Bacterial Vaginosis (BV), Candida group, Candida glabrata/Candida krusei, and Trichomonas vaginalis (TV) targets should demonstrate equivalence. (No specific numerical thresholds provided in this summary, but the implication is "high agreement"). | Met:
• BV: PPA 98.3% (56/57), NPA 99.1% (112/113)
• Candida group: PPA 97.4% (38/39), NPA 98.5% (129/131)
• Candida glab-krus: Overall PPA 100% (31/31), NPA 100% (159/159). (Fresh PPA 100% (11/11), Contrived PPA 100% (20/20))
• TV: Overall PPA 100% (32/32), NPA 100% (158/158). (Fresh PPA 100% (12/12), Contrived PPA 100% (20/20))
• Discordant results were investigated and attributed to samples near LoD or sub-LoD levels, supporting overall equivalence. |
  | Non-Determinate Rate | Implicitly, the non-determinate rates for both designs should be low and acceptable. | Met:
• Overall non-determinate rate for original design: 0.42% (1/236)
• Overall non-determinate rate for new design: 1.4% (3/220)
  These rates are considered acceptable. |
  | Interfering Substances | No clinically significant inhibitory effects from substances encountered in vaginal specimens, except where a limitation is appropriate. | Met:
• No clinically significant inhibitory effects observed for new design, with the exception of 5.5% v/v mucin (same as original design). At 4.0% mucin, no interference was observed. A limitation for ≥5.5% mucin is included in the instructions. |

2. Sample Size Used for the Test Set and Data Provenance

• Analytical Sensitivity Equivalency Study (LoD & Near Cut-off):

  • Sample Size: 20 replicates for each target at LoD/near cut-off concentration for both the original and new designs. This included testing in Simulated Vaginal Matrix (SVM) and Pooled Negative Natural Clinical Vaginal Swab Matrix (VS) for some targets.
  • Data Provenance: Not explicitly stated, but these are analytical studies meaning they used prepared samples (cultures, specific concentrations) rather than clinical patient samples.

• Equivalency Study using Clinical Specimens:

  • Sample Size:
    • Initial Enrollment: 174 participants (174 clinician-collected vaginal swabs).
    • Included in Final Analysis: 170 prospectively collected ("fresh") clinician-collected vaginal swab specimens.
    • Additional Contrived Specimens: 20 contrived C. glabrata and C. krusei specimens, and 20 contrived T. vaginalis specimens.
  • Data Provenance:
    • Country of Origin: United States (three sites).
    • Retrospective or Prospective: Prospectively collected. Clinician-collected vaginal swabs were taken from symptomatic female patients ≥ 14 years of age. All testing was performed at Cepheid (Sunnyvale, CA).

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

This submission is about demonstrating equivalence between two versions of the same diagnostic device, not evaluating the device against a clinical reference standard with expert interpretation for ground truth. Therefore, experts were not used to establish the "ground truth" for the test set in the traditional sense of clinical diagnosis.

Instead, the "ground truth" in the clinical equivalency study was the result produced by the predicate device (original design of Xpert Xpress MVP).

4. Adjudication Method for the Test Set

No adjudication method using human experts was described for the clinical equivalency study. The comparison was directly between the test results of the new device and the predicate device. Discordant results were investigated by retesting with both designs if enough sample volume remained, but these retest results were for information only and not used for adjudication in the primary data analysis.

5. (MRMC) Multi-Reader Multi-Case Comparative Effectiveness Study

• No, an MRMC comparative effectiveness study was NOT done. This document describes the analytical and clinical performance equivalence of a device modification to its predicate, not a study evaluating human reader performance with or without AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Yes, this is essentially a standalone (algorithm only) performance study. The Xpert Xpress MVP system is an automated in vitro diagnostic test that provides a qualitative result. While human operators are involved in sample preparation and loading, the "performance" described here (detection of DNA targets) is that of the automated system and its reagents/software, acting as an algorithm-only device in the context of its defined output. There isn't a human-in-the-loop component being evaluated in these studies.

7. Type of Ground Truth Used

• Analytical Sensitivity Study: The ground truth was based on known concentrations of target organisms (CFU/mL or copies/mL) spiked into matrices.
• Clinical Specimen Equivalency Study: The "ground truth" for comparison was the results obtained from the predicate device (original Xpert Xpress MVP K212213). The study aimed to show agreement with the predicate device, not with an external clinical gold standard.

8. Sample Size for the Training Set

No information about a training set is provided. This document describes validation studies for a device, not the development or training of an AI algorithm. If there were internal machine learning components in the original device, their training data would have been part of the original K212213 submission.

9. How the Ground Truth for the Training Set Was Established

As no training set is mentioned, this information is not applicable to the provided document.

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The Xpert Xpress MVP test, performed on the GeneXpert Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• . Organisms associated with bacterial vaginosis (detected organisms not reported individually)
  • o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)
  • Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) o
  • Megasphaera-1 o
• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)
• Candida glabrata/Candida krusei (species not differentiated)
• . Trichomonas vaginalis

The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.

The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis, Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. The Xpert Xpress MVP test is performed on GeneXpert Instrument Systems.

The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of the target sequences in simple or complex samples using real-time PCR assays. The systems consist of an instrument, computer, and preloaded software for running tests and viewing the results. The systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The Xpert Xpress MVP test includes reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis from vaginal swab samples. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert System instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The swab transport reagent included in the Xpert Swab Specimen Collection Kit is designed to collect and preserve patient specimens to allow transport to the laboratory prior to analysis with the Xpert Xpress MVP test.

Here's an analysis of the acceptance criteria and study proving the device meets those criteria, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets for sensitivity, specificity, and agreement rates in the provided document. However, the performance outcomes of the Xpert Xpress MVP test are presented and can be interpreted as the device meeting the performance standards considered acceptable for its intended use, especially given the FDA's 510(k) clearance based on "substantial equivalence." The document compares the device's performance to an FDA-cleared predicate device.

For the purpose of this table, "Acceptance Criteria" will be inferred from the reported performance, as it highlights what the device achieved and what was deemed sufficient for clearance.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size (Clinical Study/Test Set):
  • Patients: 1,478 female patients (14 to ≥ 50 years of age).
  • Vaginal Swabs Tested: 2,947 (one self-collected vaginal swab (SVS) and five clinician-collected vaginal swab (CVS) specimens per patient).
• Data Provenance:
  • Country of Origin of the Data: United States (multi-site clinical study with 12 sites from geographically diverse locations in the U.S.).
  • Retrospective or Prospective: Prospective observational, method comparison clinical study.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not specify the number or qualifications of experts (e.g., radiologists, pathologists) used to establish the ground truth for the clinical test set. The ground truth for the clinical study was established by comparator methods (FDA-cleared NAATs, yeast culture followed by mass spectrometry, and a PIS algorithm). These methods are analytical laboratory tests, not dependent on expert visual review.

4. Adjudication Method for the Test Set

• The document states: "When applicable, investigation of discrepant results was performed by testing specimens with another FDA-cleared NAAT."
• This indicates a form of adjudication for discrepant results, where a third, independent, FDA-cleared NAAT was used to resolve disagreements between the Xpert Xpress MVP test and the initial comparator method. The specific rule (e.g., 2 out of 3 agreement) for this discrepancy resolution is not detailed, but the use of an independent NAAT as a tie-breaker or confirming tool is implied.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

• No, an MRMC comparative effectiveness study was not done.
• This study evaluates an in vitro diagnostic (IVD) device that detects nucleic acid sequences from microorganisms using real-time PCR. It is not an imaging-based AI device that would typically involve human readers interpreting images. Therefore, the concept of human readers improving with AI vs. without AI assistance does not apply to this type of device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

• Yes, the primary performance evaluation of the Xpert Xpress MVP test in the clinical study was standalone.
• The device is an automated, qualitative in vitro diagnostic test that performs sample preparation, nucleic acid extraction and amplification, and detection, and provides results "within 60 minutes." The clinical performance tables (Table 5-13) represent the direct output of the device compared to reference methods, without human interpretation of the device's signal directly impacting the final result reported by the device itself.
• Human involvement is in specimen collection, loading the cartridge, and reviewing the system's final reported result for the pathogen. The device's diagnostic output for a given sample is fully automated.

7. The Type of Ground Truth Used

The ground truth varied by the target organism:

• Bacterial Vaginosis (BV): An FDA-cleared nucleic acid amplification test (NAAT).
• Candida group and Candida glabrata/krusei: Yeast culture followed by mass spectrometry for species identification. For Candida glabrata/krusei, there was also a "contrived" study, meaning the ground truth was based on known concentrations of the organisms.
• Trichomonas vaginalis (TV): A Patient Infected Status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture.
• Discrepancy Resolution: For all targets, a second FDA-cleared NAAT was used for investigation of discrepant results, effectively serving as an adjudication method to establish the clinical ground truth for those specific samples.

8. The Sample Size for the Training Set

The document describes the clinical study as a "performance evaluation" and "method comparison clinical study" used to demonstrate substantial equivalence. It does not explicitly reference or describe a separate "training set" for the device's algorithm in the context of machine learning, because this is a molecular diagnostic test based on PCR, not an adaptable AI algorithm that is trained on data in the traditional sense. The development of such a device involves assay design and optimization rather than machine learning training sets.

9. How the Ground Truth for the Training Set Was Established

Since there is no explicit mention of a "training set" in the context of an AI/ML algorithm for this PCR-based diagnostic device, the concept of establishing ground truth for a training set as typically described for AI/ML devices doesn't apply. The development and validation of the device would have involved extensive laboratory (non-clinical) studies, including analytical sensitivity (LoD), analytical reactivity (inclusivity), analytical specificity (exclusivity), microbial interference, competitive interference, interfering substances, and carry-over contamination studies (as described in Section 5.4), where the "ground truth" for these studies would be precisely controlled laboratory-prepared samples with known concentrations of target organisms and potential interferents.

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The BD MAX Vaginal Panel performed on the BD MAX System is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginitis/vaginosis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• · Bacterial vaginosis markers (Individual markers not reported)
  Lactobacillus spp. (L. crispatus and L. jensenii) Gardnerella vaginalis Atopobium vaginae Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) Megasphaera-1
• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)
• Candida glabrata
• Candida krusei
• Trichomonas vaginalis
  The BD MAX Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis.

The BD MAX System and the BD MAX Vaginal Panel are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, and extraction reagents. The instrument automates sample preparation including target lysis, DNA extraction and concentration, reagent rehydration, target nucleic acid amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX System software automatically interprets test results. For the BD MAX Vaginal Panel, a test result may be called as POS, NEG or UNR (Unresolved) based on the amplification status of the targets and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX System failure.

This document describes the 510(k) premarket notification for the BD MAX Vaginal Panel for use with the BD MAX System. The purpose of this submission is to demonstrate the substantial equivalence of the modified device, particularly the BD Molecular Swab Collection Kit, to its predicate device, the BD MAX Vaginal Panel (DEN160001 and K191957) which used the BD MAX UVE Specimen Collection Kit.

Here's an analysis of the acceptance criteria and supporting studies based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text focuses on demonstrating the substantial equivalence of the collection kit for an already cleared device, rather than establishing initial performance for a novel diagnostic device. Therefore, explicit acceptance criteria in terms of sensitivity, specificity, PPV, and NPV for the BD MAX Vaginal Panel itself are not directly stated in this section, as those would have been established during the original clearances (DEN160001 and K191957).

However, the performance is evaluated in comparison to the predicate's collection kit. The reported performance for the comparison study between the cleared collection device (BD MAX UVE Specimen Collection Kit) and the new collection device (BD Molecular Swab Collection Kit) demonstrated the following:

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Comparison Study: The document states that a "comparison study of performance between the cleared collection device and the new collection device tested with the BD MAX Vaginal Panel on the BD MAX System with clinical specimens" was conducted. However, the exact number of clinical specimens used in this comparison study is not explicitly provided in the text.
• Data Provenance: The data used for the comparison study are from "clinical specimens." The country of origin is not specified, and it is stated as a retrospective or prospective study.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

The document does not describe the establishment of a ground truth by experts for the comparison study of the collection kits. For molecular diagnostic assays like the BD MAX Vaginal Panel, the "ground truth" for the original device's performance validation is often established using methods such as:

• Culture: For culturable organisms like Candida species or Trichomonas vaginalis.
• Microscopy (e.g., Amsel's criteria, Nugent scoring): For bacterial vaginosis.
• Reference molecular methods: For organisms difficult to culture or quantify.

Since the focus here is on the collection kit equivalence, the ground truth would inherently refer to the original diagnostic results obtained using the predicate device's collection kit, which are then compared to the results from the new collection kit. The text does not mention any independent expert panel establishing ground truth specifically for these comparison studies.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method (such as 2+1, 3+1, or none) for the test set used in the comparison study. The comparison is between the performance of two collection kits with the same diagnostic panel, suggesting a direct comparison of results rather than an adjudication process involving multiple human readers to establish a reconciled truth.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the Effect Size

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically used for imaging or interpretation tasks where human readers play a significant role. The BD MAX Vaginal Panel is an automated in vitro diagnostic test, and its results are interpreted by the BD MAX System software, not human readers in a diagnostic capacity that would warrant an MRMC study.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done

Yes, the BD MAX Vaginal Panel operates as a standalone (algorithm-only) device. The device description explicitly states: "The BD MAX System software automatically interprets test results." There is no human-in-the-loop performance described for the interpretation of the test results themselves. The studies confirm the analytical and clinical performance of the automated system with the new collection kit.

7. The Type of Ground Truth Used

For the comparison study, the "ground truth" for evaluating the new collection kit's performance would implicitly be the results obtained when the same clinical specimens were tested using the predicate device's collection kit (BD MAX UVE Specimen Collection Kit) with the BD MAX Vaginal Panel. This is because the study aims to show the collections kits are equivalent and the performance of the BD MAX Vaginal Panel is already established with the predicate kit.

The initial ground truth for the diagnostic panel itself (BD MAX Vaginal Panel, cleared as DEN160001 and K191957) would have been established through a combination of:

• Clinical diagnosis and criteria: For example, Amsel's criteria or Nugent score for bacterial vaginosis, or clinical signs and symptoms for vaginitis.
• Culture: For culturable pathogens.
• Reference molecular methods: For specific DNA targets.

8. The Sample Size for the Training Set

The document does not provide information regarding a "training set" or its sample size. This is typical for an IVD device submission that is demonstrating substantial equivalence of a component (collection kit) for an already cleared diagnostic system. The algorithms for the BD MAX System and the Vaginal Panel would have been developed and "trained" (in a broad sense of model development) prior to the original 510(k) clearances (DEN160001 and K191957). This document does not detail the development phase of the assay.

9. How the Ground Truth for the Training Set Was Established

As no training set is discussed in this document, the method for establishing its ground truth is also not described. As mentioned above, the development and establishment of ground truth for the original assay would have occurred during its prior 510(k) clearances.

Ask a specific question about this device

The BD MAX Vaginal Panel performed on the BD MAX System is an automated qualitative in vitro diagnostic test for the direction of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginitis/vaginosis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• . Bacterial vaginosis markers (Individual markers not reported)
  Lactobacillus spp. (L. crispatus and L. jensenii) Gardnerella vaginalis Atopobium vaginae Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) Megasphaera-1
• . Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)
• Candida glabrata
• Candida krusei
• . Trichomonas vaginalis

The BD MAX Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.

The BD MAX System and the BD MAX Vaginal Panel are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, and extraction reagents. The instrument automates sample preparation including target lysis, DNA extraction and concentration, reagent rehydration, target nucleic acid amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX System software automatically interprets test results. For the BD MAX Vaginal Panel, a test result may be called as POS, NEG or UNR (Unresolved) based on the amplification status of the targets and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX System failure.

This is an FDA 510(k) summary for the BD MAX Vaginal Panel for detecting microorganisms associated with vaginitis and bacterial vaginosis. The document describes the device, its intended use, and its equivalence to a predicate device. While it mentions performance standards, it does not contain detailed acceptance criteria, device performance data, information on the study design (sample size, data provenance, ground truth establishment, expert qualifications, adjudication methods), or any multi-reader multi-case (MRMC) study results.

Therefore, many of the requested fields cannot be filled from the provided text.

Here's a breakdown of what can be extracted and what is missing:

1. Table of acceptance criteria and the reported device performance:

• Acceptance Criteria: Not explicitly stated in terms of specific performance metrics (e.g., sensitivity, specificity, accuracy thresholds). The document broadly refers to "Performance Standards" based on the Class II Special Controls Guideline for NAAT assays for Trichomonas vaginalis.
• Reported Device Performance: Not provided in this document. This summary focuses on substantial equivalence based on technological characteristics and intended use.

2. Sample size used for the test set and the data provenance: Not mentioned.

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): Not mentioned.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not mentioned.

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: Not applicable. This is a molecular diagnostic test, not an AI-assisted imaging device or a test involving human readers in the interpretation loop.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done: The device is a standalone molecular diagnostic assay. The results are "automatically interpreted" by the BD MAX System software, which indicates algorithm-only performance. However, specific standalone performance metrics (sensitivity, specificity etc.) are not provided.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc): Not mentioned for the studies supporting this 510(k) submission. For molecular tests, ground truth typically involves culture or a validated composite reference method.

8. The sample size for the training set: Not mentioned.

9. How the ground truth for the training set was established: Not mentioned.

Summary Table of Available Information:

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The Aptima BV assay is an in vitro nucleic acid amplification test that utilizes real time transcription-mediated amplification (TMA) for detection and quantitation of ribosomal RNA from bacteria associated with bacterial vaginosis (BV), including Lactobacillus (L. gasseri, L. crispatus, and L. jensenii), Gardnerella vaginalis, and Atopobium 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.

The Aptima BV assay 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. The assay involves three main steps, all of which take place in a single tube on the Panther system: target capture, target amplification by TMA, and detection of the amplification products (amplicon) by fluorescent labeled probes (torches). The assay incorporates an internal control (IC) in every test to monitor nucleic acid capture, amplification and detection. The Aptima BV assay is provided as a 100-test kit containing 8 reagents, 1 calibrator, and 2 controls.

Here's a summary of the acceptance criteria and study details for the Aptima BV Assay based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally inferred from the "Brief Description of Analytical (Non-Clinical) Studies" and "Brief Description of Clinical Studies" sections, focusing on the demonstrated acceptable performance. Specific numerical acceptance criteria are not explicitly stated as pass/fail thresholds in percentage terms, but rather performance results are reported which are presumably acceptable for clearance.

2. Sample Size Used for the Test Set and Data Provenance

• Clinical Performance Study (Symptomatic Subjects):

  • Evaluable Subjects: 1417 symptomatic women.
  • Patient-collected Aptima vaginal swab samples: 1405
  • Clinician-collected Aptima vaginal swab samples: 1413
  • Data Provenance: Prospectively-collected patient- and clinician-collected vaginal swab samples from women ≥14 years in 21 geographically diverse US private and academic family practice, obstetric-gynecologic, family planning, public health, STI, medical group clinics, and clinical research centers.

• Clinical Performance Study (Asymptomatic Subjects):

  • Evaluable Subjects: 172 asymptomatic women.
  • Clinician-collected Aptima vaginal swab samples: 172
  • Data Provenance: Prospectively-collected clinician-collected vaginal swab samples from asymptomatic women in 21 geographically diverse US sites (same as symptomatic subjects).

• Within Laboratory Precision:

  • Replicates: A minimum of 20 replicates per panel member for LoD. For precision, each operator performed 2 runs per day, with 3 replicates of each of the 11 panel members per run, across 21 days. (Total N = 168 or 165 for some panels due to exclusions).
  • Data Provenance: Laboratory study using synthetic panels (SVSM).

• Reproducibility:

  • Replicates: 3 replicates of each of the 7 panel members per run. Testing performed for at least six days at each of three sites. (Total N = 108 for each panel member).
  • Data Provenance: Multi-site laboratory study using synthetic panels (SVSM).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

The document does not explicitly state the number or specific qualifications of experts (e.g., "radiologist with 10 years of experience"). However, it mentions that for the clinical performance study, the ground truth for BV infection status was established using Nugent score evaluation, and modified Amsel criteria if necessary. This implies trained laboratory personnel and clinicians performing these established diagnostic methods.

4. Adjudication Method for the Test Set

• Clinical Performance Study:
  • "A Nugent interpretation established positive and negative BV reference status, except in cases of intermediate determinations. For intermediate Nugent interpretations, BV reference status was established using modified Amsel criteria."
  • This indicates a hierarchical adjudication or ground truth establishment method where Nugent scoring was primary, and Amsel criteria served as a secondary method for intermediate Nugent results. The document does not describe a multi-reader adjudication process in the sense of multiple experts independently reviewing and then reaching a consensus for the ground truth.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, the document does not describe a multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with AI assistance versus without AI assistance. The study evaluates the standalone performance of the Aptima BV Assay against established clinical criteria (Nugent score/Amsel criteria).

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies presented are standalone performance evaluations of the Aptima BV Assay (an in vitro nucleic acid amplification test performed on the automated Panther system). The results (BV positive or negative status) are generated by the system's software based on signal emergence times and calibration information, without human interpretation of the assay's output for diagnostic purposes in the performance studies. Its performance is compared to a ground truth established by clinical methods.

7. The Type of Ground Truth Used

• Clinical Performance Study:

  • The primary ground truth for Bacterial Vaginosis (BV) infection status was established using Nugent score evaluation.
  • For cases with intermediate Nugent interpretations, modified Amsel criteria were used to establish the BV reference status.

• Analytical and Reproducibility Studies:

  • Ground truth was based on the known composition of the synthetic panels (Simulated Vaginal Swab Matrix - SVSM) spiked with specific concentrations of target organism lysates.

8. The Sample Size for the Training Set

The document does not provide information on the sample size used for the training set of the Aptima BV Assay. This is because the Aptima BV Assay is a nucleic acid amplification test, a type of IVD, that relies on biochemical reactions and calibrated thresholds rather than machine learning algorithms that typically require explicit training data sets for model development. The "calibration information" mentioned in the description of the Panther system suggests a pre-defined set of parameters, likely established through analytical studies.

9. How the Ground Truth for the Training Set Was Established

As noted above, for this type of in-vitro diagnostic device, there isn't typically a "training set" in the machine learning sense with an associated ground truth established by experts.

Instead, the assay's operational parameters (e.g., thresholds for positivity based on signal emergence times) would be established through a rigorous process of analytical validation (like the LoD and precision studies described) using samples with known concentrations of targets. This ensures the assay's performance characteristics (sensitivity, specificity) meet predefined criteria. The "calibration information" is central to how the device makes its determination.

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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) to detect and qualitatively report results for the following organisms:

• Candida species group (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)
• Candida glabrata
• Trichomonas vaginalis

The assay differentiates between Candida glabrata and the Candida species group (C spp) by targeting the RNA component of RNAse Pribonucleoprotein; the assay does not differentiate among C spp. For Trichomonas vaginalis, the assay targets ribosomal RNA (rRNA) and differentiates the results for Candida glabrata and C spp. The assay is intended to aid in the diagnosis of vulvovaginal candidiasis and trichomoniasis on the automated Panther system using clinician-collected and patient-collected vaginal swab specimens from females with a clinical presentation consistent with vaginitis or vulvovaginitis.

The Aptima CV/TV assay is an in vitro nucleic acid amplification test for the detection and quantitation of RNA from microorganisms associated with vulvovaginal candidiasis and trichomoniasis in women with a clinical presentation consistent with vaginitis or 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 assay involves three main steps, all of which take place in a single tube on the Panther system: target capture, target amplification by TMA, and detection of the amplification products (amplicon) by fluorescent labeled probes (torches). The assay incorporates an internal control (IC) in every test to monitor nucleic acid capture, amplification and detection.

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for clinical performance in a table format with specific numerical thresholds the device must meet. Instead, it presents the achieved performance metrics (sensitivity, specificity, PPV, NPV) from the clinical study, implying these demonstrated statistics were considered acceptable for clearance. For analytical studies, acceptance is demonstrated by successfully meeting the goals of the study (e.g., all strains detected for inclusivity, no cross-reactivity beyond a certain concentration).

Therefore, for the clinical performance, the reported performance is the demonstration of meeting implied acceptance.

Note: For a medical device, acceptance criteria are typically predefined thresholds in a study protocol that the device performance must surpass. Since these aren't explicitly stated as hard "criteria" with target numbers, I'll present the reported device performance from the clinical study tables.

For Analytical Studies, acceptance was indicated by:

• Analytical Sensitivity (LoD): Predicted detection limits established through probit analysis (Table 6).
• Analytical Inclusivity: All Candida strains and 8/9 T. vaginalis strains detected at 3X LoD, with one T. vaginalis at 4X LoD.
• Cross-Reactivity and Microbial Interference: No cross-reactivity or microbial interference observed for 64 organisms and human cell lines at specified concentrations (Table 7), with minor exceptions noted for Candida famata, Tioconazole, Vaginal Moisturizing Gel, and Glacial Acetic Acid at higher concentrations than the tested limits.
• Within Laboratory Precision: 100% agreement with expected positivity for all positive and negative panel members (Table 9). Signal variability (CV%) for TTime was reported and considered acceptable (Table 10).
• Co-Infection: 100% detection for both targets present in co-infection panels (Table 11), with further testing confirming low C. glabrata and high T. vaginalis detection.
• Reproducibility: 100% agreement with expected results for all panel members across three sites (Table 21). Total %CV values for TTime ranged from 5.64% to 6.77% across organisms/panel members (Table 22), and from 4.29% to 6.89% for controls (Table 23).

Study Details

1. Sample Size Used for the Test Set and Data Provenance:

   • Total Subjects Enrolled: 1519 symptomatic women.
   • Evaluable Subjects: 1496.
   • Sample Types: Clinician-collected and patient-collected vaginal swab specimens.
   • Data Provenance:
     • Country of Origin: Geographically diverse US clinical sites (21 sites).
     • Retrospective/Prospective: Prospectively-collected.

2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

   • The document does not explicitly state the number of experts used to establish the ground truth.
   • Qualifications of Experts: Not specified. The reference methods are described (Candida culture, PCR/bi-directional sequencing, FDA-cleared molecular TV assay, FDA-cleared culture-based TV test), but the individuals interpreting these results to form the ground truth are not detailed.

3. Adjudication Method for the Test Set:

   • The document describes how the reference results for Candida and T. vaginalis were established:
     • Candida species group and C. glabrata: Based on a combination of Candida growth in culture, as well as PCR/bi-directional sequencing of both Aptima swab samples (leftover after testing) for subjects with positive Candida culture results.
     • T. vaginalis: A patient infected status (PIS) determined for each subject based on results from an FDA-cleared molecular TV assay and an FDA-cleared culture-based TV test.
   • This indicates a composite reference standard approach (multiple tests combined) rather than a simple 2+1 or 3+1 expert adjudication for diagnostic imaging, which is not applicable here.

4. 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, an MRMC comparative effectiveness study was not done. This refers to a medical device for in vitro diagnostic testing (nucleic acid amplification test) rather than an AI-assisted diagnostic imaging device/software the question implies. The study evaluates the performance of the assay itself against established reference methods.

5. If a Standalone (i.e., algorithm only without human-in-the loop performance) was done:

   • Yes, this was a standalone performance study. The Aptima CV/TV assay is an in vitro diagnostic test performed on an automated Panther system. Its performance (sensitivity, specificity) is evaluated directly against reference methods without human interpretation of the assay's output as an "assistance" to a physician. The "Panther system software uses an Aptima CV/TV assay-specific algorithm that interprets the amplification signal emergence times to generate a Positive or Negative status for each target organism in the sample." This is a completely automated interpretation by the device.

6. The Type of Ground Truth Used:

   • Composite Reference Standard / Expert Consensus (implied by combining tests):
     • For Candida species group and C. glabrata: Ground truth was established by combining Candida growth in culture and PCR/bi-directional sequencing.
     • For T. vaginalis: Ground truth (Patient Infected Status - PIS) was established using an FDA-cleared molecular TV assay and an FDA-cleared culture-based TV test.

7. The Sample Size for the Training Set:

   • The document does not provide information on a separate training set or its sample size. This is common for IVD assays where "training" refers more to assay development and optimization rather than machine learning model training on a specific clinical dataset. The clinical performance study described serves as the validation dataset.

8. How the Ground Truth for the Training Set Was Established:

   • Since no separate training set is detailed, information on how its ground truth was established is not provided. The ground truth for the clinical validation described above was established using composite reference standards, as per point 6.

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