BD MAX Vaginal Panel

K191957 · Geneohm Sciences Canada, Inc. (Bd Diagnostics) · PQA · Oct 21, 2019 · Microbiology

Device Facts

• Record ID: K191957
• Device Name: BD MAX Vaginal Panel
• Applicant: Geneohm Sciences Canada, Inc. (Bd Diagnostics)
• Product Code: PQA · Microbiology
• Decision Date: Oct 21, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3975
• Device Class: Class 2

Indications for Use

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.

Device Story

BD MAX Vaginal Panel is an automated in vitro diagnostic test performed on the BD MAX System; utilizes real-time PCR to detect DNA from specific bacteria, yeast, and parasites associated with vaginitis/vaginosis. Input: vaginal swab specimens in BD MAX UVE Sample Buffer Tubes. Process: automated sample preparation (lysis, DNA extraction/concentration, reagent rehydration, PCR amplification, detection via fluorogenic hybridization probes). Output: qualitative results for vaginitis analytes and bacterial vaginosis markers. Used in clinical laboratories; operated by trained personnel. Software automatically interprets amplification signals to provide POS, NEG, or UNR results. Modification (ADF version 3.0) improves assay tolerance and reduces non-reportable result rates while maintaining clinical performance.

Clinical Evidence

No clinical data provided in this summary; substantial equivalence is supported by the predicate device and performance standards.

Technological Characteristics

Nucleic acid-based test using real-time PCR; automated on BD MAX System. Components: microfluidic cartridges, master mixes, unitized reagent strips, extraction reagents. Detection via hydrolysis probes with fluorescent reporter dyes and quenchers. Software-controlled automated interpretation of results. Sample Processing Control (SPC) monitors extraction, amplification, and inhibition.

Indications for Use

Indicated for symptomatic women with clinical presentation of vaginitis/vaginosis to aid in diagnosis of bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis using vaginal swab specimens.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• BD MAX Vaginal Panel, BD MAX Instrument (DEN160001)

Submission Summary (Full Text)

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Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY AND INSTRUMENT

## I Background Information:

A 510(k) Number:
K191957

B Applicant:
GeneOhm Sciences Canada, Inc. (BD Diagnostics)

C Proprietary and Established Names:
BD MAX Vaginal Panel, BD MAX System

D Regulatory Information:

1. Regulation section:
21 CFR 866.3975. Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis.

2. Classification:
Class II (Special Controls)

3. Product code(s):
PQA
OUY
OOI
NSU

4. Panel:
83 - Microbiology

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## II Submission/Device Overview:

### A Purpose for Submission:

This submission describes post-market changes to the BD MAX Vaginal Panel, performed on the BD MAX System, an *in vitro* diagnostic test market-authorized under DEN160001 for the direct detection of DNA from vaginal swabs for patients who are symptomatic for vaginitis/vaginosis.

Routine post market surveillance activities informed BD of an unanticipated high rate of non-reportable result rate for the BD MAX Vaginal Panel. Through investigations, BD identified four design modifications intended to improve the tolerance of the BD MAX Vaginal Panel without significantly impacting the validated clinical and analytical performance. Utilizing the FDA Guidance Document, Deciding When to Submit a 510(k) for a Change to an Existing Device (October 2017), three of the modifications described herein are insignificant and do not require submission of a new 510(k). Reliance on the established BD Quality System reasonably assures the safety and effectiveness of the modified device for these three modifications. One of the four design modifications was determined to be significant with the potential to affect the safety or effectiveness of the device and is the focus of this submission. The cumulative changes require minor modifications to the labeling.

### B Measurand:

The assay detects and identifies nucleic acids of the following organisms:

- Bacterial vaginosis (BV) markers (Results for individual organisms are not reported. Qualitative BV results are based on detection and quantitation of targeted organisms)

- *Lactobacillus* spp (*L. crispatus* and *L. jensenii*)
- *Gardnerella vaginalis*
- *Atopobium vaginae*
- Bacterial Vaginosis Associated Bacteria-2 (BVAB-2)
- *Megasphaera*-1

- *Candida* spp. (Reported as Cgroup: includes *C. albicans*, *C. tropicalis*, *C. parapsilosis*, *C. dubliniensis*)
- *Candida glabrata*
- *Candida krusei*
- *Trichomonas vaginalis*

### C Type of Test:

The BD MAX Vaginal Panel, performed on the BD MAX System, is a nucleic acid-based test for the detection of the above listed bacteria, yeast and parasites in vaginal specimens obtained from symptomatic patients.

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## III Intended Use/Indications for Use:

### A Intended Use(s):

See Indications for Use below.

### B Indication(s) for Use:

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.

### C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

### D Special Instrument Requirements:

BD MAX System

### IV Device/System Characteristics:

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# A Device Description:

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.

# B Principle of Operation:

The BD MAX Vaginal Panel is designed for use with the BD MAX UVE Specimen Collection kit. Samples are transported to the testing laboratory in BD MAX UVE Sample Buffer Tubes (SBT). The Sample Buffer Tubes, are vortexed to release cells from the swab into the buffer. The Sample Buffer Tubes, Unitized Reagent Strips and PCR Cartridges are loaded on the BD MAX System. No further operator intervention is necessary, and the following automated procedures occur.

A combination of lytic and extraction reagents are used to perform cell lysis and DNA extraction. Nucleic acids released from the target organisms are captured on magnetic affinity beads. The beads, together with the bound nucleic acids, are washed and the nucleic acids are eluted by a combination of heat and pH. Eluted DNA is neutralized and transferred to the Master Mix Tubes to rehydrate the PCR reagents. After reconstitution, the BD MAX System dispenses a fixed volume of PCR-ready solution containing extracted nucleic acids into the PCR Cartridge. Microvalves in the cartridge are sealed by the system prior to initiating PCR in order to contain the amplification mixture and thus prevent evaporation and contamination.

The amplified DNA targets are detected using hydrolysis probes, labeled at one end with a fluorescent reporter dye (fluorophore), and at the other end, with a quencher moiety. Probes labeled with different fluorophores are used to detect the target analytes in different optical channels of the BD MAX System. When the probes are in their native state, the fluorescence of the fluorophore is quenched due to its proximity to the quencher. However, in the presence of target DNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5'-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the DNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The amount of fluorescence detected in the optical channels used for the BD MAX Vaginal Panel is directly proportional to the quantity of the corresponding probe that is hydrolyzed. The BD MAX System monitors these signals at each cycle of the PCR and interprets the data at the end of the reaction to provide qualitative test results for each vaginitis analyte as well as qualitative results for bacterial vaginosis based on detection and quantitation of targeted bacterial vaginosis markers.

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C Instrument Description Information:

| Modes of Operation | Yes | No |
| --- | --- | --- |
| Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? | ☐ | ☑ |
| Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? | ☐ | ☑ |
| Software | | |
| FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types. | ☑ | ☐ |

1. Instrument Name:
BD MAX System

2. Specimen Identification:
Specimens are identified via barcode.

3. Specimen Sampling and Handling:
Sample Buffer Tubes containing vaginal swab specimens are vortexed for one minute on the Multi-tube Vortexer, after which the user uncaps each specimen, removes the excess fluid from the swab, discards the swab and then recaps the tube with a blue septum cap. Specimens are then loaded into the BD MAX System Rack on the BD MAX System after which all additional specimen handling steps are automated.

4. Calibration:
The system is calibrated by the manufacturer on-site as part of the installation procedure as well as during biannual preventive maintenance.

5. Quality Control:
Internal Control
Each Extraction Tube contains a Sample Processing Control (SPC) comprised of plasmids containing a synthetic target DNA sequence. The SPC monitors the efficiency of DNA capture, washing and elution during the sample processing steps, as well as the efficiency of DNA amplification and detection during PCR analysis. If the SPC result fails to meet the acceptance criteria, the result of the specimen will be reported as Unresolved for the Master Mix reaction. Each Master Mix contains its own Sample Processing Control; thus, Unresolved results are determined independently for each Master Mix. An Unresolved result is indicative of specimen-associated inhibition or reagent failure. The operator is directed to repeat any specimen reported as Unresolved.

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# External Controls

External quality control materials are not provided with the BD MAX Vaginal Panel and the BD MAX System software does not require inclusion of external controls for the purpose of sample test results interpretation. However, the instructions for use indicate that one external positive control and one external negative control should be run at least daily until adequate process validation is achieved on the BD MAX System in each laboratory setting. After such validation has been completed, laboratories are directed to perform external quality control testing according to guidelines or requirements of local, state and federal accrediting organizations.

The following are recommended in the package insert for external control testing with the BD MAX Vaginal Panel.

## External Negative Controls

- Suspension of commercially available *Lactobacillus iners* strain
- Previously characterized negative clinical specimen

## External Positive Controls

- Suspension of available organisms listed in the Table below.
- Previously characterized positive clinical specimen

Table 1: Recommended Organisms for External Controls

| | Positive controls | Negative controls |
| --- | --- | --- |
| Vaginitis | Trichomonas vaginalis ATCC 30001 | Lactobacillus iners
ATCC 55195 |
| | Candida albicans ATCC 10231 | |
| | Candida glabrata ATCC 2001 | |
| | Candida krusei ATCC 6258 | |
| Vaginosis | BV Positive External Control^{a} | |

*Mixture of *Gardnerella vaginalis* and *Atopobium vaginae*

# V Substantial Equivalence Information:

## A Predicate Device Name(s):

BD MAX Vaginal Panel, BD MAX Instrument

## B Predicate 510(k) Number(s):

DEN160001

## C Comparison with Predicate(s):

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| Device & Predicate Device(s): | K191957 | DEN160001 |
| --- | --- | --- |
| Device Trade Name | Same | BD MAX Vaginal Panel |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Same | 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. |
| Specimen Type | Same | Clinician and patient-collected female vaginal swab |
| Technology | Same | PCR |
| Organisms Detected | Same | • Bacterial vaginosis markers (*Lactobacillus* spp., *Gardnerella vaginalis*, *Atopobium vaginae*, BVAB-2, *Megasphaera*-1
• *Candida* spp.
• *Candida glabrata*
• *Candida krusei*
• *Trichomonas vaginalis* |
| Sample Prep/Interpretation of Results | Same | Automated by BD MAX System |

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| Device & Predicate Device(s): | K191957 | DEN160001 |
| --- | --- | --- |
| Assay Controls | Same | Sample Processing Control |
| Collection/Transport Device | Same | MAX UVE Specimen Collection Kit |
| Interpretation of Results | Same | Qualitative |
| General Device Characteristic Differences | | |
| Software | ADF version 3.0 | ADF version 2.0 |

VI Standards/Guidance Documents Referenced:

Not Applicable

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Reproducibility Study:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Precision/Reproducibility performance. No additional testing was conducted.

2. Linearity/Assay Reportable Range:

Not Applicable

3. Traceability, Stability, Expected Values (controls, calibrators, or methods):

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Traceability, Stability and Expected Values performance. No additional testing was conducted.

4. Specimen Stability:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Specimen Stability performance. No additional testing was conducted.

5. Detection Limit:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Detection Limit performance. No additional testing was conducted.

6. Analytical Inclusivity:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Inclusivity performance. No additional testing was conducted.

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7. Mixed Infection/Competitive Interference Study:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Mixed Infection/Competitive Interference Study performance. No additional testing was conducted.

8. Analytical Specificity/Cross-reactivity:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Analytical Specificity/Cross-reactivity Study performance. No additional testing was conducted.

9. Evaluation of Potentially Interfering Substances:

A study was performed to assess the potential inhibitory effects of lubricants that may be present in vaginal swab specimens on the BD MAX Vaginal Panel results. This testing supplements the potentially interfering substances data previously FDA-cleared De Novo Premarket Notifications, DEN160001. Exogenous (e.g., prescription and Over-the-Counter drugs, creams and/or gels) substances were evaluated in samples spiked with the highest concentration expected to be present in vaginal specimens. Each potentially interfering substance was evaluated in both negative and low positive samples. Samples for targeted vaginitis analytes were spiked with low concentrations (<2x LoD) of Candida albicans, Candida glabrata, Candida krusei or Trichomonas vaginalis. Positive BV samples were spiked with organism compositions designed to generate results near the assay BD MAX Vaginal Panel cutoffs for BV (i.e., C95).

An overall summary of the analysis is provided in the Table 2 and 3 below. Three of the four substances tested at the initial concentration failed to meet the qualitative acceptance criteria. MUKO Lubricating Jelly met the qualitative acceptance criteria but not the PCR metric equivalence criteria.

The concentration of each substance was incrementally reduced in the Sample Buffer Tube until interference (either qualitative or PCR metric) was no longer observed. Substances were tested at 50μL, 10μL, 5μL and 1 μL. Acceptable levels of substance in the Sample Buffer Tube were determined only for MUKO Lubricating Jelly. No acceptable level was obtained for the remaining three substances. A limitation is included in the package insert listing all substances that demonstrated interference with the BD MAX Vaginal Panel.

Table 2: Overall Summary of Initial Testing Results
| Substance | Level Tested (in SBT) | Substance Interferinga | Vaginitis Metrics | Vaginosis Metrics | Risk of Interferenceb |
| --- | --- | --- | --- | --- | --- |
| MUKO Lubricating Jelly | 50 μL | No | Fail | Fail | Yes |
| Surgilube | | Yes | N/A | | |
| Lubricating Jelly | | | | | |
| Aquasonic Clear | | | | | |

a Substance interfering according to qualitative acceptance criteria.
b Risk of interference identified based on PCR metric equivalence analysis.

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Table 3: Overall Summary of Secondary Testing Results

| Substance | Level Tested (in SBT) ^{a} | Vaginitis Metrics | Vaginosis Metrics | Risk of Interference ^{b} |
| --- | --- | --- | --- | --- |
| MUKO Lubricating Jelly | 3.3 μL | Pass | Pass | Low |
| Surgilube | No Passing Level Obtained | | | |
| Lubricating Jelly | | | | |
| Aquasonic Clear | | | | |

a Substance interfering according to qualitative acceptance criteria.
b Risk of interference identified based on PCR metric equivalence analysis.

10. Matrix Equivalence Study:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Matrix Equivalence Study performance. No additional testing was conducted.

11. Assay Cut-off:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Assay Cut-off performance. No additional testing was conducted.

12. Carry-Over:

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Carry-Over performance. No additional testing was conducted.

B Comparison Studies:

1. Re-analysis of Clinical Performance Data:

The original clinical study database in DEN160001 was reprocessed and analyzed according to the new ADF version 3.0 and the resulting data demonstrated that the assay robustness was improved with an acceptable minimal impact on the BD MAX Vaginal Panel assay performance.

BD MAX Vaginal Panel Sensitivity and Specificity

The reanalyzed clinical performance is presented in Table 4. There was a decrease in the clinical performance for BV sensitivity (0.4% for clinician-collected and 0.9% for patient-collected vaginal swabs) and clinician-collected group sensitivity (0.2% patient-collected vaginal swabs). All other performance measurements remained unchanged or increased slightly.

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Table 4: Overall Clinical Performance Comparison – Original vs. Modified

| Target | Specimen Type | Sens./Spec. | Original estimate with 95% CI | New estimate with 95% CI | Change in Estimate (New - Original) |
| --- | --- | --- | --- | --- | --- |
| BV | Clinician-collected | Sensitivity | 90.5%
88.3-92.2 | 90.1%
88.0-91.9 | -0.4% |
| Specificity | 85.8%
83.0-88.3 | 86.2%
83.4-88.6 | 0.4% |
| Sensitivity | 90.7%
88.6-92.5 | 90.5%
88.4-92.3 | -0.2% |
| Self-collected | Specificity | 84.5%
81.6-87.0 | 84.6%
81.8-87.1 | 0.1% |
| Sensitivity | 75.9%
57.9-87.8 | 75.9%
57.9-87.8 | 0.0% |
| Specificity | 99.7%
99.3-99.9 | 99.7%
99.4-99.9 | 0.0% |
| C. glabrata | Self-collected | Sensitivity | 86.7%
70.3-94.7 | 86.7%
70.3-94.7 | 0.0% |
| Specificity | 99.6%
99.2-99.8 | 99.6%
99.2-99.8 | 0.0% |
| Sensitivity | 99.8%
99.4-99.9 | 99.8%
99.4-99.9 | 0.0% |
| C. krusei | Clinician-collected | Specificity | 100%
99.8-100 | 100%
99.8-100 | 0.0% |
| Self-collected | Specificity | 100%
99.8-100 | 100%
99.8-100 | 0.0% |
| Candida group | Clinician-collected | Sensitivity | 90.9%
88.1-93.1 | 90.9%
88.1-93.1 | 0.0% |
| Specificity | 94.1%
92.6-95.4 | 94.2%
92.7-95.5 | 0.1% |
| Self-collected | Sensitivity | 92.2%
89.5-94.2 | 92.0%
89.3-94.0 | -0.2% |
| Specificity | 91.9%
90.2-93.4 | 92.1%
90.3-93.5 | 0.2% |
| T. vaginalis | Clinician-collected | Sensitivity | 93.1%
87.4-96.3 | 93.1%
87.4-96.3 | 0.0% |
| Specificity | 99.3%
98.7-99.6 | 99.3%
98.7-99.6 | 0.0% |
| Self-collected | Sensitivity | 93.2%
87.6-96.4 | 93.2%
87.6-96.4 | 0.0% |
| Specificity | 99.3%
98.7-99.6 | 99.3%
98.7-99.6 | 0.0% |

Impact of Reanalysis on BV

Table 5 through Table 8 summarize the impact of the new ADF (version 3.0) on BV results relative to the final results for the original ADF that was presented in DEN160001. Results are presented by specimen type and reference method result. Numbers in bold indicate where the results changed status between the original ADF and the new ADF.

For the clinician-collected reference method positive samples, one vaginal swab that originally reported positive and two samples that originally reported Unresolved were reported as negatives with the new ADF (Table 5). For the clinician-collected reference

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method negative samples, a total of eighteen clinician-collected samples previously reported as Unresolved or Not Available were reported as true negatives with the new ADF (Table 6).

In the patient-collected reference method positive condition, two samples previously reported as Unresolved or Not Available were negative with the new ADF (Table 7). Lastly, in the patient-collected reference method negative condition, a total of five samples originally reported as either Unresolved or Indeterminate were reported as true negatives with the new ADF (Table 8).

Table 5: Comparison of BV Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Positive)

| BV | | New AD Version 3.0 | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 796 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 797 |
| NEG | Count | 0 | 84 | 0 | 0 | 0 | 0 | 0 | 0 | 84 |
| INV a | Count | 0 | 0 | 6 | 0 | 0 | 0 | 0 | 0 | 6 |
| Partial UNR | Count | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 3 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 |
| Total | Count | 796 | 87 | 6 | 0 | 0 | 3 | 1 | 2 | 895 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 6: Comparison of BV Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| BV | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 96 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 96 |
| NEG | Count | 0 | 582 | 0 | 0 | 0 | 0 | 0 | 0 | 582 |
| INV a | Count | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Partial UNR | Count | 0 | 14 | 0 | 0 | 0 | 0 | 0 | 0 | 14 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 3 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 8 | 0 | 0 | 8 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Not Availb | Count | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 1 | 5 |
| Total | Count | 96 | 600 | 1 | 0 | 3 | 8 | 1 | 1 | 710 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

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Table 7: Comparison of BV Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Positive)

| BV | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 803 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 803 |
| NEG | Count | 0 | 82 | 0 | 0 | 0 | 0 | 0 | 0 | 82 |
| INV a | Count | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 0 | 5 |
| Partial UNR | Count | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| Not Avail.b | Count | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Total | Count | 803 | 84 | 5 | 0 | 1 | 1 | 2 | 0 | 896 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 8: Comparison of BV Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| BV | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 108 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 108 |
| NEG | Count | 0 | 589 | 0 | 0 | 0 | 0 | 0 | 0 | 589 |
| INV a | Count | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Partial UNR | Count | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 7 | 0 | 0 | 8 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | Count | 108 | 594 | 1 | 0 | 0 | 7 | 1 | 0 | 711 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 9 summarizes the overall BV performance according to the original ADF. The reanalyzed overall BV performance is presented in Table 10. The BV sensitivity with the new ADF changed to $90.1\%$ and $90.5\%$ , compared to $90.5\%$ and $90.7\%$ for the clinical-collected and the self-collected swabs respectively. The specificity increased to $86.2\%$ and $84.6\%$ compared to $85.8\%$ and $84.5\%$ for the clinical-collected and the self-collected swabs respectively.

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Table 9: BV Overall Performance by Specimen Type – Original ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 797 | 96 | 893 |
| | N | 84 | 582 | 666 |
| | Total | 881 | 678 | 1559 |
| Sensitivity: 90.5% (88.3%, 92.2%)
Specificity: 85.8% (83.0%, 88.3%) | | | | |
| Self-collected | P | 803 | 108 | 911 |
| | N | 82 | 589 | 671 |
| | Total | 885 | 697 | 1582 |
| Sensitivity: 90.7% (88.6%, 92.5%)
Specificity: 84.5% (81.6%, 87%) | | | | |

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Table 10: BV Overall Performance by Specimen Type - New ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 796 | 96 | 892 |
| | N | 87 | 600 | 687 |
| | Total | 883 | 696 | 1579 |
| Sensitivity: 90.1% (88.0%, 91.9%) Specificity: 86.2% (83.4%, 88.6%) | | | | |
| Self-collected | P | 803 | 108 | 911 |
| | N | 84 | 594 | 678 |
| | Total | 887 | 702 | 1589 |
| Sensitivity: 90.5% (88.4%, 92.3%) Specificity: 84.6% (81.8%, 87.1%) | | | | |

# Impact of Reanalysis on C. glabrata

Table 11 through Table 14 summarize the impact of the new ADF (version 3.0) on $C$ . glabrata results relative to the final results for the original ADF that was presented in DEN160001. Results are presented by specimen type and reference method result. Numbers in bold indicate where the results changed status between the original ADF and the new ADF.

There was no impact to the results for the clinician-collected reference method positive population when reanalyzed using the new ADF (Table 11). In the clinician-collected reference method negative condition, one sample previously reported as positive and three samples originally reported as either Unresolved or Indeterminate were reported as true negatives (Table 12).

There was no impact to the results for the clinician-collected reference method positive population when reanalyzed using the new ADF (Table 13). Lastly, a total of four patient-collected samples originally reported as either Unresolved or Indeterminate were reported as true negatives according to the reference method negative result once reanalyzed (Table 14).

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Table 11: Comparison of C. glabrata Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Positive)

| C. glabrata | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV^{a} | Partial UNR | Full UNR | IND | INC | Not Available^{b} | |
| POS | Count | 22 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 22 |
| NEG | Count | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 7 |
| INV^{a} | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Partial UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not Avail.^{b} | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | Count | 22 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 29 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 12: Comparison of C. glabrata Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| C. glabrata | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV^{a} | Partial UNR | Full UNR | IND | INC | Not Available^{b} | |
| POS | Count | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 5 |
| NEG | Count | 0 | 1584 | 0 | 0 | 0 | 0 | 0 | 0 | 1584 |
| INV^{a} | Count | 0 | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 7 |
| Partial UNR | Count | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 3 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 12 | 0 | 0 | 13 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 3 |
| Not Avail.^{b} | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
| Total | Count | 4 | 1588 | 7 | 0 | 3 | 12 | 3 | 5 | 1622 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

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Table 13: Comparison of C. glabrata Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Positive)

| C. glabrata | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 26 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 26 |
| NEG | Count | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| INV a | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Partial UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not Avail, b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | Count | 26 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 30 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 14: Comparison of C. glabrata Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| C. glabrata | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
| NEG | Count | 0 | 1592 | 0 | 0 | 0 | 0 | 0 | 0 | 1592 |
| INV a | Count | 0 | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 7 |
| Partial UNR | Count | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 8 | 0 | 0 | 9 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 4 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Total | Count | 6 | 1596 | 7 | 0 | 1 | 8 | 4 | 1 | 1623 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 15 summarizes the overall C. glabrata performance according to the original ADF with the reanalyzed overall C. glabrata performance presented in Table 16. The sensitivity and specificity of C. glabrata with the new ADF did not change.

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Table 15: C. glabrata Overall Performance by Specimen Type - Original ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 22 | 5 | 27 |
| | N | 7 | 1584 | 1591 |
| | Total | 29 | 1589 | 1618 |
| Sensitivity: 75.9% (57.9%, 87.8%) Specificity: 99.7% (99.3%, 99.9%) | | | | |
| Self-collected | P | 26 | 6 | 32 |
| | N | 4 | 1592 | 1596 |
| | Total | 30 | 1598 | 1628 |
| Sensitivity: 86.7% (70.3%, 94.7%) Specificity: 99.6% (99.2%, 99.8%) | | | | |

Table 16: C. glabrata Overall Performance by Specimen Type - New ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 22 | 4 | 26 |
| | N | 7 | 1588 | 1595 |
| | Total | 29 | 1592 | 1621 |
| Sensitivity: 75.9% (57.9%, 87.8%) Specificity: 99.7% (99.4%, 99.9%) | | | | |
| Self-collected | P | 26 | 6 | 32 |
| | N | 4 | 1596 | 1600 |
| | Total | 30 | 1602 | 1632 |
| Sensitivity: 86.7% (70.3%, 94.7%) Specificity: 99.6% (99.2%, 99.8%) | | | | |

# Impact of Reanalysis on C. krusei

Table 17 and Table 18 summarize the impact of the new ADF (version 3.0) on C. krusei results relative to the final results for the original ADF that was presented in DEN160001. Results are presented by specimen type and reference method result. Numbers in bold indicate where the results changed status between the original ADF and the new ADF.

In the clinician-collected reference method negative population, three samples that originally reported as either Unresolved or Indeterminate were resolved to true negatives (Table 17).

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There was no impact to the results for the clinician-collected reference method positive population when reanalyzed using the new ADF (Table 18).

Table 17: Comparison of C. krusei Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| C. krusei | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INVa | Partial UNR | Full UNR | IND | INC | Not Availableb | |
| POS | Count | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| NEG | Count | 0 | 1614 | 0 | 0 | 0 | 0 | 0 | 0 | 1614 |
| INVa | Count | 0 | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 7 |
| Partial UNR | Count | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 3 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 12 | 0 | 0 | 13 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 3 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
| Total | Count | 4 | 1617 | 7 | 0 | 3 | 12 | 3 | 5 | 1651 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 18: Comparison of C. krusei Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| C. krusei | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INVa | Partial UNR | Full UNR | IND | INC | Not Availableb | |
| POS | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NEG | Count | 0 | 1628 | 0 | 0 | 0 | 0 | 0 | 0 | 1628 |
| INVa | Count | 0 | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 7 |
| Partial UNR | Count | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 8 | 0 | 0 | 9 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 4 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Total | Count | 0 | 1632 | 7 | 0 | 1 | 8 | 4 | 1 | 1653 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 19 summarizes the overall C. krusei performance according to the original ADF with the reanalyzed overall C. krusei performance presented in Table 20. The sensitivity and specificity of C. krusei with the new ADF did not change.

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Table 19: C. krusei Overall Performance by Specimen Type - Original ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 0 | 4 | 4 |
| | N | 0 | 1614 | 1614 |
| | Total | 0 | 1618 | 1618 |
| No Data for Sensitivity Calculation Specificity: 99.8% (99.4%, 99.9%) | | | | |
| Self-collected | P | 0 | 0 | 0 |
| | N | 0 | 1628 | 1628 |
| | Total | 0 | 1628 | 1628 |
| No Data for Sensitivity Calculation Specificity: 100% (99.8%, 100%) | | | | |

Table 20: C. krusei Overall Performance by Specimen Type - New ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 0 | 4 | 4 |
| | N | 0 | 1617 | 1617 |
| | Total | 0 | 1621 | 1621 |
| No Data for Sensitivity Calculation Specificity: 99.8% (99.4%, 99.9%) | | | | |
| Self-collected | P | 0 | 0 | 0 |
| | N | 0 | 1632 | 1632 |
| | Total | 0 | 1632 | 1632 |
| No Data for Sensitivity Calculation Specificity: 100% (99.8%, 100%) | | | | |

# Impact of Reanalysis on Candida group

Table 21 through Table 24 summarize the impact of the new ADF (version 3.0) on the Candida Group results relative to the final results for the original ADF that were presented in DEN160001. Results are presented by specimen type and reference method result. Numbers in bold indicate where the results changed status between the original ADF and the new ADF.

There was no impact to the results for the clinician-collected reference method positive population when reanalyzed using the new ADF (Table 21). In the clinician-collected reference method negative condition, one sample previously reported as positive and three

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samples originally reported as either Unresolved or Indeterminate were reported as true negatives (Table 22).

In the patient-collected reference method positive condition, one sample previously reported as Indeterminate was changed to negative (Table 23). Lastly, one patient-collected sample originally reported as positive and three samples previously reported as Unresolved were reported as true negatives according to the reference method negative result (Table 24).

Table 21: Comparison of Candida Group Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Positive)

| Candida group | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INVa | Partial UNR | Full UNR | IND | INC | Not Availableb | |
| POS | Count | 462 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 462 |
| NEG | Count | 0 | 46 | 0 | 0 | 0 | 0 | 0 | 0 | 46 |
| INVa | Count | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 3 |
| Partial UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 8 | 0 | 0 | 8 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | Count | 462 | 46 | 3 | 0 | 1 | 8 | 2 | 0 | 522 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 22: Comparison of Candida Group Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| Candida group | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INVa | Partial UNR | Full UNR | IND | INC | Not Availableb | |
| POS | Count | 64 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 65 |
| NEG | Count | 0 | 1045 | 0 | 0 | 0 | 0 | 0 | 0 | 1045 |
| INVa | Count | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 4 |
| Partial UNR | Count | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 2 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 4 | 0 | 0 | 5 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
| Total | Count | 64 | 1049 | 4 | 0 | 2 | 4 | 1 | 5 | 1129 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

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Table 23: Comparison of Candida Group Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Positive)

| Candida group | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV^{a} | Partial UNR | Full UNR | IND | INC | Not Available^{b} | |
| POS | Count | 470 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 470 |
| NEG | Count | 0 | 40 | 0 | 0 | 0 | 0 | 0 | 0 | 40 |
| INV^{a} | Count | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 3 |
| Partial UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 5 | 0 | 0 | 6 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| Not Avail.^{b} | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Total | Count | 470 | 41 | 3 | 0 | 1 | 5 | 2 | 1 | 523 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 24: Comparison of Candida Group Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| Candida group | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV^{a} | Partial UNR | Full UNR | IND | INC | Not Available^{b} | |
| POS | Count | 89 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 90 |
| NEG | Count | 0 | 1028 | 0 | 0 | 0 | 0 | 0 | 0 | 1028 |
| INV^{a} | Count | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 4 |
| Partial UNR | Count | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 3 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| Not Available^{b} | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | Count | 89 | 1032 | 4 | 0 | 0 | 3 | 2 | 0 | 1130 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 25 summarizes the overall Candida group performance according to the original ADF with the reanalyzed overall Candida group performance presented in Table 26. The sensitivity of the Candida group overall performance with the new ADF remained the same for the clinician-collected swabs. Sensitivity slightly decreased from 92.2% to 92.0% for the self-collected swabs. The specificity increased to 94.2% and 92.1% compared to 94.1% and 91.9% for the clinical-collected and the self-collected swabs respectively.

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Table 25: Candida Overall Performance by Specimen Type - Original ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 462 | 65 | 527 |
| | N | 46 | 1045 | 1091 |
| | Total | 508 | 1110 | 1618 |
| Sensitivity: 90.9% (88.1%, 93.1%) Specificity: 94.1% (92.6%, 95.4%) | | | | |
| Self-collected | P | 470 | 90 | 560 |
| | N | 40 | 1028 | 1068 |
| | Total | 510 | 1118 | 1628 |
| Sensitivity: 92.2% (89.5%, 94.2%) Specificity: 91.9% (90.2%, 93.4%) | | | | |

Table 26: Candida Overall Performance by Specimen Type - New ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 462 | 64 | 526 |
| | N | 46 | 1049 | 1095 |
| | Total | 508 | 1113 | 1621 |
| Sensitivity: 90.9% (88.1%, 93.1%) Specificity: 94.2% (92.7%, 95.5%) | | | | |
| Self-collected | P | 470 | 89 | 559 |
| | N | 41 | 1032 | 1073 |
| | Total | 511 | 1121 | 1632 |
| Sensitivity: 92.0% (89.3%, 94.0%) Specificity: 92.1% (90.3%, 93.5%) | | | | |

# Impact of Reanalysis on T. vaginalis

Table 27 through Table 30 summarize the impact of the new ADF (version 3.0) on $T$ . vaginalis results relative to the final results for the original ADF that was presented in DEN160001. Results are presented by specimen type and reference method result. Numbers in bold indicate where the results changed status between the original ADF and the new ADF.

There was no impact to the results for the clinician-collected reference method positive population when reanalyzed using the new ADF (Table 27). A total of three clinician collected samples previously reported as Unresolved or Indeterminate were reported as true negatives according to the reference method result (Table 28).

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There was no impact to the results for the clinician-collected reference method positive population when reanalyzed using the new ADF (Table 29). Lastly, a total of five patient-collected samples originally reported as either Unresolved or Indeterminate were resolved to true negatives according to the reference method negative result (Table 30).

Table 27: Comparison of T. vaginalis Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Positive)

| T. vaginalis | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 121 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 121 |
| NEG | Count | 0 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 9 |
| INV a | Count | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Partial UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 2 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | Count | 121 | 9 | 1 | 0 | 0 | 2 | 1 | 0 | 134 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 28: Comparison of T. vaginalis Results for Clinician-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| T. vaginalis | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 11 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 |
| NEG | Count | 0 | 1459 | 0 | 0 | 0 | 0 | 0 | 0 | 1459 |
| INV a | Count | 0 | 0 | 6 | 0 | 0 | 0 | 0 | 0 | 6 |
| Partial UNR | Count | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Full UNR | Count | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 2 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 10 | 0 | 0 | 11 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
| Total | Count | 11 | 1463 | 6 | 0 | 1 | 10 | 2 | 5 | 1498 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

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Table 29: Comparison of T. vaginalis Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Positive)

| T. vaginalis | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 124 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 124 |
| NEG | Count | 0 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 9 |
| INV a | Count | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Partial UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Full UNR | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IND | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | Count | 124 | 9 | 1 | 0 | 0 | 0 | 1 | 0 | 135 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 30: Comparison of T. vaginalis Results for Patient-collected Vaginal Swabs - Original vs. New ADF (Reference Method Negative)

| T. vaginalis | | New ADF | | | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Original ADF | Estimate | POS | NEG | INV a | Partial UNR | Full UNR | IND | INC | Not Available b | |
| POS | Count | 11 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 |
| NEG | Count | 0 | 1466 | 0 | 0 | 0 | 0 | 0 | 0 | 1466 |
| INV a | Count | 0 | 0 | 6 | 0 | 0 | 0 | 0 | 0 | 6 |
| Partial UNR | Count | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Full UNR | Count | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| IND | Count | 0 | 1 | 0 | 0 | 0 | 7 | 0 | 0 | 8 |
| INC | Count | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 3 |
| Not Avail.b | Count | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Total | Count | 11 | 1471 | 6 | 0 | 0 | 7 | 3 | 1 | 1499 |

a INV=POS or NEG or UNR with External Control Fail
b Not Available means no result from a valid repeat

Table 31 summarizes the overall $T$ vaginalis performance according to the original ADF with the reanalyzed overall $T$ vaginalis performance presented in Table 32. The performance of $T$ vaginalis was not affected by the new ADF.

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Table 31: T. vaginalis Overall Performance by Specimen Type – Original ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 121 | 11 | 132 |
| | N | 9 | 1459 | 1468 |
| | Total | 130 | 1470 | 1600 |
| Sensitivity: 93.1% (87.4%, 96.3%)
Specificity: 99.3% (98.7%, 99.6%) | | | | |
| Self-collected | P | 124 | 11 | 135 |
| | N | 9 | 1466 | 1475 |
| | Total | 133 | 1477 | 1610 |
| Sensitivity: 93.2% (87.6%, 96.4%)
Specificity: 99.3% (98.7%, 99.6%) | | | | |

Table 32: T. vaginalis Overall Performance by Specimen Type – New ADF

| | | Reference Method | | Total |
| --- | --- | --- | --- | --- |
| Specimen Type | BD MAX | P | N | |
| Clinician-collected | P | 121 | 11 | 132 |
| | N | 9 | 1463 | 1472 |
| | Total | 130 | 1474 | 1604 |
| Sensitivity: 93.1% (87.4%, 96.3%)
Specificity: 99.3% (98.7%, 99.6%) | | | | |
| Self-collected | P | 124 | 11 | 135 |
| | N | 9 | 1471 | 1480 |
| | Total | 133 | 1482 | 1615 |
| Sensitivity: 93.2% (87.6%, 96.4%)
Specificity: 99.3% (98.7%, 99.6%) | | | | |

## BD MAX Vaginal Panel Non-Reportable Rate

The new ADF reduced the initial Unresolved rate for combined targets by 2.7% and 2.2%, respectively for clinician and self-collected specimens. The final Unresolved rate for combined targets was reduced by 1.1% and 0.5%, respectively for clinician and self-collected specimens. A comparison of non-reportable rates are presented in Table 33 for clinician-collected vaginal swabs and in Table 34 for self-collected vaginal swabs.

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Table 33: Non-reportable Rate for Clinician-Collected Vaginal Swabs

| Master Mix | Result Stage | Result Type | Original Estimate with 95% CI | New Estimate with 95% CI | Difference |
| --- | --- | --- | --- | --- | --- |
| BV MM and Candida/TV MM combined | Initial | Incomplete | 1.4%0.9-2.1 | 1.4%0.9-2.1 | 0.0% |
| Indeterminate | 3.7%2.9-4.7 | 3.7%2.9-4.7 | 0.0% |
| Unresolved | 3.0%2.3-3.9 | 0.3%0.2-0.8 | -2.7% |
| Non-reportable | 8.1%6.9-9.5 | 5.4%4.5-6.6 | -2.7% |
| Final Valid Repeat | Incomplete | 0.2%0.1-0.5 | 0.2%0.1-0.5 | 0.0% |
| Indeterminate | 0.8%0.4-1.3 | 0.7%0.4-1.2 | -0.1% |
| Unresolved | 1.3%0.8-1.9 | 0.2%0.1-0.5 | -1.1% |
| Non-reportable | 2.2%1.6-3.0 | 1.0%0.7-1.6 | -1.2% |
| BV MM | Initial | Incomplete | 1.4%0.9-2.1 | 1.4%0.9-2.1 | 0.0% |
| Indeterminate | 3.7%2.9-4.7 | 3.7%2.9-4.7 | 0.0% |
| Unresolved | 2.6%1.9-3.5 | 0.2%0.1-0.5 | -2.4% |
| Non-reportable | 7.7%6.5-9.0 | 5.2%4.3-6.4 | -2.5% |
| Final Valid Repeat | Incomplete | 0.2%0.1-0.5 | 0.2%0.1-0.5 | 0.0% |
| Indeterminate | 0.8%0.4-1.3 | 0.7%0.4-1.2 | -0.1% |
| Unresolved | 1.2%0.8-1.8 | 0.2%0.1-0.5 | -1.0% |
| Non-reportable | 2.0%1.5-2.8 | 1.0%0.7-1.6 | -1.0% |
| Candida/TV MM | Initial | Incomplete | 1.4%0.9-2.1 | 1.4%0.9-2.1 | 0.0% |
| Indeterminate | 3.7%2.9-4.7 | 3.7%2.9-4.7 | 0.0% |
| Unresolved | 0.6%0.4-1.1 | 0.3%0.2-0.8 | -0.3% |
| Non-reportable | 5.7%4.7-6.9 | 5.4%4.5-6.6 | -0.3% |
| Final Valid Repeat | Incomplete | 0.2%0.1-0.5 | 0.2%0.1-0.5 | 0.0% |
| Indeterminate | 0.8%0.4-1.3 | 0.7%0.4-1.2 | -0.1% |
| Unresolved | 0.3%0.2-0.8 | 0.2%0.1-0.5 | -0.1% |
| Non-reportable | 1.3%0.8-1.9 | 1.0%0.7-1.6 | -0.3% |

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Table 34: Non-reportable Rate for Self-Collected Vaginal Swabs

| Master Mix | Result Stage | Result Type | Original Estimate with 95% CI | New Estimate with 95% CI | Difference |
| --- | --- | --- | --- | --- | --- |
| BV MM and Candida/TV MM combined | Initial | Incomplete | 1.4%
0.9-2.0 | 1.4%
0.9-2.0 | 0.0% |
| Indeterminate | 2.7%
2.0-3.6 | 2.7%
2.0-3.6 | 0.0% |
| Unresolved | 2.9%
2.2-3.8 | 0.7%
0.4-1.2 | -2.2% |
| Non-reportable | 7.0%
5.9-8.3 | 4.8%
3.9-5.9 | -2.2% |
| Final Valid Repeat | Incomplete | 0.2%
0.1-0.6 | 0.2%
0.1-0.6 | 0.0% |
| Indeterminate | 0.6%
0.3-1.1 | 0.5%
0.3-1.0 | -0.1% |
| Unresolved | 0.6%
0.4-1.1 | 0.1%
0.0-0.3 | -0.5% |
| Non-reportable | 1.4%
1.0-2.1 | 0.8%
0.5-1.3 | -0.6% |
| BV MM | Initial | Incomplete | 1.4%
0.9-2.0 | 1.4%
0.9-2.0 | 0.0% |
| Indeterminate | 2.7%
2.0-3.6 | 2.7%
2.0-3.6 | 0.0% |
| Unresolved | 2.4%
1.7-3.2 | 0.3%
0.1-0.7 | -2.1% |
| Non-reportable | 6.5%
5.4-7.7 | 4.4%
3.5-5.4 | -2.1% |
| Final Valid Repeat | Incomplete | 0.2%
0.1-0.6 | 0.2%
0.1-0.6 | 0.0% |
| Indeterminate | 0.6%
0.3-1.1 | 0.5%
0.3-1.0 | -0.1% |
| Unresolved | 0.5%
0.2-0.9 | 0.1%
0.0-0.3 | -0.4% |
| Non-reportable | 1.3%
0.8-1.9 | 0.8%
0.5-1.3 | -0.5% |
| Candida/TV MM | Initial | Incomplete | 1.4%
0.9-2.0 | 1.4%
0.9-2.0 | 0.0% |
| Indeterminate | 2.7%
2.0-3.6 | 2.7%
2.0-3.6 | 0.0% |
| Unresolved | 0.9%
0.5-1.4 | 0.7%
0.4-1.2 | -0.2% |
| Non-reportable | 5.0%
4.0-6.1 | 4.8%
3.9-5.9 | -0.2% |
| Final Valid Repeat | Incomplete | 0.2%
0.1-0.6 | 0.2%
0.1-0.6 | 0.0% |
| Indeterminate | 0.6%
0.3-1.1 | 0.5%
0.3-1.0 | -0.1% |
| Unresolved | 0.3%
0.1-0.7 | 0.1%
0.0-0.3 | -0.2% |
| Non-reportable | 1.1%
0.7-1.7 | 0.8%
0.5-1.3 | -0.3% |

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2. **Matrix Comparison:**

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Matrix Comparison performance. No additional testing was conducted.

C **Clinical Studies:**

1. **Clinical Sensitivity:**

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Clinical Sensitivity performance. No additional testing was conducted.

2. **Clinical Specificity:**

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Clinical Specificity performance. No additional testing was conducted.

3. **Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):**

Not Applicable

D **Clinical Cut-Off:**

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Assay Cut-off performance. No additional testing was conducted.

E **Expected Values/Reference Range:**

Please refer to previously FDA-cleared De Novo Premarket Notifications, DEN160001 for Expected Values/Reference Range. No additional testing was conducted.

F **Other Supportive Instrument Performance Characteristics Data:**

Not Applicable

VIII **Proposed Labeling:**

The labeling supports the finding of substantial equivalence for this device.

IX **Conclusion:**

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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