BD MAX Vaginal Panel, BD MAX System, BD Molecular Swab Collection Kit

K201017 · Geneohm Sciences Canada, Inc. (Bd Life Sciences) · PQA · Oct 18, 2021 · Microbiology

Device Facts

• Record ID: K201017
• Device Name: BD MAX Vaginal Panel, BD MAX System, BD Molecular Swab Collection Kit
• Applicant: Geneohm Sciences Canada, Inc. (Bd Life Sciences)
• Product Code: PQA · Microbiology
• Decision Date: Oct 18, 2021
• 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 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.

Device Story

The BD MAX Vaginal Panel is an automated in vitro diagnostic test performed on the BD MAX System. It uses vaginal swab specimens collected in BD Molecular Swab Sample Buffer Tubes. The system automates sample preparation, including cell lysis, DNA extraction using magnetic affinity beads, and real-time PCR amplification. The system detects DNA from specific bacteria associated with bacterial vaginosis, Candida species, and Trichomonas vaginalis using fluorogenic hybridization probes. The system software automatically interprets PCR signals to provide qualitative results. The device is used in clinical laboratories by trained personnel. Results aid healthcare providers in diagnosing vaginal infections in symptomatic women. The current submission replaces the previously cleared BD MAX UVE Specimen Collection Kit with the BD Molecular Swab Collection Kit.

Clinical Evidence

Clinical performance was evaluated in a prospective study of 988 evaluable symptomatic female subjects. The study compared the BD Molecular Swab Collection Kit to the predicate BD MAX UVE Specimen Collection Kit. Results for BV and T. vaginalis met acceptance criteria (PPA/NPA ≥95%). For Candida Group, PPA was 87.8% and NPA was 95.7%; further investigation of discordant results confirmed performance equivalence, attributing discrepancies to low target loads near the assay LoD. Non-reportable rates were 0.1% for the new kit vs 0.6% for the predicate.

Technological Characteristics

The system utilizes real-time PCR with fluorogenic hydrolysis probes. The collection kit consists of a polyester swab with a polystyrene shaft, sterilized by irradiation. The BD MAX System automates lysis, DNA extraction via magnetic affinity beads, and thermal cycling. Software performs automated result interpretation based on amplification status of targets and Sample Processing Control (SPC).

Indications for Use

Indicated for symptomatic women with clinical presentation of vaginitis/vaginosis to aid in diagnosis of bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis via detection of specific DNA targets from vaginal swabs.

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 (DEN160001)

Submission Summary (Full Text)

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FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY AND INSTRUMENT

## I Background Information:

A 510(k) Number

K201017

B Applicant

GeneOhm Sciences Canada, Inc. (BD Life Sciences)

C Proprietary and Established Names

BD MAX Vaginal Panel, BD MAX System, BD Molecular Swab Collection Kit

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| PQA | Class II | 21 CFR 866.3975 - Device That Detects Nucleic Acid Sequences From Microorganisms Associated With Vaginitis And Bacterial Vaginosis | MI - Microbiology |

## II Submission/Device Overview:

### A Purpose for Submission:

The purpose of this submission is to replace the BD MAX UVE Specimen Collection Kit, currently indicated for specimen collection for the BD MAX Vaginal Panel, with the BD Molecular Swab Collection Kit.

### B Measurand:

DNA sequences from the following organisms:

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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Bacterial vaginosis associated organisms (Individual organisms not reported)
- Lactobacillus spp. (L. crispatus L. jensenii)
- Gardnerella vaginalis
- Atopobium vaginae
- Bacterial Vaginosis Associated Bacteria-2 (BVAB-2)
- Megasphaera-1

Bacterial vaginitis organisms:
- Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)
- Candida glabrata
- Candida krusei
- Trichomonas vaginalis

C Type of Test:
Real-time PCR

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

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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):
For Prescription Use Only

## D Special Instrument Requirements:
The BD MAX Vaginal Panel is performed on the BD MAX System

## IV Device/System Characteristics:

### 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 Molecular Swab Collection kit. Samples are transported to the testing laboratory in BD Molecular Swab Sample Buffer Tubes. 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 is 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.

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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.

## Instrument Description Information:

1. Instrument Name:
BD MAX System

2. Specimen Identification:
Specimens are identified with a unique bar code.

3. Specimen Sampling and Handling:
Molecular Swab Sample Buffer Tubes containing vaginal swab specimens are first vortexed for one minute on the Multi-Tube Vortexer. Specimens are then loaded onto the BD MAX System after which all additional specimen handling steps, assay processing and reporting are automated.

4. Calibration:
The BD MAX System does not require user calibration. All maintenance procedures, other than daily and weekly cleaning procedures, are performed by BD qualified personnel.

5. Quality Control:
Each Extraction Tube contains a Sample Processing Control (SPC) that is comprised of DNA 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 the PCR process. 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

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result is indicative of specimen-associated inhibition or reagent failure. The operator is directed to repeat any specimen reported as Unresolved.

## 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. External controls are treated as if they were patient samples. BD MAX Molecular Swab Sample Buffer Tubes are needed to prepare external controls.

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 controls are recommended for external control testing with the BD MAX Vaginal Panel.

## External Negative Controls

- Suspension of commercially available control material (e.g., Lactobacillus iners in a BD Molecular Swab Sample Buffer Tube.
- Previously characterized negative clinical specimen

## External Positive Controls

- Suspension of available organisms listed in the Table below (specific instructions are included in the IFU).
- Previously characterized positive clinical specimen

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

*A mixture of Gardnerella vaginalis and Atopobium vaginae

## V Substantial Equivalence Information:

## A Predicate Device Name(s):

BD MAX Vaginal Panel, BD MAX Instrument

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B Predicate 510(k) Number(s):

DEN160001

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K201017 | DEN160001 |
| --- | --- | --- |
| Device Trade Name | BD MAX Vaginal Panel (Submitted Device) | BD MAX Vaginal Panel (DEN160001) |
| General Device Characteristic Similarities | | |
| Intended Use/Indications 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 | Same |

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| | bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis. | |
| --- | --- | --- |
| Assay technology | Real-time RT-PCR | Same |
| Specimen Type | Clinician and patient-collected vaginal swab | Same |
| Sample Buffer Formulation | Potassium phosphate, EDTA, Tween 20 and Proclin buffer | Same |
| Swab Type | Polyester | Same |
| Sterilization Method | Irradiation | Same |
| Swab Shaft Composition | Polystyrene | Same |
| General Device Characteristic Differences | | |
| Collection Transport Device | BD Molecular Swab Collection Kit | BD MAX UVE Specimen Collection Kit |
| Swab Bud Size | 0.156 in | 0.125 in |

VI Standards/Guidance Documents Referenced:

Class II Special Controls Guideline: Nucleic Acid Amplification Assays for the Detection of Trichomonas vaginalis, August 4, 2015.

VII Performance Characteristics (if/when applicable):

A Analytical Performance: (Refer to DEN160001 and K191957 for analytical studies conducted previously for the BD MAX Vaginal Panel)

Analytical Sensitivity Equivalency Study:

A limited dilution LoD study was conducted comparing the analytical sensitivities between the new BD Molecular Swab Collection Kit and the BD MAX UVE Specimen Collection Kit that was previously cleared for the use with the BD MAX Vaginal Panel.

The study included contrived samples prepared using both swab collection kits. Samples containing Candida albicans, C. glabrata, C. krusei and T. vaginalis were prepared in clinical vaginal matrix. Samples containing bacterial vaginosis (BV) analytes (A. vaginae, L. crispatus, and L. jensenii) were prepared using simulated vaginal matrix due to the inherent background flora present in clinical vaginal matrix. The simulated vaginal matrix used for BV samples was the same as was used in DEN160001 for preparation of BV analytical study samples. Please refer to DEN160001 for details on the matrix equivalency study results demonstrating equivalent performance between the simulated and clinical vaginal matrices.

Up to 24 sample replicates were tested per target organism and dilution level for each collection device. The acceptance criteria were based on the breakpoint defined as the level in which <95% of specimens were detected (i.e., dropoff point). If the lowest concentrated test yielded ≥23/24

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positive sample replicates, another 24 replicates at a 2-fold lower target concentration were tested until the dropoff point was identified. If the highest concentration tested with UVE device did not generate 100% positive results, 24 additional sample replicates at a 2-fold higher target concentration were tested.

The two collection devices were considered equivalent when the dropoff concentration identified for the BD Molecular Swab Collection Kit was at the same dilution level or within one dilution level of the BD MAX UVE Specimen Collection Kit.

Results for BD MAX Vaginal Panel bacterial vaginitis and bacterial vaginosis analytes are shown in Table 1 and 2 respectively, with the cells shaded in gray representing the dropoff concentration for each collection device. Results from the study showed that the dropoff point identified for the BD MAX Molecular Swab Collection Kit was within one two-fold dilution level of the BD MAX UVE swab for each of the analytes evaluated, supporting equivalent analytical performance between the two collection kits.

Table 1: LoD Equivalency Study, Vaginitis Analytes

| Organism | Dilution | UVE Sample Buffer Tube | | Molecular Swab Sample Buffer Tube | |
| --- | --- | --- | --- | --- | --- |
| | Concentration (CFU/μl) | Final Concentration (CFU/mL)* | Positivity Rate | Final Concentration (CFU/mL)* | Positivity Rate |
| Candida albicans | 2.22E+01 | 7.41E+02 | 23/23 | 8.34E+02 | 24/24 |
| | 1.11E+01 | 3.71E+02 | 23/24 | 4.17E+02 | 20/24 |
| | 5.56E+00 | 1.85E+02 | 17/24 | 2.09E+02 | 20/24 |
| | 2.78E+00 | 9.27E+01 | 6/24 | 1.04E+02 | 8/24 |
| | 1.39E+00 | 4.63E+01 | 2/24 | 5.21E+01 | 10/24 |
| | 7.00E-01 | 2.33E+01 | 3/24 | 2.63E+01 | 4/24 |
| | 3.50E-01 | 1.17E+01 | 3/24 | 1.31E+01 | 5/24 |
| Candida glabrata | 8.08E+00 | 2.69E+02 | 24/24 | 3.03E+02 | 24/24 |
| | 4.04E+00 | 1.35E+02 | 24/24 | 1.52E+02 | 24/24 |
| | 2.02E+00 | 6.73E+01 | 23/24 | 7.58E+01 | 24/24 |
| | 1.01E+00 | 3.37E+01 | 15/24 | 3.79E+01 | 16/24 |
| | 5.05E-01 | 1.68E+01 | 13/24 | 1.89E+01 | 14/24 |
| Trichomonas vaginalis | 1.76E+00 | 5.87E+01 | 24/24 | 6.60E+01 | 24/24 |
| | 8.80E-01 | 2.93E+01 | 24/24 | 3.30E+01 | 23/24 |
| | 4.40E-01 | 1.47E+01 | 24/24 | 1.65E+01 | 21/24 |
| | 2.20E-01 | 7.33E+00 | 15/24 | 8.25E+00 | 13/24 |
| | 1.10E-01 | 3.67E+00 | 12/24 | 4.13E+00 | 11/24 |
| Candida krusei | 2.48E+02 | 8.27E+03 | 24/24 | 9.30E+03 | 24/24 |
| | 1.24E+02 | 4.13E+03 | 24/24 | 4.65E+03 | 24/24 |
| | 6.21E+01 | 2.07E+03 | 23/24 | 2.33E+03 | 23/24 |
| | 3.10E+01 | 1.03E+03 | 24/24 | 1.16E+03 | 24/24 |
| | 1.55E+01 | 5.17E+02 | 24/24 | 5.81E+02 | 24/24 |
| | 7.75E+00 | 2.58E+02 | 20/24 | 2.91E+02 | 12/24 |

*The two collection devices were spiked with different volumes based on swab size/absorption volume. Final concentrations are slightly different between the two collection devices.

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Table 2: Dilution Sensitivity Results for Vaginosis Targets

| Organism name | Dilution | UVE Sample Buffer | | Molecular Swab Sample Buffer | |
| --- | --- | --- | --- | --- | --- |
| | Concentration (CFU/μl) | Final Concentration (CFU/mL)** | Positivity Rate | Final Concentration (CFU/mL)** | Positivity Rate |
| Atopobium vaginae | 7.60E+00* | 2.53E+02 | 23/24 | 2.85E+02 | 24/24 |
| | 3.80E+00 | 1.27E+02 | 22/24 | 1.43E+02 | 21/24 |
| | 1.90E+00 | 6.33E+01 | 17/24 | 7.13E+01 | 17/24 |
| | 9.50E-01 | 3.17E+01 | 3/24 | 3.56E+01 | 2/24 |
| | 4.75E-01 | 1.58E+01 | 0/24 | 1.78E+01 | 2/24 |
| Gardnerella vaginalis | 2.30E+02 | 7.68E+03 | 24/24 | 8.64E+03 | 22/24 |
| | 1.15E+02 | 3.84E+03 | 22/24 | 4.32E+03 | 24/24 |
| | 5.76E+01 | 1.92E+03 | 21/24 | 2.16E+03 | 20/24 |
| | 2.88E+01 | 9.60E+02 | 14/24 | 1.08E+03 | 16/24 |
| | 1.44E+01 | 4.80E+02 | 5/24 | 5.40E+02 | 6/24 |
| Lactobacillus crispatus | 2.60E+01 | 8.67E+02 | 24/24 | 9.75E+02 | 23/24 |
| | 1.30E+01 | 4.33E+02 | 22/24 | 4.88E+02 | 24/24 |
| | 6.50E+00 | 2.17E+02 | 23/24 | 2.44E+02 | 21/24 |
| | 3.25E+00 | 1.08E+02 | 15/24 | 1.22E+02 | 19/24 |
| | 1.63E+00 | 5.42E+01 | 16/24 | 6.09E+01 | 14/24 |
| | 8.13E-01 | 2.71E+01 | 11/24 | 3.05E+01 | 5/24 |
| Lactobacillus jensenii | 1.22E+01 | 4.08E+02 | 24/24 | 4.59E+02 | 23/24 |
| | 6.12E+00 | 2.04E+02 | 22/24 | 2.30E+02 | 21/24 |
| | 3.06E+00 | 1.02E+02 | 20/24 | 1.15E+02 | 21/24 |
| | 1.53E+00 | 5.10E+01 | 10/24 | 5.74E+01 | 9/24 |
| | 7.65E-01 | 2.55E+01 | 6/24 | 2.87E+01 | 3/24 |

*One additional (higher) concentration of Atopobium vaginae $(5.07\mathrm{E} + 02\mathrm{CFU / mL})$ was also tested. Testing generated 23/24 positive results for UVE Sample buffer replicates and 22/24 positive results for Molecular Swab Sample Buffer replicates. Since this higher concentration demonstrated an unexpectedly lower detection rate, the three false negative samples were investigated. Results from the investigation showed that the false negative results were likely due to artifact and were therefore excluded from the analysis.
**The two collection devices were spiked with different volumes based on swab size/absorption volume. Final concentrations are slightly different between the two collection devices.

# Specimen Stability

A specimen stability study was conducted with vaginal swab samples prepared or collected using the BD Molecular Swab Collection Kit. The study included multiple sample replicates and or clinical specimens at two different storage conditions (2-8°C and 33°C) to demonstrate the stability of targeted analytes in Molecular Swab Collection Kit sample buffer tubes (SBT) for up to 21 days over the claimed storage temperature range of 2-30°C. The nested study design also included evaluation of stability of up to four days for previously tested specimens (i.e., specimens with pierced caps). Specimen stability claims in the BD MAX Vaginal Panel labeling are presented in Table 3.

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Table 3: Specimen Stability Claims, Molecular Swab Collection Device

| Specimen Stability | Transport and/or Storage Time/Temperature |
| --- | --- |
| In Molecular Swab Sample Buffer Tube (unpierced cap) | Up to 21 days at 2-30°C |
| In Molecular Swab Sample Buffer Tube (after cap is pierced) | Up to 4 days at 2-30°C |

BV Panel: Multiple unique panel members with varying concentrations of BV analytes were prepared in simulated matrix in sample buffer tube (SBT) media that is included in BD Molecular Swab Collection Kits. Samples were prepared by spiking targeted BV microorganisms into simulated matrix in SBT. Similar to the LoD Equivalency Study above, simulated matrix was used for BV samples due to the inherent nature of clinical matrix containing variable concentrations of organisms that are detected by the BD MAX Vaginal Panel for BV (e.g., *Lactobacillus*). Panel members included six low positives, four high negatives, and four negatives, with each panel member containing a different organism composition containing multiple targeted BV organisms at varying concentrations. Acceptance criteria were >95% detection for low positives, and <5% for negative BV samples.

Results from the study for BV, demonstrated >95% detection of low positive samples, between 5% and 95% detection for high negative samples and 100% negative results for negative samples for up to 22 days when stored at 2-8°C or at 30°C. The study results (Table 4) support the specimen stability claims included in the BD MAX Vaginal Panel labeling (See Table 3 above).

Table 4: Specimen Stability, Bacterial Vaginosis

| Storage Condition | Total Days | Low POS (%, n/N) | High NEG (%, n/N) | NEG (%, n/N) | Disposition |
| --- | --- | --- | --- | --- | --- |
| 2-8°C | 0 | 97%, 35/36 | 61%, 22/36 | 100%, 36/36 | Pass* |
| | 4 | 94%, 34/36 | 28%, 10/36 | 100%, 36/36 | Pass** |
| | 8 | 100%, 36/36 | 36%, 13/36 | 100%, 36/36 | Pass |
| | 9 | 97%, 35/36 | 33%, 12/36 | 100%, 36/36 | Pass |
| | 14 | 100%, 36/36 | 22%, 8/36 | 100%, 36/36 | Pass |
| | 15 | 100%, 36/36 | 22%, 8/36 | 100%, 36/36 | Pass |
| | 21 | 100%, 36/36 | 19%, 7/36 | 100%, 36/36 | Pass |
| | 22 | 100%, 36/36 | 22%, 8/36 | 100%, 36/36 | Pass |

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| Storage Condition | Total Days | Low POS (%, n/N) | High NEG (%, n/N) | NEG (%, n/N) | Disposition |
| --- | --- | --- | --- | --- | --- |
| 33°C | 0 | 100%, 36/36 | 61%, 22/36 | 100%, 36/36 | Pass |
| | 4 | 100%, 36/36 | 8%, 3/36 | 100%, 36/36 | Pass |
| | 8 | 100%, 36/36 | 19%, 7/36 | 100%, 36/36 | Pass |
| | 9 | 100%, 36/36 | 14%, 5/36 | 100%, 36/36 | Pass |
| | 14 | 100%, 36/36 | 0%, 0/36 | 100%, 36/36 | Pass |
| | 15 | 100%, 36/36 | 3%, 1/36 | 100%, 36/36 | Pass |
| | 21 | 100%, 36/36 | 14%, 5/36 | 100%, 36/36 | Pass |
| | 22 | 100%, 36/36 | 17%, 6/36 | 100%, 36/36 | Pass |

* One Low Pos replicate stored at 2-8°C was negative during baseline testing. Inspection of the PCR chamber for the sample revealed bubbles in the chamber. Repeat testing of the sample with a properly filled PCR chamber yielded a positive result.

**The Low Positive panel at 2-8°C did not meet the acceptance criteria at the Day 4 timepoint (only 34 of the 36 samples were positive). All subsequent time points tested with the Low Positive samples met acceptance criteria therefore the results from the Day 4 timepoint were considered aberrant.

Candida Group (CGroup) and *T. vaginalis*: To evaluate specimen stability in SBT media for the BD Molecular Swab Collection Kit, clinical vaginal specimens were collected from twenty unique CGroup positive individuals and 20 unique *T. vaginalis* (TV) positive individuals. CGroup positive and *T. vaginalis* positive specimens were selected to include challenging concentrations based on BD MAX Vaginal Panel PCR metrics (i.e., low positive (1-1.5x LoD), and moderate positive (3-5x LoD)). True negative specimens were comprised of vaginal specimens that were negative by the BD MAX Vaginal Panel for Cgroup, TV, and all other vaginitis analytes. A total of 20 positive specimens for CGroup and 20 positive specimens for TV as well as four true negative specimens were evaluated at each time point and storage condition.

Specimen stability study results for CGroup and TV (Table 5) yielded 100% positive and 100% negative results as expected for each time point and storage temperature evaluated. The results support storage of specimens for 21 days at 2-30°C (pierced and unpierced caps).

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Table 5: Specimen Stability, CGroup and T. Vaginalis Analytes

| Storage Condition | Total Days | CGroup (%, n/N) | TV (%, n/N) | NEG (%, n/N) | Disposition |
| --- | --- | --- | --- | --- | --- |
| 2-8°C | 0 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 4 | 100%, 20/20 | 95%, 19/20 | 100%, 4/4 | Pass |
| | 8 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 9 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 14 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 15 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 21 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 22 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| 33°C | 0 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 4 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 8 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 9 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 14 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 15 | 95%, 19/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 21 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |
| | 22 | 100%, 20/20 | 100%, 20/20 | 100%, 4/4 | Pass |

B Comparison Studies:

1. Method Comparison with Predicate Device:
Not Applicable

2. Matrix Comparison:
Not Applicable

C Clinical Studies:

1. Clinical Sensitivity/Specificity:
Refer to DEN160001 for Clinical Study conducted for the BD MAX Vaginal Panel.

2. Clinical Performance Equivalency Study:
A Clinical Performance Equivalency Study was conducted to evaluate performance of the BD Molecular Swab Specimen Collection Kit in comparison to the BD MAX UVE Specimen Collection Kit (indicated specimen collection kit for the cleared BD MAX Vaginal Panel, DEN160001) with testing with the BD MAX Vaginal Panel. Clinician collected vaginal specimens were collected from 13 clinical collection sites, representing high and low prevalence settings.

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Four clinician-collected vaginal swabs, two swabs for each collection kit type, were collected in a randomized order from 1,039 symptomatic female subjects. Only one swab per collection kit was used for the primary analysis.

Inclusion and Exclusion Criteria:

Subjects meeting the following criteria were considered for inclusion in the study:

- Female subjects presenting with symptoms of vaginitis or bacterial vaginosis.
- Female subjects who provide informed consent.
- Female adult subjects age 18 years and older who meet the legal age of majority per state requirements.

Specimens meeting the following criteria were considered for inclusion in the study:

- Vaginal specimen collection method performed according to the protocol, training instructions and/or package insert.
- Use of required collection kits.
- Transport and storage times and conditions maintained within the labeled indications for clinical study and reference method specimen.

Subjects meeting the following criteria were excluded from participating in the study:

- Specimens from subsequent visits of the same subject.
- Use of collection kits not required as per the protocol and/or training instructions.
- Vaginal swab collection method not performed according to the protocol, training instructions and/or package insert using the required collection kits.
- Collection swab not broken into the collection tube immediately after collection.
- Swab not present.
- Incorrect swab type used.
- Transport and storage times and conditions not maintained within the training instructions.
- Specimens not tested within timeframes defined in study’s training instructions.

Of the 1039 enrolled subjects, four subjects were excluded resulting in 1,035 compliant subjects. Specimens collected from an additional 47 subjects were excluded from the analysis leaving 988 evaluable subjects included in the analysis. The total number of fully compliant specimens with reportable results was 973 for BV and 971 for both Candida Group and Trichomonas vaginalis analytes. Table 6 includes age group and race/ethnicity distribution of compliant subjects enrolled in the study. Table 7 includes the pregnancy status of enrolled subjects.

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Table 6: Distribution of Age Group and Race/Ethnicity of Compliant Subjects

| Characteristics | Compliant Subjects Enrolled | Percent |
| --- | --- | --- |
| Age Group | | |
| 18 - 29 | 304 | 29.4% |
| 30 - 39 | 224 | 21.6% |
| 40 - 49 | 145 | 14.0% |
| 50 and over | 362 | 35.0% |
| Total | 1035 | 100% |
| Race | | |
| American Indian or Alaska Native | 14 | 1.4% |
| Asian | 5 | 0.5% |
| Black or African American | 708 | 68.4% |
| Native Hawaiian or Other Pacific Islander | 4 | 0.4% |
| White | 275 | 26.6% |
| Mixed Ethnicity (2 or more) | 8 | 0.8% |
| Other | 21 | 2.0% |
| Total | 1035 | 100% |
| Ethnicity | | |
| Hispanic or Latino | 189 | 18.3% |
| Not Hispanic or Latino | 846 | 81.7% |
| Total | 1035 | 100% |

Table 7: Pregnancy Status, Compliant Subjects

| Pregnant | Bacterial Vaginosis | | Candida Group | | T. vaginalis | |
| --- | --- | --- | --- | --- | --- | --- |
| | Pos | Neg | Pos | Neg | Pos | Neg |
| No | 544 | 418 | 194 | 766 | 134 | 826 |
| Yes | 7 | 1 | 2 | 6 | 2 | 6 |
| Unknown | 3 | 0 | 1 | 2 | 1 | 2 |

Specimens were tested with the BD MAX Vaginal Panel on five BD MAX instruments at one internal testing laboratory. Positive and negative external controls were included with each test run.

Any sample included in a run in which an external control failed, or any sample for which an Unresolved, Indeterminate, or Incomplete result was obtained, was retested from the same Sample Buffer Tube.

The performance of the new BD Molecular Swab Collection Kit compared to the BD MAX UVE Collection kit are provided in Table 8, 9 and 10. The results for BV and T. vaginalis met the study acceptance criteria with both Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) of $\geq 95\%$ and lower bound of the $95\%$ confidence intervals exceeding $90\%$, supporting equivalent performance of the two collection devices for these analytes. Acceptance criteria for Cgroup were met for NPA but not for PPA. Further analysis of discordant results is presented below the following performance tables. Due to the lower prevalence of Candida

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glabrata and Candida krusei, the results for these two analytes were not used to assess equivalence between the two collection devices; however, these analytes were evaluated in the LoD equivalency study (see above).

Table 8: Bacterial Vaginosis, PPA/NPA for Molecular Swab Compared to MAX UVE Swab

| Molecular Swab Kit Result | MAX UVE Kit Result | | Total | PPA | NPA |
| --- | --- | --- | --- | --- | --- |
| | Positive | Negative | | | |
| Positive | 537 | 20 | 557 | 96.9% (95.1%, 98.1%) | 95.2% (92.7%, 96.9%) |
| Negative | 17 | 399 | 416 | | |
| Total | 554 | 419 | 973 | | |

Table 9: T. vaginalis, PPA/NPA for Molecular Swab Compared the MAX UVE Swab

| Molecular Swab Kit Result | MAX UVE Kit Result | | Total | PPA | NPA |
| --- | --- | --- | --- | --- | --- |
| | Positive | Negative | | | |
| Positive | 133 | 5 | 138 | 97.1% (92.7%, 98.9%) | 99.4% (98.6%, 99.7%) |
| Negative | 4 | 829 | 833 | | |
| Total | 137 | 834 | 971 | | |

Table 10: Candida Group, PPA/NPA for Molecular Swab Compared to MAX UVE Swab

| Molecular Swab Kit Result | MAX UVE Kit Result | | Total | PPA | NPA |
| --- | --- | --- | --- | --- | --- |
| | Positive | Negative | | | |
| Positive | 173 | 33 | 206 | 87.8% (82.5%, 91.7%) | 95.7% (94.1%, 96.9%) |
| Negative | 24 | 741 | 765 | | |
| Total | 197 | 774 | 971 | | |

Further analysis of Candida Group Performance:

Investigation into the 57 discordant results for Cgroup was conducted to assess if there is a potential difference in performance between the BD Molecular Swab Collection Kit and the BD MAX UVE Swab Collection Kit. The investigation showed that the clinical study included a high percentage of challenging specimens that contained organism loads near the LoD of the assay as determined by PCR metrics generated from testing with the BD MAX Vaginal Panel. A total of 20/24 specimens that were negative with the BD Molecular Swab and positive with the BD MAX UVE Swab contained estimated target loads at or below the LoD of the assay. Similarly, 30/33 specimens that were positive with the BD Molecular Swab and negative with the BD MAX UVE Swab contained estimated target loads at or below the LoD of the assay. The stratified results (Table 11) support that lower PPA observed for CGroup does not appear to be due to performance differences between collection kits, but rather due to the high percentage of specimens in the study containing target loads at or below the assay LoD.

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Table 11: Candida Group Performance: Molecular Swab Collection Kit versus BD MAX UVE Collection Kit

| Molecular Swab Collection Kit Result | BD MAX UVE Collection Kit Result | | | Total |
| --- | --- | --- | --- | --- |
| | Positive (samples with target levels above LoD) | Positive (samples with target levels at or below LoD) | Negative | |
| Positive (samples with target levels above LoD) | 64 | 17 | 3 | 84 |
| Positive (samples with target levels at or below LoD) | 5 | 87 | 30 | 122 |
| Negative | 4 | 20 | 741 | 765 |
| Total | 73 | 124 | 774 | 971 |

In summary, although the PPA for CGroup did not meet the acceptance criteria of PPA $\geq 95\%$ , the additional analysis based on estimated target load support that the two collection kits perform equivalently for this analyte. In addition, the performance for BV and $T.$ vaginalis analytes, which met the acceptance criteria, demonstrated equivalent performance for the two collection kits when used for testing with the BD MAX Vaginal Panel.

# Clinical Study, Non-Reportable Rates:

Non-reportable rates including Unresolved (UNR), Indeterminate (IND), and Incomplete (INC) are presented in Table 12 below.

The final rate was calculated using valid repeats only. A valid repeat is defined as an available and compliant repeat result with valid external control results performed within the allowed time frame (48 hours refrigerated). Only one repeat was possible with the BD MAX UVE Specimen Collection Kit. Two repeats were possible with the BD Molecular Swab Collection Kit.

The initial total non-reportable rates were $6.0\%$ for BD MAX UVE swab specimens and $4.5\%$ for Molecular Swab specimens. The final total non-reportable rates with a valid repeat test were $0.6\%$ and $0.1\%$ for BD UVE and BD Molecular Swab specimens, respectively. Non-reportable rates observed in the study were similar to those observed in the clinical study conducted for DEN160001.

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Table 12: Non-Reportable Rate for Combined Target by Collection Kit and Overall

| Kit | Unresolved Rate | | Indeterminate Rate | | Incomplete Rate | | Total Rate | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Initial (95% CI) | Final (95% CI) | Initial (95% CI) | Final (95% CI) | Initial (95% CI) | Final (95% CI) | Initial (95% CI) | Final (95% CI) |
| UVE | 1.1% | 0.3% | 3.9% | 0.3% | 1.1% | 0.0% | 6.0% | 0.6% |
| | 11/1010 | 3/1010 | 39/1010 | 3/1010 | 11/1010 | 0/1010 | 61/1010 | 6/1010 |
| | (0.6-1.9) | (0.1-0.9) | (2.8-5.2) | (0.1-0.9) | (0.6-1.9) | (0.0-0.4) | (4.7-7.7) | (0.3-1.3) |
| Molecular Swab | 0.8% | 0.0% | 3.1% | 0.1% | 0.5% | 0.0% | 4.5% | 0.1% |
| | 8/988 | 0/978 | 31/988 | 1/978 | 5/988 | 0/978 | 44/988 | 1/978 |
| | (0.4-1.6) | (0.0-0.4) | (2.2-4.4) | (0.0-0.6) | (0.2-1.2) | (0.0-0.4) | (3.3-5.9) | (0.0-0.6) |

D Clinical Cut-Off:

Not applicable

E Expected Values/Reference Range:

Refer to DEN160001

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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