BD Vaginal Panel

K223653 · Becton, Dickinson and Company · PQA · Mar 6, 2023 · Microbiology

Device Facts

• Record ID: K223653
• Device Name: BD Vaginal Panel
• Applicant: Becton, Dickinson and Company
• Product Code: PQA · Microbiology
• Decision Date: Mar 6, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3975
• Device Class: Class 2

Intended Use

The BD Vaginal Panel is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for 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 Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis. The BD Vaginal Panel is available for use with the BD MAX™ System or the BD COR™ System.

Device Story

The BD Vaginal Panel is a nucleic acid-based diagnostic test performed on the BD COR System (or BD MAX System). It processes vaginal swab specimens collected in BD Molecular Swab Sample Buffer Tubes. The BD COR System (comprising BD COR MX and PX instruments) automates sample preparation, including vortexing, aliquoting, nucleic acid extraction, and purification using magnetic affinity beads. Extracted DNA is amplified via real-time PCR using fluorogenic TaqMan probes. The system monitors fluorescence signals at each cycle to detect and differentiate specific bacterial, yeast, and parasite targets. Results are automatically interpreted by the system software as POS, NEG, or UNR (Unresolved). The device aids clinicians in diagnosing bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis in symptomatic patients. By automating the workflow from sample loading to result reporting, the system reduces manual handling, minimizes potential for contamination, and provides standardized diagnostic output to inform clinical treatment decisions.

Clinical Evidence

No new clinical trials were conducted. Substantial equivalence was established through analytical performance studies (precision, reproducibility, limit of detection, and carry-over) and a method comparison study using 700 clinical specimens (natural and contrived) tested on both BD COR and BD MAX systems. Results demonstrated high agreement (PPA/NPA ≥95%) between platforms. Statistical analysis (paired t-tests, Deming regression) confirmed that differences in Ct/SDPA values between systems were not clinically significant.

Technological Characteristics

Nucleic acid-based real-time PCR assay using fluorogenic TaqMan probes. Materials include disposable microfluidic cartridges, master mixes, and magnetic affinity beads for extraction. System is fully automated (BD COR PX/MX). Connectivity via LIS integration. Sterilization/biocompatibility not specified. Software performs automated interpretation of amplification curves.

Indications for Use

Indicated for symptomatic women with clinical presentation of vaginitis/vaginosis to detect DNA from bacterial vaginosis markers, Candida species, and Trichomonas vaginalis 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 (K201017)

Submission Summary (Full Text)

{0}------------------------------------------------

March 6, 2023

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Becton, Dickinson and Company Joseph Basore Staff Regulatory Affairs Specialist 7 Loveton Circle Sparks, Maryland 21152

Re: K223653

Trade/Device Name: BD Vaginal Panel Regulation Number: 21 CFR 866.3975 Regulation Name: Device That Detects Nucleic Acid Sequences From Microorganisms Associated With Vaginitis And Bacterial Vaginosis Regulatory Class: Class II Product Code: PQA, OUY, OOI, NSU Dated: December 5, 2022 Received: December 6, 2022

Dear Joseph Basore:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

{1}------------------------------------------------

801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

# Noel J. Gerald -S

Noel J. Gerald, Ph.D. Branch Chief Bacterial Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

## Indications for Use

510(k) Number (if known) K223653

Device Name BD Vaginal Panel

#### Indications for Use (Describe)

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

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

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

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

Type of Use (Select one or both, as applicable)

| <span style="font-family: sans-serif;"> <svg class="bi bi-check-square" fill="currentColor" height="1em" viewbox="0 0 16 16" width="1em" xmlns="http://www.w3.org/2000/svg"> <path d="M14 1H2a1 1 0 0 0-1 1v12a1 1 0 0 0 1 1h12a1 1 0 0 0 1-1V2a1 1 0 0 0-1-1zM2 0a2 2 0 0 0-2 2v12a2 2 0 0 0 2 2h12a2 2 0 0 0 2-2V2a2 2 0 0 0-2-2H2z" fill-rule="evenodd"></path> <path d="M10.97 4.97a.75.75 0 0 1 1.071 1.05l-3.992 4.99a.75.75 0 0 1-1.08.02L4.324 8.384a.75.75 0 1 1 1.06-1.06l2.094 2.093 3.473-4.425a.236.236 0 0 1 .02-.022z" fill-rule="evenodd"></path> </svg> </span> Prescription Use (Part 21 CFR 801 Subpart D) |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| <span style="font-family: sans-serif;"> <svg class="bi bi-square" fill="currentColor" height="1em" viewbox="0 0 16 16" width="1em" xmlns="http://www.w3.org/2000/svg"> <path d="M14 1H2a1 1 0 0 0-1 1v12a1 1 0 0 0 1 1h12a1 1 0 0 0 1-1V2a1 1 0 0 0-1-1zM2 0a2 2 0 0 0-2 2v12a2 2 0 0 0 2 2h12a2 2 0 0 0 2-2V2a2 2 0 0 0-2-2H2z" fill-rule="evenodd"></path> </svg> </span> Over-The-Counter Use (21 CFR 801 Subpart C) |

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

#### 510(k) Summary

BD Vaginal Panel

#### Summary Preparation Date:

12/5/2022

#### Submitted by:

BD Integrated Diagnostic Solutions Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152

#### Contact:

Joseph Basore, Ph.D., RAC Staff Regulatory Affairs Specialist Tel: [phone] Email: [e-mail]

#### Proprietary Names:

For the instrument: BD COR™ PX/MX System

For the assay: BD Vaginal Panel

#### Common Names:

For the instrument: High-throughput molecular system

For the assay: Bacterial Vaginosis Assay Vaginitis Assay TV Assay Candida Assay

#### Regulatory Information

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

Classification: Class II (Special Controls)

Panel: Microbiology (83)

Product Code(s):

{4}------------------------------------------------

Vaginitis and Bacterial Vaginosis Nucleic Acid Detection System PQA OUY Trichomonas vaginalis Nucleic Acid Amplification Test System

- OOI Real Time Nucleic Acid Amplification System
- Instrumentation for Clinical Multiplex Test Systems NSU

#### Predicate Device

BD MAX Vaginal Panel (DEN160001, K191957, K201017)

#### Device Establishment

Registration Number: 1119779

#### Intended Use

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

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

#### Special Conditions for Use Statement: For Prescription Use Only

#### Special Instrument Requirements: BD CORTM PX/MX System

#### Device Description

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

The BD COR™ System is designed to allow the user to place clinical specimens directly into designated transport racks to be loaded into the System. Once the specimens are loaded, the System will perform the necessary pre-analytical steps such as vortexing, aliquoting into a molecular tube with the

#### CONFIDENTIAL AND PROPRIETARY

{5}------------------------------------------------

correct diluent, sorting/grouping of the secondary samples for testing by assay, pre-warming and cooling of the sample (where required), and transport of the sample into a molecular analyzer, where extraction, amplification and detection will take place.

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

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

#### Test Principle

The BD Vaginal Panel when performed on the BD CORTM System 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 BD COR™ MX Instrument, when combined with the BD COR™ PX Instrument, is to be used for automated sample preparation, extraction of nucleic acids from multiple specimen types, as well as the automated amplification of target nucleic acid sequences by fluorescence-based real-time PCR.

The BD Vaginal Panel extraction reagents are dried in 96-well microtiter plates that contain binding magnetic affinity beads and Sample Processing Control (SPC). Each well is capable of binding and eluting sample nucleic acids. The SPC monitors the integrity of the reagents and the process steps involved in DNA extraction, amplification and detection, as well as for the presence of potential assay inhibitors.

The BD Vaginal Panel liquid reagent plate includes Wash, Elution and Neutralization buffers. The beads (described above), 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 Amplification reagent (described below) to rehydrate the PCR reagents. After reconstitution, the BD COR™ PX/MX System dispenses a fixed volume of PCR-ready solution containing extracted nucleic acids into the BD PCR Cartridge.

Microvalves in the BD PCR 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 (TaqMan®) 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 COR™ PX/MX 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 BD COR™ PX/MX 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.

## Substantial Equivalence1

¹ The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended and as applied under 21 CFR 807, Subpart E under which a device can be marketed without pre-market approval or reclassification. A determination of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws or ther application by the courts.

{6}------------------------------------------------

Table 3 provides the similarities and differences between the submitted device and the legally marketed predicate device.

| Table 1: Comparison to Predicate Device |
|-----------------------------------------|
|-----------------------------------------|

| Items | BD Vaginal Panel | Predicate - BD MAXTM Vaginal Panel,<br>BD MAXTM System (K201017) |
|-----------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulation | Same | 866.3975 |
| Product Code | Same | PQA, OUY, OOI, NSU |
| Device Class | Same | II |
| Intended Use | The BD Vaginal Panel is an automated<br>qualitative in vitro diagnostic test for the<br>direct detection of DNA targets from<br>bacteria associated with bacterial<br>vaginosis (qualitative results reported<br>based on detection and quantitation of<br>targeted organism markers), <i>Candida</i><br>species associated with vulvovaginal<br>candidiasis, and <i>Trichomonas vaginalis</i><br>from vaginal swabs in patients who are<br>symptomatic for vaginitis/vaginosis. The<br>test utilizes real-time polymerase chain<br>reaction (PCR) for the amplification of<br>specific DNA targets and utilizes<br>fluorogenic target-specific hybridization<br>probes to detect and differentiate DNA<br>from: Bacterial vaginosis markers<br>(Individual markers not<br>reported) <i>Lactobacillus</i> spp. ( <i>L.</i><br><i>crispatus</i> and <i>L. jensenii</i> ) <i>Gardnerella vaginalis Atopobium vaginae</i> Bacterial Vaginosis<br>Associated Bacteria-2<br>(BVAB-2) <i>Megasphaera-1 Candida</i> spp. ( <i>C. albicans, C.</i><br><i>tropicalis, C. parapsilosis, C.</i><br><i>dubliniensis</i> ) <i>Candida glabrata Candida krusei Trichomonas vaginalis</i> The BD Vaginal Panel is intended to aid<br>in the diagnosis of vaginal infections in | The BD MAX Vaginal Panel performed<br>on the BD MAX System is an automated<br>qualitative in vitro diagnostic test for the<br>direct detection of DNA targets from<br>bacteria associated with bacterial<br>vaginosis (qualitative results reported<br>based on detection and quantitation of<br>targeted organism markers), <i>Candida</i><br>species associated with vulvovaginal<br>candidiasis, and <i>Trichomonas vaginalis</i><br>from vaginal swabs in patients who are<br>symptomatic for vaginitis/vaginosis. The<br>test utilizes real-time polymerase chain<br>reaction (PCR) for the amplification of<br>specific DNA targets and utilizes<br>fluorogenic target-specific hybridization<br>probes to detect and differentiate DNA<br>from: Bacterial vaginosis markers<br>(Individual markers not<br>reported) <i>Lactobacillus</i> spp. ( <i>L.</i><br><i>crispatus</i> and <i>L. jensenii</i> ) <i>Gardnerella vaginalis Atopobium vaginae</i> Bacterial Vaginosis<br>Associated Bacteria-2<br>(BVAB-2) <i>Megasphaera-1 Candida</i> spp. ( <i>C. albicans, C.</i><br><i>tropicalis, C. parapsilosis, C.</i><br><i>dubliniensis</i> ) <i>Candida glabrata Candida krusei Trichomonas vaginalis</i> |
| Items | BD Vaginal Panel | Predicate - BD MAXTM Vaginal Panel,<br>BD MAXTM System (K201017) |
| | women with a clinical presentation<br>consistent with bacterial vaginosis,<br>vulvovaginal candidiasis and<br>trichomoniasis.<br><br>The BD Vaginal Panel is available for<br>use with the BD MAXTM System or the<br>BD CORTM System. | The BD MAX Vaginal Panel is intended<br>to aid in the diagnosis of vaginal<br>infections in women with a clinical<br>presentation consistent with bacterial<br>vaginosis, vulvovaginal candidiasis and<br>trichomoniasis. |
| <i>Indications for Use</i> | Same | Symptomatic patients |
| <i>Specimen Type</i> | Same | Clinician and patient-collected female<br>vaginal swab |
| <i>Collection/ Transport<br/>Device</i> | BD Molecular Swab Collection Kit | BD MAX UVE Specimen Collection Kit<br>BD Molecular Swab Collection Kit |
| <i>Technology</i> | Same | PCR |
| <i>Organisms Detected</i> | Same | Lactobacillus spp. (L. crispatus<br>and L.jensenii) Gardnerella vaginalis Atopobium vaginae Bacterial Vaginosis Associated<br>Bacteria-2 (BVAB-2) Megasphaera-1 Candida spp. (C. albicans, C.<br>tropicalis, C. parapsilosis, C.<br>dubliniensis) Candida glabrata Candida krusei Trichomonas vaginalis |
| <i>Sample Prep/Results</i> | Automated by BD CORTM System | Partially Automated by BD MAXTM<br>System |

{7}------------------------------------------------

## Analytical Performance

Analytical performance of the BD Vaginal Panel was evaluated on the BD MAX™ System and the results may be found under DEN160001 with updates described in subsequent submissions K191957 and K201017. As the formulation of the BD Vaginal Panel reagents for use on the BD COR™ System has not changed from those used with the BD MAX™ System, certain analytical studies performed and documented in the package insert on BD MAX™ are equally applicable to the BD COR™ System (specimen stability, analytical sensitivity, inclusivity, cross-reactivity, and interfering substances). The following sections describe the analytical studies that were performed to demonstrate that the assay performance, when used on

#### CONFIDENTIAL AND PROPRIETARY

{8}------------------------------------------------

the BD COR™ System, is unchanged from the performance demonstrated on the BD MAX™ System. The new analytical studies included: within-laboratory precision and multi-site reproducibility, confirmation of the analytical sensitivity and a cross-contamination study, all performed on the BD COR™ System.

## Precision for BD COR™ System

The precision of the BD Vaginal Panel on the BD COR™ System was confirmed to be equivalent to that of the BD MAX™ System. Within-laboratory precision was evaluated for the BD Vaginal Panel on both the BD MAX™ System and the BD COR™ System at one site with one reagent lot. Testing was performed over twelve (12) days, two (2) runs per day, two (2) replicates per panel, for a total of 48 runs. Panel members were made of target organisms (or plasmid DNA for Megasphaera-1 and BVAB-2) spiked in simulated vaginal matrix. Bacterial vaginosis panel members were prepared at varying concentrations of multiple targeted species with sample compositions designed to generate low positive, moderate positive, high negative, or negative results for bacterial vaginosis. For Candida and Trichomonas vaginalis panel members, the target organisms were spiked at concentrations based on the assay LoD. Table 4 describes the panel members evaluated.

The qualitative and quantitative precision results for BD COR™ System are presented in Table 5. Second Derivative Peak Abscissa (SDPA), an internal criterion used to determine a final assay result, was selected as a means of assessing quantitative assay reproducibility. Mean SDPA values with variance components (SD and % CV) are shown in Table 6 and Table 7.

| Concentration Designation | Bacterial Vaginosis<br>(% of positive results expected<br>based on the organism composition) | Candida and Trichomonas vaginalis<br>(x LoD) |
|---------------------------|----------------------------------------------------------------------------------------------|----------------------------------------------|
| Moderate<br>Positive | ~100 | ≥2 to ≤5 |
| Low Positive | ~95 | <2 |
| High BV<br>Negative | ~20-80 | |
| BV Negative | ~5 | |
| True Negative | 0 (No Target) | No Target |

## Table 2: Precision Study Spiking Concentrations

{9}------------------------------------------------

| Target | Level | BD CORTM | | | | BD MAXTM | | | | | |
|--------------------------|------------------------|----------|-----------|----------|------------|------------|---------|-----------|----------|------------|------------|
| | | N Total | N Correct | %Correct | 95% CI LCL | 95% CI UCL | N Total | N Correct | %Correct | 95% CI LCL | 95% CI UCL |
| Bacterial<br>Vaginosis | True<br>Negativea | 288 | 288 | 100 | 98.7 | 100 | 288 | 288 | 100 | 98.7 | 100 |
| | BV Negativea | 48 | 48 | 100 | 92.6 | 100 | 48 | 48 | 100 | 92.6 | 100 |
| | BV High<br>Negativeb,d | 192 | 153 | 79.7 | 73.4 | 84.8 | 192 | 168 | 87.5 | 82.1 | 91.5 |
| | Low Positivec | 288 | 285 | 99.0 | 97.0 | 99.6 | 288 | 288 | 100 | 98.7 | 100 |
| | Moderate<br>Positived | 192 | 191 | 99.5 | 97.1 | 99.9 | 192 | 192 | 100 | 98.0 | 100 |
| Candida<br>glabrata | True<br>Negativea | 720 | 720 | 100 | 99.5 | 100 | 720 | 719 | 99.9 | 99.2 | 100 |
| | Low Positive | 48 | 48 | 100 | 92.6 | 100 | 48 | 48 | 100 | 92.6 | 100 |
| Candida<br>krusei | True<br>Negativea | 720 | 720 | 100 | 99.5 | 100 | 720 | 720 | 100 | 99.5 | 100 |
| | Low Positive | 48 | 48 | 100 | 92.6 | 100 | 48 | 48 | 100 | 92.6 | 100 |
| Candida<br>albicans | True<br>Negativea | 720 | 720 | 100 | 99.5 | 100 | 720 | 718 | 99.7 | 99.0 | 99 |
| | Low Positive | 48 | 48 | 100 | 92.6 | 100 | 48 | 48 | 100 | 92.6 | 100 |
| | Moderate<br>Positive | 48 | 48 | 100 | 92.6 | 100 | 48 | 48 | 100 | 92.6 | 100 |
| Trichomonas<br>vaginalis | True<br>Negativea | 720 | 720 | 100 | 99.5 | 100 | 720 | 719 | 99.9 | 99.2 | 100 |
| | Low Positive | 48 | 48 | 100 | 92.6 | 100 | 48 | 48 | 100 | 92.6 | 100 |
| | Moderate<br>Positive | 48 | 48 | 100 | 92.6 | 100 | 48 | 48 | 100 | 92.6 | 100 |

## Table 3: Qualitative Precision Study Results Summary for Vaginosis and Vaginitis Targets for BD COR™ and BD MAX™ Systems

a For the True Negative and BV Negative levels, the reported agreement indicates the percent of negative results.

b For the High Negative category, the reported agreement indicates the percent of positive results.

C Performance includes combined results from replicates of six panel members containing different organism compositions.

d Performance includes combined results from replicates of four panel members containing different organism compositions.

{10}------------------------------------------------

| | | | | Within Run<br>(Residual) | | | Run | | Day | | Total |
|--------------------------|----------------------|----|-------|--------------------------|------|------|------|------|------|------|-------|
| Target | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Candida glabrata | Low<br>Positive | 48 | 30.88 | 0.83 | 2.68 | 1.00 | 3.23 | 0 | 0 | 1.30 | 4.20 |
| Candida krusei | Low<br>Positive | 48 | 28.87 | 0.23 | 0.79 | 0.13 | 0.45 | 0 | 0 | 0.26 | 0.91 |
| Candida albicans | Low<br>Positive | 48 | 27.84 | 0.26 | 0.94 | 0 | 0 | 0.10 | 0.35 | 0.28 | 1.00 |
| Candida albicans | Moderate<br>Positive | 48 | 27.12 | 0.20 | 0.75 | 0.09 | 0.32 | 0 | 0 | 0.22 | 0.82 |
| Trichomonas<br>vaginalis | Low<br>Positive | 48 | 32.70 | 0.34 | 1.04 | 0.20 | 0.60 | 0 | 0 | 0.39 | 1.20 |
| Trichomonas<br>vaginalis | Moderate<br>Positive | 48 | 31.63 | 0.30 | 0.96 | 0.05 | 0.15 | 0 | 0 | 0.31 | 0.98 |

#### Table 4: Quantitative Precision Summary of Variance Components by Vaginitis Target for BD COR™ System

| | Table 5: Quantitative Precision Summary of Variance Components by Vaginitis Target for BD | |
|--------------|-------------------------------------------------------------------------------------------|--|
| MAXTM Svstem | | |

| | | | | Within Run<br>(Residual) | | Run | | Day | | Total | |
|--------------------------|----------------------|----|-------|--------------------------|------|------|------|------|------|-------|------|
| Target | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Candida glabrata | Low<br>Positive | 48 | 31.33 | 0.88 | 2.81 | 0.73 | 2.34 | 0.36 | 1.15 | 1.20 | 3.83 |
| Candida krusei | Low<br>Positive | 48 | 28.87 | 0.32 | 1.11 | 0.16 | 0.56 | 0.17 | 0.58 | 0.40 | 1.37 |
| Candida albicans | Low<br>Positive | 48 | 28.24 | 0.25 | 0.90 | 0.09 | 0.33 | 0 | 0 | 0.27 | 0.96 |
| Candida albicans | Moderate<br>Positive | 48 | 27.26 | 0.26 | 0.95 | 0 | 0 | 0.17 | 0.62 | 0.31 | 1.14 |
| Trichomonas<br>vaginalis | Low<br>Positive | 48 | 32.64 | 0.46 | 1.42 | 0 | 0 | 0 | 0 | 0.46 | 1.42 |
| Trichomonas<br>vaginalis | Moderate<br>Positive | 48 | 31.63 | 0.24 | 0.76 | 0 | 0 | 0 | 0 | 0.24 | 0.76 |

## Reproducibility for BD COR™ System

The reproducibility of the BD Vaginal Panel on the BD COR™ System was confirmed to be equivalent to that of the BD MAX™ System using the same sample categories as defined above for the precision study (Table 4). To evaluate the site-to-site reproducibility, testing was performed at 3 sites (2 external and 1 internal) over 8 days. At each site, 2 operators performed 2 runs on alternate days, for a total of 48 runs. Reproducibility results are summarized in Table 8.

The qualitative and quantitative reproducibility results across sites and by target are presented in Table 9. Second Derivative Peak Abscissa (SDPA), an internal criterion used to determine a final assay result, was selected as a means of assessing quantitative assay reproducibility. Mean SDP A values with variance components (SD and % CV) for BD COR™ System are shown in Table 10 and Table 11.

{11}------------------------------------------------

| Target | Level | Test Site | N Total | N Correct | BD CORTM | | | BD MAXTM | | | |
|------------------------------|---------------------|-----------|---------|-----------|----------|------------|------------|-----------|-----------|------------|------------|
| | | | | | %Correct | 95% CI LCL | 95% CI UCL | N Correct | % Correct | 95% CI LCL | 95% CI UCL |
| | True Negativea | 1 | 192 | 192 | 100 | 98.0 | 100 | 192 | 100 | 98.0 | 100 |
| | | 2 | 192 | 192 | 100 | 98.0 | 100 | 192 | 100 | 98.0 | 100 |
| | | 3 | 192 | 192 | 100 | 98.0 | 100 | 192 | 100 | 98.0 | 100 |
| | | Overall | 576 | 576 | 100 | 99.3 | 100 | 576 | 100 | 99.3 | 100 |
| | BV Negativea | 1 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 2 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 3 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | Overall | 96 | 96 | 100 | 96.2 | 100 | 96 | 100 | 96.2 | 100 |
| Bacterial Vaginosis | BV High Negativeb,c | 1 | 32 | 25 | 78.1 | 61.2 | 89.0 | 13 | 40.6 | 25.5 | 57.7 |
| | | 2 | 32 | 17 | 53.1 | 36.4 | 69.1 | 29 | 90.6 | 75.8 | 96.8 |
| | | 3 | 32 | 28 | 87.5 | 71.9 | 95.0 | 30 | 93.8 | 79.9 | 98.3 |
| | | Overall | 96 | 70 | 72.9 | 63.3 | 80.8 | 72 | 75.0 | 65.5 | 82.6 |
| | Low Positived | 1 | 64 | 64 | 100 | 94.3 | 100 | 63 | 98.4 | 91.7 | 99.7 |
| | | 2 | 64 | 64 | 100 | 94.3 | 100 | 62 | 96.9 | 89.3 | 99.1 |
| | | 3 | 63 | 63 | 100 | 94.3 | 100 | 63 | 100 | 94.3 | 100 |
| | | Overall | 191 | 191 | 100 | 98.0 | 100 | 188 | 98.4 | 95.5 | 99.5 |
| | Moderate Positived | 1 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 2 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 3 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | Overall | 96 | 96 | 100 | 96.2 | 100 | 96 | 100 | 96.2 | 100 |
| Candida glabrata | True Negativea | 1 | 160 | 160 | 100 | 97.7 | 100 | 160 | 100 | 97.7 | 100 |
| | | 2 | 160 | 160 | 100 | 97.7 | 100 | 160 | 100 | 97.7 | 100 |
| | | 3 | 159 | 159 | 100 | 97.6 | 100 | 155 | 97.5 | 93.7 | 99.0 |
| | | Overall | 479 | 479 | 100 | 99.2 | 100 | 475 | 99.2 | 97.9 | 99.7 |
| | Low Positive | 1 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 2 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 3 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | Overall | 96 | 96 | 100 | 96.2 | 100 | 96 | 100 | 96.2 | 100 |
| Candida krusei | True Negativea | 1 | 160 | 160 | 100 | 97.7 | 100 | 160 | 100 | 97.7 | 100 |
| | | 2 | 160 | 160 | 100 | 97.7 | 100 | 160 | 100 | 97.7 | 100 |
| | | 3 | 159 | 159 | 100 | 97.6 | 100 | 159 | 100 | 97.6 | 100 |
| | | Overall | 479 | 479 | 100 | 99.2 | 100 | 479 | 100 | 99.2 | 100 |
| | Low Positive | 1 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 2 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 3 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | Overall | 96 | 96 | 100 | 96.2 | 100 | 96 | 100 | 96.2 | 100 |
| Candida albicans | True Negativea | 1 | 160 | 160 | 100 | 97.7 | 100 | 160 | 100 | 97.7 | 100 |
| | | 2 | 160 | 159 | 99.4 | 96.5 | 99.9 | 160 | 100 | 97.7 | 100 |
| | | 3 | 159 | 158 | 99.4 | 96.5 | 99.9 | 156 | 98.1 | 94.6 | 99.4 |
| | | Overall | 479 | 477 | 99.6 | 98.5 | 99.9 | 476 | 99.4 | 98.2 | 99.8 |
| | Low Positive | 1 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 2 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 3 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | Overall | 96 | 96 | 100 | 96.2 | 100 | 96 | 100 | 96.2 | 100 |
| Target | Level | Test Site | N Total | N Correct | BD CORTM | | | BD MAXTM | | | |
| | | | | | %Correct | 95% CI LCL | 95% CI UCL | N Correct | % Correct | 95% CI LCL | 95% CI UCL |
| | Moderate Positive | 2 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 3 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | Overall | 96 | 96 | 100 | 96.2 | 100 | 96 | 100 | 96.2 | 100 |
| | True Negativea | 1 | 160 | 160 | 100 | 97.7 | 100 | 160 | 100 | 97.7 | 100 |
| | | 2 | 160 | 160 | 100 | 97.7 | 100 | 160 | 100 | 97.7 | 100 |
| | | 3 | 159 | 159 | 100 | 97.6 | 100 | 159 | 100 | 97.6 | 100 |
| | | Overall | 479 | 479 | 100 | 99.2 | 100 | 479 | 100 | 99.2 | 100 |
| <i>Trichomonas vaginalis</i> | Low Positive | 1 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 2 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 3 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | Overall | 96 | 96 | 100 | 96.2 | 100 | 96 | 100 | 96.2 | 100 |
| | Moderate Positive | 1 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 2 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | 3 | 32 | 32 | 100 | 89.3 | 100 | 32 | 100 | 89.3 | 100 |
| | | Overall | 96 | 96 | 100 | 96.2 | 100 | 96 | 100 | 96.2 | 100 |

## Table 6: Qualitative Reproducibility by Target and Site for BD COR™ System and BD MAX™ System

CONFIDENTIAL AND PROPRIETARY

{12}------------------------------------------------

a For the True Negative and BV Negative levels, the reported agreement indicates the percent of negative results.

b For the BV High Negative category, the reported agreement indicates the percent of positive results.

© Performance includes results from replicates of a single panel member.

d Performance includes combined results from replicates of two panel members containing different organism compositions.

## Table 7: Quantitative Reproducibility Site-to-Site Summary by Vaginitis Target for BD COR™ System

| | | | | Within Run<br>(Residual) | | Between Run | | Between Day | | Between<br>Site | | | Total |
|---------------------|----------------------|----|-------|--------------------------|------|-------------|------|-------------|------|-----------------|------|------|-------|
| Target | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Candida<br>glabrata | Low Positive | 96 | 30.30 | 0.53 | 1.76 | 0 | 0 | 0 | 0 | 0.26 | 0.87 | 0.59 | 1.96 |
| Candida krusei | Low Positive | 96 | 28.93 | 0.20 | 0.71 | 0.07 | 0.23 | 0 | 0 | 0 | 0 | 0.22 | 0.74 |
| Candida | Low Positive | 96 | 26.69 | 0.38 | 1.44 | 0 | 0 | 0.16 | 0.59 | 0.07 | 0.25 | 0.42 | 1.57 |
| albicans | Moderate<br>Positive | 96 | 26.08 | 0.30 | 1.14 | 0.04 | 0.17 | 0.06 | 0.24 | 0.12 | 0.48 | 0.33 | 1.27 |
| Trichomonas | Low Positive | 96 | 32.85 | 0.38 | 1.17 | 0 | 0 | 0 | 0 | 0.15 | 0.45 | 0.41 | 1.25 |
| vaginalis | Moderate<br>Positive | 96 | 31.66 | 0.30 | 0.93 | 0 | 0 | 0.04 | 0.13 | 0 | 0 | 0.30 | 0.94 |

{13}------------------------------------------------

| | | | | Within Run<br>(Residual) | | Between Run | | Between Day | | Between<br>Site | | Total | |
|--------------------------|----------------------|----|-------|--------------------------|------|-------------|------|-------------|------|-----------------|------|-------|------|
| Target | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Candida<br>glabrata | Low Positive | 96 | 30.95 | 0.71 | 2.28 | 0 | 0 | 0.20 | 0.64 | 0.51 | 1.66 | 0.89 | 2.89 |
| Candida krusei | Low Positive | 96 | 29.09 | 0.42 | 1.44 | 0.15 | 0.53 | 0 | 0 | 0 | 0 | 0.45 | 1.54 |
| Candida albicans | Low Positive | 96 | 27.34 | 0.42 | 1.55 | 0.20 | 0.72 | 0 | 0 | 0 | 0 | 0.47 | 1.71 |
| | Moderate<br>Positive | 96 | 26.49 | 0.42 | 1.59 | 0 | 0 | 0.05 | 0.18 | 0 | 0 | 0.43 | 1.60 |
| Trichomonas<br>vaginalis | Low Positive | 96 | 32.73 | 0.46 | 1.40 | 0 | 0 | 0.21 | 0.65 | 0.24 | 0.73 | 0.56 | 1.71 |
| | Moderate<br>Positive | 96 | 31.69 | 0.42 | 1.31 | 0 | 0 | 0 | 0 | 0.08 | 0.25 | 0.42 | 1.34 |

Table 8: Quantitative Reproducibility Site-to-Site Summary by Vaginitis Target for BD MAX™ System

#### Quality Controls

External Control materials are not provided by BD; however, Quality Control procedures are included in the package insert. Various types of External Controls are recommended to allow the user to select the most appropriate for their laboratory quality control program:

- Commercially available positive control materials ●
- Trichomonas vaginalis (ATCC 30001) ●
- . Candida albicans (ATCC 10231)
- Candida glabrata (ATCC 2001) ●
- . Candida krusei (ATCC 6258)

The assay includes a Specimen 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.

#### Analytical Sensitivity Confirmation for BD COR™ System

The analytical sensitivity/Limit of Detection (LoD) of the BD Vaginal Panel on the BD COR™ System was confirmed to be equivalent to that of the BD MAX System with use of the BD Molecular Swab Collection Kit. The study design included using 20 panels of Vaginosis and/or Vaginitis targets at varying concentration levels created using the LoD previously determined on the BD MAX™ System at the target levels identified in Table 11. Samples were prepared by spiking of representative vaginosis target and/or vaginitis target in the presence of simulated vaginal matrix (SVM). Testing was conducted over more than 3 days using qualified BD Vaginal Panel reagents and included two BD COR™ PX/MX Systems and four BD MAX™ Systems.

A Two, One-Sided Test (TOST) of Equivalence was performed for the low positive (1.99x LoD) and moderate positive (5x LoD) target levels for each strain. The 90% confidence intervals for the difference in mean Ct.score between the BD COR™ System and BD MAX™ Systems were determine…