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 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.

AI/ML Overview

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

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

1. Table of Acceptance Criteria and Reported Device Performance

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

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

Analyte	Performance (with BD Molecular Swab Collection Kit vs. BD MAX UVE Specimen Collection Kit)
Bacterial Vaginosis	PPA point estimate: 96.9%
Candida species	PPA point estimate: 87.8%
Trichomonas vaginalis	PPA point estimate: 97.1%

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

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

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

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

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

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

4. Adjudication Method for the Test Set

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

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

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

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

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

7. The Type of Ground Truth Used

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

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

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

8. The Sample Size for the Training Set

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

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

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

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

GeneOhm Sciences Canada, Inc. (BD Life Sciences) Susan Werner Director, Regulatory Affairs 2555 Boul. Du Parc-Technologique Quebec, QC G1P4S5 Canada

October 18, 2021

Re: K201017

Trade/Device Name: BD MAX Vaginal Panel, BD MAX System 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 Dated: April 16, 2020 Received: April 17, 2020

Dear Susan Werner:

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

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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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Kristian Roth, Ph.D. Deputy Director, Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug AdministrationIndications for Use	Form Approved: OMB No. 0910-0120Expiration Date: 06/30/2020See PRA Statement below.
510(k) Number (if known)

. 510(k) Number (if known)

Device Name BD MAX™ Vaginal Panel

Indications for Use (Describe)

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 targetspecific 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.

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

Prescription Use (Part 21 CFR 801 Subpart D)
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.

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510(k) Summary

BD MAX™ Vaginal Panel

Summary Preparation Date:

10/18/2021

Submitted by:

BD Life Sciences Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152

Contact:

Katie Edwards Regulatory Affairs Project Manager

Tel: 410-316-4975 Email: Katie Edwards@bd.com

Proprietary Names:

For the instrument: BD MAX™ System

For the assay: BD MAX™ Vaginal Panel

Common Names:

For the instrument: Bench-top molecular diagnostics workstation

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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):

POA Vaginitis and Bacterial Vaginosis Nucleic Acid Detection System
OUY Trichomonas vaginalis Nucleic Acid Amplification Test System
OOI Real Time Nucleic Acid Amplification System
NSU Instrumentation for Clinical Multiplex Test Systems

Predicate Device

BD MAX Vaginal Panel (DEN160001 and K191957)

Performance Standards

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

Intended Use

· 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

Special Conditions for Use Statement: For Prescription Use Only

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

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Device Descrintion

Test Principle

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 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.

Substantial Equivalence

Table 1 provides the similarities and differences between the submitted device and the legally marketed predicate device.

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Items	BD MAX Vaginal Panel(Submitted Device)	BD MAX Vaginal Panel(DEN160001)
Intended Use	The BD MAX Vaginal Panel performed on the BD MAX System isan automated qualitative in vitro diagnostic test for the directdetection of DNA targets from bacteria associated with bacterialvaginosis (qualitative results reported based on detection andquantitation of targeted organism markers), Candida speciesassociated with vulvovaginal candidiasis, and Trichomonasvaginalis from vaginal swabs in patients who are symptomatic forvaginitis/vaginosis. The test utilizes real-time polymerase chainreaction (PCR) for the amplification of specific DNA targets andutilizes fluorogenic target-specific hybridization probes to detectand 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 vaginalisThe BD MAX Vaginal Panel is intended to aid in the diagnosis ofvaginal infections in women with a clinical presentation consistentwith bacterial vaginosis, vulvovaginal candidiasis andtrichomoniasis.
Specimen Type	Clinician and patient-collected female vaginal swab
Collection / Transport Device	BD Molecular Swab CollectionKit	BD MAX UVE SpecimenCollection Kit
Same Buffer Formulation	Potassium phosphate, EDTA, Tween 20 and Proclin buffer
Sample Buffer Volume	2.0 mL	1.5 mL
Swab Type	Polyester
Sterilization Method	Irradiation
Bud Size	0.156 in	0.125 in
Fiber Composition	Polyester
Shaft Composition	Polystyrene

Table 1: Comparison to Predicate Device

Performance Evaluation:

Three studies were conducted to demonstrate the substantial equivalence between the BD Molecular Swab Collection Kit (previously cleared for use with the BD MAX Vaginal Panel) and the BD MAX UVE Specimen Collection Kit:

Confirmation of equivalent analytical sensitivity with the BD Molecular Swab Collection Kit . by the limiting dilution LoD model. Limiting dilutions of specimens tested using the BD MAX UVE Specimen Collection Kit and the BD Molecular Swab Collection Kit exhibited drop-out rates at similar levels when tested using the BD MAX Vaginal Panel on the BD

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MAX System. There was no indication that the new collection device negatively impacted the analytical sensitivity of the BD MAX Vaginal Panel.

. Comparison study of performance between the cleared collection device and the new collection device tested with the BD MAX Vaginal Panel on the BD MAX System with clinical specimens demonstrated PPA point estimates 96.9%, 87.8%, and 97.1% for bacterial vaginosis, Candida species and Trichomonas vaginalis, respectively. Further statistical analysis of the PCR metrics demonstrated that specimens collected with the BD Molecular Swab Collection Kit are not significantly different from specimens collected using the BD MAX UVE Specimen Collection Kit as the two collection kits demonstrate similar performance when used for collection of vaginal specimens that are then tested with the BD MAX Vaginal Panel.
A stability study was carried out in accordance with a predefined protocol for both Bacterial ● Vaginosis and Vaginitis, using the BD Max Vaginal Panel Assay and BD Molecular Swab Collection Kit. This study demonstrated the stability of Bacterial Vaginosis and Vaginitis targets stored in BD Molecular Swab Sample Buffer Tube (non-pierced) - Up to 21 days at 2-30°C and in BD Molecular Swab Sample Buffer Tube(after the cap is pierced)- Up to 4 days at 2-30°C.

Conclusion

The studies conducted support that the modified device, BD MAX Vaginal Panel on the BD MAX System is substantially equivalent to the predicate device.

Regulation Number and Section

§ 866.3975 Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis.

(a)
Identification. A device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis is a qualitative in vitro diagnostic device intended for the detection of microbial nucleic acid sequences in vaginal specimens collected from patients with signs and symptoms of vaginitis or bacterial vaginosis. This device is intended to aid in the diagnosis of vaginitis or bacterial vaginosis when used in conjunction with clinical signs and symptoms and other laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) Documentation with a detailed device description of device components; ancillary reagents required but not provided; and explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
(ii) Documentation with information that demonstrates the performance characteristics of the device, including:
(A) Limit of Detection;
(B) Precision (reproductivity);
(C) Analytical specificity;
(D) Analytical reactivity (inclusivity);
(E) Specimen stability; and
(F) Effects of interfering substances.
(iii) Detailed documentation from a prospective clinical study. As appropriate to the intended use, the prospective clinical study must be performed on an appropriate study population, including women of various ages and ethnicities. The prospective clinical study must compare the device performance to results obtained from well-accepted comparator methods.
(iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed explanation of the interpretation of results and acceptance criteria;
(ii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, clinical performance stratified by patient demographics such as race, ethnicity, age, and pregnancy status.
(iii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, a summary of device results in an asymptomatic population with demographic characteristics appropriate to the intended use population.
(iv) For devices with an intended use that includes detection of either Candida species or bacteria associated with bacterial vaginosis, a limitation that
Candida species and bacterial compositions associated with bacterial vaginosis can be present as part of normal vaginal flora and results should be considered in conjunction with available clinical information.