BD MAX Vaginal Panel, BD MAX Instrument

• K Number: DEN160001
• Device Name: BD MAX Vaginal Panel, BD MAX Instrument
• Manufacturer: GENEOHM SCIENCES CANADA , INC (BD DIAGNOSTICS)
• Date Cleared: 2016-10-28 ( 291 days)
• Product Code: PQA
• Regulation Number: 866.3975

Intended 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) - O Lactobacillus spp. (L. crispatus and L. jensenii) - Gardnerella vaginalis о - o Atopobium vaginae - Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) o - o 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.

Predicate Devices

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Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on real-time PCR technology and automated interpretation based on amplification status, with no mention of AI or ML.

Therapeutic

No

The device is an in vitro diagnostic test designed to detect DNA targets from bacteria, Candida species, and Trichomonas vaginalis to aid in the diagnosis of vaginal infections, not to treat them.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the BD MAX Vaginal Panel is an "in vitro diagnostic test" and "is intended to aid in the diagnosis of vaginal infections." The document also describes its use in detecting DNA targets from bacteria, Candida species, and Trichomonas vaginalis from vaginal swabs to provide qualitative results for conditions such as bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis.

SaMD (Software as a Medical Device)

No

The device description explicitly states that 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, in addition to the software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "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...".

This statement clearly identifies the device as an in vitro diagnostic test.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

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)
  • O Lactobacillus spp. (L. crispatus and L. jensenii)
  • Gardnerella vaginalis о
  • o Atopobium vaginae
  • Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) o
  • o 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.

Product codes (comma separated list FDA assigned to the subject device)

POA OUY OOI NSU

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Vaginal

Indicated Patient Age Range

Adult female subjects (18 years and over).

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Description of the test set for the clinical study:
A total of 1763 subjects were enrolled in the prospective clinical study, of which 1740 subjects were compliant and 23 were non-compliant.
For clinician-collected specimens, the numbers of compliant specimens with reportable reference method and BD MAX Vaginal Panel results were 1559 for bacterial vaginosis, 1618 for Candida and 1600 for Trichomonas vaginalis.
For self-collected specimens, the numbers of compliant specimens with reportable reference method and BD MAX Vaginal Panel results were 1582 for bacterial vaginosis, 1628 for Candida and 1610 for Trichomonas vaginalis.

Data source: Specimens were collected from 10 geographically diverse specimen collection sites. Seven sites performed specimen collection only and three sites performed both specimen collection and testing. For consented adult female subjects presenting with symptoms of vaginitis or bacterial vaginosis, one self-collected and one clinician-collected vaginal swab were collected using the BD MAX UVE Specimen Collection Kit and tested independently with the BD MAX Vaginal Panel. Three additional vaginal swabs were collected for reference method testing.

Annotation protocol:
BV status was determined using a combination of Nugent Score and Amsel's criteria. Specimens with normal flora as per the Nugent Score were considered negative: those positive for BV flora were considered positive while those with intermediate BV flora were segregated into positive or negative categories using Amsel's criteria. Samples positive for 2 out of the 3 following criteria were considered Amsel's positive: vaginal pH > 4.5, presence of clue cells and positive Whiff test.
Candida spp. status was determined by selective (Candida) chromogenic medium and Sabouraud Dextrose Emmons plate cultures. PCR amplification targeting the its2 gene was performed followed by bi-directional sequencing to identify all yeast isolates recovered by culture.
Trichomonas vaginalis status was determined by a composite of microscopic visualization of motile trichomonads in saline wet mounts of vaginal secretion and by culture. A positive result either by wet mount or by culture was sufficient to categorize the patient as positive for Trichomonas vaginalis.

Description of the test set for the contrived Candida glabrata and Candida krusei studies:
Contrived specimens were prepared by spiking 50 different Candida glabrata strains into individual negative vaginal matrices. True negative specimens, containing vaginal matrix only, were interspersed with positive specimens and all specimen identities were blinded to the user. Strains were spiked at various clinically relevant organism concentrations.
Contrived specimens were prepared by spiking 50 different Candida krusei strains into individual negative vaginal matrices. True negative specimens, containing vaginal matrix only, were interspersed with positive specimens and all specimen identities were blinded to the user. Strains were spiked at various clinically relevant organism concentrations.

Data source for contrived studies: Randomly distributed among three clinical testing sites for BD MAX Vaginal Panel testing.
Annotation protocol for contrived studies: Not explicitly stated, inferred to be based on the known concentrations of spiked organisms.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Study Type: Precision Study
Sample Size:

• True Negative: 288 (Bacterial Vaginosis), 240 (Trichomonas vaginalis), 240 (Candida albicans), 240 (Candida glabrata), 240 (Candida krusei)
• Low Positive: 287 (Bacterial Vaginosis), 48 (Trichomonas vaginalis), 48 (Candida albicans), 48 (Candida glabrata), 48 (Candida krusei)
• Moderate Positive: 192 (Bacterial Vaginosis), 48 (Trichomonas vaginalis), 48 (Candida albicans)
• High BV Negative: 192 (Bacterial Vaginosis)
• BV Negative: 48 (Bacterial Vaginosis)
  Standalone Performance: Not applicable (analytical study)
  Key Results:
• Bacterial Vaginosis: True Negative 100.0% (288/288), Low Positive 100.0% (287/287), Moderate Positive 100.0% (192/192), High BV Negative 37.5% (72/192), BV Negative 100.0% (48/48).
• Trichomonas vaginalis: True Negative 100.0% (240/240), Low Positive 100.0% (48/48), Moderate Positive 100.0% (48/48).
• Candida albicans: True Negative 99.6% (239/240), Low Positive 100.0% (48/48), Moderate Positive 100.0% (48/48).
• Candida glabrata: True Negative 100.0% (240/240), Low Positive 100.0% (48/48).
• Candida krusei: True Negative 100.0% (240/240), Low Positive 100.0% (48/48).

Study Type: Reproducibility Study (Multi-site)
Sample Size:

• True Negative: 576 (Bacterial Vaginosis), 480 (Trichomonas vaginalis), 480 (Candida albicans), 480 (Candida glabrata), 480 (Candida krusei)
• Low Positive: 192 (Bacterial Vaginosis), 96 (Trichomonas vaginalis), 96 (Candida albicans), 96 (Candida glabrata), 96 (Candida krusei)
• Moderate Positive: 192 (Bacterial Vaginosis), 96 (Trichomonas vaginalis), 96 (Candida albicans)
• BV Negative: 96 (Bacterial Vaginosis)
  Standalone Performance: Not applicable (analytical study)
  Key Results: Overall Site-to-Site Reproducibility percent agreement for panel member results ranged from 98.5% to 100% for true negatives, 99.0% to 100% for low positive samples, and 99.5% to 100% for moderate positive samples.
• Bacterial Vaginosis: True Negative 100.0% (576/576), Low Positive 99.0% (190/192), Moderate Positive 99.5% (191/192), BV Negative 100.0% (96/96).
• Trichomonas vaginalis: True Negative 100.0% (480/480), Low Positive 100.0% (96/96), Moderate Positive 100.0% (96/96).
• Candida albicans: True Negative 98.5% (473/480), Low Positive 100.0% (96/96), Moderate Positive 100.0% (96/96).
• Candida glabrata: True Negative 100.0% (480/480), Low Positive 100.0% (96/96).
• Candida krusei: True Negative 99.6% (478/480), Low Positive 100.0% (96/96).

Study Type: Reproducibility Study (Lot-to-Lot)
Sample Size:

• True Negative: 576 (Bacterial Vaginosis), 480 (Trichomonas vaginalis), 480 (Candida albicans), 480 (Candida glabrata), 480 (Candida krusei)
• Low Positive: 192 (Bacterial Vaginosis), 96 (Trichomonas vaginalis), 96 (Candida albicans), 96 (Candida glabrata), 96 (Candida krusei)
• Moderate Positive: 192 (Bacterial Vaginosis), 96 (Trichomonas vaginalis), 96 (Candida albicans)
• BV Negative: 96 (Bacterial Vaginosis)
  Standalone Performance: Not applicable (analytical study)
  Key Results:
• Bacterial Vaginosis: True Negative 100.0% (576/576), Low Positive 100.0% (192/192), Moderate Positive 100.0% (192/192), BV Negative 100.0% (96/96).
• Trichomonas vaginalis: True Negative 100.0% (480/480), Low Positive 100.0% (96/96), Moderate Positive 100.0% (96/96).
• Candida albicans: True Negative 99.2% (476/480), Low Positive 100.0% (96/96), Moderate Positive 100.0% (96/96).
• Candida glabrata: True Negative 100.0% (480/480), Low Positive 100.0% (96/96).
• Candida krusei: True Negative 99.8% (479/480), Low Positive 100.0% (96/96).

Study Type: Clinical Study (Prospective)
Sample Size: 1763 subjects enrolled, 1740 compliant.

• Clinician-collected, compliant with reportable results: 1559 for BV, 1618 for Candida, 1600 for T. vaginalis.
• Self-collected, compliant with reportable results: 1582 for BV, 1628 for Candida, 1610 for T. vaginalis.
  Standalone Performance: Presented as Sensitivity, Specificity, PPV, NPV.
  Key Results:
  BV Performance:
• Clinician-collected: Sensitivity 90.5% (797/881), Specificity 85.8% (582/678), PPV 89.0%, NPV 87.7%. Prevalence: 55.8%.
• Self-collected: Sensitivity 90.7% (803/885), Specificity 84.5% (589/697), PPV 88.1%, NPV 87.8%. Prevalence: 55.8%.
  Cgroup Performance: (Candida albicans, Candida tropicalis, Candida parapsilosis and/or Candida dubliniensis)
• Clinician-collected: Sensitivity 90.9% (462/508), Specificity 94.1% (1045/1110), PPV 87.8%, NPV 95.7%. Prevalence: 31.6%.
• Self-collected: Sensitivity 92.2% (470/510), Specificity 91.9% (1028/1118), PPV 84.1%, NPV 96.2%. Prevalence: 31.6%.
  Candida glabrata Performance:
• Clinician-collected: Sensitivity 75.9% (22/29), Specificity 99.7% (1584/1589), PPV 81.6%, NPV 99.6%. Prevalence: 1.8%.
• Self-collected: Sensitivity 86.7% (26/30), Specificity 99.6% (1592/1598), PPV 81.0%, NPV 99.8%. Prevalence: 1.8%.
  Candida krusei Performance:
• Clinician-collected: Sensitivity No data, Specificity 99.8% (1614/1618).
• Self-collected: Sensitivity No data, Specificity 100.0% (1628/1628).
  Trichomonas vaginalis Performance:
• Clinician-collected: Sensitivity 93.1% (121/130), Specificity 99.3% (1459/1470), PPV 91.8%, NPV 99.4%. Prevalence: 8.2%.
• Self-collected: Sensitivity 93.2% (124/133), Specificity 99.3% (1475/1487), PPV 91.8%, NPV 99.4%. Prevalence: 8.2%.

Study Type: Contrived Specimen Study (Candida glabrata)
Sample Size: 50 different C. glabrata strains + 50 true negative specimens. Total 100.
Standalone Performance: Not applicable (analytical study)
Key Results: 100% positive agreement for all contrived positive specimens evaluated.

• High Positive (>=10 and =2 and =1 and =10 and =2 and =1 and

Regulation Number and Section

N/A

Summary

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EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR BD MAX Vaginal Panel

DECISION SUMMARY

A. DEN Number:

DEN160001

B. Purpose for Submission:

De Novo request for evaluation of automatic class III designation for the BD MAX Vaginal Panel

C. Measurands:

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

• Bacterial vaginosis (BV) markers (Results for individual organisms are not reported. . Qualitative BV results are based on detection and quantitation of targeted organisms)
  • Lactobacillus spp (L. crispatus and L. jensenii) O
  • Gardnerella vaginalis O
  • O Atopobium vaginae
  • Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) O
  • Megasphaera-1 o
• Candida spp. (Reported as Cgroup: includes C. albicans, C. tropicalis, C. parapsilosis, ● C. dubliniensis)
• Candida glabrata ●
• Candida krusei
• Trichomonas vaginalis ●

D. Type of Test:

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

E. Applicant:

GeneOhm Sciences Canada, Inc. (BD Diagnostics)

F. Proprietary and Established Names:

BD MAX™ Vaginal Panel

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BD MAX™ (Instrument)

G. Regulatory Information:

• 1. Regulation section:
     21 CFR 866.3975. Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis.
• 2. Classification:
     Class II (Special Controls)
• 3. Product code(s): POA OUY OOI NSU
• 4. Panel:

83 - Microbiology

H. Indications for Use:

• 1. 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)

  • O Lactobacillus spp. (L. crispatus and L. jensenii)
  • Gardnerella vaginalis о
  • o Atopobium vaginae
  • Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) o
  • o 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.

• 3. Special conditions for use statement(s):
     For Prescription Use Only

4. Special instrument requirements:

The BD MAX Vaginal Panel is performed on the BD MAX System.

I. 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.

J. Standard/Guidance Document Referenced:

• CLSI EP 17-A2, Evaluation of Detection Capability for Clinical Laboratory . Measurement Procedures, 2012
• CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement ● Methods, Approved Guideline, 2004
• CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance, 2008 ●

K. Test Principle:

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

A combination of lytic and extraction reagents are used to perform cell lysis and DNA extraction. Nucleic acids released from the target organisms are captured on magnetic affinity beads. The beads, together with the bound nucleic acids, are washed and the nucleic acids are eluted by a combination of heat and pH. Eluted DNA is neutralized and transferred

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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. 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.

L. Performance Characteristics:

• 1. Analytical Performance:
• a. Precision/Reproducibility Studies

Reproducibility/Precision Study Panel Member Composition

For the precision and reproducibility studies, panel members were prepared with targeted organisms (or plasmid DNA for Megasphaera-1 and BVAB-2) spiked into simulated vaginal matrix. Table 1 describes organisms that were used to prepare panel members.

MasterMix	Assay Target	Organism
Vaginosis	BV Markers	Lactobacillus crispatus
		Lactobacillus jensenii
		Gardnerella vaginalis
		Atopobium vaginae
		Megasphaera type 1
		BVAB-2
Vaginitis	Cgroup	Candida albicans
	Ckru	Candida krusei
	Cgla	Candida glabrata
	TV	Trichomonas vaginalis

Table 1: Organisms for Reproducibility/Precision Study Panel Members

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For Cgroup (Candida albicans). C. glabrata and C. krusei panel members, samples were spiked at high negative, low positive and moderate positive concentrations based on the assay Limit of Detection (LoD).

For BV panel members, sample compositions were designed to represent the flora of BV positive and negative specimens with specific target organism combinations based on results from clinical specimen testing. Because a variety of targeted BV organism combinations can be present in vaginal specimens, multiple panel members for each level were prepared with different targeted organism compositions at varying loads. Each BV negative panel member was spiked with two target organisms. Each BV low positive and moderate positive panel member was prepared with three or more target organisms. Sample compositions were determined based on assay cutoffs for positive and negative BV results.

The design for study panel members is described in Table 2.

| Concentration
Designation | Bacterial Vaginosis1
(% of positive results expected at the
designated concentration) | Candida spp. and Trichomonas
vaginalis
(x LoD) |
|------------------------------|---------------------------------------------------------------------------------------------|------------------------------------------------------|
| Moderate Positive | ~100 | $\ge$ 2 to $\le$ 5 |
| Low Positive | ~95 | 95% of replicates are detected).

To further confirm the LoD for vaginitis analytes, a total of 24 sample replicates were each tested at the LoD in both simulated and natural vaginal matrix. Because natural vaginal matrix contains BV analytes as part of the normal vaginal flora, confirmation of the LoD for BV analytes was performed only in simulated matrix.

Table 12 lists the confirmed LoD for organisms strains evaluated in the study.

| Assay
Target | Organism | Strain
ATCC# | LoD | |
|-----------------------------------|-------------------------|-----------------|---------------|-----------|
| | | | Concentration | Units |
| Vaginitis | Candida albicans | 18804 | 17787 | CFU/mL |
| | Candida glabrata | 2001 | 202 | CFU/mL |
| | Candida krusei | 6258 | 1035 | CFU/mL |
| | Candida dubliniensis | MYA-646 | 4002 | CFU/mL |
| | Candida tropicalis | 750 | 313 | CFU/mL |
| | Candida parapsilosis | 22019 | 30660 | CFU/mL |
| | Trichomonas vaginalis | 30001 | 22 | Cells/mL |
| Bacterial
Vaginosis
Markers | Atopobium vaginae | BAA-55 | 127 | CFU/mL |
| | Gardnerella vaginalis | 14018 | 962 | CFU/mL |
| | Lactobacillus crispatus | 33820 | 55 | CFU/mL |
| | Lactobacillus jensenii | 25258 | 510 | CFU/mL |
| | Megasphaera-1 | NAᵃ | 2265 | Copies/mL |
| | BVAB 2 | | 464 | Copies/mL |

a LoD determined with plasmid DNA.

e. Analytical Inclusivity:

An analytical inclusivity study was conducted to evaluate the BD MAX Vaginal Panel for detection of a variety of organism strains, taking into account phylogenetic diversity, geographic origin and temporal diversity. The microbial strains evaluated were from public collections or well-characterized clinical isolates. Testing included five strains each for targeted Candida species (C. albicans, C. dubliniensis, C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei) and nine strains of Trichomonas vaginalis (including one metronidazole resistant strain). In addition, ten strains of Gardnerella vaginalis and five strains each of Atopobium vaginae, Lactobacillus crispatus, and Lactobacillus iensenii were evaluated. Samples were inoculated at 10° PFU/mL or TCID50/mL or equivalent amount of RNA/DNA per PCR reaction. In total, 118 organisms were evaluated and those organisms are listed in Table 14 below.

For organisms that generated unexpected positive results, additional testing was performed to evaluate the organism load that no longer cross-reacts with the BD MAX Vaginal Panel. Table 13 describes organisms that demonstrated cross-reactivity and the concentrations at which detection was observed. A limitation is included in the package insert describing all cross-reactive organisms.

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| Cross Reacting Organism | BD MAX Vaginal
Panel Target | Additional Testing |
|--------------------------------------------|--------------------------------|------------------------------------------|
| Candida guillermondii1 | Cgroup | Not detected at delbrueckii subsp.
lactis | | thermophilus |
| Alcaligenes | faecalis (subsp.
faecalis) | | fornicalis | Treponema | pallidum |
| Anaerococcus | tetradius | | gasseri | Veillonella | atypica |
| | minutum | | iners | | parvula |
| Atopobium | parvulum | | johnsonii | Vibrio | parahaemolyticus |
| | rimae | | pontis | Yersinia | enterocolitica |
| Bacillus | subtilis | | sharpeae | YEASTS | |
| | caccae | | vaginalis | | catenulata |
| Bacteroides | fragilis | Legionella | pneumophila subsp.
pneumophila | | famata |
| | stercoris | Listeria | monocytogenes | | guilliermondii |
| Bifidobacterium | adolescentis | Megasphaera-2 | Megasphaera Type-2 | | haemulonii |
| | breve | Mobiluncus | curtisii | Candida | inconspicua |
| | coryneforme | | mulieris | | intermedia |
| | longum | Moraxella | catarrhalis | | kefyr |
| | minimum | Morganella | morganii subsp.
morganii | | lusitaniae |
| Brevibacterium | linens | Mycobacterium | smegmatis | | norvegica |
| Burkholderia | cepacia | Mycoplasma | genitalium | | orthopsilosis |
| Campylobacter | jejuni | | hominis | | rugosa |

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Chlamydia	trachomatis	Neisseria	gonorrhoeae		utilis
Citrobacter	freundii	Olsenella	uli	Issatchenkia	occidentalis2
Clostridium	perfringens	Pantoea	agglomerans	Kodamaea	ohmeri1
Corynebacterium	genitalium	Peptostreptococcus	anaerobius	Pichia	fermentans
Dialister	microaerophilus	Plesiomonas	shigelloides		norvegensis3
Eikenella	corrodens	Porphyromonas	asaccharolytica	Saccharomyces	cerevisiae
Enterobacter	aerogenes		melaninogenica		VIRUSES
Enterococcus	faecalis	Prevotella	oris	HBV	Human
herpesvirus 2
	faecium	Propionibacterium	acnes	HIV	HPV
Erysipelothrix	rhusiopathiae	Proteus	mirabilis	HSV type 1	Varicella-zoster
Escherichia	coli GC10
coli top 10	Providencia	stuartii	Hepatitis C Virus	virus Ellen
Fusobacterium	nucleatum subsp.
nucleatum	Salmonella	aeruginosa	PARASITES
Gemella	haemolysans	Serratia	typhimurium	Pentatrichomonas	hominis
Kingella	denitrificans	Shigella	marcescens	Trichomonas	tenax
Klebsiella	pneumoniae	Staphylococcus	flexneri

1 Also reported as Pichia ohmeri, C. guilliermondii

2 Also reported as C. sorbosa

3 Also reported as C. norvegensis

The following additional unexpected detections were observed in the study. Repeat testing indicated that these organisms do not cross-react with the BD MAX Vaginal Panel targets.

• A single replicate each containing Lactobacillus delbrueckii subsp. lactis or Chlamydia trachomatis initially generated a false positive result for Cgroup. Repeat testing generated 10/10 expected negative results for Cgroup for both of these organisms
• A single replicate each containing Bifidobacterium breve, E. coli GC10 or . Lactobacillus acetotolerans initially generated a false positive result for the A. vaginae signal. Repeat testing generated 10/10 expected negative results for A. vaginae for these three organisms

h. Evaluation of Potentially Interfering Substances/Organisms

A study was performed to evaluate potentially interfering biological and chemical substances that may be present in vaginal specimens. Exogenous (e.g., prescription and Over-the-Counter drugs, creams and/or gels) and endogenous (e.g., blood, hormones, mucus) substances were evaluated in samples spiked with the highest concentration expected to be present in vaginal specimens. Each potentially interfering substance was evaluated in both negative and low positive samples for targeted vaginitis analytes were spiked with low concentrations (12.5 µL/mL (1.25% V/V). Zovirax Acyclovir 5 % Cream and VCF Contraceptive Foam were found to interfere at levels above > 3.1 uL/mL. Preparation H Hemorrhoidal

16

Cream was found to interfere above > 0.8 uL/mL. Interference with the following substances was observed at all tested levels: Conceptrol Vaginal Contraceptive Gel, Clotrimazole Vaginal Cream, Monistat 3 Cream, Vagisil Cream, Replens Vaginal Moisturizing Gel, Metronidazole, Leukocytes. Table 15 shows results for the potentially interfering substances evaluated in the study. Substances that demonstrated interference may result in unresolved, indeterminate or false negative results. A limitation is included in the package insert listing all substances that demonstrated interference with the BD MAX Vaginal Panel.

No Interference Observed		Interference Observed
	Substance	Substance	Level Below Which No
Interference Observed
(µL/mL)
Exogenous	Tioconzole Ointment, 6.5%	VCF Contraceptive Foam	≤ 3.1
	VCF Contraceptive Film	Zovirax, Acyclovir 5% Cream	≤ 3.1
	Summer's Eve Douche	Preparation H Hemorrhoidal Cream	≤ 0.8
	FDS Feminine Deodorant
Spray	KY Jelly Personal Lubricant	≤ 12.5
	Progesterone	Conceptrol Vaginal Contraceptive Gel	Interference observed at
each level evaluated
	Estradiol	Clotrimazole Vaginal Cream, USP 2%
Monistat 3 Cream, Miconazole Nitrate, 4%
Vagisil, Benzocaine 20%, Resorcinol 3%
Replens Vaginal Moisturizing Gel
Metronidazole 0.75% Gel
Endogenous	Mucus (Bovine Cervical,
5% v/v)	Whole Blood
	Semen (5% v/v)	Leukocytes

Table 15: Exogenous and Endogenous Substances Tested for Interference®

" In total, with the BD MAX Vaginal Panel in the presence of potentially interfering substances, 2672 samples were tested for vaginosis targets and 3252 for vaginitis targets. For vaginitis targets, rates of 8.27% INR results were recorded. For BV, rates of 9.92% IND and 1.83% UNR results were recorded.

Additional testing was performed to evaluate potential interference from microorganisms included in probiotic formulations. A total of 14 probiotic Lactobacillus species listed in Table 17 were evaluated at high concentrations (> 6.7 x 10 CFU/mL of Sample Buffer) in combination with low positive vaginitis analytes, low positive BV samples as well as negative samples containing no targeted analytes.

Interference was not observed for detection of Candida albicans, Candida glabrata, Candida krusei, or Trichomonas vaginalis in samples spiked with each of the probiotic organisms. False negative results for BV were observed in the presence of the following probiotic organisms: Lactobacillus amvlovorus. Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus kefirgranum and Lactobacillus helveticus. The probiotic organisms evaluated are shown in Table 16.

17

No Interference Observed		Interference Observed
Lactobacillus plantarum	Lactobacillus casei	Lactobacillus delbrueckii subsp.
bulgaricus
Lactobacillus reuteri	Lactobacillus fermentum	Lactobacillus amylovorus
Lactobacillus rhamnosus	Lactobacillus paracasei	Lactobacillus helveticus
Lactobacillus salivarius subsp.
salivarius	Bifidobacterium animalis subsp
lactis	Lactobacillus kefirgranum
Lactobacillus brevis	Bifidobacterium longum subsp
infantis

Table 16: Interference Testing: Probiotic Microorganisms

i. Matrix Equivalence Study

Because the BV analytes detected by the BD MAX Vaginal Panel are present in normal vaginal flora, it was necessary to use a simulated vaginal matrix for preparation of samples for some analytical studies. Equivalence between the simulated matrix and natural vaginal matrices was assessed using data generated in the LoD confirmation study for Candida spp. and T. vaginalis. In this study, LoD values initially determined using samples prepared in simulated vaginal matrix were confirmed in the presence of both simulated and real vaginal matrices. A minimum of 24 sample replicates for each organism evaluated (six different Candida species and one T. vaginalis strain) were tested in both simulated and real vaginal matrices, at the LoD (95% concentration) previously determined in in simulated matrix. All targets evaluated generated 100% positive results in both matrices except for C. krusei which generated only 79.2% positive results for samples prepared in natural vaginal matrix.

To further evaluate differences for detection of C. krusei in natural and simulated matrices, higher concentrations were tested in natural matrix, resulting in 91.6% of positive results obtained at 1.99x and 2.5x LoD. These study results together with C. krusei results from contrived clinical specimens prepared in natural vaginal matrices (i.e., 50/50 specimens with C. krusei at 1.99x LoD generated positive results) demonstrated that the assay LoD for C. krusei in natural matrix was ~1.99 x the LoD for this target in simulated matrix.

In summary, the matrix equivalency study results substantiated equivalence between the simulated vaginal matrix and natural vaginal matrices for all analytes evaluated with the exception of C. krusei, which demonstrates a higher LoD in natural matrix. This difference was deemed to be acceptable because analytical study samples for C. krusei were prepared with concentrations based on the applicable LoD for the matrix used.

j. Assay Cut-off

Assay cut-offs for the BD MAX Vaginal Panel were initially determined in pre-clinical studies. Data collected in the multi-site prospective clinical study was subsequently used to validate these cut-offs. For this validation, PCR metrics from vaginitis analytes and results generated by the BV call algorithm were graphically and statistically analyzed in comparison to results from applicable reference methods. ROC curve analysis was

18

performed to confirm the optimal cutoffs for each vaginitis analyte as well for the cutoffs used to determine results for bacterial vaginosis.

• 2. Clinical Studies:
     Clinical performance characteristics for the BD MAX Vaginal Panel were evaluated in a prospective clinical study performed at 10 geographically diverse specimen collection sites. Of the 10 collection sites seven sites performed specimen collection only and three sites performed both specimen collection as well as testing with the BD MAX Vaginal Panel.

For consented adult female subjects presenting with symptoms of vaginitis or bacterial vaginosis, one self-collected and one clinician-collected vaginal swab were collected using the BD MAX UVE Specimen Collection Kit and tested independently with the BD MAX Vaginal Panel. Three additional vaginal swabs were collected for reference method testing.

The following reference methods were performed for each patient:

• . BV status was determined using a combination of Nugent Score and Amsel's criteria. Specimens with normal flora as per the Nugent Score were considered negative: those positive for BV flora were considered positive while those with intermediate BV flora were segregated into positive or negative categories using Amsel's criteria. Samples positive for 2 out of the 3 following criteria were considered Amsel's positive: vaginal pH > 4.5, presence of clue cells and positive Whiff test.
• . Candida spp. status was determined by selective (Candida) chromogenic medium and Sabouraud Dextrose Emmons plate cultures. PCR amplification targeting the its2 gene was performed followed by bi-directional sequencing to identify all yeast isolates recovered by culture.
• . Trichomonas vaginalis status was determined by a composite of microscopic visualization of motile trichomonads in saline wet mounts of vaginal secretion and by culture. A positive result either by wet mount or by culture was sufficient to categorize the patient as positive for Trichomonas vaginalis.

A total of 1763 subjects were enrolled in the prospective clinical study. Of those, 1740 subjects were compliant and 23 were found non-compliant as per protocol criteria. For clinician-collected specimens, the numbers of compliant specimens with reportable reference method and BD MAX Vaginal Panel results were 1559 for bacterial vaginosis, 1618 for Candida and 1600 for Trichomonas vaginalis. For self-collected specimens, the numbers of compliant specimens with reportable reference method and BD MAX Vaginal Panel results were 1582 for bacterial vaginosis, 1628 for Candida and 1610 for Trichomonas vaginalis.

BV Performance

Table 17 includes overall and per site performance for reporting of BV as observed in the prospective clinical study. The sensitivity and specificity for BV were 90.5% and 85.8 %

19

respectively for clinician-collected vaginal swabs, and 90.7% and 84.5 % respectively for self-collected vaginal swabs. For the population tested, this resulted in Positive Predictive Values (PPV) of 89.0 and 88.1 % for clinician-collected and self-collected specimens, respectively. Negative Predictive Values (NPV) of 87.7 % and 87.8% were obtained for clinician-collected and self-collected specimens, respectively. BV prevalence was 55.8% for patients with compliant reference method results.

Site	Clinician-collected		Self-collected
	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)
1	76.5
26/34
(60.0, 87.6)	96.6
113/117
(91.5, 98.7)	80.0
28/35
(64.1, 90.0)	94.1
111/118
(88.3, 97.1)
2	92.3
48/52
(81.8, 97.0)	78.9
30/38
(63.7, 88.9)	88.5
46/52
(77.0, 94.6)	76.9
30/39
(61.7, 87.4)
3	92.3
36/39
(79.7, 97.3)	81.0
17/21
(60.0, 92.3)	92.3
36/39
(79.7, 97.3)	70.0
14/20
(48.1, 85.5)
4	92.3
12/13
(66.7, 98.6)	66.7
4/6
(30.0, 90.3)	84.6
11/13
(57.8, 95.7)	66.7
4/6
(30.0, 90.3)
5	89.6
199/222
(84.9, 93.0)	87.9
131/149
(81.7, 92.2)	89.1
197/221
(84.4, 92.6)	88.0
139/158
(82.0, 92.2)
6	87.1
81/93
(78.8, 92.5)	87.8
72/82
(79.0, 93.2)	88.3
83/94
(80.2, 93.3)	85.4
70/82
(76.1, 91.4)
7	95.7
44/46
(85.5, 98.8)	84.8
28/33
(69.1, 93.3)	100.0
47/47
(92.4, 100.0)	80.0
28/35
(64.1, 90.0)
8	93.4
198/212
(89.2, 96.0)	75.0
87/116
(66.4, 82.0)	93.5
201/215
(89.4, 96.1)	78.5
95/121
(70.4, 84.9)
9	96.0
144/150
(91.5, 98.2)	77.6
52/67
(66.3, 85.9)	97.3
145/149
(93.3, 99.0)	73.5
50/68
(62.0, 82.6)
10	45.0
9/20
(25.8, 65.8)	98.0
48/49
(89.3, 99.6)	45.0
9/20
(25.8, 65.8)	96.0
48/50
(86.5, 98.9)
Overall	90.5
797/881
(88.3, 92.2)	85.8
582/678
(83.0, 88.3)	90.7
803/885
(88.6, 92.5)	84.5
589/697
(81.6, 87.0)

Table 17: BV Performance by Collection Type and Collection Site

Tables 18, 19 and 20 include BV performance for clinician-collected and self-collected vaginal specimens stratified respectively by age group, ethnicity and patient clinical condition.

20

Age Group	Clinician-collected		Self-collected
	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)
18 - 29	90.3
531/588
(87.6, 92.4)	84.2
341/405
(80.3, 87.4)	91.2
539/591
(88.6, 93.2)	83.0
347/418
(79.1, 86.3)
30 - 39	91.0
182/200
(86.2, 94.2)	86.7
130/150
(80.3%, 91.2)	89.9
179/199
(85.0, 93.4)	85.0
130/153
(78.5, 89.8)
40 - 49	94.8
73/77
(87.4, 98.0)	89.8
79/88
(81.7, 94.5)	94.9
75/79
(87.7, 98.0)	87.8
79/90
(79.4, 93.0)
50 and over	68.8
11/16
(44.4, 85.8)	91.4
32/35
(77.6, 97.0)	62.5
10/16
(38.6, 81.5)	91.7
33/36
(78.2, 97.1)

Table 18: BV Performance Stratified By Age Group

Table 19: BV Performance Results Stratified by Ethnicity

		Clinician-collected Specimens				Self-collected Specimens
Ethnicity	Prevalencea	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)	PPV
Percent
(95% CI)	NPV
Percent
(95% CI)	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)	PPV
Percent
(95% CI)	NPV
Percent
(95% CI)
Asian	50.9%
29/57	79.3
23/29
(61.6, 90.2)	100.0
26/26
(87.1,
100.0)	100.0
(87.3,
100.0)	82.4
(70.8,
92.4)	79.3
23/29
(61.6,
90.2)	88.9
24/27
(71.9,
96.1)	88.1
(73.3,
97.0)	80.6
(68.3,
91.1)
Black or African
American	65.2%
559/857	91.9
502/546
(89.4, 93.9)	79.1
223/282
(74.0,
83.4)	89.2
(86.9, 91.3)	84.0
(79.8,
87.6)	92.5
506/547
(90.0,
94.4)	77.0
224/291
(71.8,
81.4)	88.3
(86.0,
90.4)	84.6
(80.4,
88.2)
Hispanic/Latino	39.5%
58/147	83.9
47/56
(72.2, 91.3)	84.9
73/86
(75.8,
90.9)	78.3
(69.1,
86.5)	89.0
(82.5,
94.2)	83.9
47/56
(72.2,
91.3)	87.5
77/88
(79.0,
92.9)	81.4
(72.2,
89.2)	89.3
(82.9,
94.4)
White (not
Hispanic/Latino)	41.3%
164/397	90.7
146/161
(85.2, 94.3)	92.0
207/225
(87.7,
94.9)	88.9
(84.0,
92.8)	93.3
(89.9,
96.0)	90.2
148/164
(84.7,
93.9)	90.4
207/229
(85.9,
93.6)	86.9
(81.9,
91.0)	92.9
(89.5,
95.7)
Others/Mixed/
Unknown	58.6%
89/152	88.8
79/89
(80.5, 93.8)	89.8
53/59
(79.5,
95.3)	92.5
(86.0,
96.9)	85.0%
(76.7,
91.8)	88.8
79/89
(80.5,
93.8)	91.9
57/62
(82.5,
96.5)	94.0
(87.8,
97.8)	85.3
(77.0,
91.8)

ª Prevalence was calculated for specimens with compliant reference method results.

21

Table 26. BV Performance Stratified by Clinical Condition
Subgroup	Clinician-collected
Sensitivity
Percent
(95% CI)	Clinician-collected
Specificity
Percent
(95% CI)	Self-collected
Sensitivity
Percent
(95% CI)	Self-collected
Specificity
Percent
(95% CI)
Pregnant patients	88.9
8/9
(56.5, 98.0)	90.9
10/11
(62.3, 98.4)	88.9
8/9
(56.5, 98.0)	90.0
9/10
(59.6, 98.2)
Patients with estrogen therapy	86.4
57/66
(76.1, 92.7)	84.3
75/89
(75.3, 90.4)	91.0
61/67
(81.8, 95.8)	82.0
73/89
(72.8, 88.6)
Patients using anti-fungals	80.4
45/56
(68.2, 88.7)	93.8
75/80
(86.2, 97.3)	80.0
44/55
(67.6, 88.4)	90.9
80/88
(83.1, 95.3)
Patients with unprotected intercourse in
the last 24 h	89.7
61/68
(80.2, 94.9)	68.3
28/41
(53.0, 80.4)	89.6
60/67
(80.0, 94.8)	69.8
30/43
(54.9, 81.4)
Patients with recurrent symptoms	87.6
162/185
(82.0, 91.6)	87.1
155/178
(81.4, 91.2)	86.1
161/187
(80.4, 90.3)	85.9
159/185
(80.2, 90.2)
Patients using oral antibiotics	82.3
79/96
(73.5, 88.6)	93.8
76/81
(86.4, 97.3)	84.4
81/96
(75.8, 90.3)	83.3
70/84
(73.9, 89.8)
Patients with menses	83.3
40/48
(70.4, 91.3)	86.5
32/37
(72.0, 94.1)	85.7
42/49
(73.3, 92.9)	86.8
33/38
(72.7, 94.2)
Patients without menses	90.8
754/830
(88.7, 92.6)	85.7
546/637
(82.8, 88.2)	91.0
758/833
(88.9, 92.8)	84.3
552/655
(81.3, 86.9)

Table 20: BV Performance Stratified by Clinical Condition

Cgroup Performance

Table 21 includes overall and per site performance for detection of Cgroup (Candida albicans, Candida tropicalis, Candida parapsilosis and/or Candida dubliniensis) as observed in the prospective clinical study. The sensitivity and specificity were 90.9 and 94.1 % respectively for clinician-collected vaginal swabs, and 92.2 and 91.9 % respectively for self-collected vaginal swabs. For the population tested, this resulted in a PPV of 87.8 and 84.1 % for clinician-collected and self-collected specimens, respectively. NPV's of 95.7 and 96.2 % were obtained for clinician-collected and selfcollected vaginal swabs, respectively. The prevalence of these Candida species combined was 31.6% for patients with compliant reference method results.

22

	Clinician-collected		Self-collected
	Sensitivity	Sensitivity	Specificity	Specificity
Site	Percent
(95% CI)	Percent
(95% CI)	Percent
(95% CI)	Percent
(95% CI)
1	96.4
53/55
(87.7, 99.0)	97.0
98/101
(91.6, 99.0)	98.2
54/55
(90.4, 99.7)	93.1
95/102
(86.5, 96.6)
2	82.8
24/29
(65.5, 92.4)	93.9
62/66
(85.4, 97.6)	93.1
27/29
(78.0, 98.1)	93.9
62/66
(85.4, 97.6)
3	61.5
8/13
(35.5, 82.3)	89.1
41/46
(77.0, 95.3)	83.3
10/12
(55.2, 95.3)	91.3
42/46
(79.7, 96.6)
4	100.0
3/3
(43.9, 100.0)	100.0
17/17
(81.6, 100.0)	100.0
3/3
(43.9, 100.0)	94.1
16/17
(73.0, 99.0)
5	96.1
99/103
(90.4, 98.5)	94.4
268/284
(91.0, 96.5)	91.3
95/104
(84.4, 95.4)	90.9
259/285
(87.0, 93.7)
6	91.9
57/62
(82.5, 96.5)	96.6
114/118
(91.6, 98.7)	85.2
52/61
(74.3, 92.0)	91.6
109/119
(85.2, 95.4)
7	90.9
30/33
(76.4, 96.9)	93.9
46/49
(83.5, 97.9)	91.2
31/34
(77.0, 97.0)	87.8
43/49
(75.8, 94.3)
8	95.4
104/109
(89.7, 98.0)	93.9
214/228
(90.0, 96.3)	96.4
107/111
(91.1, 98.6)	91.0
212/233
(86.6, 94.0)
9	86.4
70/81
(77.3, 92.2)	89.1
131/147
(83.1, 93.2)	90.0
72/80
(81.5, 94.8)	93.9
138/147
(88.8, 96.7)
10	70.0
14/20
(48.1, 85.5)	100.0
54/54
(93.4, 100.0)	90.5
19/21
(71.1, 97.3)	96.3
52/54
(87.5, 99.0)
Overall	90.9
462/508
(88.1, 93.1)	94.1
1045/1110
(92.6, 95.4)	92.2
470/510
(89.5, 94.2)	91.9
1028/1118
(90.2, 93.4)

Table 21: Cgroup Performance per Collection Type and Collection Site

Table 22 includes Cgroup performance stratified by each applicable Candida species identified by the reference culture and sequencing of the its2 gene.

23

Species (its2 gene ID)	Sensitivity
	Clinician-collected	Self-collected
	Estimate
95% CI
Candida albicans	91.0%
445/489
(88.1%, 93.2%)	92.0%
451/490
(89.3%, 94.1%)
Candida albicans
(co-infected with C.
glabrata)	92.3%
12/13
(66.7%, 98.6%)	100%
13/13
(77.2%, 100.0%)
Co-infection Candida
albicans and Candida
tropicalis	100.0%
1/1
(20.7%, 100.0%)	100.0%
1/1
(20.7%, 100.0%)
Candida dubliniensis	100.0%
3/3
(43.9%, 100.0%)	100.0%
3/3
(43.9%, 100.0%)
Candida tropicalis	50.0%
1/2
(9.5%, 90.5%)	66.7%
2/3
(20.8%, 93.9%)
Overall	90.9
462/508
(88.1, 93.1)	92.2
470/510
(89.5, 94.2)

Table 22: Cgroup Performance Stratified by Candida Species

Tables 23, 24 and 25 include Cgroup performance for clinician-collected and selfcollected vaginal specimens stratified respectively by age group, ethnicity and patient clinical condition.

Age Group	Clinician-collected		Self-collected
	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)
18 - 29	90.6
326/360
(87.1, 93.2)	93.5
618/661
(91.4, 95.1)	91.2
331/363
(87.8, 93.7)	91.3
608/666
(88.9, 93.2)
30 - 39	93.9
92/98
(87.3, 97.2)	94.3
250/265
(90.9, 96.5)	96.8
92/95
(91.1, 98.9)	91.7
244/266
(87.8, 94.5)
40 - 49	90.2
37/41
(77.5, 96.1)	94.5
120/127
(89.1, 97.3)	88.4
38/43
(75.5, 94.9)	93.0
119/128
(87.2, 96.3)
50 and over	77.8
7/9
(45.3, 93.7)	100.0
57/57
(93.7, 100.0)	100.0
9/9
(70.1, 100.0)	98.3
57/58
(90.9, 99.7)

Table 23: Cgroup Performance Stratified by Age Group

24

		Clinician-collected Specimens			Self-collected Specimens
Ethnicity	Prev.a	Sensitivity	Specificity	PPV	NPV	Sensitivity	Specificity	PPV	NPV
		Percent
(95% CI)	Percent
(95% CI)	Percent
(95% CI)	Percent
(95% CI)	Percent
(95% CI)	Percent
(95% CI)	Percent
(95% CI)	Percent
(95% CI)
Asian	20.0%	90.9	97.8	91.3	97.7	90.9	93.8	78.4	97.6
	12/60	10/11	45/46			10/11	45/48
		(62.3, 98.4)	(88.7, 99.6)	(67.5, 99.7)	(90.6, 99.9)	(62.3, 98.4)	(83.2, 97.9)	(57.1, 93.9)	(90.5, 99.9)
Black or African
American	32.5%	91.3	92.8	85.9	95.7	92.4	92.3	85.3	96.2
	287/884	253/277	542/584			257/278	541/586
		(87.4, 94.1)	(90.4, 94.6)	(82.1, 89.3)	(93.9, 97.1)	(88.7, 95.0)	(89.9, 94.2)	(81.5, 88.6)	(94.5, 97.6)
Hispanic/Latino	36.1%	92.2	96.7	94.0	95.6	92.3	92.4	87.2	95.5
	53/147	47/51	88/91			48/52	85/92
		(81.5, 96.9)	(90.8, 98.9)	(85.3, 98.6)	(90.3, 98.7)	(81.8, 97.0)	(85.1, 96.3)	(78.0, 94.0)	(90.2, 98.6)
White (not
Hispanic/Latino)	30.9%	88.8	95.0	88.7	95.0	92.0	90.4	81.0	96.2
	126/408	111/125	264/278			115/125	253/280
		(82.1, 93.2)	(91.7, 97.0)	(82.9, 93.2)	(92.3, 97.1)	(85.9, 95.6)	(86.3, 93.3)	(75.1, 86.3)	(93.6, 98.0)
Others/Mixed/
Unknown	28.7%	93.2	95.5	89.3	97.2	90.9	92.9	83.6	96.2
	45/157	41/44	106/111			40/44	104/112
		(81.8, 97.7)	(89.9, 98.1)	(79.1, 95.9)	(92.9, 99.4)	(78.8, 96.4)	(86.5, 96.3)	(73.2, 91.7)	(91.7, 98.9)

Table 24: Cgroup Performance Stratified by Ethnicity

4 Prevalence was calculated for specimens with compliant reference method results.

	Clinician-collected		Self-collected
Subgroup	Sensitivity
(95% CI)	Specificity
(95% CI)	Sensitivity
(95% CI)	Specificity
(95% CI)
Pregnant patients	100.0
11/11
(74.1, 100.0)	88.9
8/9
(56.5, 98.0)	90.0
9/10
(59.6, 98.2)	88.9
8/9
(56.5, 98.0)
Patients with estrogen
therapy	96.3
52/54
(87.5, 99.0)	91.7
100/109
(85.0, 95.6)	98.1
51/52
(89.9, 99.7)	90.9
100/110
(84.1, 95.0)
Patients using anti-fungals	89.8
44/49
(78.2, 95.6)	89.7
87/97
(82.1, 94.3)	92.0
46/50
(81.2, 96.8)	86.0
86/100
(77.9, 91.5)
Patients with unprotected
intercourse in the last 24 h	94.7
36/38
(82.7, 98.5)	93.1
67/72
(84.8, 97.0)	95.0
38/40
(83.5, 98.6)	93.1
67/72
(84.8, 97.0)
Patients with recurrent
symptoms	90.3
93/103
(83.0, 94.6)	92.7
253/273
(89.0, 95.2)	93.5
100/107
(87.1, 96.8)	91.2
248/272
(87.2, 94.0)
Patients using oral
antibiotics	94.9
56/59
(86.1, 98.3)	92.2
119/129
(86.3, 95.7)	96.6
57/59
(88.5, 99.1)	86.8
112/129
(79.9, 91.6)
Patients with menses	85.7
18/21
(65.4, 95.0)	94.0
63/67
(85.6, 97.7)	95.5
21/22
(78.2, 99.2)	95.5
64/67
(87.6, 98.5)
Patients without menses	91.3
443/485
(88.5, 93.5)	94.2
978/1038
(92.6, 95.5)	92.2
448/486
(89.4, 94.3)	91.7
959/1046
(89.9, 93.2)

Table 25: Cgroup Performance Stratified by Health Condition

25

Candida glabrata Performance

Table 26 includes overall and per site performance for detection of C. glabrata as observed in the prospective clinical study. The sensitivity and specificity were 75.9 and 99.7 % respectively for clinician-collected vaginal swabs and 86.7 and 99.6 % respectively for self-collected vaginal swabs. For the population tested, this resulted in PPV of 81.6 and 81.0 % for clinician-collected and self-collected specimens, respectively. NPV of 99.6 and 99.8 % were obtained for clinician-collected and selfcollected specimens, respectively. The prevalence of C. glabrata was 1.8% for patients with compliant reference method results.

Site	Clinician-collected		Self-collected
	Sensitivity
Percent
(95% CI a)	Specificity
Percent
(95% CI a)	Sensitivity
Percent
(95% CI a)	Specificity
Percent
(95% CI a)
1	100.0
3/3
(43.9, 100.0)	100.0
153/153
(97.6, 100.0)	100.0
3/3
(43.9, 100.0)	100.0
154/154
(97.6, 100.0)
2	0.0
0/1
(0.0, 79.3)	100.0
94/94
(96.1, 100.0)	0.0
0/1
(0.0, 79.3)	100.0
94/94
(96.1, 100.0)
3	100.0
1/1
(20.7, 100.0)	100.0
58/58
(93.8, 100.0)	100.0
1/1
(20.7, 100.0)	100.0
57/57
(93.7, 100.0)
4	100.0
1/1
(20.7, 100.0)	100.0
19/19
(83.2, 100.0)	100.0
1/1
(20.7, 100.0)	100.0
19/19
(83.2, 100.0)
5	100.0
5/5
(56.6, 100.0)	99.7
381/382
(98.5, 100.0)	100.0
5/5
(56.6, 100.0)	99.2
381/384
(97.7, 99.7)
6	40.0
2/5
(11.8, 76.9)	100.0
175/175
(97.9, 100.0)	83.3
5/6
(43.6, 97.0)	100.0
174/174
(97.8, 100.0)
7	No data for
Sensitivity
calculation	100.0
82/82
(95.5, 100.0)	No data for
Sensitivity
calculation	98.8
82/83
(93.5, 99.8)
8	60.0
3/5
(23.1, 88.2)	99.1
329/332
(97.4, 99.7)	60.0
3/5
(23.1, 88.2)	99.4
337/339
(97.9, 99.8)
9	100.0
6/6
(61.0, 100.0)	99.5
221/222
(97.5, 99.9)	100.0
6/6
(61.0, 100.0)	100.0
221/221
(98.3, 100.0)
10	50.0
1/2
(9.5, 90.5)	100.0
72/72
(94.9, 100.0)	100.0
2/2
(34.2, 100.0)	100.0
73/73
(95.0, 100.0)
Overall	75.9
22/29b,c
(57.9, 87.8)	99.7
1584/1589
(99.3, 99.9)	86.7
26/30d,e
(70.3, 94.7)	99.6
1592/1598
(99.2, 99.8)

Table 26: Candida glabrata Performance by Collection Type and Collection Site

ª CI: Confidence interval

b Out of 7 C.glabrata false negative results, 6 showed chromagar results consistent with low C.glabrata load (1+ to 2+ growth level) and 1 showed chromagar result consistent with high C.glabrata load (3+ growth level)

& The BD MAX Vaginal Panel detected BV and/or Cgroup signals in 6 out of 7 specimens with C.glabrata false negative results

26

d Out of 4 C.glabrata false negative results, 3 showed chromagar results consistent with low C.glabrata load (1+ to 2+ growth level) and 1 showed chromagar result consistent with high C.glabrata load (3+ growth level) ® The BD MAX Vaginal Panel detected BV and/or Cgroup signals in the 4 specimens with C.glabrata false negative results

Tables 27, 28 and 29 include Candida glabrata performance for clinician-collected and self-collected vaginal specimens stratified respectively by age group, ethnicity and pregnancy status.

Age Group	Clinician-collected		Self-collected
	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)	Sensitivity
Percent
(95% CI)	Specificity
Percent
(95% CI)
18 - 29	73.7
14/19
(51.2, 88.2)	99.6
998/1002
(99.0, 99.8)	78.9
15/19
(56.7, 91.5)	99.7
1007/1010
(99.1, 99.9)
30 - 39	100.0
1/1
(20.7, 100.0)	100.0
362/362
(98.9, 100.0)	100.0
1/1
(20.7, 100.0)	99.4
358/360
(98.0, 99.8)
40 - 49	83.3
5/6
(43.6, 97.0)	99.4
161/162
(96.6, 99.9)	100.0
7/7
(64.6, 100.0)	99.4
163/164
(96.6, 99.9)
50 and over	66.7
2/3
(20.8, 93.9)	100.0
63/63
(94.3, 100.0)	100.0
3/3
(43.9, 100.0)	100.0
64/64
(94.3, 100.0)

Table 27: Candida glabrata Performance Stratified by Age Group

Table 28: Candida glabrata Performance Stratified by Ethnicity

Ethnicity	Prev.ᵃ	Clinician-collected Specimens				Self-collected Specimens
		Sens
Percent
(95% CI)	Spec
Percent
(95% CI)	PPV
Percent
(95% CI)	NPV
Percent
(95% CI)	Sens
Percent
(95% CI)	Spec
Percent
(95% CI)	PPV
Percent
(95% CI)	NPV
Percent
(95% CI)
Asian	3.3%
2/60	50.0
(1/2)
(9.5, 90.5)	100.0
(55/55)
(93.5, 100.0)	100.0
(6.1, 100.0)	98.3
(96.7, 100.0)	50.0
(1/2)
(9.5, 90.5)	100.0
(57/57)
(93.7, 100.0)	100.0
(6.3, 100.0)	98.3
(96.7, 100.0)
Black or African
American	1.6%
14/884	78.6
(11/14)
(52.4, 92.4)	99.6
(844/847)
(99.0, 99.9)	78.1
(54.0, 94.1)	99.7
(99.2, 99.9)	85.7
(12/14)
(60.1, 96.0)	99.5
(846/850)
(98.8, 99.8)	74.6
(53.5, 91.4)	99.8
(99.3, 100.0)
Hispanic/Latino	2.0%
3/147	66.7
(2/3)
(20.8, 93.9)	100.0
(139/139)
(97.3, 100.0)	100.0
(28.4, 100.0)	99.3
(98.1, 100.0)	100.0
(3/3)
(43.9, 100.0)	100.0
(141/141)
(97.3, 100.0)	100.0
(44.0, 100.0)	100.0
(98.5, 100.0)
White (not
Hispanic/
Latino)	1.7%
7/408	66.7
(4/6)
(30.0, 90.3)	99.7
(396/397)
(98.6, 100.0)	82.2
(41.4, 99.2)	99.4
(98.7, 99.9)	85.7
(6/7)
(48.7, 97.4)	99.7
(397/398)
(98.6, 100.0)	85.6
(51.0, 99.4)	99.8
(99.0, 100.0)
Others/Mixed/
Unknown	2.5%
4/157	100.0
4/4
(51.0, 100.0)	99.3
150/151
(96.3, 99.9)	79.8
(39.7, 99.4)	100.0
(98.4, 100.0)	100.0
4/4
(51.0, 100.0)	99.3
151/152
(96.4, 99.9)	79.9
(39.9, 99.4)	100.0
(98.4, 100.0)

ª Prevalence was calculated for specimens with compliant reference method results.

27

Subgroup	Clinician-collected		Self-collected
	Sensitivity	Specificity	Sensitivity	Specificity
	Percent (95% CI)	Percent (95% CI)	Percent (95% CI)	Percent (95% CI)
Pregnant patients	No data for Sensitivity calculation	100.0
20/20
(83.9, 100.0)	No data for Sensitivity calculation	100.0
19/19
(83.2, 100.0)

Table 29: Candida glabrata Performance in Pregnant Patients

Due to the low prevalence of Candida glabrata observed in the prospective clinical study, evaluation of contrived specimens was performed to supplement the clinical data collected. Contrived specimens were prepared by spiking 50 different Candida glabrata strains individual negative vaginal matrices. True negative specimens, containing vaginal matrix only, were interspersed with positive specimens and all specimen identities were blinded to the user. Strains were spiked at various clinically relevant organism concentrations and randomly distributed among three clinical testing sites for BD MAX Vaginal Panel testing. The study results demonstrated 100% positive agreement for all contrived positive specimens evaluated. Results for contrived specimens are presented in Table 30.

Candida glabrata	Percent Agreement
Category	Load (x LoD)	Percent
(95% CI)
High Positive	$\geq$ 10 and $8.1
140/1734
(6.9, 9.5)	2.2
38/1725
(1.6, 3.0)
Self-
collected	2.9
50/1736
(2.2, 3.8)	0.6
11/1733
(0.4, 1.1)	2.7
47/1736
(2.0, 3.6)	0.6
10/1733
(0.3, 1.1)	1.4
24/1736
(0.9, 2.0)	0.2
4/1733
(0.1, 0.6)	7.0
121/1736
(5.9, 8.3)	1.4
25/1733
(1.0, 2.1)

Table 39: Non-reportable Rates

a The final rate is calculated with valid repeats only

Evaluation of the BD MAX Vaginal Panel in Asymptomatic Women

Although the BD MAX Vaginal Panel is not intended for testing specimens from asymptomatic women, presence of Candida species, T. vaginalis and BV markers has been reported in this population. The BD MAX Vaginal Panel was evaluated for detection of Candida species, T. vaginalis and BV markers with vaginal specimens collected from 202 asymptomatic women. BD MAX Vaginal Panel vaginitis targets were detected with rates varying from 1.5% for C. krusei to 20.8% for Cgroup. Positive BV results were generated for 34.2% of asymptomatic women. Results from the study are presented in Table 40 which also includes results for the most prevalent ethnic groups enrolled. BV, Cgroup and T. vaginalis were detected in all ethnic categories.

		Table 40: BD MAX Vaginal Panel Positive Rates in Asymptomatic Women

Target	Overall	By Ethnic Group
		Black/African American	White (not Hispanic)	Othersa
BV	34.2%	40.4%	28.8%	28.6%
	69/202	(38/94)	(23/80)	(8/28)
Cgroup	20.8%	22.3%	16.3%	28.6%
	42/202	(21/94)	(13/80)	(8/28)
C. glabrata	5.9%	11.7%	0.0%	3.6%
	12/202	(11/94)	(0/80)	(1/28)
C. krusei	1.5%	1.1%	2.5%	0.0%
	3/202	(1/94)	(2/80)	(0/28)
T. vaginalis	11.4%	22.3%	1.3%	3.6%
	23/202	(21/94)	(1/80)	(1/28)

ª Including: American Indian or Alaska natives, Asian, Mixed Ethnicity and Unknown

3. Clinical Cutoff:

See Assay Cut-off Section L.1.j above.

4. Expected Values:

The incidence of each BD MAX Vaginal Panel result as observed in the prospective clinical study is presented in Table 41, stratified by clinic type and specimen type.

34

| Collection
Type | Clinic Type | Bacterial
Vaginosis | Cgroupa | Candida
glabrata | Candida
krusei | Trichomonas
vaginalis |
|-------------------------|--------------------|------------------------|---------------------|---------------------|-------------------|--------------------------|
| Clinician-
collected | STD / HIV | 72.7%
(224/308) | 34.0%
(105/309) | 2.6%
(8/309) | 0.3%
(1/309) | 15.9%
(49/309) |
| | Family
Planning | 60.7%
(683/1125) | 33.3%
(379/1138) | 1.2%
(14/1138) | 0.1%
(1/1138) | 7.5%
(85/1138) |
| | OB/Gyn | 20.6%
(52/252) | 29.6%
(75/253) | 2.0%
(5/253) | 0.8%
(2/253) | 0.4%
(1/253) |
| | Total | 56.9%
(959/1685) | 32.9%
(559/1700) | 1.6%
(27/1700) | 0.2%
(4/1700) | 7.9%
(135/1700) |
| Self-collected | STD / HIV | 74.6%
(229/307) | 33.9%
(104/307) | 2.3%
(7/307) | 0.0%
(0/307) | 16.0%
(49/307) |
| | Family
Planning | 60.1%
(687/1143) | 35.1%
(403/1147) | 1.7%
(19/1147) | 0.0%
(0/1147) | 7.7%
(88/1147) |
| | OB/Gyn | 22.0%
(56/255) | 34.5%
(88/255) | 2.4%
(6/255) | 0.0%
(0/255) | 0.4%
(1/255) |
| | Total | 57.0%
(972/1705) | 34.8%
(595/1709) | 1.9%
(32/1709) | 0.0%
(0/1709) | 8.1%
(138/1709) |

Table 41: BD MAX Vaginal Panel Positivity Rate by Clinic Type

ª Candida albicans, Candida tropicalis, Candida parapsilosis and/or Candida dubliniensis

M. Instrument Name

BD MAX System

N. System Descriptions:

1. Modes of Operation:

The BD MAX System fully automates cell lysis, nucleic acid extraction, PCR set-up, target amplification and detection. For the BD MAX Vaginal Panel, the system can process and analyze up to 12 specimens in one cartridge with two cartridges running simultaneously on the instrument. The system includes external and internal barcode reading, ensuring traceability throughout the extraction and PCR processes. The system includes a heater module, temperature sensors, and a fluorescence detection system with six optical channels.

2. Software:

FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:

Yes

• 3. Specimen Identification:
     Specimens are identified via barcode.
• 4. Specimen Sampling and Handling:
     Sample Buffer Tubes containing vaginal swab specimens are vortexed for one minute on the Multi-tube Vortexer, after which the user uncaps each specimen, removes the excess

35

fluid from the swab, discards the swab and then recaps the tube with a blue septum cap. Specimens are then loaded into the BD MAX System Rack on the BD MAX System after which all additional specimen handling steps are automated.

• 5. Calibration:
     The system is calibrated by the manufacturer on-site as part of the installation procedure as well as during biannual preventive maintenance.
• 6. Quality Control:
     See Quality Control Section above (Section L.1.c)

O. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

Not Applicable

P. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809 and the specials controls for this device type.

Q. Identified Risks to Health and Identified Mitigations:

Identified Risks to Health	Identified Mitigations
Incorrect identification or lack of identification
of a pathogenic microorganism by the device
can lead to improper patient management	General controls and special controls (1), (2), (3), and (4)
Failure to correctly interpret test results	General controls and special controls (5), (6), (7), and (8)

36

R. Benefit/Risk Analysis:

	Summary
Summary of
the Benefit(s)	The BD MAX Vaginal Panel detects nucleic acids from microorganisms associated with bacterial vaginosis, candidiasis and trichomoniasis from a clinician or self-collected vaginal swab to aid in the diagnosis of bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis. The BD MAX Vaginal Panel provides molecular detection of analytes that are typically diagnosed clinically and/or with microscopy, which may reduce human error from microscopy or clinical diagnosis of signs and symptoms. The BD MAX Vaginal Panel may reduce operator error and provide for more uniform diagnosis of bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.
Summary of
the Risk(s)	False positives and false negative results are the primary risks associated with the BD MAX Vaginal Panel. False positive results would result in an unnecessary course of oral or topical antimicrobials. False negative results could result in delayed diagnosis of bacterial vaginosis or trichomoniasis. Patients who remain symptomatic are likely to be retested, or receive empiric therapy.
Summary of
Other
Factors	None.
Conclusions
Do the
probable
benefits
outweigh the
probable
risks?	The probable benefits of the BD MAX Vaginal Panel outweigh the potential risks in light of the established special controls and applicable general controls, including design controls. The BD MAX Vaginal Panel is the first multiplex panel using nucleic acid amplification to detect multiple microorganisms associated with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis. Potential risks include false positive and false negative results, but it is highly unlikely that a patient would suffer a serious adverse event as a result of an erroneous result from the BD MAX Vaginal Panel given the clinical performance demonstrated in the prospective clinical trial and the special controls established for this device. Risks are further mitigated by the use of the device in association with clinical assessment, supplemental laboratory testing, natural progression of clinical symptoms and clinical judgment. Ultimately, the majority of risks associated with the BD MAX Vaginal Panel may be minimized with appropriate precautions and the BD MAX Vaginal Panel may better standardize the assessment of vaginosis/vaginitis.

Patient Perspectives:

This submission did not include specific information on patient perspectives for this device.

37

S. Conclusion:

The information provided in this de novo submission is sufficient to classify this device into class II under regulation 21 CFR 866.3975. FDA believes that the stated special controls, and applicable general controls, including design controls, provide reasonable assurance of the safety and effectiveness of the device type. The device is classified under the following:

Product Code:	PQA, OUY, OOI, NSU
Device Type:	Device that detects nucleic acid sequences from microorganisms
associated with vaginitis and bacterial vaginosis
Class:	II (special controls)
Regulation:	21 CFR 866.3975

• (a) Identification. A device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis is a qualitative in vitro 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). A device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis is subject to the following special controls:
  • 1. Premarket notification submissions must include a detailed device description of the following:
    • Device components: (i)
    • Ancillary reagents required but not provided; and (ii)
    • (iii) Explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
  • 2. Premarket notification submissions must include information that demonstrates the performance characteristics of the device, including:
    • Limit of Detection; (i)
    • Precision (reproducibility); (ii)
    • Analytical specificity; (iii)
    • Analytical reactivity (inclusivity); (iv)
    • (v) Specimen stability; and
    • Effects of interfering substances. (vi)
  • 3. Premarket notification submissions must include 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

38

compare the device performance to results obtained from well-accepted comparator methods.

• 4. Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardwarebased devices that incorporate software.
• 5. A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.
• 6. For indications for use that include detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, the 21 CFR 809.10(b)(12) compliant labeling must include clinical performance stratified by patient demographics such as race, ethnicity, age, and pregnancy status.
• 7. For indications for use that include detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, the 21 CFR 809.10(b)(12) compliant labeling must include a summary of device results in an asymptomatic population with demographic characteristics appropriate to the intended use population.
• 8. For indications for use that include detection of either Candida species or bacteria associated with bacterial vaginosis, the 21 CFR 809.10 compliant labeling must include 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.