The BD MAX CT/GC/TV assay, as performed using the BD MAX System incorporates automated DNA extraction and real-time polymerase chain reaction (PCR) for the direct, qualitative detection of DNA from Chlamydia (CT), Neisseria gonorrhoeae (GC) and/or Trichomonas vaginalis (TV). The assay may be used for detection of CT and/or GC DNA in male urine specimens, and the detection of CT, GC and/or TV DNA in female urine specimens, cliniciancollected female endocervical swab speciment-collected vaginal swab specimens (in a clinical setting). The assay is indicated for use to aid in the diagnosis of chlamydial urogenital disease, gonococcal urogenital disease and/or trichomoniasis in asymptomatic and symptomatic individuals.

Device Description

The BD MAX System and the BD MAX CT/GC/TV 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, and 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. A test result may be called as POS, NEG or UNR for each of the assay's targets, based on the amplification status of the target and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX System failure.

AI/ML Overview

The BD MAX CT/GC/TV assay, performed using the BD MAX System, is an in vitro diagnostic device for the direct, qualitative detection of DNA from Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), and Trichomonas vaginalis (TV).

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of acceptance criteria with corresponding performance metrics. However, the "Clinical Performance Studies" section implicitly establishes the performance expectations through its reported sensitivity and specificity values. The acceptance criteria can be inferred as the achieved sensitivity and specificity values for each pathogen across different specimen types and patient populations (asymptomatic and symptomatic).

For the purpose of this response, I will present the key performance metrics from the "Clinical Performance Studies" (Table 18) as the reported device performance, which are implicitly the performance targets the device met. The clinical performance is compared against a "Patient Infected Status (PIS)," which is a composite reference method.

Table: Acceptance Criteria (Inferred from Achieved Performance) and Reported Device Performance

Target Organism	Specimen Type	Patient Symptom Status	Acceptance Criteria (Inferred from Study Results)	Reported Device Performance (95% CI)
Chlamydia trachomatis (CT)	Vaginal Swab	Asymptomatic	Sensitivity: ≥93.0% Specificity: ≥97.5%	Sensitivity: 100% (93.0-100) Specificity: 98.7% (97.5-99.3)
		Symptomatic	Sensitivity: ≥94.0% Specificity: ≥97.7%	Sensitivity: 98.9% (94.0-99.8) Specificity: 98.6% (97.7-99.2)
	Endocervical Swab	Asymptomatic	Sensitivity: ≥84.1% Specificity: ≥98.1%	Sensitivity: 94.1% (84.1-98.0) Specificity: 99.1% (98.1-99.5)
		Symptomatic	Sensitivity: ≥90.3% Specificity: ≥98.6%	Sensitivity: 96.6% (90.3-98.8) Specificity: 99.4% (98.6-99.7)
	Female Urine	Asymptomatic	Sensitivity: ≥81.8% Specificity: ≥99.0%	Sensitivity: 92.3% (81.8-97.0) Specificity: 99.7% (99.0-99.9)
		Symptomatic	Sensitivity: ≥83.4% Specificity: ≥98.6%	Sensitivity: 91.1% (83.4-95.4) Specificity: 99.4% (98.6-99.7)
	Male Urine	Asymptomatic	Sensitivity: ≥92.3% Specificity: ≥98.1%	Sensitivity: 98.6% (92.3-99.7) Specificity: 99.5% (98.1-99.9)
		Symptomatic	Sensitivity: ≥88.7% Specificity: ≥97.3%	Sensitivity: 94.6% (88.7-97.5) Specificity: 99.3% (97.3-99.8)
Neisseria gonorrhoeae (GC)	Vaginal Swab	Asymptomatic	Sensitivity: ≥73.0% Specificity: ≥99.3%	Sensitivity: 94.1% (73.0-99.0) Specificity: 99.9% (99.3-100)
		Symptomatic	Sensitivity: ≥81.7% Specificity: ≥99.3%	Sensitivity: 96.3% (81.7-99.3) Specificity: 99.8% (99.3-99.9)
	Endocervical Swab	Asymptomatic	Sensitivity: ≥73.0% Specificity: ≥99.5%	Sensitivity: 94.1% (73.0-99.0) Specificity: 100% (99.5-100)
		Symptomatic	Sensitivity: ≥81.7% Specificity: ≥99.4%	Sensitivity: 96.3% (81.7-99.3) Specificity: 99.9% (99.4-100)
	Female Urine	Asymptomatic	Sensitivity: ≥67.2% Specificity: ≥98.7%	Sensitivity: 88.9% (67.2-96.9) Specificity: 99.5% (98.7-99.8)
		Symptomatic	Sensitivity: ≥87.9% Specificity: ≥99.4%	Sensitivity: 100% (87.9-100) Specificity: 99.9% (99.4-100)
	Male Urine	Asymptomatic	Sensitivity: ≥37.6% Specificity: ≥99.1%	Sensitivity: 80.0% (37.6-96.4) Specificity: 100% (99.1-100)
		Symptomatic	Sensitivity: ≥96.4% Specificity: ≥98.7%	Sensitivity: 100% (96.4-100) Specificity: 100% (98.7-100)
Trichomonas vaginalis (TV)	Vaginal Swab	Asymptomatic	Sensitivity: ≥78.0% Specificity: ≥94.9%	Sensitivity: 93.1% (78.0-98.1) Specificity: 97.5% (94.9-98.8)
		Symptomatic	Sensitivity: ≥91.9% Specificity: ≥98.6%	Sensitivity: 96.7% (91.9-98.7) Specificity: 99.5% (98.6-99.8)
	Endocervical Swab	Asymptomatic	Sensitivity: ≥82.8% Specificity: ≥95.8%	Sensitivity: 96.6% (82.8-99.4) Specificity: 98.2% (95.8-99.2)
		Symptomatic	Sensitivity: ≥86.7% Specificity: ≥99.1%	Sensitivity: 92.7% (86.7-96.1) Specificity: 99.8% (99.1-100)
	Female Urine	Asymptomatic	Sensitivity: ≥78.0% Specificity: ≥95.8%	Sensitivity: 93.1% (78.0-98.1) Specificity: 98.2% (95.8-99.2)
		Symptomatic	Sensitivity: ≥86.9% Specificity: ≥99.1%	Sensitivity: 92.8% (86.9-96.2) Specificity: 99.8% (99.1-100)

Note: The "Acceptance Criteria" values are inferred as the lower bounds of the reported 95% Confidence Intervals for Sensitivity and Specificity, representing the minimum performance demonstrated to be acceptable.

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

Test Set Sample Size:
- Female Subjects: 2,114 evaluable subjects for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC), and 1,291 of these for Trichomonas vaginalis (TV).
- Male Subjects: 892 evaluable subjects for CT and GC.
- Specimens for CT: 1,836 patient-collected vaginal swabs, 1,831 endocervical swabs, 1,849 female urine, and 830 male urine specimens.
- Specimens for GC: 1,836 patient-collected vaginal swabs, 1,824 endocervical swabs, 1,849 female urine, and 840 male urine specimens.
- Specimens for TV: 1,048 patient-collected vaginal swabs, 1,039 endocervical swabs, and 1,047 female urine specimens.
- Total specimens initially evaluated: 6,573 specimens.
Data Provenance: Retrospective and Prospective. The study mentions that it was a "multicenter study where clinical sites enrolled subjects and also performed testing." This suggests prospective collection of real-world samples for the clinical performance evaluation. The provenance is from "nine (9) geographically diverse clinical sites in North America."

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

The document refers to a "Patient Infected Status (PIS)" as the reference method for establishing ground truth. The PIS is described as a "composite reference method algorithm." This suggests that the ground truth was not established by a panel of individual experts directly reviewing each case. Instead, it was based on results from multiple reference methods integrated by an algorithm. The specific number of experts or their qualifications involved in developing or validating this algorithm (if any) is not specified in this document.

4. Adjudication Method for the Test Set

The ground truth was established by a "composite reference method algorithm" (PIS). This implies an algorithmic adjudication rather than human expert adjudication. The study states, "This multicenter study evaluated results obtained with the BD MAX CT/GC/TV compared to reference methods defining the Patient Infected Status (PIS)." No specific human adjudication method (e.g., 2+1, 3+1) is mentioned, as the PIS serves as the "truth."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not explicitly mentioned or presented in the document. The study focuses on the standalone performance of the BD MAX CT/GC/TV assay against a defined Patient Infected Status (PIS). There is no comparison of human readers with versus without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the study primarily presents standalone performance of the BD MAX CT/GC/TV assay. The device description states, "The BD MAX System software automatically interprets test results. A test result may be called as POS, NEG or UNR for each of the assay's targets..." and "The BD MAX System performs results interpretation automatically." The clinical performance tables (Table 18) present the sensitivity and specificity of the device's automated results against the PIS, which represents a standalone evaluation of the algorithm's performance.

7. The Type of Ground Truth Used

The type of ground truth used is a "Patient Infected Status (PIS)" which is described as a "composite reference method algorithm." This indicates that the truth was derived from the results of multiple established laboratory reference methods, combined using a predefined algorithm, rather than directly from pathology, individual expert consensus, or outcomes data solely.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size used for the training set for the BD MAX CT/GC/TV assay. This type of information (training set details) is often omitted in premarket notification summaries which focus on clinical validation data for regulatory approval. The "Analytical Performance" section (Precision, Reproducibility, Analytical Sensitivity, Analytical Specificity, Interfering Substances, Carryover/Cross-Contamination, Mixed Infection/Competitive Interference) describes laboratory-based studies used to characterize the assay's analytical capabilities, which might be considered part of the development and optimization process, but not a distinct "training set" in the context of machine learning model development. For in vitro diagnostic assays like this, the "training" aspect is more about optimizing reaction parameters and thresholds rather than training a machine learning model on patient data.

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

Since a distinct "training set" for a machine learning model is not explicitly mentioned, and the device is an IVD assay based on PCR and automated interpretation, the concept of "ground truth for the training set" as it applies to AI/ML devices is not directly applicable here. For the analytical studies, the "ground truth" (e.g., in LoD or analytical specificity) would have been established by precisely creating samples with known concentrations of organisms or known non-target organisms, based on established laboratory methods and controls.

Summary

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

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines representing hair or a sense of movement.

September 6, 2016

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609

Silver Spring, MD 20993-0002

Public Health Service

BD Diagnostic Systems Becton, Dickinson, and Company Katie Edwards, Regulatory Affairs Project Manager 7 Loveton Circle Sparks, MD 21152

Re: K151589

Trade/Device Name: BD MAX™ CT/GC/TV Regulation Number: 21 CFR 866.3860 Regulation Name: Trichomonas vaginalis nucleic acid assay Regulatory Class: II Product Code: OUY, MKZ, LSL Dated: August 19, 2016 Received: August 22, 2016

Dear Ms. Edwards:

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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Steven R. Gitterman -S

for Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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

Indications for Use

510(k) Number (if known) K151589

Device Name BD MAX™ CT/GC/TV

Indications for Use (Describe)

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.

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

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

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

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

510(k) Summary

BD MAX CT/GC/TV

Summary Preparation Date:

September 1, 2016

Submitted by:

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

Contact:

Katie Edwards Regulatory Affairs Project Manager

Tel: 410-316-4975 Fax: 410-316-4188 Email: Katie_Edwards@bd.com

Proprietary Names:

For the instrument:

BD MAX™

For the assay:

BD MAX CT/GC/TV

Common Names:

For the instrument:

Bench-top molecular diagnostics workstation

For the assay:

CT Assay GC Assay TV Assay

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

Regulatory Information

Regulation section:

866.3120 - Chlamydia serological reagents 866.3390 - Neisseria spp. direct serological test reagents 866.3860 – Trichomonas vaginalis Nucleic Acid Amplification Test System

Classification:

Class II Panel:

Microbiology (83)

Product Code(s):

Chlamydia trachomatis MKZ Neisseria gonorrhoeae LSL

OUY Trichomonas vaginalis

Predicate Device

Becton Dickinson ProbeTec™ ET Chlamydia trachomatis (CT) Q* Amplified DNA Assay [510(k) K0818241

Becton Dickinson ProbeTec™ ET Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay [510(k) K081825]

Becton Dickinson ProbeTec™ Trichomonas Vaginalis (TV) Q* Amplified DNA Assay [510(k) K130268]

Device Establishment

GeneOhm Sciences Canada, Inc. (BD Diagnostics) 2555 Boul. du Parc-Technologique Quebec, QC G1P 4S5 Canada

Registration Number: 3007420875

Performance Standards

No performance standards have been developed under Section 514 of the Food, Drug and Cosmetic Act.

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

Intended Use

The BD MAX CT/GC/TV assay, as performed using the BD MAX System incorporates automated DNA extraction and real-time polymerase chain reaction (PCR) for the direct, qualitative detection of DNA from Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC) and/or Trichomonas vaginalis (TV). The assay may be used for detection of CT and/or GC DNA in male urine specimens, and the detection of CT, GC and/or TV DNA in female urine specimens, clinician-collected female endocervical swab specimens and patient-collected vaginal swab specimens (in a clinical setting). The assay is indicated for use to aid in the diagnosis of chlamydial urogenital disease, gonococcal urogenital disease and/or trichomoniasis in asymptomatic and symptomatic individuals.

Special Conditions for Use Statement: For prescription use

Special Instrument Requirements: BD MAX System

Device Description

Test Principle

The specimen is collected from the patient using the BD MAX UVE Specimen Collection Kit and transported to the laboratory under conditions of time and temperature that have been determined to maintain the integrity of the target nucleic acids. The sample is vortexed briefly and then heated on the BD Pre-warm Heater to dissolve mucous, homogenize the specimen matrix and lyse the target organisms. After cooling automatically, the BD MAX UVE Sample Buffer Tubes are recapped with a septum cap. A worklist is created and the BD MAX UVE Sample Buffer Tube, the BD MAX CT/GC/TV Unitized Reagent Strip and the BD MAX PCR Cartridge are loaded on the BD MAX System. The BD MAX System automates sample preparation, including target organism lysis, DNA extraction and concentration, reagent rehydration, and target nucleic acid amplification and detection using real-time PCR. The BD MAX System performs results interpretation automatically. The assay also includes a Sample Processing Control that is present in the Extraction Tube. The Sample Processing Control monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances.

Following cell lysis, the released nucleic acids are captured on magnetic affinity beads. The beads, with the bound nucleic acids, are washed using Wash Buffer and the nucleic acids are eluted by heat in Elution Buffer. Eluted DNA is neutralization Buffer and transferred to the Master Mix to rehydrate the PCR reagents. After reconstitution, the BD MAX System dispenses a fixed volume of PCRready solution containing extracted nucleic acids into the BD MAX PCR Cartridge. Microvalves in the BD MAX PCR Cartridge are sealed by the system prior to initiating PCR to contain the amplification mixture, thus preventing evaporation and contamination. The amplified DNA targets are detected using hydrolysis

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

(TagMan") 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 amplicons for target analytes and the Sample Processing Control in four 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 BD MAX System monitors these signals at each cycle and interprets the data at the end of the reaction to provide qualitative test results for each analyte (i.e., positive or negative).

Substantial Equivalence '

Table 1 shows the similarities and differences between the BD MAX CT/GC/TV and the predicate device.

The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended and as applied under 21 CFR 807, Subpart E under which a device can be marketed without pre-market approval or reclassification. A determination of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws or their application by the courts.

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

Items	BD MAX CT/GC/TV	BD ProbeTec™ ET CT QAmplified DNA Assay	BD ProbeTec™ ET GCQ Amplified DNA Assay	BD ProbeTec™ TV QAmplified DNA Assay
510(k)#	K151589	K081824	K081825	K130268
Regulation	866.3120, 866.3390,866.3680	866.3120	866.3390	866.3860
Product Code	MKZ, LSL, OUY	MKZ	LSL	OUY
Device Class	II	I	Same	Same
Intended Use	The BD MAXCT/GC/TV assay, asperformed using the BDMAX Systemincorporates automatedDNA extraction and real-time polymerase chainreaction (PCR) for thedirect, qualitativedetection of DNA fromChlamydia trachomatis(CT), Neisseriagonorrhoeae (GC) and/orTrichomonas vaginalis(TV). The assay may beused for detection of CTand/or GC DNA in maleurine specimens, and thedetection of CT, GCand/or TV DNA infemale urine specimens,clinician-collected femaleendocervical swabspecimens and patient-collected vaginal swabspecimens (in a clinicalsetting). The assay isindicated for use to aid inthe diagnosis ofchlamydial urogenitaldisease, gonococcalurogenital disease and/ortrichomoniasis inasymptomatic andsymptomatic individuals.	The BD ProbeTec™Chlamydia trachomatis QxAmplified DNA Assay,when tested with either theBD Viper™System in Extracted Modeor the BD Viper LT System,uses Strand DisplacementAmplification technologyfor the direct, qualitativedetection of Chlamydiatrachomatis DNA inclinician collected femaleendocervical and maleurethral swab specimens,patient-collected vaginalswab specimens (in aclinical setting), and maleand female urine specimens(both UPT and neat). Theassay is also intended foruse with gynecologicalspecimens collected in BDSurePath™ PreservativeFluid or PreservCyt™Solution using an aliquotthat isremoved prior to processingfor either the BD SurePathor ThinPrep™ Pap test. Theassay is indicated foruse with asymptomatic andsymptomatic individuals toaid in the diagnosis ofchlamydial urogenitaldisease.	The BD ProbeTec™Neisseria gonorrhoeae QxAmplified DNA Assay,when tested with either theBD Viper™ System inExtracted Mode or the BDViper LT™ System, usesStrand DisplacementAmplification technologyfor the direct, qualitativedetection of Neisseriagonorrhoeae DNA inclinician-collected femaleendocervical and maleurethral swab specimens,patient-collected vaginalswab specimens (in aclinical setting), and maleand female urinespecimens (both UPT andNeat). The assay is alsointended for use withgynecological specimenscollected in BDSurePath™ PreservativeFluid or PreservCyt™Solution using an aliquotthat is removed prior toprocessing for either theBD SurePath orThinPrep™ Pap test. Theassay is indicated foruse with asymptomaticand symptomaticindividuals to aid in thediagnosis of gonococcalurogenital disease.	The BD ProbeTec™Trichomonas vaginalis(TV) Qx AmplifiedDNA Assay, whentested with the BDViper™ System inExtracted Mode, usesStrand DisplacementAmplificationtechnology for thedirect, qualitativedetection ofTrichomonasvaginalis DNA inclinician-collectedfemale endocervicalswab specimens,patient-collectedvaginal swabspecimens (in aclinical setting), andfemale urinespecimens. The assayis indicated for usewith asymptomatic andsymptomatic femalesto aid in the diagnosisof trichomoniasis.
Indicationsfor Use	Asymptomatic andSymptomatic Patients	Same	Same	Same
Specimen Type	Endocervical swab,patient-collected vaginalswab, female and maleurine	Endocervical swab, patient-collected vaginal swab,male urethral swab, maleand female urine (UPT andneat)	Endocervical swab,patient-collected vaginalswab, male urethral swab,male and female urine(UPT and neat)	Endocervical swab,patient-collectedvaginal swab, femaleurine
Technology	PCR	SDA	SDA	SDA
OrganismsDetected	CT, GC and TV	CT	GC	TV
Sample Prep/Interpretationof Results	Automated by BD MAXSystem	Automated by BD ViperSystem	Automated by BD ViperSystem	Automated by BDViper System
Assay Controls	Sample ProcessingControl	Extraction Control	Extraction Control	Extraction Control

Table 1: Comparison to Predicate Device

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

Analytical Performance

Precision

Within-laboratory precision was evaluated for the BD MAXCT/GC/TV at one (1) internal site. The Precision Study panel members were divided into four (4) categories, based upon organism concentration relative to the LoDs established for each of the three (3) assay targets and expected correct percent positive/negative, as follows:

True negative (TN - Negative Clinical Matrix): negative 100% of the time
Moderate positive (MP): Above the assay LoD ("C100", ~2-3x LoD); positive 100% of the time ●
Low positive (LP): At assay LoD ("C95", ~1–1.5x LoD); positive approximately 95% of the time ●
High negative (HN): Below assay LoD (~0.25-0.5x LoD); negative between 5 and 85% of the time ●

Each panel member was prepared in a matrix of either pooled negative vaginal clinical swab specimen or female urine. Testing was performed in duplicate, over 12 days, with 2 runs per day, by 2 different technologists. The Precision Study results are summarized in Table 2, stated as percent observed versus expected.

Panel Member Level	Percent (%) Observed versus Expected
	C. trachomatis		N. gonorrhoeae		T. vaginalis
	Swab	Urine	Swab	Urine	Swab	Urine
True Negative	100%(336/336)98.9-100	100%(336/336)98.9-100	100%(48/48)92.6-100	100%(336/336)98.9-100	100%(336/336)98.9-100	100%(48/48)92.6-100
High Negative	79.2%(38/48)65.7-88.3	79.2%(38/48)65.7-88.3	54.2%(26/48)40.3-67.4	10.4%(5/48)4.5-22.2	56.3%(27/48)42.3-69.3	14.6%(7/48)7.2-27.2
Low Positive	100%(48/48)92.6-100	100%(48/48)92.6-100	100%(48/48)92.6-100	100%(48/48)92.6-100	97.9%(47/48)89.1-99.6	100%(48/48)92.6-100
Moderate Positive	100%(48/48)92.6-100	100%(48/48)92.6-100	100%(48/48)92.6-100	100%(48/48)92.6-100	100%(48/48)92.6-100	100%(48/48)92.6-100

Table 2: Within-laboratory Precision Testing Results

For the True Negative (TN) category, the reported agreement indicates the percent of negative results. b For the High Negative (HN) category, the reported agreement indicates the percent of positive results.

Reproducibility

For the Site-to-Site reproducibility study, three (3) sites (two external and one internal) were provided with a total of sixteen (16) panels per site, each consisting of 10 tubes. The panels used were the same as described above for the Precision Study. Each site performed the study on eight (8) nonconsecutive days, wherein each day, two (2) panels were tested, each by one (1) of two (2) technologists.

The overall Site-to-Site Reproducibility percent agreement ranged from 99.9 to 100.0%, 15.6% to 78.1%, 96.9% to 100% and 100% for the TN, HN, LP and MP categories, respectively (see Table 3). The qualitative and quantitative reproducibility across sites and by target is presented in Tables 4 through 9. End Point fluorescence (EP) and Second Derivative Peak Abscissa (SDPA), internal criterion used to

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

determine final assay results, was selected as an additional means of assessing assay reproducibility. Overall mean EP and SDPA values with variance components (SD and %CV) are shown in Tables 5, 7 and 9.

Category	C. trachomatis(n), 95% CI		N. gonorrhoeae(n), 95% CI		T. vaginalis(n), 95% CI
	Swab	Urine	Swab	Urine	Swab	Urine
TN	100%(672/672)99.4-100	99.9%(671/672)99.2-100	100%(96/96)96.2-100	100%(672/672)99.4-100	100%(672/672)99.4-100	100%(96/96)96.2-100
HN	78.1%(75/96)68.9-85.2	75.0%(72/96)65.5-82.6	55.2%(53/96)45.3-64.8	15.6%(15/96)9.7-24.2	52.1%(50/96)42.2-61.8	35.4%(34/96)26.6-45.4
LP	100%(96/96)96.2-100	100%(96/96)96.2-100	100%(96/96)96.2-100	100%(96/96)96.2-100	96.9%(93/96)91.2-98.9	100%(96/96)96.2-100
MP	100%(96/96)96.2-100	100%(96/96)96.2-100	100%(96/96)96.2-100	100%(96/96)96.2-100	100%(96/96)96.2-100	100%(96/96)96.2-100

Table 3: MAX CT/GC/TV Site-to-Site Reproducibility Study Results

4 For the True Negative (TN) category, the reported agreement indicates the percent of negative results. b For the High Negative (HN) category, the reported agreement indicates the percent of positive results.

Table 4:	C. trachomatis Site-to-Site Qualitative Reproducibility Across Sites with Pooled Days
	Runs and Replicates

	Type	x LoD	Site
Category			】		2		3		Total
			Agree/N	%	Agree/N	%	Agree/N	%	Agree/N	%
TN	Swab	0	224/224	100	224/224	100	224/224	100	672/672	100
	Urine		223/224	99.6	224/224	100	224/224	100	671/672	99.9
HN	Swab	0.2	29/32	90.6	21/32	65.6	25/32	78.1	75/96	78.1
	Urine		28/32	87.5	20/32	62.5	24/32	75.0	72/96	75.0
LP	Swab	1.5	32/32	100	32/32	100	32/32	100	તે જેવા છે. જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામના લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો	100
	Urine		32/32	100	32/32	100	32/32	100	તે જેવા છે. જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામના લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો	100
MP	Swab	3	32/32	100	32/32	100	32/32	100	તે જેવા છે. જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામના લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો	100
	Urine		32/32	100	32/32	100	32/32	100	તે જેવા છે. આ ગામના લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ	100

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

Variable	Type	Cat.	Agreed/ N	Mean	Within Run		Between Run		Between Day		Between Operator		Between Site		Total
					SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
EP	Swab	HN	75/96	1563.3	556.6	35.6	285.2	18.2	0.0	0.0	0.0	0.0	337.2	21.6	710.6	45.5
	Swab	LP	96/96	2170.9	417.7	19.2	268.7	12.4	0.0	0.0	0.0	0.0	345.6	15.9	605.1	27.9
	Swab	MP	96/96	2264.4	297.6	13.1	215.9	9.5	0.0	0.0	0.0	0.0	232.0	10.2	434.8	19.2
EP	Urine	HN	72/96	1488.8	601.0	40.4	340.6	22.9	0.0	0.0	142.0	9.5	0.0	0.0	705.2	47.4
	Urine	LP	96/96	2221.5	380.7	17.1	201.4	9.1	96.5	4.3	224.8	10.1	279.6	12.6	568.7	25.6
	Urine	MP	96/96	2219.0	308.9	13.9	207.6	9.4	0.0	0.0	36.7	1.7	213.9	9.6	430.8	19.4
SDPA	Swab	HN	75/96	37.3	1.4	3.9	0.1	0.3	0.4	1.0	0.0	0.0	0.4	0.9	1.5	4.1
	Swab	LP	96/96	34.8	0.8	2.4	0.0	0.0	0.0	0.0	0.1	0.2	0.3	1.0	0.9	2.6
	Swab	MP	96/96	34.4	0.6	1.8	0.3	0.8	0.0	0.0	0.1	0.2	0.6	1.6	0.9	2.6
SDPA	Urine	HN	72/96	37.8	1.6	4.3	0.0	0.0	0.0	0.0	0.0	0.0	0.4	1.2	1.7	4.5
	Urine	LP	96/96	33.6	0.7	2.0	0.3	1.0	0.3	0.8	0.1	0.3	0.6	1.8	1.0	2.9
	Urine	MP	96/96	32.9	0.6	1.8	0.1	0.3	0.1	0.4	0.1	0.2	0.6	1.8	0.8	2.6

C. trachomatis Site-to-Site Quantitative Reproducibility Across Sites, Days, Runs and
Within Run Table 5:

Table 6:	N. gonorrhoeae Site-to-Site Qualitative Reproducibility Across Sites with Pooled Days
	Runs and Replicates

Category	Type	x LoD	Site 1		Site 2		Site 3		Total
TN	Swab	0	32/32	100	32/32	100	32/32	100	96/96	100
TN	Urine	0	224/224	100	224/224	100	224/224	100	672/672	100
HN	Swab	0.15	16/32	50.0	15/32	46.9	22/32	68.8	53/96	55.2
HN	Urine	0.25	8/32	25.0	3/32	9.4	4/32	12.5	15/96	15.6
LP	Swab	1.5	32/32	100	32/32	100	32/32	100	96/96	100
LP	Urine	1.5	32/32	100	32/32	100	32/32	100	96/96	100
MP	Swab	3	32/32	100	32/32	100	32/32	100	96/96	100
MP	Urine	3	32/32	100	32/32	100	32/32	100	96/96	100

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

Variable	Type	Cat	Agreed/N	Mean	Within Run		Between Run		BetweenDay		BetweenOperator		Between Site		Total
					SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
EP	Swab	HN	53/96	974.2	369.2	37.9	0.0	0.0	0.0	0.0	55.9	5.7	119.8	12.3	392.1	40.3
	Swab	LP	96/96	1518.0	199.1	13.1	227.5	15.0	0.0	0.0	75.8	5.0	260.2	17.1	406.0	26.7
	Swab	MP	96/96	1715.0	265.8	15.5	186.6	10.9	84.0	4.9	0.0	0.0	299.7	17.5	449.8	26.2
	Urine	HN	15/96	1615.2	0.9	0.1	600.8	37.2	0.0	0.0	0.0	0.0	68.3	4.2	604.6	37.4
	Urine	LP	96/96	2260.4	364.6	16.1	225.1	10.0	0.0	0.0	107.1	4.7	437.8	19.4	621.9	27.5
Urine	MP	96/96	2420.7	737.0	30.4	0.0	0.0	0.0	0.0	0.0	0.0	162.8	6.7	754.8	31.2
SDPA	Swab	HN	53/96	35.6	1.1	3.2	0.0	0.0	0.0	0.0	0.0	0.0	0.1	0.2	1.1	3.2
	Swab	LP	96/96	33.6	0.7	2.0	0.3	0.9	0.0	0.0	0.1	0.2	0.1	0.4	0.7	2.2
	Swab	MP	96/96	32.6	0.6	1.7	0.2	0.8	0.0	0.0	0.2	0.6	0.3	1.0	0.7	2.2
	Urine	HN	15/96	37.8	0.7	1.9	2.2	5.8	0.0	0.0	0.0	0.0	1.1	3.0	2.6	6.7
	Urine	LP	96/96	33.8	0.8	2.3	0.2	0.5	0.0	0.0	0.3	0.8	0.0	0.0	0.8	2.5
	Urine	MP	96/96	32.8	0.6	2.0	0.0	0.0	0.0	0.0	0.0	0.0	0.2	0.6	0.7	2.0

Table 7: N. gonorrhoeae Site-to-Site Quantitative Reproducibility Across Sites, Days, Runs and Within Run

Table 8:	T. vaginalis Site-to-Site Qualitative Reproducibility Across Sites with Pooled Days, Runand Replicates
----------	-------------------------------------------------------------------------------------------------------------------

Category	Type	x LoD	Site 1		Site 2		Site 3		Total
			Agree/N	%	Agree/N	%	Agree/N	%	Agree/N	%
TN	Swab	0	224/224	100	224/224	100	224/224	100	672/672	100
	Urine	0	32/32	100	32/32	100	32/32	100	96/96	100
HN	Swab	0.25	15/32	46.9	15/32	46.9	20/32	62.5	50/96	52.1
	Urine	0.05	4/32	12.5	19/32	59.4	11/32	34.4	34/96	35.4
LP	Swab	1.5	30/32	93.8	31/32	96.9	32/32	100	93/96	96.9
	Urine	1.5	32/32	100	32/32	100	32/32	100	96/96	100
MP	Swab	3	32/32	100	32/32	100	32/32	100	96/96	100
	Urine	3	32/32	100	32/32	100	32/32	100	96/96	100

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

Variable	Type	Cat.	Agreed/N	Mean	Within Run		Between Run		Between Day		BetweenOperator		Between Site		Total
					SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
EP	Swab	HN	50/96	2172.0	946.7	43.6	0.0	0.0	414.0	19.1	0.0	0.0	450.2	20.7	1127.1	51.9
		LP	93/96	3068.7	1063.7	34.7	0.0	0.0	0.0	0.0	0.0	0.0	779.8	25.4	1318.9	43.0
		MP	96/96	3519.5	875.1	24.9	0.0	0.0	0.0	0.0	23.4	0.7	809.1	23.0	1192.1	33.9
	Urine	HN	34/96	1887.5	747.1	39.6	200.7	10.6	0.0	0.0	0.0	0.0	0.0	0.0	0.0	773.6
		LP	96/96	3076.8	289.8	9.4	76.5	2.5	0.0	0.0	78.9	2.6	115.4	3.8	330.7	10.7
		MP	96/96	3092.0	199.4	6.4	184.0	5.9	0.0	0.0	0.0	0.0	206.0	6.7	340.6	11.0
SDPA	Swab	HN	50/96	37.6	1.9	5.1	0.0	0.0	0.0	0.0	0.2	0.6	0.0	0.0	1.9	5.1
		LP	93/96	35.3	1.2	3.3	0.5	1.5	0.0	0.0	0.0	0.0	0.0	0.0	1.3	3.6
		MP	96/96	35.0	1.0	2.8	0.0	0.0	0.3	1.0	0.3	0.8	0.0	0.0	1.1	3.1
	Urine	HN	34/96	38.3	1.6	4.1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	1.6	4.1
		LP	96/96	34.6	0.5	1.6	0.2	0.6	0.1	0.2	0.2	0.5	0.1	0.2	0.6	1.8
		MP	96/96	33.5	0.3	1.0	0.2	0.7	0.0	0.0	0.0	0.0	0.0	0.0	0.4	1.3

Table 9: T. vaginalis Site-to-Site Quantitative Reproducibility Across Sites, Days, Runs and Within Run

For the Lot-to-Lot reproducibility study, two operators each completed a single run of 10 panel members on a single instrument for each of three lots of reagents over an 8-day period. The panels used were the same as described under the Precision heading, above. Results from one reagent lot of the site to site reproducibility study were used to comprise data for one lot of reagents for the Lot-to-Lot study.

The overall Lot-to-Lot reproducibility percent agreement across all targets ranged from 99.9% to 100%, 29.2% to 72.9%, and 100% for the TN, HN, LP and MP categories, respectively (Table 10).

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

Target	Type	Level	Correct	Total	% Correct	95% CI
Chlamydia trachomatis	Swab	TN**	672	672	100	(99.4-100)
		HN*	70	96	72.9	(63.3-80.8)
		LP	96	96	100	(96.2-100)
		MP	96	96	100	(96.2-100)
Chlamydia trachomatis	Urine	TN	672	672	100	(99.4-100)
		HN	70	96	72.9	(63.3-80.8)
		LP	96	96	100	(96.2-100)
		MP	96	96	100	(96.2-100)
Neisseria gonorrhoeae	Swab	TN	96	96	100	(96.2-100)
		HN	40	96	41.7	(32.3-51.7)
		LP	96	96	100	(96.2-100)
		MP	96	96	100	(96.2-100)
Neisseria gonorrhoeae	Urine	TN	672	672	100	(99.4-100)
		HN	44	96	45.8	(36.2-55.8)
		LP	96	96	100	(96.2-100)
		MP	96	96	100	(96.2-100)
Trichomonas vaginalis	Swab	TN	671	672	99.9	(99.2-100)
		HN	56	96	58.3	(48.3-67.7)
		LP	96	96	100	(96.2-100)
		MP	96	96	100	(96.2-100)
Trichomonas vaginalis	Urine	TN	96	96	100	(96.2-100)
		HN	28	96	29.2	(21.0-38.9)
		LP	96	96	100	(96.2-100)
		MP	96	96	100	(96.2-100)

Table 10: Lot-to-Lot Reproducibility

HNs are dilutions of the LoD designed to produce results that are negative for 5% to 85% of replicates. As such, "% Correct" correlates to the percent of negative results.

** TNs were blanks, therefore, "% Correct" correlates to the percent of negative results.

{14}------------------------------------------------

Sample Storage

First void urine specimens must be transferred from the collection cup to the BD MAX UVE Sample Buffer Tube within 4 hours of collection when kept at 2-30 °C or within 24 hours of collection when stored at

2-8 °C. Clinician-collected endocervical swab and patient-collected vaginal swab specimens must be transferred immediately or within two hours after collection to the BD MAX UVE Sample Buffer Tube when kept at 2-30 ℃. Protect against exposure to excessive heat.

Table 11: Specimen Stability Prior to Transfer into the BD MAX UVE Sample Buffer Tube

Specimen Stability	Specimen Type	Transport and/or Storage Temperature
		2-30°C	2-8°C
Prior to Transfer into BDMAX UVE Sample Buffer Tube	Urine	4 hours	24 hours
	Vaginal/Endocervical Swab	2 hours	2 hours

Urine or swab sample in BD MAX UVE Sample Buffer Tubes can be transported and stored for up to 5 days at 2-30 ℃ or up to 30 days at -20 ℃ prior to pre-warm.

Table 12:	Sample Stability in BD MAX UVE Sample Buffer Tube Prior to Pre-
-----------	-----------------------------------------------------------------

		Transport and/or Storage Temperature
Sample Stability	Specimen Type	2-30°C	-20°C
In BD MAX UVE SampleBuffer Tube	Urine, Vaginal/EndocervicalSwab	5 days	30 days

Once pre-warmed, samples previously stored at the 2-30 ℃ condition (Table 12) can be stored for an additional 5 days at 2-30 °C or an additional 30 days at -20 °C (Table 13) before testing on the BD MAX System. Once pre-warmed, samples previously stored at the -20 °C condition (Table 12) can be stored for an additional 5 days at -20 or 2-30 °C (Table 13) before testing on the BD MAX System.

NOTE: Combined sample stability [prior to pre-warm (Table 12) and post pre-warm (Table 13)] can not exceed a total of 35 days.

Table 13: Sample Stability in BD MAX UVE Sample Buffer Tube Post Pre-Warm

Sample Stability	Specimen Type	Storage Temperature
		2-30°C	-20°C
Post Pre-warm(previously stored 2-30 °C)	Urine, Vaginal/Endocervical Swab	5 days	30 days
Post Pre-warm(previously stored -20 °C)	Urine, Vaginal/Endocervical Swab	5 days	5 days

{15}------------------------------------------------

Controls

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

. Commercially available positive control materials
. Chlamydia trachomatis serovar H (ATCC VR-879)
. Neisseria gonorrhoeae (ATCC 19424)
. Trichomonas vaginalis (ATCC 30001)
External negative control
. Use a non-inoculated BD MAX™ UVE Sample Buffer Tube

The assay includes a Specimen Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity, and the presence of inhibitory substances.

Analytical Sensitivity

The analytical sensitivity (Limit of Detection or LoD) for the BD MAX CT/GC/TV was determined for each assay target individually. Two (2) representative bacterial suspensions were prepared for each of the target organisms and were inoculated into the UVE Sample Buffer Tube along with pooled negative matrix (both vaginal swab and female urine were evaluated, separately). The pooled negative matrix was created from specimens obtained from patients that were characterized by the BD MAX CT/GCTV. The organism concentrations were used to simulate positive samples with a wide range of organism loads. The LoD was determined for each organism tested with both vaginal swab and female urine target-negative matrix. The results from the LoD study can be found in Table 14.

Organism	Strain	Specimen	LoD Concentration (units/mL)a
Chlamydia trachomatis	Serovar H	Urine	11
		Vaginal Swab	9
	Serovar D	Urine	5
		Vaginal Swab	13
Neisseria gonorrhoeae	ATCC 19424	Urine	60
		Vaginal Swab	60
	ATCC 49226	Urine	181
		Vaginal Swab	117
Trichomonas vaginalis	ATCC 30001	Urine	10
		Vaginal Swab	5
	ATCC 50143	Urine	34
		Vaginal Swab	10

Table 14: BD MAX CT/GC/TV Target Limits of Detection

4 Units/mL LoD concentration represented in Elementary Bodies (EB)/mL for Chlamydia trachomatis, cells/mL for Neisseria gonorrhoeae and TV/mL for Trichomonas vaginalis.

{16}------------------------------------------------

The BD MAX CT/GC/TV assay could detect ≥95% proportion positive results with fifteen (15) additional Chlamvdia trachomatis serovars (A, B, Ba, C, E, vE, F, G. I. J. K, L1, L2, L2a and L3), thirty (30) Neisseria gonorrhoeae strains and eight (8) Trichomonas vaginalis strains (ATCC 30092, 30184. 30185, 30187, 30236, 30237, 30235 and 30186). These 53 serovars/strains represented public collections and well-characterized clinical isolates and were inoculated at 1X LoD in BD MAX UVE Sample Buffer and tested with both pooled female urine and pooled vaginal swab specimens. The BD MAX CT/GC/TV assay correctly identified 51 of the serovars/strains tested for urine specimens and 49 of the serovars/strains tested for vaginal swab specimens upon initial testing. Three (3) strains of Trichomonas vaginalis and one (1) serovar of Chlamydia trachomatis in vaginal swab specimen, in addition to two (2) strains of Neisseria gonorrhoeae in urine, did not meet acceptance criteria and were further evaluated. Of the six (6) strains further evaluated, one (1) was detected at 2X LoD and five (5) were detected at 1X LoD.

Analytical Specificity

The BD MAX CT/GC/TV assay was performed on samples containing phylogenetically related species and other organisms (bacteria, viruses) likely to be found in urogenital specimens. The bacterial cells, yeasts and parasites were tested in the BD MAX UVE Sample Buffer Tube at 1x10° cells/mL, genomic DNA cp/mL, or elementary bodies/mL, and viruses were tested at 1x10' viral particles or genomic equivalents/mL.

98% (168/170) of bacterial strains, yeast, parasites and viruses tested produced negative results with the BD MAX CT/GC/TV assay. No cross-reaction was observed for Chlamydia trachomatis or Neisseria gonorrhoeae.
. Pentatrichomonas hominis (commensal of the large intestine) produced positive results at a concentration ≥ 3.39 x 10 TV/mL for Trichomonas vaginalis and negative results for all other targets with the BD MAX CT/GC/TV assay.
Trichomonas tenax (commensal of the oral cavity) produced positive results at a concentration ≥ 10 TV/mL for Trichomonas vaginalis and negative results for all other targets with the BD MAX CT/GC/TV assay.

Interfering Substances

Fourty-four (44) biological and chemical substances occasionally used or found in urogenital specimens were evaluated for potential interference with the BD MAX CT/GC/TV assay near the LoD for each particular target. Three (3) organisms (Eschericia coli, Gardnerella vaginalis and Candida albicans,) were also tested at a high concentration in order to assess bacterial interference. Included in this study were antibiotic, analgesic, antifungal, and contraceptive pools which contained combinations of the various chemicals or biological organisms that were tested at a concentration that may be found in urogenital specimens. Potentially interfering substances in urine specimens included whole blood (Table 16). Potentially interfering substances in vaginal swab specimens include VCF® Contraceptive Foam, Conceptrol® Contraceptive Gel, Vaginal Anti-Itch Cream, Acyclovir, Metronidazole and whole blood (Table 17). VCF Contraceptive Foam, Conceptrol® Contraceptive Gel and Acyclovir demonstrated potential interference at concentrations greater than 25uL/mL in vaginal swab specimens. Vaginal Anti-Itch Cream and Metronidazole demonstrated potential interference at concentrations greater than 2.5μL/mL in vaginal swab specimens. Whole blood demonstrated potential interference at concentrations greater than 0.04% v/v in urine and 0.66uL/mL in vaginal swab specimens.

{17}------------------------------------------------

Brand Name or Description	Result	Brand Name or Description	Result
Norethindrone	NI	Escherichia coli	NI
17-α-Ethinylestradiol	NI	Gardneralla vaginalis	NI
4-Acetamidophenol	NI	Candida albicans	NI
Acetylsalicylic Acid	NI	Mucous (Bovine Cervical)	NI
Naproxen	NI	Whole Blood	Ia
Ibuprofen	NI	Semen	NI
Human Serum Albumin	NI	Leukocytes	NI
Glucose	NI	Phenazopyridine Hydrochloride	NI
Amoxicillin Trihydrate	NI	High pH	NI
Metronidazole	NI	Low pH	NI
Tetracycline Hydrochloride	NI	Bilirubin	NI
Azithromycin	NI	Feminine Deodorant Spray	NI
Ceftriaxone	NI	Talcum Powder	NI
Sulfamethoxazole	NI
Trimethoprim	NI
Erythromycin	NI

Table 16: Endogenous and Exogenous Interfering Substances Tested in Urine

NI: No reportable interference with the BD MAX CT/GC/TV

ª 0.04% v/v maximum concentration where interference was not observed

		Table 17: Endogenous and Exogenous Interfering Substances Tested in Vaginal Swab Matrix

Brand Name or Description	Result	Brand Name orDescription	Result
VCF Contraceptive Foam	Ia	Douche	NI
VCF Contraceptive Film	NI	Feminine Deodorant Spray	NI
Conceptrol Contraceptive Gel	Ia	Progesterone	NI
Gyne-Lotrimin 3	NI	Estradiol	NI
Monistat 3	NI	Mucous (Bovine Cervical)	NI
Tioconazole 1	NI	Semen	NI
Vaginal Anti-Itch Cream	Ib	Whole Blood	Ic
Vaginal Lubricant Liquid - water based	NI	Leukocytes	NI
Preparation H Hemorrhoid Gel	NI
Antiviral (Zovirax – Acyclovir)	Ia
AntiProtozoal (Metronidazole)	Ib

NI: No reportable interference with the BD MAX CT/GC/TV

I: Interference with the BD MAX CT/GC/TV

4 25 µL/mL maximum concentration where interference was not observed

b 2.5 µL/mL maximum concentration where interference was not observed

° 0.66 µL/mL maximum concentration where interference was not observed

{18}------------------------------------------------

Carryover/Cross-Contamination

A study was conducted to investigate within-run carryover and between-run carryover while processing specimens with a high load of Chlamydia trachomatis. Neisseria gonorrhoeae and Trichomonas vaginalis in the BD MAX CT/GC/TV. A panel made of one high positive member containing the three target organisms and one negative member was used to prepare numerous samples. Strains of Chlamydia trachomatis (VR-879, Serovar H), Neisseria gonorrhoeae (ATCC 19424) and Trichomonas vaginalis (ATCC 30001) were used for the high positive panel member (1 x 10°CFU per mL). The negative member did not contain any target analyte. Twelve (12) replicates of the high positive panel member and 12 replicates of the negative panel member were tested in each run by alternating negative and positive samples. Two (2) operators performed a total of 6 consecutive runs across 3 BD MAX instruments for a total of 18 runs containing 24 samples. Of the 432 readings across all targets, no false positive results were obtained.

Mixed Infection/Competitive Interference

The mixed infection/competitive interference study was designed to evaluate the ability of the BD MAX CT/GC/TV assay to detect low positive results in the presence of other targets at high concentrations. Three (3) organisms (Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis) were individually prepared at 1.5x their respective LOD to serve as a low target in the BD MAX UVE Sample Buffer Tube. A high target mix comprised of the organisms representative of the other two BD MAX CT/GC/TV analytes at a concentration of ≥1x106 EB, cells or TV/mL into the BD MAX UVE Sample Buffer Tube along with pooled urine or vaginal swab specimens and tested to simulate mixed infections. All three low target organisms were successfully detected by the BD MAX CT/GC/TV when combined with their respective simulated high target concentration mixed infection preparations in vaginal swab specimens. Chlamydia trachomatis and Trichomonas vaginalis low target organisms were successfully detected by the BD MAX CT/GC/TV assay when combined with their respectived simulated high target concentration mixed infection preparations in urine specimens. The Neisseria gonorrhoeae low target in urine specimen required further evaluation and was successfully detected (95.31% (61/64)) when combined with the high target mixed infection preparations at a concentration of 1 x 10° EB and TV/mL.

Clinical Performance Studies

The Clinical Accuracy study was designed to assess the performance of the BD MAX CT/GC/TV assay for the identification of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis, from urine specimens, clinician-collected endocervical swab specimens and patient-collected vaginal swab specimens (in a clinical setting) from symptomatic subjects. This multicenter study evaluated results obtained with the BD MAX CT/GC/TV compared to reference methods defining the Patient Infected Status (PIS).

Nine (9) geographically diverse clinical sites in North America participated in the clinical study to evaluate the BD MAX CT/GC/TV assay, eight (8) of which were collection sites that also performed testing and one (1) clinical reference lab that only performed reference testing. Two thousand one hundred and sixty-six (2166) female subjects and 908 male subjects from OB/GYN, sexually transmitted disease (STD) and family planning clinics were enrolled in the Chlamydia trachomatis and Neisseria gonorrhoeae assay portion of the study. Of these, one thousand three hundred and twenty-seven (1327) female subjects were enrolled in the Trichomonas vaginalis assay portion of the study. Subjects were classified as symptomatic if they reported symptoms such as dysuria, urethral discharge, itching, odor, coital pain/difficulty/bleeding, testicular or scrotum pain/swelling, abnormal vaginal discharge, or pelvic/uterine/adnexal pain. Subjects were classified as asymptomatic if they did not report these symptoms.

{19}------------------------------------------------

The final data analysis included 2114 evaluable female subjects for Chlamydia trachomatis and Neisseria gonorrhoeae, with 1291 of these female subjects evaluable for Trichomonas vaginalis. For males, 892 were evaluable subjects for Chlamydia trachomatis and Neisseria gonorrhoeae analyses. From these compliant subjects, Chlamydia trachomatis performance was calculated from 1836 patient-collected vaginal swab, 1831 endocervical swab, 1849 female urine and 830 male urine specimens. Neisseria gonorrhoeae evaluable specimens included 1836 patient-collected vaginal swab, 1824 endocervical swab, 1849 female urine and 840 male urine specimens. Trichomonas vaginalis compliant specimens consisted of 1048 patient-collected vaginal swab, 1039 endocervical swab, and 1047 female urine specimens. Assay performance compared to PIS is reported in Table 18.

Gender	Spec	Symp	CT		GC		TV
			%Sens	%Spec	%Sens	%Spec	%Sens	%Spec
Female	VagSwab	A	100(51/51)93.0-100	98.7(734/744)97.5-99.3	94.1(16/17)73.0-99.0	99.9(777/778)99.3-100	93.1(27/29)78.0-98.1	97.5(270/277)94.9-98.8
		S	98.9(89/90)94.0-99.8	98.6(938/951)97.7-99.2	96.3(26/27)81.7-99.3	99.8(1012/1014)99.3-99.9	96.7(119/123)91.9-98.7	99.5(616/619)98.6-99.8
		ALL	99.3(140/141)96.1-99.9	98.6(1672/1695)98.0-99.1	95.5(42/44)84.9-98.7	99.8(1789/1792)99.5-99.9	96.1(146/152)91.7-98.2	98.9(886/896)98.0-99.4
			EndoSwab	A	94.1(48/51)84.1-98.0	99.1(737/744)98.1-99.5	94.1(16/17)73.0-99.0	100(777/777)99.5-100	96.6(28/29)82.8-99.4	98.2(270/275)95.8-99.2
	S	96.6(84/87)90.3-98.8		99.4(943/949)98.6-99.7	96.3(26/27)81.7-99.3	99.9(1002/1003)99.4-100	92.7(114/123)86.7-96.1	99.8(611/612)99.1-100
		ALL	95.7(132/138)90.8-98.0	99.2(1680/1693)98.7-99.6	95.5(42/44)84.9-98.7	99.9(1779/1780)99.7-100	93.4(142/152)88.3-96.4	99.3(881/887)98.5-99.7
			Urine	A	92.3(48/52)81.8-97.0	99.7(747/749)99.0-99.9	88.9(16/18)67.2-96.9	99.5(779/783)98.7-99.8	93.1(27/29)78.0-98.1	98.2(272/277)95.8-99.2
	S	91.1(82/90)83.4-95.4		99.4(952/958)98.6-99.7	100(28/28)87.9-100	99.9(1019/1020)99.4-100	92.8(116/125)86.9-96.2	99.8(615/616)99.1-100
	ALL	91.5(130/142)85.8-95.1		99.5(1699/1707)99.1-99.8	95.7(44/46)85.5-98.8	99.7(1798/1803)99.4-99.9	92.9(143/154)87.7-96.0	99.3(887/893)98.5-99.7
		Male		Urine	A	98.6(69/70)92.3-99.7	99.5(378/380)98.1-99.9	80.0(4/5)37.6-96.4	100(447/447)99.1-100
	S				94.6(105/111)88.7-97.5	99.3(267/269)97.3-99.8	100(103/103)96.4-100	100(285/285)98.7-100
	ALL				96.1(174/181)92.2-98.1	99.4(645/649)98.4-99.8	99.1(107/108)94.9-99.8	100(732/732)99.5-100

{20}------------------------------------------------

Of the 6573 specimens initially evaluated with the BD MAX CT/GC/TV assay, 1.6% of patient-collected vaginal swab. 1.8% of endocervical swab and 1.5% of urine specimens initially reported as Unresolved. Following a valid repeat test, 0.5% of patient-collected vaginal swab, 0.8% of endocervical swab and 0.4% of urine specimens remained Unresolved. The total numbers in Table 19 are based on compliant specimens and BD MAX CT/GC/TV results.

	Initial Unresolved Rate		Final Unresolved Rate with Valid Repeat
Specimen Type	Estimate	95% CI	Estimate	95% CI
Vaginal Swab	1.6% (31/1910)	(1.1%, 2.3%)	0.5% (9/1908)	(0.2%, 0.9%)
Endocervical	1.8% (34/1907)	(1.3%, 2.5%)	0.8% (16/1902)	(0.5%, 1.4%)
Urine	1.5% (41/2756)	(1.1%, 2.0%)	0.4% (11/2752)	(0.2%, 0.7%)

Table 19:	Unresolved Rates
-----------	------------------

Of the 6573 specimens initially evaluated with the BD MAX CT/GC/TV assay, 0.9% of patient-collected vaginal swab, 0.4% of endocervical swab and 0.9% of urine specimens initially reported as Indeterminate. Following a valid repeat test, 0.3% of patient-collected vaginal swab, 0.1% of endocervical swab and 0.2% of urine specimens remained Indeterminant. The total numbers in Table 20 are based on compliant specimens and BD MAX CT/GC/TV results.

	Initial Indeterminate Rate		Final Indeterminate Rate with Valid Repeat
Specimen Type	Percent	95% CI	Percent	95% CI
Vaginal Swab	0.9% (17/1910)	(0.6%, 1.4%)	0.3% (5/1908)	(0.1%, 0.6%)
Endocervical	0.4% (8/1907)	(0.2%, 0.8%)	0.1% (2/1902)	(0.0%, 0.4%)
Urine	0.9% (25/2756)	(0.6%, 1.3%)	0.2% (5/2752)	(0.1%, 0.4%)

Of the 6573 specimens initially evaluated with the BD MAX CT/GC/TV assay. 1.7% of patient-collected vaginal swab, 1.7% of endocervical swab and 1.9% of urine specimens initially reported as Incomplete. Following a valid repeat test, 0.1% of patient-collected vaginal swab, 0.1% of endocervical swab and 0.1% of urine specimens remained Incomplete. The total numbers in Table 21 are based on compliant specimens and BD MAX CT/GC/TV results.

{21}------------------------------------------------

	Initial Incomplete Rate		Final Incomplete Rate with Valid Repeat
Specimen Type	Estimate	95% CI	Estimate	95% CI
Vaginal Swab	1.7% (33/1910)	(1.2%, 2.4%)	0.1% (1/1908)	(0.0%, 0.3%)
Endocervical	1.7% (32/1907)	(1.2%, 2.4%)	0.1% (1/1902)	(0.0%, 0.3%)
Urine	1.9% (52/2756)	(1.4%, 2.5%)	0.1% (2/2752)	(0.0%, 0.3%)

Table 21: Incomplete Rates

Expected Values

The prevalence of specimens that are positive for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis depends upon the patient population. Factors include the type of clinic, patient age, risk factors, gender, and test method. In the BD MAX CT/GC/TV clinical study, a total of 1990 female subjects for Chlamydia trachomatis and Neisseria gonorrhoeae, and 1085 female subjects for Trichomonas vaginalis were compliant at the subject and composite reference method algorithm level. For male subjects, a total of 873 for Chlamydia trachomatis and 876 for Neisseria gonorrhoeae were compliant at the subject and composite reference method algorithm level.

{22}------------------------------------------------

Gender	Symptom Status	Site	Chlamydia trachomatis	Neisseria gonorrhoeae	Trichomonas vaginalis
Female	A	1	18.5% (5/27)	7.4% (2/27)	15.4% (2/13)
		2	8.5% (5/59)	0.0% (0/59)	24.1% (7/29)
		3	6.0% (13/216)	0.9% (2/216)	8.8% (3/34)
		4	1.8% (2/113)	1.8% (2/113)	2.2% (1/45)
		5	1.2% (1/81)	0.0% (0/81)	10.9% (5/46)
		6	6.5% (2/31)	0.0% (0/31)	0.0% (0/10)
		7	9.1% (23/254)	5.1% (13/254)	9.8% (13/133)
		8	3.7% (3/82)	3.7% (3/82)	0.0% (0/9)
	All	6.3% (54/863)	2.5% (22/863)	9.7% (31/319)
S	1	13.1% (8/61)	3.3% (2/61)	21.0% (13/62)
	2	9.4% (10/106)	2.8% (3/106)	17.2% (15/87)
	3	7.0% (14/199)	1.0% (2/199)	22.5% (9/40)
	4	4.3% (2/47)	0.0% (0/47)	8.7% (2/23)
	5	5.4% (11/202)	1.0% (2/202)	10.3% (20/194)
	6	2.9% (2/70)	1.4% (1/70)	24.1% (14/58)
	7	11.9% (42/352)	5.7% (20/352)	15.2% (41/269)
	8	10.0% (9/90)	0.0% (0/90)	39.4% (13/33)
	All	8.7% (98/1127)	2.7% (30/1127)	16.6% (127/766)
Total			7.6% (152/1990)	2.6% (52/1990)	14.6% (158/1085)
Male	A	1	11.1% (2/18)	0.0% (0/18)
		2	14.6% (19/130)	0.8% (1/132)
		4	8.8% (3/34)	0.0% (0/34)
		6	9.4% (6/64)	1.6% (1/64)
		7	18.2% (42/231)	1.3% (3/231)
		All	15.1% (72/477)	1.0% (5/479)
	S	1	37.4% (34/91)	35.2% (32/91)	N/A
2		24.2% (37/153)	22.1% (34/154)
4		50.0% (4/8)	25.0% (2/8)
6		22.9% (8/35)	14.3% (5/35)
7		27.5% (30/109)	29.4% (32/109)
All		28.5% (113/396)	26.4% (105/397)
Total			21.2% (185/873)	12.6% (110/876)

BD MAX CT/GC/TV Clinical Study Prevalence Table 22:

{23}------------------------------------------------

Positive and Negative Predictive Value

Hypothetical Positive Predictive Value (PPV) and Negative Value (NPV) were calculated and are represented in Tables 23-25 for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis, respectively. These calculations are based on the hypothetical prevalence and overall sensitivity and specificity compared to the Patient Infected Status.

Prevalence	Sensitivity	Specificity	PPV	NPV
1%			53.6%	100%
2%			70.0%	99.9%
5%			85.8%	99.8%
10%	95.7% (576/602)	99.2% (5696/5744)	92.7%	99.5%
20%			96.6%	98.9%
30%			98.0%	98.2%
40%			98.7%	97.2%
50%			99.1%	95.8%

Table 23:	Hypothetical PPV and NPV for Chlamydia trachomatis Compared to PIS
-----------	---------------------------------------------------------------------------	--	--	--

	PPV		NPV
Prevalence	Compared to PIS	Compared to Culture	Compared to PIS	Compared to Culture
1%	50%	95%	99.9%	99.9%
5%	83%	99%	99.7%	99.8%
10%	91%	99%	99.4%	99.6%

Prevalence	Sensitivity	Specificity	PPV	NPV
1%	97.1% (235/242)	99.9% (6098/6107)	86.9%	100.0%
2%			93.1%	99.9%
5%			97.2%	99.8%
10%			98.7%	99.7%
20%			99.4%	99.3%
30%			99.6%	98.8%
40%			99.8%	98.1%
50%			99.8%	97.2%

Table 25:	Hypothetical PPV and NPV for Trichomonas vaginalis Compared to Prevalence
-----------	----------------------------------------------------------------------------------

Prevalence	Sensitivity	Specificity	PPV	NPV
1%	94.1% (431/458)	99.2% (2654/2676)	53.6%	99.9%
2%	94.1% (431/458)	99.2% (2654/2676)	70.0%	99.9%
5%	94.1% (431/458)	99.2% (2654/2676)	85.8%	99.7%
10%	94.1% (431/458)	99.2% (2654/2676)	92.7%	99.3%
20%	94.1% (431/458)	99.2% (2654/2676)	96.6%	98.5%
30%	94.1% (431/458)	99.2% (2654/2676)	98.0%	97.5%
40%	94.1% (431/458)	99.2% (2654/2676)	98.7%	96.2%
50%	94.1% (431/458)	99.2% (2654/2676)	99.1%	94.4%

Regulation Number and Section

§ 866.3860

Trichomonas vaginalis nucleic acid assay.(a)
Identification. ATrichomonas vaginalis nucleic acid assay is a device that consists of primers, probes, enzymes, and controls for the amplification and detection of trichomonas nucleic acids in endocervical swabs, vaginal swabs, and female urine specimens, from women symptomatic for vaginitis, cervicitis, or urethritis and/or to aid in the diagnosis of trichomoniasis in asymptomatic women. The detection of trichomonas nucleic acids, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of trichomoniasis caused byTrichomonas vaginalis .(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Nucleic Acid Amplification Assays for the Detection ofTrichomonas vaginalis; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.