(452 days)
Not Found
No
The device description and performance studies focus on automated DNA extraction and real-time PCR, with automated result interpretation based on predefined criteria (amplification status of target and control). There is no mention of AI, ML, or related concepts in the provided text.
No
This device is for the diagnosis of certain diseases, not for therapeutic purposes. It detects DNA from specific pathogens to aid in diagnosis, rather than treating or preventing a condition.
Yes
The Indication for Use statement explicitly states that 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." This directly indicates its role in diagnosis.
No
The device description explicitly states that 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. While software is mentioned for result interpretation, it is part of a larger system that includes significant hardware and consumables.
Based on the provided information, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the assay is for the "direct, qualitative detection of DNA from Chlamydia (CT), Neisseria gonorrhoeae (GC) and/or Trichomonas vaginalis (TV)" and is "indicated for use to aid in the diagnosis of chlamydial urogenital disease, gonococcal urogenital disease and/or trichomoniasis". This clearly describes a test performed on biological samples (urine and swabs) to provide information for diagnosing a disease.
- Device Description: The description details a system that performs automated DNA extraction and real-time PCR on biological samples. This is a typical process for in vitro diagnostic tests.
- Anatomical Site: The samples are collected from specific anatomical sites (urine, endocervical swabs, vaginal swabs), which are biological specimens.
- Clinical Performance Studies: The document describes clinical accuracy studies where the device's performance is compared to reference methods using patient samples. This is a standard requirement for demonstrating the clinical validity of an IVD.
- Key Metrics: The document reports metrics like Sensitivity, Specificity, PPV, and NPV, which are key performance indicators for diagnostic tests.
- Predicate Devices: The mention of predicate devices (ProbeTec™ assays) which are also IVDs further supports that this device falls under the IVD category.
All these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for 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.
Product codes (comma separated list FDA assigned to the subject device)
OUY, MKZ, LSL
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Urogenital
Indicated Patient Age Range
Not Found
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
Clinical Performance Studies: 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.
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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision (Within-laboratory): Evaluated at 1 internal site. Panel members divided into 4 categories: True negative (TN - Negative Clinical Matrix), Moderate positive (MP), Low positive (LP), High negative (HN). Each panel member prepared in pooled negative vaginal clinical swab specimen or female urine. Testing performed in duplicate, over 12 days, with 2 runs per day, by 2 different technologists. Results summarized as percent observed versus expected.
- Result: For TN, agreement was 100% across all specimen types and analytes. For LP and MP, agreement was generally 97.9-100%. HN results varied (e.g., C. trachomatis Swab 79.2%, N. gonorrhoeae Urine 10.4%).
Reproducibility (Site-to-Site): Three (3) sites (two external and one internal) were provided with 16 panels each (10 tubes per panel). Same panels as Precision Study. Each site performed the study on 8 nonconsecutive days, with 2 panels tested daily by 1 of 2 technologists. Qualitative and quantitative reproducibility assessed.
- Result: Overall Site-to-Site Reproducibility percent agreement ranged from 99.9-100% for TN, 15.6-78.1% for HN, 96.9-100% for LP, and 100% for MP. EP and SDPA values showed variability across sites, days, runs, and within-run.
Reproducibility (Lot-to-Lot): Two operators completed a single run of 10 panel members on a single instrument for each of three lots of reagents over an 8-day period. Panels same as Precision Study. Data from one reagent lot for site-to-site reproducibility was used for one lot.
- Result: Overall Lot-to-Lot reproducibility percent agreement across all targets ranged from 99.9-100% for TN, 29.2-72.9% for HN, and 100% for LP and MP categories.
Analytical Sensitivity (Limit of Detection or LoD): Determined for each assay target individually using two representative bacterial suspensions. Inoculated into UVE Sample Buffer Tube with pooled negative vaginal swab and female urine matrix.
- Results:
- C. trachomatis (Serovar H): Urine 11 EB/mL, Vaginal Swab 9 EB/mL
- C. trachomatis (Serovar D): Urine 5 EB/mL, Vaginal Swab 13 EB/mL
- N. gonorrhoeae (ATCC 19424): Urine 60 cells/mL, Vaginal Swab 60 cells/mL
- N. gonorrhoeae (ATCC 49226): Urine 181 cells/mL, Vaginal Swab 117 cells/mL
- T. vaginalis (ATCC 30001): Urine 10 TV/mL, Vaginal Swab 5 TV/mL
- T. vaginalis (ATCC 50143): Urine 34 TV/mL, Vaginal Swab 10 TV/mL
- Additional strains: The assay detected ≥95% positive results for 15 additional C. trachomatis serovars, 30 N. gonorrhoeae strains, and 8 T. vaginalis strains at 1X LoD. 51 of 53 serovars/strains detected for urine specimens, 49 of 53 for vaginal swab specimens on initial testing. 6 further evaluated strains detected at 1X or 2X LoD.
Analytical Specificity: Performed on samples containing phylogenetically related species and other organisms (bacteria, viruses) likely found in urogenital specimens at 1x10^6 cells/mL or cp/mL, viruses at 1x10^4 viral particles/mL.
- Result: 98% (168/170) of bacterial strains, yeast, parasites and viruses produced negative results. No cross-reaction for C. trachomatis or N. gonorrhoeae. Pentatrichomonas hominis and Trichomonas tenax produced positive results for T. vaginalis at specific concentrations but negative for other targets.
Interfering Substances: 44 biological and chemical substances evaluated for potential interference near the LoD.
- Result: Interfering substances identified in urine: whole blood (≥0.04% v/v). Interfering substances in vaginal swab: VCF Contraceptive Foam, Conceptrol Contraceptive Gel, Vaginal Anti-Itch Cream, Acyclovir, Metronidazole, and whole blood (≥0.66 µL/mL).
Carryover/Cross-Contamination: Study on within-run and between-run carryover with high load specimens. 1 high positive and 1 negative member panel used. 12 replicates of each tested in alternating pattern across 6 consecutive runs on 3 instruments (18 runs total, 24 samples per run).
- Result: Of 432 readings, no false positive results obtained.
Mixed Infection/Competitive Interference: Evaluated detection of low positive results in presence of other targets at high concentrations (≥1x10^6 EB, cells or TV/mL).
- Result: All three low target organisms (CT, GC, TV) successfully detected when combined with high target mixed infection preparations in vaginal swab specimens. CT and TV low targets successfully detected in urine. N. gonorrhoeae low target in urine required further evaluation and was successfully detected in 95.31% of cases (61/64) when combined with high target mixed infection preparations.
Clinical Performance Studies: Multicenter study comparing BD MAX CT/GC/TV to reference methods (Patient Infected Status).
- Sample Size: 2166 female subjects and 908 male subjects for CT/GC. 1327 female subjects for TV. Final evaluable subjects: 2114 females (CT/GC), 1291 females (TV), 892 males (CT/GC).
- Specimens: CT: 1836 patient-collected vaginal swab, 1831 endocervical swab, 1849 female urine, 830 male urine. GC: 1836 patient-collected vaginal swab, 1824 endocervical swab, 1849 female urine, 840 male urine. TV: 1048 patient-collected vaginal swab, 1039 endocervical swab, 1047 female urine.
- Results: Refer to "Key Metrics" section for detailed sensitivity and specificity. Unresolved rates: Initial 1.5-1.8%, final 0.4-0.8%. Indeterminate rates: Initial 0.4-0.9%, final 0.1-0.3%. Incomplete rates: Initial 1.7-1.9%, final 0.1%.
Hypothetical Positive and Negative Predictive Value (PPV and NPV): Calculated based on hypothetical prevalence and overall sensitivity and specificity compared to PIS.
- Results (at 10% prevalence):
- C. trachomatis: PPV 92.7%, NPV 99.5% (Sensitivity 95.7%, Specificity 99.2%)
- N. gonorrhoeae: PPV 98.7%, NPV 99.7% (Sensitivity 97.1%, Specificity 99.9%)
- T. vaginalis: PPV 92.7%, NPV 99.3% (Sensitivity 94.1%, Specificity 99.2%)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Female:
- Vaginal Swab - Chlamydia trachomatis (CT):
- Asymptomatic (A): Sensitivity 100% (51/51), Specificity 98.7% (734/744)
- Symptomatic (S): Sensitivity 98.9% (89/90), Specificity 98.6% (938/951)
- ALL: Sensitivity 99.3% (140/141), Specificity 98.6% (1672/1695)
- Vaginal Swab - Neisseria gonorrhoeae (GC):
- A: Sensitivity 94.1% (16/17), Specificity 99.9% (777/778)
- S: Sensitivity 96.3% (26/27), Specificity 99.8% (1012/1014)
- ALL: Sensitivity 95.5% (42/44), Specificity 99.8% (1789/1792)
- Vaginal Swab - Trichomonas vaginalis (TV):
- A: Sensitivity 93.1% (27/29), Specificity 97.5% (270/277)
- S: Sensitivity 96.7% (119/123), Specificity 99.5% (616/619)
- ALL: Sensitivity 96.1% (146/152), Specificity 98.9% (886/896)
- Endocervical Swab - CT:
- A: Sensitivity 94.1% (48/51), Specificity 99.1% (737/744)
- S: Sensitivity 96.6% (84/87), Specificity 99.4% (943/949)
- ALL: Sensitivity 95.7% (132/138), Specificity 99.2% (1680/1693)
- Endocervical Swab - GC:
- A: Sensitivity 94.1% (16/17), Specificity 100% (777/777)
- S: Sensitivity 96.3% (26/27), Specificity 99.9% (1002/1003)
- ALL: Sensitivity 95.5% (42/44), Specificity 99.9% (1779/1780)
- Endocervical Swab - TV:
- A: Sensitivity 96.6% (28/29), Specificity 98.2% (270/275)
- S: Sensitivity 92.7% (114/123), Specificity 99.8% (611/612)
- ALL: Sensitivity 93.4% (142/152), Specificity 99.3% (881/887)
- Female Urine - CT:
- A: Sensitivity 92.3% (48/52), Specificity 99.7% (747/749)
- S: Sensitivity 91.1% (82/90), Specificity 99.4% (952/958)
- ALL: Sensitivity 91.5% (130/142), Specificity 99.5% (1699/1707)
- Female Urine - GC:
- A: Sensitivity 88.9% (16/18), Specificity 99.5% (779/783)
- S: Sensitivity 100% (28/28), Specificity 99.9% (1019/1020)
- ALL: Sensitivity 95.7% (44/46), Specificity 99.7% (1798/1803)
- Female Urine - TV:
- A: Sensitivity 93.1% (27/29), Specificity 98.2% (272/277)
- S: Sensitivity 92.8% (116/125), Specificity 99.8% (615/616)
- ALL: Sensitivity 92.9% (143/154), Specificity 99.3% (887/893)
Male:
- Male Urine - CT:
- A: Sensitivity 98.6% (69/70), Specificity 99.5% (378/380)
- S: Sensitivity 94.6% (105/111), Specificity 99.3% (267/269)
- ALL: Sensitivity 96.1% (174/181), Specificity 99.4% (645/649)
- Male Urine - GC:
- A: Sensitivity 80.0% (4/5), Specificity 100% (447/447)
- S: Sensitivity 100% (103/103), Specificity 100% (285/285)
- ALL: Sensitivity 99.1% (107/108), Specificity 100% (732/732)
Unresolved Rates:
- Initial: Vaginal Swab 1.6%, Endocervical 1.8%, Urine 1.5%
- Final with Valid Repeat: Vaginal Swab 0.5%, Endocervical 0.8%, Urine 0.4%
Indeterminate Rates:
- Initial: Vaginal Swab 0.9%, Endocervical 0.4%, Urine 0.9%
- Final with Valid Repeat: Vaginal Swab 0.3%, Endocervical 0.1%, Urine 0.2%
Incomplete Rates:
- Initial: Vaginal Swab 1.7%, Endocervical 1.7%, Urine 1.9%
- Final with Valid Repeat: Vaginal Swab 0.1%, Endocervical 0.1%, Urine 0.1%
Hypothetical PPV and NPV (Female & Male Combined):
- Chlamydia trachomatis (Overall Sensitivity 95.7%, Specificity 99.2%):
- 1% Prevalence: PPV 53.6%, NPV 100%
- 10% Prevalence: PPV 92.7%, NPV 99.5%
- 50% Prevalence: PPV 99.1%, NPV 95.8%
- Neisseria gonorrhoeae (Overall Sensitivity 97.1%, Specificity 99.9%):
- 1% Prevalence: PPV 86.9%, NPV 100.0%
- 10% Prevalence: PPV 98.7%, NPV 99.7%
- 50% Prevalence: PPV 99.8%, NPV 97.2%
- Trichomonas vaginalis (Overall Sensitivity 94.1%, Specificity 99.2%):
- 1% Prevalence: PPV 53.6%, NPV 99.9%
- 10% Prevalence: PPV 92.7%, NPV 99.3%
- 50% Prevalence: PPV 99.1%, NPV 94.4%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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)
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.
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
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.
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 Q
Amplified DNA Assay | BD ProbeTec™ ET GC
Q Amplified DNA Assay | BD ProbeTec™ TV Q
Amplified 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 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. | The BD ProbeTec™
Chlamydia trachomatis Qx
Amplified DNA Assay,
when tested with either the
BD Viper™
System in Extracted Mode
or the BD Viper LT System,
uses Strand Displacement
Amplification technology
for the direct, qualitative
detection of Chlamydia
trachomatis DNA in
clinician collected female
endocervical and male
urethral swab specimens,
patient-collected vaginal
swab specimens (in a
clinical setting), and male
and female urine specimens
(both UPT and neat). The
assay is also intended for
use with gynecological
specimens collected in BD
SurePath™ Preservative
Fluid or PreservCyt™
Solution using an aliquot
that is
removed prior to processing
for either the BD SurePath
or ThinPrep™ Pap test. The
assay is indicated for
use with asymptomatic and
symptomatic individuals to
aid in the diagnosis of
chlamydial urogenital
disease. | The BD ProbeTec™
Neisseria gonorrhoeae Qx
Amplified DNA Assay,
when tested with either the
BD Viper™ System in
Extracted Mode or the BD
Viper LT™ System, uses
Strand Displacement
Amplification technology
for the direct, qualitative
detection of Neisseria
gonorrhoeae DNA in
clinician-collected female
endocervical and male
urethral swab specimens,
patient-collected vaginal
swab specimens (in a
clinical setting), and male
and female urine
specimens (both UPT and
Neat). The assay is also
intended for use with
gynecological specimens
collected in BD
SurePath™ Preservative
Fluid or PreservCyt™
Solution using an aliquot
that is removed prior to
processing for either the
BD SurePath or
ThinPrep™ Pap test. The
assay is indicated for
use with asymptomatic
and symptomatic
individuals to aid in the
diagnosis of gonococcal
urogenital disease. | The BD ProbeTec™
Trichomonas vaginalis
(TV) Qx Amplified
DNA Assay, when
tested with the BD
Viper™ System in
Extracted Mode, uses
Strand Displacement
Amplification
technology for the
direct, qualitative
detection of
Trichomonas
vaginalis DNA in
clinician-collected
female endocervical
swab specimens,
patient-collected
vaginal swab
specimens (in a
clinical setting), and
female urine
specimens. The assay
is indicated for use
with asymptomatic and
symptomatic females
to aid in the diagnosis
of trichomoniasis. |
| Indications
for Use | Asymptomatic and
Symptomatic Patients | Same | Same | Same |
| Specimen Type | Endocervical swab,
patient-collected vaginal
swab, female and male
urine | Endocervical swab, patient-
collected vaginal swab,
male urethral swab, male
and female urine (UPT and
neat) | Endocervical swab,
patient-collected vaginal
swab, male urethral swab,
male and female urine
(UPT and neat) | Endocervical swab,
patient-collected
vaginal swab, female
urine |
| Technology | PCR | SDA | SDA | SDA |
| Organisms
Detected | CT, GC and TV | CT | GC | TV |
| Sample Prep
/Interpretation
of Results | Automated by BD MAX
System | Automated by BD Viper
System | Automated by BD Viper
System | Automated by BD
Viper System |
| Assay Controls | Sample Processing
Control | 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 | | Between
Day | | Between
Operator | | 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, Run
and 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 | | Between
Operator | | 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 BD | |||
| MAX 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 Sample | |||
| Buffer Tube | Urine, Vaginal/Endocervical | ||
| Swab | 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 or
Description | 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 | Vag | |||||||||
| Swab | 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 | ||||||||||
| Endo | ||||||||||
| Swab | 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% |