BD PROBETEC NEISSERIA GONORRHOEAE (GC) QX AMPLIFIED DNA ASSAY

K090971 · Becton, Dickinson & CO · LSL · Jun 5, 2009 · Microbiology

Device Facts

• Record ID: K090971
• Device Name: BD PROBETEC NEISSERIA GONORRHOEAE (GC) QX AMPLIFIED DNA ASSAY
• Applicant: Becton, Dickinson & CO
• Product Code: LSL · Microbiology
• Decision Date: Jun 5, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3390
• Device Class: Class 2

Intended Use

The BD ProbeTec™ Neisseria gonorrhoeae (GC) Qx Amplified DNA Assay, when tested with the BD Viper™ System in extracted mode, uses Strand Displacement Amplification (SDA) technology for the direct, qualitative detection of Neisseria gonorrhoeae DNA in clinician-collected female endocervical and male urethral swabs, patient-collected vaginal swab specimens (in a clinical setting), and female and male urine specimens. The assay is indicated for use with asymptomatic and symptomatic female and male individuals to aid in the diagnosis of gonococcal urogenital disease. The BD Viper System, when used with the BD ProbeTec amplified nucleic assay(s), is intended for the in vitro detection of targeted organisms from specimens as identified in the assay-specific reagent package insert(s).

Device Story

Assay uses Strand Displacement Amplification (SDA) to detect Neisseria gonorrhoeae DNA. Input: clinician-collected endocervical/urethral swabs, patient-collected vaginal swabs, or urine. Reagents (primers, fluorescent probes, enzymes) are dried in microwells; BD Viper System automates rehydration, incubation, and fluorescence reading. Device calculates peak fluorescence (MaxRFU) and compares against threshold to determine presence/absence of target DNA. Includes Extraction Control (EC) to validate process. System reports results as positive, negative, or EC failure. Used in clinical settings; operated by laboratory personnel. Output aids clinicians in diagnosing gonococcal urogenital disease, facilitating timely patient treatment.

Clinical Evidence

Multi-site clinical study (n=1768 compliant subjects: 994 female, 774 male) across seven North American clinics. Compared assay results against a Patient Infected Status (PIS) algorithm using two reference NAATs. Total of 6284 results evaluated. Overall sensitivity 99.3% (95% CI: 98.3% - 99.8%) and specificity 99.3% (95% CI: 99.1% - 99.5%). Performance metrics provided by specimen type (endocervical, vaginal, urethral, urine) and symptomatic status.

Technological Characteristics

Strand Displacement Amplification (SDA) technology. Uses ferric oxide particles for DNA extraction. Detection via fluorescently-labeled probes and thermally-controlled fluorescent readers. Automated processing on BD Viper System. Threshold-based qualitative result (125 MaxRFU).

Indications for Use

Indicated for asymptomatic and symptomatic males and females to aid in the diagnosis of gonococcal urogenital disease using endocervical, urethral, vaginal, or urine specimens.

Regulatory Classification

Identification

Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identify Neisseria spp. from cultured isolates. Additionally, some of these reagents consist of Neisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence of Neisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Neisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.

Predicate Devices

• BD ProbeTec Neisseria gonorrhoeae (GC) Qx Amplified DNA Assay (K081825)
• Gen-Probe Amplified Neisseria gonorrhoeae Assay (K043144)

Submission Summary (Full Text)

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JUN - 5 2009

Image /page/0/Picture/2 description: The image shows the logo for BD, a medical technology company. The logo consists of a stylized sun-like graphic to the left of the letters "BD". Below the letters is the tagline "Helping all people live healthy lives". The logo is simple and professional, conveying a sense of health and well-being.

## BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay 1690971

BD Diagnostic Systems Applicant 7 Loveton Circle Sparks, MD 21152 Establishment Registration No. 1119779 Kathryn Babka Carr, RAC Contact Person tel. [phone] fax. [phone] Kathy [e-mail] April 3, 2009 Summary Date BD ProbeTec" Neisseria gonorrhoeae (GC) Q* Amplified Proprietary Name DNA Assay DNA probe, nucleic acid amplification, Neisseria Generic Name Classification Class II Neisseria spp. direct serological test reagents Classification Name Regulation Number 866.3390 Product Code LSL BD ProbeTec"1d Neisseria gonorrhoeae (GC) O* Amplified Predicate Devices DNA Assay (K081825) Gen-Probe Amplified Neisseria gonorrhoeae Assay (K043144) Device Description

The BD ProbeTec GC Q* Amplified DNA Assay is based on the simultaneous amplification and detection of target DNA using amplification primers and a fluorescently-labeled detector probe. The reagents for SDA are dried in two separate disposable microwells: the Priming Microwell contains the amplification primers, fluorescently-labeled detector probe, nucleotides and other reagents necessary for amplification. while the Amplification Microwell contains the two enzymes (a DNA polymerase and a restriction endonuclease) that are required for SDA. The BD Viper "M System pipettes a portion of the purified DNA solution from each Extraction Tube into a Priming Microwell to rehydrate the contents. After a brief incubation, the reaction mixture is transferred to a corresponding, pre-warmed Amplification Microwell which is sealed to prevent contamination and then incubated in one of the two thermally-controlled fluorescent readers. The presence or absence of N. gonorrhoeae DNA is determined by calculating the peak fluorescence (Maximum Relative Fluorescent Units (MaxRFU)) over the course of the amplification process and by comparing this measurement to a predetermined threshold value.

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## BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay

In addition to the fluorescent probe used to detect amplified N. gonorrhoeae target DNA, a second labeled oligonucleotide is incorporated in each reaction. The Extraction Control (EC) oligonucleotide is labeled with a different dye than that used for detection of the N. gonorrhoeae -specific target and is used to confirm the validity of the extraction process. The EC is dried in the Extraction Tubes and is rehydrated upon addition of the specimen and extraction reagents. At the end of the extraction process, the EC fluorescence is monitored by the BD Viper System and an automated algorithm is applied to both the EC and N. gonorrhoeae -specific signals to report results as positive, negative, or EC failure.

#### Intended Use

The BD ProbeTec"11 Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay, when tested with the BD Viper™ System in extracted mode, uses Strand Displacement Amplification (SDA) technology for the direct, qualitative detection of Neisseria gonorrhoeae DNA in cliniciancollected female endocervical and male urethral swabs, patient-collected vaginal swab specimens (in a clinical setting), and female and male urine specimens. The assay is indicated for use with asymptomatic and symptomatic female and male individuals to aid in the diagnosis of gonococcal urogenital disease.

#### Clinical Performance Characteristics

Clinician-collected endocervical and male urethral swab specimens, patient-collected vaginal swab specimens (in a clinical setting), and male and female Or UPT and neat urine specimens were collected from 1059 symptomatic and asymptomatic female subjects and 787 symptomatic and asymptomatic male subjects attending OB/GYN, sexually transmitted disease (STD) and family planning clinics at seven geographically diverse clinical sites in North America. Subjects were classified as symptomatic if they reported symptoms such as dysuria, urethral discharge, 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 symptoms. Sixty five female subjects and 13 male subjects were excluded from the data analysis due to age requirement violations, antibiotic treatment in the last 21 days, opting to withdraw from the study after initially consenting, failure to obtain paired swab and urine specimens, urine quantity less than 20 mL, or transport and storage errors related to specimen collection. Therefore, the final data analysis included 994 compliant female subjects and 774 compliant male subjects.

Five specimens were collected from each of the 994 eligible female subjects. A urine specimen was collected and split into Q* UPT, neat urine and the two reference urine specimen collection devices followed by a vaginal swab specimen and three randomized endocervical swab specimens. Up to four specimens were collected from each of the 774 eligible male subjects. Up to three randomized urethral swab specimens were collected followed by a urine specimen that was split into O UPT, neat urine and the two reference urine specimen collection devices.

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## BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay

BD ProbeTec GC Q* assay results were generated from the Q* UPT and neat urine specimens, the vaginal swab specimen, one endocervical swab specimen and one male urethral swab specimen. The remaining two endocervical swab specimens, up to two male urethral swab specimens, and the two reference urine specimens for each male and female subject were tested using two reference methods: the BD ProbeTec ET GC/AC assay and another commercially available NAAT (Nucleic Acid Amplification Test). Specimen testing was conducted either at the site of collection or at a designated BD Viper testing site.

All performance calculations were based on the total number of BD ProbeTec GC Q* assays results for endocervical, vaginal and male urethral swab specimens, and male and female Q UPT and neat urine specimens compared to a patient infected status (PIS) algorithm for each gender. In the algorithm, the designation of a subject as being infected with GC or not was based on endocervical swab and urine specimen results from the commercially available BD ProbeTec ET GC/AC assay and the other commercially available NAAT. Subjects were considered infected with GC if two of the four endocervical swab and urine specimens (or two of the three or four urethral swab and urine specimens) tested positive in the BD ProbeTec ET GC/AC assay and the other reference NAAT (one specimen testing positive in each NAAT). Subjects were considered non-infected if less than two reference NAAT results were positive. A total of 6284 BD ProbeTec GC Q* assay results from symptomatic female and male were used to calculate sensitivity and specificity. Sensitivity and specificity by specimen type and symptomatic status are presented in Table 3.

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# BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay

## Table 3: GC Q* Assay Performance Compared to Patient Infected Status (by specimen type and symptomatic status)

| | | | Performance Compared to Patient Infected<br>Status | | | | | | |
|------------------|-------------|------|----------------------------------------------------|---------------------|----------------------|---------------------|-------|--------|------------------------|
| Specimen<br>Type | Symptomatic | N | Sensitivity | 95%<br>C.I. | Specificity | 95%<br>C.I. | PPV | NPV | Error<br>Initial/Final |
| FS | A | 450 | 96.3%<br>(26/27) | (81.0% -<br>99.9%) | 99.5%<br>(421/423) | (98.3% -<br>99.9%) | 92.5% | 99.8% | 3/0 |
| | S | 542 | 100.0%<br>(38/38) | (90.7% -<br>100.0%) | 99.8%<br>(503/504) | (98.9% -<br>100.0%) | 97.4% | 100.0% | 2/2 |
| | Total | 992 | 98.5%<br>(64/65) | (91.7% -<br>100.0%) | 99.7%<br>(924/927) | (99.1% -<br>99.9%) | 95.9% | 99.9% | 5/2 |
| FV | A | 449 | 100.0%<br>(27/27) | (87.2% -<br>100.0%) | 98.6%<br>(416/422) | (96.9% -<br>99.5%) | 82.0% | 100.0% | 0/0 |
| | S | 544 | 100.0%<br>(38/38) | (90.7% -<br>100.0%) | 99.6%<br>(504/506) | (98.6% -<br>100.0%) | 95.0% | 100.0% | 0/0 |
| | Total | 993 | 100.0%<br>(65/65) | (94.5% -<br>100.0%) | 99.1%<br>(920/928) | (98.3% -<br>99.6%) | 88.5% | 100.0% | 0/0 |
| FNU | A | 450 | 96.3%<br>(26/27) | (81.0% -<br>99.9%) | 99.3%<br>(420/423) | (97.9% -<br>99.9%) | 89.8% | 99.8% | 0/0 |
| | S | 543 | 97.4%<br>(37/38) | (86.2% -<br>99.9%) | 99.6%<br>(503/505) | (98.6% -<br>100.0%) | 94.8% | 99.8% | 0/0 |
| | Total | 993 | 96.9%<br>(63/65) | (89.3% -<br>99.6%) | 99.5%<br>(923/928) | (98.7% -<br>99.8%) | 93.1% | 99.8% | 0/0 |
| FUPT | A | 450 | 100.0%<br>(27/27) | (87.2% -<br>100.0%) | 99.5%<br>(421/423) | (98.3% -<br>99.9%) | 92.7% | 100.0% | 0/0 |
| | S | 543 | 97.4%<br>(37/38) | (86.2% -<br>99.9%) | 99.8%<br>(504/505) | (98.9% -<br>100.0%) | 97.3% | 99.8% | 0/0 |
| | Total | 993 | 98.5%<br>(64/65) | (91.7% -<br>100.0%) | 99.7%<br>(925/928) | (99.1% -<br>99.9%) | 95.8% | 99.9% | 0/0 |
| MS | A | 508 | 100.0%<br>(12/12) | (73.5% -<br>100.0%) | 99.2%<br>(492/496) | (97.9% -<br>99.8%) | 75.5% | 100.0% | 0/0 |
| | S | 257 | 100.0%<br>(100/100) | (96.4% -<br>100.0%) | 98.7%<br>(155/157) | (95.5% -<br>99.8%) | 98.0% | 100.0% | 1/0 |
| | Total | 765 | 100.0%<br>(112/112) | (96.8% -<br>100.0%) | 99.1%<br>(647/653) | (98.0% -<br>99.7%) | 95.0% | 100.0% | 1/0 |
| Specimen<br>Type | Symptomatic | N | Sensitivity | 95%<br>C.I. | Specificity | 95%<br>C.I. | PPV | NPV | Error<br>Initial/Final |
| MNU1 | A | 517 | 100.0%<br>(12/12) | (73.5% -<br>100.0%) | 99.2%<br>(501/505) | (98.0% -<br>99.8%) | 74.6% | 100.0% | 0/0 |
| MNU1 | S | 257 | 100.0%<br>(100/100) | (96.4% -<br>100.0%) | 98.1%<br>(154/157) | (94.5% -<br>99.6%) | 97.1% | 100.0% | 0/0 |
| MNU1 | Total | 774 | 100.0%<br>(112/112) | (96.8% -<br>100.0%) | 98.9%<br>(655/662) | (97.8% -<br>99.6%) | 93.9% | 100.0% | 0/0 |
| MUPT1 | A | 517 | 100.0%<br>(12/12) | (73.5% -<br>100.0%) | 99.2%<br>(501/505) | (98.0% -<br>99.8%) | 74.6% | 100.0% | 1/0 |
| MUPT1 | S | 257 | 100.0%<br>(100/100) | (96.4% -<br>100.0%) | 98.7%<br>(155/157) | (95.5% -<br>99.8%) | 98.0% | 100.0% | 0/0 |
| MUPT1 | Total | 774 | 100.0%<br>(112/112) | (96.8% -<br>100.0%) | 99.1%<br>(656/662) | (98.0% -<br>99.7%) | 95.0% | 100.0% | 1/0 |
| Total | | 6284 | 99.3%<br>(592/596) | (98.3% -<br>99.8%) | 99.3%<br>(5650/5688) | (99.1% -<br>99.5%) | 93.7% | 99.9% | 7/2 |

1 Clinical Trial enrollment for asymptomatic male subjects was extended to obtain the total number of clinical positives for this sub-population.

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Image /page/4/Picture/0 description: The image shows the BD logo, which consists of a stylized sunburst graphic to the left and the letters 'BD' in bold font to the right. Below the letters, there is a tagline that reads 'Helping all people live healthy lives'. The logo is simple and professional, conveying a sense of health and well-being.

# BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay

Asymptomalic Chi
Film
Fürft Confidence Interval Female Neat Urine
Female endocervical swab Female urine in Q* UPT FV
MNU Female vaginal swab r omato vaginal Swas
Male urethral swab
Male urethrall swab
Male urine in Q* UPT
number MS
MUPT ហ S Symptomatic

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Image /page/5/Picture/1 description: The image shows the BD logo. The logo consists of a stylized image of a person with arms raised in front of a sun, followed by the letters "BD" in bold font. Below the logo is the text "Helping all people live healthy lives."

BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay

A total of 6284 GC Q* Assay results was evaluated at seven geographically diverse clinical sites. A frequency distribution of the initial MaxRFU values for the GC Q" assay with an assay cutoff of 125 MaxRFU is shown in Figure A.

Image /page/5/Figure/4 description: The image shows the title of a figure. The title is "Figure A: Frequency Distribution of MaxRFU for the GC Q* Assay." The title is written in a bold, sans-serif font.

Image /page/5/Figure/5 description: The image is a bar graph that shows the frequency of MaxRFU values. The x-axis represents the MaxRFU ranges, and the y-axis represents the frequency. The highest frequency is in the 0-49 range, with a value of 5636. The frequency for >=800 is 617.

#### Conclusions

The clinical study results for the BD ProbeTec Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay support the determination of substantial equivalence with the intended use as stated in the product labeling for the addition of asymptomatic males specimens.

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/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 words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract depiction of an eagle, with three stylized wing segments.

#### Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

# JUN - 5 2009

Ms. Kathryn Babka Carr Regulatory Affairs Specialist BD Diagnostics Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152 ·

K090971 Re:

Trade/Device Name: BD Probetec ™ Nesseria gonorrhoeae (GC) Qx Amplified DNA Assay

Regulation Number: 21 CFR 866.3390 Regulation Name: Nesseria spp. Direct serological test reagents Regulatory Class: Class II Product Code: LSL Dated: April 3, 2009 Received: April 6, 2009

Dear Ms. Carr:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours,

Sally attapra

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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#### Indications for Use

60999971 510(k) Number (if known):

Device Name: BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay

Indications For Use:

The BD ProbeTect™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay, when tested with the BD Viper™ System in extracted mode, uses Strand Displacement Amplification (SDA) technology for the direct, qualitative detection of Neisseria gonorrhoeae DNA in cliniciancollected female endocervical and male urethral swabs, patient-collected vaginal swab specimens (in a clinical setting), and female and male urine specimens. The assay is indicated for use with asymptomatic and symptomatic female and male individuals to aid in the diagnosis of gonococcal urogenital disease.

The BD Viper System, when used with the BD ProbeTec amplified nucleic assay(s), is intended for the in vitro detection of targeted organisms from specimens as identified in the assay-specific reagent package insert(s).

Prescription Use V (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Vhe Schef

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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