BD PROBETEC NEISSERIA GONORRHOEAE (GC) QX AMPLIFIED DNA ASSAY

K091730 · Becton, Dickinson & CO · LSL · Nov 13, 2009 · Microbiology

Device Facts

• Record ID: K091730
• Device Name: BD PROBETEC NEISSERIA GONORRHOEAE (GC) QX AMPLIFIED DNA ASSAY
• Applicant: Becton, Dickinson & CO
• Product Code: LSL · Microbiology
• Decision Date: Nov 13, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3390
• Device Class: Class 2

Intended Use

The BD ProbeTec™ Neisseria gonorrhoeae (GC) Q® Amplified DNA Assay, when tested with the BD Viper™ System in Extracted Mode, 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 using an aliquot that is removed prior to processing for the BD SurePath™ Pap test. The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of gonococcal urogenital disease.

Device Story

Assay uses Strand Displacement Amplification (SDA) to detect Neisseria gonorrhoeae DNA in clinical specimens. Processed on BD Viper System; involves automated chemical cell lysis, DNA binding to para-magnetic particles, washing, and elution. Reagents (primers, enzymes, fluorescent probes) are contained in disposable microwells. System monitors fluorescence (MaxRFU) during amplification; automated algorithm compares peak fluorescence to threshold to determine presence/absence of target DNA. Includes Extraction Control (EC) to validate extraction process. Used in clinical laboratory settings by trained personnel. Output provides qualitative results (positive, negative, or EC failure) to assist clinicians in diagnosing gonococcal urogenital disease.

Clinical Evidence

Clinical study evaluated 1715 female subjects across 11 sites. Compared BD SurePath specimen results to a Patient Infected Status (PIS) algorithm based on three reference endocervical swab methods. Overall sensitivity was 100% (51/51) and specificity was 99.9% (1662/1664). Performance was consistent across symptomatic and asymptomatic populations.

Technological Characteristics

Uses Strand Displacement Amplification (SDA) with fluorescently-labeled detector probes. Automated extraction via paramagnetic particles. Instrumentation: BD Viper System (robotic platform). Connectivity: Standalone system. Software: Automated algorithm for signal processing and result interpretation. Sterilization: Not specified.

Indications for Use

Indicated for asymptomatic and symptomatic individuals to aid in the diagnosis of gonococcal urogenital disease. Specimens include female endocervical/vaginal swabs, male urethral swabs, male/female urine, and gynecological specimens in BD SurePath™ Preservative Fluid.

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) Q⁸ Amplified DNA Assay (K081825)
• Gen-Probe APTIMA Assay for Neisseria gonorrhoeae (AGC) (K062440)

Submission Summary (Full Text)

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

K091730

Image /page/0/Picture/1 description: The image shows the BD logo. The logo consists of a stylized sun and human figure on the left, followed by the letters "BD" in bold, sans-serif font. Below the letters, there is a tagline that reads "Helping all people live healthy lives" in a smaller font.

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

510(k) Summary

| Applicant | BD Diagnostic Systems<br>7 Loveton Circle<br>Sparks, MD 21152 |
|----------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | NOV 13 2009 |
| Establishment Registration No. 1119779 | |
| Contact Person | Saba Modjarrad<br>tel. [phone]<br>fax. [phone]<br>[e-mail] |
| Summary Date | June 10, 2009 |
| Proprietary Name | BD ProbeTec ^TM Neisseria gonorrhoeae (GC) Q* Amplified<br>DNA Assay |
| Generic Name | DNA Reagents, Neisseria |
| Classification | Class II |
| Classification Name | Neisseria spp. direct serological test reagents |
| Regulation Number | 866.3390 |
| Product Code | LSL |
| Predicate Devices | BD ProbeTec ^TM Neisseria gonorrhoeae (GC) Q* Amplified<br>DNA Assay (K081825),<br>Gen-Probe APTIMA Assay for Neisseria gonorrhoeae (AGC)<br>(K062440) |

### 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 10 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

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

Image /page/1/Picture/1 description: The image shows the logo for BD, a medical technology company. The logo consists of two parts: a graphic symbol on the left and the letters "BD" on the right. The graphic symbol appears to be a stylized representation of a person with arms raised under a sunburst. Below the letters "BD" is the tagline "Helping all people live healthy lives" in a smaller font.

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

fluorescence (Maximum Relative Fluorescent Units (MaxRFU)) over the course of the amplification process and by comparing this measurement to a predetermined threshold value.

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. gonorrhoede -specific signals to report results as positive, negative, or EC failure.

## Intended Use

The BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay, when tested with the BD Viper™ System in Extracted Mode, 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 using an aliquot that is removed prior to processing for the BD SurePath™ Pap test. The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of gonococcal urogenital disease.

### Summarv and Principles of Operation

When used with the BD Viper System, the BD ProbeTec GC Q* Amplified DNA Assay involves automated extraction of DNA from clinical specimens through the chemical lysis of cells, followed by binding of DNA to para-magnetic particles, washing of the bound nucleic acid and elution in an amplification-compatible buffer. When present, N. gonorrhoeae DNA is then detected by Strand Displacement Amplification (SDA) of a specific target sequence in the presence of a fluorescently labeled detector probe.

## Analytical Performance Characteristics

## Limit of Detection (Analytical Sensitivity)

The Limits of Detection (LODs) for the GC O* Assay with Neisseria gonorrhoeae strain ATCC 19424 in BD SurePath specimens when extracted on the BD Viper System were determined to be ≤ 100 GC cells per mL. The GC Q* Assay on the BD Viper System in extracted mode was able to detect 17 GC strains with > 95% proportion positive at a concentration of 50 cells per mL in clean diluted BD SurePath Preservative Fluid.

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

Image /page/2/Picture/1 description: The image shows the logo for BD, a medical technology company. The logo consists of a stylized sun-like symbol with a human figure at the bottom left, followed by the letters "BD" in bold font. Below the letters, there is a tagline that reads "Helping all people live healthy lives".

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

### Interfering Substances

Potential interfering substances which may be encountered in BD SurePath specimens were extracted from diluted BD SurePath matrix in the absence and presence of GC target (300 GC cells/mL) and tested with the BD ProbeTec GC Q* Amplified DNA Assay on the BD Viper System. Results are summarized in Table 2.

#### Table 2 Interfering Substances

| Interpretation | BD SurePath |
|--------------------------|----------------------------------------------------------------------------------------------------------------------|
| No Interference Observed | Blood (≤ 1%)<br>Seminal Fluid<br>Mucus<br>Over The Counter vaginal products and contraceptives<br>Hemorrhoidal cream |
| | Prescription vaginal treatments<br>Leukocytes (1x106 cells/mL)<br>1x106 EB/mL Chlamydia trachomatis |

### Clinical Performance Characteristics

Endocervical swab specimens and BD SurePath specimens were collected from 1728 compliant female subjects attending family planning, OB/GYN, and sexually transmitted disease clinics at eleven geographically diverse clinical sites in North America. Subjects were classified as symptomatic if they reported symptoms such as dysuria, coital pain/difficulty/bleeding, abnormal vaginal discharge, or pelvic/uterine/adnexal pain. Subjects were classified as asymptomatic if they did not report symptoms.

Three randomized endocervical swab specimens and a BD SurePath specimen were collected from each female subject. The three reference endocervical swabs were tested with the BD ProbeTec ET CT/GC/AC assay, the BD ProbeTec GC Q* assay, and another commercially available NAAT (Nucleic Acid Amplification Test). Sensitivity and specificity for BD SurePath specimens were calculated by comparing results to a patient infected status (PIS) algorithm. The designation of positive or negative PIS was based on the endocervical swab specimen results from the three reference methods. At least two positive reference results were required to establish a subject as PIS-positive. At least two negative reference results were required to establish a subject as PIS-negative. Sensitivity and specificity by symptomatic status are presented in Table 4.

The distribution of cervical sampling devices used in the clinical study according to clinical collection site is summarized in Table 3.

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

Image /page/3/Picture/1 description: The image contains the logo for BD, a medical technology company. The logo consists of a stylized sun-like symbol with a human figure in the center, followed by the letters "BD" in bold, sans-serif font. Below the letters, there is a tagline that reads "Helping all people live healthy lives" in a smaller font size.

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

#### Summary of Cervical Sampling Devices Used in the BD SurePath Specimen Table 3 Clinical Study

| | Clinical Collection Site Number | | | | | | | | | | | |
|----------------------------------|---------------------------------|----|-----|----|-----|-----|-----|----|-----|----|----|-------|
| Cervical Sampling<br>Device Used | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | Total |
| Broom-Type<br>Device | 54 | 50 | 511 | 18 | 374 | 0 | 127 | 0 | 0 | 71 | 0 | 1205 |
| Spatula/Cytobrush | 0 | 25 | 0 | 0 | 182 | 112 | 32 | 24 | 103 | 8 | 37 | 523 |

#### Table 4 GC Q* Assay Performance for BD SurePath Specimens Compared to Patient Infected Status (By Symptomatic Status)

| | | Performance Compared to Patient Infected<br>Status | | | | | | |
|-----------------------|-------|----------------------------------------------------|---------------------|----------------------|---------------------|--------|--------|------------------------|
| Symptomatic<br>Status | N | Sensitivity | 95% C.I. | Specificity | 95%<br>C.I. | PPV | NPV | Error<br>Initial/Final |
| A | 1157 | 100.0%<br>(32/32) | (89.1% -<br>100.0%) | 99.8%<br>(1123/1125) | (99.4% -<br>100.0%) | 93.5% | 100.0% | 2/0 |
| S | 558 | 100.0%<br>(19/19) | (82.4% -<br>100.0%) | 100.0%<br>(539/539) | (99.3% -<br>100.0%) | 100.0% | 100.0% | 0/0 |
| Total | 1715' | 100.0%<br>(51/51) | (93.0% -<br>100.0%) | 99.9%<br>(1662/1664) | (99.6% -<br>100.0%) | 96.9% | 100.0% | 2/0 |

¹ Of the 1728 compliant female subjects did not have a GC Q assay result for the BD SurePath specimen, therefore the final data analysis included 1715 compliant female subjects.

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

Image /page/4/Picture/1 description: The image shows the BD logo. The logo consists of a stylized sun-like graphic on the left and the letters "BD" in bold, sans-serif font on the right. Below the letters, there is a tagline that reads "Helping all people live healthy lives" in a smaller font size.

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

A total of 1715 GC Q* Assay results from BD SurePath specimens was evaluated from eleven geographically diverse clinical sites. A frequency distribution of the initial MaxRFU values for the GC Q+ assay is shown in Figure A. .

#### Frequency Distribution of MaxRFU for the GC Q* Assay (BD SurePath Figure A Specimens)

Image /page/4/Figure/5 description: The image is a bar graph showing frequency on the y-axis and MaxRFU on the x-axis. The first bar, representing 0-49 MaxRFU, has a frequency of 1659. The other bars have much lower frequencies, with 50-99 at 2, 100-124 at 1, and >=800 at 53, while the rest are at 0.

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

Image /page/5/Picture/1 description: The image shows the logo for BD, a medical technology company. The logo consists of two parts: a graphic symbol on the left and the letters "BD" on the right. Below the letters, there is a tagline that reads "Helping all people live healthy lives." The graphic symbol appears to be a stylized representation of a person with arms outstretched under a sun-like shape.

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

## Reproducibility

A reproducibility study of the BD Viper System using the BD ProbeTec GC Q* Assay was also evaluated for Liquid Based Cytology (LBC) specimens at three clinical sites on one BD Viper System per site. A panel of simulated specimens comprising CT and GC organisms seeded into LBC Specimen Dilution Tubes containing LBC medium was tested with the BD ProbeTec GC O Assay. Uninoculated LBC Specimen Dilution Tubes containing LBC medium were used for the GC negative samples. Nine replicates of each panel member were tested every day for five days on each BD Viper System. The data are summarized in Table 5.

Two additional levels were included in the panels to characterize the reproducibility of test results (i.e., proportion positive or negative) at target levels below the analytical Limit of Detection (LOD) of the BD ProbeTec GC Q* Assay. These additional specimens comprised CT and GC organisms seeded into LBC Specimen Dilution Tubes containing LBC medium at dilutions of 1:10 and 1:100 of the respective analytical LODs of each analyte. These levels were selected to fall within the dynamic range of the analytical LOD curves for the BD ProbeTec CT Of and GC Q* assays. Nine replicates of each panel member were tested every day for five days across the three BD Viper Systems. The data are summarized in Table 6.

| | | | | | Within Run | | Between<br>Runs<br>Within Site | | Between<br>Site | |
|---------------|----------------|---------------------|---------------------|----------------|------------|--------|--------------------------------|------|-----------------|-------|
| CT<br>EB's/mL | GC<br>Cells/mL | % Correct | 95% CI | Mean<br>MaxRFU | SD | %CV | SD | %CV | SD | %CV |
| 0 | 0 | 100.0%<br>(135/135) | (97.3% -<br>100.0%) | 1.21 | 4.00 | 330.38 | 0.00 | 0.00 | 0.00 | 0.00 |
| 30 | 0 | 100.0%<br>(135/135) | (97.3% -<br>100.0%) | 0.98 | 7.47 | 761.30 | 0.00 | 0.00 | 0.17 | 17.04 |
| 0 | 100 | 100.0%<br>(135/135) | (97.3% -<br>100.0%) | 1982.77 | 83.92 | 4.23 | 0.00 | 0.00 | 0.00 | 0.00 |
| 30 | 250 | 100.0%<br>(135/135) | (97.3% -<br>100.0%) | 1983.66 | 87.76 | 4.42 | 0.00 | 0.00 | 24.80 | 1.25 |
| 75 | 100 | 100.0%<br>(135/135) | (97.3% -<br>100.0%) | 1920.14 | 81.94 | 4.27 | 59.45 | 3.10 | 0.00 | 0.00 |

#### Summary of Reproducibility Data for LBC Specimens on the BD Viper Table 5 System for the GC O* Assay

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

Image /page/6/Picture/1 description: The image shows the logo for BD, a medical technology company. The logo consists of two parts: a graphic symbol on the left and the letters "BD" on the right. The graphic symbol appears to be a stylized representation of a person with arms raised under a sun-like burst. Below the letters "BD" is the tagline "Helping all people live healthy lives" in a smaller font.

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

#### Characterization of System Reproducibility at Target Levels below the Table 6 Analytical Limit of Detection for the GC Q* Assay for LBC Specimens

| Dilution<br>of<br>Analytical<br>LOD | % Positive | 95% CI<br>(Positive) | MaxRFU<br>Mean<br>(Positive) | % Negative | 95% CI<br>(Negative) | MaxRFU<br>Mean<br>(Negative) |
|-------------------------------------|----------------|----------------------|------------------------------|----------------|----------------------|------------------------------|
| 1:10 | 74.1 (100/135) | (65.8 - 81.2) | 1159.2 | 25.9 (35/135) | (18.8 - 34.2) | 21.2 |
| 1:100 | 8.9 (12/135) | (4.7 - 15.0) | 1136.5 | 91.1 (123/135) | (85.0 - 95.3) | 6.6 |

### Conclusions

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

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

Image /page/7/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract image of an eagle.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002

NOV 1 3 2009

Ms. Saba Modjarrad Regulatory Affairs Specialist BD Diagnostics Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152

K091730 Re: K091750
Trade/Device Name: BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay Regulation Number: 21 CFR 866.3390 Regulation Name: Neisseria spp. direct serological test reagents Regulatory Class: Class II Product Code: LSL Dated: November 5, 2009 Received: November 6, 2009

Dear Ms. Saba Modjarrad:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced we mare revelour your boomer on (e) } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } } enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, enerolded to the Medical Device Amendments, or to devices that have been reclassified in the chance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require accordalice with the provisions of the reason (PMA). You may, therefore, market the device, subject to approval or a promations of the Act. The general controls provisions of the Act include the general ochiles pro revistration, 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 IT your device is classinod (300 able to) into emajor regulations affecting your device can be found in Title Subject to such architems (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 1 carar states and regarding, but not limited to: registration and listing (21 CFR Part 807); labeling (21 Act 3 requirements, moraans, on manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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

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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained 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/dsma/dsmamain.html.

Sincerely yours,

Jallåtyne
Hoivat, M. Sc., Ph.D.

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

Enclosure

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

### Indications for Use

# 510(k) Number (if known): < 0 1730

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

Indications For Use:

The BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay, when tested with the BD Viper™ System in Extracted Mode, 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 using an aliquot that is removed prior to processing for the BD SurePath™ Pap test. The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of gonococcal urogenital disease.

Prescription Use _____________________________________________________________________________________________________________________________________________________________ ج (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)

M.Md. W.W.L. for
Uwe Scherf
Division Sign-Off

**Division Sign-Off**

office of In Vitro Diag e Evaluation and

510(k) K5091730

Page 1 of 1

BD Diagnostic Systems Becton, Dickinson and Company

Page ix