Predicate Devices

K11860

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description focuses on automated sample processing and real-time PCR with embedded calculation algorithms, not AI/ML.

Therapeutic

No.
The device is an in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA, identifying antepartum GBS colonization. It is not intended to diagnose or monitor treatment of GBS infection, nor does it provide therapeutic intervention.

Diagnostic

Yes
The device is described as a "qualitative in vitro diagnostic test designed to detect Group B Streptococus (GBS) DNA" and is "indicated for the identification of antepartum GBS colonization." The term "diagnostic" is explicitly used in its intended use, indicating its purpose in identifying a medical condition.

SaMD (Software as a Medical Device)

No

The device description clearly outlines physical components (microfluidic cartridges, Sample Buffer Tube, Disposable Transfer Tool) and relies on a hardware instrument (revogene™) for processing and detection. While software is involved in interpreting results, it is integral to a larger hardware-based system.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use: The description explicitly states it is a "qualitative in vitro diagnostic test designed to detect Group B Streptococus (GBS) DNA". The term "in vitro diagnostic" is used directly in the intended use.
Device Description: The description details how the device is used to analyze a biological sample (enriched vaginal/rectal swab specimens) outside of the body ("in vitro") to provide diagnostic information (detection of GBS DNA).
Performance Studies: The document includes a summary of clinical performance studies comparing the device's results to a reference method, which is a standard practice for demonstrating the clinical validity of an IVD.
Predicate Device: The mention of a "Predicate Device" with a K number (K111860; BD MAX™ GBS Assay) indicates that this device is being compared to a previously cleared IVD, further confirming its classification.

All of these points align with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The GenePOC™ GBS LB assay performed on the revogene™ instrument is a qualitative in vitro diagnostic test designed to detect Group B Streptococus (GBS) DNA from 18-24 hour LIM broth enrichments of vaginal/rectal specimen swabs obtained from pregnant women. The GenePOC GBS LB assay utilizes automated sample processing and real-time polymerase chain reaction (PCR) to detect a cfb gene sequence specific to the Streptococcus agalactiae genome.

The GenePOC GBS LB assay is indicated for the identification of antepartum GBS colonization and does not provide susceptibility results. It is not intended to diagnose or monitor treatment of GBS infection. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

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

NJR, OOI

Device Description

The GenePOC GBS LB assay is a single-use test for the qualitative detection of Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens using realtime Polymerase Chain Reaction (PCR) technology with fluorogenic detection of the amplified DNA. The GenePOC GBS LB assay utilizes the GBS LB microfluidic cartridge for the simultaneous detection of the target GBS DNA and the internal process control (PrC) DNA (to monitor processing, amplification, and the absence of reaction inhibitors). The GenePOC GBS LB assay is an automated assay performed on the revogene™ including sample processing.

The GenePOC Group B Strep (GBS) LB is composed of a GBS specific disposable microfluidic cartridges, Sample Buffer Tube (SBT) and Disposable Transfer Tool (DTT). These components are used to lyse and dilute the sample, amplify, and detect GBS nucleic acid from vaginal/rectal swabs following LIM broth enrichment. User intervention is required for sample preparation, discharging the LIM broth enriched sample into the SBT, transferring the sample into the cartridge and loading/unloading the cartridge into the revogene instrument. Once the sample is added into the cartridge, the process is then fully automated.

Each GenePOC GBS LB Test kit contains 24 individual pouches, and each pouch has components for 1 test including 1 cartridge, 1 SBT, and 1 DTT. The GBS LB Test is run on the revogene instrument which can process from one up to a maximum of 8 samples simultaneously in the same run. On completion of a run, the results are interpolated by the revogene™ from measured fluorescent signals and embedded calculation algorithms. For the GBS application, two spectral signals are processed: GBS target and Internal Process Control. The output results include positive, negative, indeterminate, and unresolved. On completion of a run, the user removes the used cartridges and disposes of them in normal biological waste. Results may be viewed, printed, transferred, and/or stored by the user.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

vaginal/rectal specimen swabs

Indicated Patient Age Range

pregnant women

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

GenePOC conducted a prospective multicenter trial at 4 geographically diverse clinical trial sites; specifically, two Canadian and two US clinical sites. A vaginal/rectal swab specimen was collected from n=839 pregnant women at 35-37 weeks of gestation for whom GBS diagnostic procedures were ordered. For each patient, the swab was used for the composite reference method consisting of LIM Broth enrichment of the vaginal/rectal swab followed by a subculture on blood agar plate and biochemical identification of GBS. All specimens with a negative bacterial culture result were re-tested using the same standard operating procedures required for bacterial culture. Residual de-identified LIM Broth samples were used for testing with the GenePOC GBS LB assay. Of those, 63 specimens were regarded as noncompliant per the composite reference method and/or GBS LB assay protocol criteria, 1 specimen was regarded as noncompliant in terms of transport and storage conditions and 4 specimens were regarded as noncompliant due to missing test results. Two (2) fully compliant specimens gave final non-reportable PCR results. A total of 771 specimen results were used to determine the clinical performance of the GBS LB assay in comparison to the composite reference method. A total of 170 GBS positive and 601 GBS negative samples were collected across the four sites.

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

Precision/Reproducibility: The reproducibility study was conducted at three sites (two external sites and GenePOC laboratories) to evaluate the within-run, between-run (three runs per day) and between-day (five days, consecutive or not) reproducibility and variance with multiple operators (n=6; two operators per site). Precision was evaluated based on the within-site variability over 5 days. Three revogene instruments (one per site) and a single lot of the GenePOC GBS LB assay were used by each site (total of three reagent lots).
Three GBS strains were tested at two different concentrations in each run: low positive (LP; 735 CFU/mL SB) and moderate positive (MP; 1,125 CFU/mL SB). The GBS strains used in the panels were the hemolytic serotype Ia S. agalactiae strain ATCC 12400, the hemolytic serotype III S. agalactiae strain ATCC 12403 and the non-hemolytic S. agalactiae strain ATCC 13813. Two true negative (TN) samples were included in each run.
After the testing of 720 replicates (270 low positive, 270 moderate positive, and 180 true negative samples) with the GenePOC GBS LB assay, the overall analysis showed 100% agreement for negative samples, 98.9% agreement for low positive samples, and 98.5% agreement for moderate positive samples.

Detection Limit: The analytical sensitivity (Limit of Detection or LoD) of the GBS LB assay was determined using clinical LIM broth matrix previously tested negative for GBS and spiked with different concentrations of GBS bacterial suspensions. Two strains of GBS (ATCC 12403 and ATCC 13813) were tested in 24 replicates per concentration by 2 operators using 3 different lots of GBS LB kits. The LoD is defined as the lowest concentration at which 95% of all replicates tested positive. The LoD of the GBS LB assay ranged from 200 to 375 CFU/mL of SB (200 CFU/mL for ATCC 13813 and 375 CFU/mL for ATCC 12403).

Analytical Inclusivity: The analytical reactivity was determined with 12 strains of S. agalactive representing 11 known serotypes and one non-haemolytic strain. Each strain was tested in 8 replicates per dilution per lot of material. All strains were detected at concentrations ranging from 1x to 15x LoD.

Analytical Specificity (Cross Reactivity): A total of 75 non-specific analytes were tested. The total reactivity rate of the GenePOC GBS LB test with the selected non-specific analytes is 0%.

Interference with Non-Target Organisms: Microbial interference on the GenePOC GBS LB assay was evaluated with 29 potentially interfering microorganisms in absence and in presence of 2 GBS strains tested at 735 CFU/mL of SB. Samples were grouped together into 7 pools of interferences. Each of the 7 pools were tested in triplicate across 3 reagent lots for a total of 9 replicates by pool were analyzed to determine the presence or absence of interference. Results of the study showed no interference against the GBS target (735 CFU/mL of SB) was detected for 26 out of 29 microorganisms when present in high loads (10^5 or 10^6 CFU/mL of SB). However, strains Enterococcus faecalis ATCC 19433, Enterococcus faecium ATCC 19434 and Lactobacillus acidophilus ATCC 4356 showed interference against the GBS target (735 CFU/mL of SB) when they were present at >10^4 CFU/mL of SB. No interference on the Process Control was observed when microorganisms were present in high loads (10^5 or 10^6 CFU/mL of SB).

Interference with Exogenous and Endogenous Substances: Interference on the GenePOC GBS LB assay was evaluated with 31 potentially interfering exogenous and endogenous substances in absence and in presence of 2 GBS strains tested at 735 CFU/mL SB across 3 reagent lots. Results demonstrated no reportable interference on PrC. Only the combination of loperamide hydrochloride (e.g. Imodium®), bismuth subsalicylate (e.g. Pepto-Bismol™) and sennosides (e.g. Senokot®) at concentrations of 0.023 ug/mL, 0.675 ug/mL and 0.011 ug/mL SB, respectively, showed a potentially inhibitory effect on detection of GBS. When tested individually, these substances showed no reportable interference with the GBS LB assay.

Carryover and Cross Contamination Studies: The carry-over and cross-contamination study showed that there is no evidence of amplicon carry-over or sample contamination when using the revogene with the GenePOC GBS LB assay. A total of 80 samples in the within-run study and 80 samples in the between run study were tested and none gave a false positive result.

Clinical Studies: GenePOC conducted a prospective multicenter trial at 4 geographically diverse clinical trial sites. A total of 771 specimen results were used to determine the clinical performance of the GBS LB assay in comparison to the composite reference method. A total of 170 GBS positive and 601 GBS negative samples were collected across the four sites.
Overall performance: Sensitivity: 95.9% (95%CI: 91.7 - 98.0 %), Specificity: 95.5% (95%CI: 93.5 - 96.9 %).
A 5 out of 7 false negative GenePOC GBS LB results were tested on a FDA-cleared molecular device and yielded negative results.
10 out 27 false positive GenePOC GBS LB results were tested on a FDA-cleared molecular device and yielded positive results.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Sensitivity: 95.9% (95%CI: 91.7 - 98.0 %)
Specificity: 95.5% (95%CI: 93.5 - 96.9 %)

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.

K11860

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

Regulation Number and Section

§ 866.3740

Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health and 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 a stylized image of three human profiles facing right, with a design above them that resembles wings or feathers.

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

May 25, 2017

GENEPOC INC. GUY SEVIGNY SENIOR REGULATORY AFFAIRS SPECIALIST 360 RUE FRANQUET QUEBEC G1P 4N3 CA

Re: K170557 Trade/Device Name: GenePOC GBS LB Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcus spp. serological reagents Regulatory Class: I Product Code: NJR, OOI Dated: February 23, 2017 Received: February 24, 2017

Dear Mr. Sevigny:

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 (OS) 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,

Ribhi Shawar -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

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Indications for Use

510(k) Number (if known) K170557

Device Name GenePOC GBS LB

Indications for Use (Describe)

The GenePOC™ GBS LB assay performed on the revogene™ instrument is a qualitative in vitro diagnostic test designed to detect Group B Streptococus (GBS) DNA from 18-24 hour LIM broth enrichments of vaginal/rectal specimen swabs obtained from pregnant women. The GenePOC GBS LB assay utilizes automated sample processing and real-time polymerase chain reaction (PCR) to detect a cfb gene sequence specific to the Streptococcus agalactiae genome.

The GenePOC GBS LB assay is indicated for the identification of antepartum GBS colonization and does not provide susceptibility results. It is not intended to diagnose or monitor treatment of GBS infection. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

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)

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510K SUMMARY

A. GENERAL INFORMATION

Submission Date:	February 23, 2017
------------------	-------------------

Submitter Information:

| Submitted By: | GenePOC Inc.
360 rue Franquet, Suite 100 Porte 3
Québec (Québec) G1P 4N3 |
|-----------------|--------------------------------------------------------------------------------|
| Contact Person: | Guy Sevigny
Sr. Regulatory Affairs Specialist
GenePOC Inc. |
| | Telephone: +1 418 650-3535 ext. 261
Fax: |
| | Email: guy.sevigny@genepoc.ca |

B. PURPOSE FOR SUBMISSION:

To obtain a substantial equivalence determination for the GenePOC Group B Step (GBS) LB test

C. MEASURAND:

cfb gene of Streptococcus agalactiae (Group B Streptococcus, GBS)

D. TYPE OF TEST:

Real-time Polymerase chain reaction (rtPCR)

E. DEVICE INFORMATION:

1. Trade Name: GenePOC GBS LB
1. Regulation: 21 CFR 866.3740 - Streptococcal spp. serological reagents
1. Classification: Class I
1. Product Code: NJR - Nucleic Acid Amplification Assay System, Group B Streptococcus, Direct Specimen

4

OOI - Real-time nucleic acid amplification

1. Panel: 83, Microbiology

F. INTENDED USE:

1. Intended Use and Indications for Use:
  The GenePOC™ GBS LB assay performed on the revogene™ instrument is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from 18-24 hour LIM broth enrichments of vaginal/rectal specimen swabs obtained from pregnant women. The GenePOC GBS LB assay utilizes automated sample processing and real-time polymerase chain reaction (PCR) to detect a cfb gene sequence specific to the Streptococcus agalactiae genome.

The GenePOC GBS LB assay is indicated for the identification of antepartum GBS colonization and does not provide susceptibility results. It is not intended to diagnose or monitor treatment of GBS infection. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

1. Special conditions for use statement(s): Prescription Use Only
1. Special instrument requirements: revogene™

G. DEVICE DESCRIPTION:

The GenePOC GBS LB assay is a single-use test for the qualitative detection of Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens using realtime Polymerase Chain Reaction (PCR) technology with fluorogenic detection of the amplified DNA. The GenePOC GBS LB assay utilizes the GBS LB microfluidic cartridge for the simultaneous detection of the target GBS DNA and the internal process control (PrC) DNA (to monitor processing, amplification, and the absence of reaction inhibitors). The GenePOC GBS LB assay is an automated assay performed on the revogene™ including sample processing.

The GenePOC Group B Strep (GBS) LB is composed of a GBS specific disposable microfluidic cartridges, Sample Buffer Tube (SBT) and Disposable Transfer Tool (DTT). These components are used to lyse and dilute the sample, amplify, and detect GBS nucleic acid from vaginal/rectal swabs following LIM broth enrichment. User intervention is required for sample preparation, discharging the LIM broth enriched sample into the SBT, transferring the sample into the cartridge and loading/unloading the cartridge into the revogene instrument. Once the sample is added into the cartridge, the process is then fully automated.

5

Each GenePOC GBS LB Test kit contains 24 individual pouches, and each pouch has components for 1 test including 1 cartridge, 1 SBT, and 1 DTT. The GBS LB Test is run on the revogene instrument which can process from one up to a maximum of 8 samples simultaneously in the same run. On completion of a run, the results are interpolated by the revogene™ from measured fluorescent signals and embedded calculation algorithms. For the GBS application, two spectral signals are processed: GBS target and Internal Process Control. The output results include positive, negative, indeterminate, and unresolved. On completion of a run, the user removes the used cartridges and disposes of them in normal biological waste. Results may be viewed, printed, transferred, and/or stored by the user.

H. SUBSTANTIAL EQUIVALENCE INFORMATION:

1. Predicate Device Name: BD MAX™ GBS Assay
1. Predicate 510(k) Number: K11860
1. Comparison with Predicate:

| Item | GenePOC GBS LB
(Subject Device) | BD MAX GBS Assay
(Predicate Device) |
|-----------------------------------|-------------------------------------------------------------------|----------------------------------------|
| K Number | K170557 | K111860 |
| SIMILARITIES | | |
| Classification | Class I | Same |
| Intended Use | Intended Use for detection of GBS | Same |
| Specimen type | Vaginal-Rectal Swab (Enriched Lim Broth) | Same |
| Collection and
Transport Media | Liquid Amies or Stuart | Same |
| Sample Preparation
Method | Manual; swab enriched overnight in Lim Broth | Same |
| DNA Extraction | Automated by instrument | Same |
| Assay Format | • Amplification: Real Time PCR
• Detection: Fluorogenic | Same |
| Automatic Assay | Yes-result interpretation | Same |
| Internal Process
Control | Extraction and PCR internal control is a process monitor | Same |
| External Control | Materials available commercially but not required to run the test | Same |
| DIFFERENCES | | |
| DNA Target | 190 bp region of the cfb gene | 124 bp region of cfb gene |
| Probe Design | TaqMan® | Scorpion |

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| Item | GenePOC GBS LB
(Subject Device) | BD MAX GBS Assay
(Predicate Device) |
|--------------------------------|------------------------------------------------------------------------------------|-------------------------------------------------------------------|
| GBS Assay
Format | Fully integrated sample processing
and PCR reaction/detection in a
cartridge | Requires combination of a
reagent strip and a PCR
cartridge |
| Single Use | Cartridge can be used once | Cartridge can be used twice |
| Time to Result | ~70 min | 2-3 hours |
| Instrument Optical
Channels | revogene™ contains 4 channels | BD MAX Instrument
contains 6 optical channels |

I. STANDARDS/GUIDANCE DOCUMENTS REFERENCED:

CLSI Guideline EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; . Approved Guideline.

J. TEST PRINICIPLE:

Vaginal-rectal specimen are collected and used to inoculate selective LIM broth. After incubation at 35-37℃ for 18-24 hours in ambient, 15 µL of the inoculated broth is transferred to the Sample Buffer Tube (SBT). After vortexing the SBT for 15 seconds, approximately 150 µL of the inoculated sample buffer is transferred into the GenePOC microfluidic cartridge using the Disposable Transfer Tool (DTT). The loaded GBS LB cartridge is placed into the revogene for further sample processing. No operator intervention is necessary once the clinical sample is loaded onto the revogene.

Each GBS LB microfluidic cartridge is a completely integrated and self-contained device. Each sample is transferred by centrifugation from one microfluidic chamber to the next in sequence, and all reagents specific for the PCR reaction are incorporated and dried within the PCR wells. The stepwise process includes sample homogenization, lysis of cells, and specimen dilution followed by the subsequent real-time PCR steps within 1 PCR well in the cartridge. An internal Process Control (PrC) is contained in the homogenization chamber and is therefore present in every test to monitor critical steps of the analytical process (including sample lysis, dilution and nucleic acid amplification and detection) for the presence of potential inhibitory substances as well as system or reagent failures. The amplified products are detected in real time using target-specific TaqMan® chemistry-based probes. The GBS LB specific designed primers and probe detect a target region of 190 base pairs of the cfb gene specific to the Streptococcus agalactiae genome. The results are interpolated by the revogene from measured fluorescent signals and embedded calculation algorithms.

K. PERFORMANCE CHARACTERISTICS:

1. Analytical Performance

a. Precision/Reproducibility

The reproducibility study was conducted at three sites (two external sites and GenePOC laboratories) to evaluate the within-run, between-run (three runs per

7

day) and between-day (five days, consecutive or not) reproducibility and variance with multiple operators (n=6; two operators per site). Precision was evaluated based on the within-site variability over 5 days. Three revogene instruments (one per site) and a single lot of the GenePOC GBS LB assay were used by each site (total of three reagent lots).

Three GBS strains were tested at two different concentrations in each run: low positive (LP; 735 CFU/mL SB) and moderate positive (MP; 1,125 CFU/mL SB). The GBS strains used in the panels were the hemolytic serotype Ia S. agalactiae strain ATCC 12400, the hemolytic serotype III S. agalactiae strain ATCC 12403 and the non-hemolytic S. agalactiae strain ATCC 13813. Two true negative (TN) samples were included in each run.

After the testing of 720 replicates (270 low positive, 270 moderate positive, and 180 true negative samples) with the GenePOC GBS LB assay, the overall analysis showed 100% agreement for negative samples, 98.9% agreement for low positive samples, and 98.5% agreement for moderate positive samples as summarized in the table below.

| Sample | Strain | Site 1 | Site 2 | Site 3 | Overall
Assay
Results/Total | % Agreement |
|----------------------------------------------|-------------------------------------------------|---------------------|------------------|-----------------|-----------------------------------|-------------|
| | | Assay Results/Total | | | | |
| Low Positive
(735 CFU/mL of
SB) | ATCC 13813 | 29/30 | 30/30 | 30/30 | 89/90 | 98.9% |
| | ATCC 12403 | 28/30 | 30/30 | 30/30 | 88/90 | 97.8% |
| | ATCC 12400 | 30/30 | 30/30 | 30/30 | 90/90 | 100% |
| | Overall
Results/Total
(% Agreement) | 87/90
(96.7%) | 90/90
(100%) | 90/90
(100%) | 267/270 | 98.9% |
| Moderate Positive
(1,125 CFU/mL of
SB) | ATCC 13813 | 28/30 | 29/30 | 30/30 | 87/90 | 96.7% |
| | ATCC 12403 | 29/30 | 30/30 | 30/30 | 89/90 | 98.9% |
| | ATCC 12400 | 30/30 | 30/30 | 30/30 | 90/90 | 100% |
| | Overall
Results/Total
(% Agreement) | 87/90
(96.7%) | 89/90
(98.9%) | 90/90
(100%) | 266/270 | 98.5% |
| True Negative | NA
Overall
Results/Total
(% Agreement) | 60/60
(100%) | 60/60
(100%) | 60/60
(100%) | 180/180 | 100% |

Summary of the Percent Agreement Analysis across all Sites

The quantitative results for the between strain, between-site, between-operator and between-day reproducibility for Ct values are summarized below:

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GBS Ct; Low Positive (735 CFU/mL)
Variance component	N*	Variance	%	Mean	SD	rSD
(%CV)
Residual		2.57	68.5%		1.6	4.4%
Strain		0.32	8.5%		0.6	1.6%
Site	267	0.73	19.4%	36.4	0.9	2.3%
Operator (Site)		0.14	3.6%		0.4	1.0%
Day (Site x Op)		0.00	0.0%		0.0	0.0%
All components		1.18	31.5%		1.1	3.0%
GBS Ct; Moderate Positive (1,125 CFU/mL)
Variance component	N*	Variance	%	Mean	SD	rSD
(%CV)
Residual		2.33	72.4%		1.5	4.3%
Strain		0.11	3.6%		0.3	1.0%
Site	266	0.65	20.1%	35.7	0.8	2.3%
Operator (Site)		0.11	3.4%		0.3	0.9%
Day (Site x Op)		0.02	0.5%		0.1	0.4%
All components		0.89	27.6%		0.9	2.6%
PrC Ct; All specimens
Variance component	N*	Variance	%	Mean	SD	rSD
(%CV)
Residual		1.22	65.8%		1.1	3.5%
Strain/NEG		0.01	0.7%		0.1	0.4%
Site		0.56	29.9%	31.9	0.7	2.3%
Operator (Site)	718	0.05	2.5%		0.2	0.7%
Day (Site x Op)		0.02	1.1%		0.1	0.4%
All components		0.64	34.2%		0.8	2.5%

Summary of the Overall SD and % CV for the Ct values for the Reproducibility Study

			Ct GBS		Inter-site	Inter-operator		Inter-day		Overall
Load	Strain	N	Mean Ct	SD	% CV	SD	% CV	SD	% CV	SD	% CV
	ATCC 13813	89	36.4	2.6	7.1	2.4	6.6	3.9	10.6	5.2	14.4
Low Positive (1-2xLoD)	ATCC 12403	88	36.9	3.2	8.5	2.7	7.3	4.3	11.5	5.9	16.1
	ATCC 12400	90	35.8	2.6	7.4	2.2	6.2	3.8	10.5	5.1	14.3
Overall Low Positive		267	36.4	2.9	8.0	2.6	7.0	4.1	11.2	5.6	15.5
	ATCC 13813	87	ਤੇ 'ਚ	2.5	7.1	2.5	7.0	4.0	11.2	5.4	15.0
Moderate Positive (3xLoD)	ATCC 12403	89	35.9	2.8	7.8	2.4	6.7	3.9	10.7	5.3	14.9
	ATCC 12400	90	35.3	2.7	7.6	2.2	6.4	3.7	10.4	5.1	14.4
Overall Moderate Positive		266	35.7	2.7	7.6	2.4	6.8	3.9	10.8	5.3	14.9
		Ct PrC		Inter-site		Inter-operator		Inter-day		Overall
Load	Strain	N	Mean	SD	% CV	SD	% CV	SD	% CV	SD	% CV
True Negative	N/A	180	31.9	1.7	5:5	1.8	5.7	2.9	9.2	3.9	12.1

A summary of the SD and % CV for the Ct values for the quantitative withinsite analysis are presented below.

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		Site 1			Site 2				Site 3
		Mean Ct, SD and %CV GBS
Target Load	Strain	N	Mean	SD	% CV	N	Mean	SD	% CV	N	Mean	SD	% CV
True Negative	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Low Positive (735	ATCC 13813	ਨਰ	37.6	1.8	4.9	30	36.3	1.0	2.8	30	35.4	1.5	4.3
CFU/mL)	ATCC 12403	28	37.7	2.4	6.4	30	37.0	1.6	4.3	30	36.1	1.3	3.5
	ATCC 12400	30	36.7	1.6	4.4	30	35.4	1.5	4.1	30	35.2	1.5	4.2
Overall (Low positive sample only)
Result/expected result		87	37.3	2.0	5.4	90	36.3	1.5	4.2	90	35.5	1.5	4.1
	ATCC 13813	28	37.2	1.9	5.2	29	36.0	1.1	3.2	30	34.7	1.2	3.3
Moderate Positive (1125	ATCC 12403	29	36.6	2.1	5.7	30	35.9	1:5	4.1	30	35.2	1.2	3.4
CFU/mL)	ATCC 12400	30	36.0	1.2	3.5	30	35.1	1.3	3.6	30	34.7	2.0	5.8
Overall (Moderate positive sample only)
Result/expected result		87	36.6	1.8	5.0	89	35.7	1.4	3.8	90	34.9	1.5	4.3
		Mean Ct, SD and %CV PrC
Target Load	Strain	N	Mean	SD	% CV	N	Mean	SD	% CV	N	Mean	SD	% CV
True Negative	NA	60	32.1	1.2	3.7	60	32.7	0.7	3.2	60	30.8	1.1	2.4
Low Positive (735	ATCC 13813	30	32.5	1.0	3.0	30	32.4	0.9	2.6	30	31.2	1.0	3.1
CFU/mL)	ATCC 12403	30	32.5	2.2	6.9	30	32.2	0.9	2.7	30	31.2	1.6	5.0
	ATCC 12400	30	32.4	1.5	4.7	30	31.9	0.9	2.8	30	31.1	0.7	2.4
Overall (Low positive sample only)
Result/expected result		90	32.5	1.6	5.1	90	32.2	0.9	2.7	90	31.2	1.1	3.7
	ATCC 13813	30	32.7	1.2	3.8	30	32.9	1.2	3.5	30	31.0	0.9	3.1
Moderate Positive (1125
CFU/mL)	ATCC 12403	30	31.6	0.9	2.9	30	32.5	1.1	3.5	30	30.8	0.8	2.6
	ATCC 12400	29	32.1	0.8	2.5	30	32.1	0.8	2.4	29	31.3	1.0	3.3
Overall (Moderate positive sample only)
Result/expected result		89	32.1	1.1	3.4	90	32.5	1.1	3.3	89	31.0	0.9	3.0

Summary of the SD and % CV for the Ct values for the Within-Site Precision Study

b. Linearity/Assay Reportable Range

Not applicable. The GenePOC GBS LB Test is a qualitative assay.

c. Traceability, Stability, Expected Values (controls, calibrators, or methods) Commercial control material (e.g. Streptococcus agalactiae ATCC® 13813) can be used as a Positive External Control. It is recommended that bacterial strains be freshly prepared in LIM broth. Transfer a 15 uL aliquot of a 18-24 hours culture in LIM broth into a SBT. Pure LIM broth is recommended for use as a Negative External Control.
An Internal Process Control (PrC) is provided in each GenePOC GBS LB test. The PrC is extracted, amplified, and detected along with each specimen tested and monitors the efficacy of the cell lysis, dilution and PCR amplification and detection processes.

d. Detection Limit

The analytical sensitivity (Limit of Detection or LoD) of the GBS LB assay was determined using clinical LIM broth matrix previously tested negative for GBS and spiked with different concentrations of GBS bacterial suspensions. Two

10

strains of GBS (ATCC 12403 and ATCC 13813) were tested in 24 replicates per concentration by 2 operators using 3 different lots of GBS LB kits. The LoD is defined as the lowest concentration at which 95% of all replicates tested positive. The LoD of the GBS LB assay ranged from 200 to 375 CFU/mL of SB (200 CFU/mL for ATCC 13813 and 375 CFU/mL for ATCC 12403).

e. Analytical Inclusivity

The analytical reactivity was determined with 12 strains of S. agalactive representing 11 known serotypes and one non-haemolytic strain. Each strain was tested in 8 replicates per dilution per lot of material. All strains were detected at concentrations ranging from 1x to 15x LoD.

| Strain¹ | Serotype | Concentration at which replicates are 100% positive
CFU/mL of SB |
|---------------|---------------|---------------------------------------------------------------------|
| ATCC 12400 | Ia | 735 |
| ATCC 51487 | Ib | 5,625 |
| ATCC 27591 | Ic | 1,875 |
| ATCC 12973 | II | 735 |
| ATCC 12403 | III | 375 |
| ATCC 49446 | IV | 2,625 |
| ATCC BAA-611 | V | 1,875 |
| ATCC BAA-2671 | VI | 1,125 |
| ATCC BAA-2670 | VII | 2,625 |
| ATCC BAA-2669 | VIII | 3,750 |
| ATCC BAA-2668 | IX | 1,125 |
| ATCC 13813 | Non-hemolytic | 500 |

f. Analytical Specificity

Cross Reactivity:

A total of 75 non-specific analytes were tested in this study and listed in the table below. The various analytes selected are found in clinical vaginal-rectal specimens (different from Streptococcus agalactiae) including commensal and pathogenic microorganisms (yeasts, viruses, parasites and bacteria) from urogenital and intestinal tracts; species phylogenetically similar to S. agalactiae; and human DNA. Bacteria and yeasts were diluted at a concentration of ≥100 CFU/mL SB whereas viruses, parasites and human DNA were prepared at ≥105 DNA or RNA cp/mL SB.

Assays were carried with 3 reagent kit lots on 2 revogene instruments. All samples were tested in triplicate (4 yeasts, 4 viruses, 2 parasites, human DNA and 64 bacteria). The total reactivity rate of the GenePOC GBS LB test with the selected non-specific analytes is 0%.

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Bacteria (strain or gDNA)	Name
Acinetobacter baumannii	Mycoplasma genitalium gDNA
Aerococcus viridans	Mycoplasma hominis gDNA
Aeromonas hydrophila	Neisseria gonorrhoeae
Bacillus cereus	Peptostreptococcus anaerobius
Bacillus subtilis	Porphyromonas asaccharolytica
Bacteroides fragilis	Prevotella melaninogenica
Bifidobacterium adolescentis	Propionibacterium acnes
Bifidobacterium breve	Proteus mirabilis
Brevibacterium linens	Pseudomonas aeruginosa
Campylobacter jejuni	Salmonella enterica subsp. enterica serovar
Dublin
Chlamydia trachomatis gDNA	Salmonella enterica subsp. enterica serovar
Minneapolis
Citrobacter freundii	Salmonella enterica subsp. enterica serovar
typhimurium
Clostridium difficile	Salmonella enterica subsp. enterica serovar
Newport
Clostridium perfringens	Serratia marcescens
Corynebacterium genitalium	Shigella sonnei
Enterobacter aerogenes	Staphylococcus aureus
Enterobacter cloacae	Staphylococcus aureus (Cowan)
Enterococcus avium	Staphylococcus epidermidis
Enterococcus dispar	Staphylococcus saprophyticus
Enterococcus durans	Streptococcus anginosus
Enterococcus faecalis	Streptococcus bovis
Enterococcus faecium	Streptococcus dysgalactiae subsp.
disgalactiae
Escherichia coli	Streptococcus dysgalactiae equisimilis
Escherichia fergusonii	Streptococcus intermedius
Gardnerella vaginalis	Streptococcus oralis
Klebsiella oxytoca	Streptococcus pneumoniae
Klebsiella pneumoniae	Streptococcus pyogenes
Lactobacillus acidophilus	Streptococcus salivarius
Name	Name
Lactobacillus brevis	Streptococcus sanguinis
Lactobacillus casei	Streptococcus uberis
Lactobacillus delbreuckii	Ureaplasma urealyticum gDNA
Lactobacillus jensenii	Yersinia enterocolitica
Yeasts
Candida albicans	Candida parapsilosis
Candida glabrata	Candida tropicalis
Viruses (gDNA or RNA)
HerpesSimplexVirus-1 gDNA	Norovirus GII RNA
HerpesSimplexVirus-2 gDNA	Human Papillomavirus (HPV) gDNA
Parasites (gDNA)
Blastocystis hominis gDNA	Trichomonas vaginalis gDNA

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g. Interference with Non-Target Organisms

Microbial interference on the GenePOC GBS LB assay was evaluated with 29 potentially interfering microorganisms in absence and in presence of 2 GBS strains tested at 735 CFU/mL of SB. Samples were grouped together into 7 pools of interferences. Each of the 7 pools were tested in triplicate across 3 reagent lots for a total of 9 replicates by pool were analyzed to determine the presence or absence of interference. Results of the study showed no interference against the GBS target (735 CFU/mL of SB) was detected for 26 out of 29 microorganisms when present in high loads (105 or 106 CFU/mL of SB). However, strains Enterococcus faecalis ATCC 19433, Enterococcus faecium ATCC 19434 and Lactobacillus acidophilus ATCC 4356 showed interference against the GBS target (735 CFU/mL of SB) when they were present at >104 CFU/mL of SB. No interference on the Process Control was observed when microorganisms were present in high loads (105 or 106 CFU/mL of SB).

h. Interference with Exogenous and Endogenous Substances

Interference on the GenePOC GBS LB assay was evaluated with 31 potentially interfering exogenous and endogenous substances in absence and in presence of 2 GBS strains tested at 735 CFU/mL SB across 3 reagent lots. The interferences tested included the following: whole blood, leukocytes, amniotic fluid, mucous, seminal fluid. urine, feces, meconium. human DNA. Fungicide, Hemorrhoid cooling gel, Lubricating gel, Body powder, moisturizing lotion, body oil, Deodorant spray, enemas. Antimicrobials, Radiology oral compounds, gastritis medications, Non-Steroidal Anti-Inflammatory, Medications, gastritis medications, anti-Diarrheal medication, Laxatives, Spermicidal, and Moist Towelettes. Results demonstrated no reportable interference on PrC. Only the combination of loperamide hydrochloride (e.g. Imodium®), bismuth

13

subsalicylate (e.g. Pepto-Bismol™) and sennosides (e.g. Senokot®) at concentrations of 0.023 ug/mL, 0.675 ug/mL and 0.011 ug/mL SB, respectively, showed a potentially inhibitory effect on detection of GBS. When tested individually, these substances showed no reportable interference with the GBS LB assay.

Carryover and Cross Contamination Studies i.

The carry-over and cross-contamination study showed that there is no evidence of amplicon carry-over or sample contamination when using the revogene with the GenePOC GBS LB assay. A total of 80 samples in the within-run study and 80 samples in the between run study were tested and none gave a false positive result. For each study various combinations of high positive and GBS negative samples were run for each of the 10 runs per study across 3 reagent lots. For each sample, quantitated culture of the organism was diluted in negative matrix. The high positive (>1x106 CFU/mL of SBT) suspension tested in this study was prepared with the S. agalactiae strain Serotype III ATCC 12403.

2. Comparison Studies

a. Method Comparison with predicate device Not applicable.
b. Matrix Comparison Not applicable.

3. Clinical Studies

GenePOC conducted a prospective multicenter trial at 4 geographically diverse clinical trial sites; specifically, two Canadian and two US clinical sites. A vaginal/rectal swab specimen was collected from n=839 pregnant women at 35-37 weeks of gestation for whom GBS diagnostic procedures were ordered. For each patient, the swab was used for the composite reference method consisting of LIM Broth enrichment of the vaginal/rectal swab followed by a subculture on blood agar plate and biochemical identification of GBS. All specimens with a negative bacterial culture result were re-tested using the same standard operating procedures required for bacterial culture. Residual de-identified LIM Broth samples were used for testing with the GenePOC GBS LB assay. Of those, 63 specimens were regarded as noncompliant per the composite reference method and/or GBS LB assay protocol criteria, 1 specimen was regarded as noncompliant in terms of transport and storage conditions and 4 specimens were regarded as noncompliant due to missing test results. Two (2) fully compliant specimens gave final non-reportable PCR results. A total of 771 specimen results were used to determine the clinical performance of the GBS LB assay in comparison to the composite reference method. A total of 170 GBS positive and 601 GBS negative samples were collected across the four sites.

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| Overall performance | | Composite
Reference
Method | | |
|-------------------------------------------|----------|----------------------------------|----------|-------|
| | | Positive | Negative | Total |
| GBS LB | Positive | 163 | 27B | 190 |
| assay | Negative | 7A | 574 | 581 |
| | Total | 170 | 601 | 771 |
| Sensitivity: 95.9% (95%CI: 91.7 - 98.0 %) | | | | |
| Specificity: 95.5% (95%CI: 93.5 - 96.9 %) | | | | |

Overall performance characteristics of the GBS LB assay in comparison to the composite reference method.

A 5 out of 7 false negative GenePOC GBS LB results were tested on a FDA-cleared molecular device and yielded negative results.

B 10 out 27 false positive GenePOC GBS LB results were tested on a FDA-cleared molecular device and yielded positive results.

Site	Sensitivity	Specificity	Prevalence1
1	87.8%	92.8%	21.1%
	(36/41)	(142/153)	(41/194)
2	98.0%	97.5%	19.8%
	(48/49)	(194/199)	(49/248)
3	100%	97.0%	20.3%
	(43/43)	(164/169)	(43/212)
4	97.3%	92.5%	31.6%
	(36/37)	(74/80)	(37/117)
Total	95.9%	95.5%	22.0%
	(163/170)	(574/601)	(170/771)

Summary of performance characteristics of the GBS LB assay per site

1 Prevalence was calculated with samples compliant at culture composite reference method and GenePOC™ GBS LB assay levels.

4. Clinical Cut-off

Not applicable.

5. Expected Values/Reference Range

In the investigational study for the GenePOC GBS LB assay, a total of 771 reportable results from specimens compliant at the culture and PCR levels were obtained from 4 geographically diverse regions. Overall, GBS prevalence rate was 22.0 % (170/771) with a 95 % CI of 19.3 – 25.1 %.

15

L. INSTRUMENT NAME:

revogene™M

M. SYSTEM DESCRIPTIONS:

1. Modes of Operation:
  Real-time Polymerase chain reaction with fluorogenic detection of amplified DNA.
1. Software:
  FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:

Yes X_ or No _________________________________________________________________________________________________________________________________________________________

1. Specimen Identification:
  Barcodes are used to identify patient specimens. The GenePOC GBS LB assay's Sample Buffer Tube (SBT) and microfluidic cartridge (PIE) both are pre-labeled with a unique barcode to identify both specimen and assay. The instrument has two barcode readers to identify reagents and patient specimens. It provides traceability of the sample ID to the PIE ID, SBT ID, and assay ID.

Specimen Sampling and Handling: 4.

User intervention is required for discharging the patient sample into the SBT, transferring a 150 uL aliquot of the sample into the microfluidic cartridge and for loading the microfluidic cartridge into the revogene. All further specimen handling is automated.

1. Calibration:
  The system is factory calibrated by the manufacturer as well as during annual preventive maintenance.
1. Quality Control:
  An Internal Process Control (PrC) provided in each microfluidic cartridge of the GenePOC GBS LB assay. The PrC is lysed, amplified, and detected along with each specimen tested and monitors the efficacy of the DNA extraction and PCR amplification processes.

Commercial control material (e.g. Streptococcus agalactiae ATCC® 13813) can be used as a Positive External Control. It is recommended that bacterial strains be freshly prepared in LIM broth. Transfer a 15 uL aliquot of a 18-24 hours culture in LIM broth into a SBT. Pure LIM broth is recommended for use as a Negative External Control.

16

N. OTHER SUPPORTIVE INSTRUMENT PERFORMANCE CHARACTERISTICS DATA NOT COVERED IN THE "PERFORMANCE CHARACTERISTICS" SECTION:

Not applicable.

O. PROPOSED LABELING:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

P. CONCLUSION:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.