(87 days)
Not Found
No
The description details a standard real-time PCR assay and its associated automated system. There is no mention of AI, ML, or any algorithms beyond basic cycle threshold (Ct) computation for qualitative determination.
No
Explanation: This device is an in vitro diagnostic test designed to detect Group B Streptococcus DNA. It aids in determining GBS colonization status and does not diagnose, treat, or monitor GBS infections, nor does it provide susceptibility results. Its function is solely for diagnostic purposes, not for therapy.
Yes
The device is explicitly described as an "in vitro diagnostic test" intended to "aid in determining the GBS colonization status of antepartum women."
No
The device description clearly outlines a multi-step process involving sample lysis, nucleic acid capture and elution, and RT-PCR, all performed on the "Hologic Panther Fusion system." This system is a hardware platform that executes the assay steps, making the device a combination of hardware and software, not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Panther Fusion GBS assay is an automated qualitative in vitro diagnostic test utilizing real-time PCR for detection of Group B Streptococcus DNA..."
This statement clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The Panther Fusion GBS assay is an automated qualitative in vitro diagnostic test utilizing real-time PCR for detection of Group B Streptococcus DNA from either Lim or Carrot enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18-24 hours incubation.
This test is performed on the Hologic Panther Fusion system and is intended to aid in determining the GBS colonization status of antepartum women. This assay does not diagnose or monitor treatment for GBS infections. The Panther Fusion GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.
Product codes
NJR, OOI
Device Description
The Panther Fusion GBS assay involves the following steps: Sample lysis, nucleic acid capture and elution, and multiplex RT-PCR where analytes (when present) are simultaneously amplified, detected and differentiated. Nucleic acid capture and elution takes place in a single tube on the Panther Fusion system. The eluate is transferred to the Panther Fusion system reaction tube containing the assay reagents. RT-PCR is then performed for the eluted nucleic acid on the Panther Fusion system.
Sample Collection and Enrichment: After collecting and transporting a swab sample to the laboratory, the swab is placed in Lim Broth or Carrot Broth for 18 to 24 hours of enrichment. Prior to testing on the Panther Fusion system, enriched specimens are then transferred to a tube containing specimen transport media (STM) that lyses the cells, releases target nucleic acid and protects them from degradation during storage.
Nucleic Acid Capture and Elution: Specimens are then first incubated in an alkaline reagent (FER-X) to enable cell lysis. The Internal Control (IC-X) is added to each test specimen and controls via the working Panther Fusion capture Reagent-X (wFCR-X). The IC-X monitors specimen processing, amplification and detection. Magnetic particles with covalently bound oligonucleotides, contained in Panther Fusion capture Reagent-X (FCR-X), mediate the nucleic acid capture by hybridizing to total nucleic acid in the test specimen. The capture nucleic acids are then separated from residual specimen matrix in a magnetic field by a series of wash steps with a mild detergent. The captured nucleic acid is then eluted from the magnetic particles with a reagent of low ionic strength (Panther Fusion Elution Buffer).
Elution transfer and PCR: During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion Reaction tube already containing oil and reconstituted mastermix. PCRbased target amplification subsequently occurs with target-specific forward and reverse primers, generating a fluorescence signal. The Panther Fusion GBS Software computes a cycle threshold result (Ct) to qualitatively determine the presence of the analyte targets and corresponding fluorescent channels used in the Panther Fusion GBS Assay are summarized in the Table 1 below.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
vaginal/rectal swabs
Indicated Patient Age Range
antepartum women
Intended User / Care Setting
Professional use
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
Prospective Clinical Study:
This prospective study was performed at three sites using leftover enriched culture samples in Lim broth and Carrot broth from vaginal/rectal specimens collected from antepartum women during routine GBS screening. The leftover culture samples were selected according to the inclusion and exclusion criteria, patient information was de-identified and each specimen was given a unique ID number. All samples were tested with both the Panther Fusion GBS Assay and the reference culture method following CDC recommendations.
Data Source: Clinical evaluation at three geographically distinct sites in the United States.
Sample Size: A total of 947 clinical leftover samples, meeting the inclusion criteria.
Annotation Protocol: Results obtained using the Panther Fusion GBS Assay were compared to those obtained with the reference method to calculate the clinical sensitivity and specificity of the Panther Fusion GBS Assay.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Analytical (Non-Clinical) Studies and Clinical Study
Analytical Sensitivity and Limit of Detection (LoD) of GBS in Vaginal/Rectal Swab Specimens:
Sample Size: 30 replicates for each of 11 GBS serotypes and one non-hemolytic (NH) isolate, tested with three reagent lots, for a combined total of 90 replicates per dilution.
Key Results: Probit analysis was performed for each reagent lot with the reported 95% LoD based upon the worst estimate. LoD values ranged from 84.0 CFU/mL (Serotype IV) to 301.0 CFU/mL (Serotype IX) for different GBS serotypes and 300.2 CFU/mL for NH.
Interferences:
Study: Evaluated the impact of amniotic fluid, blood, urine, stool and other potentially interfering endogenous and exogenous substances on assay performance.
Key Results: All substances tested found to have no impact on the performance of the Panther Fusion GBS assay at the concentrations tested.
Analytical Specificity and Microbial Interference:
Study: Evaluated a panel of 110 microorganisms (viral, bacterial, fungal, parasite, protozoan, yeast) at specific concentrations (1x10^6 CFU/mL for bacteria/yeast, 1x10^5 PFU/mL for viruses/fungi/parasites/protozoan). Organisms were tested with and without GBS spiked at 3X LoD.
Key Results: All microorganisms tested were found to have no impact on the performance or analytical specificity of the Panther Fusion GBS assay.
Carryover/Cross-Contamination:
Study: High positive samples (> 1x 10^6 CFU/mL (> 5,000X LoD)) alternated with negative samples. Ten separate runs in a checkerboard pattern, plus four runs of negative specimens over two instruments.
Sample Size: 300 positive and 420 negative samples.
Key Results: 0.0% false positive results observed (no false positives).
Assay Precision:
Sample Size: 7-member panel tested by three operators on five separate runs per day, using three reagent lots on one Panther Fusion system over 12 non-consecutive days.
Key Results: 100% agreement with expected results for GBS III, GBS V, GBS NH positive samples (1-2X LoD and 3X LoD) and negative samples. Overall Ct variability ranged from 1.14% to 1.46%.
Reproducibility:
Study: Evaluated at three US sites using a seven panel members. Testing performed by six operators (two per site), two times per day during five non-consecutive days. Each run had three replicates of each panel member.
Key Results: Agreement with expected results was 100% in negative and moderate positive panel members, and ≥98.9% in low-positive panel members for the three GBS strains evaluated. Total GBS signal variability (%CV) ranged from 1.51% to 2.25% in low and moderate positive panel members.
Clinical Study:
Study Type: Prospective Clinical Study
Sample Size: 947 clinical leftover samples (643 Lim Broth, 304 Carrot Broth).
Key Results:
- Lim Broth Specimens: Sensitivity = 100% (95% CI: 96.9% - 100%), Specificity = 96.9% (95% CI: 95.1% - 98.1%), Positive Predictive Value = 88.2% (95% CI: 81.7% - 92.6%), Negative Predictive Value = 100% (95% CI: 99.3% - 100%).
- Carrot Broth Specimens: Sensitivity = 100% (95% CI: 95.6% - 100%), Specificity = 95.5% (95% CI: 91.9% - 97.5%), Positive Predictive Value = 89.3% (95% CI: 81.3% - 94.1%), Negative Predictive Value = 100% (95% CI: 98.2% - 100%).
- Combined Lim & Carrot Broth Specimens: Sensitivity = 100% (95% CI: 98.1% - 100%), Specificity = 96.5% (95% CI: 94.9% - 97.6%), Positive Predictive Value = 88.7% (95% CI: 83.9% -92.1%), Negative Predictive Value = 100% (95% CI: 99.5% - 100%).
- Overall prevalence of GBS colonization by Panther Fusion GBS Assay was 24.2% (229/947), and by conventional culture was 21.4% (203/947).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Sensitivity:
- Lim Broth: 100% (95% CI: 96.9% - 100%)
- Carrot Broth: 100% (95% CI: 95.6% - 100%)
- Combined: 100% (95% CI: 98.1% - 100%)
Clinical Specificity:
- Lim Broth: 96.9% (95% CI: 95.1% - 98.1%)
- Carrot Broth: 95.5% (95% CI: 91.9% - 97.5%)
- Combined: 96.5% (95% CI: 94.9% - 97.6%)
Positive Predictive Value:
- Lim Broth: 88.2% (95% CI: 81.7% - 92.6%)
- Carrot Broth: 89.3% (95% CI: 81.3% - 94.1%)
- Combined: 88.7% (95% CI: 83.9% -92.1%)
Negative Predictive Value:
- Lim Broth: 100% (95% CI: 99.3% - 100%)
- Carrot Broth: 100% (95% CI: 98.2% - 100%)
- Combined: 100% (95% CI: 99.5% - 100%)
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.
Cepheid Xpert® GBS LB (K121539)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3740
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.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" and "ADMINISTRATION" in blue text.
July 27, 2018
Diagenode % Jinjie Hu Principle Consultant Axteria BioMed Consulting Inc. 8040 Cobble Creek Circle Potomac, Maryland 20854
Re: K181156
Trade/Device Name: Panther Fusion GBS Assay Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcus spp. serological reagents Regulatory Class: Class I Product Code: NJR, OOI Dated: May 1, 2018 Received: May 1, 2018
Dear Jinjie Hu:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Noel J. Gerald -S
For
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K181156
Device Name Panther Fusion GBS Assay
Indications for Use (Describe)
The Panther Fusion GBS assay is an automated qualitative in vitro diagnostic test utilizing real-time PCR for detection of Group B Streptococcus DNA from either Lim or Carrot enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18-24 hours incubation.
This test is performed on the Hologic Panther Fusion system and is intended to aid in determining the GBS colonization status of antepartum women. This assay does not diagnose or monitor treatment for GBS infections. The Panther Fusion GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(K) SUMMARY
A. GENERAL INFORMATION
SUBMITTER
| | Diagenode SA
Rue du Bois Saint-Jean, 3
4102 Seraing
Belgium |
|------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact person: | Jinjie Hu,
Axteria BioMed Consulting Inc.
8040 Cobble Creek Circle
Potomac, MD 20854
Tel: 1-(301)814-4985
Email: jinjiehu@axteriabiomed.com |
| Date prepared: | July 9, 2018 |
| Purpose of Submission: | To obtain a substantial equivalence for the Panthe
Fusion GBS Assay |
B. MEASURAND
SIP and Cfb genes of Streptococcus agalactiae (Group B Streptococcus, GBS)
C. DEVICE INFORMATION
| Proprietary Name of the device: | Panther Fusion GBS Assay |
|---|---|
| Classification name: | Streptococcus spp. serological reagents and Real- |
| time Nucleic Acid Amplification | |
| Regulation number: | 21 CFR 866.3740 and 862.2570 |
| Classification Name and Reference: | Class 1 (Not exempt) |
| Device product Code | NJR and OOI |
| Panel: | 83, Microbiology |
D. INTENDED USE/INDICATIONS FOR USE
The Panther Fusion GBS assay is an automated qualitative in vitro diagnostic test utilizing realtime PCR for detection of Group B Streptococcus DNA from either Lim or Carrot enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18-24 hours incubation.
4
This test is performed on the Hologic Panther Fusion system and is intended to aid in determining the GBS colonization status of antepartum women. This assay does not diagnose or monitor treatment for GBS infections. The Panther Fusion GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.
E. DEVICE DESCRIPTION
The Panther Fusion GBS assay involves the following steps: Sample lysis, nucleic acid capture and elution, and multiplex RT-PCR where analytes (when present) are simultaneously amplified, detected and differentiated. Nucleic acid capture and elution takes place in a single tube on the Panther Fusion system. The eluate is transferred to the Panther Fusion system reaction tube containing the assay reagents. RT-PCR is then performed for the eluted nucleic acid on the Panther Fusion system.
Sample Collection and Enrichment: After collecting and transporting a swab sample to the laboratory, the swab is placed in Lim Broth or Carrot Broth for 18 to 24 hours of enrichment. Prior to testing on the Panther Fusion system, enriched specimens are then transferred to a tube containing specimen transport media (STM) that lyses the cells, releases target nucleic acid and protects them from degradation during storage.
Nucleic Acid Capture and Elution: Specimens are then first incubated in an alkaline reagent (FER-X) to enable cell lysis. The Internal Control (IC-X) is added to each test specimen and controls via the working Panther Fusion capture Reagent-X (wFCR-X). The IC-X monitors specimen processing, amplification and detection. Magnetic particles with covalently bound oligonucleotides, contained in Panther Fusion capture Reagent-X (FCR-X), mediate the nucleic acid capture by hybridizing to total nucleic acid in the test specimen. The capture nucleic acids are then separated from residual specimen matrix in a magnetic field by a series of wash steps with a mild detergent. The captured nucleic acid is then eluted from the magnetic particles with a reagent of low ionic strength (Panther Fusion Elution Buffer).
Elution transfer and PCR: During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion Reaction tube already containing oil and reconstituted mastermix. PCRbased target amplification subsequently occurs with target-specific forward and reverse primers, generating a fluorescence signal. The Panther Fusion GBS Software computes a cycle threshold result (Ct) to qualitatively determine the presence of the analyte targets and corresponding fluorescent channels used in the Panther Fusion GBS Assay are summarized in the Table 1 below.
| Analyte | Gene Targeted | Instrument Channel |
|---|---|---|
| GBS | SIP and Cfb | FAM |
| Internal Control | Not applicable | RED677 |
Table 1: Analytes and Detection Channels
5
Assay Components
The reagents required to perform the Panther Fusion GBS assay are packed together in the Panther Fusion GBS assay box. A description of the components that are required to perform the Panther Fusion GBS assay are detailed in Table 2.
| Box | Components |
|---|---|
| 1 | Panther Fusion GBS Cartridges |
| 2 | Panther Fusion Extraction Reagent-X |
| - Panther Fusion Capture Reagent-X | |
| - Panther Fusion Enhancer Reagent-X | |
| 3 | Panther Fusion Internal Control-X |
| 4 | Panther Fusion Elution Buffer |
| 5 | Panther Fusion Reconstitution Buffer I |
| 6 | Panther Fusion Oil |
| 7 | Panther Fusion GBS Assay Controls |
| - Panther Fusion GBS Assay Positive Control | |
| - Panther Fusion GBS Assay Negative Control |
Table 2: Reagents Required to Perform the Panther Fusion GBS Assay
Instrumentation
The Panther Fusion GBS assay has been designated for and validated on the Panther Fusion system. The Panther Fusion system is an integrated hardware and software system that together with the Panther Fusion GBS assay automates all the steps necessary to perform the assay.
The Panther Fusion system integrates Hologic's commercialized Panther instrument system with an add-on sidecar, the Panther Fusion module, which extends the functionality of the Panther system by increasing the assay processing capabilities to include multiplex real-time RT-PCR. The Panther Fusion module includes instrument hardware and can be installed on existing Panther instruments or ordered with new Panther instruments.
The Panther Fusion system employs non-specific target capture (NSTC) for the purification of RNA and DNA from the sample, followed by nucleic acid amplification and real-time fluorescent detection. The process involves sample loading and preparation (i.e. nucleic acid extraction) on the Panther instrument using the same workflow and processing steps as for other commercialized Hologic Aptima Transcription Mediated Amplification (TMA) assays. The extracted nucleic acid for each sample is transferred to the Panther Fusion module where PCR amplification and detection occurs.
6
SUBSTANTIAL EQUIVALENCE INFORMATION F.
Predicate device
Cepheid Xpert® GBS LB (K121539).
Comparison with Predicate
A comparison of the Panther Fusion GBS assay to the predicate is summarized in Table 3 (similarities) and Table 4 (differences).
| | Proposed Device:
Panther Fusion GBS assay | Predicate Device:
Cepheid Xpert® GBS LB assay
(K121539) |
|--------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Classification | Class I | Same |
| Technology Principle
of Operation | Fully automated Real Time nucleic acid
amplification, detection and result
interpretation | Same |
| Analyte | Genomic DNA | Same |
| Organism Detected | Group B Streptococcus | Same |
| Patient Population | Antepartum women | Same |
| Specimen Types | From 18-24 hour enriched-media cultures
of vaginal/rectal swab | Same |
| Intended Use | The Panther Fusion GBS assay is an
automated qualitative in vitro diagnostic
test utilizing real-time PCR for detection
of Group B Streptococcus DNA from
either Lim or Carrot enrichment broth
cultures of vaginal/rectal swabs from
antepartum women following 18-24
hours incubation.
This test is performed on the Hologic
Panther Fusion system and is intended to
aid in determining the GBS colonization
status of antepartum women. This assay
does not diagnose or monitor treatment
for GBS infections. The Panther Fusion
GBS assay does not provide
susceptibility results.
Culture isolates are needed for
performing susceptibility testing as
recommended for penicillin-allergic
women. | The Cepheid Xpert GBS LB Assay,
performed on the GeneXpert®
Instrument Systems, is a qualitative in
vitro diagnostic test designed to detect
Group B Streptococcus (GBS) DNA
from enriched vaginal/rectal swab
specimens, using fully automated real-
time polymerase chain reaction (PCR)
with fluorogenic detection of the
amplified DNA. Xpert GBS LB Assay
testing is indicated as an aid in
determining GBS colonization status in
antepartum women.
The Xpert GBS LB Assay is used for
antepartum testing on enriched Lim broth
cultures of vaginal/rectal swabs after 18-
24 hours of incubation.
The Xpert GBS LB assay does not
provide susceptibility results. Culture
isolates are needed for performing
susceptibility testing as recommended
for penicillin allergic women. |
| Users | Professional use | Same |
| | Proposed Device:
Panther Fusion GBS assay | Predicate Device:
Cepheid Xpert® GBS LB assay
(K121539) |
| Platform | Panther Fusion System | GeneXpert® Dx System (Cepheid)
GeneXpert® Infinity-48 System (Cepheid)
GeneXpert ® Infinity-80 System (Cepheid) |
| Assay Format | Extraction: Hologic Non- Specific
Target Capture
Amplification: Real-time PCR
Detection: Fluorogenic target-specific
hybridization | Extraction: Solid Phase Capture
Amplification: Real-time PCR
Detection: Fluorogenic target-specific
hybridization |
| DNA Target Sequence | SIP and cfb genes | 3'untranslated region of the cfb gene |
| Specimen Enrichment | Lim Broth and Carrot Broth | Lim Broth |
| Time to Obtain
Results | ≤ 2.5 hours total after sample loading
on the Panther Fusion system | ≤ 55 minutes total after sample addition
to the cartridge |
Table 3 : Similarities between Panther Fusion GBS Assay and Predicate Device
7
Table 4 : Differences between Panther Fusion GBS Assay and Predicate Device
G. PERFORMANCE CHARACTERISTICS DATA
The following performance data were provided to support the substantial equivalence determination.
Brief Description of Analytical (Non-Clinical) Studies
The following analytical studies (non-clinical) were conducted to support the clearance of the Panther Fusion GBS Assay on the Panther Fusion System.
Analytical Sensitivity and Limit of Detection (LoD) of GBS in Vaginal/Rectal Swab Specimens
The LoD of the Panther Fusion GBS assay was determined by testing serial dilutions of 11 GBS serotypes and one non-hemolytic (NH) isolate in Lim Broth clinical negative matrix. Thirty replicates were tested with each of the three reagent lots for a combined total of 90 replicates per dilution. Probit analysis was performed for each reagent lot with the reported 95% LoD based upon the worst estimate, as shown in Table 5. Serotype specific LoD predictions were verified by testing an additional 20 replicates with one reagent lot.
8
| GBS Serotype | 95% LoD in CFU/mL (95% CI) |
|---|---|
| Ia | 137.4 (103.7 – 209.7) |
| Ib | 140.5 (100.6 – 234.7) |
| Ic | 136.3 (99.2 – 220.5) |
| II | 179.0 (135.1 – 276.2) |
| III | 168.0 (125.2 – 261.5) |
| IV | 84.0 (63.0 – 130.4) |
| V | 122.3 (92.2 – 186.8) |
| VI | 282.0 (201.9 – 475.8) |
| VII | 250.8 (180.2 – 424.8) |
| VIII | 231.3 (167.3 – 380.9) |
| IX | 301.0 (202.0 – 567.7) |
| NH | 300.2 (212.0 – 523.0) |
Table 5 : GBS Limit of Detection (LoD)
CFU= colony forming units, CI= confidence interval, NH= non-hemolytic
Interferences
Amniotic fluid, blood, urine, stool and other potentially interfering endogenous and exogenous substances that may be present in vaginal/rectal specimens were evaluated in the Panther Fusion GBS assay. Concentrations exceeding clinically relevant amounts of the potentially interfering substances were added to Lim Broth clinical negative matrix and tested un-spiked or spiked with GBS analyte at a 3X LoD concentration. The substances consisted of topical medications, lubricants, deodorants, laxatives and contraceptives as shown in Table 6.
All of the substances tested were found to have no impact on the performance of the Panther Fusion GBS assay, at the concentrations tested.
Table 6 : Potentially Interfering Substances
| Substance Name | Ingredient(s) | Concentration |
|---|---|---|
| Human Amniotic Fluid | N/A | 4% v/v |
| Human Whole Blood EDTA | N/A | 4% v/v |
| Human Whole Blood Na Citrate | N/A | 4% v/v |
| Human Serum | N/A | 4% v/v |
| Human Urine Sample | N/A | 4% v/v |
| Human Fecal Sample | N/A | 4% v/v |
| Topical Hemorrhoid Ointment | ||
| (Preparation H Cream) | Mineral Oil, Petrolatum, Phenylephrine | |
| HCl | 3.4% w/v | |
| Anti-Diarrheal Medication | ||
| (Pepto Bismol) | Bismuth subsalicylate | 4% v/v |
| Personal Lubricant | ||
| (K-Y Jelly Personal Lubricant) | Glycerine, Methylparaben, | |
| Propylparaben | 2.2% w/v | |
| Substance Name | Ingredient(s) | Concentration |
| Lubricating gel (Aquagel) | N/A | 2.1% w/v |
| Vaginal Anti-itch Cream (OTC) (Vagisil) | Benzocaine, Resorcinol | 3.9% w/v |
| Vaginal Anti-itch Cream (OTC) | ||
| (Gyno-Daktarin) | Miconazole nitrate | 3.8% w/v |
| Vaginal Antifungal Cream (OTC) | ||
| (Monistat) | Miconazole nitrate | 3.1% w/v |
| Vaginal Antifungal Gel | Candida albicans 27X HPUS, Candida | |
| parapsilosis 27X HPUS, Pulsatilla 27X | ||
| HPUS | 3.0% w/v | |
| Anti-Diarrheal Caplet (Kaopectate) | Bismuth subsalicylate | 1.1% w/v |
| Deodorant Powder (Vagisil) | Zea Mays Starch, Magnesium Stearate, | |
| Sodium Bicarbonate, Aloe Barbadensis | ||
| Leaf extract, Tocopheryl Acetate, | ||
| Tricalcium Phosphate, Mineral Oil, |
| 1.1% w/v |
| Deodorant Suppositories
(Norforms Suppositories) | PEG-20, PEG-32, PEG-20 Stearate,
Benzethonium Chloride,
Methylparaben, Lactic Acid,
Fragrance, Neutresse (Odor synthesis) | 2.1% w/v |
| Deodorant Spray
(FDS) | Isopropyl Myristate, Zea Mays Starch,
Magnesium Stearate, Fragrance, Zinc
Ricinoleate, Laureth-3, Benzyl alcohol,
Mineral Oil (Paraffinum Liquidum,
Huile Minérale), Tetrahydroxypropyl
Ethylenediamine, Sodium Bicarbonate,
Citronellol, Linalool, Propylene
Glycol, Butylphenyl Methylpropional,
Lanolin Alcohol, Anise Alcohol, Oleyl
Alcohol, Benzyl Benzoate,
Chamomilla Recutita, Flower extract,
Tocopheryl Acetate, Aloe Barbadensis
Leaf extract | 1.5% w/v |
| Body Powder (Gold Bond Powder) | Menthol | 0.4% w/v |
| Body Oil | Isopropyl Myristate, sesame seed oil,
PEG-40, Sorbitan Peroleate,
Propylparaben, BHT, Fragrance | 4% v/v |
| Spermicidal Foam | Nonoxynol-9 | 2.1% w/v |
| Oral Laxative
(Metamucil Fiber Supplement) | Psyllium husk | 2.2% w/v |
| Grains de Vals (SennosideB) | Sennocide B | 0.4% w/v |
| Oral Laxative
(Phillips Milk of Magnesia) | Magnesium hydroxide | 7.3% w/v |
| Stool Softener | Bisacodyl | 0.9% w/v |
| Astroglide Liquid personal lubricant | Glycerin, Propylene Glycol,
Polyquaternium 15, Methylparaben,
Propylparaben | 2.7% w/v |
| Enema Solution
(Fleet enema) | Dinatriumhydrogenphosphat-
Dodecahydrat /
Natriumhydrogenphosphat-Dihydrat | 4% v/v |
9
10
Analytical Specificity and Microbial Interference
The analytical specificity of the Panther Fusion GBS assay was evaluated by testing a panel of 110 microorganisms (as listed in Table 7), consisting viral, bacterial, fungal, parasite, protozoan and yeast strains representing pathogens or flora commonly present in the vaginal/rectal tract or related to the GBS family. Bacteria and yeast were tested at 1 x106 CFU/mL, except where noted. Viruses, fungi, parasites and protozoan were tested at 1x 105 PFU/mL, except where noted. Organisms were tested both with and without GBS spiked at a concentration 3X the established LoD. All of the microorganisms tested were found to have no impact on the performance or analytical specificity of the Panther Fusion GBS assay.
| Pathogen | Concentration*
(CFU/mL or
PFU/mL) | Pathogen | Concentration*
(CFU/mL or
PFU/mL) |
|--------------------------------------------------|-----------------------------------------|--------------------------------------------|-----------------------------------------|
| Bacillus cereus | 1x106 | Streptococcus anginosus | 1x106 |
| Yersinia enterocolitica subsp.
enterocolitica | 1x106 | Prevotella oralis | 1x106 |
| Anaerococcus prevotii | 1x106 | Streptococcus canis | 1x106 |
| Propionibacterium acnes | 1x106 | Lactobacillus delbrueckii subsp.
lactis | 1x106 |
| Clostridium difficile | 1x106 | Corynebacterium sp
(genitalium) | 1x106 |
| Fusobacterium nucleatum | 1x106 | Neisseria gonorrhoeae | 1x106 |
| Bifidobacterium adolescentis
Reuter | 1x106 | Streptococcus pneumoniae (oral
group) | 1x106 |
| Candida albicans (NIH 3147) | 1x106 | Streptococcus mutans (oral
group) | 1x106 |
| Candida glabrata (CBS 138) | 1x106 | Corynebacterium urealyticum | 1x106 |
| Candida tropicalis | 1x106 | Lactobacillus reuteri | 1x106 |
| Cryptococcus neoformans | 1x105* | Lactobacillus sp. | 1x106 |
| Klebsiella pneumoniae | 1x106 | Lactobacillus casei | 1x106 |
| Proteus mirabilis | 1x106 | Lactobacillus acidophilus | 1x106 |
| Alcaligenes faecalis | 1x106 | Streptococcus gordonii (oral
group) | 1x106 |
| Enterobacter aerogenes | 1x106 | Bulkholderia cepacia | 1x106 |
| Stenotrophomonas maltophilia | 1x106 | Aeromonas hydrophila | 1x106 |
| Campylobacter jejuni | 1x106 | Moraxella atlantae | 1x106 |
| Providencia stuartii | 1x106 | Prevotella bivia | 1x106 |
| Micrococcus luteus | 1x106 | Pasteurella aerogenes | 1x106 |
| Staphylococcus haemolyticus | 1x106 | Rhodococcus equi | 1x106 |
| Enterococcus faecalis | 1x106 | Listeria monocytogenes | 1x106 |
| Pseudomonas fluorescens | 1x106 | Lactobacillus gasseri | 1x106 |
| Staphylococcus saprophyticus | 1x106 | Peptoniphilus asaccharolyticus | 1x106 |
| Proteus vulgaris | 1x106 | Atopobium vaginae | 1x106 |
| Toxoplasma gondii | 1x105* | Bifidobacterium brevis | 1x106 |
| Enterococcus faecium | 1x106 | Abiotropha defectiva | 1x106 |
| Escherichia coli | 1x106 | Anaerococcus tetradius | 1x106 |
11
| Pathogen | Concentration*
(CFU/mL or
PFU/mL) | Pathogen | Concentration*
(CFU/mL or
PFU/mL) |
|---------------------------------------------|-----------------------------------------|--------------------------------------------------------------|-----------------------------------------|
| Enterobacter cloacae | 1x106 | Finegoldia magna | 1x106 |
| Morganella morganii | 1x106 | Peptostreptococcus anaerobius | 1x106 |
| Shigella flexneri | 1x106 | Anaerococcus lactolyticus | 1x106 |
| Streptococcus pyogenes
(group A) | 1x106 | Human herpesvirus 4 (EBV) | 1x105* |
| Streptococcus ratti | 1x106 | Bacteroides fragilis | 1x106 |
| Staphylococcus lugdunensis | 1x106 | Bordetella pertussis | 1x106 |
| Acinetobacter baumannii | 1x106 | Chlamydia trachomatis | 1x106 |
| Staphylococcus aureus | 1x106 | Human herpesvirus 5 (CMV) | 1x105* |
| Staphylococcus epidermidis | 1x106 | Hafnia alvei | 1x106 |
| Shigella sonnei | 1x106 | Trichomonas vaginalis | 1x105* |
| Citrobacter freundii | 1x106 | Human immuno-deficiency
virus-1 (HIV-1) | 1x105* |
| Enterococcus gallinarum | 1x106 | Moraxella catarrhalis | 1x106 |
| Acinetobacter lwoffii | 1x106 | Mycoplasma genitalium | 1x106 |
| Pseudomonas aeruginosa | 1x106 | Prevotella melaninogenica | 1x106 |
| Streptococcus criceti | 1x106 | Rubella Virus | 1x105* |
| Haemophilus influenzae | 1x106 | Serratia marcescens | 1x106 |
| Klebsiella oxytoca | 1x106 | Streptococcus intermedius | 1x106 |
| Streptococcus bovis (group D) | 1x106 | Human Papilloma Virus Type
16 (HPV16) | 1x105* |
| Streptococcus parasanguinis | 1x106 | Hepatitis B Virus | 1x105* |
| Streptococcus equi subsp. equi
(group D) | 1x106 | Hepatitis C Virus | 1x105* |
| Enterococcus durans | 1x106 | Herpes Simplex Virus-1 (HSV-
-
| 1x105* |
| Lactobacillus plantarum | 1x106 | Herpes Simplex Virus-2 (HSV-
2) | 1x105* |
| Streptococcus dysgalactiae | 1x106 | Human herpesvirus 3 (VZV) | 1x105* |
| Streptococcus constellatus | 1x106 | Arcanobacterium pyogenes | 1x106 |
| Streptococcus oralis (oral
group) | 1x106 | Mobiluncus curtisii subsp.
curtisii | 1x106 |
| Bacillus coagulans | 1x106 | Gardnerella vaginalis | 1x106 |
| Streptococcus pseudoporcinus | 1x106 | Salmonella enterica subsp.
enterica ser. dublin (group D) | 1x106 |
| Streptococcus mitis
(oral group) | 1x106 | Streptococcus acidominus | 1x106 |
*Microorganisms evaluated as extracted DNA were tested in Copies/mL
12
Carryover/Cross-Contamination
The carryover/cross-contamination study was performed with Lim Broth clinical negative samples alternately placed between high positive samples and tested. High positive samples were prepared by spiking GBS at > 1x 106 CFU/mL (> 5,000X LoD). A total of ten separate runs with negative samples and positive samples placed in a checkerboard pattern were tested in addition to four runs of negative specimens over two different instruments a combined total of 300 positive and 420 negative samples. There were no false positive results observed for a carry-over rate of 0.0%.
Assay Precision
Panther Fusion GBS Assay precision was evaluated with a 7-member panel. The panel was tested by three operators on five separate runs per day, using three reagent lots on one Panther Fusion systems over 12 non-consecutive days. The panel members are described in Table 8 along with a summary of the agreement with expected results for each target.
| Panel Member | % Positive
(Pos n/valid n) | % Agreement
(95% CI) |
|------------------------------------|-------------------------------|-------------------------|
| GBS III Low Positive (1-2X LoD) | 100% (180/180) | 100% (97.9-100) |
| GBS III Moderate Positive (3X LoD) | 100% (180/180) | 100% (97.9-100) |
| GBS V Low Positive (1-2X LoD) | 100% (180/180) | 100% (97.9-100) |
| GBS V Moderate Positive (3X LoD) | 100% (180/180) | 100% (97.9-100) |
| GBS NH Low Positive (1-2X LoD) | 100% (180/180) | 100% (97.9-100) |
| GBS NH Moderate Positive (3X LoD) | 100% (180/180) | 100% (97.9-100) |
| Negative | 0% (0/180) | 100% (97.9-100) |
Table 8 : Percent Agreement to the Expected Result
CI= confidence interval, LoD= limit of detection, NH= non-hemolytic
13
Table 9 presents the mean and variability analysis between reagent lots, between operators, between days, between runs and within runs, and overall (total) for Ct.
| Panel | Mean
Ct | Between
Reagents Lots | | Between
Operators | | Between Days | | Between Runs | | Within Runs | | Total | |
|---------------------|------------|--------------------------|-------|----------------------|-------|--------------|-------|--------------|-------|-------------|-------|-------|-------|
| Member | | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) |
| GBS III
1-2X LoD | 36.3 | 0.06 | 0.16% | 0.16 | 0.45% | 0.11 | 0.31% | 0.33 | 0.91% | 0.43 | 1.18% | 0.53 | 1.46% |
| GBS III
3X LoD | 35.4 | 0.17 | 0.48% | 0.12 | 0.35% | 0.13 | 0.36% | 0.34 | 0.95% | 0.32 | 0.90% | 0.43 | 1.22% |
| GBS V
1-2X LoD | 36.4 | 0.13 | 0.37% | 0.13 | 0.35% | 0.17 | 0.46% | 0.29 | 0.78% | 0.50 | 1.36% | 0.55 | 1.51% |
| GBS V
3X LoD | 35.4 | 0.13 | 0.38% | 0.11 | 0.31% | 0.12 | 0.34% | 0.28 | 0.79% | 0.41 | 1.14% | 0.46 | 1.31% |
| GBS NH
1-2X LoD | 35.7 | 0.23 | 0.65% | 0.12 | 0.35% | 0.14 | 0.39% | 0.31 | 0.86% | 0.38 | 1.06% | 0.46 | 1.28% |
| GBS NH
3X LoD | 34.8 | 0.19 | 0.55% | 0.04 | 0.12% | 0.10 | 0.29% | 0.28 | 0.81% | 0.29 | 0.84% | 0.40 | 1.14% |
| Negative | 31.5 | 0.24 | 0.77% | 0.08 | 0.24% | 0.14 | 0.43% | 0.32 | 1.03% | 0.27 | 0.86% | 0.41 | 1.32% |
Table 9 : Signal Variability
Ct= threshold cycle, CV= coefficient of variation, LoD= limit of detection, SD= standard deviation
Reproducibility
Panther Fusion GBS Assay reproducibility was evaluated at three US sites using a seven panel members. Testing was performed using one lot of assay reagents and six operators (two at each site). At each site, testing was performed two times per day during five non-consecutive days. Each run had three replicates of each panel member. A negative panel member was created using Lim Broth matrix. Positive panel members were created by spiking GBS at 1-2X LoD (low-positive) or 3X LoD (moderate-positive) concentrations of the target analyte into Lim Broth matrix. The agreement with expected results was 100% in the negative and moderate positive panel members and ≥98.9% in low-positive panel members for the three GBS strains evaluated (serotypes III, V and non-hemolytic isolate- NH), as shown in Table 10.
| Table 10 : Agreement of Panther Fusion GBS Assay Results with Expected Results | |||
|---|---|---|---|
| | Panels | | Expected
Result | Agreement with Expected
Result | |
|-----------------------------|-------------|---------------------------|--------------------|-----------------------------------|--------------------|
| Description | Composition | Concentration
(CFU/mL) | GBS | N | % (95% CI) |
| GBS III Low Positive | 1-2X LoD | 262 | + | 90/90 | 100% (95.9-100%) |
| GBS III Moderate Positive | 3X LoD | 504 | + | 90/90 | 100% (95.9-100%) |
| GBS V Low Positive | 1-2X LoD | 188 | + | 89/90 | 98.9% (94.0-99.8%) |
| GBS V Moderate Positive | 3X LoD | 367 | + | 90/90 | 100% (95.9-100%) |
| GBS NH Low Positive | 1-2X LoD | 523 | + | 90/90 | 100% (95.9-100%) |
| GBS NH Moderate
Positive | 3X LoD | 900 | + | 90/90 | 100% (95.9-100%) |
| Nec. | Negative | N/A | - | 90/90 | 100% (95.9-100%) |
14
The total GBS signal variability measured as %CV ranged from 1.51% to 2.25% in low and moderate positive panel members. Across the sources of variation, excluding within run, %CV values were ≤ 1.33%, as shown in Table 11.
| Panel
Description | Mean | | Between
Sites | | Between
Operators | | Between
Days | | Between
Runs | | Within
Runs | | Total | |
|----------------------|------|------|------------------|-----------|----------------------|-----------|-----------------|-----------|-----------------|-----------|----------------|-----------|-------|-----------|
| | N | Ct | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) | SD | CV
(%) |
| GBS III Low Pos | 90 | 37.1 | 0.49 | 1.33% | 0.47 | 1.26% | 0.18 | 0.48% | 0.14 | 0.37% | 0.55 | 1.47% | 0.77 | 2.09% |
| GBS III Mod Pos | 90 | 36.2 | 0.45 | 1.24% | 0.41 | 1.12% | 0.15 | 0.41% | 0.05 | 0.14% | 0.42 | 1.15% | 0.66 | 1.81% |
| GBS V Low Pos | 90 | 37.3 | 0.44 | 1.17% | 0.41 | 1.09% | 0.09 | 0.23% | 0.11 | 0.31% | 0.68 | 1.82% | 0.84 | 2.25% |
| GBS V Mod Pos | 90 | 36.3 | 0.31 | 0.84% | 0.31 | 0.85% | 0.26 | 0.72% | 0.08 | 0.23% | 0.48 | 1.33% | 0.61 | 1.69% |
| GBS NH Low Pos | 90 | 36.2 | 0.27 | 0.75% | 0.27 | 0.74% | 0.14 | 0.40% | 0.10 | 0.28% | 0.50 | 1.37% | 0.58 | 1.61% |
| GBS NH Mod Pos | 90 | 35.4 | 0.20 | 0.57% | 0.20 | 0.55% | 0.16 | 0.45% | 0.03 | 0.08% | 0.46 | 1.31% | 0.53 | 1.51% |
| Negative (IC) | 90 | 31.9 | 0.32 | 1.00% | 0.30 | 0.95% | 0.06 | 0.20% | 0.16 | 0.50% | 0.26 | 0.83% | 0.56 | 1.77% |
Table 11 : Signal Variability of the Panther Fusion GBS Assay by Panel Member
The signal variability as measured as % CV was ≤1.35% between sites/operators, between days/runs, or overall for the Panther Fusion GBS assay positive control and negative control, as shown in Table 12.
Table 12 : Signal Variability of the Panther Fusion GBS Assay Controls
| Control | N | Mean Ct | Between
Sites/Operators | | Between
Days/ Runs | | Total | |
|----------|----|---------|----------------------------|--------|-----------------------|--------|-------|--------|
| | | | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Positive | 15 | 31.9 | 0.17 | 0.53% | 0.10 | 0.32% | 0.22 | 0.70% |
| Negative | 15 | 28.3 | 0.20 | 0.72% | 0.27 | 0.94% | 0.38 | 1.35% |
Ct= threshold cycle, CV= coefficient of variation, SD= standard deviation
15
H. COMPARISON STUDIES
Method Comparison
Not applicable.
Matrix Comparison
GBS strains (serotypes III and V and non-hemolytic) were serially diluted in each negative clinical matrix (Lim Broth and Carrot Broth) to their respective concentrations at ½2x, 2x, or 5x LoD. 30 replicates per strain per concentration and per broth were processed along with at least 5 replicates of negative clinical matrix for each type of broth. All positives and negative specimen were correctly identified by the Panther Fusion GBS Assay.
According to the acceptance criteria, the equivalence between Lim Broth and Carrot Broth was demonstrated at 2x and 5x LoD concentrations for the 3 tested GBS strains. Equivalence below the LoD level is not demonstrated for these enrichment broths. This concentration has been chosen as a most challenging scenario and is not clinically relevant considering that the Panther Fusion GBS Assay is intended to aid for GBS diagnosis after 24 hours enrichment. The concentration of GBS target in either broth is not expected to be below the LoD after enrichment.
I. CLINICAL STUDY
Prospective Clinical Study
This prospective study was performed at three sites using leftover enriched culture samples in Lim broth and Carrot broth from vaginal/rectal specimens collected from antepartum women during routine GBS screening. The leftover culture samples were selected according to the inclusion and exclusion criteria, patient information was de-identified and each specimen was given a unique ID number. All samples were tested with both the Panther Fusion GBS Assay and the reference culture method following CDC recommendations. Results obtained using the Panther Fusion GBS Assay were compared to those obtained with the reference method to calculate the clinical sensitivity and specificity of the Panther Fusion GBS Assay.
This study was performed from January 2018 to March 2018 at clinical evaluation at three geographically distinct sites in the United States in compliance with Good Clinical Practices (GCP). Among the three sites, two sites enrolled specimen enriched in Lim Broth and one site enrolled leftover specimen enriched in Carrot Broth. A total of 947 clinical leftover samples, meeting the inclusion criteria, were enrolled in the study with an average GBS prevalence of 24% (229 positive) in culture.
Results showed a clinical sensitivity of 100% in both matrices and a clinical specificity of 96.9% and 95.5% in Lim Broth and Carrot Broth respectively. Overall performance of the Panther Fusion Assay demonstrated a clinical sensitivity of 100% and a clinical specificity of 96.5%. Study results are summarized in Table 13, Table 14 and Table 15.
16
Table 13 : Lim Broth Specimens
| Reference Method | ||||
|---|---|---|---|---|
| Lim Broth | Positive | Negative | Total | |
| Panther Fusion GBS Assay | Positive | 120 | 16* | 136 |
| Negative | 0 | 507 | 507 | |
| Total | 120 | 523 | 643 | |
| Sensitivity | 120/120 = 100% (95% CI: 96.9% - 100%) | |||
| Specificity | 507/523 = 96.9% (95% CI: 95.1% - 98.1%) | |||
| Positive Predictive Value | 120/136 = 88.2% (95% CI: 81.7% - 92.6%) | |||
| Negative Predictive Value | 507/507 = 100% (95% CI: 99.3% - 100%) |
- Of 16 False Positives, 14 (87.5%) were positive on the Becton Dickinson BD MAX GBS Assay
Table 14 : Carrot Broth Specimens
| Carrot Broth: Carolinas | Reference Method | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| Panther Fusion GBS | |||||
| Assay | Positive | 83 | 10* | 93 | |
| Negative | 0 | 211 | 211 | ||
| Total | 83 | 221 | 304 | ||
| Sensitivity | 83/83 = 100% (95% CI: 95.6% - 100%) | ||||
| Specificity | 211/221 = 95.5% (95% CI: 91.9% - 97.5%) | ||||
| Positive Predictive Value | 83/93 = 89.3% (95% CI: 81.3% - 94.1%) | ||||
| Negative Predictive Value | 211/211 = 100% (95% CI: 98.2% - 100%) |
Table 15 : Combined Lim Broth and Carrot Broth Specimens
| Lim & Carrot Broth Combined | Reference Method | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| Panther Fusion GBS Assay | Positive | 203 | 26 | 229 | |
| Negative | 0 | 718 | 718 | ||
| Total | 203 | 744 | 947 | ||
| Sensitivity | 203/203 = 100% (95% CI: 98.1% - 100%) | ||||
| Specificity | 718/744 = 96.5% (95% CI: 94.9% - 97.6%) | ||||
| Positive Predictive Value | 203/229 = 88.7% (95% CI: 83.9% -92.1%) | ||||
| Negative Predictive Value | 718/718 = 100% (95% CI: 99.5% - 100%) |
17
Expected Values/Reference Range
The performance of the Panther Fusion GBS assay was evaluated in a prospective Clinical Study on clinical vaginal specimen from antepartum women conducted at three sites in the U.S. Overall, the prevalence of GBS colonization as determined by the Panther Fusion GBS Assay was 24.2% (229/947) whereas by conventional culture it was 21.4% (203/947) as shown in Table 16.
| Culture Medium | Clinical Site | N | Panther Fusion GBS Assay | Conventional Culture | ||
|---|---|---|---|---|---|---|
| N Positive | % Prevalence | N Positive | % Prevalence | |||
| Lim Broth | 1 | 300 | 65 | 21.7% | 60 | 20.0% |
| Lim Broth | 2 | 343 | 71 | 20.7% | 60 | 17.5% |
| Overall | 643 | 136 | 21.2% | 120 | 18.7% | |
| Carrot Broth | 3 | 304 | 93 | 30.6% | 83 | 27.3% |
| Combined | Overall | 947 | 229 | 24.2% | 203 | 21.4% |
Table 16 : Panther Fusion GBS Assay and Culture Prevalence
J. CONCLUSIONS
The analytical and the clinical study results demonstrate that the Panther Fusion GBS assay on the Panther Fusion system performs comparably to the predicate device that is currently marketed for the same intended use. Hardware and software verification and validation demonstrate that the Panther Fusion GBS Assay on the Panther Fusion system will perform as intended. The submitted information in this premarket notification support a substantial equivalence decision.