(154 days)
The Great Basin Portrait™ GBS Assay, performed on the PA500 Portrait™ Analyzer System, is a qualitative in vitro diagnostic test (IVD) for the detection of Group B Streptococcus (GBS) DNA from vaginal/rectal swabs from antepartum women, following enrichment in LIM Broth for 18 - 29 hours. The assay utilizes automated sample preparation and polymerase chain reaction (PCR) to amplify a cfb gene sequence specific to the Streptococcus agalactiae (GBS) genome which is detected by hybridization probes immobilized on a silica chip surface.
Results from the Portrait™ GBS Assay can be used as an aid in determining colonization status in antepartum women. The Portrait™ GBS Assay does not provide susceptibility results. Cultured isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.
The Portrait™ GBS Assay is intended for use in clinical laboratory, and reference laboratory settings. The Portrait™ GBS Assay is not intended for point of care use.
The Great Basin PA500 Portrait Analyzer System is a fully automated system that includes the Portrait Analyzer, single-use Portrait GBS Assay Test Cartridges, and the Portrait data analysis software. The PA500 Portrait Analyzer System is designed to perform automated sample preparation, PCR, and optical chip-based detection with integrated data analysis in approximately 90 minutes. The Great Basin Portrait™ GBS Assay utilizes automated hot-start PCR technology to amplify target nucleic acid sequences that are detected using species-specific S. agalactiae DNA hybridization probes immobilized on a modified silicon chip surface.
Here's a breakdown of the acceptance criteria and the study details for the Portrait™ GBS Assay based on the provided document:
Acceptance Criteria and Reported Device Performance
Device Name: Portrait™ GBS Assay
| Acceptance Criteria | Reported Device Performance (%) (95% CI) |
|---|---|
| Sensitivity | 97.9% (92.7% - 99.4%) |
| Specificity | 96.0% (93.5% - 97.6%) |
| Positive Predictive Value (PPV) | 86.9% (79.2% - 92.0%) |
| Negative Predictive Value (NPV) | 99.4% (97.9% - 99.8%) |
Note: The document does not explicitly state pre-defined acceptance criteria values for sensitivity, specificity, PPV, or NPV in the "510(k) Summary" section. Instead, these are presented as the "overall assay performance" observed during the clinical study.
Study Details
2. Sample size used for the test set and the data provenance:
- Sample Size: 448 compliant clinical samples.
- Data Provenance: From three clinical sites in the United States. The study was prospective, as samples were "run over the course of four months to evaluate the performance."
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document states that the Portrait™ GBS Assay performance was compared "to the reference GBS clinical microbiology protocol." This implies standard laboratory culture methods were used as the gold standard. There is no mention of human experts establishing the ground truth for the test set in this context.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- None explicitly mentioned as human adjudication; the reference standard was the "GBS clinical microbiology protocol" (culture).
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, an MRMC comparative effectiveness study involving human readers and AI assistance was not performed or described. This device is an in vitro diagnostic (IVD) assay for molecular detection, not an AI-powered image analysis or diagnostic support tool for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the clinical performance study evaluated the Portrait™ GBS Assay as a standalone diagnostic tool, comparing its results directly against the reference culture method. The "algorithm" here refers to the automated PCR technology, sample preparation, and optical chip-based detection with integrated data analysis within the PA500 Portrait™ Analyzer System.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth used was GBS culture testing (the "reference GBS clinical microbiology protocol"). This is a recognized laboratory gold standard for detecting GBS colonization.
8. The sample size for the training set:
- The document does not specify a separate training set sample size. The analytical studies describe various experiments (LoD, inclusivity, exclusivity, interference, carry-over, reproducibility) that might contribute to the development and refinement of the assay and its software, but these are not explicitly labeled as a "training set" in the context of machine learning, which is not the primary mechanism of this device. For an IVD like this, validation often involves demonstrating performance across various analytical and clinical scenarios rather than "training" an AI model.
9. How the ground truth for the training set was established:
- As no explicit "training set" for an AI model is described, the mention of ground truth establishment for such a set is not applicable. For the analytical studies, the ground truth for spiked samples was known by design (e.g., specific GBS strains at known concentrations, or known interfering substances).
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 31, 2016
GREAT BASIN CORPORATION CHUCK OWEN DIRECTOR, REGULATORY AFFAIRS & QUALITY ASSURANCE 2441 SOUTH 3850 WEST SALT LAKE CITY, UT 84120
Re: K143312
Trade/Device Name: Portrait™ GBS Assay Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcus spp. serological reagents Regulatory Class: I Product Code: NJR, NSU Dated: March 20, 2015 Received: March 23, 2015
Dear Mr. Owen:
This letter corrects our substantially equivalent letter of April 21, 2015.
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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) K143312
Device Name Portrait™ GBS Assay
Indications for Use (Describe)
The Great Basin Portrait™ GBS Assay, performed on the PA500 Portrait™ Analyzer System, is a qualitative in vitro diagnostic test (IVD) for the detection of Group B Streptococcus (GBS) DNA from vaginal/rectal swabs from antepartum women, following enrichment in LIM Broth for 18 - 29 hours. The assay utilizes automated sample preparation and polymerase chain reaction (PCR) to amplify a cfb gene sequence specific to the Streptococcus agalactiae (GBS) genome which is detected by hybridization probes immobilized on a silica chip surface.
Results from the Portrait™ GBS Assay can be used as an aid in determining colonization status in antepartum women. The Portrait™ GBS Assay does not provide susceptibility results. Cultured isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.
The Portrait™ GBS Assay is intended for use in clinical laboratory, and reference laboratory settings. The Portrait™ GBS Assay is not intended for point of care use.
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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Image /page/3/Picture/1 description: The image shows the business card for Great Basin Corporation. The card includes the company's logo, which features a series of blue circles arranged in a curved line above the company name. The address is listed as 2441 S 3850 W, SLC UT 84120, and the phone and fax numbers are 801.990.1055 and 801.990.1051, respectively. The website, gbscience.com, is also included on the card.
April 17, 2015
510(k) Summary: Portrait GBS Assay
A. Submitted by:
Great Basin Corporation 2441 South 3850 West Salt Lake City, Utah 84120 Phone: 801-990-1055 Fax: 801-990-1051
Contact Information
Chuck Owen, Director of Requlatory Affairs Phone: 385-215-3313 Fax: 801-990-1051 Email: cowen@gbscience.com
B. Name of Device
Proprietary Name: Portrait™ GBS Assay
Common or Usual Names: Group B Streptococcus Assay Group B Strep Assay ઉંકર
- C. Predicate Device: K112125, illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
D. Requlatory Information:
- a. Regulation Section: 21 CFR 866.3740 Streptococcus spp. Serological reagents
- b. Classification: Class I ( non-exempt)
- c. Classification panel: Microbiology Devices, OIVD (83) Microbiology
- d. Product Code: NJR Nucleic Acid Amplification Assay, Group B Streptococcus, Direct Specimen
NSU-Instrumentation for Clinical Multiplex Test Systems
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E. Intended use(s)/Indications for Use:
The Great Basin Portrait™ GBS Assay, performed on the PA500 Portrait™ Analyzer System, is a qualitative in vitro diagnostic test (IVD) for the detection of Group B Streptococcus (GBS) DNA from vaginal/rectal swabs from antepartum women following enrichment in LIM Broth for 18 -29 hours. The assay utilizes automated sample preparation and polymerase chain reaction (PCR) to amplify a cfb gene sequence specific to the Streptococcus agalactiae (GBS) genome which is detected by hybridization probes immobilized on a silica chip surface.
Results from the Portrait™ GBS Assay can be used as an aid in determining colonization status in antepartum women. The Portrait™ GBS Assay does not provide susceptibility results. Cultured isolates are needed for performing susceptibility testing as recommended for penicillinallergic women.
The Portrait™ GBS Assay is intended for use in clinical laboratory, hospital laboratory, and reference laboratory settings. The Portrait™ GBS Assay is not intended for point of care use.
F. Device Description:
Test Principle:
The Great Basin Portrait™ GBS Assay on the PA500 Portrait™ Analyzer System utilizes automated hot-start PCR technology to amplify target nucleic acid sequences that are detected usinq species-specific S. agalactiae DNA hybridization probes immobilized on a modified silicon chip surface.
Genomic DNA is extracted from microbial cells and diluted to reduce potential inhibitors of the PCR reaction. In a duplex PCR, biotin-labeled primers enable amplification of specific nucleic acid sequences within a unique and conserved region of the cfb gene (CAMP factor) for identification of S. agalactiae species and to an additional sample processing control (SPC) bacterial construct. Following PCR, biotin-labeled, amplified target DNA sequences are hybridized to sequence specific capture probes immobilized on the silicon chip surface, then incubated with anti-biotin antibody conjugated to the horseradish peroxidase enzyme (HRP). The unbound conjugate is removed by washing and tetramethylbenzidine (TMB) is added to produce a colored precipitate at the location of the probe/target sequence complex. The resulting signal is detected by the automated Portrait™ Optical Reader within the PA500 Portrait™ Analyzer System.
Test Device:
The Great Basin PA500 Portrait Analyzer System is a fully automated system that includes the Portrait Analyzer, single-use Portrait GBS Assay Test Cartridges, and the Portrait data analysis software. The PA500 Portrait Analyzer System is designed to perform automated sample preparation, PCR, and optical chip-based detection with integrated data analysis in approximately 90 minutes. The Great Basin Portrait™ GBS Assay utilizes automated hot-start PCR technology to amplify target nucleic acid sequences that are detected using species-specific S. agalactiae DNA hybridization probes immobilized on a modified silicon chip surface. The PA500 Portrait Analyzer System was recently granted clearance for use with the Portrait™ Toxigenic C. difficile Assay (DEN120013).
G. Substantial Equivalence Information:
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- a. Predicate Device: illumigene Group B Streptococcus (GBS) DNA Amplification Assay
- b. Predicate 510(k) number: K112125
- Comparison with Predicate ﻥ
| Item | Portrait GBS AssayPredicate (K112125) | |
|---|---|---|
| Manufacturer | Great Basin Scientific, Inc. | illumigene |
| Trade Name | PortraitTM GBS Assay | illumigene® Group B Streptococcus (GBS) DNAAmplification Assay |
| 510(k) Number | K143312 | K112125 |
| Similarities | ||
| Classification | Class I | same |
| IntendedUse/Indications forUse | Detection of Group B Streptococcus (GBS) DNAfrom vaginal/rectal swabs from antepartum womenfollowing enrichment in LIM broth (18 - 29 hours) | Detection of Group B Streptococcus (GBS) DNA fromvaginal/rectal swabs from antepartum womenfollowing enrichment in LIM broth or TransVag broth(18-24 hours) |
| Qualitative/Quantitative | Qualitative | same |
| Single-Use TestCartridge | Disposable, single-use, self-contained fluidic testcartridge | same |
| Automated | Yes | same |
| Test Principle | DNA Amplification Assay | same |
| Sample Types | Vaginal/rectal swabs enriched in LIM broth | same |
| OrganismDetection | Group B Streptococcus ( S. agalactiae ) | same |
| Calibration | Not required | same |
| Differences | ||
| Sample TypeEnrichment Culture | LIM broth cultures only | LIM broth and TransVag broth cultures |
| DNA AmplificationTechnology | Polymerase chain reaction (PCR) | Loop-mediated isothermal DNA amplificatioin (LAMP) |
| Target SequenceDetected | Unique sequence region of the S. agalactiae cfbgene | 213 base pair (bp) sequence residing in the 593-805bp region of S. agalactiae genome Segment 3 |
| Instrument | PA500 Portrait Analyzer | illumipro-10 Automated Isothermal Amplification andDetection System |
| Time to Result | 90 minutes | 60 minutes |
| Detection Method | Colorimetric target specific hybridization to probe ona chip surface, optical reader, automated softwarewith built-in result interpretation | Visible light Transmission, automated software withbuilt-in result interpretation |
| Clinical Sensitivity | 97.9% [95% CI: 92.7% - 99.4%] | 97.4% (95% CI: 91.9 - 99.0%) |
| Clinical Specificity | 96.0% [95% CI: 93.5%- 97.6%] | 92.3% (95% CI: 90.0 - 94.1%) |
H. Performance Data - Analytical Studies
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Analytical Sensitivity a.
The Limit of Detection (LoD) of the Portrait GBS Assay for Group B Streptocccus was assessed and confirmed by using strains of two different serotypes: ATCC strain BAA1177(serotype la) and ATCC strain 12403(serotype III). Each strain was spiked into negative LIM broth matrix and then serially diluted. Testing was performed on 20 replicates for each strain to establish the following LoDs in Table 1. For ATCC strain BAA1177, the LoD is reported as 5x103 CFU/mL (2.4 CFU/PCR) and for ATCC strain 12403 the LoD is 8x103 CFU/mL (3.9 CFU/PCR).
| GBS strains | Serotype | Tested SerialDilutions(CFU/mL) | EstimatedCFU in PCR | Group BStreptococcusPOSITIVE |
|---|---|---|---|---|
| ATCC BAA1177 | Ia | 5000 | 2.4 | 20/20 |
| ATCC 12403 | III | 8000 | 3.9 | 20/20 |
Table 1. Performance of the Portrait GBS Assay on 20 replicates of two Group B Streptococcus strains for establishing LoD.
b. Analytical Reactivity (Inclusivity)
The analytical reactivity of the Portrait GBS Assay was tested in triplicate against an additional 14 GBS strains representing an additional 11 serotypes at approximately 2X LoD (1.6x10" CFU/mL) spiked in negative LIM broth matrix. All GBS strains were correctly identified as Positive by the Portrait GBS Assay (Table 2).
| GBS strains | Serotype | Group BStreptococcusPOSITIVE |
|---|---|---|
| CDC 62587 | la | 3/3 |
| ATCC 12401 | Ib | 3/3* |
| ATCC 27591 | Ic | 3/3 |
| ATCC BAA1175 | II | 3/3 |
| ATCC BAA22 | III | 3/3 |
| ATCC 49446 | IV | 3/3 |
| ATCC BAA611 | V | 3/3 |
| CDC 49282 | VI | 3/3 |
| CDC 61303 | VII | 3/3 |
| CDC 43587 | VIII | 3/3 |
| CDC 62706 | IX | 3/3 |
| NCTC 9993 | untyped | 3/3 |
| ATCC 13813 | non-hemolytic | 3/3 |
| NCIMB 701348 | untyped | 3/3 |
Table 2. Analytical Reactivity (Inclusivity) Panel.
- this set of runs also contained one 'Invalid' run
c. Analytical Specificity (Exclusivity)
Great Basin Corporation 2441 S. 3850 W. West Valley City, UT 84120 www.gbscience.com phone: 801-990-1055 fax: 801-990-1051
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Studies were performed to assess the potential cross-reactivity of the Portrait GBS Assay with human DNA and 60 non-target microflora (51 bacterial, 5 yeast, and 4 viral stock strains) spiked into a negative LIM broth matrix (Table 3). The non-target bacterial and yeast strains were spiked into the negative clinical LIM broth matrix at a minimum concentration of 106 CFU/mL. The human genomic DNA was tested at a concentration of 1.2x10° copies/mL. The viral stocks were spiked into the negative LIM broth matrix at a target concentration close to 10° TCID50/mL. A minimum of 3 replicates was performed for each of the human DNA and bacterial, yeast, and viral strains evaluated and none of the tested DNA or strains interfered with the internal controls and all of the calls were 'Group B Streptococcus NEGATIVE,' indicating no cross-reactivity.
| Bacteria | ||
|---|---|---|
| Acinetobacter baumannii | Klebsiella pneumonia | Pseudomonas fluorescens |
| Aeromonas hydrophilia | Lactobacillus acidophilus | Serratia marescens |
| Bacillus cereus | Lactobacillus casei | Shigella flexneri |
| Bacteroides fragilis | Lactobacillus delbrueckii lactis | Shigella sonnei |
| Campylobacter jejuni | Lactobacillus fermentum | Staphylococcus aureus |
| Citrobacter freundii | Lactococcus lactis | Staphylococcus epidermidis |
| Clostridium difficile | Listeria monocytogenes | Staphylococcus haemolyticus |
| Clostridium perfringins | Micrococcus luteus | Staphylococcus lugdunensis |
| Corynebacterium urealyticum | Moraxella catarrhalis | Streptococcus anginosus |
| Enterobacter aerogenes | Morganella morganii | Streptococcus bovis |
| Enterobacter cloacae | Neisseria gonorrhoeae | Streptococcus dysgalactiae |
| Enterococcus durans | Peptostrepococcus anaerobius | Streptococcus equi subsp. equi |
| Enterococcus faecalis | Prevotella melaninogenica | Streptococcus mitis |
| Enterococcus faecium | Propionibacterium acnes | Streptococcus oralis |
| Escherichia coli | Proteus mirabilis | Streptococcus pneumoniae |
| Gardnerella vaginalis | Proteus vulgaris | Streptococcus pyogenes |
| Klebsiella oxytoca | Pseudomonas aeruginosa | Yersinia enterocolitica |
| Yeasts | ||
| Candida albicans | Candida krusei | Candida tropicalis |
| Candida glabrata | Candida parapsilosis | |
| Viruses | ||
| CMV | Norovirus | |
| HPV-16 | VZV | |
| Human DNA | ||
| Human DNA | ||
| Human genomic DNA |
| Table 3. Analytical Specificity (Exclusivity) Panel. | ||||
|---|---|---|---|---|
| -- | -- | -- | ------------------------------------------------------ | -- |
d. Microbial Interference
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The Portrait GBS Assay was further evaluated for interference by the same panel of human DNA and 60 non-target microflora (51 bacterial, 5 yeast, and 4 viral stock strains; Table 3). The same high concentrations of potentially interfering DNA and microorganisms were spiked into negative clinical LIM broth matrix containing Group B Streptoccus cells at low positive concentrations of approximately 2X LoD, 1x10* CFU/mL for ATCC strain BAA1177 (serotype la) and 1.6x10* CFU/mL for ATCC strain 12403 A minimum of three replicate Portrait GBS Assays were performed for each of the (serotype III). human DNA and bacterial, yeast, and viral strains tested. With the exception of Enterococcus durans, none of the potentially interfering DNA or microflora interfered with the detection of either of the Group B Streptococcus strains, resulting in 'Group B Streptococcus POSITIVE' calls as expected. Interference was observed for GBS strain ATCC 12403 at 2X LoD (1.6x104 CFU/mL) in the presence of 106 CFU/mL E. durans, but not when the GBS strain concentration was increased to 3X LoD (2.4x104 CFU/mL).
e. Interfering Substances (Chemical Interference)
The Portrait GBS Assay was evaluated for chemical interference by the following panel of 21 different substances (Table 4). Substances were spiked into a negative clinical LIM broth matrix containing Group B Streptococcus cells at low positive concentrations of approximately 2X LoD, 1x10° CFU/mL for ATCC strain BAA1177 (serotype la) and 1.6x10* CFU/mL for ATCC strain 12403 (serotype III).. A minimum of three replicate assays was performed with none of the chemical substances interfering with the detection of either Group B Streptococcus strain resulting in 'Group B Streptococcus POSITIVE' calls as expected.
| Interfering Substances | Commercial Product Name | Concentration in Sample Matrix |
|---|---|---|
| Exogenous Substances | ||
| Anti-Diarrheal Medication | Immodium AD | 2% v/v |
| Body Oil | Neutrogena Body Oil | 2% v/v |
| Body Powder | Gold Bond Body Powder | 1% w/v |
| Contraceptive Foam | VCF Contraceptive Foam | 1 swab/5mL Broth |
| Contraceptive Gel | Options Gynol II Vaginal Contraceptive Gel | 2% of swab |
| Deodarant Spray | Summer's Eve Island Splash | 2% v/v |
| Enema Solution | Wallgreens Enema Saline Laxative | 0.25% v/v |
| Hemorrhoid Cream | Preparation H Cream Max Strength | 1 swab/5mL Broth |
| Lubricating Gel | KY Ultragel | 1 swab/5mL Broth |
| Moisturizing Lotion | Jergens Body Lotion | 1 swab/5mL Broth |
| Oral Laxative | Dulcolax Laxative Tablets | 1% w/v |
| Stool Softener | Equate Stool Softener Pluse stimulant Laxative | 0.0016% w/v |
| Vaginal Anti-fungal Med | Monstat 1 Tiococnazole Ointment 6.5% | 1 swab/5mL Broth |
| Vaginal Anti-itch Cream | Vagisil Medicated Anti-Itch Crème | 1 swab/5mL Broth |
| Endogenous Substances | ||
| Human Amniotic Fluid | LEE Biosciences | 2% v/v |
| Human DNA | Roche Human Genomic DNA | 1.2x10^6 copies/mL |
| Human Feces | In-house | 2% v/v |
| Human Meconium | LEE Biosciences | 2% w/v |
| Human Urine | In-house | 2% v/v |
| Human Whole Blood | In-house | 2% v/v |
| Mucous | Mucin, Sigma M2378 | 0.05% w/v |
| Table 4. Interfering Substances Panel. | ||
|---|---|---|
f. Carry-over/Cross-Contamination Study
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A study was performed to assess the carry-over/cross-contamination of the Portrait GBS Assay by alternatively testing high titered Group B Streptococus samples (ATCC 12403) spiked into negative clinical LIM broth matrix at 5.6x10' CFU/mL followed by true negative samples comprised of only negative clinical LIM broth matrix. By running a series of alternating runs of high titered and negative samples on multiple Portrait Analyzers, any possible carry-over/cross-contamination would be detected.
Table 5 lists the alternating pattern of high positives (HP) and true negatives (TN) performed on six different Portrait Analyzers. All of the 'calls' were in concordance with expected 'calls'. Therefore, there was no evidence of carry-over or cross-contamination in any of the tests.
| Sample | RESULTING CALL FOR GROUP B STREPTOCOCCUS | ||||||
|---|---|---|---|---|---|---|---|
| PortraitAnalyzer 5.01 | PortraitAnalyzer 5.35 | PortraitAnalyzer 5.49 | PortraitAnalyzer 5.96 | PortraitAnalyzer 5.108 | PortraitAnalyzer 5.112 | ||
| Run 1 | High Positive | POSITIVE | POSITIVE | POSITIVE | POSITIVE | POSITIVE | POSITIVE |
| Run 2 | True Negative | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE |
| Run 3 | High Positive | POSITIVE | POSITIVE | POSITIVE | POSITIVE | POSITIVE | POSITIVE |
| Run 4 | True Negative | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE |
| Run 5 | High Positive | POSITIVE | POSITIVE | POSITIVE | POSITIVE | POSITIVE | POSITIVE |
| Run 6 | True Negative | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE | NEGATIVE |
| Table 5. Carry-Over/Cross-Contamination Study. | |
|---|---|
q. Reproducibility
For the Reproducibility studies of the Portrait GBS Assay, a panel of five prepared samples was tested consisting of two Group B Streptococcus strains: ATCC strain BAA1177 (serotype la), and ATCC strain 12403 (serotype III) at a 'Moderate Positive' concentration (3X LoD; 1.5x10* CFU/mL for ATCC strain BAA1177 and 2.4x10* CFU/mL for ATCC strain 12403) and a 'Low Positive' concentration (1.5X LoD; 7.5x103 CFU/mL for ATCC strain BAA1177 and 1.2x104 CFU/mL for ATCC strain 12403). These samples were made by spiking in the respective cultures into a neqative clinical LIM broth matrix. In addition, a True Negative sample consisting of only a neqative clinical LIM broth matrix was tested.
The Reproducibility studies were performed in-house and at two external clinical sites using blindcoded panels and six different GBS Assay cartridge lots. At each site, these studies were performed over the course of 5 non-consecutive days. For each day, two runs were performed with three replicates of each sample per run on each day. A minimum of two operators performed the runs at each site.
Table 6 summarizes the cumulative data for the Portrait GBS Assay across all three sites for the Reproducibility studies. Results for the Reproducibility studies of the Portrait GBS Assay were within the expected percent agreement across all three sites. The only exception to this was at Site 1 where 4 out of the 30 True Negatives run resulted in Group B Streptococcus POSITIVE calls instead of NEGATIVE calls. By definition, the True Neqative samples consist of only neqative clinical LIM broth matrix and therefore should not result in a positive call. Due to the high sensitivity of molecular-based PCR assays, such as the Portrait GBS Assay, laboratory workspace contamination is a possibility. The other two sites did not experience any issues with the True Negative samples run during this study, resulting in 100% agreement, as expected.
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| Sample Type (Panel) | % agreement* | |||
|---|---|---|---|---|
| In-house site | Site 1 | Site 2 | All Sites | |
| 1. Moderate Positive ATCC 12403 | 30/30 100.0% | 30/30 100% | 30/30 100% | 90/90 100.0% |
| 2. Low Positive (C95) ATCC 12403 | 27/30 90.0% | 29/30 97.0% | 30/30 100% | 86/90 95.6% |
| 3. Moderate Positive ATCC BAA1177 | 30/30 100.0% | 30/30 100% | 30/30 100% | 90/90 100.0% |
| 4. Low Positive (C95) ATCC BAA1177 | 29/30 97.0% | 30/30 100% | 30/30 100% | 89/90 98.9% |
| 5. True Negative | 30/30 100.0% | 26/30 86.7% | 29/29‡ 97.0% | 85/89 95.5% |
Table 6. Results of the Reproducibility Studies
- For Moderate Positive and Low Positive samples, % agreement = 'Group B Streptococcus POSITIVE' calls/total runs.
For True Negative samples, % agreement = 'Group B Streptococcus NEGATIVE' calls/total runs.
‡ This reflects 29 runs not 30 because an 'Invalid' run in this case was not re-run.
I. Performance Data - Prospective Clinical Studies
The clinical performance of the Portrait GBS Assay was determined in three sites in the United States. 448 compliant clinical samples (18-29 hr LIM broth enrichment) were run over the course of four months to evaluate the performance of the Portrait GBS Assay in comparison to the reference GBS clinical microbiology protocol. Samples were obtained according to the established quidelines for the collection of rectal/vaginal swabs from antepartum women (35 – 37 weeks) and enriched in LIM broth. Results from the studies of all three clinical sites combined are summarized in Table 7. The overall initial sample invalid rate was 2.01%. All invalids reported during the study were resolved upon repeated testing resulting in a final invalid rate of 0%. Overall assay performance vs. GBS culture testing is as follows: Overall assay performance vs. GBS culture testing is as follows: Sensitivity = 97.9%, Specificity = 96.0%, PPV = 86.9%, and NPV = 99.4%.
| Table 7. Performance characteristics of Portrait GBS Assay vs. GBS culture testing | |
|---|---|
| ------------------------------------------------------------------------------------ | -- |
| Reference culturePositive | Negative | ||
|---|---|---|---|
| Test Positive | 93 | 14 | 107 |
| Test Negative | 2 | 339 | 341 |
| 95 | 353 | 448 | |
| Lower Cl95 | Upper Cl95 | ||
| Sensitivity | 97.9% | 92.7% | 99.4% |
| Specificity | 96.0% | 93.5% | 97.6% |
| PPV | 86.9% | 79.2% | 92.0% |
| NPV | 99.4% | 97.9% | 99.8% |
| Prevalence | 21.2% |
Great Basin Corporation 2441 S. 3850 W. West Valley City, UT 84120 www.gbscience.com phone: 801-990-1055 fax: 801-990-1051
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J. Conclusion
The submitted information in this product notification is complete and supports a substantial equivalence decision.
§ 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.