(49 days)
Not Found
No
The device description focuses on PCR technology and fluorescence analysis, with software performing basic analysis of amplification curves and reporting predefined results (positive, negative, uncertain, inhibited). There is no mention of AI/ML algorithms for pattern recognition, prediction, or complex data interpretation beyond standard PCR analysis.
No.
The device is an in vitro diagnostic (IVD) test kit used for the qualitative detection of Yersinia pestis DNA, which aids in the diagnosis of plague, not for treating or preventing disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is a "real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences of Yersinia pestis." The term "in vitro diagnostic" (IVD) confirms its use for diagnostic purposes.
No
The device description explicitly states that the system is composed of a portable instrument, laptop computer, and software, in addition to the detection kit. This indicates the presence of hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Plague Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences of Yersinia pestis."
The "Device Description" also refers to the system as a "fully integrated IVD system".
N/A
Intended Use / Indications for Use
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Plague Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences of Yersinia pestis. The kit can be used to test human whole blood collected in sodium citrate or sputum collected aseptically from individuals greater than 18 years of age suspected of having septic or pneumonic plague. In addition, positive blood cultures and colonies may be tested. The JBAIDS Plague Target 2 assay is used as a supplementary test only after a positive result with the Target I Assay.
The JBAIDS Plague Target 1 and Target 2 assays are run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of Y. pestis in conjunction with culture and other laboratory tests. The definitive identification of Y. pestis from colony growth, liquid blood culture growth, or from blood or sputum specimens requires additional testing and confirmation procedures in consultation with public health or other authorities for whom reports are required.
The diagnosis of plague must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of Y. pestis from cultures or directly from whole blood or sputum specimens.
The JBAIDS Plague Detection Kit is intended for use by trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Plague Detection Kit. The level of Y. pestis that would be present in blood or sputum from individuals with early systemic infection is unknown. Due to the difficulty in obtaining clinical specimens, these assays were not evaluated with blood or sputum from individuals with septic or pneumonic plague.
Product codes (comma separated list FDA assigned to the subject device)
OIH
Device Description
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Plague Detection System is a fully integrated IVD system composed of the portable JBAIDS instrument, laptop computer and software and the JBAIDS Plague Detection Kit with two different freeze-dried PCR assays for detection of Yersinia pestis DNA. The system has been validated using four different sample preparation kits for isolating DNA from wole blood (IT 1-2-3TM Platinum Path and QFLOWdana Sample Purification Kits), sputum (IT 1-2-3TM Platinum Path and IT 1-2-3TM VIBE), positive blood cultures (IT 1-2-3TM SWIPE Sample Purification Kit), and plate cultures (IT 1-2-3TM Platinum Path and SWIPE Sample Purification Kits). Use of the JBAIDS DNA Extraction Control Kit is also recommended.
Prior to testing, specimens are processed using BioFire Diagnostic's IT 1-2-3 Sample Purification Kits. The resulting purified sample is added to Target 1 Unknown and Target 1 Inhibition Control vials, along with reconstitution buffer. Target 1 Positive Control and Negative Control vials are prepared using reconstitution buffer and water. When Y. pestis DNA is present, a fragment of Y. pestis DNA is amplified. The amplicon is detected by fluorescence using a specific hydrolysis probe. Each probe is labeled on one end with a fluorescent reporter moiety (6-carboxyfluorescein (6-FAM)) and elsewhere with a quencher moiety (carboxy tetramethylrhodamine (TAMRA)). When the probe is intact, the quencher absorbs the light emitted by the reporter moiety. During PCR, the probe hybridizes to the target sequence before the exonuclease activity of Taq polymerase hydrolyzes the probe, separating the fluorophore from the quencher and permitting detection of the fluorescent signal generated by the reporter. The fluorescent signal increases as additional templates are amplified and more probes are hydrolyzed.
JBAIDS Software analyzes the fluorescence amplification curves and reports results as positive, negative, uncertain or inhibited. A failure of the Positive or Negative Control will result in the entire run being called invalid. Retesting is required to resolve uncertain, invalid or inhibited results. The Target 2 assay is used as a supplementary test only after a positive result is obtained with the Target 1 assay.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
whole blood, sputum
Indicated Patient Age Range
greater than 18 years of age
Intended User / Care Setting
trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Plague Detection Kit.
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
Clinical Performance - Testing of Surrogate Whole Blood Clinical Specimens
Sample Size: 100 surrogate whole blood samples (50 spiked with inactivated Y. pestis, 50 not spiked)
Data Source: prospectively collected specimens from febrile volunteers from November 2012 to April 2013.
Annotation Protocol: Samples processed using both new (Platinum Path) and original (QFLOWdana) nucleic acid extraction methods, then tested with JBAIDS Plague Detection Kit. JBAIDS operators were blinded to analyte content. Success defined as identical JBAIDS results for both extraction methods, with QFLOWdana results being considered correct.
Clinical Performance - Testing of Surrogate Sputum Clinical Specimens
Sample Size: 100 surrogate sputum samples (50 spiked with inactivated Y. pestis, 50 not spiked)
Data Source: frozen residual sputum specimens.
Annotation Protocol: Samples processed using both new (Platinum Path) and original (VIBE) nucleic acid extraction methods, then tested with JBAIDS Plague Detection Kit. JBAIDS operators were blinded to analyte content.
Limit of Detection - Whole Blood
Sample Size: 20 independent whole blood specimens
Data Source: Not specified, but "spiked with Y. pestis at the previously established LoD level".
Annotation Protocol: Processed with IT 1-2-3 Platinum Path Sample Purification Kit and detected with JBAIDS Plague Detection Kit.
Limit of Detection - Sputum
Sample Size: 20 independent sputum specimens
Data Source: Not specified, but "spiked with Y. pestis at the LoD level".
Annotation Protocol: Processed with IT 1-2-3 Platinum Path Sample Purification Kit and detected with JBAIDS Plague Detection Kit.
Reproducibility - Whole Blood
Sample Size: Panel of 12 blood samples, tested twice a day for four days at each of three testing sites (total 96 tests per target). Panel comprised four samples spiked at 5xLoD, four at 1xLoD, and four not spiked.
Data Source: Not specified.
Annotation Protocol: Sample processed with IT 1-2-3 Platinum Path Sample Purification Kit prior to testing with JBAIDS Plague Detection Kit.
Reproducibility - Sputum
Sample Size: Panel of nine sputum samples, tested twice a day for five days at each of three testing sites (total 90 tests per target). Panel comprised three samples spiked at 5xLoD, three at 1xLoD, and three not spiked.
Data Source: Not specified.
Annotation Protocol: Sample processed with IT 1-2-3 Platinum Path Sample Purification Kit prior to testing with JBAIDS Plague Detection Kit.
Detection of Direct Culture Samples Processed with the IT 1-2-3 Platinum Path Sample Purification Kit
Sample Size: 10 Yersinia pestis colonies and 10 non-Y. pestis colonies.
Data Source: Not specified.
Annotation Protocol: Colonies processed using a modified Platinum Path protocol, then tested with the JBAIDS Plague Detection Kit.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance - Testing of Surrogate Whole Blood Clinical Specimens
Study Type: Clinical evaluation using surrogate specimens.
Sample Size: 100 surrogate whole blood samples.
Key Results: Overall percent agreement between the two purification kits was 99% with a lower bound of the 95% confidence interval at 94%. The IT 1-2-3 QFLOWdna and Platinum Path Sample Purification Kits performed equivalently with respect to detection of Y. pestis in surrogate whole blood specimens tested with the JBAIDS Plague Detection Kit. One false positive result was obtained for a specimen spiked at the 1xLoD level for which the result was positive for the Platinum Path purified sample, but negative for the QFLOWdna purified sample.
Clinical Performance - Testing of Surrogate Sputum Clinical Specimens
Study Type: Clinical evaluation using surrogate specimens.
Sample Size: 100 surrogate sputum samples.
Key Results: Overall percent agreement between the two purification kits was 99% (99/100; 95% CI = 94.6-100%). The IT 1-2-3 VIBE and Platinum Path Sample Purification Kits performed equivalently with respect to detection of Y. pestis in surrogate sputum samples tested with the JBAIDS Plague Detection Kit. A single Platinum Path-purified sputum sample not spiked with Y. pestis gave a false positive result.
Selected Analytic Studies - Limit of Detection ( Whole Blood)
Study Type: Analytical study to confirm LoD.
Sample Size: 20 independent whole blood specimens.
Key Results: Twenty out of 20 independent whole blood specimens spiked with Y. pestis at the previously established LoD level and processed with the IT 1-2-3 Platinum Path Sample Purification Kit were detected with the JBAIDS Plague Detection Kit. This confirmed the LoD of 50 CFU/mL in whole blood.
Selected Analytic Studies - Limit of Detection (Sputum)
Study Type: Analytical study to confirm LoD.
Sample Size: 20 independent sputum specimens.
Key Results: Twenty out of 20 independent sputum specimens spiked with Y. pestis at the LoD level and processed with the IT 1-2-3 Platinum Path Sample Purification Kit were detected with the JBAIDS Plague Detection Kit. This confirmed the LoD of 670 CFU/mL in sputum.
Reproducibility (Whole Blood)
Study Type: Multicenter reproducibility study.
Sample Size: 12 blood samples in a panel, tested twice daily for 4 days at 3 sites (96 tests per target).
Key Results: The detection rate was >99% for whole blood samples containing Y. pestis spiked near or above the LoD. True negative whole blood samples did not have 100% negative results for each individual target assay, but since both targets must be detected for a final positive result for Plague, there were no final false positive results for unspiked samples. The JBAIDS Plague Detection System is reproducible when used to test whole blood samples processed with the IT 1-2-3 Platinum Path Sample Purification Kit.
Reproducibility (Sputum)
Study Type: Multicenter reproducibility study.
Sample Size: 9 sputum samples in a panel, tested twice daily for 5 days at 3 sites (90 tests per target).
Key Results: The detection rate was >99% for sputum samples containing Y. pestis spiked near or above the LoD. True negative sputum samples did not have 100% negative results for each individual target assay, but since both targets must be detected for a final positive result for Plague, there were no final false positive results for unspiked samples. The JBAIDS Plague Detection System is reproducible when used to test sputum samples processed with the IT 1-2-3 Platinum Path Sample Purification Kit.
Detection of Direct Culture Samples Processed with the IT 1-2-3 Platinum Path Sample Purification Kit
Study Type: Analytical study for direct culture detection.
Sample Size: 10 Y. pestis colonies and 10 non-Y. pestis colonies.
Key Results: All ten Y. pestis colonies were detected with the JBAIDS Plague Detection Kit, while the non-Y. pestis colonies were not detected.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Whole Blood Clinical Performance:
Positive Percent Agreement (PPA): 100% (49/49) with 95% CI 92.7-100%
Negative Percent Agreement (NPA): 98% (50/51) with 95% CI 89.6-99.9%
Sputum Clinical Performance:
Positive Percent Agreement (PPA): 100% (50/50) with 95% CI 92.9-100%
Negative Percent Agreement (NPA): 98% (49/50) with 95% CI 89.4-100%
Reproducibility - Whole Blood (All Sites):
Medium Positive (5xLoD) - Plague Target 1: AAR 100% (96/96) with 95% CI 96.2-100%
Medium Positive (5xLoD) - Plague Target 2: AAR 100% (96/96) with 95% CI 96.2-100%
Low Positive (1xLoD) - Plague Target 1: AAR 100% (96/96) with 95% CI 96.2-100%
Low Positive (1xLoD) - Plague Target 2: AAR 98.9% (95/96) with 95% CI 94.3-99.9%
Negative - Plague Target 1: AAR 98.9% (95/96) with 95% CI 94.3-99.9% (0/96 positive results)
Negative - Plague Target 2: AAR 97.9% (94/96) with 95% CI 92.7-99.7% (1/96 positive result)
Reproducibility - Sputum (All Sites):
Medium Positive (5xLoD) - Plague Target 1: AAR 98.9% (89/90) with 95% CI 94.0-99.9%
Medium Positive (5xLoD) - Plague Target 2: AAR 100% (90/90) with 95% CI 96.0-100%
Low Positive (1xLoD) - Plague Target 1: AAR 100% (90/90) with 95% CI 96.0-100%
Low Positive (1xLoD) - Plague Target 2: AAR 100% (90/90) with 95% CI 96.0-100%
Negative - Plague Target 1: AAR 98.9% (89/90) with 95% CI 94.0-99.9% (0/90 positive results)
Negative - Plague Target 2: AAR 100% (90/90) with 95% CI 96.0-100% (0/90 positive results)
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.
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
N/A
0
Image /page/0/Picture/1 description: The image is a seal for the Department of Health & Human Services - USA. The seal is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is a stylized image of three human profiles facing to the right. The profiles are stacked on top of each other, with the top profile being the largest and the bottom profile being the smallest.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
February 20, 2019
CYNTHIA PHILLIPS, Ph.D. VICE PRESIDENT OF REGULATORY AND CLINICAL AFFAIRS BIOFIRE DEFENSE, LLC 79 W. 4500 SOUTH, SUITE 14 SALT LAKE CITY UT 84107
Re: K131729 Trade/Device Name: JBAIDS Plague Detection Kit Regulatory Class: Unclassified Product Code: OIH Dated: June 10, 2013
Dear Dr. Phillips:
Received: June 12, 2013
This letter corrects our substantially equivalent letter of July 31, 2013.
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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
Page 2-Dr. Phillips
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance 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" (21CFR 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 Small Manufacturers, International and Consumer Assistance 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,
Uwe Scherf -S
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
2
Indications for Use
510(k) Number: K131729 Device Name: JBAIDS Plague Detection System
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Plague Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences of Yersinia pestis. The kit can be used to test human whole blood collected in sodium citrate or sputum collected aseptically from individuals greater than 18 years of age suspected of having septic or pneumonic plague. In addition, positive blood cultures and colonies may be tested. The JBAIDS Plague Target 2 assay is used as a supplementary test only after a positive result with the Target I Assay.
The JBAIDS Plague Target 1 and Target 2 assays are run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of Y. pestis in conjunction with culture and other laboratory tests. The definitive identification of Y. pestis from colony growth, liquid blood culture growth, or from blood or sputum specimens requires additional testing and confirmation procedures in consultation with public health or other authorities for whom reports are required.
The diagnosis of plague must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of Y. pestis from cultures or directly from whole blood or sputum specimens.
The JBAIDS Plague Detection Kit is intended for use by trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Plague Detection Kit. The level of Y. pestis that would be present in blood or sputum from individuals with early systemic infection is unknown. Due to the difficulty in obtaining clinical specimens, these assays were not evaluated with blood or sputum from individuals with septic or pneumonic plague.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Image /page/2/Picture/10 description: The image shows the text "John-Hobson-S 2013.07.31 10:04:30 -04'00'". The text is overlaid on top of a logo. The date and time are clearly visible in the center of the image.
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510(k) Summary BioFire Diagnostics, Inc.
Modification of the JBAIDS Plague Detection Kit for use with the IT 1-2-3TM Platinum Path Sample Purification Kit Accessory
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitted by:
BioFire Diagnostics, Inc. 390 Wakara Way Salt Lake City, UT 84108
Telephone: 801-736-6354 Facsimile: 801-588-0507
Contact: Cynthia Phillips, ext. 370
Date Submitted: June 10, 2013
Device Name and Classification:
Trade Name: JBAIDS Plague Detection Kit Classification: Unclassified Product Code: OIH
Predicate Device:
JBAIDS Plague Detection Kit (K072631)
Intended Use:
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Plague Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences of Yersinia pestis. The kit can be used to test human whole blood collected in sodium citrate or sputum collected aseptically from individuals greater than 18 years of age suspected of having septic or pneumonic plague. In addition, positive blood cultures and colonies may be tested. The JBAIDS Plague Target 2 assay is used as a supplementary test only after a positive result with the Target 1 Assay.
The JBAIDS Plague Target 1 and Target 2 assays are run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of Y, nestis in
4
conjunction with culture and other laboratory tests. The definitive identification of Y. pestis from colony growth, liquid blood culture growth, or from blood or sputum specimens requires additional testing and confirmation procedures in consultation with public health or other authorities for whom reports are required.
The diagnosis of plague must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of Y. pestis from cultures or directly from whole blood or sputum specimens.
The JBAIDS Plague Detection Kit is intended for use by trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Plague Detection Kit. The level of Y. pestis that would be present in blood or sputum from individuals with early systemic infection is unknown. Due to the difficulty in obtaining clinical specimens, these assays were not evaluated with blood or sputum from individuals with septic or pneumonic plague.
Device Description:
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Plague Detection System is a fully integrated IVD system composed of the portable JBAIDS instrument, laptop computer and software and the JBAIDS Plague Detection Kit with two different freeze-dried PCR assays for detection of Yersinia pestis DNA. The system has been validated using four different sample preparation kits for isolating DNA from wole blood (IT 1-2-3TM Platinum Path and QFLOWdana Sample Purification Kits), sputum (IT 1-2-3TM Platinum Path and IT 1-2-3TM VIBE), positive blood cultures (IT 1-2-3TM SWIPE Sample Purification Kit), and plate cultures (IT 1-2-3™ Platinum Path and SWIPE Sample Purification Kits). Use of the JBAIDS DNA Extraction Control Kit is also recommended.
Prior to testing, specimens are processed using BioFire Diagnostic's IT 1-2-3 Sample Purification Kits. The resulting purified sample is added to Target 1 Unknown and Target 1 Inhibition Control vials, along with reconstitution buffer. Target 1 Positive Control and Negative Control vials are prepared using reconstitution buffer and water. When Y. pestis DNA is present, a fragment of Y. pestis DNA is amplified. The amplicon is detected by fluorescence using a specific hydrolysis probe. Each probe is labeled on one end with a fluorescent reporter moiety (6-carboxyfluorescein (6-FAM)) and elsewhere with a quencher moiety (carboxy tetramethylrhodamine (TAMRA)). When the probe is intact, the quencher absorbs the light emitted by the reporter moiety. During PCR, the probe hybridizes to the target sequence before the exonuclease activity of Taq polymerase hydrolyzes the probe, separating the fluorophore from the quencher and permitting detection of the fluorescent signal generated by the reporter. The fluorescent signal increases as additional templates are amplified and more probes are hydrolyzed.
JBAIDS Software analyzes the fluorescence amplification curves and reports results as positive, negative, uncertain or inhibited. A failure of the Positive or Negative Control will result in the entire run being called invalid. Retesting is required to resolve uncertain,
5
invalid or inhibited results. The Target 2 assay is used as a supplementary test only after a positive result is obtained with the Target 1 assay.
Substantial Equivalence:
The JBAIDS Plague Detection Kit is substantially equivalent to the previously cleared JBAIDS Plague Detection Kit. The following tables compare the modified JBAIDS Plague Detection Kit to the previously cleared JBAIDS Plague Detection Kits (K072631). The first table outlines the similarities between the two systems and the second table outlines the differences.
| Element | New Device:
JBAIDS Plague Detection Kit | Predicate:
JBAIDS Plague Detection Kit
(K072631) |
|----------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------|
| Intended Use | Identification of Plague infection
through the detection of two DNA
sequence targets unique to Yersinia
pestis. Results are used in conjunction
with clinical information, culture, and
other laboratory tests as an aid in the
diagnosis of systemic Plague infection
in individuals suspected of having the
disease. | Same |
| Technology | Real-time PCR using hydrolysis probes | Same |
| Organism
Detected | Qualitative in vitro detection of
Yersinia pestis DNA | Same |
| Specimen
Types | Whole blood (collected in 3.2% sodium
citrate), sputum collected aseptically
from individuals greater than 18 years
of age suspected of having septic or
pneumonic plague, blood culture
(grown in soybean-casein digest broth)
or bacterial culture (grown on blood
agar) | Same |
| Platform | JBAIDS Instrument | Same |
| Time Required
for Analysis of
Specimen | Less than 3 hours | Same |
Table 1. Similarities between the New Device and the Predicate
Table 2. Differences between the New Device and the Predicate
| Element | New Device:
JBAIDS Plague Detection Kit | Predicate:
JBAIDS Plague Detection Kit
(K072631) |
| --------- | -------------------------------------------- | -------------------------------------------------------- |
|---|
6
| DNA
Extraction
Methods | Whole blood purified with IT 1-2-3 TM
Platinum Path or IT 1-2-3 TM QFLOWdna
Sample Purification Kits (or validated
equivalent). | Whole blood purified with IT 1-2-3 TM
QFLOWdna Sample Purification Kit (or
validated equivalent). |
|------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------|
| | Sputum purified with IT 1-2-3 TM
Platinum Path or IT 1-2-3 TM VIBE
Sample Purification Kits (or validated
equivalent). | Sputum purified with IT 1-2-3 TM VIBE
Sample Purification Kits (or validated
equivalent). |
| | Blood culture purified with IT 1-2-3 TM
SWIPE Sample Purification Kit (or
validated equivalent). | Same |
| | Direct bacterial culture purified with IT
1-2-3 TM Platinum Path or IT 1-2-3 TM
SWIPE Sample Purification Kit (or
validated equivalent). | Direct bacterial culture purified with IT
1-2-3 TM SWIPE Sample Purification Kit
(or validated equivalent). |
Summary of Performance Data
Clinical Performance
True clinical specimens from patients infected with Yersinia pestis (plague), are not available for testing due to the extreme rarity of natural infection with these organisms. Therefore, two clinical evaluations using surrogate specimens were performed to validate the use of the IT 1-2-3TM Platinum Path Sample Purification Kit for use with the JBAIDS Plague Detection Kit. For the evaluation using blood samples, whole blood specimens were prospectively collected from patients with fever, after which the samples were spiked with inactivated Y. pestis, purified by both the new and old extraction methods, and then tested. For the evaluation using sputum samples, residual frozen sputum specimens were spiked with inactivated Y. pestis, purified by both the new and old extraction methods, and then tested.
Testing of Surrogate Whole Blood Clinical Specimens
One hundred (100) surrogate whole blood samples were prepared using prospectively collected specimens that were collected from febrile volunteers from November of 2012 into April of 2013. Fifty (50) of the specimens were spiked with inactivated Y. pestis at concentrations near and above the system LoD, while the remaining 50 specimens were not spiked with Y. pestis. Samples were then processed using both the new nucleic acid extraction method (Platinum Path) and the original nucleic acid extraction method (IT I-2-3TM QFLOWdana Sample Purification Kit; QFLOWdad by testing with the JBAIDS Plague Detection Kit. JBAIDS operators were blinded to the analyte content of the samples. Table 3 presents the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) for the surrogate whole blood specimen testing. In this study, a success was defined as a surrogate sample having identical JBAIDS results for both the Platinum Path and QFLOWana processed samples, where the JBAIDS result for a sample purified using from the QFLOWda® kit was considered the correct result. Overall percent agreement between the two purification kits was 99% with a lower bound of the 95%
7
confidence interval at 94%. The IT 1-2-3 QFLOWdar and Platinum Path Sample Purification Kits performed equivalently with respect to detection of Y. pestis in surrogate whole blood specimens tested with the JBAIDS Plague Detection Kit.
| Positive Agreement | Negative Agreement | ||||||
|---|---|---|---|---|---|---|---|
| QFLOWdna + | |||||||
| Platinum | |||||||
| Path + | QFLOWdna + | ||||||
| Platinum | |||||||
| Path - | PPA | 95% | |||||
| CIa | QFLOWdna - | ||||||
| Platinum | |||||||
| Path - | QFLOWdna - | ||||||
| Platinum | |||||||
| Path + | NPA | 95% CI | |||||
| 49 | 0 | 100% | |||||
| (49/49) | 92.7- | ||||||
| 100% | 50 | 1b | 98% | ||||
| (50/51) | 89.6- | ||||||
| 99.9% |
Table 3. JBAIDS Plague Detection Kit Performance on Spiked Whole Blood Samples Processed with the IT 1-2-3 Platinum Path and OFLOWdna Sample Purification Kits
a C.J. Clopper and E.S. Pearson. 1934. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26:404-413.
b One false positive result was obtained for a specimen spiked at the 1×LoD level for which the result was positive for the Platinum Path purified sample, but negative for the QFLOW®® purified sample. When a sample is spiked at the 1×LoD level, ≥ 95% of results are expected to be positive. Occasional negative results are therefore expected (approximately 1 out of 20), with the consequence in this case of a false positive result for a specimen spiked at the 1×LoD level.
Testing of Surrogate Sputum Clinical Specimens
One hundred (100) surrogate sputum samples were prepared using frozen residual sputum specimens. Fifty (50) of the samples were spiked with inactivated Y. pestis at concentrations near and above the system LoD, while the remaining 50 specimens were not spiked with Y. pestis. Samples were then processed using both the new nucleic acid extraction method (Platinum Path) and the original nucleic acid extraction method (IT /-2-3TM VIBE Sample Purification Kit) followed by testing with the JBAIDS Plague Detection Kit. JBAIDS operators were blinded to the analyte content of the samples. Table 4 presents the PPA and NPA for the surrogate sputum clinical specimen testing. Overall percent agreement between the two purification kits was 99% (99/100; 95% CI = 94.6-100%). The IT 1-2-3 VIBE and Platinum Path Sample Purification Kits performed equivalently with respect to detection of Y. pestis in surrogate sputum samples tested with the JBAIDS Plague Detection Kit.
Table 4. JBAIDS Plague Detection Kit Performance on Spiked Sputum Samples Processed with the IT 1-2-3 Platinum Path and VIBE Sample Purification Kits
| Positive Agreement | Negative Agreement | |||||
|---|---|---|---|---|---|---|
| VIBE + | ||||||
| Plat Path |
- | VIBE +
Plat Path
- | PPA | VIBE -
Plat Path - | VIBE -
Plat Path
- | NPA | 95% CIa |
8
| 50 | 0 | 100%
(50/50) | 92.9-
100% | 49 | 1b | 98%
(49/50) | 89.4-
100% |
| ---- | --- | ----------------- | --------------- | ---- | ---- | ---------------- | --------------- |
|---|
ª C.J. Clopper and E.S. Pearson. 1934. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26:404-413.
b A single Platinum Path-purified sputum sample not spiked with Y. pestis gave a false positive result. It may have been contaminated with Y. pestis during processing or testing, as PCR amplification of that sample was delayed relative to samples spiked at the 1×LoD level, and no other false positive results were obtained during the study.
Selected Analytic Studies
Limit of Detection
Twenty out of 20 independent whole blood specimens spiked with Y. pestis at the previously established LoD level and processed with the IT 1-2-3 Platinum Path Sample Purification Kit were detected with the JBAIDS Plague Detection Kit. This confirmed the LoD of 50 CFU/mL in whole blood that was previously established for whole blood samples processed using the IT 1-2-3 OFLOWd10 Sample Purification Kit.
Twenty out of 20 independent sputum specimens spiked with Y. pestis at the LoD level and processed with the IT 1-2-3 Platinum Path Sample Purification Kit were detected with the JBAIDS Plague Detection Kit. This confirmed the LoD of 670 CFU/mL in sputum previously established for sputum samples processed using the IT 1-2-3 VIBE Sample Purification Kit.
Table 5. Confirmation of the Y. pestis LoDs for Platinum Path-Purified Whole Blood and Sputum Samples Tested with the JBAIDS Plague Detection Kit
| Sample
Matrix | Spiked Y.
pestis
Concentration
(CFU/mL) | Plague
Assay | #
Positive | %
Positive | Plague Target
Assay Mean Cp
+/- Std Dev |
|------------------|--------------------------------------------------|-----------------|---------------|---------------|-----------------------------------------------|
| Whole
Blood | 50 | Target 1 | 20/20 | 100.0% | 34.25 ± 1.18 |
| Whole
Blood | | Target 2 | 19/20 | 95.0% | 34.67 ± 1.01 |
| Sputum | 670 | Target 1 | 20/20 | 100.0% | 31.17 ± 0.93 |
| Sputum | | Target 2 | 20/20 | 100.0% | 31.91 ± 1.68 |
Reproducibility
A multicenter study was performed to determine the overall system reproducibility when whole blood and sputum samples were processed with the IT 1-2-3 Platinum Path Sample Purification Kit prior to testing with the JBAIDS Plague Detection Kit.
A panel of 12 blood samples was tested twice each day for four days at each of three testing sites. The panel contained four samples spiked with inactivated Y. pestis CO92 strain at a medium positive (5×LoD) level, four samples spiked at a low positive level (1×LoD), and four samples that were not spiked. Results for whole blood testing are summarized in Table 6.
A panel of nine sputum samples was similarly tested twice each day for five days at each of three testing sites. This panel contained three samples spiked with inactivated Y. pestis CO92 strain at a medium positive (5×LoD) level, three samples spiked at a low positive
9
level (1×LoD), and three samples that were not spiked. Results for sputum testing are summarized in Table 7. The detection rate was >99% for both whole blood and sputum samples containing Y. pestis spiked near or above the LoD for the respective sample matrix. True negative whole blood and sputum samples did not have 100% negative results for each individual target assay, but since both targets must be detected for a final positive result for Plague, there were no final false positive results for unspiked samples. The JBAIDS Plague Detection System is reproducible when used to test whole blood and sputum samples processed with the IT 1-2-3 Platinum Path Sample Purification Kit.
| Plague Target 1 | Plague Target 2 | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Blood Spike Level | Test Location | Number Positive | Number Negative | % Agreement with Expected Result | 95% CI | Mean Cp | Std Dev | %CV | Number Positive | Number Negative | % Agreement with Expected Result | 95% CI | Mean Cp | Std Dev | %CV |
| Medium | |||||||||||||||
| Positive | |||||||||||||||
| (5xLoD) | Site 1 | 32/32 | 0/32 | 100% | 29.66 | 0.95 | 3.20 | 32/32 | 0/32 | 100% | 32.52 | 0.86 | 2.64 | ||
| Site 2 | 32/32 | 0/32 | 100% | 28.75 | 0.87 | 3.03 | 32/32 | 0/32 | 100% | 31.80 | 0.83 | 2.61 | |||
| Site 3 | 32/32 | 0/32 | 100% | 28.51 | 1.40 | 4.91 | 32/32 | 0/32 | 100% | 31.04 | 0.93 | 3.00 | |||
| All | |||||||||||||||
| Sites | 96/96 | 0/96 | 100% | 96.2-100 | 28.98 | 1.20 | 4.14 | 96/96 | 0/96 | 100% | 96.2-100 | 31.79 | 1.06 | 3.33 | |
| Low | |||||||||||||||
| Positive | |||||||||||||||
| (1xLoD) | Site 1 | 32/32 | 0/32 | 100% | 31.16 | 0.98 | 3.15 | 31/32a | 0/32 | 96.9% | 33.88 | 1.16 | 3.42 | ||
| Site 2 | 32/32 | 0/32 | 100% | 30.08 | 1.27 | 4.22 | 32/32 | 0/32 | 100% | 32.67 | 1.01 | 3.09 | |||
| Site 3 | 32/32 | 0/32 | 100% | 29.55 | 0.96 | 3.25 | 32/32 | 0/32 | 100% | 32.09 | 0.65 | 2.03 | |||
| All | |||||||||||||||
| Sites | 96/96 | 0/96 | 100% | 96.2-100 | 30.26 | 1.27 | 4.20 | 95/96 | 0/96 | 98.9% | 94.3-99.9 | 32.88 | 1.21 | 3.68 | |
| Negative | Site 1 | 0/32 | 32/32 | 100% | 1/32 | 31/32 | 96.9% | 36.40d | |||||||
| Site 2 | 0/32 | 31/32b | 96.9% | 0/32 | 31/32c | 96.9% | |||||||||
| Site 3 | 0/32 | 32/32 | 100% | 0/32 | 32/32 | 100% | |||||||||
| All | |||||||||||||||
| Sites | 0/96 | 95/96 | 98.9% | 94.3-99.9 | 1/96 | 94/96 | 97.9% | 92.7-99.7 | 36.40d |
Table 6. Reproducibility of the Plague Target 1 and Target 2 Assays in the JBAIDS Plague Detection Kit for Whole Blood Samples Purified with the IT 1-2-3 Platinum Path Purification Kit
ª One initial Uncertain result; retest also Uncertain.
b One initial Inhibited result; retest Inhibited for undiluted sample and negative for 1:10 dilution; no further testing.
· One initial Inhibited result; inadequate volume for retesting.
d Mean Cp for single false positive sample
Table 7. Reproducibility of the Plague Target 2 Assays in the JBAIDS Plague Detection Kit for Sputum Samples Purified with the IT 1-2-3 Platinum Path Purification Kit
| F | S | p.i.k | e | o | 1 | o | 5 | 4 | Plague Target 1 | Plague Target 2 |
|---|---|---|---|---|---|---|---|---|---|---|
| --- | --- | ------- | --- | --- | --- | --- | --- | --- | ----------------- | ----------------- |
10
| | | Number Positive | Number Negative | % Agreement with
Expected Result | 95% CI | Mean Cp | Std Dev | %CV | Number Positive | Number Negative | % Agreement with
Expected Result | 95% CI | Mean Cp | Std Dev | %CV |
|----------------------------|--------------|-----------------|-----------------|-------------------------------------|---------------|---------|---------|------|-----------------|-----------------|-------------------------------------|--------------|---------|---------|------|
| Medium Positive
(5xLoD) | Site 1 | 29/30 | 1/30 | 96.7% | | 29.82 | 0.70 | 2.35 | 30/30 | 0/30 | 100% | | 32.70 | 0.70 | 2.14 |
| | Site 2 | 30/30 | 0/30 | 100% | | 28.60 | 0.59 | 1.88 | 30/30 | 0/30 | 100% | | 31.61 | 0.57 | 1.80 |
| | Site 3 | 30/30 | 0/30 | 100% | | 27.59 | 0.58 | 2.10 | 30/30 | 0/30 | 100% | | 30.80 | 0.53 | 1.72 |
| | All
Sites | 89/90 | 1/90 | 98.9% | 94.0-
99.9 | 28.65 | 1.10 | 3.84 | 90/90 | 0/90 | 100% | 96.0-
100 | 31.70 | 0.99 | 3.12 |
| Low Positive
(1xLoD) | Site 1 | 30/30 | 0/30 | 100% | | 32.60 | 0.77 | 2.36 | 30/30 | 0/30 | 100% | | 35.62 | 1.19 | 3.34 |
| | Site 2 | 30/30 | 0/30 | 100% | | 31.31 | 0.58 | 2.03 | 30/30 | 0/30 | 100% | | 34.40 | 0.59 | 1.72 |
| | Site 3 | 30/30 | 0/30 | 100% | | 30.36 | 0.67 | 2.21 | 30/30 | 0/30 | 100% | | 33.48 | 0.72 | 2.15 |
| | All
Sites | 90/90 | 0/90 | 100% | 96.0-
100 | 31.42 | 1.14 | 3.63 | 90/90 | 0/90 | 100% | 96.0-
100 | 34.50 | 1.23 | 3.57 |
| Negative | Site 1 | 0/30 | 30/30 | 100% | | | | | 0/30 | 30/30 | 100% | | | | |
| | Site 2 | 0/30 | 29/30a | 96.7% | | | | | 0/30 | 30/30 | 100% | | | | |
| | Site 3 | 0/30 | 30/30 | 100% | | | | | 0/30 | 30/30 | 100% | | | | |
| | All
Sites | 0/90 | 89/90 | 98.9% | 94.0-
99.9 | | | | 0/90 | 90/90 | 100% | 96.0-
100 | | | |
ª One initial Uncertain result; retest also Uncertain.
Detection of Direct Culture Samples Processed with the IT 1-2-3 Platinum Path Sample Purification Kit
Y. pestis colonies can be detected using a modified Platinum Path protocol to process the colonies followed by testing with the JBAIDS Plague Detection Kit. Ten Yersinia pestis colonies were purified alongside ten non- Y. pestis colonies. All ten Y. pestis colonies were detected with the JBAIDS Plague Detection Kit, while the non- Y. pestis colonies were not detected.
| Table 8. Plague Target 1 and Target 2 Detection from Colonies Purified with Platinum Path | |
|---|---|
| Plague Target 1 | Plague Target 2 |
| Colony Type | Plague Target 1 | Plague Target 2 | ||||
|---|---|---|---|---|---|---|
| Positive Results/Total | Cp (cycles) Mean | SD | Positive Results/Total | Cp (cycles) Mean | SD | |
| Y. pestis | 10/10 | 19.25 | 0.74 | 10/10 | 20.70 | 0.67 |
| Non- Y. pestis | 0/10 | - | - | 0/10 | - | - |