(34 days)
Not Found
No
The description focuses on real-time PCR technology and software analysis of fluorescence curves, which is standard for this type of diagnostic test and does not indicate the use of AI or ML. There are no mentions of AI, ML, or related concepts like deep learning or neural networks.
No
Explanation: This device is an in vitro diagnostic (IVD) test kit used for the qualitative detection of Francisella tularensis DNA. It is intended to aid in the diagnosis of tularemia by identifying the pathogen, not to treat or directly manage the disease. Therefore, it is a diagnostic device, not a therapeutic one.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences of Francisella tularensis" and "intended to aid in the diagnosis of individual presenting with signs and symptoms of pneumonic or typhoidal tularemia." This language clearly indicates its purpose is for diagnosis.
No
The device description explicitly states that the system is a "fully integrated IVD system composed of the portable JBAIDS instrument, laptop computer and software and the JBAIDS Tularemia Detection Kit". This indicates the device includes significant hardware components (instrument, laptop, kit) in addition to the 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) Tularemia 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 Francisella tularensis."
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) Tularemia 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 Francisella tularensis. The system 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 tularemia. In addition, positive blood cultures and colonies may be tested. This assay is intended to aid in the diagnosis of individual presenting with signs and symptoms of pneumonic or typhoidal tularemia. It is not intended to aid in the diagnosis of glandular, ulceroglandular, oculoglandular, or oropharyngeal tularemia.
The JBAIDS Tularemia Detection Kit is run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of F. tularensis in conjunction with culture and other laboratory tests. The definitive identification of F. tularensis from colony growth. liguid blood culture growth, blood specimens, 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 tularemia must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of the target either from colonies, blood culture whole blood or sputum specimens.
The JBAIDS Tularemia Detection Kit is intended for use by trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Tularemia Detection Kit. The level of F. tularensis that would be present in blood or sputum from individuals with early systemic or pneumonic infection is unknown. Due to the difficulty in obtaining clinical specimens, this assay was not evaluated with blood or sputum from individuals presenting with signs and symptoms of tularemia who have subsequently developed pneumonic or typhoidal tularemia pneumonic or typhoidal tularemia.
Product codes (comma separated list FDA assigned to the subject device)
OEH
Device Description
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Tularemia Detection System is a fully integrated IVD system composed of the portable JBAIDS instrument, laptop computer and software and the JBAIDS Tularemia Detection Kit with one freeze-dried PCR assay for detection of Francisella tularensis DNA. The system has been validated using four different sample preparation kits for isolating DNA from whole blood (IT /-2-3TM Platinum Path and QFLOWana Sample Purification Kits), sputum (IT I-2-3TM Platinum Path and IT 1-2-3TM VIBE Sample Purification Kits), positive blood cultures (IT 1-2-3 TM SWIPE Sample Purification Kit), and plate cultures (IT /-2-3TM Platinum Path and IT 1-2-3TM 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 I-2-3 Sample Purification Kits. The resulting purified sample is added to Unknown and Inhibition Control vials, along with reconstitution buffer. Positive Control and Negative Control vials are prepared using reconstitution buffer and water. When F. tularensis DNA is present, a fragment of F. tularensis 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 tetramethyIrhodamine (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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
whole blood, sputum, blood cultures, colonies
Indicated Patient Age Range
greater than 18 years of age
Intended User / Care Setting
trained clinical laboratory personnel
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
Testing of Surrogate Whole Blood Clinical Specimens
One hundred (100) surrogate whole blood specimens 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 F. tulurensis at concentrations near and above the system LoD, while the remaining 50 specimens were not spiked with F. tularensis. The level of inactivated F. tularensis used to spike these samples was relative to the LoD (1500 CFU/mL) established for Platinum Pathpurified whole blood specimens.
Once spiked, samples were then processed using both the new nucleic acid extraction method (Platinum Path) and the original nucleic acid extraction method (IT 1-2-37M QFLOWdana Sample Purification Kit; QFLOWdad) followed by testing with the JBAIDS Tularemia Detection Kit. JBAIDS operators were blinded to the analyte content of the samples.
Testing of Surrogate Sputum Clinical Specimens
One hundred (100) surrogate specimens were prepared using frozen residual sputum specimens. Fifty (50) of the specimens were spiked with inactivated F, tularensis at concentrations near and above the system LoD, while the remaining 50 specimens were not spiked with F. tularensis. 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 VIBE Sample Purification Kit) followed by testing with the JBAIDS Tularemia Detection Kit. JBAIDS operators were blinded to the analyte content of the samples.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance
True clinical specimens from patients infected with Francisella tularensis (tularemia), are not available for testing due to the extreme rarity of natural infection with this organism. Therefore, two clinical evaluations using surrogate specimens were performed to validate the use of the IT 1-2-3TM Platinum Path Sample Purification Kit with the JBAIDS Tularemia Detection Kit.
Testing of Surrogate Whole Blood Clinical Specimens
The final Tularemia interpretation for samples purified using the Platinum Path kit had a positive percent agreement (PPA) of 100% as compared to samples purified using the QFLOW(00 kit (50/50; 95% CI = 92.9-100%). The final JBAIDS Tularemia interpretation for samples purified using Platinum Path was negative for 50 out of 50 samples that were negative when purified using OFLOWdag. This represents a negative percent agreement (NPA) of 100% (50/50; 95% CI = 92.9-100%).
Testing of Surrogate Sputum Clinical Specimens
The final Tularemia result for samples purified using the Platinum Path kit had a positive percent agreement (PPA) of 100% as compared to samples purified using VIBE (49/49; 95% CI = 92.8-100%). The final JBAIDS Tularemia result for samples purified using Platinum Path was negative for 49 out of 51 samples that were negative when purified using VIBE. This represents a negative percent agreement (NPA) of 96.1% (49/51; 95% CI = 86.5-99.5%).
Selected Analytic Studies
Limit of Detection
The originally established LoD of 300 CFU/mL in whole blood purified using the IT I-2-3 OFLOW" Sample Purification Kit could not be confirmed using the Platinum Path Sample Purification Kit. Therefore, the system LoD for whole blood samples was increased by five-fold to 1500 CFU/mL. Twenty out of 20 independent whole blood specimens spiked with F. tularensis at the new LoD level and processed with the IT 1-2-3 Platinum Path Sample Purification Kit were detected with the JBAIDS Tularemia Detection Kit, establishing the new system LoD of 1500 CFU/mL F. tularensis in whole blood.
Nineteen (19) out of 20 independent sputum specimens spiked with F. tularensis at the LoD level and processed with the IT 1-2-3 Platinum Path Sample Purification Kit were detected with the JBAIDS Tularemia Detection Kit. This confirmed the LoD of 2000 CFU/mL in sputum that was originally established for sputum samples processed using the IT /-2-3 VIBE Sample Purification Kit.
Reproducibility
A multicenter study was performed to determine the overall system reproducibility when whole blood and sputum samples were processed with the IT /-2-3 Platinum Path Sample Purification Kit prior to testing with the JBAIDS Tularemia 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 F. tularensis at a medium positive (5x LoD) level, four samples spiked at a low positive level (1x LoD), and four samples that were not spiked. The level of inactivated F. tularensis used to spike these samples was relative to the system LoD (1500 CFU/mL) established for Platinum Path-purified whole blood specimens. Samples spiked F. tularensis at the low positive (1x LoD) level yielded final positive results 86.5% of the time overall. Examination of Cp values indicates these samples were likely under-spiked to approximately the 0.5x LoD level, where detection is expected to be below 95%. Detection at this low positive level was reproducibly less than 100% across the sites, and the JBAIDS Tularemia Detection System is reproducible when used to test whole blood samples processed with the IT /-2-3 Platinum Path Sample Purification Kit.
A panel of 9 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 F. tularensis at a medium positive (5xLoD) level, three samples spiked at a low positive level (1xLoD), and three samples that were not spiked. The detection rate was >=97.8% for all sputum samples containing F. tularensis spiked near or above the LoD, and there were no false positive results for unspiked samples. The JBAIDS Tularemia Detection System is reproducible when used to test sputum samples processed with the IT 7-2-3 Platinum Path Sample Purification Kit.
Detection of Direct Culture Samples Processed with the IT 1-2-3 Platinum Path Sample Purification Kit
F. tularensis colonies can be detected using a Platinum Path protocol to process the colonies followed by testing with the JBAIDS Tularemia Detection Kit. Ten F. tularensis colonies were purified alongside ten non- F. tularensis colonies. All ten F. tularensis colonies were detected with the JBAIDS Tularemia Detection Kit, while the non- F. tularensis colonies were not detected.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Whole Blood Clinical Specimens
Positive Percent Agreement (PPA) of 100% (50/50; 95% CI = 92.9-100%).
Negative Percent Agreement (NPA) of 100% (50/50; 95% CI = 92.9-100%).
Sputum Clinical Specimens
Positive Percent Agreement (PPA) of 100% (49/49; 95% CI = 92.8-100%).
Negative Percent Agreement (NPA) of 96.1% (49/51; 95% CI = 86.5-99.5%).
Limit of Detection
Whole Blood: 1500 CFU/mL, 20/20 positive results (100.0%).
Sputum: 2000 CFU/mL, 19/20 positive results (95.0%).
Reproducibility - Whole Blood
Medium Positive (5x LoD): 100% agreement (96/96) across all sites.
Low Positive (1x LoD): 86.5% agreement (83/96) across all sites, with 5/96 uncertain results.
Negative: 100% agreement (96/96) across all sites.
Reproducibility - Sputum
Medium Positive (5x LoD): 100% agreement (90/90) across all sites.
Low Positive (1x LoD): 97.8% agreement (88/90) across all sites, with 1/90 uncertain result.
Negative: 100% agreement (90/90) across all sites.
Detection of Direct Culture Samples
F. tularensis colonies: 10/10 positive results.
Non-F. tularensis colonies: 0/10 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
§ 866.3280
Francisella tularensis serological reagents.(a)
Identification. Francisella tularensis serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toFrancisella tularensis in serum or to identifyFrancisella tularensis in cultured isolates derived from clinical specimens. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyFrancisella tularensis directly from clinical specimens. The identification aids in the diagnosis of tularemia caused byFrancisella tularensis and provides epidemiological information on this disease. Tularemia is a desease principally of rodents, but may be transmitted to humans through handling of infected animals, animal products, or by the bites of fleas and ticks. The disease takes on several forms depending upon the site of infection, such as skin lesions, lymph node enlargements, or pulmonary infection.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.
0
JUL 3 1 2013
10 510(k) Summary
510(k) Summary BioFire Diagnostics, Inc.
Modification of the JBAIDS Tularemia Detection Kit for use with the IT 1-2-37M 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 25, 2013
Device Name and Classification:
Trade Name: JBAIDS Tularemia Detection Kit Regulation Number: 21 CFR 866.3280
Classification Name: Reagent Kit: F. tularensis, Class II
Product Code: OEH
Predicate Device:
JBAIDS Tularemia Detection Kit (K072547)
Intended Use:
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Tularemia 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 Francisella tularensis. The system can be used to test human whole blood collected in sodium citrate
1
or sputum collected aseptically from individuals greater than 18 years of age suspected of having tularemia. In addition, positive blood cultures and colonies may be tested. This assay is intended to aid in the diagnosis of individual presenting with signs and symptoms of pneumonic or typhoidal tularemia. It is not intended to aid in the diagnosis of glandular, ulceroglandular, oculoglandular, or oropharyngeal tularemia.
The JBAIDS Tularemia Detection Kit is run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of F. tularensis in conjunction with culture and other laboratory tests. The definitive identification of F. tularensis from colony growth. liguid blood culture growth, blood specimens, 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 tularemia must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of the target either from colonies, blood culture whole blood or sputum specimens.
The JBAIDS Tularemia Detection Kit is intended for use by trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Tularemia Detection Kit. The level of F. tularensis that would be present in blood or sputum from individuals with early systemic or pneumonic infection is unknown. Due to the difficulty in obtaining clinical specimens, this assay was not evaluated with blood or sputum from individuals presenting with signs and symptoms of tularemia who have subsequently developed pneumonic or typhoidal tularemia pneumonic or typhoidal tularemia.
Device Description:
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Tularemia Detection System is a fully integrated IVD system composed of the portable JBAIDS instrument, laptop computer and software and the JBAIDS Tularemia Detection Kit with one freeze-dried PCR assay for detection of Francisella tularensis DNA. The system has been validated using four different sample preparation kits for isolating DNA from whole blood (IT /-2-3TM Platinum Path and QFLOWana Sample Purification Kits), sputum (IT I-2-3TM Platinum Path and IT 1-2-3TM VIBE Sample Purification Kits), positive blood cultures (IT 1-2-3 TM SWIPE Sample Purification Kit), and plate cultures (IT /-2-3TM Platinum Path and IT 1-2-3TM 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 I-2-3 Sample Purification Kits. The resulting purified sample is added to Unknown and Inhibition Control vials, along with reconstitution buffer. Positive Control and Negative Control vials are prepared using reconstitution buffer and water. When F. tularensis DNA is present, a fragment of F. tularensis 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 tetramethyIrhodamine (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
2
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.
Substantial Equivalence:
The JBAIDS Tularemia Detection Kit is substantially equivalent to the previously cleared JBAIDS Tularemia Detection Kit. The following tables compare the modified JBAIDS Tularemia Detection Kit to the previously cleared JBAIDS Tularemia Detection Kit (K072547). The first table outlines the similarities between the two systems and the second table outlines the differences.
| Element | New Device:
JBAIDS Tularemia Detection Kit
with addition of Platinum Path
Sample Purification Kit | Predicate:
JBAIDS Tularemia Detection Kit
(K072547) |
|----------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------|
| Intended Use | Presumptive identification of Tularemia
infection through the detection of a
DNA sequence unique to Francisella
tularensis. Results are used in
conjunction with clinical information,
culture, and other laboratory tests as an
aid in the diagnosis individuals
presenting with signs and symptoms of
pneumonic or typhoidal tularemia. | Same |
| Technology | Real-time PCR using hydrolysis probes | Same |
| Organism
Detected | Qualitative in vitro detection of
Francisella tularensis 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 tularemia,
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
3
| Element | New Device:
JBAIDS Tularemia Detection Kit
with addition of Platinum Path
Sample Purification Kit | Predicate:
JBAIDS Tularemia Detection Kit
(K072547) |
|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------|
| DNA
Extraction
Methods | Whole blood purified with IT 1-2-3TM
Platinum Path or IT 1-2-3TM QFLOWdna
Sample Purification Kits (or validated
equivalent): | Whole blood purified with IT 1-2-3TM
QFLOWdna Sample Purification Kit (or
validated equivalent). |
| | Sputum purified with IT 1-2-3TM
Platinum Path or IT 1-2-3TM VIBE
Sample Purification Kits (or validated
equivalent). | Sputum purified with IT 1-2-3TM VIBE
Sample Purification Kits (or validated
equivalent). |
| | Blood culture purified with IT 1-2-3TM
SWIPE Sample Purification Kit (or
validated equivalent). | Same |
| | Direct bacterial culture purified with IT
1-2-3TM Platinum Path or IT 1-2-3TM
SWIPE Sample Purification Kit (or
validated equivalent). | Direct bacterial culture purified with IT
1-2-3TM SWIPE Sample Purification Kit
(or validated equivalent). |
Summary of Performance Data
Clinical Performance
True clinical specimens from patients infected with Francisella tularensis (tularemia), are not available for testing due to the extreme rarity of natural infection with this organism. Therefore, two clinical evaluations using surrogate specimens were performed to validate the use of the IT 1-2-3TM Platinum Path Sample Purification Kit with the JBAIDS Tularemia Detection Kit.
Testing of Surrogate Whole Blood Clinical Specimens
One hundred (100) surrogate whole blood specimens 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 F. tulurensis at concentrations near and above the system LoD, while the remaining 50 specimens were not spiked with F. tularensis. The level of inactivated F. tularensis used to spike these samples was relative to the LoD (1500 CFU/mL) established for Platinum Pathpurified whole blood specimens.
Once spiked, samples were then processed using both the new nucleic acid extraction method (Platinum Path) and the original nucleic acid extraction method (IT 1-2-37M QFLOWdana Sample Purification Kit; QFLOWdad) followed by testing with the JBAIDS Tularemia 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. The results obtained with the Platinum Path processed samples were compared to the results obtained with the
4
QFLOW 400 processed samples. The JBAIDS result for a sample purified using from the OFLOWana kit was considered the correct result. The final Tularemia interpretation for samples purified using the Platinum Path kit had a positive percent agreement (PPA) of 100% as compared to samples purified using the QFLOW(00 kit (50/50; 95% CI = 92.9-100%). The final JBAIDS Tularemia interpretation for samples purified using Platinum Path was negative for 50 out of 50 samples that were negative when purified using OFLOWdag. This represents a negative percent agreement (NPA) of 100% (50/50; 95% CI = 92.9-100%). Using samples spiked near the LoD for samples purified with the Platinum Path kit (1500 CFU/mL), the IT /-2-3 QFLOWd10 and Platinum Path Sample Purification Kits performed equivalently with respect to detection of F. tulgrensis in surrogate whole blood specimens tested with the JBAIDS Tularemia Detection Kit.
Table 3. JBAIDS Tularemia Detection Kit Performance on Spiked Whole Blood Samples Processed with the IT 1-2-3 Platinum Path and OFLOWda2 Sample Purification Kits
| Positive Agreement | Negative Agreement | ||||||
|---|---|---|---|---|---|---|---|
| QFLOW + | |||||||
| Platinum | |||||||
| Path + | QFLOW + | ||||||
| Platinum | |||||||
| Path - | PPA | 95% CIª | QFLOW - | ||||
| Platinum | |||||||
| Path - | QFLOW - | ||||||
| Platinum | |||||||
| Path + | NPA | 95% CIª | |||||
| 50 | 0 | 100% | |||||
| (50/50) | 92.9- | ||||||
| 100% | 50 | 0 | 100% | ||||
| (50/50) | 92.9- | ||||||
| 100% |
4 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.
Testing of Surrogate Sputum Clinical Specimens
One hundred (100) surrogate specimens were prepared using frozen residual sputum specimens. Fifty (50) of the specimens were spiked with inactivated F, tularensis at concentrations near and above the system LoD, while the remaining 50 specimens were not spiked with F. tularensis. 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 VIBE Sample Purification Kit) followed by testing with the JBAIDS Tularemia Detection Kit. JBAIDS operators were blinded to the analyte content of the samples. Table 4 presents the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) for the surrogate sputum specimen testing. The results obtained with the Platinum Path processed samples were compared to the results obtained with the VIBE processed samples. The JBAIDS result for a sample purified using from the VIBE kit was considered the correct result. The final Tularemia result for samples purified using the Platinum Path kit had a positive percent agreement (PPA) of 100% as compared to samples purified using VIBE (49/49; 95% CI = 92.8-100%). The final JBAIDS Tularemia result for samples purified using Platinum Path was negative for 49 out of 51 samples that were negative when purified using VIBE. This represents a negative percent agreement (NPA) of 96.1% (49/51; 95% CI = 86.5-99.5%). The IT J-2-3 VIBE and Platinum Path Sample Purification Kits performed equivalently with respect to detection of F. tularensis in surrogate sputum specimens tested with the JBAIDS Tularemia Detection Kit.
5
| Positive Agreement | Negative Agreement | ||||||
|---|---|---|---|---|---|---|---|
| VIBE + | |||||||
| Plat Path |
- | VIBE +
Plat Path
- | PPA | 95% CIª | VIBE -
Plat Path - | VIBE -
Plat Path
- | NPA | 95% CIª |
| 49 | 0 | 100%
(49/49) | 92.8-
100% | 49 | 2b | 96.1%
(49/51) | 86.5-
99.5% |
Table 4. JBAIDS Tularemia Detection Kit Performance on Spiked Sputum Samples Processed with the IT 1-2-3 Platinum Path and VIRE Sample Purification Kits
4 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.
False positive results obtained for one unspiked sample processed with Platinum Path, and for one sample spiked at the 1× LoD level (positive result after Platinum Path processing, but negative after VIBE processing). 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 comparative result for a sample spike at the 1× LoD level.
Selected Analytic Studies
Limit of Detection
The originally established LoD of 300 CFU/mL in whole blood purified using the IT I-2-3 OFLOW" Sample Purification Kit could not be confirmed using the Platinum Path Sample Purification Kit. Therefore, the system LoD for whole blood samples was increased by five-fold to 1500 CFU/mL. Twenty out of 20 independent whole blood specimens spiked with F. tularensis at the new LoD level and processed with the IT 1-2-3 Platinum Path Sample Purification Kit were detected with the JBAIDS Tularemia Detection Kit, establishing the new system LoD of 1500 CFU/mL F. tularensis in whole blood.
Nineteen (19) out of 20 independent sputum specimens spiked with F. tularensis at the LoD level and processed with the IT 1-2-3 Platinum Path Sample Purification Kit were detected with the JBAIDS Tularemia Detection Kit. This confirmed the LoD of 2000 CFU/mL in sputum that was originally established for sputum samples processed using the IT /-2-3 VIBE Sample Purification Kit.
| Sample
Matrix | Spiked F. tularensis
Concentration
(CFU/mL) | # Positive | %
Positive | Tularemia Target
Assay Mean Cp
+/- Std Dev |
|------------------|---------------------------------------------------|------------|---------------|--------------------------------------------------|
| Whole Blood | 1500a | 20/20 | 100.0% | 36.50 ± 1.81 |
| Sputum | 2000 | 19/20 | 95.0% | 36.47 ± 1.70 |
Table 5. Confirmation of the F. tularensis LoDs for Platinum Path-Purified Whole Blood and Sputum Samples Tested with the JBAIDS Tularemia Detection Kit
4 The JBAIDS Tularemia LoD determined in Platinum Path-purified whole blood samples is five-fold greater (indicating decreased sensitivity) than the originally established JBAIDS Tularemia LoD determined in QFLOWana-purified whole blood samples.
6
Reproducibility
A multicenter study was performed to determine the overall system reproducibility when whole blood and sputum samples were processed with the IT /-2-3 Platinum Path Sample Purification Kit prior to testing with the JBAIDS Tularemia 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 F. tularensis at a medium positive (5× LoD) level, four samples spiked at a low positive level (1× LoD), and four samples that were not spiked. The level of inactivated F. tularensis used to spike these samples was relative to the system LoD (1500 CFU/mL) established for Platinum Path-purified whole blood specimens. Results for whole blood testing are summarized in Table 6. Samples spiked F. tularensis at the low positive (1× LoD) level yielded final positive results 86.5% of the time overall. Examination of Cp values indicates these samples were likely under-spiked to approximately the 0.5× LoD level, where detection is expected to be below 95%. Detection at this low positive level was reproducibly less than 100% across the sites, and the JBAIDS Tularemia Detection System is reproducible when used to test whole blood samples processed with the IT /-2-3 Platinum Path Sample Purification Kit.
| Blood Spike Levela | Test Location | Number Positive | Number Uncertain | Number Negative | % Agreement with Expected Result | 95% CI | Mean Cpb | Std Dev | %CV |
|---|---|---|---|---|---|---|---|---|---|
| Medium Positive (5× LoD) | Site 1 | 32/32 | 0/32 | 0/32 | 100% | 35.16 | 0.77 | 2.19 | |
| Site 2 | 32/32 | 0/32 | 0/32 | 100% | 35.83 | 1.40 | 3.91 | ||
| Site 3 | 32/32 | 0/32 | 0/32 | 100% | 33.88 | 1.34 | 3.96 | ||
| All Sites | 96/96 | 0/96 | 0/96 | 100% | 96.2-100 | 35.00 | 1.43 | 4.09 | |
| Low Positive (1× LoD) | Site 1 | 28/32 | 0/32 | 4/32 | 87.5% | 38.47 | 2.31 | 6.00 | |
| Site 2 | 24/32 | 5/32 | 3/32 | 75% | 39.38 | 2.32 | 5.89 | ||
| Site 3 | 318/32 | 0/32 | 1/32 | 96.9% | 36.53 | 2.32 | 6.35 | ||
| All Sites | 83/96 | 5/96 | 8/96 | 86.5%h | 78.0-92.6 | 38.13 | 2.59 | 6.79 | |
| Negative | Site 1 | 0/32 | 0/32 | 32/32 | 100% | ||||
| Site 2 | 0/32 | 0/32 | 32/32 | 100% | |||||
| Site 3 | 0/32 | 0/32 | 32/32 | 100% | |||||
| All Sites | 0/96 | 0/96 | 96/96 | 100% | 96.2-100 |
Table 6. Reproducibility of the Tularemia Target Assay in the JBAIDS Tularemia Detection Kit for Whole Blood Samples Purified with the IT 1-2-3 Platinum Path Purification Kit
4 The level of inactivated F. ularensis used to spike these samples was relative to the reset system LoD (1500 CFU/mL) established for Platinum Path-purified whole blood specimens.
0 Co values included for the samples that amplified only.
& Three results were initially uncertain but were positive when retested.
d Two results were initially uncertain but were negative when retested.
e Eight results were initially uncertain but were positive when retested.
f Five results were initially uncertain and were uncertain when retested.
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8Three results were initially uncertain but were positive when retested.
4 Samples spiked at the low positive level (1× LoD) yielded final positive results 86.5% of the time overall, with retesting required for initial uncertain results reproducibly observed at all three sites. Examination of Cp values indicates these samples were likely under-spiked to approximately the 0.5× LoD level, where detection is expected to be below 95%.
A panel of 9 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 F. tularensis at a medium positive (5×LoD) level, three samples spiked at a low positive level (1×LoD), and three samples that were not spiked. Results for sputum testing are summarized in Table 7. The detection rate was ≥97.8% for all sputum samples containing F. tularensis spiked near or above the LoD, and there were no false positive results for unspiked samples. The JBAIDS Tularemia Detection System is reproducible when used to test sputum samples processed with the IT 7-2-3 Platinum Path Sample Purification Kit.
Table 7. Reproducibility of the Tularenia Target Assay in the JBAIDS Tularemia Detection Kit for Sputum Samples Purified with the IT 1-2-3 Platinum Path Purification Kit
| Sputum Spike Level | Test Location | Number Positive | Number Uncertain | Number Negative | % Agreement with
Expected Result | 95% CI | Mean Cpa | Std Dev | %CV |
|--------------------------|---------------|-----------------|------------------|-----------------|-------------------------------------|-----------|----------|---------|------|
| Medium Positive (5× LoD) | Site 1 | 30/30 | 0/30 | 0/30 | 100% | | 35.35 | 1.46 | 4.13 |
| | Site 2 | 30/30 | 0/30 | 0/30 | 100% | | 34.65 | 0.66 | 1.90 |
| | Site 3 | 30/30 | 0/30 | 0/30 | 100% | | 34.37 | 0.53 | 1.54 |
| | All Sites | 90/90 | 0/90 | 0/90 | 100% | 96.0-100 | 34.79 | 1.05 | 3.02 |
| Low Positive (1× LoD) | Site 1 | 28b/30 | 1c/30 | 1/30 | 93.3% | | 39.19 | 2.62 | 6.69 |
| | Site 2 | 30d/30 | 0/30 | 0/30 | 100% | | 38.49 | 2.37 | 6.16 |
| | Site 3 | 30e/30 | 0/30 | 0/30 | 100% | | 38.15 | 2.22 | 5.82 |
| | All Sites | 88/90 | 1/90 | 1/90 | 97.8% | 92.2-99.7 | 38.60 | 2.43 | 6.30 |
| Negative | Site 1 | 0/30 | 0/30 | 30/30 | 100% | | | | |
| | Site 2 | 0/30 | 0/30 | 30/30 | 100% | | | | |
| | Site 3 | 0/30 | 0/30 | 30/30 | 100% | | | | |
| | All Sites | 0/90 | 0/90 | 90/90 | 100% | 96.0-100 | | | |
4 Cp values included for the samples that amplified only.
Four results were initially uncertain but were positive when retested.
C One result was initially uncertain and was uncertain when retested.
d Two results were initially uncertain but were positive when retested.
& One result was initially uncertain and was positive when retested.
Detection of Direct Culture Samples Processed with the IT 1-2-3 Platinum Path Sample Purification Kit
F. tularensis colonies can be detected using a Platinum Path protocol to process the colonies followed by testing with the JBAIDS Tularemia Detection Kit. Ten F. tularensis
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colonies were purified alongside ten non- F. tularensis colonies. All ten F. tularensis colonies were detected with the JBAIDS Tularemia Detection Kit, while the non- F. tularensis colonies were not detected.
| Colony Type | Tularemia Target | ||
|---|---|---|---|
| Positive Results/Total | Cp (cycles) | ||
| Mean | SD | ||
| F. tularensis | 10/10 | 21.00 | 0.31 |
| Non- F. tularensis | 0/10 | - | - |
Table 8. Tularemia Target Detection from Colonies Purified with Platinum Path
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
CYNTHIA PHILLIPS, Ph.D. MANAGER, JBAIDS REGULATED PRODUCTS BIOFIRE DIAGNOSTICS, INC. 390 WAKARA WAY SALT LAKE CITY UT 84108
July 31, 2013
Re: K131936
Trade/Device Name: JBAIDS Tularemia Detection Kit Regulation Number: 21 CFR 866.3280 Regulation Name: Francisella tularensis Serological Reagents Regulatory Class: II Product Code: OEH Dated: June 25, 2013 Received: June 27, 2013
Dear Dr. Phillips:
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.
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Page 2-Ms. 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.lda.gov/MedicalDevices/ResourcesforYou/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/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometries/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 for
Sally A. Hojvat, 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): K131936 Device Name: JBAIDS Tularemia Detection System
The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Tularemia 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 Francisella tularensis. The system 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 tularemia. In addition, positive blood cultures and colonies may be tested. This assay is intended to aid in the diagnosis of individual presenting with signs and symptoms of pneumonic or typhoidal tularemia. It is not intended to aid in the diagnosis of glandular, ulceroglandular, oculoglandular, or oropharyngeal tularemia.
The JBAIDS Tularemia Detection Kit is run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of F. tularensis in conjunction with culture and other laboratory tests. The definitive identification of F, tularensis from colony growth, liquid blood culture growth, blood specimens, 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 tularemia must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of the target either from colonies, blood culture, whole blood or sputum specimens.
The JBAIDS Tularemia Detection Kit is intended for use by trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Tularemia Detection Kit. The level of F. tularensis that would be present in blood or sputum from individuals with early systemic or pneumonic infection is unknown. Due to the difficulty in obtaining clinical specimens. this assay was not evaluated with blood or sputum from individuals presenting with signs and symptoms of tularemia who have subsequently developed pneumonic or typhoidal tularemia pneumonic or typhoidal tularemia.
Prescription Use (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
Page 1 of 2
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Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
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