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The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Anthrax Detection System is a real-time polymerase chain reaction (PCR) test system intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences on the pXO1 plasmid (Target 1) and the pXO2 plasmid (Target 2) from Bacillus anthracis. The system can be used to test the following:

• Human whole blood collected in sodium citrate from individuals suspected of having anthrax
• Positive blood cultures
• Cultured organisms grown on blood agar plates.
  The JBAIDS Anthrax Target 2 assay is used as a supplementary test only after a positive result with the Target 1 Assay.
  The JBAIDS Anthrax Target 1 and Target 2 Assays are run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of B. anthracis, in conjunction with culture and other laboratory tests. The following considerations also apply:
• The diagnosis of anthrax infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence, in addition to the identification of pXO1 and pXO2 targets either from cultures or from direct blood specimens.
• The assays have not been evaluated with blood from individuals without clinical signs or symptoms who were presumed exposed and who subsequently developed anthrax (inhalation or other forms of the disease), or from individuals with any form of anthrax (inhalational, cutaneous, or gastrointestinal).
• The level of plasmid targets that would be present in blood from individuals with early systemic infection is unknown.
• The definitive identification of B. anthracis from colony growth, liquid blood culture growth, or from blood specimens requires additional testing and confirmation procedures in consultation with public health or other authorities for whom reports are required.
  The safety and effectiveness of other types of tests or sample types (not identified as "For in vitro diagnostic use") have not been established.

The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Anthrax Detection System is a fully integrated IVD system composed of the portable JBAIDS instrument, laptop computer and software, the JBAIDS Anthrax Detection Kit with two different freeze-dried PCR assays for detection of pathogenic Bacillus anthracis DNA. The system has been validated using four different sample preparation kits for isolating DNA from whole blood (IT 1-2-3TM Platinum Path, QFLOWdma, FLOW Sample Purification Kits), positive blood cultures (IT I-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 B. anthracis DNA is present, a fragment of B. anthracis 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.

Here's a breakdown of the acceptance criteria and study information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The submission primarily focuses on demonstrating equivalence of a new DNA extraction method (Platinum Path) to an existing one (QFLOWdna) for use with the JBAIDS Anthrax Detection Kit. Therefore, the "acceptance criteria" are implicitly defined by the performance of the predicate device with the QFLOWdna kit, and the "reported device performance" is how the new Platinum Path kit compares.

2. Sample Size Used for the Test Set and Data Provenance

• Clinical Performance (Surrogate Whole Blood):

  • Sample Size: 100 surrogate whole blood specimens (50 spiked with B. anthracis, 50 not spiked). Each sample was processed by both new (Platinum Path) and old (QFLOWdna) extraction methods and then tested.
  • Data Provenance: Prospectively collected from febrile volunteers in the USA (November 2012 to April 2013). These were surrogate specimens spiked with inactivated B. anthracis, not true clinical anthrax samples.

• Limit of Detection:

  • Sample Size: 20 independent whole blood specimens, each spiked with B. anthracis at the LoD level.
  • Data Provenance: Not explicitly stated, but implied to be laboratory-prepared samples for analytical validation.

• Reproducibility:

  • Sample Size: A panel of 12 blood samples (4 medium positive, 4 low positive, 4 negative). Each sample was tested twice a day for four days at each of three testing sites. Total individual tests for each target would be 12 samples * 2 tests/day * 4 days * 3 sites = 288 for each target (Target 1 and Target 2).
  • Data Provenance: Multicenter study, locations are "Site 1, Site 2, Site 3." Country of origin not explicitly stated, but typically assumed to be domestic for FDA submissions unless otherwise specified.

• Detection of Direct Culture Samples:

  • Sample Size: 10 B. anthracis colonies and 10 non-B. anthracis colonies.
  • Data Provenance: Not explicitly stated, but implied to be laboratory-prepared cultures.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

The ground truth for the surrogate clinical specimens and analytical studies was established by:

• Spiking Status: Knowing which samples were spiked with inactivated B. anthracis and at what concentration, and which were not. This is a controlled laboratory process, not dependent on human expert interpretation for definitive classification.
• Predicate Device Performance: For the surrogate clinical specimens, the "correct result" was defined by the JBAIDS result when processed with the QFLOWdna kit, which is the predicate/established method. This avoids the need for external expert consensus on the B. anthracis status of a sample that has already been spiked.

Therefore, no external clinical experts were used to establish the ground truth in the traditional sense for these studies. The ground truth was based on the controlled spiking of samples and comparison to an established method.

4. Adjudication Method for the Test Set

Not applicable in the traditional sense. The "ground truth" for the surrogate clinical specimens was determined by the results from the predicate extraction method (QFLOWdna), and for the analytical studies, it was determined by the known spiking status of the samples. There was no need for expert adjudication of conflicting results as the comparison was against a predetermined "truth."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This device is a molecular diagnostic test for B. anthracis DNA, not an imaging device that would typically involve human readers interpreting images. The study focuses on the analytical and clinical (surrogate) performance of the extraction method and PCR kit.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies presented are standalone (algorithm only). The JBAIDS system, with its software, analyzes the fluorescence amplification curves and reports results (positive, negative, uncertain, inhibited). The operators were blinded to the analyte content, meaning their human "interpretation" was limited to running the instrument and following its automated output. The performance metrics (PPA, NPA, LoD, reproducibility) are based directly on the device's output.

7. The Type of Ground Truth Used

• Clinical Performance (Surrogate Whole Blood): Known spiking status of the samples from a laboratory perspective, and the performance of the predicate DNA extraction method (QFLOWdna) as the "correct result" for comparison.
• Limit of Detection: Known concentration of spiked B. anthracis in laboratory-prepared whole blood specimens.
• Reproducibility: Known concentration of spiked B. anthracis (medium, low, or unspiked).
• Detection of Direct Culture Samples: Known identity of the bacterial colonies (either B. anthracis or non-B. anthracis) through laboratory culture and identification.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for the device itself. This submission is for modifications to an existing device (the JBAIDS Anthrax Detection Kit) by adding compatibility with a new sample purification kit (IT 1-2-3 Platinum Path). The JBAIDS system and its algorithm were presumably developed and validated previously. The studies described here are a validation of the new sample preparation method, not the training of a new algorithm.

9. How the Ground Truth for the Training Set Was Established

Since there is no explicit mention of a "training set" for a new algorithm within this submission, this question is not directly applicable. The JBAIDS Anthrax Detection System already existed and was previously cleared (K051713 and K071188). The ground truth for its initial development and validation would have followed similar principles of known positive and negative samples, likely through spiking and confirmed cultures, as is typical for molecular diagnostic assays.

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