LogoFDA 510(k) Search
K Number
K173498
Device Name
Simplexa Bordetella Direct, Simplexa Bordetella Positive Control Pack
Manufacturer
DiaSorin Molecular LLC
Date Cleared
2018-08-13

(273 days)

Product Code
OZZ
Regulation Number
866.3980
Type
Traditional
Panel
MI
Reference & Predicate Devices
K163626
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

Simplexa™ Bordetella Direct MOL2750
The DiaSorin Molecular Simplexa™ Bordetella Direct MOL2750 assay is an in vitro diagnostic test intended for use on the LIAISON® MDX instrument for the qualitative detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids from frozen nasopharyngeal (NPS) specimens from patients with signs and symptoms of Bordetella infection of the respiratory tract.
The Simplexa™ Bordetella Direct assay is performed on the LIAISON® MDX instrument and utilizes realtime PCR amplification to detect B. pertussis by targeting the IS481 insertional element of the B. pertussis genome and to detect B. parapertussis by targeting the IS1001 insertional element of the B. parapertussis genome. The IS481 insertional element can also be present in B. holmesii and B. bronchiseptica. Specimens collected from patients with respiratory infection caused by B. pertussis, B. holmesii or B. bronchiseptica may yield positive test results in IS481 assays. B. holmesii infection may cause clinical illness similar to B. pertussis, and mixed outbreaks involving both B. pertussis and B. holmesii infection have been reported. Additional testing should be performed if necessary to differentiate B. holmesii and B. pertussis. B. bronchiseptica is a rare cause of infection in humans. When clinical factors suggest that B. pertussis may not be the cause of respiratory infection, other clinically appropriate investigation(s) should be carried out in accordance with published guidelines.
Negative results for the Simplexa™ Bordetella Direct assay do not preclude Bordetella infection and positive results do not rule out co-infection with other respiratory pathogens. Results from the Simplexa™ Bordetella Direct assay should be used with other clinical findings and epidemiological information as an aid in diagnosis of Bordetella infection. Test results should not be used as the sole basis for treatment or other patient management decisions.
Simplexa™ Bordetella Positive Control Pack MOL 2760
The Simplexa™ Bordetella Positive Control Pack MOL2760 is intended to be used as a control with the Simplexa™ Bordetella Direct kit. This control is not intended for use with other assays or systems.

Device Description

The Simplexa™ Bordetella Direct assay system is a real-time PCR assay that enables the direct amplification, detection and differentiation of Bordetella pertussis and Bordetella parapertussis DNA from unprocessed nasopharyngeal swabs (NPS) without nucleic acid extraction. The system consists of the Simplexa™ Bordetella Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc and associated accessories.
In the Simplexa™ Bordetella Direct assay, primers and fluorescent probes are used together to amplify and detect Bordetella pertussis, Bordetella parapertussis and internal control targets. Insertion sequences IS481 and IS1001 are targeted to identify Bordetella pertussis and Bordetella parapertussis DNA respectively in the specimen. An internal control is used to detect PCR failure and/or inhibition.
The DiaSorin Molecular Simplexa™ Bordetella Direct kit contains sufficient reagents for 24 reactions. Upon receipt, store at -10 to -30ºC (do not use a frost-free freezer). Each vial contains sufficient material for a single reaction. Use within 30 minutes of thawing.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets those criteria, based on the provided text:

Acceptance Criteria and Reported Device Performance

Criteria CategoryAcceptance Criteria (Implicit)Reported Device Performance
Clinical PerformanceAcceptable Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a composite reference method.**Bordetella pertussis (Prospective Samples):**PPA: 91.9% (68/74); 95% CI: 83.4% to 96.2%NPA: 98.7% (1026/1039); 95% CI: 97.9% to 99.3%**Bordetella parapertussis (Prospective Samples):**PPA: 100.0% (13/13); 95% CI: 77.2% to 100.0%NPA: 99.6% (1096/1100); 95% CI: 99.1% to 99.9%**Bordetella parapertussis (Contrived Samples):**PPA: 100.0% (56/56); 95% CI: 93.6% to 100.0%NPA: 100.0% (56/56); 95% CI: 93.6% to 100.0%
ReproducibilityHigh agreement with expected results across different sites, days, and operators, with low variability (low %CV for Ct values).Overall Agreement with Expected Results: 100.0% (540/540) for all tested panel members (B. pertussis LP, MP; B. parapertussis LP, MP; negative; positive control). 95% CI: 99.3% to 100.0%.
Avg. Ct %CV: Ranged from 0.7% to 3.9% across sites and targets.
Analytical Sensitivity (LoD)Detection of Bordetella species at low concentrations (lowest concentration detected as positive >95% of the time).B. pertussis (strains A639 & BAA-589): 14.7 CFU/mL and 20.9 CFU/mL respectively.
B. parapertussis (strains A747 & E595): 347.3 CFU/mL and 239.0 CFU/mL respectively.
Analytical ReactivityDetection of various Bordetella strains.Twelve B. pertussis strains detected at or below 80 CFU/mL (3/3 detection for all). Six B. parapertussis strains detected at or below 590 CFU/mL (3/3 detection for all). In silico BLAST analysis predicted detection of 294 additional B. pertussis and 5 additional B. parapertussis strains.
Analytical Specificity (Cross-Reactivity)No detection of closely related organisms, organisms causing similar symptoms, or normal flora (except expected cross-reactivity).No cross-reactivity observed with 96 out of 97 tested organisms. Exception: Bordetella holmesii showed 100% detection (8/8) for the B. pertussis (IS481) target, which was expected due to the presence of the IS481 element in B. holmesii.
InterferenceNo interference from common substances found in nasopharynx.No evidence of interference caused by 16 tested substances (e.g., Albuterol, Blood, Mucin) on the detection of B. pertussis or B. parapertussis at 2-4 X LoD. (100% detection for all tested interferences except initial Rifampicin for B. parapertussis, which was resolved with additional replicates)
Competitive InterferenceNo interference between detection of B. pertussis and B. parapertussis when one is present at high concentration and the other at low.Low level of B. pertussis was detected in the presence of a high level of B. parapertussis (3/3 detection for both). Low level of B. parapertussis was detected in the presence of a high level of B. pertussis (3/3 detection for both).
Inhibition by Other MicroorganismsNo inhibition of Bordetella detection when other microorganisms are present.No inhibitory effects observed for B. pertussis and B. parapertussis (at 2X LoD) when spiked with 97 different potentially inhibitory organisms. 100% detection for both targets across all tested organisms including baseline (total of 45 tests for baseline and 3 tests per organism).
Carry-over ContaminationNo carry-over contamination between high positive and negative samples."No evidence of carry-over contamination was observed."

Study Details from the Provided Text:

2. Sample size used for the test set and the data provenance:

  • Test Set Sample Size (Clinical Performance/Method Comparison):
    • 1113 evaluable prospectively collected frozen nasopharyngeal swab (NPS) samples.
    • An additional 112 samples: 56 contrived Bordetella parapertussis samples (at 2-50 X LoD) and 56 negative samples, randomized together.
  • Data Provenance:
    • Country of Origin: Not explicitly stated, but samples were "prospectively collected and frozen from five (5) geographically diverse sites" (Page 7). This often implies within the USA for FDA submissions, but not definitively confirmed.
    • Retrospective or Prospective: Primarily prospective.
      • "One thousand one hundred and forty-two (1142) samples were prospectively collected and frozen..." (Page 7).
      • "The Bordetella pertussis prospectively banked frozen sample results are shown in Table 1." (Page 7).
      • "The Bordetella parapertussis prospectively banked frozen sample results are shown in Table 2 and the Bordetella parapertussis contrived sample results are shown in Table 3." (Page 7).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

  • The text does not specify the number or qualifications of experts directly establishing ground truth. Instead, it describes a "composite reference method."

4. Adjudication method for the test set:

  • The ground truth was established using a "composite reference method [which] consisted of two well-characterized real-time PCR assays followed by confirmation of positive PCR amplification products with bi-directional sequencing, per target."
  • "Samples were characterized as positive if one or both composite reference methods were positive and confirmed by bi-directional sequencing. Samples were characterized as negative if both composite reference methods were negative." (Page 7).
  • This suggests a form of consensus/confirmation, but not a 2+1 or 3+1 expert adjudication in the typical human-in-the-loop sense for imaging. It's an algorithmic/laboratory "adjudication" against established molecular methods.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

  • No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) PCR assay, not an AI-assisted imaging device. Its performance is evaluated directly against a reference method, not in comparison to human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

  • Yes, the primary clinical performance ("Method Comparison") and all analytical studies (Reproducibility, LoD, Reactivity, Specificity, Interference, etc.) represent the standalone performance of the Simplexa™ Bordetella Direct assay. It's an automated molecular diagnostic assay, designed to operate without human interpretation of the primary signal for diagnosis.

7. The type of ground truth used:

  • The ground truth was established using a composite reference method consisting of:
    • Two "well-characterized real-time PCR assays."
    • "Confirmation of positive PCR amplification products with bi-directional sequencing, per target." (Page 7).

8. The sample size for the training set:

  • The document describes performance studies for a finalized device. It does not provide information about a separate "training set" in the context of machine learning, because this is a PCR assay with defined primers and probes, not a machine learning model that requires training data in that sense. The analytical and clinical studies serve to validate the assay's performance.

9. How the ground truth for the training set was established:

  • Not applicable, as this is not a machine learning device with a distinct "training set" ground truth. The development of the assay (designing primers, probes, optimizing conditions) is an engineering process, not a data-driven model training process.

§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.

(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.