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The TruDiagnosis® System is an in vitro diagnostic device intended for processing and genotyping multiple genetic variants in a DNA sample utilizing on-slide PCR gel-drop microarray technology. The TruDiagnosis® System consists of the TruDx® 2000 Imager, the TruArray® Warfarin Sensitivity Test Kit, and the ProFlex™ PCR System using the ProFlex™ 2x Flat Sample Block.

The TruDx® 2000 Imager is an instrument intended for processing and genotyping multiple genetic variants in a DNA sample utilizing on-slide PCR gel-drop microarray technology.

The TruArray® Warfarin Sensitivity Test Kit is an in vitro diagnostic test for the detection and genotyping of the 2C92, 2C93 alleles of the cytochrome P450 (CYP450) 2C9 gene locus and Vitamin K epoxide reductase CL, VKORCI, gene promoter polymorphism (-1639) from genomic DNA of human saliva samples collected using the Oragene® Dx Device (OGD-500) as an aid in the identification of patients at risk for increased warfarin sensitivity. The TruArray® Warfarin Sensitivity Test Kit is a qualitative assay for use in clinical laboratories upon prescription by the attending physician.

The TruDiagnosis® System is an in vitro diagnostic device intended for processing and genotyping multiple genes in a DNA sample utilizing on-slide Polymerase Chain Reaction (PCR) gel-drop microarray technology. The TruDiagnosis® System consists of the:

• Hardware: TruDx® 2000 Imager ●
• Software: TruSpot™ Software ●
• . Test Kit: TruArray® Warfarin Sensitivity Test Kit
  • TruArray® Test Slide o
  • o TruPlex™ reagents
• Thermal Cycler: ProFlex™ PCR System using the ProFlex™ 2x Flat Sample Block ●

Hardware: Akonni's microarray imager (TruDx®2000) is an instrument that consists of a highintensity green light emitting diode (LED), custom optics, and a digital grayscale camera.

• . The purpose of the TruDx® 2000 Imager is to capture a fluorescence image of the microarray after completing the test.
• The user inserts the TruArray® Test Slide into the TruDx® 2000 Imager and follows . the on-screen prompts. The resulting microarray image is automatically analyzed and reported with the TruSpot™ Software.

Software: Akonni's TruSpot™ Software, integrated within the imager, locates and segments each fluorescently labeled microarray Gel-Element and reports signal-to-noise ratios (SNR). Assay results interpreted by TruSpot™ Software program are assigned a genotype and presented to the end user in a report format.

Test Kit: The TruArray® Warfarin Sensitivity Test Kit includes consumables and reagents necessary to perform multiplex on-slide PCR amplification, and fluorogenic target-specific microarray-based hybridization. Specifically:

• The TruArray® Test Slide (loaded with target DNA) undergoes thermal cycling via . asymmetric amplification to enrich single stranded fluorescently labeled complimentary strands to capture probes printed on the microarray (asymmetric PCR and allele specific hybridization occur in the same chamber). After hybridization, arrays are washed and dried, and the user then inserts the microarray into the TruDx® 2000 Imager and follows the on-screen prompts.

The warfarin assay performed with the test kit is an in vitro diagnostic test for the detection and genotyping of the 2C92, 2C93 alleles of the cytochrome P450 (CYP450) 2C9 gene locus and Vitamin K epoxied reductase C1, VKORC1 3673, gene promotor polymorphism (-1639) mutations from genomic DNA of human saliva samples collected using the Oragene® Dx OGD-500 Device (K110701).

Thermal Cycler: The ProFlex™ PCR System with the ProFlex™ 2x Flat Sample Block, a component of the TruDiagnosis System, is an end-point thermal cycler, specifically designed for the amplification of nucleic acids using the Polymerase Chain Reaction (PCR) process. The user interface includes a touchscreen with a graphical display that shows the time, status, and temperature for each run. A touchscreen keypad allows you to enter information into fields on the display screen.

Here's an analysis of the acceptance criteria and the studies that prove TruDiagnosis® System meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Based on the provided document, the acceptance criteria are not explicitly stated as distinct pass/fail thresholds in simple terms. Instead, the studies demonstrate the device's performance, aiming for high "Correct Call Rate" and agreement with Sanger sequencing, especially after addressing "No Calls". A reasonable interpretation of the implicit acceptance criteria, based on the studies, would be a high percentage of accurate genotype calls and 100% concordance with the reference method (Sanger sequencing) upon resolution of initial "No Calls".

• 125 ng: 98.4% Correct Call Rate (96.8% LCB)
• 25 ng: 98.3% Correct Call Rate (96.7% LCB)
• 2.5 ng: 94.4% Correct Call Rate (92.0% LCB)
• 0.25 ng: 64.7% Correct Call Rate (60.4% LCB)
  Final Result (after repeating No Calls):
• 125 ng, 25 ng, 2.5 ng: 100.0% Correct Call Rate (99.2% LCB or higher)
• 0.25 ng: 63.9% Correct Call Rate (59.6% LCB) - Incorrect calls were not repeated at this concentration. |
  | Method Comparison | 100% agreement with bi-directional DNA sequencing. | First Pass Calls (Overall): 98.7% Correct Call Rate (97.0% LCB).
  Final Result (after repeating No Calls): 99.7% Correct Call Rate (98.4% LCB). "All 3 No Calls were resolved upon the second repeat runs. The Final Results yielded 100% agreement between the TruArray® Warfarin Sensitivity Test Kit results and bi-directional DNA sequencing." (One incorrect call was identified as a sample mix-up, and not re-run). |
  | Endogenous Interference | 100% agreement with bi-directional DNA sequencing. | Final Results (after repeating No Calls): 100.0% agreement between the TruArray® Warfarin Sensitivity Test Kit results and bi-directional DNA sequencing for all test substances, demonstrating no effect of any interfering substances on genotyping. |
  | Exogenous Interference | 100% agreement with bi-directional DNA sequencing. | Final Results (after repeating No Calls): 100.0% agreement between the TruArray® Warfarin Sensitivity Test Kit results and bi-directional DNA sequencing. |
  | Reproducibility | 100% correct call rate across sites, operators, and lots after repeating No Calls. | First Pass Results (Overall): 84.2% (by sample genotype), 85.8% (by SNPs across all loci).
  Final Results (after repeating No Calls): 100.0% Correct Call Rate across all sample genotypes, sites, operators, and lots (95.1% LCB or higher, 99.2% overall LCB for genotypes, 99.7% overall LCB for SNPs). |

2. Sample Sizes and Data Provenance for Test Set

• Limit of Detection Study:

  • Sample Size: 3 genomic DNA samples (Donors 1, 2, 3), tested at various concentrations with 40 replicates each (total 3 * 4 * 40 = 480 replicates for initial runs, but 362 samples were ultimately tested, implying some initial runs were repeated due to control failures, and some individual test samples were re-run).
  • Data Provenance: Genotypes for these 3 donors are provided (*1/*1, *1/*3, AA; *1/*2, *1/*3, AG; *2/*2, *1/*1, GG). The origin of these DNA samples (e.g., country) is not specified. It is a retrospective study since the DNA samples were presumably pre-collected and genotyped by Sanger sequencing.

• Method Comparison Study:

  • Sample Size: 303 unique human genomic DNA samples.
  • Data Provenance: Origin of the data (e.g., country) is not specified, but the samples were isolated from human saliva specimens. It is a retrospective study as the samples were pre-collected using the Oragene® Dx OGD-500 device, extracted, and a reference genotype established.

• Interference Studies (Endogenous and Exogenous):

  • Endogenous: 5 donors, each providing saliva samples, divided into 5 aliquots (spiked with interferents or un-spiked control). Three extractions performed on each spiked/un-spiked sample. (Total 5 donors * 5 conditions * 3 extractions = 75 samples).
  • Exogenous: 5 activity groups (Eating, Drinking, Chewing Gum, Mouth Wash, Smoking) with 5 donors each. Each donor provided 2 saliva samples (baseline and 30 min post-activity), tested in triplicate. (Total 5 groups * 5 donors * 2 timepoints * 3 replicates = 150 samples).
  • Data Provenance: Saliva samples from human donors. Origin not specified. Retrospective.

• Reproducibility Study:

  • Sample Size: Six specific saliva samples (genotypes provided in the table). Each sample was processed in triplicate by 4 operators over 5 non-consecutive days (15 tests per operator per genotype). 6 genotypes * 4 operators * 15 tests = 360 samples.
  • Data Provenance: Saliva samples from human donors. Origin not specified. Retrospective for samples, but prospective for the testing process across different sites/operators.

3. Number of Experts and Qualifications for Ground Truth

The document explicitly states that the ground truth for all performance studies (Limit of Detection, Method Comparison, Interference, and Reproducibility) was established by bi-directional Sanger sequencing. It does not mention the use of human experts or their qualifications for establishing this ground truth. Sanger sequencing is a widely accepted gold standard for DNA sequencing and thus acts as the independent reference for genotyping.

4. Adjudication Method for the Test Set

The document describes an adjudication method for "No Calls" found during the initial runs. For "No Calls," the samples were repeated (re-run). Incorrect calls, however, were generally not repeated ("Incorrect Calls were not repeated" in the LoD study footnote, and for the Method Comparison, an incorrect call was attributed to a sample mix-up and "was not re-run"). This indicates an adjudication process where "no-calls" lead to re-testing, but "incorrect calls" (when a result was given but it was wrong) are investigated for root cause and not necessarily re-run for a different result in the study context.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was mentioned. The device, the TruDiagnosis® System, is an in vitro diagnostic device for genotyping, which typically involves laboratory testing rather than interpretation by multiple human readers (like radiology images). Therefore, a multi-reader study is not applicable in this context.

6. Standalone Performance

Yes, a standalone performance study was done. The entire performance evaluation (Limit of Detection, Method Comparison, Interference, Reproducibility) assesses the TruDiagnosis® System (which includes the TruArray® Warfarin Sensitivity Test Kit, TruDx® 2000 Imager, and TruSpot™ Software acting together as an algorithm/system) against an independent reference method (bi-directional Sanger sequencing). This is a direct measure of the algorithm's diagnostic accuracy without human intervention in the genotype interpretation after the system generates a result.

7. Type of Ground Truth Used

The ground truth used for all studies was bi-directional Sanger sequencing.

8. Sample Size for the Training Set

The document does not provide information regarding a training set or its sample size. This is typical for a 510(k) submission where the focus is on the validation of the finished device and its performance characteristics against a predicate, rather than the development and training of the underlying algorithm. The "TruSpot™ Software" is mentioned as integrated within the imager and interpreting assay results, implying it's an algorithmic component, but details on its development or training are not included in this summary.

9. How Ground Truth for the Training Set Was Established

Since no information on a training set is provided, there is no detail on how its ground truth was established.

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Oragene Dx devices are intended for use in the non-invasive collection of saliva samples. Human DNA from the saliva sample is isolated, stabilized, and suitable for use in FDA cleared molecular diagnostic applications. Saliva may be collected by spitting directly into the Oragene Dx container or may be transferred into the Oragene Dx container using a sponge. Saliva samples collected using Oragene Dx are stabilized and can be transported and/or stored long term at ambient conditions.

The Oragene-Dx family of products offers reliable collection, transportation and long-term room temperature storage of human DNA from saliva. Oragene Dx is a non-invasive alternative for collecting high quality and quantity DNA for use in molecular diagnostic applications. Oragene-Dx is a device family available in multiple device formats or models.

Oragene-Dx device formats OGD-510, OGD-600, OGD-610 and OGD-675, have the same collection principle and intended use as the FDA cleared Oragene-Dx formats (K110701). All Oragene-Dx formats consist of a collection tube, a DNA stabilizing liquid and optional sponges for assisted collection. In addition, Oragene·Dx device formats are made from the same physical and chemical materials. Oragene Dx formats differ in the amount of DNA stabilizing liquid in the tube and in the difference in the amount of saliva to be collected. The ratio of final sample to stabilizing liquid volume remains the same.

Saliva collection can take place at home, in a laboratory setting, physician's office, or in the field by untrained (naïve) or professional users. Saliva samples are collected into the device directly by spitting or by using the provided sponges. After saliva is collected, the stabilizing liquid is mixed with the sample. Upon contacting saliva cells, the stabilizing liquid lyses cellular and nuclear membranes to release and stabilize nucleic acids (DNA). Oragene-Dx Samples can be immediately processed, transported or stored for future use. Samples can be shipped at ambient temperature to the laboratory for processing.

Oragene-Dx device pre-collection shelf life is 24 months at room temperature from the date of manufacture. Post collection, Oragene Dx samples are stable at room temperature for up to 12 months. Oragene Dx device performance and sample integrity are maintained during typical ambient transport and storage conditions.

This document (K152556) describes a 510(k) premarket notification for the Oragene®Dx OGD-510, Oragene®Dx OGD-600, Oragene®Dx OGD-610, and Oragene®Dx OGD-675 devices. These devices are intended for the non-invasive collection of saliva samples, from which human DNA can be isolated, stabilized, and used in FDA-cleared molecular diagnostic applications. The submission references studies performed for the predicate device (Oragene®Dx OGD-500, K110701) to support the substantial equivalence of the new devices.

1. Table of acceptance criteria and reported device performance:

Since the document bases its claims on substantial equivalence to a predicate device (K110701) and applicable studies mentioned in that predicate, specific numerical acceptance criteria for the new devices are not explicitly stated in a tabular format within this document. Instead, the document states that the performance of the new devices is "the same as predicate" or that "both OGD-510 and OGD-500 samples met acceptance criteria for DNA concentration, total DNA yield, A260/A280 ratio and performance on the eSensor Warfarin Sensitivity Saliva Test."

The key performance characteristics and their reported outcomes, primarily referencing the predicate K110701, are summarized below:

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

The document refers to studies in the predicate K110701 for most performance characteristics. For the new comparison study performed for OGD-510 vs. OGD-500, the sample size is not explicitly mentioned. The data provenance is implied to be from Canada, as the submitter, DNA Genotek Inc., is located in Ottawa, Ontario, Canada. The studies are retrospective references to the predicate device or a new comparison study.

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

This information is not explicitly provided in the document. The ground truth for comparative performance (genotyping) would likely be established by the "bidirectional sequencing" method, but details on the experts involved in interpreting this or verifying the ground truth for other studies (e.g., stability) are not given.

4. Adjudication method for the test set:

Not applicable or provided for this type of device and performance testing. The "ground truth" for genotyping involved comparison to bidirectional sequencing.

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:

Not applicable. This device is a sample collection and stabilization device, not an AI-assisted diagnostic tool requiring human reader interpretation.

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

Not applicable. This is a physical device for sample collection, not an algorithm. The "performance" refers to the ability to collect and preserve DNA for downstream molecular diagnostic applications. The comparison studies against the eSensor® Warfarin Sensitivity Saliva Test (K110786) are standalone evaluations of the collected sample's compatibility with a molecular diagnostic test.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

For the analytical performance (genotyping agreement), the ground truth was established by bidirectional sequencing. For other performance characteristics like stability and reproducibility, the ground truth would be based on established laboratory methods and controls to demonstrate the integrity and functionality of the DNA.

8. The sample size for the training set:

Not applicable. This device is a physical sample collection device, not an algorithm that requires a training set.

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

Not applicable. No training set is involved for this type of device.

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