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The Xpert® FII & FV test is a qualitative in vitro diagnostic genotyping test for the detection of Factor V alleles from sodium citrate or EDTA anticoagulated whole blood. The test is performed on the GeneXpert® Instrument Systems. This test is intended to provide results for Factor II (G20210A) and Factor V Leiden (G1691A) mutations as an aid in the diagnosis in individuals with suspected thrombophilia.

Xpert FII & FV is an automated genotyping test for detecting Factor II and Factor V normal and mutant alleles directly from sodium citrate or EDTA anticoagulated whole blood specimens. Blood specimens are drawn into either sodium citrate or EDTA anticoagulant tubes. Following brief mixing of the sample. 50 uL of the blood sample is transferred to the bottom wall of the Sample opening of the Xpert FII & FV test cartridge. The user initiates a test from the system user interface and places the cartridge into the GeneXpert Instrument System.

The Xpert FII & FV test includes reagents for the detection of Factor II and Factor V normal and mutant alleles. The primers and probes in the Xpert FII & FV test determine the genotype of the Factor II gene (at position 20210) and/or the Factor V gene (at position 1691). The test includes a Sample Processing Control (SPC) to confirm adequate processing and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The GeneXpert Instrument Systems family is comprised of GeneXpert Dx System, GeneXpert Infinity System, and GeneXpert System with Touchscreen. The GeneXpert Instrument Systems automate and integrate sample processing, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time polymerase chain reaction (PCR). The systems consist of an instrument, computer or touchscreen, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of singleuse disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The GeneXpert Instrument Systems have 1 to 80 modules (depending upon the instrument) that are each capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

The Xpert FII & FV test performed on the GeneXpert Instrument Systems provides results in approximately 30 minutes.

This document is a 510(k) summary for the Xpert FII & FV diagnostic test, seeking to remove a limitation statement and make minor branding/catalog number changes. It does not contain a study explicitly detailing acceptance criteria and performance against those criteria for the current submission. Instead, it refers to prior clearance (K082118) for the clinical validation supporting the removal of the limitation statement, and asserts that the current changes do not impact performance.

Therefore, the following information is extracted or inferred based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance:

The document explicitly states: "No new performance data were provided in this submission." The basis for substantial equivalence relies on the device being identical to its predicate (K223046) in all technological characteristics relevant to performance. The one significant change (removal of the pediatric patient limitation) is supported by prior clinical validation data (K082118). Since no new performance data or acceptance criteria are presented for this specific submission, this table cannot be fully completed from the provided text.

However, based on the nature of a genetic mutation detection system, typical acceptance criteria would involve analytical sensitivity, analytical specificity, and clinical performance (e.g., concordance with a gold standard). Without the original K082118 submission, specific numerical criteria are not available.

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

• Sample Size: Not explicitly stated in this document. The document refers to "clinical validation data that was submitted and reviewed as part of the original device clearance (K082118)" as the basis for removing the pediatric limitation. The sample size for that original study is not provided here.
• Data Provenance: Not explicitly stated in this document. Given it's a 510(k) for a US market device, it is likely the original clinical validation (K082118) included US data, but this is not confirmed. It refers to "clinical validation data," which typically implies prospective collection of patient samples.

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

• Not explicitly stated in this document. This level of detail would typically be found in the original clinical validation report (K082118). For genotyping, ground truth is usually established by orthogonal molecular methods, not primarily by expert consensus in the same way as imaging or pathology interpretation.

4. Adjudication Method for the Test Set:

• Not applicable/Not mentioned. For genetic tests where the ground truth is often established through well-defined molecular techniques (e.g., Sanger sequencing or a validated reference method), adjudication by multiple experts in the traditional sense (like for imaging reads) is generally not performed. The ground truth is objective.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

• No, an MRMC comparative effectiveness study was not done. This type of study is relevant for interpretive tasks (e.g., radiologists reading images) where human performance is being evaluated and compared with and without AI assistance. The Xpert FII & FV is an automated genotyping test; it does not involve human readers interpreting results in the same manner.

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

• Yes, the performance characteristics mentioned (e.g., analytical sensitivity, specificity) for a molecular diagnostic test like the Xpert FII & FV are inherently "standalone" in nature. The device itself performs the assay and provides a qualitative genotype call. The results are automated and interpreted by the diagnostic software.

7. The Type of Ground Truth Used:

• Not explicitly stated in this document, but for genetic tests, the ground truth is typically established by orthogonal molecular methods, such as Sanger sequencing or another highly accurate, validated reference genotyping method. It is not based on expert consensus, pathology, or outcomes data in the way these terms are typically used for imaging or disease diagnosis.

8. The Sample Size for the Training Set:

• Not explicitly stated in this document. The device uses real-time PCR for detection, and while there might be algorithm tuning within the software, the foundational "training" often refers to the design and optimization of primers and probes, and establishment of cut-offs, rather than machine learning on a large training set of clinical samples. The document refers to "clinical validation data" for performance, but not specifically to a training set size for an algorithm.

9. How the Ground Truth for the Training Set was Established:

• Not explicitly stated in this document. This would be part of the original developmental studies for the device (predating K082118). For a PCR-based test, ground truth for developing and optimizing the assay would involve samples with known genotypes confirmed through reference methods.

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The Xpert® FII & FV test is a qualitative in vitro diagnostic genotyping test for the detection of Factor II and Factor V alleles from sodium citrate or EDTA anticoagulated whole blood. The test is performed on the Cepheid GeneXpert® Instrument Systems. This test is intended to provide results for Factor II (G20210A) and Factor V Leiden (G1691A) mutations as an aid in the diagnosis in individuals with suspected thrombophilia.

The Cepheid Xpert® FII & FV is a rapid, automated DNA test for detecting FII and FV normal and mutant alleles directly from sodium citrate or EDTA anticoagulated whole blood specimens. Blood specimens are drawn into either sodium citrate or EDTA anticoagulant tubes. Following brief mixing of the sample, 50 uL of the blood sample is transferred to the bottom wall of the Sample opening of the Xpert FII & FV test cartridge. The user initiates a test from the system user interface and places the cartridge into the GeneXpert® Instrument system instrument platform (comprised of the GeneXpert Dx Systems and GeneXpert Infinity Systems), which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA. In the GeneXpert Instrument Systems platform, sample preparation, amplification, and real-time detection are all fully-automated and completely integrated.

The GeneXpert Instrument Systems have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real- time PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

The Xpert FII & FV test includes reagents for the detection of Factor II and Factor V normal and mutant alleles. The primers and probes in the Xpert FII & FV test determine the genotype of the Factor II gene (at position 20210) and the Factor V gene (at position 1691). The test includes a Sample Processing Control to confirm adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The test is performed on the Cepheid GeneXpert Instrument Systems, which automate and integrate sample purification, nucleic acid amplification of the target sequences in simple or complex samples using real-time PCR. The systems consist of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, crosscontamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fully- automated and completely integrated. The Xpert FII & FV test performed on the GeneXpert Instrument Systems provides results in approximately 30 minutes.

The FDA 510(k) summary for the Cepheid Xpert® FII & FV device outlines its performance and validation, primarily focusing on demonstrating substantial equivalence to a predicate device when used with new instrument systems (GeneXpert Infinity Systems).

Here's an analysis of the provided information against your requested criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not provide a formal table of quantitative acceptance criteria with corresponding performance metrics like sensitivity, specificity, accuracy, etc. This is typical for a Special 510(k) submission where the primary objective is to demonstrate that a change (new instrument compatibility) does not negatively impact the existing, previously cleared performance.

Instead, the "Performance Data" section states:

• Acceptance Criteria (Implicit): That the performance claims of the Xpert FII & FV test were not impacted by the use of the GeneXpert Infinity Systems.
• Reported Device Performance: This was assessed through verification studies, including a "Cartridge Hold Time study" and a "Functional Testing study." The document explicitly states that the results "determined that the performance claims of the Xpert FII & FV test were not impacted."

Therefore, the performance is essentially stated as "comparable to the predicate device and original claims," rather than providing new specific rates (e.g., "99% sensitivity," "98% specificity").

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

The document does not explicitly state the sample sizes for the "Cartridge Hold Time study" and "Functional Testing study." It only mentions that these were "verification studies."

• Data Provenance: Not specified in terms of country of origin.
• Retrospective or Prospective: Not explicitly stated, but typically, verification studies like these for in vitro diagnostic devices would involve prospective testing of samples under controlled conditions to assess functionality and stability on the new instrument.

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

This type of information is not applicable to this device and study. The Xpert® FII & FV test is a qualitative in vitro diagnostic genotyping test for detecting specific DNA mutations (Factor II and Factor V alleles). The "ground truth" for such a device is established by the known genetic status of the samples used in the studies (e.g., confirmed Factor II or Factor V mutation presence/absence via reference methods or defined synthetic constructs), not by expert human interpretation of images or other subjective data. No human experts are used to establish ground truth for this kind of molecular diagnostic test performance.

4. Adjudication Method for the Test Set

Not applicable. As explained above, the "ground truth" for a genotyping test is based on direct molecular confirmation, not on subjective interpretations requiring adjudication.

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

Not applicable. The Xpert® FII & FV is an automated diagnostic test that provides a definitive genetic result. It does not involve human readers interpreting output that would be improved with AI assistance, nor is it a diagnostic imaging device where MRMC studies are common.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

This is the primary mode of operation for this device. The Xpert® FII & FV test is an automated system as described: "perform[s] hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA." The results ("Result," "Not Detected," or "Invalid") are generated by the instrument's internal algorithms based on PCR amplification signals. The human interaction is limited to sample loading and initiating the test. Therefore, the "Functional Testing study" and "Cartridge Hold Time study" effectively assess the standalone performance of the algorithm and instrument system.

7. The Type of Ground Truth Used

The ground truth for a genotyping test is based on the presence or absence of specific DNA sequences/mutations. While not explicitly stated how this truth was established for the specific "verification studies," for molecular diagnostic tests, ground truth is typically confirmed using:

• Reference molecular methods: Such as Sanger sequencing or highly validated in-house PCR assays.
• Characterized samples: Samples with known genetic status (e.g., from biobanks, synthetic constructs, or previously validated patient samples).
• Clinical diagnosis/outcomes data: In some cases, to correlate the genetic findings with the clinical presentation, although for genotyping tests, the primary ground truth is molecular.

Given the nature of this device, it would be based on the confirmed genetic status of the samples.

8. The Sample Size for the Training Set

This information is not provided. As this is a Special 510(k) for an instrument change, the focus is on verification rather than a full re-validation involving new training sets. The underlying algorithms and core test technology (primers, probes, PCR) remain the same as the predicate device. Training sets would have been used in the original development and validation of the Xpert® FII & FV test (K082118).

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

Not provided in this document as it pertains to the original development of the predicate device (K082118), not this Special 510(k). For the original development, ground truth would have been established as described in point 7 (reference molecular methods, characterized samples).

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The cobas® Factor II and Factor V Test is an in vitro diagnostic device that uses real-time PCR for the detection and genotyping of the Factor II (Prothrombin) G20210A mutation and the Factor V Leiden G1691A mutation in genomic DNA obtained from K2EDTA whole blood specimens as an aid in diagnosis of patients with suspected thrombophilia. The cobas® Factor II and Factor V Test and the cobas z 480 analyzer are used together for automated amplification and detection.

The cobas® Factor II and Factor V Test is a real-time polymerase chain reaction (PCR) test for the qualitative detection and genotyping of a single point mutation in the human Factor V gene (G to A at position 1691, referred to as the Factor V Leiden mutation) and a single point mutation in the human Factor II gene (G to A at position 20210), in genomic DNA isolated from peripheral whole blood, as an aid in diagnosis of patients with suspected thrombophilia.

DNA is extracted offline from whole blood specimens collected in K2EDTA tubes. The userselected DNA extraction method must provide DNA of sufficient concentration. Automated realtime PCR is then performed on the cobas z 480 analyzer. The Factor II and Factor V mutations are detected simultaneously in the same real-time PCR reaction. Depending upon the test order, results for one or both mutations are reported for each DNA sample.

The assay consists of one reagent kit and a system platform. The reagent kit provides the necessary reagents and controls to perform automated real-time PCR amplification and detection. The system platform consists of a real-time PCR thermal cycler (cobas z 480 analyzer) and a control unit (cobas® 4800 System CU). The amplification reactions generate a Factor II specific amplicon and a Factor V specific amplicon in all samples, and utilize four fluorescent-dye labeled oligonucleotide probes for detection of the Factor II and Factor V genotypes.

Acceptance Criteria and Study for cobas® Factor II and Factor V Test

This document outlines the acceptance criteria and the studies performed to demonstrate that the cobas® Factor II and Factor V Test meets these criteria.

1. Table of Acceptance Criteria and Reported Device Performance

Factor II (Prothrombin) G20210A Mutation Detection:

Factor V Leiden G1691A Mutation Detection:

Analytical Sensitivity (Lower Limit of Detection):

Analytical Sensitivity (Upper Limit of Detection):

DNA Extraction Method Study:

Lot-to-Lot Repeatability:

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

Method Comparison Study:

• Sample Size: 300 specimens.
• Data Provenance: The specimens were obtained from patients whose routine medical care called for Factor II and/or Factor V measurements, representing an intended use population. The commercial vendors provided these samples. The type of data (retrospective/prospective) is not explicitly stated, but the description of samples being "obtained to represent the intended use population" and collected for "routine medical care" suggests a retrospective collection or at least samples collected for clinical indications. The provenance is likely a mix of clinical labs or commercial biobanks.

Clinical Reproducibility Study:

• Sample Size: A 9-member panel was used, consisting of 4 unique K2EDTA blood samples, 3 contrived blood samples, and 2 extracted genomic DNA samples. Each panel member was tested multiple times across different sites, operators, instruments, runs, and days. A total of 540 tests were performed (with 539 valid results and 1 invalid).
• Data Provenance: The samples included K2EDTA whole blood samples and extracted genomic DNA samples. The "contrived blood samples" suggest laboratory-prepared samples. The "unique K2EDTA blood samples" were likely sourced from similar vendors as the method comparison study. The study was conducted at three test sites (2 external and 1 internal), implying a multi-center study on potentially diverse datasets.

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

The ground truth for both the Method Comparison Study and the Clinical Reproducibility Study was established by bi-directional Sanger sequencing. The document does not specify the number of experts or their qualifications for performing or interpreting the Sanger sequencing results. However, Sanger sequencing is a widely accepted gold standard for genetic mutation detection, and it's typically performed by trained laboratory professionals.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for the test set where discrepancies between results from the cobas® test and Sanger sequencing were adjudicated by experts. The performance metrics are reported as direct agreements or disagreements with the Sanger sequencing results. In the DNA Extraction Method Study, for instance, one inconsistent triplicate result with a method was re-tested, and all results were correct upon re-testing, implying an internal review for outlier data.

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

No, an MRMC comparative effectiveness study was not done. The cobas® Factor II and Factor V Test is an in vitro diagnostic device for automated amplification and detection of genetic mutations. It is an algorithm-only device; therefore, human readers are not directly involved in its performance or interpretation in a way that would necessitate an MRMC study.

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

Yes, the studies presented are standalone performance evaluations. The cobas® Factor II and Factor V Test is described as an "in vitro diagnostic device that uses real-time PCR for the detection and genotyping" and used with the "cobas z 480 analyzer for automated amplification and detection." This indicates an automated system where the algorithm performs the detection and genotyping without direct human intervention in the result generation process. Human interaction is limited to sample preparation and loading, and interpreting the final automated result.

7. The Type of Ground Truth Used

The type of ground truth used for both the Method Comparison Study and the Clinical Reproducibility Study was expert consensus through bi-directional Sanger sequencing. Sanger sequencing is generally considered the "gold standard" for confirming DNA sequences, and thus, genotypes.

8. The Sample Size for the Training Set

The document does not provide information regarding a separate training set or its sample size. The studies described are performance evaluations (method comparison, reproducibility, analytical sensitivity, etc.) which typically use independent test data to assess the device's accuracy and reliability, assuming the algorithm was developed and optimized prior to these evaluation studies. As this is not an AI/ML device in the traditional sense, but a PCR-based diagnostic, the concept of a "training set" for an algorithm's learning phase is not directly applicable in the same way as it would be for an image recognition AI, for example. The "training" for such a system would involve optimizing primers, probes, and reaction conditions during product development.

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

As mentioned above, the document does not discuss a separate training set. For the validation studies, ground truth was established by bi-directional Sanger sequencing.

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The Invader® Factor II test is an in vitro diagnostic test intended for the detection and genotyping of a single point mutation (G to A at position 20210) of the human Factor II gene in isolated genomic DNA obtained from whole blood potassium EDTA samples from patients with suspected thrombophilia.

The Invader Factor II test consists of the following components: Factor II Oligo Mix, Universal Buffer, Universal Enzyme Mix, No DNA Control, Factor II Wild Type Control, Factor II Heterozygous Control, Factor II Mutant Control, Invader Call Reporter™ Software, Invader® Factor II Software.

This document describes the Invader® Factor II test, an in vitro diagnostic test for detecting a specific mutation (G20210A) in the human Factor II gene, associated with thrombophilia.

Here's an analysis of the acceptance criteria and supporting studies:

1. Table of Acceptance Criteria and Reported Device Performance

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

• External Reproducibility (Study #1):
  • Sample Size: 9 unique leukocyte-depleted whole blood samples (3 WT, 3 HET, 3 MUT), tested in duplicate over 5 days by 2 operators at 3 sites. Total tests: 9 samples * 2 duplicates * 5 days * 2 operators * 3 sites = 540 initial tests.
  • Data Provenance: Not explicitly stated, but implied to be from internal and external validation sites. Likely retrospective as they were "spiked cell lines."
• Lot-to-Lot Reproducibility (Study #9):
  • Sample Size: 4 genomic DNA samples (3 WT, 1 HET), tested in quadruplicate using 3 different kit lots. Total tests: 4 samples * 4 replicates * 3 lots = 48 tests.
  • Data Provenance: Not explicitly stated. Likely retrospective as they are "genomic DNA samples."
• Real-Time Stability Study (Study #5):
  • Sample Size: 3 controls (WT, HET, MUT) and 4 gDNA samples (WT, WT, HET, MUT), tested in quadruplicate at each time point (T0, T4, T7) for 3 lots. Total tests are not explicitly summed, but 7 sample types * 4 replicates * 3 time points * 3 lots = 252 tests.
  • Data Provenance: Not explicitly stated. Likely retrospective (genomic DNA and controls).
• Reagent Freeze-Thaw Stability Study (Study #6):
  • Sample Size: 3 Controls (WT, HET, MUT) and 3 gDNA samples (WT, HET, MUT) with varying numbers of replicates tested at each of 15 freeze/thaw cycles. Total tests: 255.
  • Data Provenance: Not explicitly stated. Likely retrospective (genomic DNA and controls from cell lines).
• Analytical Sensitivity and Normal Range (Study #3):
  • Sample Size: 2 genomic DNA samples (1 HET, 1 WT), each diluted to 8 concentrations and tested in 40 replicates. Total tests: 2 samples * 8 concentrations * 40 replicates = 640 tests.
  • Data Provenance: Whole blood collected in potassium EDTA, then extracted and diluted. Retrospective for the samples, but the dilution and testing process is controlled.
• Analytical Specificity (Interfering Substances) (Study #4):
  • Sample Size: 4 whole blood samples differing genotype (3 WT, 1 HET), each with 9 different interfering substances/conditions. Total tests: 4 samples * 2 (with/without substance) * number of replicates not specified, but results given as "8 of 8" for percent agreement, suggesting at least 8 replicates per condition/sample. Total presented data points: 8 conditions * 8 replicates = 64 tests.
  • Data Provenance: Whole blood samples. Retrospective.
• Pre-Analytical Equivalency Study (Study #7):
  • Sample Size: 30 human whole blood samples and 10 leukocyte-depleted whole blood samples (total 40 samples), extracted using 4 different methods. Each resulting DNA analyzed in singlicate. Total tests: 40 samples * 4 extraction methods = 160 tests.
  • Data Provenance: Human whole blood samples. Implied retrospective for the samples themselves.
• Instrument Equivalency (Study #8):
  • Sample Size: 29 human whole blood samples and 10 leukocyte-depleted whole blood samples (total 39 samples), extracted (using 2 methods). These extracts tested with the device on 3 thermal cyclers and raw data acquired on 3 fluorometers. Total presented for agreement: 78 tests per thermal cycler/fluorometer combination (likely 39 samples tested in duplicate, or 39 samples * 2 extraction methods = 78 sample preparations). Total 78 across all combinations * 3 thermal cyclers * 3 fluorometers = 702 measurements.
  • Data Provenance: Human whole blood samples. Implied retrospective.
• Secondary Polymorphism Impact (Study #10):
  • Sample Size: 6 samples (1 homozygous normal, 1 heterozygous, 4 homozygous normal each with a known secondary polymorphism). 40 replicates for each sample. Total tests: 6 samples * 40 replicates = 240 tests.
  • Data Provenance: Samples with known genotypes and secondary polymorphisms. Likely retrospective.
• Method Comparison (Study #2):
  • Sample Size: 336 human whole blood samples.
  • Data Provenance: Human whole blood samples. Retrospective.

3. Number of Experts and Qualifications for Ground Truth

• General Ground Truth Method: The primary and most frequently cited ground truth method across all studies is bi-directional DNA sequencing.
• Number of Experts: The document does not specify the number of experts used for establishing ground truth via bi-directional DNA sequencing. Sequencing is typically a highly automated process with results interpreted by trained molecular biologists or laboratory staff, rather than a consensus of "experts" in the clinical sense (like radiologists).
• Qualifications of Experts: Not specified. It's assumed that standard molecular biology laboratory practices for sequencing and interpretation were followed.

4. Adjudication Method for the Test Set

• Not Applicable in the traditional sense. For diagnostic tests like this, adjudication by multiple human experts (e.g., radiologists) is not a typical part of ground truth establishment.
• The ground truth is established by a definitive molecular method (bi-directional DNA sequencing).
• In the external reproducibility study (Study #1), two initial "No Call" results were resolved by retesting, which then agreed with the sequencing results. This implies a retesting/re-evaluation process for indeterminate results, rather than expert adjudication of the initial "No Call."

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

• No, an MRMC comparative effectiveness study was not done.
• This device is an in vitro diagnostic test for genotyping, where the output is a molecular result (genotype). It does not involve human readers interpreting images or data where AI assistance would directly improve human performance in the same way as, for example, a radiology AI.
• The "Invader Call Reporter™ Software" mentioned is for data analysis and conversion of raw fluorescence data into genotype calls, not for assisting human interpretation that would typically be evaluated in an MRMC study.

6. Standalone Performance Study

• Yes, a standalone performance study was done.
• The entire set of analytical performance studies (Reproducibility, Stability, Analytical Sensitivity, Analytical Specificity, Extraction Equivalency, Instrument Equivalency, Secondary Polymorphism Impact) and the method comparison study against bi-directional sequencing demonstrate the standalone performance of the algorithm/device system.
• The device takes raw fluorescence data and, through its software ("Invader Call Reporter™ Software" and "Invader® Factor II Software"), outputs a genotype call. The studies rigorously validate that these automated calls are accurate and reproducible compared to the gold standard of sequencing. The system is designed to provide automated calls, not to serve as an aid to a human reader's interpretation in a separate step.

7. Type of Ground Truth Used

• The primary ground truth used across all key performance studies is bi-directional DNA sequencing. This is considered a gold standard molecular method for determining specific genetic mutations.
• For controls, "expected genotype" based on the composition of the control material (e.g., cell lines) is used.

8. Sample Size for the Training Set

• The document does not explicitly describe a separate "training set" for the device's algorithm.
• For molecular diagnostic assays like this, the algorithm (e.g., for converting fluorescence data to genotype calls) is typically developed based on known statistical models and pre-defined thresholds related to the chemistry, rather than being "trained" on a large dataset of classified samples in the machine learning sense.
• The various controls (No DNA, WT, HET, MUT) are used within each run to validate performance and inform signal-to-noise calculations, serving as internal calibration rather than an external training set for an AI model.

9. How Ground Truth for the Training Set Was Established

• As a formal "training set" is not explicitly mentioned or implied in the context of supervised machine learning, the process of establishing ground truth for such a set is not described.
• However, the underlying principles for the chemistry and software's interpretive rules would have been developed using well-characterized samples with ground truth established by methods like DNA sequencing during the research and development phase before formal validation studies.

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The Factor II (Prothrombin) G20210A Kit is an in vitro diagnostic test for the detection and genotyping of a single point mutation (G to A at position 20210) of the human Factor II gene, from DNA isolated from human whole peripheral blood. The test is intended to be used on the LightCycler using SW 3.5. The sample preparation must be performed according to the workflow procedure described in the package insert. The Factor II (Prothrombin) G20210A Kit is indicated as an aid to diagnosis in the evaluation of patients with suspected thrombophilia.

The Factor II (Prothrombin) G20210A Kit is an in vitro diagnostic test for the detection and genotyping of the Factor II (Prothrombin) G20210A mutation, from DNA isolated from human whole peripheral blood.

Acceptance Criteria and Device Performance Study for K033612

This analysis describes the acceptance criteria and the study used to demonstrate that the Factor II (Prothrombin) G20210A Kit meets these criteria, as detailed in the provided 510(k) summary (K033612).

1. Table of Acceptance Criteria and Reported Device Performance

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