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The LIAISON® H. pylori IgG assay uses chemiluminescent immunoassay (CLIA) technology for the qualitative determination of IgG antibodies to Helicobacter pylori in human serum from symptomatic adults as an aid in the diagnosis of Helicobacter pylori infection. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions. The test has to be performed on the LIAISON® XL Analyzer.

The LIAISON® H. pylori IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® H. pylori IgG assay.

The method for qualitative determination of IgG antibodies to Helicobacter pylori (H.pv/ori IgG) is a two-step, indirect chemiluminescence immunoassay (CLIA). The principal components of the test are magnetic particles (solid phase) coated with Helicobacter pylori antigen and a conjugate of anti-human IgG monoclonal antibodies to linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, H. pylori antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the monoclonal antibody conjugate reacts with H. pylori lgG that is already bound to the solid phase. After each incubation, unbound material is removed with a wash cycle.

Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and therefore, the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of H. pylori IgG in calibrators, samples or controls.

All assay steps and incubations are performed by the LIAISON® XL Analyzer.

The provided text describes a 510(k) premarket notification for the "LIAISON® H. pylori IgG" assay, an in vitro diagnostic device. This document focuses on demonstrating the substantial equivalence of the new device to a legally marketed predicate device (Siemens IMMULITE 2000 H. pylori IgG Assay).

Here's an analysis of the acceptance criteria and study data based on the provided text, using the requested framework:

Acceptance Criteria and Device Performance

The document doesn't explicitly state "acceptance criteria" in a table format with specific numerical targets. Instead, it presents performance data for comparison against a predicate device. The implied acceptance criteria are that the new device's performance (specifically, accuracy as measured by percent agreement) is comparable to that of the predicate device within acceptable statistical variation.

Here's a table summarizing the reported device performance, which serves as evidence of meeting the implied acceptance criteria for equivalence:

Table 1: Device Performance (Comparative Clinical Study)

Note: The document also includes extensive precision/reproducibility data (Within-Laboratory Precision and Reproducibility at multiple sites), which are crucial for establishing the reliability and consistency of the assay. While not direct "acceptance criteria" in terms of accuracy against a true disease state, these data demonstrate the device's analytical performance meets expected standards for an in vitro diagnostic.

Study Details

Here's a breakdown of the specific information requested, based on the provided text:

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

• Sample Size: 504 samples
• Data Provenance:
  • Country of Origin: Multiple geographical locations in the U.S.
  • Retrospective or Prospective: Prospective study. Samples were collected from non-selected adult subjects sent to the laboratory for H. pylori IgG serological testing.

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

• Not Applicable / Not Provided: For this type of in vitro diagnostic device (immunoassay for antibodies), the "ground truth" for the comparative clinical study is established by the results of a legally marketed predicate device, not by expert interpretation of images or other clinical data. Hence, there is no mention of experts establishing a ground truth in the context of radiologists or similar clinical reviewers.

4. Adjudication Method for the Test Set:

• Not Applicable / Not Provided: Adjudication methods (e.g., 2+1, 3+1) are typically used in studies involving human interpretation (e.g., image reading) where there might be disagreement. In this comparative study with a predicate device, the comparison is directly between the new device's results and the predicate device's results, with no mention of human adjudication of results. The "ground truth" is effectively the predicate device's result.

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 is not applicable as this is an in vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers. The device performs the test autonomously.

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

• Yes: This device (LIAISON® H. pylori IgG assay) is inherently a standalone diagnostic test. Its performance is evaluated based on its ability to detect antibodies independently. The clinical study compares its standalone performance against another standalone device (the predicate).

7. The Type of Ground Truth Used:

• Predicate Device Results: For the comparative clinical study, the "ground truth" against which the LIAISON® H. pylori IgG assay was evaluated was the results from the FDA-cleared predicate device (Siemens IMMULITE 2000 H. pylori IgG Assay).

8. The Sample Size for the Training Set:

• Not Applicable / Not Provided: This is an immunoassay, not an AI/machine learning algorithm that requires a "training set" in the conventional sense. The development of reagents and assay parameters is based on biochemical and analytical principles, not on training data in the way an AI model would be.

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

• Not Applicable / Not Provided: As noted above, there is no "training set" in this context. The assay's performance characteristics (e.g., cutoff values) are established through analytical validation and optimization, often against known positive and negative samples, but not through a "ground truth" establishment process for a training set as would be done for an AI algorithm.

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The LIAISON® Anti-HAV assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of total antibodies to hepatitis A (anti-HAV) in human serum and sodium heparin plasma samples using the LIAISON® Analyzer family. The assay is indicated as an aid in the laboratory diagnosis of current or previous HAV infections in conjunction with other serological and clinical information and to determine the presence of an antibody response to HAV in vaccine recipients.

This assay is not intended for screening blood or solid or soft tissue donors. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. The user is responsible for establishing assay performance characteristics in these populations. Caution: U.S. Federal Law restricts this device to sale by or on the order of a physician.

The LIAISON® XL Analyzer is an automated discrete continuous loading chemiluminescent immunoassay (CLIA) analyzer for in vitro diagnostic analysis of CLIAs on human specimens cleared for use on the analyzer. It is only to be used with FDA cleared chemiluminescent immunoassays that are marketed by DiaSorin for the LIAISON® XL Analyzer. The analyzer can be connected to a third party Laboratory Automation System (LAS) which has been previously cleared for use with FDA cleared assays.

The LIAISON® Control Anti-HAV (negative and positive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Anti-HAV assay.

The performance characteristics of LIAISON® controls have not been established for any other assays or instrument platforms different from LIAISON® XL and LIAISON® XL with LIAISON® XL Workcell Upgrade Kit.

The LIAISON® XL Analyzer is an in vitro diagnostic device consisting of loading areas (for samples, Reagent Integrals, ancillary reagents, Starter Reagents, Cuvettes, Disposable Tips, water, Wash Buffer, maintenance liquid); incubator, wash station, reader, and a barcode reader for reagents and samples. Installation of the LIAISON® XL Workcell Upgrade Kit allows the LIAISON® XL Analyzer to be used with a compatible LAS and extends the sample pipetting capabilities to a point-in-space located external to the analyzer.

This submission (K141116) describes the LIAISON® XL Workcell Upgrade Kit, which allows the LIAISON® XL Analyzer (predicate device K103529) to connect to a Laboratory Automation System (LAS) and extends its sample pipetting capabilities. The device itself (the Workcell Upgrade Kit) is essentially a modification to the LIAISON® XL Analyzer, enabling new functionality rather than being a diagnostic assay with specific performance metrics like sensitivity or specificity for a disease.

Therefore, the acceptance criteria and study proving its efficacy are focused on demonstrating that the modified LIAISON® XL Analyzer (with the Workcell Upgrade Kit) performs equivalently to the predicate LIAISON® XL Analyzer for its intended use (running the LIAISON® Anti-HAV assay).

Here's an analysis based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't provide a typical table of acceptance criteria and performance for a diagnostic assay (e.g., sensitivity, specificity, accuracy). Instead, the acceptance criteria for this device modification are implicitly about maintaining the performance and functional equivalence of the predicate device when the upgrade kit is installed and used, especially when connected to a Laboratory Automation System.

The "device performance" reported is that the new device (LIAISON® XL with Workcell Upgrade Kit) is "substantially equivalent" to the predicate device (LIAISON® XL Analyzer) for its existing intended use with the LIAISON® Anti-HAV assay.

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

The document does not specify a sample size for a "test set" in the traditional sense of a diagnostic assay evaluation (e.g., number of patient samples for sensitivity/specificity). This submission is for a device modification (an upgrade kit for an existing analyzer) rather than a novel diagnostic assay.

The evaluation would likely involve:

• Functional testing: Verifying that the Workcell Upgrade Kit integrates correctly with the LIAISON® XL Analyzer and a Laboratory Automation System.
• Performance verification: Ensuring that the LIAISON® Anti-HAV assay, when run on the LIAISON® XL Analyzer with the Workcell Upgrade Kit (especially through LAS integration), yields results consistent with those obtained on the predicate device without the upgrade. This would involve running a series of samples (controls, patient samples) to confirm precision, accuracy, and overall analytical performance are maintained.

Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for a device modification, the studies would typically be prospective functional and performance verification studies conducted in a controlled laboratory environment.

3. Number of Experts Used to Establish Ground Truth and Qualifications:

Not applicable. This is not a study assessing diagnostic accuracy against a clinical ground truth established by experts. It is a technical submission for a device modification.

4. Adjudication Method:

Not applicable for a device modification study focused on functional and performance equivalence.

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

Not applicable. This is not a study evaluating human reader performance, with or without AI assistance.

6. Standalone Performance:

Yes, a standalone performance was done in the sense that the studies demonstrated that the LIAISON® XL Analyzer with the Workcell Upgrade Kit still functions as a standalone analyzer (where samples are placed directly into the sample bay, as in the predicate device). The capabilities are maintained ("Same (in the stand alone mode)"). Additionally, the primary purpose of the upgrade is to enable the "LAS mode" functionality. The non-clinical studies would have verified the performance of the analyzer both in standalone mode and with the LAS integration.

7. Type of Ground Truth Used:

The "ground truth" for this type of submission would be the established and cleared performance characteristics (e.g., precision, linearity, analytical sensitivity, cut-off values) of the LIAISON® Anti-HAV assay when run on the predicate LIAISON® XL Analyzer. The studies would have demonstrated that the modified analyzer's performance for this assay does not deviate significantly from these established values.

8. Sample Size for the Training Set:

Not applicable. This is not a machine learning or AI device that requires a distinct training set for algorithm development. The "training" in this context would refer to the development and internal testing of the hardware and software modifications of the Workcell Upgrade Kit to ensure it performs as intended.

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

Not applicable, as there's no machine learning "training set" in the context of this device modification. The "ground truth" for verifying the functional and performance aspects of the Workcell Upgrade Kit would be derived from:

• Engineering specifications and design requirements for the Workcell itself and its integration with LAS.
• The established performance specifications of the LIAISON® Anti-HAV assay on the predicate LIAISON® XL Analyzer.
• Industry standards and regulatory guidelines for laboratory automation and immunoassay systems.

In summary, this 510(k) is about demonstrating substantial equivalence for a modification to an existing device rather than establishing novel diagnostic performance for an assay. The studies focus on ensuring that the new functionalities (LAS connectivity, extended pipetting) correctly integrate without negatively impacting the already cleared performance of the LIAISON® XL Analyzer when running the LIAISON® Anti-HAV assay.

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The LIAISON® N-TACT® PTH Gen II is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of intact human parathyroid hormone in serum, EDTA and Lithium Heparin plasma samples. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism. The test is to be performed on the LIAISON® XL Analyzer.

The LIAISON® N-TACT® PTH Gen II Control Set is intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® N-TACT® PTH Gen II assay.

The LIAISON® N-TACT® PTH Gen II Calibration Verifiers are assayed quality control materials intended for the quantitative verification of calibration and reportable range of the LIAISON® N-TACT® PTH Gen II assay.

The LIAISON® N-TACT® PTH Gen II assay is a modified two-step, two-site sandwich assay that uses two goat polyclonal antibodies for capture and detection of intact PTH. Results are determined by a 2 point calibration conversion of the master curve to a working curve. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of intact PTH present in the calibrators, controls or samples.

LIAISON® N-TACT® PTH Gen II Control set contains:
2 levels controls containing 80% human plasma spiked with 1-84 PTH, and preservatives; 4 vials each level; lyophilized
The target concentration for control level 1 is 20 pg/mL. The target concentration for control Level 2 is 300 pg/mL.
The range of concentrations of each control is reported on the certificate of analysis provided with each LIAISON® N-TACT® PTH Gen II Control set.

LIAISON® N-TACT® PTH Gen II Calibration Verifier set contains:
4 levels containing 80% human plasma spiked with 1-84 PTH, with preservative, . 1 vial each level, lyophilized
The target concentration for cal verifier A is 10 pg/mL. The target concentration for cal verifier B is 150 pg/mL. The target concentration for cal verifier C is 650 pg/mL. The target concentration for cal verifier D is 1600 pg/mL.
The range of concentrations of each calibration verifier is reported on the certificate of analysis provided with each LIAISON® N-TACT® PTH Gen II Calibration Verifier set.

Here's an analysis of the acceptance criteria and study details for the LIAISON® N-TACT® PTH Gen II device based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

The 510(k) summary for the LIAISON® N-TACT® PTH Gen II primarily demonstrates substantial equivalence to a predicate device. As such, the "acceptance criteria" are generally implied by the performance of the predicate device and the demonstration that the new device performs comparably or better, meeting established clinical laboratory guidelines. Specific numeric acceptance criteria are not explicitly stated in a "PASS/FAIL" format for each performance characteristic, but rather the study results are presented to show satisfactory performance.

Here's a table summarizing the performance characteristics and their reported results, which implicitly serve as the demonstration of meeting acceptance:

Study Details for LIAISON® N-TACT® PTH Gen II

1. Sample sizes used for the test set and data provenance:

   • Method Comparison: 198 patient samples. The provenance is not explicitly stated as country of origin, but the reference range study mentions "northern and southern regions of the U.S.", suggesting US-based samples for some studies. The study is retrospective, utilizing existing patient samples.
   • Sample Matrix Comparison: 65 matched patient sets (EDTA plasma, serum, SST serum, and Lithium Heparin plasma). Data provenance is not explicitly stated beyond being "patient sets." Retrospective.
   • Reference Range: 125 apparently healthy adults aged 21-70 years from mixed ethnic backgrounds (32.5% dark-skinned, 66.7% light-skinned, 0.8% unknown) from the northern and southern regions of the U.S. This is a prospective or retrospective collection of samples for establishing a reference interval.
   • Precision: 7 frozen EDTA plasma samples (coded panel) and 2 lots of LIAISON® N-TACT® PTH Gen II controls (2 levels). Samples were tested on two lots of reagents. This is a controlled lab study, not involving patient data per se beyond the initial source of the plasma samples.
   • Linearity: One sample pool of each type: serum, SST serum, EDTA plasma, and Lithium Heparin plasma. These were diluted. Controlled lab study.
   • High Dose Hook Effect: A zero sample spiked with PTH. Controlled lab study.
   • Recovery Study: 5 high concentration EDTA plasma samples and 5 low concentration EDTA plasma samples. Controlled lab study, not directly patient data.
   • Analytical Specificity (Cross-Reactivity & Interference): Samples spiked with specific substances. These are controlled lab studies.
   • Limit of Blank, Limit of Detection, Limit of Quantitation: Not explicitly stated, usually involves multiple replicates of blank and low-concentration samples. Controlled lab study.

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

   • This device is an in vitro diagnostic (IVD) immunoassay, not an image-based AI device. The "ground truth" is established through analytical methods and comparison to established, cleared diagnostic devices (predicate device) and clinical standards, rather than expert human interpretation.
   • For the method comparison, the "ground truth" for the test set is the result from the predicate device, Siemens ADVIA® CENTAUR INTACT Parathyroid Hormone (iPTH) Assay, which is an FDA-cleared device.
   • For other analytical performance studies (precision, linearity, recovery, etc.), the ground truth relies on carefully prepared samples with known concentrations or expected behaviors, measured against established analytical principles and validated laboratory methods. There are no "experts" establishing image-based ground truth here.

3. Adjudication method for the test set:

   • Not applicable as this is an IVD immunoassay, not a diagnostic imaging AI where human adjudication of ambiguous cases is typically required. The comparison is objective, numerical data between two analytical methods or against defined analytical targets.

4. 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 is an IVD assay, not an AI-powered diagnostic imaging tool that assists human readers. The performance is assessed against a predicate device and analytical standards.

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

   • The LIAISON® N-TACT® PTH Gen II assay is a standalone device in the sense that it provides quantitative results for PTH concentration. It operates autonomously on the LIAISON® XL Analyzer without direct human interpretation of the result generation process. Interpretation of the PTH level in a clinical context (e.g., diagnosis of hyper/hypocalcemia) still involves human clinicians, but the device provides the raw measurement itself without human input into the measurement.

6. The type of ground truth used:

   • For Method Comparison: Results from the predicate device (Siemens ADVIA® CENTAUR INTACT PTH (iPTH) Assay, K020217).
   • For other analytical studies (Precision, Linearity, Recovery, etc.): Typically based on known concentrations of analytes in spiked samples or reference materials, or expected analytical behaviors according to established CLSI guidelines (e.g., EP5-A2 for Precision, EP6-A for Linearity, EP7-A2 for Interference, EP17-A2 for Detection Capability). For the reference range, it's derived from a healthy population cohort carefully selected using specific clinical criteria.

7. The sample size for the training set:

   • This document describes performance characteristics for an IVD kit, not an AI/Machine Learning model. Therefore, there isn't a "training set" in the sense of data used to train an algorithm. The development of the assay itself would involve internal optimization and validation, but these stages are not typically referred to as "training sets" in the context of conventional IVDs in 510(k) summaries.

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

   • As there is no "training set" in the AI/ML context, this question is not applicable. The assay's analytical characteristics are developed and verified through standard laboratory practices and comparison to reference methods, not through an iterative learning process with labeled data.

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The DiaSorin LIAISON® XL HCG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer for the quantitative determination of total human chorionic gonadotropin (hCG and ßhCG) in human serum for early detection of pregnancy. Total hCG is the measurement of intact and beta-hCG.

The method for the quantitative determination of hCG is a sandwich chemiluminescence immunoassay. A specific mouse monoclonal antibody is coated on the magnetic particles (solid phase); another monoclonal antibody is linked to an isoluminol derivative (isoluminol-antibody conjugate). All assay steps and incubations are performed by the LIAISON® XL Analyzer.

During the first incubation, hCG present in calibrators, samples or controls binds to the solid phase monoclonal antibody, and subsequently after a washing step in a second incubation the antibody conjugate reacts with hCG already bound to the solid phase.

Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU, relative light units) and is directly related to hCG concentration present in calibrators, samples or controls.

Here's an analysis of the DiaSorin LIAISON® XL HCG Premarket Notification (K131037) based on the provided text, focusing on acceptance criteria and study details:

Acceptance Criteria and Device Performance for DiaSorin LIAISON® XL HCG

The DiaSorin LIAISON® XL HCG assay is a chemiluminescent immunoassay (CLIA) for the quantitative determination of total human chorionic gonadotropin (hCG and βhCG) in human serum for early detection of pregnancy. The submission aims to demonstrate substantial equivalence to the Roche ELECSYS® HCG +Beta Test (K003178).

The document details several performance studies to support the device's claims.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state "acceptance criteria" as pass/fail thresholds for each performance characteristic. Instead, it reports the results of the performance studies which implicitly serve as the basis for demonstrating substantial equivalence. For the purpose of this analysis, I will infer the intended acceptance of "good performance" based on the reported values and comparison to the predicate where applicable.

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

• Method Comparison: One hundred sixty-three (163) serum samples. The data provenance is not explicitly stated (e.g., country of origin) but is implied to be clinical samples spanning the assay's reportable range. The study was performed according to CLSI EP9-A2 guideline. It is a retrospective analysis using collected samples.
• Reference Range/Expected Values:
  • 74 healthy, non-pregnant premenopausal women (<50 years old).
  • 70 healthy, postmenopausal women (≥ 50 years old).
  • The study was performed according to CLSI Approved Guideline C28-A3. Data provenance is not explicitly stated.
• Reproducibility/Precision: A coded panel comprised of 6 frozen serum samples (low, medium, high levels) and 3 commercial controls. Each sample/control was tested 160 times (N=160 in the table). This study was performed at DiaSorin Inc., implying internal, controlled data. The CLSI document EP05-A2 was consulted.
• Dilution Linearity: Two serum pools containing high hCG concentrations. Details on individual sample numbers beyond "two serum pools" are not provided. The study followed CLSI EP6-A.
• LoB/LoD/LoQ: The methodology followed CLSI EP17-A2, which typically involves multiple replicates of blank and low-concentration samples. Specific sample sizes are not explicitly stated for individual calculations but are implied by the CLSI standard.
• Recovery: Five levels of spiked samples (prepared from five human sera), tested in duplicates.
• Interfering Substances: Controlled studies at two hCG levels for each interfering substance, implying multiple tests per substance. The testing was based on CLSI-EP7-A2.

The data appears to be primarily from internal studies (e.g., DiaSorin Inc. for reproducibility) or clinical samples whose specific origin (e.g., country) is not disclosed but collected according to CLSI guidelines, indicating a general clinical relevance. All studies appear to be retrospective analyses of collected samples or controlled laboratory experiments.

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

For this type of in-vitro diagnostic device (an immunoassay for HCG), the "ground truth" for the test set is established by the actual concentration of hCG in the samples, measured through established reference methods or spiking procedures. This is typically determined by laboratory equipment calibration against recognized standards (e.g., WHO reference standard IS 75/537, as noted for traceability). It does not involve human experts (like radiologists) interpreting images or clinical cases to establish ground truth.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are common in studies involving human interpretation of data (e.g., image-based diagnosis). Since this is an immunoassay for quantitative measurement of a biomarker, "adjudication" in that sense is not applicable. The accuracy of measurements is assessed against established reference materials or methods, and potential discrepancies would be investigated through re-testing, calibration checks, or review of laboratory protocols.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are typically performed for diagnostic imaging devices where different human readers interpret cases with and without AI assistance. This submission pertains to an automated in-vitro diagnostic assay for a biochemical marker, which does not involve human readers interpreting "cases" in the same way.

6. Standalone (Algorithm Only) Performance

Yes, the performance data presented (Method Comparison, Reference Range, Reproducibility, Dilution Linearity, LoB/LoD/LoQ, Recovery, Interfering Substances) is the standalone performance of the DiaSorin LIAISON® XL HCG assay. As an automated immunoassay, it operates without direct human intervention in the measurement process once the sample is loaded and the assay initiated. The results are generated directly by the LIAISON® XL Analyzer.

7. The Type of Ground Truth Used

The ground truth used for the performance studies is primarily:

• Reference Intervals: Established by testing samples from well-defined healthy populations (premenopausal, postmenopausal women) whose non-pregnant status is the established biological ground truth.
• Known Concentrations: For method comparison, linearity, LoB/LoD/LoQ, and recovery, the ground truth is often established through:
  • Predicate Device Measurements: In method comparison, the predicate device results (Roche Elecsys® HCG +Beta Test) serve as a comparative ground truth.
  • Spiked Samples: For recovery and linearity studies, samples are "spiked" with known concentrations of hCG (traceable to WHO reference standard IS 75/537), providing a known expected value.
  • Reference Materials: Calibration and accuracy are traceable to the 3rd WHO reference standard IS 75/537, which is the ultimate gold standard for hCG concentration.
  • CLSI Guidelines: Adherence to CLSI guidelines ensures standardized and accepted methods for determining these performance characteristics.

8. The Sample Size for the Training Set

The document does not specify a "training set" size. This is because the DiaSorin LIAISON® XL HCG assay is a traditional immunoassay, not an AI/machine learning model that requires a distinct training phase on a dataset of images or complex inputs to learn patterns. The "training" in this context refers to the development and optimization of the assay reagents, protocols, and instrument parameters by DiaSorin scientists, not the algorithmic training of an AI system.

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

As noted above, there is no "training set" in the context of an AI/machine learning system. For the development and optimization of the immunoassay, the "ground truth" would have been established through a rigorous process of:

• Analytical Chemistry and Biology: Ensuring antibody specificity, optimal reaction conditions, signal detection, and calibration against internationally recognized standards (like the WHO hCG reference standard).
• Internal Development and Verification: DiaSorin's R&D team would have used a wide range of precisely characterized HCG samples (known concentrations, spiked samples, clinical samples) to develop and refine the assay. The ultimate "ground truth" during this phase would be the known concentration of HCG in these samples, traceable to the WHO standard.

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The LIAISON® 25 TOTAL-D assay is a chemiluminescent immunoassay (CLIA) intended for the quantitative determination of 25-hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum, EDTA and Lithium heparin plasma. The LIAISON® 25 TOTAL-D assay is to be used as an aid in the assessment of vitamin D sufficiency in adults. The DiaSorin LIAISON® 25 TOTAL-D is intended to be used on the LIAISON® XL Analyzer.

The DiaSorin LIAISON® 25 TOTAL-D Control Set is intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® 25 TOTAL-D assay.

The DiaSorin LIAISON® 25 TOTAL-D Calibration Verifiers are assayed quality control materials intended for use in the quantitative verification of calibration and reportable range of the LIAISON® 25 TOTAL-D assay when performed on the LIAISON® XL Analyzer.

The LIAISON® 25 TOTAL-D consists of one Reagent Intergral with calibrators, which consists of: Magnetic Particles (2.4 mL) coated with goat antibody against 25 OH Vitamin D, protein, phosphate buffer, < 0.1% sodium azide. Assay Buffer (28.0 mL) with 7.5% ethanol, surfactants and 0.2% ProClin® as a preservative. Conjugate (4.5 mL) 25 OH Vitamin D conjugated to an isoluminol derivative. in phosphate buffer with10% ethanol, EDTA and 0.1% benzoic acid as a preservative. Calibrator 1 (1.2 mL) Human serum, BSA, <0.1% sodium azide and 25 OH Vitamin D. The calibrator concentrations (ng/mL) are referenced to standard preparations containing highly purified 25 OH Vitamin D. Calibrator 2 (1.2 mL) Human serum, BSA, <0.1% sodium azide and 25 OH Vitamin D. The calibrator concentrations (ng/mL) are referenced to standard preparations containing highly purified 25 OH Vitamin D.

The LIAISON® 25 TOTAL-D control consists of 2 levels of human serum, BSA, <0.1% sodium azide and 25 OH Vitamin D.

The LIAISON® 25 TOTAL-D calibration verifier consists of 4 levels of human serum, BSA. <0.1% sodium azide and 25 OH Vitamin D.

The DiaSorin LIAISON® 25 TOTAL-D assay is a chemiluminescent immunoassay (CLIA) for the quantitative determination of 25-hydroxyvitamin D and other hydroxylated vitamin D metabolites in human serum, EDTA, and Lithium heparin plasma. It is intended to be an aid in the assessment of vitamin D sufficiency in adults.

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as pass/fail thresholds for each metric in the provided text. However, the study results are presented with implied acceptance based on the comparison to the predicate device and established clinical laboratory guidelines (e.g., CLSI documents).

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

• Method Comparison: 403 serum samples (391 included in analysis after excluding 12 below measuring range).
  • Data Provenance: De-identified residual serum samples obtained from a sample procurement organization (U.S. and/or European patients). Retrospective.
• Matrix Comparison: 64 matched patient sets (serum, lithium heparin plasma, and EDTA plasma samples).
  • Data Provenance: Not explicitly stated, but implied to be patient samples. Prospective.
• Reference Range Study: 395 samples.
  • Data Provenance: Adults (21-90 years) recruited from four sites in the contiguous US (northern, southern, central US). Prospective.
• Reproducibility/Precision: 6 coded frozen serum samples (panel) and 2 kit controls.
  • Data Provenance: Internal samples/controls.
• Dilution Linearity: Separate serum, SST (serum separator tubes), EDTA plasma, and lithium heparin plasma pools (original number of samples to create pools not specified).
  • Data Provenance: Internal pools created for the study.
• LoB/LoD/LoQ:
  • LoB: 6 blank sample aliquots.
  • LoD: 4 samples.
  • LoQ: 8 samples.
  • Data Provenance: Internal samples.
• Recovery: 5 high concentration serum samples and 5 low concentration serum samples.
  • Data Provenance: Internal samples.
• Interfering Substances: Vitamin D samples (30 ng/mL and 60 ng/mL) spiked with interfering substances.
  • Data Provenance: Internal samples.
• Cross-reactivity: Three serum pools (15, 50, 75 ng/mL 25 OH D) spiked with potential cross-reactants.
  • Data Provenance: Internal serum pools.

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

There is no mention of experts being used to establish ground truth in the traditional sense (e.g., radiologists interpreting images). For this type of in-vitro diagnostic device, the "ground truth" or reference values are established by other analytical methods or reference materials:

• Method Comparison: The predicate device, LIAISON® 25 OH Vitamin D TOTAL assay (K112725), served as the comparative "reference."
• Traceability and Value Assignment: Calibrators, controls, and calibration verifiers are traceable to UV spectrophotometric analysis of an in-house standard preparation using a commercially available 25-Hydroxyvitamin D. Master calibrators are prepared from a stock solution whose concentration is determined spectrophotometrically.
• Reference Range: The "ground truth" is the distribution of 25 OH Vitamin D levels in a statistically defined "apparently healthy" population, rather than expert consensus on individual cases.

4. Adjudication Method for the Test Set

Not applicable. This device is an in-vitro diagnostic (IVD) assay predicting a biochemical concentration, not a diagnostic imaging device requiring expert adjudication.

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

No. This is an in-vitro diagnostic device, not an imaging device that would typically involve human readers. Therefore, an MRMC study and analysis of AI vs. human reader improvement is not applicable.

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

Yes, the performance studies described (Method Comparison, Matrix Comparison, Linearity, LoB/LoD/LoQ, Recovery, Interfering Substances, Cross-reactivity, Reproducibility/Precision) evaluate the device's analytical performance in a standalone manner, without human interpretation of results beyond standard laboratory practices. The "algorithm" here is the chemiluminescent immunoassay technology performed on the LIAISON® XL Analyzer.

7. The Type of Ground Truth Used

The ground truth or reference values used for validation include:

• Comparison to a Predicate Device: For method comparison studies, the results from the previously cleared LIAISON® 25 OH Vitamin D TOTAL assay (K112725) served as the reference.
• Reference Standards/Spectrophotometric Analysis: For traceability, calibration, and control value assignment, established spectrophotometric methods using highly purified 25 OH Vitamin D standards were used.
• Defined Blanks and Spiked Samples: For LoB/LoD/LoQ, Recovery, Interfering Substances, and Cross-reactivity studies, samples with known (or zero) concentrations of the analyte or interfering substances were used.
• Population-Based Data: For reference range, the "ground truth" is derived from statistical analysis of a representative "apparently healthy" subject population.

8. The Sample Size for the Training Set

No explicit "training set" is mentioned in the context of machine learning. This device is a biochemical assay. The "training" for such devices typically involves:

• Method Development & Optimization: Internal studies and experiments conducted during the development phase to optimize reagent concentrations, incubation times, and other assay parameters.
• Calibration: The device uses a two-point calibrator to generate a stored master curve, which is essentially the "model" or "prediction function" for the assay. This calibration is derived from master calibrators whose values are assigned using reference materials.

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

Not applicable in the machine learning sense. For the calibration and internal optimization processes:

• The ground truth for calibrators is established through UV spectrophotometric analysis of an in-house standard preparation using commercially available 25-Hydroxyvitamin D.
• Master calibrators are then used to assign values to the kit calibrators, controls, and calibration verifiers by running them on multiple LIAISON XL analyzers with different reagent lots and taking mean results.

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The LIAISON® Toxo IgG II assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer for the qualitative determination of specific IgG antibodies to Toxoplasma gondii in human serum. The results of this assay can be used as an aid in the assessment of the patient's serological status to infection with Toxoplasma gondii and in the determination of immune status of individuals including pregnant women. This assay has not been cleared/approved by the FDA for blood/plasma donor screening. U.S. Federal Law restricts this device to sale by or on the order of a physician.

Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, neonatal specimens, or infants.

The LIAISON® Control Toxo IgG II (negative and positive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Toxo IgG II assay on the LIAISON® XL Analyzer.

The method for qualitative determination of IgG antibodies to Toxoplasma gondii (anti-Toxo IgG) is an indirect chemiluminescence immunoassay (CLIA). The principal components of the test are magnetic particles (solid phase) coated with Toxoplasma gondii and a conjugate of mouse monoclonal antibodies to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, Toxoplasma gondii antibodies present in diluted calibrators, samples or controls bind to the solid phase. During the second incubation, the monoclonal antibody conjuqate reacts with anti-Toxo IgG that is already bound to the solid phase. After each incubation, unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and therefore, the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of anti-Toxo IqG in calibrators, samples or controls.

All assay steps and incubations are performed by the LIAISON® XL Analyzer.

The DiaSorin LIAISON® Toxo IgG II assay is intended for the qualitative determination of specific IgG antibodies to Toxoplasma gondii in human serum using chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer. The results aid in assessing a patient's serological status to Toxoplasma gondii infection and in determining the immune status of individuals, including pregnant women.

The study supporting this device's acceptance focused on comparative clinical studies against a predicate device and a CDC panel study.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state "acceptance criteria" in a quantitative format for clinical performance (e.g., minimum sensitivity/specificity thresholds). However, substantial equivalence is claimed based on agreement with a predicate device and a CDC panel. The performance data presented indicates the device aims to accurately identify positive and negative Toxoplasma gondii IgG samples.

Here's a summary of the reported device performance from the studies:

2. Sample Sizes and Data Provenance

• Prospective US Population Test Set:
  • Sample Size: 204 individuals
  • Data Provenance: Prospective, US subjects sent to the lab for Toxoplasma gondii IgG testing.
• Prospective European Population Test Set:
  • Sample Size: 600 individuals
  • Data Provenance: Prospective, European subjects sent to the lab for Toxoplasma gondii IgG testing.
• Prospective Pregnant Population Test Set:
  • Sample Size: 202 females
  • Data Provenance: Prospective, pregnant women.
• Retrospective/Pre-Selected Population Test Set:
  • Sample Size: 42 individuals
  • Data Provenance: Retrospective, samples from individuals with a positive Toxoplasma gondii IgG result by the comparator assay.
• CDC Panel Study Test Set:
  • Sample Size: 100 frozen blind specimens (70 true positive, 30 true negative)
  • Data Provenance: CDC Toxoplasma 1998 Human Serum Panel.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test sets derived from the comparative clinical studies (US, European, Pregnant, Retrospective populations). The comparison was made against a "comparator assay" (Diamedix Is-Toxoplasma IgG ELISA). For the CDC panel study, the results were submitted to the "CDC (Reference Immunodiagnostic Lab, Biology and Diagnostic Branch Division of Parasitic Diseases) for data analysis," implying that CDC's established ground truth, likely based on expert consensus and/or confirmatory testing, was used.

4. Adjudication Method

The document does not describe a formal adjudication method for discrepancies in the comparative clinical studies. It presents agreement percentages between the new device and the comparator assay. For the CDC panel, the results were submitted to and analyzed by the CDC, which inherently implies an adjudication (or definitive classification) by that reference lab.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This device is an automated in vitro diagnostic assay, not an imaging or interpretive AI device that would typically involve multiple human readers.

6. Standalone Performance

Yes, a standalone performance study was done. The "Comparison to Predicate Device" section and the "Performance Data: Comparative Clinical Studies" detail the performance of the LIAISON® Toxo IgG II assay (the algorithm/device only) in comparison to a predicate device and a CDC reference panel. The results (e.g., percent agreement, sensitivity, specificity) demonstrate its performance independent of human interpretation other than reading the instrument's output.

7. Type of Ground Truth Used

• For Comparative Clinical Studies (Prospective and Retrospective populations): The ground truth was established by a "comparator assay," specifically the Diamedix Is-Toxoplasma IgG ELISA (K981498). This is a form of expert consensus or reference standard based on an FDA-cleared predicate device.
• For CDC Panel Study: The ground truth was based on the "CDC Toxoplasma 1998 Human Serum Panel," which had true positive and true negative samples validated by the CDC Reference Immunodiagnostic Lab. This represents a highly authoritative, verified ground truth.

8. Sample Size for the Training Set

The document does not specify a separate "training set" sample size. For in vitro diagnostic assays, the development process (which might involve internal optimization, calibration, and iterative testing) is usually distinct from the formal clinical validation studies submitted for regulatory clearance. The provided data focuses on the validation/test sets.

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

As no explicit "training set" is mentioned with details on its ground truth establishment, this information is not available in the provided text. The performance data presented relates to the validation of the finalized device, not its developmental training.

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The LIAISON® Toxo IgM II assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer for the qualitative determination of IgM antibodies to Toxoplasma gondii in human serum samples. It is intended for use as an aid in the presumptive diagnosis of acute or recent Toxoplasma gondii infection, including pregnant women. It is recommended that the LIAISON® Toxo IgM II assay be performed in conjunction with a Toxoplasma gondii IgG assay. This assay has not been cleared/approved by the FDA for blood/plasma donor screening.

The LIAISON Control Toxo IgM II (negative and positive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON Toxo IgM II assay on the LIAISON® XL Analyzer.

The method for qualitative determination of specific IgM to Toxoplasma gondii is an antibody capture chemiluminescence immunoassay (CLIA). The principal components of the test are magnetic particles (solid phase) coated with IgG (mouse, monoclonal) is used for coating magnetic particles (solid phase) and a mouse monoclonal antibody to human IgM, Toxoplasma gondii antigen, and a conjugate of mouse monoclonal antibodies to Toxoplasma gondii linked to an isoluminol derivative (isoluminol-antibody coniugate).

During the first incubation, IgM antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the mouse monoclonal antibody conjugate reacts with Toxoplasma gondii antigen and the immune complex thus formed reacts with IgM already bound to the solid phase. After the incubations, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of Toxoplasma gondii IgM concentration present in calibrators, samples or controls.

All assay steps and incubations are performed by the LIAISON® XL Analyzer.

The provided text describes the LIAISON® Toxo IgM II assay, a chemiluminescent immunoassay (CLIA) for the qualitative determination of IgM antibodies to Toxoplasma gondii. Here's a breakdown of the acceptance criteria and the studies performed:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the LIAISON® Toxo IgM II assay are primarily demonstrated through comparative clinical studies, particularly in terms of agreement with a comparator assay and a CDC panel. The document doesn't explicitly state numerical acceptance criteria thresholds (e.g., "must achieve X% sensitivity"), but rather presents the achieved performance. Based on the data provided, implied criteria are high agreement percentages for both negative and positive samples.

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

• Prospective US Population: 204 individuals. Data provenance: US, prospective.
• Prospective European Population: 600 individuals. Data provenance: European, prospective.
• Pregnant Women Population: 201 females. Data provenance: Not specified (likely US or European as part of prospective studies), prospective.
• Retrospective/Pre-Selected Population: 33 samples. Data provenance: Not specified (likely US or European), retrospective.
• CDC Panel Study: 100 frozen blind specimens (32 true positive, 65 true negative, 3 dilutions of 3 true positive samples). Data provenance: CDC (reference panel), retrospective.
• Precision and Reproducibility:
  • Precision study: 80 measurements per sample (one site).
  • Reproducibility study: 480 measurements per sample (three sites).

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

The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical study test sets. It mentions a "comparator assay" and "references" for the CDC panel, implying established methods or expert determinations, but details are not provided.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the clinical study test sets. The "comparator assay" served as the basis for classification in the prospective and retrospective studies. For the CDC panel, the CDC itself provided the "true positive" and "true negative" categorizations.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is a diagnostic assay (an in-vitro diagnostic, IVD), not an image-based AI device designed for human reader assistance. Therefore, the concept of human readers improving with or without AI assistance does not apply.

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

Yes, the performance studies for the LIAISON® Toxo IgM II assay were conducted in a standalone manner. The assay, which is an automated chemiluminescent immunoassay, directly measures and reports results (qualitative determination of IgM antibodies) without human intervention in the interpretation process of the assay's output itself. The results are generated by the LIAISON® XL Analyzer.

7. The Type of Ground Truth Used

• Clinical Studies (Prospective and Retrospective): The ground truth was established by a "comparator assay" (Diamedix Is-Toxoplasma IgM Capture Test System (K001707)).
• CDC Panel Study: The ground truth was established by the "CDC (Reference Immunodiagnostic Lab, Biology and Diagnostic Branch Division of Parasitic Diseases)" which categorized samples as "Toxoplasma IgM true positive" and "Toxoplasma IgM true negative." This represents a form of expert consensus and reference laboratory determination.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for an algorithm, as this is an IVD assay, not a machine learning model in the typical sense. The assay is built on established biochemical principles and reagents. Therefore, the concept of a training set for an AI/algorithm is not directly applicable. If one were to interpret "training" in the context of assay development, it would refer to the optimization and validation experiments conducted during the assay's development prior to the reported clinical studies, but no sample sizes for such development phases are provided.

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

Since there is no explicit "training set" for an AI algorithm, this question is not directly applicable. The assay's analytical characteristics and performance are based on its chemical and immunological design, calibrated against reference materials and validated using clinical samples.

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The DiaSorin LIAISON® TSH assay is an in vitro chemiluminescent immunoassay intended for the quantitative determination of thyroid stimulating hormone (TSH), also known as thyrotropin and thyrotropic hormone, in human serum. The test has to be performed on the LIAISON® XL Analyzer. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

The DiaSorin LIAISON® Control Thyroid 1, LIAISON® Control Thyroid 2 and LIAISON® Control Thyroid 3 are intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® TSH assay.

The DiaSorin LIAISON® TSH assay is an in vitro chemiluminescent immunoassay for the quantitative determination of thyroid stimulating hormone (TSH), also known as thyrotropin and thyrotropic hormone, in human serum. The test has to be performed on the LIAISON® XL Analyzer. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

The DiaSorin LIAISON® Control Thyroid 1, LIAISON® Control Thyroid 2 and LIAISON® Control Thyroid 3 are intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® TSH assay.

The method for the quantitative determination of TSH is a sandwich chemiluminescence immunoassay. A specific mouse monoclonal antibody is coated on the magnetic particles (solid phase); another monoclonal antibody is linked to an isoluminol derivative (isoluminol-antibody conjugate). All assay steps and incubations are performed by the LIAISON® XL Analyzer.

Results are determined by a 2 point calibration conversion of the master curve to a working curve. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is inversely related to TSH concentration present in calibrators, patient samples or controls.

The LIAISON® Control Thyroid 1, 2 and 3 are prepared from human serum at target values of 0.5-0.78 mIU/L. 7.0-9.48 mIU/L and 42.7-57.7 mIU/L.

The provided document describes the DiaSorin LIAISON® TSH assay, an in vitro chemiluminescent immunoassay for the quantitative determination of thyroid stimulating hormone (TSH) in human serum, and associated quality controls (LIAISON® Control Thyroid 1, 2, and 3). The submission aims to demonstrate substantial equivalence to a predicate device.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of "acceptance criteria" but rather describes various performance characteristics and their results, which serve as evidence of the device meeting certain performance standards for substantial equivalence. I will infer the acceptance criteria from the context of typical lab assay performance and the results presented.

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

• Method Comparison: 181 samples. Data provenance is not explicitly stated (e.g., country of origin, retrospective/prospective), but it is implied to be clinical human serum samples.
• Reference Range/Expected Values: 130 apparently healthy human serum samples. Data provenance is not explicitly stated.
• Reproducibility/Precision: A coded panel of 6 frozen serum samples (low, medium, high), plus 3 levels of LIAISON® Control Thyroid. The study was performed at DiaSorin Inc., suggesting a prospective in-house study.
• Linearity: One high TSH sample serially diluted to generate 7 concentrations.
• LoB/LoD/LoQ: Six serum specimens at low TSH doses, assayed in 72 determinations.
• Interfering Substances: Not explicitly stated how many samples per substance, but implied to be controlled laboratory experiments.

The provenance (country of origin) is not provided for clinical samples. The studies for reproducibility, linearity, LoB/LoD/LoQ, and interfering substances appear to be prospective laboratory studies.

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

For this type of in vitro diagnostic device (quantitative immunoassay), the "ground truth" for the test set is established by the reference methods or established values, not human expert consensus.

• Method Comparison: The predicate or commercially available immunoassay serves as the reference for comparison. No human experts are used for ground truth for individual samples; the accuracy of the comparator assay is assumed.
• Reference Range: "Apparently healthy test subjects" were used. Their health status would have been determined by clinical criteria, likely by medical professionals (e.g., physicians) but specific numbers or qualifications of experts are not relevant or provided in this context.
• Reproducibility/Precision, Linearity, LoB/LoD/LoQ, Interfering Substances, Traceability: These performance characteristics are evaluated against known standards, spiked samples, or by repeated measurements, not through expert consensus on individual results. The "ground truth" for these studies is typically defined by the experimental setup and reference materials.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1, 3+1) are typically used in studies where human readers are part of the ground truth establishment (e.g., interpretation of medical images). This is not applicable to a quantitative immunoassay where numerical values are measured and compared against established analytical performance goals or a predicate device. The "adjudication" is based on statistical methods (e.g., Passing & Bablok regression, %CV calculations) comparing the device's numerical output to expected values or reference 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

An MRMC study is not applicable as this is an in vitro diagnostic immunoassay, not an AI-assisted diagnostic imaging or interpretation device that involves human readers. Therefore, no such study was performed, and no effect size for human reader improvement with AI assistance is provided.

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

This device is an automated immunoassay system (LIAISON® XL Analyzer) that quantitatively determines TSH levels. Its performance is inherently "standalone" in the sense that the analyzer yields a numerical result without human interpretation of raw signals; human involvement is in sample loading, calibration, quality control, and result review. The studies described (Method Comparison, Precision, Linearity, LoB/LoD/LoQ, Interference) all evaluate the performance of the automated assay system in generating these numerical results.

7. The Type of Ground Truth Used

• Method Comparison: The results obtained from a "commercially available immunoassay" (predicate or similar) served as the comparative truth.
• Reference Range: Established by measuring TSH levels in "apparently healthy test subjects."
• Reproducibility/Precision: Determined by repeated measurements of samples (frozen serum, controls) with expected concentrations.
• Linearity: Established by serially diluting a high TSH sample, where the concentration of each dilution is known relative to the original sample.
• LoB/LoD/LoQ: Established through statistical methods on samples with very low or zero analyte concentrations.
• Interfering Substances: Established by comparing results from samples spiked with known interfering substances against unspiked control samples.
• Traceability: Traceable to the WHO reference material: 2nd IRP WHO 80/558 standard.

In essence, the ground truth is based on reference methods, known concentrations of reference materials, and established clinical characteristics (e.g., healthy individuals).

8. The Sample Size for the Training Set

This document describes performance validation studies for a diagnostic assay, not a machine learning or AI model that typically has a distinct "training set." Therefore, a "training set" in that context is not applicable. The development of the assay itself would have involved extensive R&D and optimization, but those details are not provided as specific "training set" sizes here.

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

As noted above, the concept of a "training set" in the context of an AI/ML model with corresponding ground truth establishment is not directly applicable to this immunoassay device approval. The "ground truth" for the various analytical performance characteristics (e.g., linearity, precision, interference) are established via standard analytical chemistry and immunoassay validation practices using reference materials, spiked samples, and comparative methods, as described in point 7.

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The DiaSorin LIAISON® FT4 assay is an in vitro chemiluminescent immunoassay intended for the quantitative determination of free thyroxine (FT4) in human serum using the LIAISON® Analyzer. It is intended for use as an aid in the clinical assessment of thyroid status.

The DiaSorin LIAISON® Control Thyroid 1, LIAISON® Control Thyroid 2 and LIAISON® Control Thyroid 3 are intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® FT4 assay.

The DiaSorin LIAISON® FT4 assay's method for quantitative determination of FT4 is based on the Solid Phase Antigen Linked Technique (SPALT) principle. A T4-protein-conjugate is coated on the magnetic particles (solid phase); a monoclonal antibody is linked to an isoluminol derivative (isoluminol-antibody conjugate). All assay steps and incubations are performed by the LIAISON® Analyzer.

Results are determined by a 2 point calibration conversion of the master curve to a working curve. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is inversely related to FT4 concentration present in calibrators, patient samples or controls.

The DiaSorin LIAISON® FT4 assay is an in vitro chemiluminescent immunoassay intended for the quantitative determination of free thyroxine (FT4) in human serum using the LIAISON® Analyzer. It is intended for use as an aid in the clinical assessment of thyroid status.

The DiaSorin LIAISON® Control Thyroid 1, LIAISON® Control Thyroid 2 and LIAISON® Control Thyroid 3 are intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® FT4 assay.

Here's an analysis of the provided text regarding acceptance criteria and the study proving the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The documents do not explicitly list formal "acceptance criteria". However, performance data is presented, which implicitly demonstrates the device's acceptable performance. For clarity, I've inferred common performance metrics for this type of device and presented the reported results.

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

• Method Comparison: 201 samples.
• Reference Range Determination: 130 apparently healthy adult human serum samples.
• Reproducibility/Precision (20-Day Study): A coded panel of 4 frozen serum samples prepared by DiaSorin, plus 3 levels of LIAISON® Control Thyroid. Each sample/control tested 80 times (2 replicates/run, 2 runs/day, 20 days).
• Reproducibility/Precision (5-Day Study): A panel of three frozen serum samples prepared by DiaSorin with FT4 concentrations near medical decision points. Each sample tested 60 times (12 replicates/run, 1 run/day, 5 days).
• Dilution Linearity: One spiked sample, diluted into ten evenly spaced intervals, tested in four replicates for each dilution.
• LoB/LoD/LoQ: Not explicitly stated, but typically involves multiple replicates of blank and low-concentration samples.
• Interfering Substances: Not explicitly detailed, but involved testing various potential interferents.
• Specificity (Cross-Reactivity): Not explicitly detailed regarding sample count, but involves specific cross-reactants.

Data Provenance:
The studies appear to be prospective, performed internally by DiaSorin Inc. (e.g., "A twenty day reproducibility/precision study was performed at DiaSorin Inc.", "An additional five day precision study was performed at DiaSorin"). The "country of origin" is implied to be the US, given the submission to the FDA by DiaSorin Inc. in Stillwater, MN.

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

For an in vitro diagnostic (IVD) device like a Free Thyroxine Assay, the "ground truth" is typically established by reference methods or established laboratory practices, not by expert interpretation in the same way an imaging device might use radiologists.

• Method Comparison: The comparison was made against a "commercially available immunoassay," which serves as the reference or "ground truth" for comparative performance. The specific details of how its "ground truth" was established are not provided, but it is implied to be a legally marketed, accepted method (the Roche Elecsys® FT4, K961489, is named as the predicate device).
• Reference Range: Established by testing samples from "130 apparently healthy adults." These samples themselves represent the "ground truth" of a healthy population.
• Reproducibility/Precision, Dilution Linearity, LoB/LoD/LoQ, Interfering Substances, Specificity: These studies rely on scientifically controlled preparations (e.g., spiked samples, controls, known concentrations) and established assay principles, rather than expert consensus on patient data.

Therefore, the concept of "number of experts" and their "qualifications" for ground truth establishment, as it might apply to image-based diagnostics, is not directly applicable here. The "ground truth" for the test set is either a comparative, legally marketed device or samples with analytically defined characteristics.

4. Adjudication Method for the Test Set

Not applicable. As described above, the "ground truth" for this type of IVD device is based on analytical measurements against a comparative method or defined standards, not on subjective interpretations requiring adjudication among experts.

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 is an in vitro diagnostic (IVD) assay, not an AI-powered diagnostic imaging device that involves human readers. Therefore, an MRMC study to assess human reader improvement with AI assistance is not relevant to this submission.

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

This device is a standalone algorithm, in the sense that it is a fully automated immunoassay system that quantitatively determines FT4 concentration without human interpretative input on the result itself (beyond clinical interpretation of the quantitative value). The performance data presented (Method Comparison, Precision, Linearity, etc.) represents the standalone performance of the LIAISON® FT4 assay. There is no human "in the loop" for the measurement process; the LIAISON® Analyzer performs all assay steps and incubates.

7. The Type of Ground Truth Used

The ground truth used for various performance evaluations includes:

• Comparative Device: For method comparison, the Roche Elecsys® FT4 Test (K961489) served as the reference.
• Clinically Defined Samples: For reference range determination, samples from "apparently healthy adults" were used to establish expected values.
• Analytically Defined Standards/Samples: For precision, linearity, LoB/LoD/LoQ, interfering substances, and specificity, the ground truth was established by:
  • Commercial Controls: LIAISON® Control Thyroid (1, 2, 3), whose target values are established through rigorous internal procedures involving multiple analyzers and kit lots.
  • Internal Panels/Spiked Samples: Frozen serum samples prepared by DiaSorin, or buffer samples spiked with known concentrations of T4 and other substances.

8. The Sample Size for the Training Set

The document describes performance studies, not a machine learning model. IVD assays like the LIAISON® FT4 are based on well-established chemical and immunological principles, not on "training sets" in the context of AI. The "training" in this context refers to the development and optimization of the assay itself and its reagents.

However, if we interpret "training set" more broadly as data used to develop and optimize the assay, rather than for final validation:

• Calibrator Value Assignment: Master standards are prepared and concentrations are assigned by testing in "10 different assays against the Primary Reference Standard." Kit calibrator values are then assigned using "multiple LIAISON® analyzers with several kits calibrators over several runs." This is part of the internal development and calibration process.
• Control Value Assignment: A minimum of "60 valid test results for each control" are used to establish the target value and range, using "a minimum of 3 LIAISON® Analyzers, using 2 different approved LIAISON® FT4 assay kit lots, at a minimal time period of 3 days." This data essentially "trains" the acceptable control ranges.

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

Again, this is not an AI model, so "training set ground truth" is interpreted in the context of IVD assay development.

• Calibrator "Ground Truth": The calibrators are referenced to an "in-house Primary Reference Standard preparation." This primary standard itself would be meticulously characterized and traceable to internationally recognized standards if available, or rigorously defined internally. Concentrations are assigned via testing against this standard.
• Control "Ground Truth": The target values for the LIAISON® Controls (Thyroid 1, 2, 3) are established by calculating the mean from a minimum of 60 valid test results, spanning multiple analyzers, kit lots, and days. The "ground truth" for control values is therefore derived empirically from the performance of the LIAISON® FT4 assay itself, establishing an expected range for quality control.

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The DiaSorin LIAISON® Testosterone assay is a direct, competitive, chemiluminescence immunoassay (CLIA) intended for the quantitative determination of testosterone in human serum and plasma on the LIAISON®Analyzer. The assay is intended for in vitro diagnostic use.

Measurement of testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in male subjects and, in female subjects hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.

The DiaSorin LIAISON® Testosterone Control Set is intended for use as assayed quality control samples to monitor the accuracy and precision of the DiaSorin LIAISON® Testosterone immunoassay.

The LIAISON® Testosterone assay's method for quantitative determination of testosterone is a direct, competitive, chemiluminescence immunoassay (CLIA). Specific antibody to testosterone is bound to magnetic particles (solid phase) and testosterone is linked to an isoluminol derivative. During the incubation, testosterone is dissociated from its binding protein and competes with labeled testosterone for binding sites on the antibody. After the incubation, the unbound material is removed with a wash cycle, Subsequently, the starter reagents are added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of testosterone present in calibrators, controls, or samples. All assay steps and incubations are performed by the LIAISON® Analvzer.

Two point kit calibrators are used to establish specific working curves based on assay master curves stored on the Analyzer.

The LIAISON® Testosterone reagent kit consists of a reagent intrgral which contains antibody coated magnetic particles (2.3 mL), conjugate (12 mL) and assay buffer (12 mL) reagents. Two levels of ready to use calibrators (2 vials each level, 2.0 mL per vial) are provided with each kit. Each kit consists of 100 tests.

The DiaSorin LIAISON® Testosterone assay and Control Set are subject to a 510(k) premarket notification for substantial equivalence to a predicate device. This submission outlines performance data to demonstrate that the device meets acceptance criteria.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" as a separate, defined set of thresholds for each performance metric, but rather presents the results of various studies and compares them to the predicate device and established guidelines (e.g., CLSI guidelines). The performance data implicitly serves as the evidence that the device meets the necessary standards for its intended use.

Here's a summary of the reported device performance:

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

• Method Comparison: One hundred eighty-four (184) serum samples were initially tested. One sample was above the upper limit, and 21 samples were below the measuring range of the LIAISON® Testosterone assay and were excluded. Therefore, 162 serum samples were used for the analysis.
  • Data Provenance: Not explicitly stated, but clinical samples (human serum) used to span the reportable range of each assay. Implied to be retrospective as they were collected and then analyzed. The country of origin is not specified.
• Reproducibility/Precision: A coded panel comprised of 6 frozen serum samples (2 low, 2 medium, 2 high) and 2 levels of LIAISON® Testosterone Controls were tested. The total number of measurements for each sample/control across all sites and runs was 480.
  • Data Provenance: DiaSorin Inc. prepared the coded panel. Testing was performed at DiaSorin Inc. and 2 external sites. Implied to be prospective for the purpose of the study. The country of origin is not specified.
• LoB/LoD/LoQ: Sample size not explicitly stated for this particular determination, but it generally involves multiple replicates of blank and low-concentration samples.
  • Data Provenance: Not specified.
• Reference Range/Expected Values:
  • Males 18-49 years: N=161
  • Males ≥ 50 years: N=132
  • Females 18-49 years: N=202
  • Females ≥ 50 years: N=127
  • Data Provenance: Human serum samples from "apparently healthy adults." Implied to be clinical samples, likely prospective for the purpose of establishing reference ranges. The country of origin is not specified.
• Dilution Linearity: Three (3) samples of each sample type (serum, SST serum, EDTA plasma) were used, diluted to span the measuring range.
  • Data Provenance: Not specified.
• Specificity and Interfering Substances: Tested by adding known substances to serum pools. Sample size refers to the number of substances tested rather than individual patient samples.
  • Data Provenance: Not specified.

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

This device is an in vitro diagnostic (IVD) assay for quantitative determination of a hormone (testosterone). The "ground truth" for such devices is established by reference methods, comparison with predicate devices, and the inherent chemical/biological properties of the analytes. It does not involve human expert interpretation of images or clinical data for individual cases in the same way as, for example, an AI imaging device.

• No "experts" in the sense of clinicians or radiologists establishing ground truth for individual cases are mentioned or relevant for this type of device.
• The ground truth for the method comparison study is implicitly the results obtained from the predicate device, the Roche Cobas® Testosterone II Test (K093421), run on the Elecsys analyzer, which is a previously cleared and accepted method for testosterone measurement.

4. Adjudication Method for the Test Set:

Not applicable. As this is an IVD assay measuring an analyte, there is no adjudication process involving multiple human observers for results. The accuracy is determined by analytical performance against known standards and comparison with accepted methods.

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 typically relevant for interpretative devices (e.g., imaging AI) where human readers are making diagnoses. For an IVD assay, the performance is evaluated on its analytical accuracy and precision.

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

Yes, the studies presented (Method Comparison, LoB/LoD/LoQ, Reproducibility/Precision, Dilution Linearity, Specificity, Interfering Substances, Reference Range) all represent the standalone performance of the DiaSorin LIAISON® Testosterone assay without human interpretation or intervention in the measurement process itself, beyond the standard operation of the instrument. The results (e.g., testosterone concentration in ng/dL) are automatically generated by the LIAISON® Analyzer.

7. The Type of Ground Truth Used:

• Method Comparison: The results from the predicate device (Roche Cobas® Testosterone II Test) were used as the reference "ground truth" for comparison.
• Reproducibility/Precision, LoB/LoD/LoQ, Dilution Linearity, Specificity, Interfering Substances: These studies use analytically derived ground truth, often involving:
  • Known concentrations of analytes (e.g., spiked samples for specificity, control materials).
  • Reference materials.
  • Statistical methods to determine limits.
  • Comparison to expected values from dilution series.
• Reference Range/Expected Values: Healthy human serum samples were used to establish the statistical distribution of testosterone in various populations, serving as the "ground truth" for normal physiological ranges.

8. The Sample Size for the Training Set:

This document describes a 510(k) submission for a chemiluminescence immunoassay (CLIA), which is a traditional laboratory-based analytical device, not an AI/Machine Learning model. Therefore, the concept of a "training set" in the context of machine learning is not applicable.

• The assay's "training" or calibration relies on a master curve stored on the Analyzer and specific working curves established with two-point kit calibrators provided with each kit. These calibrators contain known concentrations of testosterone.

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

As noted above, this is not an AI/ML device, so there is no "training set" in that sense. The "ground truth" for the calibrators (which are analogous to the data used to "train" a traditional assay) is established through:

• Manufacturing and Analytical Certification: Calibrators are precisely manufactured with known, certified concentrations of testosterone. These concentrations are typically determined using highly accurate reference methods (e.g., isotope dilution mass spectrometry - ID-MS), which serve as the gold standard for analyte quantification.
• Master Curves: The assay relies on a "master curve" stored on the LIAISON® Analyzer. This master curve is developed using a comprehensive set of reference materials with certified testosterone concentrations to define the relationship between the signal (RLU) and the analyte concentration across the entire measuring range. The two-point calibrators then adjust this master curve for each specific kit and run to account for minor variations.

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