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The CoaguChek XS Plus System is intended for use by professional healthcare providers for quantitative prothrombin time testing for the monitoring of warfarin therapy. The system uses fresh capillary or non-anticoagulated venous whole blood.

The CoaguChek XS Plus system is a portable coagulation monitoring system to monitor prothrombin time (PT) in patients receiving oral anticoagulant therapy. The system uses the amperometric detection of thrombin in the blood sample. A test strip is used to determine a PT value from 8 µL of whole blood. Onboard quality control is available on every test strip and the system also features an optional external quality control material (CoaguChek XS PT Control).

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Elecsys Phospho-Tau (181P) Plasma is an in vitro electrochemiluminescence immunoassay (ECLIA) intended for the measurement of the phosphorylated Tau 181 protein in human plasma on cobas e immunoassay analyzers.

The Elecsys Phospho-Tau (181P) Plasma assay result is intended to be used as an aid in the initial assessment for Alzheimer's disease and other causes of cognitive decline in adult patients aged 55 years and older, presenting with signs, symptoms, or complaints of cognitive decline. The result should be interpreted in conjunction with other clinical information.

A negative test result is consistent with a negative amyloid positron emission tomography (PET) scan result and reduced likelihood that a patient's cognitive impairment is due to amyloid pathology. These patients should be investigated for other causes of cognitive decline.

A positive test result may not be consistent with a positive amyloid PET scan result. Patients with an initial positive result should be further investigated to determine whether the amyloid pathology can be a cause of cognitive impairment.

In vitro electrochemiluminescence immunoassay (ECLIA) intended for the measurement of the phosphorylated Tau 181 protein (pTau181p) in human plasma.

Elecsys Phospho-Tau (181P) Plasma utilizes a sandwich test principle and has a total duration time of 18 minutes.

• 1st incubation: 30 µL of sample, biotinylated monoclonal antibody specific for phosphorylation at threonine 181, and a monoclonal tau-specific antibody labeled with a ruthenium complex^a) react to form a sandwich complex.
• 2nd incubation: After addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.
• The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell II M. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier.
• Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the cobas link.

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Immunoassay for the in vitro quantitative determination of cortisol in human urine. The determination of cortisol is used for the recognition and treatment of functional disorders of the adrenal gland.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

The Elecsys Cortisol III immunoassay employs a competitive test principle using a cortisol-specific biotinylated monoclonal antibody and a cortisol-derivative labeled with a ruthenium complex. The Elecsys Cortisol III immunoassay is intended for the in vitro quantitative determination of cortisol in human urine. The determination of cortisol is used for the recognition and treatment of functional disorders of the adrenal gland on the cobas e immunoassay analyzers.

Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the cobas link.

The Elecsys Cortisol III immunoassay reagent Rack Pack comprises the following:

M Streptavidin-coated microparticles (transparent cap), 1 bottle, 12.4 mL:
Streptavidin-coated microparticles 0.72 mg/mL; preservative.

R1 Anti-cortisol-Ab~biotin (gray cap), 1 bottle, 21.0 mL:
Biotinylated monoclonal anti-cortisol antibody (mouse) 18 ng/mL; danazol 20 μg/mL; MES buffer 100 mmol/L, pH 6.0; preservative.

R2 Cortisol-peptide~Ru(bpy) (black cap), 1 bottle, 21.0 mL:
Cortisol derivative (synthetic), labeled with ruthenium complex, 5 ng/mL; danazol 20 μg/mL; MES buffer 100 mmol/L, pH 6.0; preservative.

MES = 2-morpholino-ethane sulfonic acid

The provided 510(k) summary for the Elecsys Cortisol III device focuses primarily on non-clinical performance evaluations to demonstrate substantial equivalence to a predicate device. It does not describe a study to prove performance against specific acceptance criteria for diagnostic accuracy (e.g., sensitivity, specificity, or agreement with ground truth in a clinical context) with a test set of patient samples.

Here's an analysis of the available information:

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in the traditional sense for diagnostic performance metrics like sensitivity, specificity, or agreement against a clinical ground truth. Instead, it details performance specifications for various analytical aspects and states that these "met the predefined acceptance criteria." These are primarily related to the analytical performance of the assay itself.

2. Sample Size and Data Provenance for Test Set

• Precision (Repeatability & Intermediate Precision): Human urine samples (24-hour urine) and controls. Two replicates per run, two runs per day for 21 days for each of 4 human urine samples and 2 controls. (Total of $4 \text{ samples} \times 2 \text{ replicates/run} \times 2 \text{ runs/day} \times 21 \text{ days} = 336$ measurements for human urine, plus $2 \text{ controls} \times 2 \text{ replicates/run} \times 2 \text{ runs/day} \times 21 \text{ days} = 168$ measurements for controls. Or potentially 42 total runs for each sample/control).
• Analytical Sensitivity (LoB, LoD, LoQ): Not specified beyond "reagents and calibrators" likely being used.
• Linearity/Assay Reportable Range: Dilution series contained a minimum of 9 concentrations. Number of samples not explicitly stated but implies a set of samples specifically created to span the measuring range.
• HAMA: Not specified.
• Endogenous Interferences: Human urine samples (24-hour urine) were used. The number of samples is not explicitly stated.
• Analytical Specificity/Cross-Reactivity: Human urine (24-hour urine) samples. Specific numbers not provided beyond "samples were measured in the presence and absence of the potential cross-reactants."
• Exogenous Interferences – Drugs: In vitro tests performed on 12 commonly used pharmaceuticals and additional special drugs. This implies spiked samples rather than a "test set" of patient samples.
• Method Comparison: "Native 24 h urine samples" for comparison with the predicate device. The number of samples is not specified.
• Reference Range Study: Samples collected from an "apparently healthy population in the United States" across three study sites. The exact number of samples is not provided, but it's sufficient for establishing 2.5th and 97.5th percentiles (typically requires 120+ samples according to CLSI EP28-A3c).

Data Provenance: The document explicitly states "human urine samples (24-hour urine)" for most studies and for the reference range, "collected across three study sites... in the United States." This indicates prospective collection for the reference range study specifically for generating normal values applicable to the US population. For other analytical performance claims, the sample type (human urine) is generally mentioned, suggesting a similar provenance, likely for prospective testing within the manufacturer's lab or clinical sites.

3. Number of Experts and Qualifications for Ground Truth

Not applicable for the Elecsys Cortisol III. This is an in vitro diagnostic device (IVD) that quantitatively measures a biomarker (cortisol). The "ground truth" for such devices is typically established through recognized analytical standards, reference methods, and comparison to a legally marketed predicate device, rather than expert consensus on diagnostic images or clinical assessments. The closest to "ground truth" in this context would be the accuracy against a gold standard analytical method or purified cortisol standards. These details are not provided but are implicit in the validation that relies on CLSI guidelines.

4. Adjudication Method for the Test Set

Not applicable. As this is a quantitative IVD for a biomarker, diagnostic classification and adjudication by experts are not relevant to the described analytical studies. The performance is assessed by comparison to expected analytical results or a predicate device.

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

Not applicable. MRMC studies are typically for imaging devices or software that assist human readers in making a diagnosis. The Elecsys Cortisol III is an automated in vitro diagnostic immunoassay for quantitative measurement of cortisol in urine. It does not involve human readers interpreting cases with or without AI assistance.

6. Standalone Performance Study

Yes, the entire submission describes standalone performance. The Elecsys Cortisol III is an immunoassay designed to operate on cobas e immunoassay analyzers. All the performance data (precision, sensitivity, linearity, interference, cross-reactivity, method comparison) are generated directly from the device's measurement of cortisol in urine samples. The device itself performs the quantitative determination without human-in-the-loop interpretation impacting the measurement results. The method comparison study directly compares its quantitative output to the predicate device's quantitative output.

7. Type of Ground Truth Used

For an IVD like Elecsys Cortisol III, the "ground truth" for the test set is established by:

• Reference standards/Calibrators: For analytical sensitivity (LoB, LoD, LoQ) and linearity studies, known concentrations of cortisol (or materials traceable to them) are used.
• Predicate device comparison: For method comparison, the results from the Elecsys Cortisol III are compared to those obtained from the legally marketed ARCHITECT Cortisol (K062204), which serves as the established "truth" or benchmark for demonstrating substantial equivalence.
• Spiked samples/characterized samples: For interference and cross-reactivity studies, samples with known concentrations of interferents or cross-reactants are used to determine the device's accuracy in their presence.
• Clinically characterized healthy population samples: For the reference range study, samples from healthy individuals are used to establish normal ranges, though this isn't a "ground truth" for diagnostic accuracy.

8. Sample Size for the Training Set

The document does not mention "training set" in the context of an AI/ML algorithm. This device is an immunoassay, which relies on chemical reactions and optical detection, not an AI/ML model that requires a training set. The term "training set" is therefore not applicable here.

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

Not applicable. As noted above, there is no AI/ML training set for this immunoassay device.

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Elecsys Anti-SARS-CoV-2 is an immunoassay intended for the in vitro qualitative detection of total antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in human serum and Li-heparin, K2-EDTA and K3-EDTA plasma collected on or after 15 days post-symptom onset. The test is intended as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e 601 immunoassay analyzer.

Elecsys Anti-SARS-CoV-2 is a qualitative, serological, double-antigen sandwich principle immunoassay to be used on the cobas e 601 analyzer with an 18-minute test time. Results are determined automatically by the software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by calibration. The Elecsys Anti‑SARS‑CoV-2 assay uses a recombinant protein representing the nucleocapsid (N) antigen for the determination of antibodies against SARS‑CoV‑2.

The reagent working solutions include: rackpack (kit placed on the analyzer)

• M Streptavidin-coated microparticles (transparent cap), 1 bottle, 12 mL: Streptavidin-coated microparticles 0.72 mg/mL; preservative.
• R1 SARS-CoV-2-Ag~biotin, (gray cap), 1 bottle, 16 mL: Biotinylated SARS‑CoV‑2‑specific recombinant antigen (E. coli) < 0.5 mg/L; HEPES^a) buffer 50 mmol/L, pH 7.7; preservative.
• R2 SARS-CoV-2 Ag~Ru(bpy) (black cap), 1 bottle, 16 mL: SARS‑CoV‑2‑specific recombinant antigen labeled with ruthenium complex < 0.5 mg/L; HEPES^(b) buffer 50 mmol/L, pH 7.7; preservative.

^(a) HEPES = [4-(2-hydroxyethyl)-piperazine]-ethane sulfonic acid

The Elecsys Anti-SARS-CoV-2 assay includes two liquid calibrators, which are packed with the test kit:

• ACOV2 Cal1 Negative calibrator 1 (white cap), 2 bottles of 0.67 mL: Human serum, non-reactive for anti‑SARS‑CoV‑2 antibodies; buffer; preservative.
• ACOV2 Cal2 Positive calibrator 2 (black cap), 2 bottles of 0.67 mL: Human serum, reactive for anti‑SARS‑CoV‑2 antibodies; buffer; preservative.

The provided FDA 510(k) clearance letter and summary describe the acceptance criteria and the study that proves the device, Elecsys Anti-SARS-CoV-2, meets those criteria.

Here's the breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as clear numerical targets for PPA and NPA prior to presenting the results. However, implied acceptance criteria for qualitative serology tests typically involve a high percentage of agreement. Based on the reported performance, we can infer the acceptance criteria were met by these results.

Additional Non-Clinical Acceptance Criteria (Met for all):

• Precision: Standard Deviation (SD) and Coefficient of Variance (CV) values within predetermined limits for repeatability, between-run, between-day, between-lot, and between-site precision.
• Hook Effect: No hook effect observed.
• Potential Interference (Endogenous Substances): Biotin tolerance $\le$ 1200 ng/mL; no interference within specification for Intralipid, Bilirubin, Hemoglobin, Rheumatoid Factor, IgG, IgM, IgA, human serum albumin, ANA, cholesterol, and triglycerides.
• Analytical Cutoff Sensitivity: Cutoff of 1.00 COI corresponds to 1.137 BAU/mL (demonstrated alignment with international standard).
• Analytical Specificity- Potential Cross-Reactivity: False positive rate for cross-reacting antibodies within acceptable limits (2 false positives out of 7 MERS-CoV glycoprotein samples observed, overall 1836 samples tested).
• Exogenous Interference: Results within specification for 17 common drugs and 18 special drugs (with the exception of Ritonavir, which was within specification at 1x daily dose).
• Matrix Comparison: Matrix equivalency demonstrated for serum, Li-Heparin, K2-EDTA, K3-EDTA plasma, and separation gel tubes.
• Reagent, Calibrator, and Control Stability: Met stated storage times and conditions (e.g., 28 days on-board reagent, 10 hours on-board PreciControl, 30 days refrigerator after first opening, 28 days after first opening for PreciControl, 25 days lot calibration stability, 7 days on-board calibration stability).
• Specimen Stability: Met stated storage times and conditions (e.g., 7 days at 15-25°C, 14 days at 2-8°C, 28 days at -20°C, 3 freeze-thaw cycles).
• Fresh/Frozen Study: All results within specification for fresh vs. frozen samples.

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

• Negative Percent Agreement (NPA):
  • Sample Size: 9007 pre-pandemic specimens.
  • Data Provenance: Not explicitly stated (e.g., country of origin), but implicitly "pre-pandemic" suggests samples collected before December 2019. This is retrospective data.
• Positive Percent Agreement (PPA) - Traditional Clinical Study:
  • Sample Size: 254 specimens collected $\ge$ 15 days post symptom onset (DPSO), excluding COVID-19 vaccinated individuals and immunocompromised subjects.
  • Data Provenance: Not explicitly stated (e.g., country of origin), but described as collected under "routine laboratory conditions." This is retrospective or potentially a mix of retrospective and prospective, reflecting real clinical samples.
• PPA - Real-World Data:
  • Sample Size: 285 samples from non-immunocompromised subjects who did not receive the COVID-19 vaccine, collected $\ge$ 15 DPSO.
  • Data Provenance: Collaborating institution in the United States, collected from March 2020 – March 2021. This is retrospective data.

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

For this serology test, the ground truth is established through laboratory methods, not by human expert readers in the way an imaging AI would be adjudicated.

• NPA: Ground truth was "presumed to be negative for anti-SARS-CoV-2 antibodies" based on collection before December 2019, prior to the widespread circulation of SARS-CoV-2.
• PPA (Traditional Clinical Study): Ground truth was established by a composite comparator method comprised of 3 SARS-CoV-2 serology assays (including the predicate assay). Seropositivity was determined by majority rule ($\ge$ 2 out of 3). Additionally, these individuals had a history of SARS-CoV-2 infection confirmed by a prior FDA authorized RT-PCR test.
• PPA (Real-World Data): Ground truth was established by PCR as the comparator. Data was collected from electronic medical records and laboratory information systems.

Qualifications of Experts: Not applicable in the context of serology ground truth determination as it relies on other laboratory assays.

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

• NPA: No adjudication method as samples were "presumed negative" based on collection date.
• PPA (Traditional Clinical Study): A form of "majority rule" for the composite comparator method was used: $\ge$ 2 out of 3 serology assays. This is akin to a 2/3 agreement rule, but applied to the reference method rather than human readers adjudicating an AI's output. The confirmatory RT-PCR also served as a strong initial ground truth.
• PPA (Real-World Data): PCR was the direct comparator, so no explicit adjudication method beyond the result of the PCR test itself.

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

This is a clinical laboratory immunoassay (serology test), not an AI software intended for medical image interpretation or human-in-the-loop assistance. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

The device itself is a standalone immunoassay system (Elecsys Anti-SARS-CoV-2 on the cobas e 601 analyzer) that provides a qualitative result (positive/negative) automatically. The entire clinical performance evaluation section describes the standalone performance of this device against established ground truths. Thus, a standalone performance evaluation was indeed done.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

• NPA: Pre-pandemic sample collection date (before December 2019), implying presumed negative status. This serves as a strong epidemiological ground truth for SARS-CoV-2 negativity.
• PPA (Traditional Clinical Study):
  • Composite Comparator Method: Majority rule ($\ge$ 2 out of 3) of other FDA-de novo and EUA-authorized Anti-SARS-CoV-2 serology assays.
  • Confirmatory RT-PCR: Individuals had a history of SARS-CoV-2 infection confirmed by a prior FDA authorized RT-PCR test.
• PPA (Real-World Data): FDA authorized RT-PCR test results from electronic medical records and laboratory information systems.

In summary, the ground truth primarily relies on a combination of other FDA-authorized laboratory tests (serology and RT-PCR) and epidemiological/temporal evidence.

8. The Sample Size for the Training Set

This document describes the validation of a serology immunoassay, not a machine learning or AI model. Therefore, there is no "training set" in the context of AI model development. The "training" for such an assay would typically involve analytical development and optimization of reagents and protocols, not a data-driven training set in the AI sense.

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

As there is no AI training set described or applicable for this type of device, this question is not relevant to the provided information. The ground truth for performance evaluation was established as described in point 7.

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Immunoassays for the in vitro quantitative determination of the soluble fms like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio in human serum.

The sFlt-1/PlGF ratio is indicated as an aid in the risk assessment of pregnant women, with a singleton pregnancy (23+0 to 34+6/7 weeks' gestation) hospitalized for hypertensive disorders of pregnancy (preeclampsia, chronic hypertension with or without superimposed preeclampsia, or gestational hypertension), to develop preeclampsia with severe features within two weeks from testing. The sFit-1/PlGF ratio should be used in conjunction with clinical assessment and routine laboratory testing.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

The Elecsys sFlt-1 and Elecsys PlGF assays employ a sandwich principle using electrochemiluminescence immunoassay "ECLIA" technology. The total duration of each assay is 18 minutes. Samples are incubated with biotinylated and ruthenium-labeled monoclonal antibodies specific to sFlt-1 or PlGF, forming a sandwich complex. Streptavidin-coated microparticles are added, binding the complex to the solid phase. The microparticles are magnetically captured, unbound substances are removed, and a voltage is applied to induce chemiluminescent emission, which is measured by a photomultiplier. Results are determined via a calibration curve generated by 2-point calibration and a master curve provided via the reagent barcode. The reagents for each assay are combined in a "rackpack".

Here's a breakdown of the acceptance criteria and study information for the Elecsys sFlt-1 and Elecsys PlGF assays, based on the provided document.

Acceptance Criteria and Device Performance

Study Details

1. Sample Size used for the Test Set and Data Provenance:

   • Clinical Performance Study (PRAECIS): N=556 pregnant women.
   • Data Provenance: The document does not explicitly state the country of origin for the PRAECIS study's clinical data, but it refers to the study as a "validation of the Roche sFlt-1/PlGF ratio cut-off." The reference range study (mentioned as a separate activity) collected samples from "$US" (United States) to establish normal reference ranges. Given the context, it's highly probable the PRAECIS clinical validation study also involved US patient data, though not explicitly stated for that specific study section.
   • Retrospective or Prospective: The document describes the study as "Praecis 'Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification'" and states it included women "admitted to the hospital with (or develop while hospitalized) a hypertensive disorder." This strongly suggests a prospective design within the hospital setting, though "retrospective" is not explicitly excluded for patient inclusion/data collection aspects. However, the nature of "risk assessment...to develop preeclampsia with severe features within two weeks from testing" implies a prospective observation period.

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

   • The document does not specify the number of experts or their qualifications used to establish the ground truth for the clinical test set. The ground truth (preeclampsia with severe features within two weeks) would typically be established by clinicians based on diagnostic criteria, but further details are not provided.

3. Adjudication Method for the Test Set:

   • The document does not specify an adjudication method (e.g., 2+1, 3+1, none) for establishing the clinical ground truth.

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

   • No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not mentioned or conducted in this submission. This device is an in-vitro diagnostic (IVD) immunoassay, not an imaging AI device that relies on human reader interpretation. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not directly applicable here.

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

   • Yes, the clinical performance evaluation (PRAECIS study) presents the standalone performance of the sFlt-1/PlGF ratio at a specified cutoff (38). It assesses the test's ability to predict clinical outcome (preeclampsia with severe features) directly. The "human-in-the-loop" aspect is that the results are "used in conjunction with clinical assessment and routine laboratory testing" by a physician, but the performance statistics presented (Sensitivity, Specificity, NPV, PPV) are for the assay's output itself.

6. Type of Ground Truth Used:

   • Clinical Outcome Data: The ground truth used was the "development of preeclampsia with severe features within two weeks from testing," as defined by established medical guidelines (likely ACOG, given its mention for the predicate device). This is a clinical outcome.

7. Sample Size for the Training Set:

   • The document does not explicitly describe a separate "training set" for an algorithm in the traditional sense, as these are immunoassays. The clinical validation study (PRAECIS) evaluates the performance of the established cutoff (38) for the sFlt-1/PlGF ratio. The cutoff itself might have been derived from earlier studies or internal research, which would implicitly act as a form of "training" or "development" data, but it's not detailed here with sample sizes. The reference range study for healthy pregnant women used 380 evaluable subjects to establish expected values.

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

   • As there isn't an explicitly described "training set" for an algorithm to learn from, this question largely pertains to the development of the assay and its interpretive cutoffs. The cutoff of 38 for the sFlt-1/PlGF ratio is stated to be "validated" in the PRAECIS study. The process for initial establishment or derivation of this cutoff (38) is not detailed in this document. It's common for such cutoffs to be determined through prior multicenter clinical trials and statistical analysis to achieve optimal predictive performance targets.

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The Tina-quant Lipoprotein (a) Gen.2 Molarity assay is an in vitro test for the quantitative determination of lipoprotein (a) [Lp(a]] in human serum and plasma on cobas c systems. The measurement of Lp(a) is useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk, when used in conjunction with clinical evaluation and other lipoprotein tests.

The Tina-quant Lipoprotein (a) Gen.2 Molarity assay is an in vitro test for the quantitative determination of lipoprotein (a) [Lp(a)] in human serum and plasma on cobas c systems. The measurement of Lp(a) is useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk, when used in conjunction with clinical evaluation and other lipoprotein tests.

Tina-quant Lipoprotein (a) Gen.2 Molarity assay quantifies lipoprotein (a) in human serum and plasma and reports the values in nmoVL with calibrator values traceable to the WHO/IFCC SRM2B reference material.

Reagents - working solutions
R1: Glycine buffer: 170 mmol/L. pH 7.0: stabilizers: BSA: rabbit serum 0.1 %, preservative
R3: Latex particles coated with polyclonal anti-human lipoprotein (a) antibodies (rabbit): 0.5 %; glycine buffer: 170 mmol/L, pH 7.3, BSA; preservative

Here's a breakdown of the acceptance criteria and study details for the Tina-quant Lipoprotein (a) Gen.2 Molarity assay, based on the provided document:

This device is an in vitro diagnostic (IVD) assay, not an AI/ML-driven device. Therefore, the concepts of human readers, multi-reader multi-case (MRMC) studies, ground truth establishment by experts for images, training sets, and adjudication methods are not directly applicable in the typical sense as they would be for an AI model that interprets medical images. The "acceptance criteria" here refer to the predefined performance specifications for an analytical assay.

Device Name: Tina-quant Lipoprotein (a) Gen.2 Molarity

1. Table of Acceptance Criteria and Reported Device Performance

The document states, "All acceptance criteria were met" for the non-clinical performance evaluation sections (Precision, Analytical Sensitivity, Linearity, Dilution, High Dose Hook Effect, Endogenous Interferences, Analytical Specificity/Cross-Reactivity, Sample Matrix Comparison, Method Comparison, and Stability). Specific pre-defined acceptance criteria are generally internal to the manufacturer's quality system and not explicitly listed in this 510(k) summary (which focuses on summarizing the results against those criteria). However, the reported device performance is provided, which demonstrates that the device met the manufacturer's internal criteria.

2. Sample Sizes and Data Provenance

• Precision (Repeatability): n = 84 (number of individual measurements per sample level).
• Precision (Intermediate Precision): 2 aliquots per run, 2 runs per day, 21 days.
• LoB: One analyte-free sample measured with three reagent lots, 6 runs, 10-fold determination per run, distributed over >3 days.
• LoD: 5 serum samples with low analyte concentrations measured with three reagent lots, 2-fold determination per run, 6 runs distributed over 5 days.
• LoQ: 5 serum samples measured with three reagent lots, 5 runs distributed over 5 days.
• Linearity: 1 run using 3 reagent lots and 5 replicates per sample. A dilution series prepared from human serum (sample High) and NaCl 0.9% (sample Blank) to obtain 16 levels.
• Method Comparison (to Lp(a) ELISA): n = 126 native human serum samples.
• Sample Matrix Comparison: ≥ 50 samples.
• Reference Range Study:
  • Caucasian/White: n = 425
  • African-American/Black: n = 111
  • Asian: n = 128
  • Hispanic/Latino (among Caucasian/White): n = 110
  • Non-Hispanic/Non-Latino (among Caucasian/White): n = 311
  • Data Provenance for Reference Range Study: Samples from apparently healthy adults in the United States, with equal representation of males and females. This suggests prospective collection for the purpose of establishing reference ranges. Other studies (e.g., method comparison, precision) would typically use laboratory samples which could be retrospective or specifically prepared for the study. The document does not specify "retrospective" or "prospective" for all tests, but the nature of these analytical performance studies often involves controlled, prepared, or collected samples without a specific patient encounter context. The "native human serum samples" for method comparison generally implies biological samples.

3. Number of Experts and Qualifications for Ground Truth

For this in vitro diagnostic device, "ground truth" is established by reference methods or validated analytical measurements, not by human expert interpretation in the way it would be for an AI image analysis tool.

• Not Applicable in the traditional sense for AI/ML image analysis. The "ground truth" for analytical performance tests like precision, linearity, or interference is an established analytical value or the characteristic of the sample itself (e.g., known concentration, presence/absence of interfering substance). For "method comparison," the ground truth is provided by the designated "Lp(a) ELISA reference method."

4. Adjudication Method for the Test Set

• Not Applicable in the traditional sense for AI/ML image analysis. Adjudication is usually performed by multiple human experts reviewing a case. For an IVD, the "adjudication" is inherent in the rigorous analytical protocols, statistical methods (e.g., CLSI guidelines), and the use of reference methods or certified reference materials for traceability.

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

• Not Applicable. This is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging system that would involve human readers interpreting cases.

6. Standalone (i.e. algorithm only without human-in-the loop performance) Performance

• Yes, implicitly. The performance studies (Precision, Analytical Sensitivity, Linearity, Interference, Method Comparison) evaluate the device (assay on the cobas c 503 analyzer) as a standalone system. There is no human intervention in the measurement or calculation of results once the sample is loaded. The device generates a quantitative value for Lp(a).

7. The Type of Ground Truth Used

• Reference Method/Analytical Standards:
  • Precision, Sensitivity, Linearity, Interferences: Ground truth is based on known concentrations in control materials, spiked samples, or by using analyte-free samples, following standardized laboratory practices and CLSI guidelines (e.g., CLSI EP05-A3, EP17-A2, EP06-A-Ed2).
  • Method Comparison: The "ground truth" or reference values were derived from the Lp(a) ELISA reference method.
  • Traceability: The device's calibration values are traceable to the WHO/IFCC SRM2B reference material for nmol/L, indicating a standardized and accepted reference for accuracy.

8. The Sample Size for the Training Set

• Not applicable in the AI/ML sense. This is a traditional IVD assay, not an AI model that requires a "training set" to learn features. The assay is based on well-understood principles of immunoturbidimetry and does not involve machine learning training.

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

• Not Applicable. As there is no AI/ML training set, this question is not relevant to this device. The assay's "knowledge" is built into its chemical reagents, optical detection system, and pre-programmed algorithms for calculating concentration from turbidity measurements, based on established analytical principles and calibration to reference materials.

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Binding assay for the in vitro quantitative determination of folate in erythrocytes (red blood cells, RBC). Folate measurements are used in the diagnosis and treatment of anemia. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

Elecsys Folate III is a binding assay that makes use of a competitive test principle using a ruthenium labeled folate-binding assay.
Elecsys Folate III is a binding assay for the in vitro quantitative determination of folate in erythrocytes (red blood cells, RBC). Folate measurements are used in the diagnosis and treatment of anemia. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Whole blood treated with anticoagulants (heparin or EDTA) is mixed with ascorbic acid solution and incubated for approximately 90 minutes at 20-25 °C. Lysis of the erythrocytes takes place, with liberation and stabilization of the intracellular folate. The resulting hemolysate sample is then used for subsequent measurement.
Results are determined via a calibration curve, which is instrument-specifically generated by 2point calibration, and a master curve provided via the cobas link.

Here's a summary of the acceptance criteria and study details for the Elecsys Folate III device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes and Data Provenance

• Precision (Repeatability & Intermediate Precision): Not explicitly stated, but typically involves multiple replicates over several days/runs with multiple instruments. Specific sample types are "Hemolysate 1" to "Hemolysate 5".
• Lot-to-lot Reproducibility: "three reagent lots" were used.
• Analytical Sensitivity (LoB, LoD, LoQ): Not explicitly stated, but determined according to CLSI EP17-A2, which involves specific numbers of blank and low-concentration samples.
• Linearity and Dilution: "At least seven concentrations using hemolysate samples" for linearity. Dilution study used "high concentration hemolysate samples".
• Endogenous Interferences: Not explicitly stated, but "various endogenous substances" were evaluated.
• Analytical Specificity/Cross-Reactivity: Not explicitly stated.
• Exogenous Interferences: "17 commonly and 1 specially used pharmaceutical" compounds.
• Sample Matrix Comparison: "Whole blood samples were drawn into Na-Heparin and K3-EDTA tubes." (Number not specified).
• Method Comparison to Predicate: 119 samples with concentrations between 132 and 618 ng/mL.
• Reagent Stability (On-board), Lot Calibration Stability, On-board Calibration Stability: Tested on "one cobas e 801 analyzer".

Data Provenance: The document states "NON-CLINICAL PERFORMANCE EVALUATION" and refers to CLSI (Clinical and Laboratory Standards Institute) guidelines, which are standard for in-vitro diagnostic device performance studies. The data is internal to Roche Diagnostics, a company with global operations. The specific country of origin for the studies is not stated, but given the submission is to the U.S. FDA, the studies are expected to meet international and U.S. regulatory standards. These are retrospective studies in the context of device development and validation.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

This device is an in-vitro diagnostic (IVD) assay that produces quantitative measurements of folate. It does not involve human interpretation of images or other subjective data. Therefore, the "ground truth" for its performance is established by reference methods, calibrated standards, and accurate measurement principles, rather than human expert consensus. No human experts were used to establish ground truth in the way one would for an AI imaging device.

4. Adjudication Method (Test Set)

Not applicable, as this is an IVD device producing quantitative results, not an AI imaging device requiring expert adjudication.

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

Not applicable. This is an in-vitro diagnostic device, not an AI device assisting human readers with interpreting cases.

6. Standalone (Algorithm Only) Performance

Yes, the studies described are standalone performance evaluations of the Elecsys Folate III assay (the "algorithm" in a broad sense for an IVD) without human intervention in the measurement process. The device performs the quantitative determination of folate using its defined binding assay and electrochemiluminescence immunoassay (ECLIA) method.

7. Type of Ground Truth Used

The ground truth for evaluating the Elecsys Folate III's performance is established through:

• Reference materials/standards: For analytical sensitivity (LoB, LoD, LoQ) and linearity, where known concentrations are used.
• Performance against a predicate method: For method comparison, the results are compared to a previously cleared, established method (Elecsys Folate RBC).
• CLSI guidelines: Adherence to established scientific and statistical methodologies for validating assay performance, implying well-defined benchmarks for accuracy, precision, and interference.

8. Sample Size for the Training Set

Not explicitly stated. For an IVD like the Elecsys Folate III, a traditional "training set" as understood in machine learning is not directly applicable. The "training" for such a system would involve the development and optimization of the reagent formulations, assay parameters, and calibration curve algorithms, using various samples and experiments during the research and development phase. However, a specific training set size with corresponding ground truths is not documented in the same way as an AI algorithm.

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

As above, a formal "training set ground truth" isn't directly applicable in the machine learning sense. The "ground truth" during the development and optimization (analogous to training) would have been established through:

• Known concentrations: Using purified folate standards or spiked samples.
• Reference methods: Comparing early-stage assay performance against established, often more labor-intensive or gold-standard methods for folate determination.
• Clinical correlation: (Though "clinical testing" is marked Not Applicable for this 510(k), early development might involve correlation with clinical status or outcomes).
• Statistical optimization: Adjusting reagent ratios, incubation times, and instrument settings to achieve optimal analytical performance characteristics (sensitivity, specificity, precision, linearity) based on these known values and reference method comparisons.

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Immunoassay for the in vitro quantitation of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia. This assay can be used intraoperatively. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers

Both the Elecsys PTH and Elecsys PTH STAT immunoassays make use of a sandwich test principle using a biotinylated monoclonal PTH-specific antibody labeled with a ruthenium complex. Both the Elecsys PTH and Elecsys PTH STAT immunoassays are intended for the in vitro quantitative determination of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia. These assays can be used intraoperatively. They are intended for use on the cobas e immunoassay analyzers.

Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode.

The reagent working solutions include: Rack Pack (kit placed on the analyzer)

• M Streptavidin coated microparticles (transparent cap), 1 bottle, 6.5 mL: Streptavidin . coated microparticles 0.72 mg/mL; preservative.
• . R1 Anti PTH Ab~biotin (gray cap), 1 bottle, 7 mL: Biotinylated monoclonal anti PTH antibody (mouse) 2.3 mg/L; phosphate buffer 100 mmol/L, pH 7.0; preservative.
• . R2 Anti PTH Ab~Ru(bpy) (black cap), 1 bottle, 7 mL: Monoclonal anti PTH antibody (mouse) labeled with ruthenium complex 2.0 mg/L; phosphate buffer 100 mmol/L, pH 7.0; preservative.

Unfortunately, the provided text does not describe a study involving an AI/Machine Learning powered medical device, nor does it contain information about typical acceptance criteria for such devices (e.g., sensitivity, specificity, AUC).

Instead, the document details a 510(k) premarket notification for Elecsys PTH and Elecsys PTH STAT, which are immunoassays for quantitative determination of intact parathyroid hormone. These are laboratory diagnostic tests, not AI-powered devices.

The document focuses on demonstrating substantial equivalence to a previously cleared predicate device (K070709) by:

• Comparing technological characteristics (Table 1 and Table 2).
• Providing non-clinical performance evaluations such as precision, analytical sensitivity (Limit of Blank, Limit of Detection, Limit of Quantitation), linearity, high dose hook effect, interference studies, and sample matrix comparison.
• Presenting a method comparison to the predicate devices.
• Reporting on stability and a reference range study.

Therefore, I cannot fulfill the request to describe the acceptance criteria and study that proves an AI device meets acceptance criteria based on this input. The information required for your questions (e.g., sample size for test set, data provenance, number of experts for ground truth, MRMC study, standalone performance, training set details) are specific to AI/ML device evaluations and are not present in this document about an immunoassay.

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ONLINE TDM Methotrexate is an in vitro test for the quantitative determination of methotrexate in human serum and plasma on cobas c systems. The determination of methotrexate is used for monitoring levels of methotrexate to ensure appropriate therapy.

The ONLINE TDM Methotrexate assay is an in vitro test for the quantitative determination of methotrexate in human serum and plasma on cobas c systems. The determination of methotrexate is used for monitoring levels of methotrexate to ensure appropriate therapy.

The ONLINE TDM MTX assay is a two-reagent system used for the detection of methotrexate in serum and plasma. In this technology drug hapten attached to the enzyme glucose 6 phosphate dehydrogenase (G6PDH) serves as the binding partner to anti-methotrexate antibody. A competitive reaction to a limited amount of specific anti-methotrexate antibody takes place between the enzyme bound hapten and free methotrexate in the sample. Enzyme activity is reduced with bound antibody. Only active enzymes reduce NAD+ to NADH. The rate of NADH formation during the reaction correlates to the methotrexate concentration and is measured photometrically.

The ONLINE TDM MTX assay is a homogeneous enzyme-immunoassay.

Reagents - working solutions

R1: Anti-methotrexate antibody (rabbit monoclonal), 3 µg/mL; NAD, G6P, bovine serum albumin in water, pH 6.3; preservative

R3: Methotrexate hapten conjugated to G6PDH, 0.3 µg/mL; bovine serum albumin in buffer, pH 7.8; preservative

The provided document describes the analytical performance evaluation of the "ONLINE TDM Methotrexate" assay. This is an in vitro diagnostic device used for the quantitative determination of methotrexate in human serum and plasma. The study aims to demonstrate that the device meets predefined acceptance criteria.

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

1. Table of Acceptance Criteria & Reported Device Performance:

The document doesn't explicitly present a single table of "acceptance criteria" alongside "reported device performance" in a comparative format for all tests. Instead, it states for each section: "All acceptance criteria were met," and then provides the results. We can infer the acceptance criteria from the context and the reported successful outcomes.

Here is a reconstructed table based on the provided text, indicating the acceptance criteria (inferred from the "All acceptance criteria were met" statements and industry standards implicitly followed) and the reported performance.

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

• Precision (Repeatability & Intermediate Precision):
  • Repeatability: n = 84 measurements (total across all samples/controls).
  • Intermediate Precision: Not explicitly stated as a single 'n'. It involved 2 aliquots per run, 2 runs per day, over 21 days for controls and human serum samples.
• Analytical Sensitivity (LoB, LoD, LoQ):
  • LoB: One analyte-free sample measured with three reagent lots, in 6 runs, each with 10-fold determination, distributed over 3 days.
  • LoD: 5 serum samples measured on three lots with 2-fold determination per run, across 6 runs distributed over 3 days.
  • LoQ: 5 serum samples measured with three reagent lots, across 6 runs distributed over 3 days.
• Linearity/Assay Reportable Range:
  • A dilution series spanning ≥ 9 levels, assayed on one analyzer using 3 reagent lots and 4 replicates per sample.
• Endogenous Interferences: Not explicitly stated as a numerical sample size but implies a study design for each substance.
• Analytical Specificity/Cross-Reactivity (DAMPA):
  • Two human serum sample pools.
• Exogenous Interferences (Drugs): Not explicitly stated as a numerical sample size but implies a study design for each drug.
• Sample Matrix Comparison:
  • ≥ 50 samples compared across serum and various plasma types.
• Method Comparison:
  • 105 native human plasma and serum samples.

Data Provenance: The studies were conducted on "human serum" and "human plasma" samples. No specific country of origin is mentioned for the samples. The studies are retrospective in nature, as they involve testing existing samples (or creating spiked samples from existing matrices) within a laboratory setting to characterize the device performance. This is a typical approach for IVD device validation.

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

This information is not provided in the document. The type of device (in vitro diagnostic for quantitative determination of a drug) means that "ground truth" is typically established via a reference method (like LC-MS/MS), not by expert human graders.

4. Adjudication Method for the Test Set:

This information is not applicable for this type of in vitro diagnostic device study. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where human readers evaluate medical images and their interpretations need to be reconciled. For a quantitative assay like this, the 'ground truth' is established by a reference analytical method.

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

No, a MRMC comparative effectiveness study was not done. This type of study is relevant for AI-powered devices that assist human interpretation (e.g., radiologists reading images). This device is a fully automated in vitro diagnostic assay, so human interpretation assistance is not part of its function.

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

Yes, this entire study describes the standalone performance of the "ONLINE TDM Methotrexate" assay. It is an automated laboratory test that measures methotrexate levels, meaning it operates "without human-in-the-loop performance" during the measurement process. The results are quantitative values generated directly by the instrument using the assay's reagents.

7. The Type of Ground Truth Used:

The primary type of "ground truth" used for performance evaluation, particularly for method comparison and potentially for linearity/dilution studies, is a validated comparator method, specifically LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry). This is a highly accurate and precise analytical technique often considered a reference method for drug quantification. The document explicitly states: "The target value was determined with the LC-MS/MS" for dilution checks and "A method comparison of the ONLINE TDM Methotrexate on the cobas c 503 analyzer versus a validated comparator method on LC-MS/MS was completed."

For other tests like precision, sensitivity, interference, matrix comparison, ground truth is established by the known concentrations of controls, spiked samples, or comparison against established acceptable ranges as per CLSI (Clinical and Laboratory Standards Institute) guidelines.

8. The Sample Size for the Training Set:

The document does not provide any details about a training set. This is expected because this device is an in vitro diagnostic reagent assay, not an AI/Machine Learning model that undergoes a "training" phase. The assay relies on established biochemical reactions (homogeneous enzyme-immunoassay) and instrumental calibration rather than iterative learning from a dataset.

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

As there is no training set for this type of IVD device (it's not an AI/ML product), this question is not applicable. The "ground truth" for the performance evaluation (test set) relied on validated analytical methods and known sample concentrations.

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