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For in vitro diagnostic use with the IMMULITE® 2000 Analyzer -- for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. The test results are to be used in conjunction with clinical findings and other laboratory tests.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support. Incubation Cycles: 2 × 30 minutes.

The Siemens Healthcare Diagnostics Inc. IMMULITE® 2000 3gAllergy™ Specific IgE Assay is intended for the quantitative measurement of allergen-specific IgE in human serum, to aid in the clinical diagnosis of IgE-mediated allergic disorders.

1. Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria for precision, linearity, or clinical performance in numerical terms for the new allergens to be cleared. However, the study results are presented to demonstrate acceptable analytical performance and comparability to clinical data.

Precision:
Precision was evaluated by calculating the intra-assay (Within-Run) and inter-assay (Total) percent coefficients of variation (%CV) for positive samples. The reported CVs are generally low, with within-run CVs mostly below 5% (with some exceptions like Positive #4 for Lime at 9.15%) and total CVs mostly below 6% (with some exceptions like Positive #4 for Lime at 11.47%). The document states that "acceptable analytical performance including precision" was demonstrated, implying these values met internal or regulatory expectations.

Linearity:
Linearity was assessed by comparing observed to expected data from 2-fold serial dilutions. The regression equations show slopes very close to 1 and intercepts close to 0, with 95% confidence intervals for both slope and intercept generally containing 1 and 0 respectively. This indicates good linearity across the tested range. The document states "acceptable analytical performance including linearity" was demonstrated.

Specificity (Inhibition Studies):
Specificity was confirmed through competitive inhibition testing. The acceptance criterion was explicitly stated as achieving a target % inhibition of 50% for the highest inhibitor concentration tested. The reported performance is that this target was met for all tested allergens.
Additional inhibition studies for cross-reactivity used a criterion of results being below 9.9% for specific allergens when tested with unrelated allergen extracts. The reported performance states that results were below 9.9% for Asparagus, Blueberry, Cauliflower, and Perch when tested with unrelated extracts, and for Apricot, Chili Pepper, Chub Mackerel, Ginger, Lime, and Whey.

Clinical Performance:
The document presents an agreement rate with clinical data. The acceptance criteria for clinical performance are implicitly defined by the reported lower and upper confidence intervals, which fall within generally accepted ranges for such diagnostic assays.

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For in vitro diagnostic use with the IMMULITE® 2000 Analyzer - for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support. Incubation Cycles: 2 × 30 minutes.

The Siemens Healthcare Diagnostics Inc. IMMULITE® 2000 3gAllergy™ Specific IgE Assay is an in vitro diagnostic device intended for the quantitative measurement of allergen-specific IgE in human serum, to aid in the clinical diagnosis of IgE-mediated allergic disorders. The provided document focuses on the clearance of 27 additional specific allergens for use with this existing assay.

Here's an analysis of the acceptance criteria and study data provided:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for precision, linearity, or specificity (inhibition). Instead, it presents the study results and concludes that they demonstrate "acceptable analytical performance." For clinical performance, it discusses general agreement with clinical data.

Therefore, the table below will summarize the reported performance metrics, implying that these results were deemed acceptable by the manufacturer and the FDA for substantial equivalence.

• Concentration-dependent inhibition.
• Target of 50% inhibition met at the highest inhibitor concentration tested (5 mg/mL, or the starting concentration for Haddock, Red Snapper, and Sole). |
  | Clinical Performance | Good agreement with clinical documentation of allergen sensitivity. | Sensitivity: 66.2% (Lower Conf 64%, Upper Conf 69%)
  Specificity: 98.9% (Lower Conf 99%, Upper Conf 99%)
  Overall Agreement: 89.1% (Lower Conf 88%, Upper Conf 90%) |

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

• Precision: Three positive samples and one negative sample were tested for each allergen. Each sample was assayed in two aliquots, two runs per day, on 20 different days, for three allergen lots. This setup aims to assess within-run and total precision across different batches and extended testing periods.
• Linearity: For each allergen, two samples were diluted in 2-fold serial dilutions to 5 levels. Each diluted and undiluted sample was tested.
• Specificity (Inhibition): A "single serum sample or pool of sera" was used for competitive inhibition testing for each allergen. A negative sample was used as a background control. Inhibition experiments involved 70uL of undiluted and minimally 4-5 levels of serially diluted inhibitor extract (5, 1, 0.2, 0.04, 0.008 mg/mL, and sometimes more dilute levels). Each sample mixture with inhibitor extract and controls was assayed with 1 lot of each allergen.
• Clinical Performance: 4,118 samples were tested: 1,238 from clinically positive individuals and 2,880 from clinically normal (non-atopic) individuals.
• Data Provenance: The document does not explicitly state the country of origin or whether the data is retrospective or prospective for any of these studies. It can be inferred that these are prospective studies conducted by the manufacturer, Siemens Healthcare Diagnostics Inc., for regulatory submission.

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

• Precision, Linearity, Specificity: For these analytical performance studies, the "ground truth" is based on the inherent properties of the measurements and controls, rather than expert interpretation of a diagnostic outcome. The accuracy of the assay itself is being evaluated.
• Clinical Performance: For the clinical performance study, the "ground truth" (clinical data for IgE-mediated allergic disorders) was established based on "clinically diagnosed atopic and non-atopic individuals." The document does not specify the number or qualifications of the experts (e.g., allergists, physicians) who performed these clinical diagnoses.

4. Adjudication Method for the Test Set

• Precision, Linearity, Specificity: Not applicable. These are analytical studies where results are quantitative measurements against known standards or controls.
• Clinical Performance: The document states that the ground truth for clinical performance was based on "clinical data" to define individuals as "clinically diagnosed atopic and non-atopic individuals." There is no mention of an adjudication method (like 2+1, 3+1 consensus) explicitly detailed for the clinical diagnoses themselves. It implies that these were established clinical classifications prior to testing with the IMMULITE® 2000.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an imaging device or AI algorithm intended to assist human readers in interpretation. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply here.

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

Yes, the studies evaluating the IMMULITE® 2000 3gAllergy™ Specific IgE Assay are fundamentally standalone. The device performs quantitative measurements of IgE levels in serum, and its performance (precision, linearity, specificity, and comparison to clinical diagnoses) is assessed based on these measurements. There is no "human-in-the-loop" component in the analytical operation of the assay or the interpretation of its quantitative output for the purpose of these performance studies. Clinicians then use these quantitative results, alongside other clinical information, for diagnosis.

7. Type of Ground Truth Used

• Precision, Linearity: Ground truth is based on known concentrations or expected values derived from serial dilutions.
• Specificity (Inhibition): Ground truth is based on the known presence and concentration of the inhibitor extract and the expected inhibition of the specific allergen reaction.
• Clinical Performance: The ground truth was "clinical data," referring to the diagnosis of "clinically diagnosed atopic and non-atopic individuals." This would typically involve a combination of patient history, physical examination, and potentially other diagnostic tests (e.g., skin prick tests, other lab results, patient symptoms, and outcomes). It is not solely pathology or "outcomes data" in a broader sense but relies on a clinical determination of allergy status.

8. Sample Size for the Training Set

The document describes performance studies for the device itself, not the development of an algorithm that would require a distinct "training set" in the context of machine learning or AI. Therefore, the concept of a training set for an AI algorithm is not applicable to this submission. The studies detailed are for validation of the assay performance.

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

As explained in point 8, the concept of a "training set" for an AI algorithm is not applicable to these studies for this in vitro diagnostic device.

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The ADVIA® Chemistry Hemoglobin A1c method is for in vitro diagnostic use in the quantitative determination of Hemoglobin A1c, a diabetes marker, in whole blood on the ADVIA Chemistry systems. Such measurements are used for monitoring the long-term glycemic control of persons with diabetes. The A1c and total hemoglobin (tHb) values generated as part of the HbA1cN and HbA1cI results are intended for use in the calculation of the A1c / total hemoglobin ratio, and must not be used individually for diagnostic purposes.

*Note: HbA1cN reports HbA1c in % and HbA1cI reports HbA1c in mmol/mol

The ADVIA® Chemistry A1c Calibrators are for in vitro diagnostic use in the calibration of the A1c and total hemoglobin methods (Automated and Manual Pretreatment) on the ADVIA Chemistry Systems.

The concentration of A1c and the concentration of total hemoglobin are measured and the ratio is reported (either as % or mmol/mol).

There are two different sample pretreatment methods available on the ADVIA Chemistry System. The first method is an Automated Pretreatment that uses 4 reagents: A1c Denaturant Reagent, Total Hemoglobin Reagent (tHb 2), A1c Agglutinator Reagent (R1) and A1c Antibody Reagent (R2). In this Automated Pretreatment step, the whole blood sample is mixed with the A1c Denaturant Readent. The red blood cells are lysed and the hemoglobin chains are hydrolyzed by the protease present in the reagent.

The second method is a Manual Pretreatment that uses the same reagents as the first method except that the A1c Denaturant Reagent is replaced with the Hemoglobin Denaturant Reagent. For this method, there is an off-line pretreatment that is followed bv a 10 minute incubation.

For the measurement of total hemoglobin, the Total Hemoglobin Reagent is used. The method is based on the conversion of all hemoglobin derivatives into alkaline hematin in an alkaline solution of a nonionic detergent

A latex agglutination inhibition method is used for the measurement of specific A1c. The A1c present in the sample competes with the agglutinator (synthetic latex containing multiple copies of the immunoreactive portion of A1c) for the anti-A1c antibody; thereby reducing the rate of agglutination. A concentration curve is obtained by monitoring the change in scattered light as a change of absorbance. The actual change in absorbance is inversely proportional to the concentration of A1c in the sample. The HbA1cN NGSP result (%) or the HbA1cl IFCC result (mmol/mol) is calculated using the A1c and total hemoglobin values.

The ADVIA® Chemistry A1c Calibrators are used to calibrate the methods. The calibrators consist of four (4) levels of lyophilized whole blood containing varying concentrations of HbA1c and total hemoglobin. There is a single level calibration for total hemoglobin (Cal 1) and a multi-level calibration (six levels) for A1c. Four calibrator levels (designated Cal 1 - 4) are provided in a single kit and each level is 0.5 g/vial. The other two levels consist of Saline (Cal 0) and Cal 5 (prepared by the system from Cal 4 using 1.4 times the volume used for Cal 4).

The target value of each calibrator (calibration) level is:

• Calibration Level 1 (Cal 0): 0.00 umol/L A1c, 0.0 g/dL Total Hemoglobin ●
• Calibration Level 2 (Cal 1): 2.30 µmol/L A1c, 11.0 g/dL Total Hemoglobin .
• Calibration Level 3 (Cal 2): 3.65 umol/L A1c .
• Calibration Level 4 (Cal 3): 5.15 umol/L A1c .
• Calibration Level 5 (Cal 4): 6.80 umol/L A1c .
• Calibration Level 6 (Cal 5): 8.20 umol/L A1c

The Siemens Healthcare Diagnostics ADVIA® Chemistry Hemoglobin A1c Assay and Calibrators were evaluated for substantial equivalence to predicates. The study demonstrated performance through various tests, including imprecision, method comparison, interfering substances, matrix equivalency, and analytical range.

1. Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria for the performance characteristics. Instead, it presents the results of these performance studies and concludes that they are "acceptable results compared to the Predicate Device" and "support that the ADVIA Chemistry Hemoglobin A1c assay... is substantially equivalent to the Tosoh G7 HPLC Hemoglobin A1c method." However, based on the provided data, we can infer implied acceptance around certain metrics. The performance metrics are reported in comparison to the predicate device or a reference method.

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

• Sample Size for Method Comparison (Test Set): 80 samples for both Automated and Manual Pretreatment methods.
• Data Provenance: Not explicitly stated (e.g., country of origin). The data appears to be from internal studies conducted by Siemens Healthcare Diagnostics. It is retrospective in the sense that samples were likely collected and then tested, but not explicitly labeled as prospective.

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

Not applicable. This device is an in vitro diagnostic (IVD) assay measuring a biochemical marker (HbA1c). The "ground truth" for the test set in this context is established by a reference method or a predicate device, not by expert interpretation of images or other subjective assessments.

4. Adjudication Method for the Test Set

Not applicable. As this is an IVD assay, ground truth is established by an objective, traceable reference method (NGSP Reference Method, specifically Tosoh G7 in this case), not through expert consensus requiring adjudication.

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

Not applicable. This is an in vitro diagnostic device, not an imaging device or AI-assisted diagnostic tool that involves human readers interpreting cases. Therefore, an MRMC study and the concept of human reader improvement with AI assistance are not relevant to this submission.

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

Yes, the studies presented (imprecision, method comparison, interfering substances, analytical range) demonstrate the standalone performance of the ADVIA Chemistry Hemoglobin A1c Assay. The device directly measures HbA1c concentrations and calculates the ratio, functioning independently of human interpretation of the final measurement.

7. Type of Ground Truth Used

The ground truth used for the method comparison study was established using the NGSP Reference Method (Tosoh G7 Automated HPLC Analyzer - HbA1c Variant Analysis Mode). The document states that the Tosoh G7 is certified by NGSP and used as a reference method for establishing traceable results to the Diabetes Control and Complications Trial (DCCT). This indicates a highly standardized and traceable method for establishing the true HbA1c values.

8. Sample Size for the Training Set

Not explicitly stated. The document focuses on the performance studies (validation) of the finished device. For IVD assays, "training sets" are usually involved in the initial assay development and optimization, rather than being a distinct, reported phase like in AI/ML device development. The calibrators themselves are used to "train" or calibrate the instrument on an ongoing basis.

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

For IVD assays like this, the "ground truth" for calibrators is typically established through a process of assigning traceable values. The ADVIA® Chemistry A1c Calibrators are stated to be "Traceable to NGSP*** and Traceable to IFCC by Master Equation." This means the assigned values for the calibrators are determined through rigorous analytical methods that link them back to internationally recognized standardization programs (NGSP and IFCC), ensuring accuracy and consistency across different laboratories and instruments. This would involve a hierarchy of reference methods and materials.

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The ADVIA Centaur Cyclosporine assay is an in vitro diagnostic immunoassay for the quantitative determination of cyclosporine in human whole blood using the ADVIA Centaur systems. This assay is intended for use as an aid in the management of cyclosporine therapy in kidney, heart, and liver transplant patients.

The ADVIA Centaur® Cyclosporine assay is a competitive immunoassay using direct chemiluminescent technology. Cyclosporine in the patient sample competes with acridinium ester-labeled cyclosporine in the Lite Reagent for a limited amount of biotin-labeled monoclonal mouse anti-cyclosporine antibody. Biotinlabeled anti-cyclosporine binds to streptavidin that is covalently coupled to paramagnetic particles in the Solid Phase. In the ADVIA Centaur® Cyclosporine assay the sample is manually pretreated to lyse the cells and solubilize the cyclosporine. An inverse relationship exists between the amount of cyclosporine present in the patient sample and the amount of relative light units (RLUs) detected by the system.

Here's a breakdown of the acceptance criteria and study details for the ADVIA Centaur® Cyclosporine Assay, based on the provided text:

Acceptance Criteria and Reported Device Performance

The provided document describes comparison studies for the ADVIA Centaur® Cyclosporine assay against two reference methods: Tandem Mass Spectrometry (Tandem-MS) and the Abbott TDx®TDxFLx® Cyclosporine Monoclonal Whole Blood assay (and also Abbott AxSym). The "acceptance criteria" are implied by the ranges of statistical measures (slope, intercept, and correlation coefficient) that demonstrate substantial equivalence to the predicate devices and reference method. While explicit acceptance thresholds aren't stated as pass/fail criteria, the reported performance metrics indicate the device's acceptable agreement with established methods.

Here's a table summarizing the reported device performance, categorized by the comparative method and patient group/site:

Table 1: Acceptance Criteria (Implied) and Reported Device Performance for ADVIA Centaur® Cyclosporine Assay

2. Sample Size and Data Provenance

• Test Set Sample Size:

  • Against Tandem-MS:
    • Kidney transplant patients: 108 samples
    • Liver transplant patients: 75 samples
    • Heart transplant patients: 67 samples
    • Total against Tandem-MS: 250 samples (across all transplant types)
    • Total against Tandem-MS (by site): 250 samples (97 at site 1, 105 at site 2, 48 at site 3)
    • Total against Tandem-MS (by trough/peak): 250 samples (182 trough, 68 peak)
  • Against Abbott TDx: 242 samples (97 at site 1, 97 at site 2, 48 at site 3)
  • Against Abbott AxSym: 219 samples (at site 1)

• Data Provenance: The samples were from "three transplant patient groups (heart, kidney and liver)" and "three external sites." The text does not specify the country of origin, but given the submitter is Siemens Healthcare Diagnostics in Tarrytown, New York, USA, and the FDA submission, it's highly likely the data includes US patients. The study is retrospective, as it uses existing patient samples for comparison.

3. Number of Experts and Qualifications for Ground Truth

The study does not involve human readers/experts in the traditional sense of interpreting images or clinical data. Instead, it compares the performance of the ADVIA Centaur® Cyclosporine assay against established analytical methods. Therefore, the concept of "experts establishing ground truth" as it applies to subjective assessments is not directly relevant here.

The "ground truth" is established by:

• Tandem Mass Spectrometry (Tandem-MS): This is a highly accurate and precise analytical method often considered a gold standard for quantifying small molecules like cyclosporine. The operators of these machines are typically highly trained laboratory professionals.
• Abbott TDx®TDxFLx® Cyclosporine Monoclonal Whole Blood assay: This is a legally marketed predicate device, representing an established and accepted method for cyclosporine measurement.
• Abbott AxSym: Another legally marketed device for comparison.

4. Adjudication Method for the Test Set

No adjudication method is described, as the "test set" involves analytical measurements rather than subjective interpretations requiring consensus. The "comparison" is statistical (Deming regression) between the new device and established reference methods.

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

No, an MRMC comparative effectiveness study was not done. This type of study is typically used for diagnostic imaging or subjective clinical assessments where multiple human readers interpret cases. The ADVIA Centaur® Cyclosporine assay is an in vitro diagnostic assay that produces a quantitative numerical result; its performance is evaluated by comparison to other quantitative methods, not by improvements in human reader performance.

6. Standalone (Algorithm Only) Performance

Yes, this entire study is a standalone performance study. The ADVIA Centaur® Cyclosporine assay itself (the "algorithm" in this context, albeit a chemical immunoassay) is being tested for its direct, unassisted performance in quantifying cyclosporine. There is no human-in-the-loop component being evaluated for its direct impact on the assay's result.

7. Type of Ground Truth Used

The ground truth used is based on:

• Analytical Reference Method: Tandem Mass Spectrometry (Tandem-MS), which is typically considered a highly accurate and precise reference method for cyclosporine quantification.
• Predicate Device Performance: The results from the legally marketed Abbott TDx®TDxFLx® Cyclosporine Monoclonal Whole Blood assay and Abbott AxSym are used as a comparative "truth" to establish substantial equivalence.

8. Sample Size for the Training Set

The document does not provide information about a separate "training set" for the assay. Immunoassays like the ADVIA Centaur® Cyclosporine assay are developed and optimized through laboratory procedures, reagent formulation, and calibration curves, rather than being "trained" on a dataset in the way a machine learning algorithm would be. The data presented in the tables are for performance validation (the "test set" in an ML context).

9. How Ground Truth for the Training Set Was Established

As noted above, the concept of a "training set" and its "ground truth" doesn't directly apply here in the way it would for a machine learning model. The assay's internal calibration and performance characteristics would have been established during its development and manufacturing process, likely using characterized reference materials and calibrators, not through a "ground truth" dataset in the clinical study sense. The reference calibrators themselves (ADVIA Centaur® Cyclosporine Calibrator) have their own manufacturing and quality control processes to establish their known concentrations.

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The neonatal bilirubin test intended use on the Rapidlab 1245 and Rapidlab 1265 analyzers is an in vitro diagnostic test for the determination of total neonatal bilirubin (nBili) concentration in the whole blood of newborn infants. Measurement of nBili aids in assessing the risk of kernicterus.

Neonatal Bilirubin (nBili) is a new parameter enabled on models 1245 and 1265 of the Rapidlab® 1200 blood gas family of instruments. It is intended as an in vitro diagnostic test for the determination of total neonatal Bilirubin (nBili) concentration in the whole blood of newborn infants. Enabling the nBill measurement is accomplished through software design changes introduced in Rapidlab Software Version 2.1. No hardware /mechanical changes were needed.

Here's an analysis of the provided text, focusing on the acceptance criteria and the study that proves the device meets those criteria:

Acceptance Criteria and Device Performance for Neonatal Bilirubin (nBili) on Rapidlab® 1200 Blood Gas Systems

1. Table of Acceptance Criteria and Reported Device Performance:

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

• Sample Size: 2,241 samples.
• Data Provenance: The samples were described as "unconjugated bilirubin in oxygenated whole blood (neonatal type samples)". The text does not explicitly state the country of origin or if the data was retrospective or prospective, but the nature of the samples suggests clinical relevance to neonates. It was an "internal evaluation study."

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

The document does not provide information on the number of experts, their qualifications, or their role in establishing the ground truth if a gold standard method was used. The study primarily compares the device's measurement against predicate devices, rather than an expert human interpretation.

4. Adjudication Method for the Test Set:

Not applicable. The study involved instrumental measurements, not human interpretation that would require adjudication.

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

No, an MRMC comparative effectiveness study was not done. The device measures a biochemical marker (bilirubin concentration) rather than interpreting medical images or clinical observations that would typically involve human readers. The study compared the device's performance against predicate devices.

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

Yes, a standalone study was performed. The "nBili internal evaluation study" assessed the performance of the Rapidlab 1245 and 1265 in measuring neonatal bilirubin concentrations. This device, being a diagnostic instrument (blood gas system), inherently operates in a standalone manner to provide quantitative results. The human involvement is in operating the device and interpreting its output, not in performing the measurement itself.

7. Type of Ground Truth Used:

The ground truth for the test set was established by comparing the Rapidlab 1200 systems' nBili measurements against "predicate devices" (Radiometer ABL735 and ABL800 FLEX). The study aimed to demonstrate "substantial equivalence" to these established devices across the reporting range. Therefore, the ground truth was effectively the measurements obtained from these predicate devices.

8. Sample Size for the Training Set:

The document does not provide information about a separate training set or its sample size. The focus is on the performance of the device's software, which "was enabled through software changes." The 2,241 samples appear to be for validation/testing, not for training a machine learning model. This suggests that the "software changes" were likely based on established physiological models or signal processing algorithms, rather than iterative machine learning training.

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

Not applicable, as no explicit training set for a machine learning model is mentioned. The device's measurement technology relies on "multiple wavelength spectrophotometry (CO-oximetry)" and "iterative least squares analysis" to determine bilirubin values, which are then "corrected for hematocrit." This description points to a deterministic algorithm based on scientific principles and calibration, rather than a system trained on data with established ground truth.

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The ADVIA CHEMISTRY C-Reactive Protein_2 assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin) on the ADVIA Chemistry systems. Such measurements are used in the evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. Increases in CRP values are non-specific for many disease processes and should not be interpreted without a complete clinical evaluation.

The ADVIA Chemistry C-Reactive Protein_2 Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the C-Reactive Protein 2 (CRP 2) method.

The ADVIA Chemistry C-Reactive Protein_2 (CRP_2) assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein in human serum and plasma on the ADVIA® Chemistry systems. The ADVIA Chemistry C-Reactive Protein_2 Calibrators are used to calibrate this method. The proposed labeling indicates the ADVIA Chemistry CRP_2 reagents and Calibrators are for use on the family of ADVIA Chemistry Systems (1200 / 1650 / 1800 / 2400).

The CRP_2 latex reagent is a suspension of uniform polystyrene latex particles coated with rabbit anti-CRP antibody. When serum or plasma containing CRP is mixed with the latex reagent, agglutination takes place resulting in an increase in the turbidity. This turbidity is measured at 571 nm. The CRP concentration in serum or plasma is determined from a calibration curve that is generated with the calibrators.

The ADVIA® Chemistry C-Reactive Protein_2 Calibrators consist of six (6) levels of protein stabilized matrices containing varying concentrations of recombinant human CRP. The Calibrators have targeted expected values (lot specific) of 0, 5, 20, 40, 160, and 320 mg/L.

The calibrators (1 mL/vial) and ready to use. Storage is at 2 - 8℃.

Here's an analysis of the acceptance criteria and study detailed in the provided 510(k) summary:

This document describes an in vitro diagnostic (IVD) device, specifically an assay and calibrators for measuring C-Reactive Protein (CRP). The acceptance criteria are primarily focused on demonstrating substantial equivalence to existing predicate devices through performance studies.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this IVD device are implicitly defined by demonstrating performance that is comparable to or better than the predicate device across various analytical characteristics.

Table of Acceptance Criteria and Reported Device Performance:

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Immulite 2500 OM-MA: For in vitro diagnostic use with the IMMULITE 2500 Analyzer- for the quantitative measurement of CA125 antigen in human serum, as an aid in monitoring the response to therapy for patients with epithelial ovarian cancer and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures.

Immulite Tumor Marker Controls: TMC is an assayed, serum-based, tri-level control containing analytes associated with malignancy which are commonly measured by immunoassay. It is intended strictly for in vitro use as an aid in monitoring the day-to-day performance of assays for these constituents.

The IMMULITE 2500 OM-MA Immunoassay is a solid-phase, two-site, chemiluminescent immunometric assay for use with the IMMULITE 2500 Automated Analyzer.

The provided text is a 510(k) summary for the IMMULITE® 2500 OM-MA Immunoassay. It describes the device's intended use and classification, and states that it has been found substantially equivalent to a predicate device (IMMULITE 2000 OM-MA Immunoassay).

However, the document does not contain information about acceptance criteria, detailed study results proving device performance against those criteria, sample sizes for test and training sets, data provenance, expert qualifications, adjudication methods, MRMC studies, or standalone algorithm performance.

Therefore, I cannot fulfill your request for a table of acceptance criteria and reported device performance or other detailed study information, as this information is not present in the provided text.

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The DCA Vantage™ is a semi-automated, benchtop system. It is designed to quantitatively measure the percent Hemoglobin A1c in blood and low concentrations of albumin in urine (microalbuminuria), creatinine in urine, and the albumin/creatinine ratio in urine.

The measurement of hemoglobin A1c concentration is recommended for monitoring the longterm glycemic control of persons with diabetes.

Testing for microalbuminuria (low concentration of albumin in urine) is recommended in patients with insulin-dependent diabetes mellitus (IDDM) as well as patients with non-insulin dependent diabetes mellitus (NIDDM). It is intended for use in both screening for, and monitoring treatment of, microalbuminuria.

Measurement of creatinine is used as a calculation basis to adjust the albumin/creatinine ratio result for varying urine concentrations.

The reporting of albumin/creatinine ratio is recommended for the early detection of kidney diseases.

The DCA Vantage system is for use in laboratories such as: physician office laboratories, clinics, and hospitals.

Tests performed using the DCA Vantage™ are intended for in vitro diagnostic use.

The DCA Vantage is a device modification to the previously cleared DCA 2000+. It is a semi-automated, benchtop analyzer designed to quantitatively measure the percent Hemoglobin A1c (HbA1c) in blood and low concentrations of albumin in urine (microalbuminuria), creatinine in urine, and the albumin/creatinine ratio in urine.

Identical to the DCA 2000+, all testing takes place at the analyzer. User steps to introduce the sample to the cartridge and the cartridge to the analyzer are unchanged. To perform a test, the user needs to collect test sample in the capillary holder, insert holder into the cartridge, scan cartridge into the barcode track, place cartridge in its compartment, remove the flexible tab and close the door to automatically start the test. Test results are displayed on screen and measurement is completed in 6-7 minutes.

Here's an analysis of the provided text regarding the DCA Vantage device, focusing on acceptance criteria and the supporting study:

Acceptance Criteria and Device Performance

The provided document describes a Special 510(k) submission for the DCA Vantage, a device modification of the DCA 2000+. The primary goal of the study was to demonstrate substantial equivalence to the predicate device (DCA 2000+), not necessarily to predefined "acceptance criteria" in the sense of absolute performance thresholds against a gold standard. Instead, the acceptance criteria are implicitly met if the DCA Vantage performs comparably to the DCA 2000+.

The study aimed to show that the DCA Vantage meets accuracy and precision requirements relative to the DCA 2000+.

Table of Acceptance Criteria and Reported Device Performance:

Note: The document does not provide specific numerical ranges or statistical thresholds for "accuracy requirements" or "precision performance requirements." It states that these requirements were "met," implying that the statistical analysis (Linear Regression) confirmed a comparable performance to the predicate device.

Study Details:

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

   • Sample Size:
     • Fifty (50) whole blood specimens for HbA1c.
     • Fifty (50) urine specimens for microalbumin/creatinine.
   • Data Provenance: The study was an "internal study," suggesting it was conducted by the manufacturer (Siemens Medical Solutions Diagnostics). The document does not specify the country of origin of the data or whether it was retrospective or prospective. Given the nature of a 510(k) submission for a device modification, it's likely prospective clinical samples collected for this specific validation, but this is not explicitly stated.

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

   • Not Applicable. The ground truth for this study was established using the predicate device (DCA 2000+) itself, not human expert consensus. The study aimed to show equivalence to an existing, legally marketed device.

3. Adjudication method for the test set:

   • Not Applicable. Since the predicate device served as the reference for comparison, there was no need for expert adjudication.

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:

   • No. This was not an MRMC study. The device is a "semi-automated, benchtop analyzer" for quantitative measurements, not an imaging device that requires human interpretation or AI assistance for image analysis.

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

   • Yes. This was a standalone performance evaluation of the DCA Vantage device. While it is a "semi-automated" system requiring user interaction for sample introduction, its core function is independent measurement and reporting, not human-in-the-loop assistance for interpretation. The study directly compared the measurements produced by the DCA Vantage to those from the DCA 2000+.

6. The type of ground truth used:

   • The "ground truth" or reference standard in this equivalence study was the DCA 2000+ Analyzer. The performance of the modified device (DCA Vantage) was compared against the measurements obtained from the predicate device (DCA 2000+) using the same clinical specimens and quality controls.

7. The sample size for the training set:

   • Not Applicable / Not Specified. This device is a spectrophotometer that analyzes physical properties; it is not based on machine learning or AI that requires a "training set" in the traditional sense. The device's operation is based on established analytical principles and pre-programmed algorithms.

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

   • Not Applicable. As noted above, there is no "training set" for this type of device mentioned in the documentation.

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The ADVIA® Chemistry Microalbumin Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the ADVIA Chemistry Microalbumin method is used for in vitro quantitation of albumin in urine).

The ADVIA® Chemistry Microalbumin 2 Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the ADVIA Chemistry Microalbumin 2 method (this method is used for in vitro quantitation of albumin in urine).

The ADVIA® Chemistry Microalbumin Calibrators and ADVIA® Chemistry Microalbumin 2 Calibrators are each 5 level liguid aqueous buffered solutions containing varying concentrations of purified human serum albumin. The Microalbumin Calibrators have expected values (lot specific) of 1, 2.5, 5, 10, and 20 mg/dL, and the Microalbumin 2 Calibrators have expected values (lot specific) of 1, 4, 10, 20, and 40 mg/dlL.

The calibrators (2 mL/vial) are liquid and ready to use. Storage is at 2 - 8℃.

This submission describes a calibration device, not an AI/ML powered diagnostic device. As such, the information typically requested for AI/ML device evaluations (e.g., sample sizes for test and training sets, ground truth establishment, MRMC studies, standalone performance) is not applicable or provided in this document.

However, I can extract the acceptance criteria as presented in the comparative table, which focuses on device characteristics and performance related to its function as a calibrator, and then summarize the study's conclusions regarding these criteria.

Here's the closest interpretation of your request based on the provided text, focusing on the "acceptance criteria" through comparison to a predicate device:

1. Table of Acceptance Criteria (Inferred from Comparison) and Reported Device Performance

For this type of device (calibrators), "acceptance criteria" are implicitly met if the new device demonstrates substantial equivalence to a legally marketed predicate device across key performance characteristics. The table below outlines these characteristics and how the new devices compare to the predicate, demonstrating their "performance" relative to these criteria.

Study Proving Device Meets Acceptance Criteria:

The study involved demonstrating "traceability, value assignment, and stability" of the ADVIA® Chemistry Microalbumin and ADVIA® Chemistry Microalbumin_2 Calibrators. These validations followed "procedures of Siemens Medical Solutions Diagnostics." The conclusion drawn from this internal validation and comparative analysis is that:

"The ADVIA® Chemistry Microalbumin Calibrators and ADVIA® Chemistry Microalbumin_2 Calibrators are substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed DCL Microalbumin Multi-Calibrator Set (K042243) in intended use, matrix, expected values, and stability."

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

• Sample Size: Not explicitly mentioned in terms of a "test set" as for a diagnostic device. The "performance" assessment is based on the characteristics of the calibrators themselves (e.g., stability over time, value assignment) rather than clinical samples.
• Data Provenance: The study was conducted internally by Siemens Medical Solutions Diagnostics. Information regarding country of origin or whether it was retrospective/prospective is not provided, but given it's a calibrator, it would involve laboratory-based testing rather than patient data.

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

This is not applicable as the device is a calibrator, not a diagnostic device that requires expert ground truth for interpretation of results. The "ground truth" for a calibrator relates to its assigned values and stability, which are determined through metrological principles and internal validation processes, likely by qualified scientists or chemists within Siemens.

4. Adjudication Method for the Test Set:

Not applicable for a calibrator device.

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

No, an MRMC study was not done. This type of study is relevant for diagnostic devices where human readers interpret results, typically from medical images, and an AI assists in that interpretation. This device is a calibrator, which is a reagent used to standardize other assays.

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

Not applicable. This is not an algorithm-based device. Its performance is inherent to its chemical properties and manufacturing consistency.

7. The Type of Ground Truth Used:

The "ground truth" for a calibrator refers to its assigned concentration values and its consistent performance over time (stability). This is likely established through:

• Reference Methods/Materials: Traceability to established reference methods or certified reference materials for human serum albumin.
• Analytical Validation: Rigorous analytical testing to confirm the stated concentrations and assess the stability of the calibrator solutions under various conditions.

8. The Sample Size for the Training Set:

Not applicable. This device is a calibrator, not an AI/ML model that requires a training set.

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

Not applicable as there is no training set for this type of device.

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For in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma, and urine on the ADVIA Chemistry Systems. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.

The ADVIA Chemistry Enzymatic Creatinine_2 is used for the in vitro quantitative determination of creatinine in human serum, plasma and urine on the ADVIA® Chemistry Systems. The proposed labeling indicates the ADVIA Chemistry Enzymatic Creatinine 2 reagents can be used on the ADVIA Chemistry 1200 / 1650 / 1800 / 2400 Systems.

The principle of the method is based on the enzymatic method employing creatininase, creatinase, sarcosine oxidase, horseradish peroxidase and N-(3-sulfopropy))-3methoxy-5-methylaniline (HMMPS) as the color agent. When a sample is mixed with Reagent 1 and Reagent 2, creatinine in the sample is converted to creatine by the action of creatininase. The creatine formed is hydrolyzed by creatinase to produce sarcosine and urea. The sarcosine is then decomposed by sarcosine oxidase to form glycine, formaldehyde and hydrogen peroxide. In the presence of peroxidase (POD), the hydrogen peroxide formed yields a blue pigment by quantitative oxidative condensation with N-(3-sulfopropy)-3-methoxy-5-methylaniline (HMMPS) and 4aminoantipyrine. The creatinine concentration is obtained by measuring the absorbance of blue color. The increase in optical absorbance is determined as an endpoint assay, which is proportional to the concentration of creatinine in the sample.

Here's a summary of the acceptance criteria and study findings for the ADVIA® Chemistry Enzymatic Creatinine_2 (ECRE_2) device, based on the provided 510(k) submission:

1. Table of Acceptance Criteria and Reported Device Performance

The submission demonstrates substantial equivalence by testing various performance characteristics and comparing them to predicate devices. The "acceptance criteria" are implied by showing the new device's performance to be comparable to, and within an acceptable range of, the predicate devices.

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

• Imprecision Study (Serum): Levels tested were 1.29 mg/dL through 8.80 mg/dL. The number of samples for each level or total sample size is not explicitly stated but implied to be sufficient for precision calculations (CV%).
• Imprecision Study (Urine): Levels tested were 41.56 mg/dL through 130.59 mg/dL. The number of samples for each level or total sample size is not explicitly stated.
• Method Comparison (Correlation):
  • Serum: 60 samples (for comparison against Creatinine_2 predicate), 28 or 42 samples (for comparison against Enzymatic Creatinine predicate), depending on the system (ADVIA 1200, 1650, 2400).
  • Urine: 44 to 49 samples (for comparison against Creatinine_2 predicate), depending on the system.
• Interfering Substances: Specific sample sizes are not explicitly stated for each interferent test but are implied to be sufficient to determine the effect at specific analyte and interferent concentrations.
• Data Provenance: The document does not specify the country of origin of the data or explicitly state whether the studies were retrospective or prospective. Given the nature of an in vitro diagnostic device validation, these are typically prospective studies using well-characterized samples or spiked samples.

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

This type of information (number and qualifications of experts) is generally not applicable or provided for in vitro diagnostic (IVD) device submissions like this one, especially for quantitative assays. The "ground truth" for creatinine measurements in this context is established by the direct measurement by the predicate devices or by well-established reference methods (e.g., ID-MS, HPLC candidate reference method as mentioned for standardization), not by human expert consensus or clinical interpretation of images.

4. Adjudication Method for the Test Set

Not applicable. As noted above, the "ground truth" for an IVD quantitative assay like creatinine is based on instrument measurements and reference methods, not subjective human assessment requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This device is an in vitro diagnostic assay (a laboratory test) that directly measures creatinine levels, not an imaging device or an AI-assisted diagnostic tool that would involve human "readers" or clinical interpretations.

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

Yes, this entire submission represents the "standalone" performance of the assay itself. The ADVIA Chemistry Enzymatic Creatinine_2 assay is an automated in vitro diagnostic test system. All the performance data (imprecision, method comparison, interference, analytical range) reflect the performance of the algorithm/reagent system as a standalone measurement tool. There is no human interpretation or "in-the-loop" component in the direct measurement of creatinine by the device itself.

7. The Type of Ground Truth Used

The ground truth for the comparison studies was established by:

• Predicate Devices: The measurements obtained from the legally marketed predicate devices: ADVIA Chemistry Creatinine_2 (Jaffe method) and ADVIA Chemistry Enzymatic Creatinine (Enzymatic Deiminase/GLDH method). The new device's performance was evaluated against these established methods.
• Standardization: The new device (ECRE_2) uses ID-MS (SRM 967) for standardization. The predicate devices used an HPLC candidate reference method. These reference methods serve as the ultimate "ground truth" for standardization and traceability of the creatinine measurements.

8. The Sample Size for the Training Set

The document does not explicitly delineate a "training set" in the context of deep learning or AI model development, as this is a chemical assay, not an AI algorithm in that sense. The "training" in this context would refer to the optimization and verification during the assay's development. The data presented here are validation data for the established final product.

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

As explained above, there isn't a traditional "training set" in the AI sense for this chemical assay. The development of the assay (analogous to "training") would involve establishing the chemical reactions, optimizing reagent concentrations, and calibrating the system. The "ground truth" for this development/optimization would be based on:

• Known concentrations of creatinine standards.
• Traceability to recognized reference methods (like ID-MS and HPLC).
• Performance established by predicate devices.

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