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For in vitro diagnostic and laboratory professional use.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma (K2-EDTA and K3-EDTA) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator

For use in the calibration of the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiO Immunodiagnostic System, VITROS 3600 Immunodiagnostic System, VITROS 5600 Integrated System and VITROS XT 7600 Integrated System) providing fully automated random-access testing.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls on the VITROS Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack is supplied as ready to use and contains:

• 100 wells coated with 100ng/well of recombinant SARS-CoV-2 spike antigen derived from human cells.
• 18.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent)
• 20.4 mL conjugate reagent [anti-human IgG (murine monoclonal) conjugated to horseradish peroxidase, 5ng/mL] in buffer with bovine protein stabilizers and antimicrobial agent.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator contains:

• 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 1gG Calibrator 0 (anti-SARS-CoV-2 IgG in anti-SARS-CoV-2 IgG negative human serum with antimicrobial agent, 1 mL)
• Lot calibration card
• Protocol card
• 8 calibrator bar code labels

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls contain:

• 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls 1 and 2 (defibrinated human plasma with anti-microbial agent, 2 mL). Control 1 is non-reactive and Control 2 is reactive

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is designed for use on the VITROS Systems. The VITROS Systems use the following ancillary reagents (general purpose reagents):

• VITROS Immunodiagnostic Products Signal Reagent
• VITROS Immunodiagnostic Products Universal Wash Reagent

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Device: VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack, VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator (Chemiluminescent Immunoassay)

Purpose: Qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma, intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

1. Table of Acceptance Criteria and Reported Device Performance

The document describes the performance of the device rather than explicitly stating pre-defined acceptance criteria in a dedicated table. However, we can infer the implicit acceptance criteria from the observed results and the FDA's decision to grant the De Novo request.

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For in vitro diagnostic and laboratory professional use.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma (K-EDTA. K-EDTA and lithium heparin) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

For use in the calibration of the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiQ Immunodiagnostic System, VITROS 3600 Immunodiagnostic System, VITROS 5600 Integrated System and VITROS XT 7600 Integrated System) providing fully automated random-access testing.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls on the VITROS Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack is supplied as ready to use and contains:

• . 100 coated wells (streptavidin, bacterial; binds ≥3 ng biotin per well; biotin recombinant SARS-CoV-2 antigen 0.1 ug/mL)
• 6.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent) .
• . 16.2 mL conjugate reagent (HRP-recombinant SARS-CoV-2 antigen) in buffer with bovine protein stabilizers and antimicrobial agent

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator contains:

• . 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator (anti-SARS-CoV-2 in anti-SARS-CoV-2 negative human plasma with antimicrobial agent, 1 mL)
• . Lot calibration card
• . Protocol card
• . 8 calibrator bar code labels

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls contain:

• . 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls 1 and 2 (defibrinated human plasma with anti-microbial agent, 2 mL). Control 1 is non-reactive and Control 2 is reactive.
  The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is designed for use on the VITROS Systems. The VITROS Systems use the following ancillary reagents (general purpose reagents):
• . VITROS Immunodiagnostic Products Signal Reagent
• VITROS Immunodiagnostic Products Universal Wash Reagent .

The document describes the evaluation of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator, a chemiluminescent immunoassay intended for qualitative detection of total antibodies to SARS-CoV-2.

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

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" for the clinical performance in a single, clear table with pass/fail thresholds. However, the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are the key clinical performance metrics presented. The FDA's decision to grant De Novo status implies that the reported performance met their internal criteria for safety and effectiveness for its intended use.

Here's a summary of the reported clinical performance:

Note: The PPA for samples collected early (0-7 days and 8-14 days post-symptom onset) is considerably lower (e.g., 36.00% to 44.00% for 0-7 days), reflecting the time required for antibody development. The indication for use specifies "samples collected on or after 15 days post-symptom onset," making the PPA for ≥15 days the most relevant for the primary intended use.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Test Set Sample Size:

  • PPA (Clinical Sensitivity Equivalent): 296 samples from individuals with prior SARS-CoV-2 positive RT-PCR results were initially acquired. However, the "Number of Subjects Tested" varies slightly per analyzer, typically around 282-286 for individual system reporting, and 237-239 for the ≥15 days post-symptom onset group which is the most relevant for the device's claims.
  • NPA (Clinical Specificity Equivalent): 513 presumed SARS-CoV-2 negative samples collected prior to the COVID-19 pandemic. The "Presumed Negative" count also varies slightly per analyzer, typically around 505-511.

• Data Provenance:

  • Country of Origin: All samples were collected within the United States.
  • Retrospective or Prospective: The samples were collected retrospectively. Population 1 (positive samples) was collected between April 2020 and April 2021. Population 2 (negative samples) was collected prior to December 2019.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is an in vitro diagnostic device for antibody detection, not an imaging AI system. Therefore, the "ground truth" for the clinical study was established by RT-PCR test results for SARS-CoV-2 infection (for positive samples) and collection of samples prior to the COVID-19 pandemic (for negative samples). There is no mention of human experts (e.g., pathologists or radiologists) adjudicating the ground truth for this type of test.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable for this type of in vitro diagnostic test where RT-PCR is the comparator and pre-pandemic samples define the negative group. Discrepancy resolution with expert radiologists would be relevant for imaging-based AI studies, not serology tests.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is an in vitro diagnostic (IVD) device for laboratory use, not an AI-assisted diagnostic tool for human readers (e.g., radiologists interpreting images). Its performance is evaluated as a standalone laboratory test.

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

Yes, the clinical performance (PPA and NPA) presented for the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is its standalone performance as an automated laboratory assay. There is no human-in-the-loop component for the interpretation or usage of the result beyond the laboratory professional's decision to report the qualitative positive/negative result.

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

• For Positive Samples (PPA): Ground truth was established by prior SARS-CoV-2 positive RT-PCR test results. The document states, "...using a comparator that FDA determined is appropriate (RT-PCR test)."
• For Negative Samples (NPA): Ground truth was established by collection date prior to the widespread outbreak of COVID-19 (i.e., prior to December 2019), deeming them "presumed SARS-CoV-2 negative samples."

8. The sample size for the training set

This document describes the validation of a commercial in vitro diagnostic (IVD) product, not an AI/machine learning model where a distinct 'training set' of patient data in the typical AI sense would be used to train the algorithm. The "training" of this device involves the development and optimization of the chemical reagents, assay parameters, and cutoff values performed internally by the manufacturer (Ortho-Clinical Diagnostics).

The closest equivalent to a "training" activity described in the context of setting the device's operational parameters is the Assay Cut-Off determination study (page 12-13). This study used:

• "a collection of negative samples collected prior to the COVID-19 pandemic"
• "samples collected from individuals with a prior SARS-CoV-2 RT-PCR positive result."

The specific numbers of these samples for the cutoff determination are not explicitly stated, but are implied to be part of the broader pool of samples available to the manufacturer during development. The ROC curve analysis was performed on these samples to optimize sensitivity and specificity at the S/C = 1.00 cutoff.

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

As noted in point 8, this isn't an AI model with a conventional training set. For the "samples" used in the Assay Cut-Off determination (analogous to internal optimization/training data):

• Negative Ground Truth: Established by "negative samples collected prior to the COVID-19 pandemic."
• Positive Ground Truth: Established by "samples collected from individuals with a prior SARS-CoV-2 RT-PCR positive result."

This implies a similar method to the clinical validation set for establishing true positive and true negative status, but performed during the device development phase to define the S/C cutoff.

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For in vitro diagnostic use only

VITROS Chemistry Products HbA1c reagent is used on VITROS 5.1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the quantitative determination of percent glycated hemoglobin Alc (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in human whole blood.

The test is to be used as an aid in diabetes, as an aid in identifying patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus.

For in vitro diagnostic use only

VITROS Calibrator Kit 31 is used to calibrate the VITROS 5.1 FS Chemistry System. VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the determination of percent glycated hemoglobin (HbA1c) in human whole blood.

For in vitro diagnostic use only

VITROS Chemistry Products %A1c Performance Verifiers are assayed controls used on the VITROS 5.1 FS Chemistry System, the VITROS 4600 Chemistry System and the VITROS 5600 Integrated System to monitor performance of the VITROS d%A1c and VITROS HbA1c Reagent Kits.

The determination of % glycated hemoglobin (HbA1c) is performed using the VITROS Chemistry Products HbA1c Reagent Kit in conjunction with the VITROS Chemistry Products Calibrator Kit 31 on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. The VITROS Chemistry Products HbA1c Reagents are two dual chambered packages containing ready-to-use liquid reagents. Whole blood samples are hemolyzed on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. The concentration of HbA1c and total Hb are measured in the hemolyzed samples, controls and calibrators.

Hemoglobin A1c and Hemoglobin

Whole blood samples are hemolyzed on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. Calibrators, controls and hemolyzed whole blood samples are mixed with Reagent 1 containing anti-HbA1c antibody to form a soluble antigen-antibody complex. Hemoglobin in the hemolyzed whole blood is converted with Reagent 1 to a hematin derivative that is measured bichromatically at 340 nm and 700 nm. Unbound anti-HbA1c antibody reacts with polyhapten (hexapeptide-glycan, A1c Reagent 2) to form an insoluble antibodypolyhapten immune complex, which is measured turbidimetrically at 340 nm. After a calibration has been performed for each reagent lot, the hemoglobin A1c and Hb concentrations in each unknown sample can be determined using the stored calibration curves and the measured absorbance obtained in the assay of the hemolyzed sample.

%A1c

% A 1c is a derived test calculated from the quantitative measurements of hemoglobin and hemoglobin A1c.

The VITROS® Chemistry Products Calibrator Kit 31 are prepared from a hemolysate derived from human and ovine blood to which surfactants, stabilizer, and preservative have been added. The calibrators are used to calibrate the VITROS 5,1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the determination of percent glycated hemoglobin (HbA1c) in human whole blood.

VITROS %A1c Performance Verifiers I and II are prepared from a hemolysate derived from human and ovine blood to which surfactants, stabilizer, and preservatives have been added.

The VITROS® Chemistry Products FS Reconstitution Diluent is a common reagent that is used by multiple assays on VITROS® 5,1 FS Chemistry Systems, VITROS® 4600 Chemistry Systems, and VITROS® 5600 Integrated Systems. There are no active ingredients, the fluid is proceesed water and is supplied in a 5 mL vial for reconstitution of lyophilized materials.

The VITROS® 5,1 FS Chemistry System and VITROS 4600 Chemistry Systems are clinical chemistry instruments that provide automated use of the VITROS® Chemistry Products MicroTip® and MicroSlides® range of products. The VITROS® 5,1 FS System was cleared for market by 510(k) premarket notification (K031924). The VITROS® 4600 Chemistry System is commercialized under the FDA's Guidance for Industry and Staff: Reagent Replacement and Instrument Family Member Policy (December 11, 2003) as a family member of the VITROS 5,1 FS Chemistry System (K031924). The VITROS® 5600 Integrated Systems are clinical laboratory instruments that provide automated use of the VITROS® Chemistry Products MicroTip® and MicroSlides® range of products and VITROS® Immunodiagnostic Products MicroWells® range of products. The VITROS 5600® Integrated System was cleared for market by 510(k) premarket notification (K081543).

Here's the information about the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

• VITROS 5,1 FS: -0.08 + 1.01x
• VITROS 4600: -0.14 + 1.02x
• VITROS 5600: -0.06 + 1.00x | Not applicable (high correlation demonstrated) |
  | Precision/Reproducibility | All acceptance criteria for precision were met. (Specific numerical criteria are not detailed in the summary but were likely internally defined and met based on the statement). | Total precision (%CV) for VITROS 5,1 FS: Controls (VITROS PV1 2.03%, BBI 5% 1.83%, BBI 6.5% 2.09%, BBI 8% 2.69%, BBI 12% 2.03%). Patients (5% 2.21%, 6.5% 2.01%, 8% 1.92%, 12% 2.52%).
  Total precision (%CV) for VITROS 4600: Controls (VITROS PV1 1.32%, BBI 5% 1.19%, BBI 6.5% 1.62%, BBI 8% 1.43%, BBI 12% 2.01%). Patients (5% 1.10%, 6.5% 1.19%, 8% 1.66%, 12% 2.09%).
  Total precision (%CV) for VITROS 5600: Controls (VITROS PV1 1.18%, BBI 5% 1.41%, BBI 6.5% 1.40%, BBI 8% 1.27%, BBI 12% 1.76%). Patients (5% 1.05%, 6.5% 1.12%, 8% 1.28%, 12% 1.94%). | Yes |
  | Linearity/Measuring Range | Not explicitly stated as a numerical criterion for approval. | Linear range for % A1c: 3.034-15.444% (NGSP derived test).
  Linear range for HbA1c: 9.6-145.3 mmol/mol (SI derived test).
  (Specific r^2 values are given, all are >0.997). | Yes (linearity shown) |
  | Detection Limit (LoD) | Claim of 2.580% NGSP for LoQ | LoB for %A1c: 2.396% NGSP (2.67 mmol/mol SI)
  LoD for %A1c: 2.580% NGSP (4.68 mmol/mol SI)
  LoQ for %A1c: 2.580% NGSP (4.68 mmol/mol SI) | Yes |
  | Analytical Specificity (Interference) | Bias ≤ 0.5% A1c (≤ 5 HbA1c (mmol/mol)) at ~6.5% A1c; Bias ≤ 0.6% A1c (≤ 7 HbA1c (mmol/mol)) at ~8.5% A1c for listed substances. Hemoglobin variants HbA0, HbA1a, HbA1b, C, D, E, S should not interfere. | Listed Substances (e.g., Acetaminophen, Bilirubin, Glucose): Found not to interfere at specified concentrations.
  Hemoglobin Variants: HbS up to 41%, HbC up to 38%, HbD up to 38%, HbE up to 26% of total hemoglobin do not interfere. Anti-HbA1c antibodies do not cross-react with HbA0, HbA1a, HbA1b at stated levels. HbF >7% may result in lower than expected values. | Yes (with a caveat for high HbF) |
  | NGSP Certification | NGSP certification received. | NGSP certification was received for the VITROS HbA1c assay on all three noted systems. | Yes |

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

• Accuracy (Method Comparison): 357 samples were used. The samples were distributed across the range of the assay.
• Precision/Reproducibility:
  • Quality Control Materials (hemolysate and whole blood-based): 20-22 days of testing, samples per data point varied (e.g., 756 or 792 for controls for 3 lots across multiple analyzers).
  • Intermediate Precision Study (whole blood patient samples): 4 days of testing, 144 samples per patient level.
• Linearity: Low and high pools were mixed to give 16 intermediate concentration pools.
• Detection Limit: 500 determinations based on 5 low-level samples.
• Analytical Specificity (Interference): Specific numbers of patient samples for Hb variants were tested (e.g., 70 for HbA1a/A1b, 22 for HbA2, 31 for HbC, 21 for HbD, 30 for HbE, 40 for HbS, 43 for HbF). The list of interfering substances does not specify sample size per substance but indicates testing was done “for each substance tested” on control and test substance pools.
• Data Provenance: The document implies the data was generated specifically for this 510(k) submission (prospective), likely from internal studies or contract research organizations. The country of origin for the data is not explicitly stated, but the submission is to the US FDA by Ortho-Clinical Diagnostics, Inc. in Rochester, New York, suggesting US-based studies unless otherwise specified. The reference method for accuracy was a "secondary reference laboratory of the NGSP," implying a credible, standardized source.

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

• The ground truth for the accuracy study was established using a "secondary reference laboratory of the NGSP." The number and specific qualifications of experts within this laboratory are not specified in this document. However, the NGSP (National Glycohemoglobin Standardization Program) implies adherence to a highly standardized and validated reference method for HbA1c, which inherently involves expert-level procedures and validation.

4. Adjudication Method

• For the analytical performance studies (accuracy, precision, linearity, detection limits, analytical specificity), an adjudication method is not typically described as it would be for clinical image interpretation or diagnostic performance involving human assessment. The "ground truth" is established by highly controlled and validated laboratory reference methods. The comparison is quantitative against these reference methods.

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

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging AI devices where human reader performance is being assessed and compared with and without AI assistance. The VITROS Chemistry Products HbA1c Reagent Kit is an in vitro diagnostic assay, not an imaging AI device with a human-in-the-loop component for interpretation.

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

• Yes, the performance data presented is for the standalone device (the VITROS Chemistry Products HbA1c Reagent Kit and associated systems/calibrators/verifiers) without human-in-the-loop performance being a variable. The studies assess the analytical performance of the assay itself.

7. Type of Ground Truth Used

• The ground truth used for relevant studies (e.g., accuracy) was:
  • Reference Method: Traceability to the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) Reference Method, and certification by the National Glycohemoglobin Standardization Program (NGSP) which is traceable to the Diabetes Control and Complications Trial (DCCT) Reference Method. This represents a highly standardized and validated laboratory-based reference standard.

8. Sample Size for the Training Set

• This information is not provided. For an in vitro diagnostic reagent kit, there isn't typically a "training set" in the machine learning sense. The device's "training" or optimization would happen during its development phase using various experimental designs and samples, rather than a distinct, documented "training set" like in AI/ML performance studies. The document focuses on the validation or test set performance.

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

• As mentioned above, a "training set" in the AI/ML context isn't directly applicable here. The development of the assay (analogous to "training") would involve extensive R&D, chemical optimization, and preliminary testing against known samples and reference methods. The ground truth for these developmental internal studies would be established using similar highly accurate and traceable laboratory reference methods.

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VITROS Immunodiagnostic Products 25-OH Vitamin D Total Reagent Pack:

For in vitro diagnostic use only

For the quantitative measurement of total 25-OH vitamin D in human serum using the VITROS ECi/ECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System.

The results of the VITROS 25-OH Vitamin D Total assay are used in the assessment of Vitamin D sufficiency. Assay results may be used in conjunction with other clinical or laboratory data to assist the clinician in patient management.

VITROS Immunodiagnostic Products 25-OH Vitamin D Total Calibrators:

For in vitro diagnostic use only.

For use in the calibration of the VITROS ECi/ECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic Systems and the VITROS 5600 Integrated System for the quantitative measurement of total 25-OH vitamin D in human serum.

The VITROS Immunodiagnostic Products Vitamin D test system comprises three main elements:

• 1. The VITROS Immunodiagnostic range of products. In this case the VITROS Immunodiagnostic Products 25-OH Vitamin D Total Reagent Pack and the VITROS Immunodiagnostic Products 25-OH Vitamin D Total Calibrators are required to perform a VITROS Vitamin D test.
• The VITROS Immunodiagnostic and Integrated Systems: Instrumentation, which 2. provides automated use of the immunoassay kits.

The VITROS ECi/ECiQ Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919). This product was updated to the VITROS ECiQ Immunodiagnostic System by addition of a flat panel monitor with an accompanying articulating arm, cosmetic changes to the instrument cabinetry, and with FDA notification in January of 2004.

The VITROS 3600 Immunodiagnostic System: Instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K083173).

The VITROS 5600 Integrated System: Instrumentation, which provides automated use of the immunoassay kits. The VITROS Integrated System was cleared for market by a separate 510(k) pre-market notification (K081543).

• 3. Common reagents used by the VITROS System in each assay: The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).
     The VITROS Immunodiagnostic and Integrated Systems and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products.

The provided 510(k) summary describes the acceptance criteria and performance data for the VITROS® Immunodiagnostic Products 25-OH Vitamin D Total Reagent Pack and Calibrators.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a single, consolidated table with pass/fail remarks. Instead, it presents performance study results. The implied acceptance criteria are the demonstrated performance characteristics (e.g., precision, linearity, limit of detection, specificity, and method comparison results meeting statistical thresholds).

Table: Implied Acceptance Criteria and Reported Device Performance

• ECI/ECIQ System 1 Lot 1: 5.5-15.3%
• ECI/ECIQ System 2 Lot 2: 5.4-16.4%
• 3600 System 1 Lot 1: 6.0-16.5%
• 3600 System 1 Lot 3: 4.8-15.8%
• 5600 System 1 Lot 2: 5.6-12.8% |
  | Linearity/Measuring Range | Assay should be linear across the claimed measuring range. | Linear from 12.8 to 126 ng/mL (32.0 to 315 nmol/L). |
  | Limit of Detection (LoD) | LoD should be adequately low for clinical utility. | 8.64 ng/mL (21.6 nmol/L) (with 10% bias at indicated concentrations in 25-OH Vitamin D concentrations of 30-80 ng/mL, with the exception of Paricalcitol (Zemplar). |
  | Specificity (Cross-Reactivity) | Cross-reactivity should be characterized and acceptable. | 25-OH Vitamin D2: 104.9%
  25-OH Vitamin D3: 98.9%
  (Other listed substances showed lower or context-dependent cross-reactivity/bias) |
  | Method Comparison (Correlation with Predicate) | Strong correlation (high 'r' value) and acceptable slopes/intercepts compared to predicate device. | VITROS 5600 vs IDS-iSYS: r = 0.92, Slope CI (0.86-1.12), Intercept CI (-10.2 to -0.53)
  VITROS 3600 vs IDS-iSYS: r = 0.93, Slope CI (0.96-1.22), Intercept CI (-12.4 to -2.95)
  VITROS ECi/ECiQ vs IDS-iSYS: r = 0.94, Slope CI (0.86-1.09), Intercept CI (-14.2 to -4.69) |

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

• Precision: 3 patient samples and 1 commercial control sample per system/lot condition. Each sample tested as 2 replicates per day, on at least 20 different days (total 80 observations per sample per system/lot combination).
• Linearity: Two pools of patient samples (low and high) were used to create 7 intermediate pools.
• Limit of Detection: 1 blank and 6 low-level samples, with 700 determinations in total.
• Specificity (Interference/Cross-reactivity): Patient samples near 30 ng/mL and 80 ng/mL Vitamin D. The exact number of individual samples for interference testing is not specified, but the cross-reactivity table shows results for specific compounds.
• Method Comparison: A minimum of 117 human serum samples were used.
• Reference Range: 399 apparently healthy adults.
• Data Provenance:
  • For the reference range study, samples came from individuals in the North, South, and Central regions of the United States, collected in both summer and winter. This indicates prospective collection of samples specifically for this study.
  • For other studies (precision, linearity, method comparison), the document mentions "patient samples" and "human serum samples." The specific country of origin or whether these were purely retrospective or prospectively collected is not explicitly stated, but they are clearly human-derived samples.

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

Not applicable. For in vitro diagnostic (IVD) assays like this one, "ground truth" is typically established by reference methods or comparison to a legally marketed predicate device, rather than expert consensus on images or interpretations. The product measures a specific analyte concentration.

4. Adjudication method for the test set

Not applicable. This is an IVD device for quantitative measurement of a biomarker, not a diagnostic imaging device requiring expert adjudication of interpretations.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is an in vitro diagnostic (IVD) device, not an AI-assisted diagnostic imaging or interpretation device that would involve human readers.

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

Yes, the device is a standalone in vitro diagnostic (IVD) system. Its performance (e.g., precision, linearity, limit of detection, and quantitative measurements in method comparison studies) represents the "algorithm only" performance, as it directly quantifies 25-OH Vitamin D in human serum samples on automated immunodiagnostic systems without human interpretation of results influencing the measurement itself.

7. The type of ground truth used

The "ground truth" for this quantitative assay is established by:

• Reference measurements/Predicate Device Comparison: The method comparison study uses a legally marketed predicate device, the IDS-iSYS® 25-Hydroxy Vitamin D Assay, as the reference for comparison, and demonstrates substantial equivalence.
• Internal analytical validation: Performance claims (precision, linearity, LoD/LoQ, specificity) are established through rigorous analytical testing against recognized CLSI guidelines, implying accepted analytical standards for correctness.

8. The sample size for the training set

The document does not explicitly mention "training set" or "validation set" in the context of an algorithm. For IVD devices, a "training set" in the machine learning sense is not typically used. Instead, the analytical performance (precision, linearity, etc.) is established using various samples, and calibration is performed using specific calibrators.

• The linearity study used two pools of patient samples.
• The precision study used patient samples and commercial controls.
• The specificity studies used patient samples.

These samples are used to characterize the device's performance, not to "train" an algorithm.

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

Not applicable, as a "training set" in the machine learning sense for an algorithm is not described. For the types of samples used in analytical studies:

• Patient samples: Their ground truth would be their actual 25-OH Vitamin D concentration, as measured by a highly accurate or reference method at the time of study or by the predicate device (as in the method comparison).
• Commercial control samples: These have assigned target values for specific analytes, often established through an internal reference method or inter-laboratory consensus.

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