Search Results

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.

Ask a specific question about this device

VITROS Immunodiagnostic Products TSH Reagent Pack: For the in vitro quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin) using the VITROS ECi/ECiQ Immunodiagnostic Systems and VITROS 5600 Integrated System to aid in the differential diagnosis of thyroid disease.
VITROS Immunodiagnostic Products TSH Calibrators: For in vitro use in the calibration of the VITROS ECI/ECIQ Immunodiagnostic Systems and VITROS 5600 Integrated System for the quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin).
VITROS Chemistry Products PHYT Slides: For in vitro diagnostic use only. VITROS Chemistry Products PHYT Slides quantitatively measure phenytoin (PHYT) concentration in serum and plasma using VITROS 250/350/950 and 5,1 FS Chemistry Systems and the VITROS 5600 Integrated System.
VITROS Chemistry Products Calibrator Kit 9: For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 9 is used to calibrate VITROS 250/350/950 and 5.1 FS Chemistry Systems and the VITROS 5600 Integrated System for the quantitative measurement of ACET, CRBM, DGXN, PHBR, and PHYT.
VITROS 5600 Integrated System: For use in the in vitro quantitative, semi-quantitative measurement of a variety of analytes of clinical interest, using VITROS Chemistry Products Slides, VITROS Chemistry Products MicroTip Reagents and VITROS Immunodiagnostic Products Reagents.

The VITROS Immunodiagnostic Products TSH assay and VITROS Chemistry Products PHYT assay are intended for use on the VITROS 5600 Integrated System. The VITROS 5600 Integrated System combines the existing VITROS 5,1 FS Chemistry System (K031924) and the VITROS ECi/ECiQ Immunodiagnostic System (K962919) into a single system. All technology, methodologies and analytical methods currently available on the existing two systems are available on the new integrated system.

This is a 510(k) premarket notification for modifications to existing assays (VITROS Immunodiagnostic Products TSH and VITROS Chemistry Products PHYT) to be used with a new integrated system (VITROS 5600 Integrated System). The submission focuses on demonstrating substantial equivalence to previously cleared devices.

Therefore, the typical "acceptance criteria" and "study that proves the device meets the acceptance criteria" in the context of a new diagnostic algorithm's performance are not explicitly detailed in the provided text. This is because the submission is for a system modification rather than a new algorithmic diagnostic device with performance metrics like sensitivity, specificity, etc.

However, based on the context of a 510(k) for a laboratory diagnostic system, we can infer the types of performance criteria that would be relevant for demonstrating substantial equivalence for the modified use of the assays on the new system. These would typically include:

• Method Comparison: Showing that results obtained on the new integrated system are comparable to those obtained on the predicate systems.
• Precision: Demonstrating acceptable within-run and between-run variability on the new system.
• Linearity/Analytical Measurement Range: Confirming the ability to accurately measure analytes across a defined range on the new system.
• Interference: Ensuring common interfering substances do not significantly impact results on the new system.
• Stability: Verifying the stability of reagents and calibrators when used with the new system.
• Reference Range: Confirming the appropriate reference intervals for the assays on the new system.

Since the provided text does not contain detailed study results for these specific performance characteristics (as it's a summary document), I cannot fill out all sections. I will address what can be inferred or is explicitly stated:

1. Table of Acceptance Criteria and the Reported Device Performance:

The document doesn't explicitly state numerical acceptance criteria for performance metrics (e.g., "TSH bias must be within X%") or report detailed performance data. Instead, the submission relies on the concept of "substantial equivalence" of the modified device to the predicate devices. This implies that the performance on the new combined system is expected to be equivalent to the already cleared separate systems.

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

• Sample Size: Not explicitly stated in the summary document. For method comparison studies in IVDs, hundreds of clinical samples are typically used across the analytical range.
• Data Provenance: Not explicitly stated. Assumed to be clinical samples relevant to the intended use.

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 not applicable in the context of this 510(k) for an in vitro diagnostic (IVD) system. For IVDs, "ground truth" is typically established by reference methods, comparison to predicate devices, or spiking studies, not by expert interpretation of images or clinical data.

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

Not applicable. Diagnostic assays like TSH and PHYT use quantitative measurements, and "adjudication" in the sense of resolving discrepancies between human readers is not relevant. The comparison would be between the numerical results of the new system and the predicate system.

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 IVD system for quantitative measurement, not an AI-assisted diagnostic imaging device that involves human reader interpretation.

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

The device (VITROS 5600 Integrated System running the TSH and PHYT assays) is a standalone automated system for quantitative measurement. Its performance is evaluated intrinsically through analytical studies (precision, accuracy, method comparison, etc.) as described under point 1.

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

For this type of IVD device, ground truth would typically be established by:

• Reference Methods: Comparison against established, highly accurate analytical methods.
• Predicate Device Comparison: Demonstrating statistical equivalence of results when compared to the existing cleared devices (VITROS ECi/ECiQ and VITROS 5,1 FS Chemistry System) on the same samples.
• Spiked Samples: Using samples with known concentrations of the analyte.

The submission heavily relies on the "substantial equivalence" to predicate devices, indicating that the predicate device's performance effectively serves as the "ground truth" for comparison.

8. The sample size for the training set:

Not applicable in the AI/machine learning sense. For IVD systems, "training" refers to calibration and quality control. The training of the system for measuring TSH and PHYT would involve:

• Calibration: Using the specific calibrators (VITROS Immunodiagnostic Products TSH Calibrators and VITROS Chemistry Products Calibrator Kit 9). The sample sizes for calibration materials are determined by statistical design to ensure accurate curve fitting.
• Quality Control: Regular testing of quality control materials to ensure the system is performing within specifications.

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

• Calibrators: The ground truth (assigned value) for the calibrators is established through a rigorous process by the manufacturer, typically involving reference methods, traceability to international standards (if available for TSH), and extensive internal validation studies.
• Quality Control Materials: Similar to calibrators, assigned values for quality control materials are established by the manufacturer through reference methods and internal validation.

Ask a specific question about this device

For in vitro diagnostic use only. VITROS Chemistry Products BARB Reagent is used on VITROS 5,1 FS Chemistry Systems for the semi-quantitative or qualitative determination of barbiturates (BARB) in human urine using a cutoff of either 200 ng/mL or 300 ng/mL. Measurements obtained with the VITROS BARB method are used in the diagnosis and treatment of barbiturates use or overdose.

The VITROS Chemistry Products BARB assay is intended for use by professional laboratory personnel. It provides only a preliminary test result. A more specific alternative chemical method must be used to confirm a result obtained with this assay. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when evaluating a preliminary positive result.

For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 26 is used to calibrate VITROS 5,1 FS Chemistry Systems for the qualitative or semi-quantitative measurement of drugs of abuse.

For in vitro diagnostic use only. VITROS Chemistry Products FS Calibrator 1 is used in conjunction with VITROS Chemistry Products Calibrator Kits to calibrate VITROS 5,1 FS Chemistry Systems.

For in vitro diagnostic use only. VITROS Chemistry Products DAT Performance Verifiers are assayed controls used to monitor performance of urine drugs of abuse screening assays on VITROS 5,1 FS Chemistry Systems.

The VITROS BARB assay is a homogeneous enzyme immunoassay that is performed using the VITROS Chemistry Products BARB Reagent with the VITROS Chemistry Products Calibrator Kit 26, VITROS Chemistry Products FS Calibrator 1, and VITROS Chemistry Products FS Diluent Pack 4 (DAT Diluent / DAT Diluent 2) on VITROS 5,1 FS Chemistry Systems.

The VITROS BARB Reagent is a dual chambered package containing ready-to-use liquid reagents that are used to detect barbiturates in urine. Sample, calibrators, and controls are automatically treated with surfactant (DAT Diluent 2) prior to addition of reagents. Treated sample is added to Reagent 1 containing antibody reactive to secobarbital, glucose-6-phosphate and nicotinamide adenine dinucleotide (NAD*), followed by Reagent 2 containing secobarbital labeled with the enzyme glucose-6phosphate dehydrogenase (G6P-DH). The assay is based on competition between barbiturates in the treated urine sample and secobarbital labeled with the enzyme glucose-6phosphate dehydrogenase (G6P-DH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, therefore the concentration of barbiturates in the urine sample is directly proportional to measured enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD') to NADH, resulting in an absorbance change that is measured spectrophotometrically at 340 nm.

The VITROS Chemistry Products Calibrator Kit 26 is prepared from human urine to which drugs of abuse, metabolites of drugs of abuse, organic salt, surfactants, and preservative have been added. VITROS Chemistry Products FS Calibrator 1 is prepared from sodium chloride and processed water. These standards are used to calibrate VITROS 5,1 FS Chemistry Systems for the qualitative and semiquantitative measurement of barbiturates (BARB).

The VITROS Chemistry Products DAT Performance Verifiers I, II, III, IV, and V are quality control materials prepared from a human urine pool to which analytes, surfactant, and preservative have been added. These are assayed controls used to monitor performance of the VITROS BARB assay on VITROS 5,1 FS Chemistry Systems.

The VITROS Chemistry Products FS Diluent Pack 4 (DAT Diluent / DAT Diluent 2 is a common reagent that is used by multiple assays on the VITROS 5,1 FS Chemistry System. This is a dual chambered package containing two ready-to-use liquid diluents. DAT Diluent is prepared from human urine to which organic salt, surfactants, and preservative have been added. DAT Diluent 2 is prepared from processed water to which surfactant and preservative have been added.

The VITROS 5,1 FS Chemistry System is a clinical chemistry instrument that provides 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 provided text describes a 510(k) premarket notification for the VITROS Chemistry Products BARB Reagent and associated calibrators and verifiers. This is a submission for an in-vitro diagnostic device, which typically involves demonstrating substantial equivalence to a predicate device rather than conducting a new clinical efficacy study with acceptance criteria often seen in device approvals.

Therefore, the information traditionally requested for acceptance criteria and a study proving a device meets these criteria (such as sample sizes for test and training sets, expert qualifications, adjudication methods, MRMC studies, standalone performance, and ground truth types) is not directly applicable or available in this type of submission.

Instead, the document focuses on demonstrating substantial equivalence to existing legally marketed predicate devices. The "study" described is a comparison study against a predicate device.

Here's a breakdown of what can be extracted or inferred from the provided text, framed within your request:

1. Table of Acceptance Criteria and Reported Device Performance

Formal, pre-defined acceptance criteria (e.g., target specificity/sensitivity thresholds) for performance against a gold standard are not explicitly stated as they would be for a novel device efficacy claim. Instead, the "acceptance" hinges on demonstrating "good agreement" and "similar performance characteristics" to the predicate device.

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

• Test Set Sample Size: Not explicitly stated. The document mentions "patient samples" were used to demonstrate equivalence. The exact number of patient samples used in the comparison study is not provided.
• Data Provenance: Not specified, but likely from a clinical laboratory or labs in the US, given the submission to the FDA. The term "patient samples" suggests a retrospective or prospective collection, but this detail is also not specified.

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

• Ground Truth Establishment: For in vitro diagnostic assays for drugs of abuse, the "ground truth" is typically established by a highly sensitive and specific reference method, not by expert consensus (e.g., pathologists or radiologists). The document explicitly states: "A more specific alternative chemical method must be used to confirm a result obtained with this assay. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method."
• Expert Qualifications: Not applicable in the context of establishing ground truth for this type of assay.

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

• Not applicable. Adjudication methods like 2+1 or 3+1 are typically used in imaging studies where subjective interpretation is common. For an in vitro diagnostic assay with a quantitative gold standard (GC/MS), this process would not be used.

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 not an imaging or AI-assisted diagnostic device that involves human readers interpreting results. It is an automated laboratory assay.

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

• The VITROS BARB assay is an automated homogeneous enzyme immunoassay performed on the VITROS 5,1 FS Chemistry System. Therefore, its performance is inherently standalone (algorithm/instrument only) as it provides a result without direct human interpretation of the reaction signals, though human laboratory personnel operate the system and interpret the final reported numerical or qualitative result. This study implicitly demonstrates standalone performance relative to the predicate device.

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

• The implicit "ground truth" for confirmation is Gas Chromatography/Mass Spectrometry (GC/MS), which is stated as the preferred confirmatory method for positive results. The calibration traceability is also tied to secobarbital confirmed by GC/MS. This is a highly accurate analytical chemistry method.

8. The sample size for the training set

• Not applicable. For this type of immunoassay, there isn't a "training set" in the machine learning sense. The assay is developed based on chemical and biological principles (antibody-antigen reactions, enzyme kinetics) rather than being trained on a dataset. Reference standards and controls are used for calibration and quality control, but this is distinct from a machine learning training set.

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

• Not applicable, as there is no "training set" in the machine learning context. The calibrators and controls used are prepared standards with known concentrations, traceable to secobarbital with GC/MS confirmation (as mentioned for calibration traceability).

Ask a specific question about this device

VITROS Chemistry Products THC Reagent: For in vitro diagnostic use only. VITROS Chemistry Products THC Reagent is used on VITROS 5,1 FS Chemistry Systems for the semi-quantitative or qualitative determination of cannabinoids (THC) in human urine using a cutoff of either 20 ng/mL or 50 ng/mL. Measurements obtained with the VITROS THC method are used in the diagnosis and treatment of cannabinoid use or overdose.

The VITROS Chemistry Products THC assay is intended for use by professional laboratory personnel. It provides only a preliminary test result. A more specific alternative chemical method must be used to confirm a result obtained with this assay. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when evaluating a preliminary positive result.

VITROS Chemistry Products Calibrator Kit 30: For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 30 is used to calibrate VITROS 5,1 FS Chemistry Systems for the qualitative or semi-quantitative measurement of cannabinoids (THC).

VITROS Chemistry Products FS Calibrator 1: For in vitro diagnostic use only. VITROS Chemistry Products FS Calibrator 1 is used in conjunction with VITROS Chemistry Products Calibrator Kits to calibrate VITROS 5,1 FS Chemistry Systems.

VITROS Chemistry Products DAT Performance Verifiers I, II, III, IV and V: For in vitro diagnostic use only. VITROS Chemistry Products DAT Performance Verifiers are assayed controls used to monitor performance of urine drugs of abuse screening assays on VITROS 5,1 FS Chemistry Systems.

The VITROS THC assay is a homogeneous enzyme immunoassay that is performed using the VITROS THC Reagent with the VITROS Calibrator Kit 30, VITROS FS Calibrator 1 and VITROS FS Diluent Pack 4 (DAT Diluent / DAT Diluent 2) on VITROS 5,1 FS Chemistry Systems.

The VITROS THC Reagent is a dual chambered package containing ready-to-use liquid reagents that are used to detect cannabinoids in urine. Sample, calibrators, and controls are automatically treated with surfactant (DAT Diluent 2) prior to addition of reagents. Treated sample is added to Reagent 1 containing antibodies reactive to delta-9-tetrahydrocannabinol (delta-9-THC), glucose-6-phosphate and nicotinamide adenine dinucleotide (NAD+), followed by Reagent 2 containing delta-9-THC labeled with the enzyme glucose-6-phosphate dehydrogenase (G6P-DH), The assay is based on competition between delta 9-THC metabolites in the treated urine sample and the delta 9 -THC labeled with the enzyme glucose-6-phosphate dehydrogenase (G6P-DH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, therefore the concentration of delta-9-THC metabolites in the urine sample is directly proportional to measured enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD+) to NADH, resulting in an absorbance change that is measured spectrophotometrically at 340 nm.

VITROS Calibrator Kit 30 is prepared from human urine to which analyte, surfactant, and preservatives have been added. The VITROS FS Calibrator 1 is composed of processed water and 0.9% w/v sodium chloride (Saline). These calibrators are used to calibrate VITROS 5,1 FS Chemistry Systems for the qualitative or semiquantitative measurement of cannabinoids (THC).

VITROS DAT Performance Verifiers I, II, III, IV and V are prepared from a human urine pool to which analytes, surfactant, and preservative have been added. These are assayed controls used to monitor performance of the VITROS THC assay on VITROS 5,1 FS Chemistry Systems.

The VITROS FS Diluent Pack 4 (DAT Diluent/ DAT Diluent 2) is a common reagent that is used with several drugs of abuse assays to dilute calibrators and samples on the VITROS 5,1 FS System. This is a dual chambered package containing two ready-to-use liquid diluents. DAT Diluent is prepared from human urine to which organic salt, surfactants, and preservative have been added. DAT Diluent 2 is prepared from processed water to which surfactant and preservative have been added.

The VITROS 5,1 FS Chemistry System is a clinical chemistry instrument that provides automated use of the VITROS MicroTip® and MicroSlides® range of products. The VITROS 5,1 FS System was cleared for market by 510(k) Premarket Notification (K031924).

1. Table of Acceptance Criteria and Reported Device Performance:

The document describes the VITROS THC assay, which is a homogeneous enzyme immunoassay for the semi-quantitative or qualitative determination of cannabinoids (THC) in human urine. The acceptance criteria are implicitly defined by the device's substantial equivalence to predicate devices, meaning its performance should be comparable to or better than previously cleared devices.

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

• Sample Size: The document states that "patient samples" were used for correlation studies. However, the exact number or size of the test set is not explicitly provided in the summary.
• Data Provenance: Not explicitly stated, but the context of an FDA 510(k) submission for a diagnostic product generally implies regulated, clinical laboratory-generated data. The mention of "patient samples" suggests a clinical setting. The country of origin is not specified but is implicitly in the US due to the FDA submission. The study is retrospective in the sense that it uses existing data or samples to compare the new device to already marketed devices.

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

• Number of Experts: Not applicable or not specified. In this type of diagnostic device submission, the "ground truth" for the test set is established by the results from the predicate devices (SYVA® EMIT® II Plus Cannabinoid Assay on OLYMPUS® AU400™ and SYVA® 30R Biochemical System) or by a "more specific alternative chemical method" like GC/MS for confirmation.
• Qualifications of Experts: Not applicable, as expert consensus is not the method for establishing ground truth described here. The predicate devices themselves are considered the established standard.

4. Adjudication Method for the Test Set:

• Not applicable as expert adjudication is not described. The study compared the VITROS THC assay results directly to the results obtained from the predicate devices. For positive results, confirmation by Gas Chromatography/Mass Spectrometry (GC/MS) is stated as the preferred method, implying a definitive or "gold standard" for confirmation, rather than human 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:

• A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) chemistry product, not an imaging or AI-assisted diagnostic tool that involves human readers interpreting output. Its performance is assessed directly against chemical measurements.

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

• This device is inherently a standalone algorithm/device in its function. It performs an automated chemical analysis on a sample and provides a result (qualitative or semi-quantitative for THC). Human involvement is limited to sample loading, system operation, and interpretation of the numerical result as per clinical guidelines, not in generating the primary diagnostic output itself.

7. The Type of Ground Truth Used:

• The ground truth for the test set was established by comparison to predicate immunoassay methods (SYVA® EMIT® II Plus Cannabinoid Assay) and implied confirmatory methods such as Gas Chromatography/Mass Spectrometry (GC/MS) for preliminary positive results, as stated in the intended use. This represents a form of established diagnostic standard/reference method.

8. The Sample Size for the Training Set:

• The document does not provide information regarding a specific "training set" or its sample size. This is typical for such diagnostic assays, which are developed through iterative optimization and validation processes rather than machine learning training on a distinct "training set" in the common sense. The extensive bench testing for precision, linearity, specificity, and LOD would involve numerous samples, but these are part of the overall development and validation, not a separate "training set" for an AI model.

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

• As a distinct "training set" is not described in the context of this traditional IVD product, the method for establishing its ground truth is not applicable. The underlying chemical principles and established reference methods (like GC/MS) guide the development and optimization of such assays.

Ask a specific question about this device

For in vitro diagnostic use only. VITROS Chemistry Products PCP Reagent is used on VITROS 5,1 FS Chemistry Systems for the semi-quantitative or qualitative determination of phencyclidine (PCP) in human urine using a cutoff of 25 ng/mL. Measurements obtained with the VITROS PCP method are used in the diagnosis and treatment of phencyclidine use or overdose.

The VITROS Chemistry Products PCP assay is intended for use by professional laboratory personnel. It provides only a preliminary test result. A more specific alternative chemical method must be used to confirm a result obtained with this assay. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when evaluating a preliminary positive result.

For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 26 is used to calibrate VITROS 5,1 FS Chemistry Systems for the qualitative or semi-quantitative measurement of drugs of abuse.

For in vitro diagnostic use only. VITROS Chemistry Products FS Calibrator 1 is used in conjunction with VITROS Chemistry Products Calibrator Kits to calibrate VITROS 5,1 FS Chemistry Systems.

For in vitro diagnostic use only. VITROS Chemistry Products DAT Performance Verifiers are assayed controls used to monitor performance of urine drugs of abuse screening assays on VITROS 5,1 FS Chemistry Systems.

The VITROS PCP assay is a homogeneous enzyme immunoassay that is performed using the VITROS Chemistry Products PCP Reagent with the VITROS Chemistry Products Calibrator Kit 26, VITROS Chemistry Products FS Calibrator 1 and VITROS Chemistry Products FS Diluent Pack 4 (DAT Diluent / DAT Diluent 2) on VITROS 5,1 FS Chemistry Systems. The VITROS PCP Reagent is a dual chambered package containing ready-to-use liquid reagents that are used to detect phencyclidine in urine. Samples, calibrators, and controls are automatically treated with surfactant (DAT Diluent 2) prior to addition of reagents. Treated sample is added to Reagent 1 containing antibody reactive to phencyclidine, glucose-6-phosphate and nicotinamide adenine dinucleotide (NAD), followed by Reagent 2 containing phencyclidine labeled with the enzyme glucose-6-phosphate dehydrogenase (G6P-DH). The assay is based on competition between phencyclidine in the treated urine sample and phencyclidine labeled with the enzyme glucose-6-phosphate dehydrogenase (G6P-DH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, therefore the concentration of phencyclidine in the urine sample is directly proportional to measured enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that is measured spectrophotometrically at 340 nm. VITROS Chemistry Products Calibrator Kit 26 is prepared from human urine to which drugs of abuse, metabolites of drugs of abuse, organic salt, surfactants, and preservative have been added. VITROS FS Calibrator 1 is prepared from sodium chloride and processed water. VITROS Calibrator Kit 26 is used in conjunction with VITROS FS Calibrator 1 to calibrate VITROS 5.1 FS Chemistry Systems for the qualitative or semi-quantitative measurement of phencyclidine (PCP). VITROS Chemistry Products DAT Performance Verifiers I. II, and V are prepared from a human urine pool to which analytes, surfactant, and preservative have been added. These are assaved controls used to monitor performance of the VITROS PCP assay on VITROS 5,1 FS Chemistry Systems. The VITROS Chemistry Products FS Diluent Pack 4 (DAT Diluent/ DAT Diluent 2) is a common reagent that is used with several drugs of abuse assays to dilute calibrators and samples on the VITROS 5,1 FS System. This is a dual chambered package containing two ready-to-use liquid diluents. DAT Diluent is prepared from human urine to which organic salt, surfactants, and preservative have been added. DAT Diluent 2 is prepared from processed water to which surfactant and preservative have been added. The VITROS 5,1 FS Chemistry System is a clinical chemistry instrument that provides 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).

This document describes the VITROS Chemistry Products PCP Reagent, VITROS Chemistry Products Calibrator Kit 26, VITROS Chemistry Products FS Calibrator 1, and VITROS Chemistry Products DAT Performance Verifiers, which are devices used for the semi-quantitative or qualitative determination of phencyclidine (PCP) in human urine.

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

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly list "acceptance criteria" as a separate section with specific numerical targets. Instead, it demonstrates the device's performance through comparison with legally marketed predicate devices. The primary acceptance criterion implicit in the 510(k) submission process is substantial equivalence to the predicate device.

The study aimed to show good agreement between the VITROS PCP assay and the predicate device (DADE BEHRING Syva® EMIT® II Plus Phencyclidine Assay).

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

The document states: "Equivalence to the predicates was demonstrated using a commercially available assay along with patient samples."

• Test Set Sample Size: The exact number of "patient samples" used is not specified in the provided text.
• Data Provenance: The document does not explicitly state the country of origin. The use of "patient samples" implies these were real human urine samples, likely collected in a clinical setting. It is a retrospective or prospective study with patient samples, but the specific design isn't detailed beyond that.

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

The document mentions "Calibration traceability: Phencyclidine with confirmation by GC/MS".

• Number of Experts: This information is not provided. GC/MS is an analytical method, not directly managed by "experts" in the sense of clinicians making diagnoses. While skilled laboratory personnel operate and interpret GC/MS results, the document doesn't quantify them or their specific qualifications.
• Qualifications of Experts: Not specified beyond the implication of trained laboratory personnel for GC/MS.

4. Adjudication Method for the Test Set:

• The document implies that Gas Chromatography/Mass Spectrometry (GC/MS) serves as the primary "ground truth" or confirmatory method. This is a highly accurate analytical technique. There is no mention of a traditional expert adjudication method (e.g., 2+1, 3+1) in the context of clinical expert agreement. The results of the VITROS PCP assay were compared to results obtained from the predicate device, which itself would have been validated against GC/MS.

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

• No MRMC study was done. This device is an automated in vitro diagnostic (IVD) assay. Its performance is compared to another automated IVD assay and a reference method like GC/MS, not to human readers' interpretations. Therefore, there's no concept of human readers improving with AI assistance in this context.

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

• Yes, a standalone study was done. The entire comparison described is a standalone performance assessment of the VITROS PCP assay (an "algorithm" in the sense of an automated test) against a predicate device and ground truth (GC/MS) without human-in-the-loop interpretation as a primary measure. The instrument ("VITROS 5,1 FS Chemistry Systems") automates the process.

7. Type of Ground Truth Used:

• The primary ground truth used is phencyclidine concentration confirmed by Gas Chromatography/Mass Spectrometry (GC/MS). The document explicitly states: "Phencyclidine with confirmation by GC/MS" under "Calibration traceability." GC/MS is considered the "preferred confirmatory method" for drug-of-abuse test results.

8. Sample Size for the Training Set:

• The document does not provide information on a separate "training set" or its size. As this is an in vitro diagnostic device, the "training" for the assay itself would involve optimization during development, rather than a distinct machine learning-style training set of clinical data after the assay's chemical formulation is finalized. Calibrators are defined, but these aren't typically referred to as a "training set" in the context of machine learning.

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

• As a distinct "training set" is not mentioned in the provided text, the method for establishing its ground truth is not applicable/not provided. The calibrators (VITROS Chemistry Products Calibrator Kit 26 and VITROS Chemistry Products FS Calibrator 1) are prepared from human urine with drugs of abuse added, and their values are established through reference methods (implied to be traceable to GC/MS for phencyclidine). These calibrators are used to establish the measurement curve for the assay.

Ask a specific question about this device

For in vitro diagnostic use only. VITROS Chemistry Products HCY Reagent is used to quantitatively measure total homocysteine (HCY) concentration in human serum and plasma. Serum and plasma homocysteine levels can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia and homocystinuria.

For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 27 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of homocysteine (HCY).

For in vitro diagnostic use only. VITROS Chemistry Products HCY Performance Verifiers are assayed controls used to monitor performance of VITROS HCY Reagents on VITROS 5,1 FS Chemistry Systems.

The VITROS Chemistry Products HCY Reagent is used in conjunction with the VITROS Chemistry Products Calibrator Kit 27 and VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) on VITROS 5,1 FS Chemistry Systems to quantitatively measure total homocysteine (HCY) concentration in human serum and plasma.
The quantitative measurement of homocysteine (HCY) is performed using the VITROS Chemistry Products HCY Reagent in conjunction with the VITROS Chemistry Products Calibrator Kit 27 and on the VITROS 5,1 FS Chemistry Systems. The VITROS Chemistry Products HCY Reagent consists of two dual chambered reagent packs containing three ready-to- use liquid reagents. Disulfide linked homocysteine (oxidized forms) in the sample is reduced by Tris (2-Carboxyethyl) phosphine hydrochloride (TCEP) to form reduced homocysteine. Reduced homocysteine reacts with serine in the presence of cystathionine ß-synthase (CBS) to form L-cystathionine. L-cystathionine is broken down by cystathionine ß-lyase (CBL) to produce homocysteine, pyruvate and ammonia. Pyruvate is reduced to lactate by lactate dehydrogenase (LDH) using NADH as coenzyme. The concentration of HCY is directly proportional to the amount of NADH converted to NAD and is measured spectrophotometrically at 340 nm. Once a calibration has been performed, the HCY concentration in each unknown sample can be determined using the stored calibration curve and the measured absorbance obtained in the assay of the sample.

The VITROS Chemistry Products Calibrator Kit 27 are prepared from an aqueous solution containing amino acids and inorganic acid. These standards are used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of homocysteine (HCY).

The VITROS Chemistry Products HCY Performance Verifiers I, II and III are prepared from processed human serum to which amino acid and preservative have been added. These are assayed controls used to monitor performance of VITROS HCY Reagents on VITROS 5.1 FS Chemistry Systems.

The VITROS Chemistry Products FS Diluent Pack 2 (Saline/BSA) is a common reagent that is used by multiple assays on the VITROS 5,1 FS Chemistry System. This is a dual chambered package containing two ready-to-use liquid diluents. Diluent 1 is prepared from processed water to which inorganic salt has been added. Diluent 2 is prepared from processed water to which bovine serum albumin, inorganic salts and preservatives have been added.

The VITROS 5.1 FS Chemistry System is a clinical chemistry instrument that provides automated use of the VITROS Chemistry Products MicroTip® and MicroSlides® range of products.

The provided text describes the 510(k) summary for the VITROS Chemistry Products HCY Reagent, Calibrator Kit 27, and HCY Performance Verifiers. It states that the device is substantially equivalent to predicate devices and provides a summary of the studies performed. Here's a breakdown of the requested information based on the provided text:

1. Table of acceptance criteria and the reported device performance

The document does not explicitly present a table of "acceptance criteria" against which the device performance is directly measured in a pass/fail manner. Instead, it demonstrates substantial equivalence through correlation studies and other bench testing. The primary performance metric presented for substantial equivalence is the correlation with a predicate device.

Other bench testing was also performed, including:

• Assay precision
• Linearity
• Specificity
• Expected values
• Limit of detection
• Dilution
• Specimen matrix

However, specific acceptance criteria and detailed results for these tests are not provided in this summary.

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

• Test Set Sample Size: The document mentions "patient samples" were used in the correlation studies but does not specify the exact number of samples.
• Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It only mentions "patient samples."

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

This information is not provided in the document. The ground truth for the HCY assay's performance is established by comparison to a "commercially available system BIO-RAD HOMOCYSTEINE by HPLC test," which is itself a medical device. This implies that the BIO-RAD device's results are considered the reference or "truth" for this comparison, rather than requiring expert consensus on individual patient samples.

4. Adjudication method for the test set

This information is not applicable as the comparison is against an existing commercial assay, not a subjective interpretation by experts 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 a diagnostic assay (reagent, calibrator, and verifiers) for measuring homocysteine concentration. It is not an AI-based system designed to assist human readers (e.g., radiologists interpreting images), and therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not relevant or described.

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

• Yes, in essence. The entire study described is a standalone performance evaluation of the VITROS Chemistry Products HCY assay. The system (analyzer + reagents) measures HCY concentration autonomously. Its performance is then compared to an existing predicate device, not to human interpretation of raw data.

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

The ground truth for the HCY assay was established through comparison to a legally marketed predicate device, the BIO-RAD® HOMOCYSTEINE by HPLC test (K993107). The results from this predicate device served as the reference standard for evaluating the new VITROS HCY assay's performance.

8. The sample size for the training set

The document does not specify a training set sample size. This is typical for a traditional in-vitro diagnostic assay rather than a machine learning or AI algorithm that requires explicit training data. The "training" of such a system involves the development and calibration of the assay itself, for which specific data sizes are usually proprietary or part of internal validation but not explicitly called out as a "training set" in the context of this 510(k) summary.

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

As described above, the concept of a "training set" with separate ground truth establishment is not directly applicable in the context of this traditional IVD assay's 510(k) summary. The ground truth for evaluating the device's performance (its "test set") was the predicate device's results. The development and internal validation of the assay (which could be considered analogous to "training" in a very loose sense) would have involved extensive analytical studies to ensure its accuracy, precision, and other performance characteristics, likely using certified reference materials and well-characterized samples, but this is not detailed as a "ground truth for a training set" in this document.

Ask a specific question about this device

For in vitro diagnostic use only. VITROS Chemistry Products AAT Reagent is used to quantitatively measure α₁-antitrypsin concentration in human serum. The measurement of α₁-antitrypsin in serum aids in the diagnosis of cirrhosis of the liver and pulmonary emphysema.

For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 99 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of α₁-antitrypsin (AAT).

For in vitro diagnostic use only. VITROS Chemistry Products AAT Performance Verifiers are assayed controls used to monitor performance of VITROS AAT Reagents on VITROS 5,1 FS Chemistry Systems.

The VITROS Chemistry Products AAT Reagent is used in conjunction with the VITROS Chemistry Products Calibrator Kit 99 and VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) on VITROS 5,1 FS Chemistry Systems for the quantitative measurement of α₁-antitrypsin (AAT) in human serum.

The VITROS AAT Reagent is a dual chambered package containing ready-to-use liquid reagents. Samples, calibrators and controls are automatically diluted in saline from VITROS FS Diluent Pack 2 and mixed with Reagent 1 containing a polymer. Addition of antisera specific for human α₁-antitrypsin (Reagent 2) produces an immunochemical reaction yielding antigen/antibody complexes. The light scattering properties of the antigen/antibody complexes increase solution turbidity proportional to α₁-antitrypsin concentration in the sample. The turbidity is measured spectrophotometrically at 340 nm. Once a calibration has been performed for each reagent lot, the a1-antitrypsin concentration in each unknown sample can be determined using the stored calibration curve and the measured absorbance obtained in the assay of the sample.

The VITROS Chemistry Products Calibrator Kit 99 are prepared from processed human serum to which inorganic salts, buffers, and preservatives have been added. These standards are used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of α₁-antitrypsin (AAT).

The VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) is a common reagent that is used by multiple assays on the VITROS 5,1 FS System. This is a dual chambered package containing two ready-to-use liquid diluents. Diluent 1 is prepared from processed water to which inorganic salt has been added. Diluent 2 is prepared from processed water to which bovine serum albumin, inorganic salts and preservatives have been added.

The VITROS 5,1 FS Chemistry System is a clinical chemistry instrument that provides 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 Chemistry Products AAT Performance Verifiers I, II and III are prepared from processed human serum to which inorganic salts, buffers, and preservatives have been added. These are assayed controls used to monitor performance of VITROS AAT Reagent on VITROS 5,1 FS Chemistry Systems.

Here's an analysis of the acceptance criteria and supporting studies for the VITROS Chemistry Products AAT Reagent, Calibrator Kit 99, and Performance Verifiers, based on the provided text.

Note: This document describes an in vitro diagnostic device, not an AI/ML-driven medical device for image analysis as might be typical for some of these questions. Therefore, some of the requested categories (e.g., number of experts for ground truth, adjudication method, MRMC study, sample size for training set) are not directly applicable or are not explicitly detailed in the provided text for this type of device. I will address the relevant sections and note when information is not present or applicable.

1. Table of Acceptance Criteria and Reported Device Performance

The provided 510(k) summary focuses on demonstrating substantial equivalence to a predicate device rather than setting explicit, quantifiable acceptance criteria with specific performance targets (like sensitivity/specificity for clinical decisions). Instead, performance is shown through correlation and comparison to the predicate.

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

• Test Set Sample Size: The document mentions that equivalence was demonstrated "using a commercially available assay along with patient samples." However, the exact number of patient samples used in the correlation studies (test set) is not specified in the provided text.
• Data Provenance: The data provenance is stated as "patient samples," but the country of origin or whether it was retrospective or prospective data is not specified.

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

This question is not applicable in the context of this in vitro diagnostic device. The "ground truth" for an AAT assay would typically be established by comparing its results to a well-established reference method or a predicate device on patient samples, based on quantitative measurements rather than expert interpretation of images or clinical cases.

4. Adjudication Method for the Test Set

This question is not applicable for this in vitro diagnostic device. Adjudication methods like 2+1 or 3+1 are typically used for subjective assessments (e.g., image interpretation where experts disagree), not for quantitative chemical measurements.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are typically used for diagnostic imaging devices where human readers interpret cases, and performance with/without AI assistance is evaluated. This document describes a chemical assay, not an imaging device with human readers.

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

Yes, a standalone performance study was done. The entire submission describes the performance of the VITROS AAT assay system (reagent, calibrator, verifiers, and instrument) as a standalone device to measure α₁-antitrypsin concentration in human serum. Its performance is compared to a predicate device and validated through various bench tests (specificity, expected values, limit of detection, dilution, specimen matrix). The "algorithm" in this context is the immunoturbidimetric chemical reaction and the spectrophotometric measurement by the VITROS 5,1 FS Chemistry System.

7. The Type of Ground Truth Used

The ground truth for validating the VITROS Chemistry Products AAT assay was established through comparison to a predicate device (IMMAGE® Immunochemistry Systems AAT assay) using patient samples, and through bench testing for various analytical performance characteristics (specificity, limit of detection, etc.). For a quantitative chemical assay, the "ground truth" is typically a known, well-characterized value or the result obtained from a recognized reference method.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/ML algorithm. For an IVD assay like this, product development involves a series of experiments and optimizations to establish reagent formulations, calibration curves, and analytical procedures. The phrase "training set" doesn't directly apply in the same way it would for AI model development. The development data used to optimize the assay would implicitly serve this purpose, but its sample size is not specified.

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

As noted above, the concept of a "training set" ground truth as applied to AI/ML isn't directly applicable here. The development of the assay would involve establishing the expected concentrations of AAT in various samples, using reference methods or characterized materials, to ensure the assay accurately measures the analyte. The specific methodology or exact sample sizes for this developmental phase are not provided in the summary.

Ask a specific question about this device

1. For in vitro diagnostic use only. VITROS Chemistry Products CAFFN Reagent Kit is used on the VITROS 5,1 FS Chemistry System to quantitatively measure caffeine (CAFFN) concentration in human serum and plasma of subjects undergoing therapy with caffeine, especially for cases of neonatal apnea.
2. For in vitro diagnostic use only. VITROS TDM Performance Verifier is an assayed control used to monitor performance of ACET, CRBM, DGXN, PHBR, PHYT and CAFFN on VITROS Chemistry Systems.

The VITROS 5,1 FS Chemistry System is a fully automated clinical chemistry analyzer intended for use in the in vitro determination of various analytes in human specimens. The VITROS 5,1 FS Chemistry System is designed for use with VITROS Chemistry Products MicroTip and Thin Film assays.

The system is comprised of four main elements:

1. The VITROS 5,1 FS Chemistry System instrumentation, which provides automated use of the chemistry reagents. The VITROS 5,1 FS Chemistry System was cleared for market by a separate 510(k) premarket notification (K031924).
2. The VITROS Chemistry Products range of MicroTip assays, in this case the VITROS Chemistry Products CAFFN Reagent Kit (Reagents 1 and 2, Buffer and Calibrators) and the VITROS Chemistry Products TDM Performance Verifiers, which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS CAFFN assay.
3. The VITROS Chemistry Products Thin Film range of products, which are dry, multilavered, analytical elements, coated on polyester supports. The thin film products each have their own 510(k) clearance numbers and were cleared for market for use on the VITROS 5.1 FS Chemistry System through submission of information required by the ODE Guidance Document: "Data For Commercialization Of Original Equipment Manufacturer, Secondary and Generic Reagents For Automated Analyzers". The required information was provided in the VITROS 5,1 FS Chemistry System premarket notification (K031924).
4. Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 3).

The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

This document describes a 510(k) premarket notification for the VITROS Chemistry Products CAFFN Reagent Kit and VITROS Chemistry Products TDM Performance Verifiers I, II, and III.

The primary study establishing substantial equivalence for the CAFFN Reagent Kit is a correlation study comparing its performance to a legally marketed predicate device, the SYVA® Emit® Caffeine Assay.

While the document confirms the device meets the acceptance criteria for substantial equivalence, it does not provide detailed acceptance criteria values or specific performance results in a structured table as requested. However, it does state the key finding of the correlation study.

Here's the information extracted from the provided text, structured to answer your questions:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in a numerical format. Instead, it demonstrates substantial equivalence through a correlation study and other supporting studies (precision, expected values, linearity, and specificity summaries are referenced but not detailed). The primary performance metric presented is the correlation between the new device and the predicate device.

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

• Sample Size for Test Set: The document mentions "patient samples" were used in the equivalence study but does not specify the exact number or sample size of patients or samples.
• Data Provenance: Not specified. It's implied to be retrospective or a controlled clinical sample collection, but the country of origin is not mentioned.

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

• Number of Experts: Not applicable. The ground truth (or reference standard in this context) for the test set was established by the predicate device's measurements, not by human expert interpretation.
• Qualifications of Experts: N/A

4. Adjudication Method for the Test Set

• Adjudication Method: Not applicable. The comparison is directly between the new device's readings and the predicate device's readings. There is no human adjudication process involved as it's a quantitative chemical assay.

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

• MRMC Study Done: No. This is a chemical assay, not an imaging or diagnostic interpretation device that would typically involve human readers.

6. Standalone Performance Study (Algorithm only without Human-in-the-loop performance)

• Standalone Study Done: Yes. The correlation study and other tests (precision, linearity, specificity) represent the standalone performance of the VITROS Chemistry Products CAFFN Reagent Kit on the VITROS 5,1 FS Chemistry System. The results are compared against the predicate device, which also operates in a standalone manner.

7. Type of Ground Truth Used

• Type of Ground Truth: The "ground truth" for the comparison study was the measurements obtained from the legally marketed predicate device (SYVA® Emit® Caffeine Assay). It can also be considered an "established reference method" for comparing new devices.

8. Sample Size for the Training Set

• Sample Size for Training Set: Not applicable. This device is a chemical reagent kit for an immunoassay, not a machine learning or AI algorithm that typically has a "training set" in the conventional sense. The development of such assays involves analytical validation, not statistical model training.

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

• How Ground Truth for Training Set Was Established: Not applicable, as there is no training set in the AI/ML context for this type of device. The development and optimization of the assay would involve various laboratory methods and reference materials, but these are not referred to as "training sets" with associated "ground truth" in this context.

Ask a specific question about this device

For in vitro diagnostic use only. VITROS Chemistry Products TRFRN Reagent is used to quantitatively measure transferrin (TRFRN) concentration in human serum and plasma.

For in vitro diagnostic use. VITROS Chemistry Products Calibrator Kit 20 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of transferrin, C3, C4, IgA, IgG and IgM.

For in vitro diagnostic use only. VITROS Chemistry Products Protein Performance Verifiers are assayed controls used to monitor the performance of TRFRN, C3, C4, IgA, IgG and IgM Reagents on VITROS 5,1 FS Chemistry Systems.

The VITROS 5.1 FS Chemistry System is a fully automated clinical chemistry analyzer intended for use in the in vitro determination of various analytes in human specimens (serum, plasma, urine, and cerebrospinal fluid). The VITROS 5,1 FS System is designed for use with VITROS Chemistry Products MicroTip and Thin Film assays.

The system is comprised of four main elements:

1 The VITROS 5,1 FS Chemistry System instrumentation, which provides automated use of the chemistry reagents. The VITROS 5,1 FS Chemistry System was cleared for market by a separate 510(k) premarket notification (K031924).
2 The VITROS Chemistry Products MicroTip range of liquid reagent products (in this case VITROS Chemistry Products TRFRN Reagent, VITROS Chemistry Products Calibrator Kit 20 and VITROS Chemistry Products Protein Performance Verifiers I. II and III), which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS TRFRN assay.
3 The VITROS Chemistry Products Thin Film range of dry products, which are dry, multilayered, analytical elements, coated on polyester supports. The thin film products each have their own 510(k) clearance numbers and were cleared for market for use on the VITROS 5,1 FS Chemistry System through submission of information required by the ODE Guidance Document: "Data For Commercialization Of Original Equipment Manufacturer, Secondary and Generic Reagents For Automated Analyzers". The required information was provided in the VITROS 5,1 FS Chemistry System premarket notification (K031924).
4 Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 2).

The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

The provided text describes the substantial equivalence of the VITROS Chemistry Products TRFRN Reagent, Calibrator Kit 20, and Protein Performance Verifiers to predicate devices. It does not contain information about acceptance criteria and a study design in the way one would typically describe a clinical validation for a medical imaging AI device. Instead, it focuses on demonstrating equivalence through comparison of assay characteristics and a correlation study.

Here's an attempt to extract relevant information and note the absence of others, aligning with your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a quantitative, pre-defined manner for the performance of the new device relative to a gold standard. Instead, it demonstrates performance by showing correlation and similarity to a legally marketed predicate device.

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

• Sample Size: The document states that "patient samples" were used, but does not specify the exact sample size for the correlation study or other performance studies (precision, sensitivity, specificity, expected values).
• Data Provenance: The document states that "commercially available reagents along with patient samples" were used. There is no information provided regarding the country of origin of the data or whether it was retrospective or prospective.

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

This type of information is not applicable to this submission. The "ground truth" for a quantitative diagnostic assay like transferrin measurement is typically the result obtained from a reference method or another validated diagnostic device (in this case, the predicate device). There is no mention of human experts establishing a ground truth for individual cases in this context, unlike a qualitative diagnostic device (e.g., an AI imaging algorithm).

4. Adjudication Method for the Test Set

This type of information is not applicable to this submission. Adjudication methods (like 2+1 or 3+1) are typically used for qualitative assessments where multiple human readers might disagree, and a consensus needs to be formed to establish ground truth or interpret results. For a quantitative assay, the comparison is directly between numerical results.

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 type of information is not applicable to this submission. An MRMC study is relevant for AI-assisted diagnostic tools that interpret images or other qualitative data, showing how AI impacts human reader performance. This submission is for a fully automated in vitro diagnostic assay with no human interpretation component in the direct measurement of transferrin.

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

Yes, this describes a standalone performance study. The VITROS Chemistry Products TRFRN Reagent is designed to quantitatively measure transferrin concentration on the VITROS 5,1 FS Chemistry System. The correlation study compares the results generated by this new automated system (algorithm/device only) directly with the results from the predicate automated system. There is no human intervention in the result generation itself that would constitute a "human-in-the-loop" component.

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

The "ground truth" in this context is the quantitative measurement of transferrin by the predicate device, the IMMAGE® Immunochemistry System TRF Transferrin Reagent on the Beckman IMMAGE® Immunochemistry System (K963427). This is a common approach for demonstrating substantial equivalence for new in vitro diagnostic devices, where the predicate device's established performance serves as the benchmark.

8. The Sample Size for the Training Set

The document does not provide information on a "training set" in the context of an AI/machine learning model. This submission is for a conventional chemical reagent and assay system, not an AI algorithm that undergoes a distinct training phase with a dedicated dataset. The correlation study mentioned uses "patient samples" which would typically be a test set for assessing performance.

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

As there is no mention of a "training set" in the context of AI/machine learning, this question is not applicable. For the performance evaluation, the predicate device results served as the reference for comparison.

Ask a specific question about this device

For in vitro diagnostic use only. VITROS Chemistry Products ApoA1 Reagent is used to quantitatively measure apolipoprotein A1 (ApoA1) concentration in human serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 21 is used to calibrate VITROS 5.1 FS Chemistry Systems for the quantitative measurement of apolipoprotein A 1 (ApoA1). For in vitro diagnostic use only. VITROS Chemistry Products ApoA1 Performance Verifier I is an assayed controls used to monitor the performance of ApoA1 Reagent on VITROS 5,1 FS Chemistry Systems.

For in vitro diagnostic use only. VITROS Chemistry Products ApoB Reagent is used to quantitatively measure apolipoprotein B (ApoB) concentration in human serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 22 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of apolipoprotein B (ApoB). For in vitro diagnostic use only. VITROS Chemistry Products ApoB Performance Verifier I is an assayed controls used to monitor the performance of ApoB Reagent on VITROS 5,1 FS Chemistry Systems.

The VITROS 5,1 FS Chemistry System is a fully automated clinical chemistry analyzer intended for use in the in vitro determination of various analytes in human specimens (serum, plasma, urine, and cerebrospinal fluid). The VITROS 5,1 FS is designed for use with VITROS Chemistry Products MicroTip and Thin Film assays.

The system is comprised of four main elements:

1. The VITROS 5,1 FS Chemistry System instrumentation, which provides automated use of the chemistry reagents. The VITROS 5,1 FS Chemistry System was cleared for market by a separate 510(k) premarket notification (K031924).
2. The VITROS Chemistry Products MicroTip range of liquid reagent products (in this case VITROS Chemistry Products ApoA1 Reagent and VITROS Chemistry Products Calibrator Kit 21, VITROS Chemistry Products ApoB Reagent and VITROS Chemistry Products Calibrator Kit 22, VITROS Chemistry Products ApoA1 Performance Verifier I and VITROS Chemistry Products ApoB Performance Verifier I ), which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS ApoA1 and ApoB assays.
3. The VITROS Chemistry Products Thin Film range of dry products, which are dry, multilayered, analytical elements, coated on polyester supports. The thin film products each have their own 510(k) clearance numbers and were cleared for market for use on the VITROS 5,1 FS Chemistry System through submission of information required by the ODE Guidance Document: "Data For Commercialization Of Original Equipment Manufacturer, Secondary and Generic Reagents For Automated Analyzers". The required information was provided in the VITROS 5,1 FS Chemistry System premarket notification (K031924).
4. Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 1).

The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

Here's a breakdown of the acceptance criteria and study information for the VITROS Chemistry Products ApoA1 and ApoB assays, Calibrator Kits, and Performance Verifiers, based on the provided text:

Acceptance Criteria and Device Performance

The provided document primarily focuses on demonstrating substantial equivalence to predicate devices, rather than defining explicit numerical acceptance criteria for novel performance claims. The key "acceptance criterion" for substantial equivalence is the demonstration of similar performance characteristics and intended use compared to the legally marketed predicate devices.

The study presented here is a correlation study comparing the new devices to the predicate devices.

Table of Acceptance Criteria and Reported Device Performance

Note: The document also states that "studies were performed to determine the precision, specificity, linearity, antigen excess, lower limit of detection, and expected values of the VITROS ApoA1 and ApoB assays," with summaries in the Instructions for Use. However, the specific acceptance criteria and results for these additional studies are not provided in this summary document.

Study Details

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

   • The document states: "Equivalence to predicate(s) was demonstrated using commercially available reagents along with patient samples."
   • Specific sample size for the test set is NOT provided.
   • Data Provenance: The origin (e.g., country) of the patient samples is NOT specified. The study appears to be retrospective in the sense that existing patient samples were used to perform the correlation with a legally marketed predicate device.

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

   • This is a predicate comparison study for an in vitro diagnostic (IVD) assay, not a study involving human expert interpretation of images or clinical data.
   • No "experts" in the sense of clinicians or radiologists were used to establish ground truth. The "ground truth" for the test set is established by the results obtained from the predicate device's assay, which is itself a legally marketed and presumably validated quantitative test.

3. Adjudication method for the test set:

   • Not applicable. This study does not involve human interpretation or adjudication as it's a quantitative measurement device comparison.

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 is an IVD device, not an AI-assisted diagnostic tool that involves human readers interpreting cases. Therefore, an MRMC study is not relevant.

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

   • Yes, effectively. The study assessed the performance of the VITROS ApoA1 and ApoB assays as standalone quantitative measurement devices by comparing their results directly to those of the predicate assays. There is no human-in-the-loop component for the measurement itself, as it is an automated chemistry system.

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

   • The "ground truth" is established by the results obtained from the legally marketed predicate devices (Dade Behring N Antisera to Human Apolipoprotein A-1 Reagent assay and Dade Behring N Antisera to Human Apolipoprotein B Reagent assay) when measuring the same patient samples. This is a common approach for demonstrating substantial equivalence for new IVD assays.

7. The sample size for the training set:

   • Not applicable. This document describes a predicate comparison study for an IVD kit, which does not involve a "training set" in the context of machine learning or AI. The development of the assay itself would have involved internal validation and method optimization, but that is distinct from a "training set" for an algorithm.

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

   • Not applicable. As stated above, there is no "training set" in the context of this regulatory submission for an IVD assay.

Ask a specific question about this device