(146 days)
For in vitro diagnostic use only. VITROS® Chemistry Products HCY 2 Reagent is used on VITROS® Systems to quantitatively measure total homocysteine 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 HCY 2 Performance Verifiers are assayed controls used to monitor performance of VITROS® Chemistry Products HCY and VITROS® Chemistry Products HCY 2 Reagents on VITROS® Systems.
The VITROS® Chemistry Products HCY 2 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, VITROS® 4600 Chemistry Systems, and the VITROS® 5600 Integrated Systems to quantitatively measure total homocysteine concentration in human serum and plasma.
The VITROS® Chemistry Products HCY 2 Reagent consists of one dual chambered reagent pack containing two ready-to-use liquid reagents, one in each chamber. 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 Lcystathionine. 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 homocysteine is directly proportional to the amount of NADH converted to NAD and is measured spectrophotometrically at 340 nm.
The VITROS® Chemistry Products Calibrator Kit 27 is prepared from an aqueous solution containing amino acids and inorganic acid. These standards are used to calibrate the VITROS® 5.1 FS Chemistry Systems, VITROS® 4600 Chemistry Systems, and VITROS® 5600 Integrated Systems for the quantitative measurement of homocysteine.
The VITROS® Chemistry Products HCY 2 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® Chemistry Products HCY and VITROS® Chemistry Products HCY 2 Reagents on VITROS® Systems.
The VITROS® Chemistry Products FS Diluent Pack 2 (Saline/BSA) is a common reagent that is used by multiple assays on VITROS® Systems. 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.
Here's a breakdown of the acceptance criteria and study information for the VITROS® Chemistry Products HCY 2 Reagent and Performance Verifiers, based on the provided text:
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 explicitly listing hard-coded "acceptance criteria" in the traditional sense (e.g., a specific sensitivity or specificity threshold that must be met). Instead, the performance is evaluated through correlation studies and various bench testing parameters, compared against the predicate device.
The primary "acceptance criterion" for this type of submission is demonstrating substantial equivalence to the predicate device, which is concluded based on the presented data. The study compares the new device's performance to the predicate device.
| Performance Characteristic | Acceptance Criteria (Implied for Substantial Equivalence to Predicate) | Reported Device Performance (VITROS® HCY 2 Reagent) |
|---|---|---|
| Correlation with Predicate Device (VITROS® 5.1 FS Chemistry System) | Strong linear correlation (r approaching 1.0, slope near 1.0, intercept near 0) | y = 1.00 x + 0.42 (umol/L), r = 0.997 (n=110) |
| Correlation with Predicate Device (VITROS® 4600 Chemistry System) | Strong linear correlation (r approaching 1.0, slope near 1.0, intercept near 0) | y = 0.98 x + 0.60 (umol/L), r = 0.997 (n=123) |
| Correlation with Predicate Device (VITROS® 5600 Integrated System) | Strong linear correlation (r approaching 1.0, slope near 1.0, intercept near 0) | y = 0.99 x + 0.46 (umol/L), r = 0.993 (n=111) |
| Reportable Range | Comparable to predicate device (1.0-50.0 µmol/L) | 2.0-50.0 µmol/L |
| Sensitivity (LoQ) | Comparable to predicate device (0.96 µmol/L) | 1.29 µmol/L |
| Other Bench Testing | Precision, linearity, specificity, expected values, limit of detection, dilution, and specimen matrix considered comparable to predicate. | (Specific values not provided in summary) |
For the VITROS® Chemistry Products HCY 2 Performance Verifiers I, II & III, the acceptance criteria relate to their function as assayed controls and their equivalence to the predicate verifiers.
| Performance Characteristic (Verifiers) | Acceptance Criteria (Implied for Substantial Equivalence to Predicate) | Reported Device Performance (VITROS® HCY 2 Performance Verifiers) |
|---|---|---|
| Analytes Reported | Homocysteine | Homocysteine in VITROS® HCY and HCY 2 Reagents |
| Vial Volume | Acceptable for intended use (predicate 5 mL/vial) | 1.5 mL/vial |
| Intended Use Statement | Consistent with monitoring performance | Monitoring performance of VITROS® HCY and HCY 2 Reagents |
| Matrix | Processed human serum with preservatives | Processed human serum with preservatives |
| Product Type | Assayed Control | Assayed Control |
| Format | Liquid | Liquid |
| Number of levels | Three | Three |
| Nominal Values | Comparable to predicate device (7.0, 12, and 46 µmol/L) | 7.0, 12.5, and 25 µmol/L |
2. Sample Sizes Used for the Test Set and Data Provenance
- Test Set Sample Sizes:
- VITROS® 5.1 FS Chemistry System: n = 110
- VITROS® 4600 Chemistry System: n = 123
- VITROS® 5600 Integrated System: n = 111
- Data Provenance: The data refers to "patient samples." The country of origin is not specified but is implicitly from a clinical setting, given the nature of the device. The data is retrospective, as it compares the new device to an already commercially available predicate device using these samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of immunoassay device submission does not typically involve human expert interpretation for "ground truth" establishment in the same way an imaging AI device would. The "ground truth" for the test set is effectively the quantitative measurement of total homocysteine concentration obtained by the predicate device (VITROS® Chemistry Products HCY Assay). Therefore, the concept of "number of experts" and "qualifications of those experts" does not directly apply here in the context of human reviewers.
4. Adjudication Method for the Test Set
Not applicable. As described above, the ground truth is established by the predicate device's quantitative measurements, not through expert adjudication of qualitative findings.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay for quantitative measurement of homocysteine, not an imaging or AI interpretation device designed to assist human readers. Therefore, the concept of "human readers improve with AI" is not relevant to this submission.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are standalone performance studies of the device (reagent and verifiers) itself. It's an automated chemistry assay system, meaning it operates without continuous human intervention during the measurement process. The results are quantitative measurements directly produced by the system.
7. The Type of Ground Truth Used
The ground truth used for the comparative effectiveness study (correlation studies) was the quantitative measurement of total homocysteine concentration obtained by the predicate device (VITROS® Chemistry Products HCY Assay). This serves as the reference standard against which the new device's measurements are compared.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an algorithm or machine learning model. This is a traditional IVD submission for a chemistry assay, not an AI/ML-based device. The development process would involve internal optimization and validation studies, but these are not typically referred to as "training sets" in the AI sense within such a 510(k) summary.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, the concept of a "training set" with established ground truth as understood in AI/ML is not directly applicable here. The development of the assay would involve standard chemical and analytical methodologies to ensure accuracy and precision, with reference to known standards and controls, rather than human-curated ground truth for training an algorithm.
§ 862.1377 Urinary homocystine (nonquantitative) test system.
(a)
Identification. A urinary homocystine (nonquantitative) test system is a device intended to identify homocystine (an analogue of the amino acid cystine) in urine. The identification of urinary homocystine is used in the diagnosis and treatment of homocystinuria (homosystine in urine), a heritable metabolic disorder which may cause mental retardation.(b)
Classification. Class II.