(43 days)
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.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Correlation with Predicate Device (Homocysteine Reagent) | Strong correlation coefficient (likely >0.95 or similar for substantial equivalence) and a linear relationship close to y=x. | y = 0.98 x + 1.0 umol/L, with a correlation coefficient = 0.97 (where y = VITROS HCY assay and x = BIO-RAD® HOMOCYSTEINE by HPLC test). |
| Device Similarities/Differences (HCY Reagent) | Intended use, analyte, sample type, measurement type should be similar. | Similarities: Intended Use, Analyte measured, Sample Type, Measurement Type (Quantitative). Differences: Reportable Range (1.0-50.0 umol/L vs 0.5-100 umol/L), Sensitivity (1.0 umol/L vs 0.5 µmol/L), Calibrator levels, format, and matrix, Instrumentation (automated clinical chemistry analyzer vs Isocratic HPLC System), Reference Interval, Method (Homogeneous Enzymatic vs Chromatography). |
| Device Similarities/Differences (Performance Verifiers) | Intended use, matrix, product type, format, and number of levels should be similar. | Similarities: Indications for Use, Matrix, Product Type (Assayed Control), Format (Liquid), Number of levels (Three). Differences: Analytes Reported (Homocysteine vs $\alpha_1$ -Antitrypsin). |
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.
§ 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.