(22 days)
Reagents: ST AIA-PACK Homocysteine is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of homocysteine in human serum, heparinized plasma or EDTA plasma using a Tosoh AlA System Analyzer. Homocysteine measurements are used in the diagnosis and treatment of hyperhomocysteinemia or homocystinuria. Calibrators: ST AIA-PACK Homocysteine Calibrator Set is intended for IN VITRO DIAGNOSTIC USE ONLY for the callbration of the ST AIA PACK Homocysteine assay using a Tosoh AIA System Analyzer. Controls: The AIA-PACK Homocysteine Control Set is intended for IN VITRO DIAGNOSTIC USE ONLY for performing quality control procedures with the ST AIA-PACK Homocysteine Assay.
The ST AIA-PACK Homocysteine is a competitive enzyme immunoassay which, after sample pretreatment, is performed entirely in the ST AIA-PACK Homocysteine test cups. Oxidized homocysteine is reduced by tris (2-carboxyethyl) phosphine (TCEP) to the free form and converted to S-adenosyl-L-homocysteine (SAH) by the SAH hydrolase and excess adenosine prior to the immunoassay. SAH present in the pretreated sample competes with immobilized SAH on magnetic beads for binding sites of the enzyme-labeled anti-SAH mouse monoclonal antibody. The magnetic beads are washed to remove unbound anti-SAH mouse monoclonal antibody and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The rate of fluorescence produced by the enzyme reaction indicates the amount of enzyme-labeled anti-SAH mouse monoclonal antibody. The amount of antibody that binds to the beads is inversely proportional to the homocysteine concentration in the test sample. A standard curve is constructed, and unknown sample concentrations are calculated using this curve.
Here's a breakdown of the acceptance criteria and study information for the ST AIA-PACK Homocysteine device, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criteria Category | Specific Criteria/Study Goal | Reported Device Performance |
|---|---|---|
| Precision | Within-run (Intra-assay): To demonstrate consistency of results within a single run. | Coefficient of Variation (CV) ranged from 3.1% to 4.3% across various sample types (EDTA Plasma, HEP Plasma, Serum) and homocysteine concentrations. |
| Total Precision (Inter-assay): To demonstrate consistency of results across multiple runs and days. | Coefficient of Variation (CV) ranged from 3.6% to 5.0% across various sample types (EDTA Plasma, HEP Plasma, Serum) and homocysteine concentrations. | |
| Linearity/Reportable Range | To demonstrate that the assay accurately measures homocysteine concentrations across a specified range. | Demonstrated to be linear from 0.5 to 50.0 µmol/L. |
| Detection Limit | To determine the lowest concentration of homocysteine that can be reliably detected. | Limit of Detection (LoD) estimated at 0.334 µmol/L. |
| Interference | To ensure that common endogenous and exogenous substances do not significantly affect assay results (recovery within 100 +/- 10%). | No interference observed from: Hemoglobin (up to 1445 mg/dL), free bilirubin (up to 18 mg/dL), conjugated bilirubin (up to 18 mg/dL), Lipemia (up to 1667 mg/dL triglyceride), Added protein (up to 50 mg/ml human g-globulin), Ascorbic acid (up to 20 mg/dL), EDTA-2K (up to 5.0 mg/mL), Heparin (up to 100 U/mL). |
| Specificity (Cross-reactivity) | To determine the extent to which other compounds similar to homocysteine are incorrectly identified as homocysteine. | Cross-reactivity: < 1% for Adenosine, L-Cystathionine, L-Cysteine, L-Glutathione, L-Methionine. < 7% (6.99%) for DL-Homocysteine thiolactone. S-Adenosyl-L-methionine showed 1.26% cross-reactivity. |
| Method Comparison | To demonstrate agreement between the new device and an existing legally marketed device (predicate device). | Correlation Coefficient (R): 0.984 against an alternate method for 138 EDTA plasma specimens. Deming regression: Slope = 1.079, Intercept = 0.193. Regular regression: Slope = 1.061, Intercept = 0.499. |
| Matrix Comparison | To demonstrate comparable results across different specimen types (EDTA plasma vs. heparinized plasma, EDTA plasma vs. serum). | EDTA plasma vs. Heparinized plasma (N=98): Corr Coef (R) = 0.991; Deming Slope = 1.007, Intercept = -0.235. EDTA plasma vs. Serum (N=98): Corr Coef (R) = 0.991; Deming Slope = 1.007, Intercept = -0.235. |
| Reference Range | To establish the expected range of homocysteine values in a healthy population. | Established reference interval: 6.6 - 17.8 µmol/L (central 95% of 130 apparently healthy individuals). |
| Stability | To determine the shelf life and in-use stability of the reagents and components. | Shelf life: 12 months (all components at 2-8°C). In-use stability: Test cups (40 hrs at 18-25°C, 30 days at 2-8°C), Calibrator Set (1 day at 2-8°C), Sample Diluting Solution (9 days semi-automated at 18-25°C, 90 days manual at 2-8°C), Pretreatment Reagent (20 hrs at 18-25°C, 1 day manual at 2-8°C), Control Set (14 days at 2-8°C, 1 day at 18-25°C). |
Study Details:
-
Sample Size Used for the Test Set and the Data Provenance:
- Precision (Within-run & Total): 9 pooled samples (3 each of EDTA plasma, heparinized plasma, and serum). Undisclosed country of origin, prospective (presumably created and tested for the study).
- Linearity: Not specified as a separate test set, but determined as part of the method validation.
- Limit of Detection: 60 replicates of a blank sample and 10 replicates each of 6 low-level samples. Undisclosed country of origin, prospective.
- Interference: Human specimens (number not specified) for EDTA plasma, heparinized plasma, and serum. Undisclosed country of origin, prospective.
- Specificity (Cross-reactivity): Unspecified number of formulations with various compounds. Undisclosed country of origin, prospective.
- Method Comparison: 138 unaltered EDTA plasma specimens. Undisclosed country of origin. The term "patient samples" suggests retrospective clinical samples.
- Matrix Comparison: 98 unaltered specimens for EDTA plasma vs. heparinized plasma; 98 unaltered specimens for EDTA plasma vs. serum. Undisclosed country of origin. The term "unaltered specimens" suggests retrospective clinical samples.
- Reference Range: 130 apparently healthy individuals. Undisclosed country of origin, prospective.
-
Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:
- This is an in vitro diagnostic (IVD) device, specifically an immunoassay for measuring homocysteine levels in biological samples. The "ground truth" for such devices is typically established through a combination of:
- Reference Methods/Materials: For quantitative measurements, there isn't a "ground truth" derived from expert consensus in the same way as an imaging device. Instead, accuracy is assessed against highly characterized reference materials (like NIST SRM 1955 mentioned for traceability) or established reference methods.
- Predicate Device Comparison: The study also compares the device's results to a legally marketed predicate device (Siemens IMMULITE 2000 Homocysteine Immunoassay), which serves as a clinical benchmark.
- Therefore, the concept of "experts" establishing a diagnostic ground truth for individual cases, as would be common in imaging or pathology studies, does not directly apply in this context. The methodologies (CLSI protocols) define the acceptance criteria for analytical performance.
- This is an in vitro diagnostic (IVD) device, specifically an immunoassay for measuring homocysteine levels in biological samples. The "ground truth" for such devices is typically established through a combination of:
-
Adjudication Method for the Test Set:
- Not Applicable. As mentioned above, this is an IVD device measuring a biomarker. The performance is assessed against analytical standards (precision, linearity, detection limit) and agreement with reference methods/predicate devices, not through a diagnostic adjudication process by experts.
-
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 automated in vitro diagnostic test. It does not involve human readers or AI assistance in interpreting diagnostic images or clinical cases.
-
If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done:
- Yes, this is an entirely standalone algorithm/device performance. The ST AIA-PACK Homocysteine assay is a competitive enzyme immunoassay performed on a TOSOH AIA System Analyzer. The result is a quantitative measurement of homocysteine, directly reported by the instrument based on its internal algorithms and calibration. There is no human intervention in the result generation or interpretation beyond operating the analyzer and reviewing the numerical output.
-
The Type of Ground Truth Used:
- Analytical Ground Truth / Reference Standards / Clinical Correlation.
- For traceability, the calibrators are referred to NIST Standard Reference Material 1955, which represents a highly characterized and accurate reference for homocysteine.
- For method comparison, the "ground truth" is effectively the results obtained from the predicate device (alternate method), as per clinical practice.
- For other analytical performance characteristics (precision, linearity, LoD, interference), the "ground truth" is based on the expected behavior of known concentrations of analytes and interferents, often prepared in a laboratory setting or derived from well-characterized clinical samples according to CLSI guidelines.
- For the reference range, the "ground truth" is the statistical distribution of homocysteine levels in a healthy population, determined by measuring 130 apparently healthy individuals.
- Analytical Ground Truth / Reference Standards / Clinical Correlation.
-
The Sample Size for the Training Set:
- Not applicable / Not explicitly stated for a typical "training set." As an immunoassay, this device's "training" involves the development and optimization of reagents, antibodies, and the assay protocol itself, along with the establishment of calibration curves. These are informed by biochemical principles and extensive in-house R&D, rather than a discrete "training set" of labeled data in the context of machine learning or AI. The provided text describes analytical performance verification and validation.
-
How the Ground Truth for the Training Set Was Established:
- Not applicable in the context of explicit machine learning training sets. The "ground truth" for the development of the assay (analogous to training) would derive from fundamental chemistry and immunology principles, combined with the use of purified homocysteine standards and knowledge of biological matrices. The process involves iterative optimization and validation against known concentrations and established analytical performance metrics, guided by international standards like CLSI.
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510(k) Summary
JUN 1 5 2012
ST AIA-PACK HOMOCYSTEINE
-
- Date:
2. Submitter:
-
- Contact Person:
- Device Name:
Device Name: Classification
Device Name: Classification
- Predicate Device:
May 17, 2012 Tosoh Bioscience, Inc 3600 Gantz Road Grove City, OH 43123
Judith K. Ogden Director, Compliance and Market Development 6000 Shoreline Ct., Ste. 101 South San Francisco, CA 94080 Phone: 650-636-8112 Fax: 650-636-8113 Email: Judy.Ogden@tosoh.com
ST AIA-PACK Homocysteine Classification: Class II LPS Clinical Chemistry 21 CFR 862.1377
ST AIA-PACK Homocysteine Calibrator Set Class II JIT Clinical Chemistry 21 CFR 862.1150
AIA-PACK Homocysteine Control Set Class I, Reserved JX Clinical Chemistry 21 CFR 862.1660
k 003597 Siemens IMMULITE 2000 Homocysteine Immunoassay
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6. Intended Use
Reagents:
ST AIA-PACK Homocysteine is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of homocysteine in human serum, heparinized plasma or EDTA plasma using a TOSOH AIA System Analyzer. Homocysteine measurements are used in the diagnosis and treatment of hyperhomocysteinemia or homocysteinuria.
Calibrators:
ST AIA-PACK Homocysteine Calibrator Set is intended for IN VITRO DIAGNOSTIC USE ONLY for the calibration of the ST AIA-PACK Homocysteine assay using a Tosoh AIA System Analyzer.
Controls:
The AIA-PACK Homocysteine Control Set is intended for IN VITRO DIAGNOSTIC USE ONLY for performing quality control procedures with the ST AIA-PACK Homocysteine Assay.
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7. Device Description
The ST AIA-PACK Homocysteine is a competitive enzyme immunoassay which, after sample pretreatment, is performed entirely in the ST AIA-PACK Homocysteine test cups.
Oxidized homocysteine is reduced by tris (2-carboxyethyl) phosphine (TCEP) to the free form and converted to S-adenosyl-L-homocysteine (SAH) by the SAH hydrolase and excess adenosine prior to the immunoassay. SAH present in the pretreated sample competes with immobilized SAH on magnetic beads for binding sites of the enzyme-labeled anti-SAH mouse monoclonal antibody. The magnetic beads are washed to remove unbound anti-SAH mouse monoclonal antibody and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The rate of fluorescence produced by the enzyme reaction indicates the amount of enzyme-labeled anti-SAH mouse monoclonal antibody. The amount of antibody that binds to the beads is inversely proportional to the homocysteine concentration in the test sample. A standard curve is constructed, and unknown sample concentrations are calculated using this curve.
8. Substantial Equivalence Information
-
- Predicate Device Name:
IMMULITE 2000 Homocysteine
- Predicate Device Name:
-
- Comparison with predicate
Similarities
| Parameter | ST AIA-PACKHomocysteine | IMMULITE 2000Homocysteine |
|---|---|---|
| Intended use | ST AIA-PACK Homocysteine isdesigned for IN VITRODIAGNOSTIC USE ONLY for thequantitative measurement ofhomocysteine in human EDTAplasma, heparinized plasma orserum on TOSOH AIA SystemAnalyzers. | For in vitro diagnostic use withthe IMMULITE 2000 Analyzer —for the quantitative determinationof L-homocysteine in humanplasma or serum. This devicecan assist in the diagnosis andtreatment of patients suspectedof having hyperhomocysteinemiaor homocystinuria |
| Specimen type | EDTA plasma, heparinizedplasma or serum | EDTA plasma, heparinizedplasma or serum |
| Assay range | 0.50 to 50.0 µmol/L | 0.5 to 50 µmol/L |
| Sensitivity | 0.50 µmol/L | 0.50 µmol/L |
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Differences
| Parameter | ST AIA-PACKHomocysteine | IMMULITE 2000Homocysteine |
|---|---|---|
| Interference | Hb, Biliirubin, Lipemia, Protein,Ascorbic Acid, Trisodium Citrate,EDTA, Heparinized Sodium, RHfactor tested with no interference | Bilirubin, Hb and Lipemia testedwith no interference |
| Reference Range | 6.6 - 17.8 µmol/L | 5 - 12 µmol/L |
| Assay Technology | Immunofluorescence | Chemiluminescent |
| Limit of detection | 0.334 µmol/L | 0.5 µmol/L |
| Incubation Time | 10 minute cycle | 60 Minute Cycle |
| Calibration | Calibrators at 0,2,4,8,15 and 55µmol/L | Calibration Adjusters range of 2to 50 µmol/L |
| Calibration Frequency | 90 Days | 28 Days |
9. Standard/Guidance Document Reference
- User Evaluation of Precision Performance of Clinical Chemistry Devices: Approved . Guideline (CLSI EP5-A2)
- . Evaluation of the Linearity of Quantitative Measurement Procedures: a Statistical Approach: Approved Guideline (CLSI EP6-A2)
- . How to Define and Determine Reference Intervals in the Clinical Laboratory: Approved Guideline (C28-A2)
- . Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline (CLSI EP17-A).
- Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline-. Second Edition (CLSI EP9-A2)
- Estimation of Total Analytical Error for Clinical Laboratory Methods (CLSI EP21-A) .
10. Test Principle
The ST AIA-PACK Homocysteine is a competitive enzyme immunoassay which, after sample pretreatment, is performed entirely in the ST AIA-PACK Homocysteine test cups.
Oxidized homocysteine is reduced by tris (2-carboxyethyl) phosphine (TCEP) to the free form and converted to S-adenosyl-L-homocysteine (SAH) by the SAH hydrolase and excess adenosine prior to the immunoassay. SAH present in the pretreated sample competes with immobilized SAH on magnetic beads for binding sites of the enzyme-labeled anti-SAH mouse monoclonal antibody. The magnetic beads are washed to remove unbound anti-SAH mouse monoclonal antibody and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The rate of fluorescence produced by the enzyme reaction indicates the amount of enzyme-labeled anti-SAH mouse monoclonal antibody. The amount of antibody that binds to the beads is inversely proportional to the homocysteine concentration in the test sample. A standard curve is constructed, and unknown sample concentrations are calculated using this curve.
WARNING: Specimens from patients who are on drug therapy involving S-adenosyl-methionine may show falsely elevated levels of homocysteine. Specimens from patients taking methotrexate, carbamazepine, phenytoin, nitrous oxide or 6-azauridine triacetate may have elevated levels of homocysteine due to their effect on the metabolic pathway.
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11. Performance Characteristics
1. Analytical Performance:
a. Precision/Reproducibility
The precision for ST AIA-PACK Homocysteine was determined based on guidance from CLSI Protocol EP5-A2.
Within run precision was determined using nine pooled samples (3 each of EDTA plasma, heparinized plasma and serum) in a total of 20 runs. Within each run, one set of duplicates per sample was assayed. The mean of each duplicate was used to obtain the pooled standard deviation (SD), which was then used to calculate the coefficient of variation (CV).
| Standard | Coefficient | ||
|---|---|---|---|
| Mean | Deviation | of Variation | |
| Sample | (μmol/L) | (μmol/L) | (%) |
| EDTA Plasma A3 | 7.4 | 0.2 | 3.3 |
| EDTA Plasma B3 | 17.4 | 0.7 | 3.9 |
| EDTA Plasma C3 | 44.0 | 1.4 | 3.1 |
| HEP Plasma A3 | 7.0 | 0.2 | 3.2 |
| HEP Plasma B3 | 14.4 | 0.5 | 3.4 |
| HEP Plasma C3 | 32.2 | 1.1 | 3.5 |
| Serum A3 | 5.6 | 0.2 | 4.3 |
| Serum B3 | 14.3 | 0.5 | 3.6 |
| Serum C3 | 40.9 | 1.3 | 3.2 |
Intra-assay (within run) Precision
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| Mean | StandardDeviation | Coefficientof Variation | |
|---|---|---|---|
| Sample | ( $μmol/L$ ) | ( $μmol/L$ ) | (%) |
| EDTA Plasma A3 | 7.4 | 0.3 | 4.1 |
| EDTA Plasma B3 | 17.4 | 0.8 | 4.5 |
| EDTA Plasma C3 | 44.0 | 1.6 | 3.6 |
| HEP Plasma A3 | 7.0 | 0.3 | 4.4 |
| HEP Plasma B3 | 14.4 | 0.6 | 4.0 |
| HEP Plasma C3 | 32.2 | 1.6 | 4.9 |
| Serum A3 | 5.6 | 0.3 | 5.0 |
| Serum B3 | 14.3 | 0.7 | 4.7 |
| Serum C3 | 40.9 | 1.8 | 4.4 |
The total precision was determined by the duplicate assay of nine pooled samples (3 each of EDTA plasma, heparinized plasma and serum) in 20 separate runs. The means of each run were used to calculate the pooled standard deviation (SD) and coefficient of variation (CV).
Linearity/assay reportable range b.
The linearity for the ST AIA-PACK Homocysteine was determined, based on guidance from CLSI Protocol EP6-A. The linearity was measured on the AIA-2000 instrument and has been demonstrated to be linear from 0.5 to 50.0 µmol/L.
- Traceability, C.
The ST AIA-PACK Homocysteine Calibrator Set contains assigned concentrations of Sadenosyl -L-homocysteine. The assigned value is determined on a lot-by-lot basis and is designed to provide an assay calibration range of 0.5 to 50.0 µmol/L of homocysteine. The calibrators in this set are referred to NIST (National Institute of Standards & Technology) Standard Reference Material 1955.
The Tosoh AIA-PACK Control Set contains two controls of buffered bovine serum albumin with each control containing approximately 12 umol/L and 25 umol/L of homocysteine with sodium azide as a preservative.
- ದ. Stability
The shelf life of the ST AIA-PACK Homocysteine test cups. ST AIA-PACK Homocysteine Calibrator Set, ST AIA-PACK Homocysteine Sample Diluting Solution, ST AIA-PACK Homocysteine Pretreatment Set and the AIA PACK Homocysteine Control Set is 12 months from the date of manufacture when stored at 2-8° C.
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The in-use stability of the ST AIA-PACK Homocysteine test cups, is 40 hours at a room temperature of 18-25°C. When stored at 2-8°C, the test cups can be used for up to 30 days.
The in-use stability of the ST AIA-PACK Homocysteine Calibrator Set is 1 day when stored at 2 - 8° C.
The in-use stability of the ST AIA-PACK Homocysteine Sample Diluting Solution is 9 days provided: 1) it is used for automatic dilutions, 2) it is at 18-25° C for only 8 hours per day, and 3) the vials are closed and kept refrigerated immediately after use. In-use stability is 90 days provided: 1) it is used for manual dilutions ONLY, and 2) the vials are closed and refrigerated immediately after use.
The in-use stability of the ST AIA-PACK Homocysteine Pretreatment Reagent is stable at 18-25° C for 20 hours. The in-use stability is stable at 2-8° C for 1 day provided: 1) it is used for manual pretreatment ONLY, and 2) the bottles are closed and refrigerated immediately after use.
The in-use stability of the AIA-PACK Homocysteine CONTROL is 14 days at 2-8° C. If stored at 18-25 degree C the in-use stability is 1 day.
e. Detection limit:
Limit of detection: The limit of detection of the ST AIA-PACK Homocysteine was determined based on CLSI guideline EP17-A. A blank sample was measured in 60 replicates. Six low level samples were measured in 10 replicates each. As a result, the limit of detection was estimated to be 0.334 umol/L.
The reportable range for the assay is 0.5 to 50.0 umol/L.
f. Interference/Analytical specificity:
Interference
Interference is defined, for the purposes of this study, with recovery outside of 100 +/-10% of the known concentration of the specimen after the following substances are added to human specimens. Three studies were conducted using EDTA plasma, heparinized plasma and serum
- Hemoglobin (up to 1445 mg/dL),
- . free bilirubin (up to 18 mg/dL) and conjugated bilirubin (up to 18 mg/dL) do not interfere with the assay.
- Lipemia, as indicated by triglyceride concentration (up to 1667 mg/dL), does not interfere with the assay.
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- . Added protein (up to 50 mg/ml), as indicated by human g-globulin concentrations, for a total protein concentration of approximately 120 mg/ml, does not interfere with the assay.
- . Ascorbic acid (up to 20 mg/dL) does not interfere with the assay
- EDTA-2K (up to 5.0 mg/mL) does not interfere with the assay. 트
- Heparin (up to 100 U/mL) does not interfere with the assay.
Specificity
The following substances were tested for cross-reactivity. The cross-reactivity (%) is the percent of the compound which will be identified as Homocysteine. If these compounds are present in the specimen at the same concentration as Homocysteine, the final result will be increased by these percentages.
| Compound | Concentration(µmol/L) | Cross-reactivity (%) |
|---|---|---|
| Adenosine | 5.10 | 0.045 |
| S-Adenosyl-L-methionine | 4.74 | 1.26 |
| L-Cystathionine | 0.486 | 0.159 |
| L-Cysteine | 103 | 0.003 |
| L-Glutathione | 99.6 | 0.005 |
| L-Methionine | 0.399 | 0.059 |
| DL-Homocysteinethiolactone | 0.257 | 6.99 |
- Assay cut off g. Not applicable
2. Comparison Studies:
- Method comparison a.
The methods comparison study was developed with the reference to the CLSI protocol entitled: Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline (EP9-A2).
A total of 138 unaltered EDTA plasma specimens were assayed in singleton utilizing the ST AIA-PACK Homocysteine assay on the AIA-2000 analyzer and the alternate method. The regression analysis for the correlation between the alternate method (x) and the ST AIA-PACK Homocysteine is as follows:
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| Deming | Regular | |
|---|---|---|
| Slope: | 1.079 | 1.061 |
| Intercept: | 0.193 | 0.499 |
| Standard Error Estimate: | 2.268 | 2.257 |
| Corr Coef( R): | 0.984 | |
| Points (Plotted/Total): | 138/138 | |
| Result Ranges: | 2.8 to 48.3 µmol/L |
b. Matrix comparison
The correlation between EDTA plasma (x) and heparinized plasma (y) on the ST AlA-PACK Homocysteine was carried out using 98 unaltered specimens.
| Deming | Regular | |||
|---|---|---|---|---|
| Slope: | 1.007 | (0.979 to 1.035) | 0.998 | (0.970 to 1.025) |
| Intercept: | -0.235 | (-0.591 to 0.121) | -0.124 | (-0.480 to 0.231) |
| Standard ErrorEstimate: | 0.682 | 0.680 | ||
| Corr Coef(R): | 0.991 | |||
| Result Ranges | EDTA | 6.25-38.3 μmol/L | Heparin | 6.15 - 37.5 μmol/L |
The correlation between EDTA plasma (x) and serum (y) on the ST AIA-PACK Homocysteine was carried out using 98 unaltered specimens.
| Deming | Regular | ||
|---|---|---|---|
| Slope: | 1.007 (0.979 to 1.035) | 0.998 (0.970 to 1.025) | |
| Intercept: | -0.235 (-0.591 to 0.121) | -0.124 (-0.480 to 0.231) | |
| Standard ErrorEstimate: | 0.682 | 0.680 | |
| Corr Coef(R): | 0.991 | ||
| Result Ranges | EDTA 6.25-38.3 µmol/L | Heparin 6.15 - 37.5 µmol/L |
నే. Clinical Studies:
Not applicable .
- Clinical cut-off: Not applicable
-
- Expected values/Reference range: The interval given here was determined in unaltered EDTA plasma samples from 130 apparently healthy individuals.
A reference range study was conducted based on guidance from Clinical and Laboratory Standards Institute (CLSI) Protocol C28-A2.
- Expected values/Reference range: The interval given here was determined in unaltered EDTA plasma samples from 130 apparently healthy individuals.
Number of Samples (n) 130 6.6 - 17.8 umol/L Reference Interval
The central 95% of the reference range was used to determine the reference interval.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/9/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized eagle with its wings spread, facing to the right. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The seal is black and white.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Tosoh Bioscience, Inc c/o Judith K. Ogden 6000 Shoreline Court Suite 101 South San Francisco, CA 94080
JUN 1 5 2012
Re: K121533
Trade Name: ST AIA-PACK Homocysteine,
ST AIA-PACK Homocysteine Calibrator Set
AIA-PACK Homocysteine Control Set
Regulation Number: 21 CFR §862.1377 Regulation Name: Urinary homocysteine (non-quantitative) test system Regulatory Class: Class II Product Codes: LPS, JIT, JJX Dated: May 22, 2012 Received: May 25, 2012
Dear Ms. Ogden:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA). it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please 11 you deally office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 prease note the roganized on regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 01160 of Dar remestions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical
Devices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance...
You may obtain other general information on your responsibilities under the Act from the Tou may of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm
Sincerely yours.
signature
Countney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use Form
510(k) Number (if known): K121533
Device Name: ST AIA-PACK Homocysteine; ST AIA-PACK Homocysteine Calibrator Set; AIA-PACK Homocysteine Control Set
Indications for Use:
Reagents:
ST AIA-PACK Homocysteine is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of homocysteine in human serum, heparinized plasma or EDTA plasma using a Tosoh AlA System Analyzer. Homocysteine measurements are used in the diagnosis and treatment of hyperhomocysteinemia or homocysteinuria. Calibrators:
ST AIA-PACK Homocysteine Calibrator Set is intended for IN VITRO DIAGNOSTIC USE ONLY for the callbration of the ST AIA PACK Homocysteine assay using a Tosoh AIA System Analyzer.
Controls:
The AIA-PACK Homocysteine Control Set is intended for IN VITRO DIAGNOSTIC USE ONLY for performing quality control procedures with the ST AIA-PACK Homocysteine Assay.
Over-The-Counter Use Prescription Use AND/OR (Part 21 CFR 801 Subpart D (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Buttle Chube
Division Sian-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) k 1 2 1 5 3 3
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§ 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.