(47 days)
Method: For the quantitative measurement of myoglobin in human serum and plasma on the Dimension Vista™ System as an aid in the rapid diagnosis of acute myocardial infarction.
Calibrator: For the calibration of the myoglobin (MYO) method on the Dimension Vista™ System.
Method: The MYO method is a homogenous sandwich chemiluminescent immunoassay based on Luminescent Oxygen Channeling Immunoassay (1.OCI™) technology. LOCI™ reagents include two latex bead reagents and a biotinylated anti-myoglobin monoclonal antibody fragment. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with a second anti-myoglobin monoclonal antibody and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibody to form a beadmyoglobin-biotinylated antibody sandwich. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from Sensibeads which diffuses into Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the myoglobin concentration in the sample.
Calibrator: The Dade Behring MYO Calibrator is a three level (A, B, C), frozen liquid product containing purified human heart myoglobin in a 6% bovine albumin matrix with stabilizers and preservatives. The kit contains 3 vials of each level (A= 2.0 mL. B= 1.0 mL. C= 1.5 mL).
Here's a breakdown of the acceptance criteria and the study details for the Dade Behring Dimension Vista™ MYO reagent cartridge and calibrator, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" but rather presents a comparison to a predicate device and then reports the performance of the new device. The implied acceptance criteria are that the new device should perform comparably to the predicate device and meet certain analytical performance characteristics.
| Performance Metric | Implied Acceptance Criteria (relative to predicate or analytical standards) | Reported Device Performance (Dimension Vista™ MYO) |
|---|---|---|
| Method Comparison | Slope near 1.00, intercept near 0, high correlation coefficient (e.g., >0.98) | Slope: 1.003, Intercept: 6.98 ng/mL, Correlation Coefficient: 0.998 |
| Analytical Sensitivity | Lower or equal to predicate (1 ng/mL) | 0.5 ng/mL (Improved) |
| Reportable Range | Wider or equal to predicate (1 to 1000 ng/mL) | 0.5 - 1000 ng/mL (Wider) |
| Interferences | No significant interference from common interferents at specified levels | Bilirubin (conj/unconj) up to 60 mg/dL, Hemoglobin up to 1000 mg/dL, Triglycerides up to 3000 mg/dL (Improved for triglycerides compared to predicate) |
| Hook Effect | No high dose effect up to high concentrations | No high dose effect (up to 300,000 ng/mL) |
| Calibration Interval | Stable for a reasonable period | Six levels every 30 days with the same reagent lot |
| Sample Volume | Optimized for efficiency | 2 uL (Reduced from predicate's 20 uL) |
| Serum/Plasma Comparison | Good agreement between sample types (slope near 1.0, high correlation) | Serum vs. lithium heparin: Slope 1.05, Correlation 1.0, Intercept -5.12 ng/mL (n=37)Lithium vs. sodium heparin: Slope 1.00, Correlation 1.0, Intercept -0.54 ng/mL (n=115) |
| Reproducibility (Precision) | Acceptable SD and %CV for various myoglobin levels | Pool 1 (110.3 ng/mL): %CV 5.0Pool 2 (501.5 ng/mL): %CV 3.7Pool 3 (830.8 ng/mL): %CV 3.3Control Level 1 (113.5 ng/mL): %CV 3.6 |
2. Sample Sizes and Data Provenance:
- Method Comparison Test Set: 160 patient samples (serum and heparinized plasma).
- Data Provenance: Not explicitly stated, but typically these samples would be from a clinical laboratory or reference lab, retrospective. The document does not specify country of origin.
- Serum/Plasma Comparison Test Set:
- 37 matched serum and lithium heparin pairs.
- 115 lithium and sodium heparin samples.
- Data Provenance: Not explicitly stated regarding country or retrospective/prospective. Assumed to be from a clinical setting.
- Reproducibility Test Set: Three human serum pools and one commercial cardiac marker control. The number of individual measurements for repeatability and within-lab is not specified, but it states "a single test from two independent cups was analyzed twice per day" according to NCCLS guideline EP5-A2, which typically involves multiple days of testing.
3. Number of Experts and Qualifications for Ground Truth:
- This submission describes an analytical performance study for an in vitro diagnostic (IVD) device, not a clinical study involving interpretation of images or patient outcomes for which human experts would establish a ground truth.
- Therefore, the concept of "experts establishing ground truth" as it applies to image interpretation or clinical diagnosis is not applicable here. The ground truth for such devices is typically the true concentration of the analyte, established by reference methods or validated materials.
4. Adjudication Method for the Test Set:
- Not applicable. This relates to clinical studies where multiple human readers assess a case. For an IVD device, the "adjudication" is inherent in the analytical process, where the instrument measures an analyte and its performance is assessed against a predicate device or established analytical standards.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. An MRMC study is not relevant for this type of IVD device. This device analytically measures myoglobin concentration, and its performance is compared to a predicate device, not against human readers' diagnostic accuracy, nor is it designed to assist human readers in image interpretation.
6. Standalone Performance Study:
- Yes. The entire submission details the standalone performance of the Dimension Vista™ MYO system (reagent and calibrator) by demonstrating its analytical characteristics (sensitivity, range, interference, precision, method comparison, serum/plasma comparison). The results presented are solely the performance of the algorithm/device itself.
7. Type of Ground Truth Used:
- For the method comparison and serum/plasma comparison, the ground truth is essentially the measurement obtained from the predicate device (Dade Behring Dimension® MYO immunoassay). The goal is to show the new device produces equivalent results.
- For analytical characteristics like sensitivity, range, and reproducibility, the ground truth is established using reference materials, calibrators, and characterized human serum pools with known or assigned myoglobin concentrations.
8. Sample Size for the Training Set:
- The document does not provide information on a "training set" in the context of machine learning. This is an immunoassay device, and while it would have undergone extensive development and optimization (which could be considered analogous to "training" in a broad sense), the specific term "training set" for an algorithm, as used in AI/ML, isn't applicable here and thus no sample size is reported.
9. How Ground Truth for Training Set was Established:
- Not applicable as there is no explicitly defined "training set" as understood in AI/ML for this immunoassay device. The "ground truth" during the development phase would involve using validated reference materials and methods to optimize the reagent formulations and assay parameters.
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K 053576
SUMMARY OF SAFETY AND EFFECTIVENESS INFORMATION
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| Submitter's Name: | George M. PlummerDade Behring Inc.P.O. Box 6101Newark, DE 19714-6101 |
|---|---|
| Date of Preparation: | December 20, 2005 |
| Name of Product(s): | Dimension Vista™ MYO reagent cartridge andDimension Vista™ MYO calibrator |
| FDA Classification Name(s): | Myoglobin, Antigen, Antiserum, Control and associated calibrator |
| FDA Guidance Documents: | Not applicable |
| Predicate Device(s): | Dade Behring MYO immunoassay and Calibrator(K984191/K984193) |
Device Description(s):
Method
The MYO method is a homogenous sandwich chemiluminescent immunoassay based on Luminescent Oxygen Channeling Immunoassay (1.OCI™) technology. LOCI™ reagents include two latex bead reagents and a biotinylated anti-myoglobin monoclonal antibody fragment. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with a second anti-myoglobin monoclonal antibody and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibody to form a beadmyoglobin-biotinylated antibody sandwich. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from Sensibeads which diffuses into Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the myoglobin concentration in the sample.
Calibrator
The Dade Behring MYO Calibrator is a three level (A, B, C), frozen liquid product containing purified human heart myoglobin in a 6% bovine albumin matrix with stabilizers and preservatives. The kit contains 3 vials of each level (A= 2.0 mL. B= 1.0 mL. C= 1.5 mL).
Intended Use:
Method
For the quantitative measurement of myoglobin in human serum and plasma on the Dimension Vista™ System as an aid in the rapid diagnosis of acute myocardial infarction.
Calibrator
For the calibration of the myoglobin (MYO) method on the Dimension Vista™ System.
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Comparison to Predicate Device:
Method
A summary of the features of the Dade Behring Dimension Vista™ MYO reagent cartridge and the A summal y of the reatures of the Dade Bearing = mmunoassay (K984191/K984193) is provided in the following charts.
| Feature | Dimension® MYO | Dimension Vista™ MYO |
|---|---|---|
| Intended Use | For the in vitro quantitativedetermination of myoglobin inhuman serum and heparinizedplasma as an aid in the diagnosis ofmyocardial infarction. | For the in vitro quantitativedetermination of myoglobin in humanserum and heparinized plasma as anaid in the diagnosis of myocardialinfarction. |
| Assay Type(detection) | photometric immunoassay | chemiluminescent immunoassay |
| Reportable Range | 1 to 1000 ng/mL | 0.5 - 1000 ng/mL |
| Antibody | Dade Behring mouse monoclonal | Dade Behring mouse monoclonal |
| AnalyticalSensitivity | 1 ng/mL | 0.5 ng/mL |
| AnalyticalSpecificity | There are no known cross reactivematerials. | There are no known cross reactivematerials. |
| Interferences | No significant interference from:bilirubin up to 60 mg/dL,hemoglobin up to 1000 mg/dL andtriglycerides up to 1500 mg/dL | No significant interference from:bilirubin, conj. up to 60 mg/dLbilirubin, unconjugated up to 60mg/dL, hemoglobin up to 1000mg/dL and triglycerides up to 3000mg/dL |
| Hook Effect | No high dose effect(up to 300,000 ng/mL) | No high dose effect(up to 300,000 ng/mL) |
| Calibration Interval | Calibration curve updated for eachlot, using five levels and every 90days, thereafter with the samereagent lot. | Calibration curve updated for eachlot, using six levels every 30 dayswith the same reagent lot. |
| Sample Volume | 20 uL | 2 uL |
| Feature | Dimension® MYO | Dimension Vista™ MYO |
| Intended Use | MYO method calibration | MYO method calibration |
| Analyte | Human heart myoglobin | Human heart myoglobin |
| Matrix | Bovine serum albumin | Bovine serum albumin |
| Form | Liquid | Frozen liquid |
| Volume | 10 vials, 2 at each level, 1 mL each | 9 vials, 3 at each level, 2.0, 1.0, 1.5 mL for level A, B, C, respectively |
| Levels | 5 levels (0, 35, 100, 500, and 1060 ng/mL) | 3 levels provided (0, 125 and 1050 ng/mL); 3 additional levels made on-board (36.7, 367 and 733 ng/mL) |
Method:
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Calibrator:
Method performance Summary:
Analytical Results
Method Comparison
A split sample method comparison demonstrated good agreement between the Dade Behring Dimension Vista™ MYO method and the predicate Dade Behring Dimension® MYO immunoassay with serum and heparinized plasma patient samples.
| ComparativeMethod | Slope | Intercept(ng/mL) | CorrelationCoefficient | n |
|---|---|---|---|---|
| Dimension® MYO | 1.003 | 6.98 | 0.998 | 160 |
The model equation for linear regression statistics is: [results for Dimension Vista™ MYO] = slope x [comparative method results] + intercept. The range of MYO values in the correlation study was: 12 to 932 ng/mL.
Serum/Plasma Comparison
Serum and heparin plasma matched pairs were examined on the Dimension Vista™ system. Serum samples (n=37) ranging from 28 to 600 ng/mL when compared to lithium heparin samples gave a slope of 1.05, correlation coefficient of 1.0, and an intercept of -5.12 ng/mL using linear least squares regression statistics.
A separate study was conducted to evaluate the comparison of 115 lithium and sodium heparin samples ranging from 16 ng/mL to approximately 823 ng/mL. A linear least squares regression analysis comparing the lithium to sodium heparin samples gave a slope of 1.00, a correlation coefficient of 1.0, and an intercept of -0.54 ng/mL.
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Reproducibility Typical precision observed for the Dimension Vista™ MYO method is summarized below:
| Sample | Mean (ng/mL) | Repeatability | Within Lab | ||
|---|---|---|---|---|---|
| SD (ng/mL) | %CV | SD (ng/mL) | %CV | ||
| Human Serum Pool | |||||
| Pool 1 | 110.3 | 5.4 | 4.9 | 5.5 | 5.0 |
| Pool 2 | 501.5 | 17.3 | 3.4 | 18.7 | 3.7 |
| Pool 3 | 830.8 | 23.1 | 2.8 | 27.6 | 3.3 |
| Biorad Liquichek™Cardiac Marker Control LT | |||||
| Level 1 | 113.5 | 2.7 | 2.4 | 4.0 | 3.6 |
- Liquichek™ is a registered trademark of Biorad Laboratories, Irvine CA.
The reproducibility testing was conducted in accordance with the NCCLS (CLSI) Approved Guideline for User Evaluation of Precision Performance of Clinical Chemistry Devices EP5-A2. For each test level, a single test from two independent cups was analyzed twice per day. The within-run and total standard deviations were calculated by the analysis of variance method.
Calibrator
The Dimension Vista™ MYO calibrator is similar to other calibrator products associated with their assays, such as the Dimension® MYO calibrator.
Comments on Substantial Equivalence:
Both the Dimension Vista™ MYO reagent cartridge and the Dimension® MYO immunoassays are intended for the quantitative determination of myoglobin. Comparative data for serum and human plasma samples demonstrate good analytical and clinical agreement between the methods.
Conclusion:
The Dade Behring Dimension Vista™ MYO and the predicate Dade Behring Dimension® MYO immunoassays (K984191/K984193) are substantially equivalent based on their intended use and performance characteristics as described above. The calibrator products are also equivalent in their design and intended use with their respective assay systems.
Gmt. Plummer
George M. Plummer Regulatory Affairs and Compliance Manager December 20, 2005
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized eagle with its wings spread, and the words "U.S. Department of Health & Human Services - USA" are arranged in a circle around the eagle. The eagle is black, and the text is also black. The background is white.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
FEB 7 2006
Mr. George M. Plummer Regulatory Affairs & Compliance Manager Dade Behring Inc. Glasgow Business Community Bldg. 500. M.S. 514 PO Box 6101 Newark, DE 19714-6101
K053576 Re:
Trade/Device Name: Dimension Vista™ MYO reagent cartridge and Dimension Vista™ MYO calibrator Regulation Number: 21 CFR§ 866.5680 Regulation Name: Myoglobin immunological test system Regulatory Class: Class II Product Code: DDR, JIT Dated: December 20, 2005 Received: December 23, 2005
Dear Mr. Plummer:
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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 --
This letter will allow you to begin marketing your device as described in your Section 510(k) rms lot notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Alberto Garcia, Ph.D.
Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE STATEMENT
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510(k) Number (If Known):
Device(s) Name(s):
Dimension Vista™ MYO reagent cartridge and Dimension Vista™ MYO calibrator
Indications for Use:
Method
For the quantitative measurement of myoglobin in human serum and plasma on the Dimension Vista™ System as an aid in the rapid diagnosis of acute myocardial infarction.
Calibrator
Prescription Use
For the calibration of the myoglobin (MYO) method on the Dimension Vista™ System.
Prescription Use
(Part 21 CFR 801 Subpart D)
and/or
Over-the-counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) ============================================================================================================================================================================= ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Qim Chappie
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.