(21 days)
The Tina-quant® Myoglobin Assay is an immunoturbidometric assay for the quantitative determination of Myoglobin in serum and plasma using automated clinical chemistry analyzers. Measurement of myoglobin aids in the rapid diagnosis of heart and renal disease.
The myoglobin determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing myoglobin is transferred into a EDTA/glycine buffer solution (R1 reagent). In the second step, an aliquot of solution containing fine latex particles coated with polyclonal anti-human myoglobin antibodies (R2 reagent) is added to mixture of the first step. The antibody-coated particles will bind to the myoglobin in the sample to form "aggregates" such that the amount of aggregate formed is proportionate to the amount of myoglobin present in the sample. The resulting agglutination complex is measured turbidimetrically whereby increased turbidity is reflected through an increase in optical density. Therefore, the amount of myoglobin in the sample is directly proportional to the amount of turbidity formed.
This document describes the Boehringer Mannheim Tina-quant® Myoglobin Assay, an immunoturbidometric assay for the quantitative determination of Myoglobin in serum and plasma. The study presented aims to demonstrate substantial equivalence to a predicate device, the Behring N Latex Myoglobin Assay.
Here's an analysis of the provided information regarding acceptance criteria and the supporting study:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" but rather presents a comparison of performance characteristics between the subject device (Tina-quant® Myoglobin) and its predicate (N Latex Myoglobin). The implication is that performance comparable to or better than the predicate device constitutes acceptable performance.
| Feature | Acceptance Criteria (Implied from Predicate) | Reported Tina-quant® Myoglobin Performance |
|---|---|---|
| Precision (Intra-Assay) | Low: N=20, Mean ~85 µg/L, SD ~2.0, %CV ~2.4 | Control 1: N=20, Mean 32.3 ng/mL, SD 0.8, %CV 2.6 |
| Mid: N=20, Mean ~160 µg/L, SD ~2.4, %CV ~1.5 | Control 2: N=20, Mean 71.3 ng/mL, SD 0.6, %CV 0.9 | |
| High: N=20, Mean ~310 µg/L, SD ~2.9, %CV ~0.9 | Control 3: N=20, Mean 471.5 ng/mL, SD 1.6, %CV 0.3 | |
| Precision (Inter-Assay) | Low: N=15, Mean ~85 µg/L, SD ~4.8, %CV ~5.6 | Sample 1: N=20, Mean 71.3 ng/mL, SD 0.6, %CV 0.9 |
| Mid: N=15, Mean ~160 µg/L, SD ~4.2, %CV ~2.6 | Sample 2: N=20, Mean 471.5 ng/mL, SD 1.6, %CV 0.3 | |
| High: N=15, Mean ~310 µg/L, SD ~5.0, %CV ~1.6 | ||
| Lower Detection Limit | 25 µg/L | 3.0 ng/mL |
| Linearity | 25.0 - 400 µg/L | 3.0 - 560 ng/mL |
| Method Comparison (vs. Predicate) | N/A (Predicate itself is the comparison) | Least Squares: y = 1.06x + 0.35, r = 0.989, SEE = 19.61, N = 41 |
| Passing/Bablok: y = 1.07x + 3.6, r = 0.989, SEE = 13.61, N = 41 | ||
| Interfering Substances | Bilirubin: No interference | Bilirubin: No interference at 60 mg/dL |
| Hemoglobin: No interference | Hemoglobin: No interference at 0.5 g/dL | |
| Lipemia: No interference | Lipemia: No interference at 1500 mg/dL | |
| Rheumatoid Factor: <3000 IU/ml | Rheumatoid Factor: 100 IU/mL | |
| Specificity (% Cross-reactivity) | Human cardiac myoglobin: N/A | Human cardiac myoglobin: 102.4% |
| Human skeletal myoglobin: N/A | Human skeletal myoglobin: 99.7% | |
| Hemoglobin: N/A | Hemoglobin: 0.0% | |
| Human IgG: N/A | Human IgG: 0.0% | |
| Human Serum Albumin: N/A | Human Serum Albumin: 0.0% |
Notes on the table:
- The units for Myoglobin are inconsistent between the provided predicate data (µg/L) and the subject device data (ng/mL) for precision, detection limit, and linearity. It's assumed 1 µg/L = 1 ng/mL for direct comparison in this table based on typical clinical ranges, but this is a critical point that would require clarification for a full regulatory assessment. For instance, the Tina-quant's detection limit of 3.0 ng/mL is significantly lower (better) than the N Latex's 25 µg/L, assuming equivalence of ng/mL and µg/L.
- The "Acceptance Criteria" column is derived from the reported performance of the predicate device. The study aims to show that the Tina-quant® Myoglobin performs comparably or better.
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Test Set Sample Sizes:
- Intra-Assay: 20 samples per control level (Control 1, Control 2, Control 3).
- Inter-Assay: 20 samples per control level (Sample 1, Sample 2).
- Method Comparison Test Set Sample Size: N=41 samples.
- Data Provenance: The document does not explicitly state the country of origin or whether the data is retrospective or prospective. It is a 510(k) submission from 1997, so it's likely the data was generated specifically for this submission (prospective) and likely from studies conducted by Boehringer Mannheim or their contractors, though the location is not specified.
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 study. The device is an in-vitro diagnostic (IVD) assay that measures a biomarker (Myoglobin) quantitatively. The "ground truth" for the test set is established by the reference method or the predicate device itself (for method comparison), not by expert consensus in interpreting images or clinical cases.
4. Adjudication Method for the Test Set
This is not applicable as there is no expert adjudication involved in determining the "truth" for quantitative biomarker measurements. The accuracy is assessed by comparing results to a reference method or predicate device, or by evaluating reproducibility.
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. This type of study is relevant for diagnostic imaging interpretation devices where human readers interpret cases with and without AI assistance. This document describes an IVD assay, not an imaging device.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was Done
Yes, the performance presented for the Tina-quant® Myoglobin Assay is inherently standalone. It describes the analytical performance of the assay itself (precision, detection limit, linearity, interference, specificity) and its correlation with a predicate device, without any human-in-the-loop steps being part of the primary performance evaluation. The device functions as an automated quantitative measurement system on clinical chemistry analyzers.
7. The Type of Ground Truth Used
- For precision and linearity studies, the "ground truth" is typically established by using quality control materials (e.g., control 1, 2, 3 listed for precision) or spiked samples with known concentrations.
- For method comparison, the "ground truth" for the comparison itself is the predicate method/device (N Latex Myoglobin Assay) or, as implied for the predicate itself, a radioimmunnoassay (RIA) Myoglobin. The document states that the Tina-quant® was compared "Vs N Latex® Myoglobin" and the N Latex Myoglobin was compared "Vs Radioimmunnoassay Myoglobin." This suggests the RNA assay served as a previous reference standard.
- For interfering substances and specificity, the "ground truth" is based on controlled experiments where known amounts of the interfering substance or cross-reacting substance are added to samples, and the assay's response is measured against expected values.
8. The Sample Size for the Training Set
The document does not provide information regarding a training set sample size. This is common for traditional IVD assays, where the "model" (the assay chemistry and principles) is established through biochemical and analytical development, not typically through machine learning "training" on a data set in the same way an AI algorithm would be. The development of the assay chemistry relies on understanding biological interactions rather than statistical learning from a large dataset.
9. How the Ground Truth for the Training Set was Established
As there is no explicit "training set" in the context of an AI/ML algorithm, the ground truth establishment method for a training set is not applicable. The underlying principles of the Tina-quant® Myoglobin Assay are based on established immunoturbidimetric methods, which are developed and optimized through chemical and biological experiments, not data-driven machine learning training.
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JUL 2 8 1997
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| 510(k) Summary | |
|---|---|
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
| 1. Submitter name, address, contact | Boehringer Mannheim Corporation2400 Bisso LaneP.O. Box 4117Concord, CA 94524-4117(510) 674 - 0690, extension 8413Fax: (510) 687-1850Contact Person: Yvette Lloyd |
| Date Prepared: July 2, 1997 | |
| 2. Device name | Proprietary name: Tina-quant® Myoglobin AssayCommon name: Immunoturbidometric assay for the determination of Myoglobin.Classification name: Myoglobin immunological test system |
| 3. Predicate device | The Boehringer Mannheim Tina-quant® Myoglobin is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Behring N Latex Myoglobin Assay. |
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10(k) Summary, Continued
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The myoglobin determination is based upon turbidimetric immunoinhibition 4.Device (TINIA) using a serum or plasma blood sample. The sample containing f Description myoglobin is transferred into a EDTA/glycine buffer solution (R1 reagent). In the second step, an aliquot of solution containing fine latex particles coated with polyclonal anti-human myoglobin antibodies (R2 reagent) is added to mixture of the first step. The antibody-coated particles will bind to the myoglobin in the sample to form "aggregates" such that the amount of aggregate formed is proportionate to the amount of myoglobin present in the sample.
The resulting agglutination complex is measured turbidimetrically whereby increased turbidity is reflected through an increase in optical density. Therefore, the amount of myoglobin in the sample is directly proportional to the amount of turbidity formed.
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BOEHRING BO(k) Summary, Continued ORPORATION
ﺮ
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| 5.Intended use | Immunoturbidometric assay for the quantitative in-vitro determination of myoglobin. |
|---|---|
| 6.Comparisonto predicatedevice | The Boehringer Mannheim Tina-quant® Myoglobin is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Behring N Latex Myoglobin Assay (K902154).The following table compares the Tina-quant® Myoglobin with the predicate device, Behring Nephlometer Myoglobin Assay. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device in provided in attachment 6.Similarities:•Intended Use: Immunoassay for the in vitro quantitative determination of Myoglobin•Sample type: Serum and plasma |
•Product performance
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0(k) Summary, Continued સમાનિયા
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- Comparison to predicate device cont.
Differences:
| Feature | Tina-quant® Myoglobin | N Latex Myoglobin |
|---|---|---|
| Reaction testprinciple | Spectrophotometric570 nm | Nephlometry |
| Instrumentrequired | Hitachi 911 | Nephlometer |
Performance Characteristics:
| Feature | Tina-quant® Myoglobin | N Latex Myoglobin |
|---|---|---|
| Precision | Intra-Assay Precision (ng/mL): | Modified NCCLS:Within run Precision(µg/L) |
| Level | Control 1 Control 2 Control3 | Low Mid High |
| N | 20 20 20 | 20 20 20 |
| Mean | 32.3 71.3 471.5 | 85 160 310 |
| SD | 0.8 0.6 1.6 | 2.0 2.4 2.9 |
| %CV | 2.6 0.9 0.3 | |
| Inter-Assay Precision (ng/mL): | Day to Day Precision (µg/L): | |
| Sample 1 Sample 2 | ||
| N | 20 20 | Low Mid High |
| Mean | 71.3 471.5 | 15 15 15 |
| SD | 0.6 1.6 | 85 160 310 |
| %CV | 0.9 0.3 | 4.8 4.2 5 |
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BOEHRING 90(k) Summary, Continued ANNHE CORPORATION
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- Comparison to predicate device, (cont.) Performance Characteristics:
| Feature | Tina-quant® Myoglobin | N Latex Myoglobin | |
|---|---|---|---|
| LowerDetectionLimit | 3.0 ng/mL | 25 µg/L | |
| Linearity | 3.0 - 560 ng/mL | 25.0 - 400 µg/L | |
| MethodComparison | Vs N Latex® Myoglobin | Vs RadioimmunnoassayMyoglobin | |
| Least Squares | Least Squares | ||
| $y=1.06x + 0.35$ | $y =0.95x-4.33$ | ||
| $r=0.989$ | |||
| $SEE=19.61$ | |||
| $N=41$ | |||
| Passing/Bablok | |||
| $y =1.07x + 3.6$ | |||
| $r=0.989$$SEE=13.61$$N=41$ |
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BOEHRINGER10(k) Summary, Continued MANNHEIM CORPORATION
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Comparison
to predicate
device, (cont.)
Performance Characteristics:
| Feature | Tina-quant® Myoglobin | N Latex Myoglobin |
|---|---|---|
| Interferingsubstances | No interference at: | |
| Bilirubin | 60 mg/dL | No interference |
| Hemoglobin | 0.5 g/dL | No interference |
| Lipemia | 1500 mg/dL | No interference |
| RheumatoidFactor | 100 IU/mL | <3000 IU/ml |
| Specificity | % Cross-reactivity | % Cross-reactivity |
| Human cardiacmyoglobin | 102.4% | N/A |
| Human skeletalmyoglobin | 99.7% | N/A |
| Hemoglobin | 0.0 | N/A |
| Human IgG | 0.0 | N/A |
| Human SerumAlbumin | 0.0 | N/A |
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JUL 28 1997
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Yvette R. Lloyd Requlatory Affairs Specialist Boehringer Mannheim Corporation 2400 Bisso Lane P.O. Box 4117 Concord, California 94524-4117
K972513 Re : Tina-quant® Myoglobin Assay Requlatory Class: II Product Code: DDR Dated: July 2, 1997 Received: July 7, 1997
Dear Ms. Lloyd:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 aqainst misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the CMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations .
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Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 510(k) premarket 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 advice for your device on our labeling requlation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".
Sincerely yours,
Steven Litman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Page / of /
510(k) Number (if known): N/A
Device Name: Tina-quant® Myoglobin Assay
Indications For Use:
The Tina-quant® Myoglobin Assay is an immunoturbidometric assay for the quantitative determination of Myoglobin in serum and plasma using automated clinical chemistry analyzers. Measurement of myoglobin aids in the rapid diagnosis of heart and renal disease.
(PLEASE DO NOT WRITE BELOW THIS LÌNE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Deyice Evaluation (ODE)
Lions
Acting Branch Chief
(Division Sign-Off
Division of Clinical Laboratory Devices
510(k) Number K9725/7
Prescription Use (Per 21 CFR 801.109)
OR
Over-The-Counter Use_
(Optional Format 1-2-96)
§ 866.5680 Myoglobin immunological test system.
(a)
Identification. A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.(b)
Classification. Class II (performance standards).