(275 days)
Immunological.in. vitro immunoturbidometric.test for the quantitative determination of ferritin.in . .... human serum and plasma using clinical-chemistry analyzers.
The Ferritin determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing ferritin is transferred into a TRIS buffer solution (R₁ reagent). In the second step, an aliquot of solution containing fine latex particles coated with polyclonal anti-human ferritin antibodies (R₂ reagent) is added to mixture of the first step. The antibody-coated particles will bind to the ferritin in the sample to form "aggregates" such that the amount of aggregate formed is proportionate to the amount of ferritin 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 ferritin in the sample is directly proportional to the amount of turbidity formed.
The provided text describes the "Tina-quant® Ferritin Assay" and its substantial equivalence to a predicate device, the "Enzymun-Test® Ferritin assay." It includes performance characteristics and comparisons, which serve as the acceptance criteria and the results of the study.
Here's a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly state "acceptance criteria" as a set of pass/fail thresholds. Instead, it presents the performance characteristics of the new device (Tina-quant® Ferritin) and compares them to the predicate device (Enzymun-Test® Ferritin). The implied acceptance criteria are that the performance of the Tina-quant® Ferritin assay should be comparable to or better than the predicate device.
| Feature | Acceptance Criteria (Implied - based on predicate device performance) | Tina-quant® Ferritin Performance (Reported Device Performance) |
|---|---|---|
| Precision (Intra-Assay %CV) | Low: ≤ 6.2%Mid: ≤ 2.7%High: ≤ 2.5% | Low: 3.8%Mid: 1.4%High: 1.1% |
| Precision (Inter-Assay %CV) | Low: ≤ 6.4%Mid: ≤ 4.3%High: ≤ 4.9% | Low: 2.6%Mid: N/A (Sample 1 & 2 only)High: N/A |
| Lower Detection Limit | Generally comparable to or better than 1.0 ng/mL | 3 ng/mL |
| Linearity | Generally comparable to or wider than 1.0 - 1000 ng/mL | 3 - 800 ng/mL |
| Method Comparison (Passing/Bablok) | r close to 1, SEE low | Vs Enzymun-Test® Ferritin: y=1.04x + 4.8 r=0.996 SEE =13.68 N=44 |
| Method Comparison (Least Squares) | r close to 1, SEE low | y = 1.00x + 13.1 r = 0.997 SEE = 13.52 N = 44 |
| Interfering Substances (Bilirubin) | ≤ 10% error at 64.5 mg/dL | No interference at 68 mg/dL (≤ 10% error) |
| Interfering Substances (Hemoglobin) | ≤ 10% error at 1 g/dL | No interference at 500 mg/dL (≤ 10% error) |
| Interfering Substances (Lipemia) | ≤ 10% error at 1250 mg/dL | No interference at 1500 mg/dL (≤ 10% error) |
| Interfering Substances (Rheumatoid Factor) | N/A (predicate) | No interference at 100 IU/mL (≤ 10% error) |
| Specificity (Liver Ferritin) | 100% | 114.6% |
| Specificity (Spleen Ferritin) | 89% | 112.0% |
2. Sample size used for the test set and the data provenance
- Precision:
- Intra-Assay: 21 samples for each of the three levels (Low, Mid, High).
- Inter-Assay: 2 samples (Sample 1, Sample 2).
- Method Comparison: 44 samples (N=44) for comparison against the Enzymun-Test® Ferritin using Passing/Bablok and Least Squares methods.
- Interfering Substances: The document does not specify the exact sample size for interfering substances, but it indicates "No interference at" certain concentrations.
- Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. It is a submission to the U.S. Food and Drug Administration (FDA), implying it was conducted for regulatory purposes in the US. The context suggests these were performance studies conducted with the device, likely prospective for the purpose of demonstrating performance.
3. 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 for quantitative determination of Ferritin. The "ground truth" for such devices is typically established through reference methods or highly accurate analytical techniques, not by human expert assessment in the same way an imaging device would be.
- The document mentions the use of NIBSC standard 80/602 and 80/578 (human liver and spleen) for calibration. These are recognized international standards for Ferritin, which serve as a form of "ground truth" for accuracy and calibration.
- No human experts are mentioned for establishing ground truth for the analytical performance of this type of quantitative assay.
4. Adjudication method for the test set
Not applicable for an in-vitro diagnostic analytical assay where ground truth is established chemically/biochemically using reference standards and methods, not through human interpretation 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 is an in-vitro diagnostic device, not an AI-powered image analysis or diagnostic support system for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance characteristics provided (Precision, Detection Limit, Linearity, Method Comparison, Interfering Substances, Specificity) are measurements of the standalone performance of the Tina-quant® Ferritin assay. This device is designed to provide quantitative results directly from a clinical chemistry analyzer, without requiring human interpretation or "human-in-the-loop" decision-making for each result.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for this in-vitro diagnostic assay is established through:
- Reference standards: NIBSC standard 80/602 and 80/578 (human liver and spleen) are used for calibration and presumably for validating accuracy.
- Comparative methods: The device's performance is compared against another legally marketed device (Enzymun-Test® Ferritin assay), which implies using the results from the predicate as a reference for method comparison studies.
- Known concentrations: For studies like linearity and interfering substances, samples with known concentrations of ferritin or interfering substances would be used.
8. The sample size for the training set
Not explicitly stated. For IVDDs, particularly those based on established immunoturbidimetric principles, "training sets" in the AI sense are not typically used. The development process involves optimizing reagents and reaction conditions, followed by validation studies. However, the data for optimization or early development are generally not referred to as a "training set" in the context of this type of device.
9. How the ground truth for the training set was established
Not applicable in the AI sense of a "training set." For method development and optimization, ground truth would be established similarly to the test set: using reference materials, spiked samples with known concentrations, and comparisons to established analytical methods.
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or a stylized human figure with outstretched arms.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Yvette Lloyd BOEHRINGER MANNEHEIM CORPORATION 2400 Bisso Lane P.O. Box 4117 Concord, CA 94524-4117 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
JUL 30 1597
K964282/S002 Re: Trade Name: Tina-quant® Ferritin Assay Regulatory Class: II Product Code: JMG Dated: April 28, 1997 Received: May 1, 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 against 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 GMP 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 regulation (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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Putman
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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K 9641882
JUL 3 0 1997
(
| 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 8413 |
|---|---|
| Contact Person: Yvette LloydDate Prepared: October 17, 1996 | |
| 2. Device name | Proprietary name: Tina-quant® Ferritin AssayCommon name: Immunoturbidometric assay for the determination of Ferritin. |
| Classification name: Ferritin immunological test system | |
| 3. Predicate device | The Boehringer Mannheim Tina-quant® Ferritin is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Enzymun-Test® Ferritin assay (K860137). |
| Continued on next page |
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BOEHRINGER 10(k) Summary, Continued ORPORATION
| Function |
|---|
| 1 |
| : 8 : |
| 14- |
| 100 |
| 4.DeviceDescription | The Ferritin determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing ferritin is transferred into a TRIS buffer solution (R₁ reagent). In the second step, an aliquot of solution containing fine latex particles coated with polyclonal anti-human ferritin antibodies (R₂ reagent) is added to mixture of the first step. The antibody-coated particles will bind to the ferritin in the sample to form "aggregates" such that the amount of aggregate formed is proportionate to the amount of ferritin 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 ferritin in the sample is directly proportional to the amount of turbidity formed. |
|---|---|
| 5.Intended use | Immunoturbidometric assay for the quantitative in-vitro determination of Ferritin. |
| 6.Comparisonto predicatedevice | The Boehringer Mannheim Tina-quant® Ferritin is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Enzymun- Test® Ferritin assay (K860137). |
Continued on next page
·
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0(k) Summary, Continued
The following table compares the Tina-quant® Ferritin with the predicate 6. The following table compares in assay. Specific data on the performance of
device, Enzymun-Test® Ferritin assay. Specific data on the performance of Comparison device, Enzymun-Tester Formin usehe draft labeling in attachment 5.
the test have been incorporated into the draft labeling in attachment 5. to predicate the test have occh moorporate device in provided in attachment 6. device cont.
Similarities:
•Intended Use: Immunoassay for the in vitro quantitative determination of Ferritin
·Sample type: Serum and plasma
Differences:
| Feature | Tina-quant® Ferritin | Enzymun-Test® Ferritin |
|---|---|---|
| Reaction test principle | Immunoturbidimetric | ELISA/1-step sandwich assay with streptavidin technology |
| Instrument required | Hitachi | ES 300 |
| Calibration | NIBSC standard 80/602 and80/578 (human liver and spleen) | NIBSC standard 80/602(human liver) |
Performance Characteristics:
| Feature | Tina-quant® Ferritin | Enzymun-Test® Ferritin | ||||
|---|---|---|---|---|---|---|
| Precision | Intra and InterAssay (ng/mL): | Modified NCCLS (ng/mL): | ||||
| Level | Low | Mid | High | Low | Mid | High |
| N | 21 | 21 | 21 | 120 | 120 | 120 |
| Intra-Assay Mean | 31.9 | 144.4 | 645.1 | 10.4 | 368.8 | 821.5 |
| %CV | 3.8 | 1.4 | 1.1 | 6.2 | 2.7 | 2.5 |
| Level | Sample 1 | Sample 2 | ||||
| Inter-Assay Mean | 76.4 | 347.4 | 10.4 | 368.8 | 821.5 | |
| %CV | 2.6 | 2.2 | 6.4 | 4.3 | 4.9 |
Continued on next page
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BOEHRINGEN 10(k) Summary, Continued 1000 CORPORATION
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Performance Characteristics:
Comparison to predicate
device, (cont.)
| Feature | Tina-quant® Ferritin | Enzymun-Test® Ferritin |
|---|---|---|
| Lower DetectionLimit | 3 ng/mL | 1.0 ng/mL |
| Linearity | 3 - 800 ng/mL | 1.0 - 1000 ng/mL |
| MethodComparison | Vs Enzymun-Test® FerritinPassing/Bablok$y=1.04x + 4.8$ $r=0.996$ $SEE =13.68$ $N=44$ | Vs Enzymun-Test® FerritinPassing/Bablok$y=1.15x - 2.8$ $r=0.992$ $SEE =44.9$ $N=56$ |
| Least Squares:$y = 1.00x + 13.1$ $r = 0.997$ $SEE = 13.52$ $N = 44$ |
Continued on next page
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HRINGER10(k) Summary, Continued 20 1 CORPORATION
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Acres
Comparison
to predicate
device, (cont.)
Performance Characteristics:
| Feature | Tina-quant® Ferritin | Enzymun-Test® Ferritin |
|---|---|---|
| Interferingsubstances | No interference at:(≤ 10% error) | No interference at:(≤ 10% error) |
| BilirubinHemoglobinLipemia | 68 mg/dL500 mg/dL1500 mg/dL | 64.5 mg/dL1 g/dL1250 mg/dL |
| RheumatoidFactor | 100 IU/mL | N/A |
| Specificity | Liver Ferritin 114.6%Spleen Ferritin 112.0%Heart Ferritin 1.7% | Liver Ferritin 100%Spleen Ferritin 89% |
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510(k) Number (if known):
Device Name: Tinaquant Ferritin Assay
Indications For Use:
Immunological.in. vitro immunoturbidometric.test for the quantitative determination of ferritin.in . .... human serum and plasma using clinical-chemistry analyzers.
A variety of methods are available for determing ferritin, e.g. radio-immunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), fluorescence immunoassay (FIA)luminescence immunoassay (LIA) and nephelometric immunoassay.
The assay is unaffected by icterus (bilirubin up to 60 mg/dl), hemolysis (Hb < 0.5 g/d), lipemia (triglycerides < 1500 mg/d} and rheumatoid factor (< 100 IU/ml).
(Criterion: recovery within ± 10% of initial value.)
For diagnostic purposes, the ferritin findings should always be assessed in conjunction with the patient's medical history, clinical examination and other findings.
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use OR Over-The-Counter Use
(Per 21 CFR 801.109) (Optional Format 1-2-96)
Peter E. Martin
§ 866.5340 Ferritin immunological test system.
(a)
Identification. A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.(b)
Classification. Class II (performance standards).