(52 days)
Immunoturbidmetric assay for the in vitro quantitative determination of apolipoprotein B in human serum and plasma on automated clinical chemistry analyzers.
A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders and atherosclerosis.
A device for the measurement of human apolipoprotein B in serum or plasma. Anti-apolipoprotein B antibodies react with the antigen in the sample to form antigen/antibody complexes which, following agglutination, are measured turbidimetrically.
The provided text describes a 510(k) premarket notification for the "Tina-quant Apolipoprotein B ver.2" device. This device is an immunoturbidimetric assay for the quantitative determination of apolipoprotein B in human serum and plasma. The submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, the Dade Behring N Antisera to Human Apolipoprotein A-1 and Apolipoprotein B assay (K860894), rather than providing a detailed study that establishes specific acceptance criteria against a defined clinical endpoint.
Therefore, the following information is extracted from the provided text, recognizing that it primarily details performance characteristics for demonstrating equivalence, not a standalone clinical validation against specific "acceptance criteria" in the way a new diagnostic test might typically undergo:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly state "acceptance criteria" in a quantitative, pre-defined manner for clinical utility against a specific disease outcome. Instead, it presents performance characteristics of the new device and compares them to a predicate device to establish substantial equivalence.
| Feature | Acceptance Criteria (Implied by Predicate Equivalence) | Reported Device Performance (Tina-quant Apolipoprotein B ver.2) |
|---|---|---|
| Precision | Similar to predicate device (see predicate performance) | Within run CV: 1.5% @ 29 mg/dL (serum), 0.5% @ 112 mg/dL (serum), 0.8% @ 69 mg/dL (control), 0.5% @ 152 mg/dL (control) Between Day CV: 2.5% @ 26 mg/dL (serum), 1.1% @ 127 mg/dL (serum), 1.0% @ 80 mg/dL (control), 1.9% @ 155 mg/dL (control) |
| Method Comparison | Correlation with predicate and/or nephelometric method | $y = 1.127 - 2.849$ mg/dL (vs. Nephelometric method X), $r = 0.884$ |
| Hook Effect | Not present within expected range | No effect up to 600 mg/dL |
| Analytical Sensitivity | Similar to predicate | 1.5 mg/dL |
| Interference (Icterus) | No significant interference | No significant interference up to an I index of 60 mg/dL (conjugated and unconjugated) |
| Interference (Hemolysis) | No significant interference | No significant interference up to an H index of 1000 |
| Interference (Lipemia) | No significant interference | No significant interference up to an L index of 1000 |
| Cross-reactivity | No cross-reactivity with related substances | Anti-human apolipoprotein B antibodies from sheep show no cross-reactivity with apolipoprotein A-I or A-II |
2. Sample size used for the test set and the data provenance
The document does not explicitly state the sample size used for the test set in the context of clinical validation. The reported performance characteristics (precision, method comparison, etc.) would typically be derived from studies with a certain number of samples, but these numbers are not specified.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The studies described are performance studies for the device itself, likely conducted in a lab setting.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This device is an in vitro diagnostic (IVD) quantitative assay. The "ground truth" for such devices is established by reference methods or validated comparative methods, not by expert consensus in the same way as, for example, image-based diagnostic AI.
4. Adjudication method for the test set
Not applicable. As described above, the ground truth is based on quantitative reference methods, not subjective expert reviews 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 automated in vitro diagnostic assay, not an AI-assisted diagnostic tool that involves human readers or interpretation of complex data.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies described are standalone performance evaluations of the Tina-quant Apolipoprotein B ver.2 assay. The performance characteristics (precision, method comparison, sensitivity, interference, hook effect) are inherent to the assay and instrument combination, without human interpretation influencing the measurement result itself.
7. The type of ground truth used
The "ground truth" for the device's performance evaluation is established through:
- Comparative methods: Against a "Nephelometric method" for method comparison, and implicitly against the predicate device's performance.
- Validated laboratory reference standards and controls: Used for precision, sensitivity, and linearity studies.
8. The sample size for the training set
Not applicable. This is not a machine learning or AI device that requires a "training set" in the conventional sense. The assay is based on established immunoturbidimetric principles.
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" for this type of IVD device.
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| NOV | 1 6 2001 |
|---|---|
| ----- | ---------- |
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. |
|---|---|
| Submitter name, address, contact | Roche Diagnostics Corporation 9115 Hague Road Indianapolis, IN 46250 (317) 521 - 3544 |
| Contact Person: Kay A. Taylor | |
| Date Prepared: September 24, 2001 | |
| Device Name | Proprietary name: Tina-quant Apolipoprotein ver.2 |
| Common name: Apolipoprotein B | |
| Classification name: Low-density lipoprotein immunological test system | |
| Device Description | A device for the measurement of human apolipoprotein B in serum or plasma. Anti-apolipoprotein B antibodies react with the antigen in the sample to form antigen/antibody complexes which, following agglutination, are measured turbidimetrically. |
| Intended use | Immunoturbidmetric assay for the in vitro quantitative determination of apolipoprotein B in human serum and plasma on automated clinical chemistry analyzers. |
| Indications for Use | A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders and atherosclerosis. |
:
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Substantial Equivalence
The Tina-quant Apolipoprotein B ver.2 is substantially equivalent to other devices legally marketed in the United States. We claim equivalence to the Dade Behring N Antisera to Human Apolipoprotein A-1 and Apolipoprotein B assay (K860894).
Substantial equivalence similarities
The following table compares the Tina-quant Apolipoprotein B ver.2 Assay with the predicate device.
| Feature | Tina-quantApolipoprotein B ver.2 | Apolipoprotein B (predicate) |
|---|---|---|
| Intended Use | Immunoturbidmetric assayfor the in vitro quantitativedetermination ofapolipoprotein B in humanserum and plasma onautomated clinicalchemistry analyzers. | In vitro diagnostic reagent forthe quantitative determinationof apolipoprotein B in humanserum with the Behringnephelometers. |
| Indication for Use | For the quantitativedetermination ofapolipoprotein B in serumand plasma. A lipoproteintest system is a deviceintended to measurelipoprotein in serum andplasma. Lipoproteinmeasurements are used inthe diagnosis and treatmentof lipid disorders andatherosclerosis. | For the quantitativedetermination ofapolipoprotein B in serumand plasma. A lipoproteintest system is a deviceintended to measurelipoprotein in serum andplasma. Lipoproteinmeasurements are used inthe diagnosis and treatmentof lipid disorders andatherosclerosis. |
| Assay Protocol | Immunoturbidometric | Immunoturbidometric |
| Traceability /Standardization | Standardized with regard tothe IFCC referencepreparation SP3-07. | Not provided in insert |
| CalibrationInterval | • After each lot• as required by QCprocedures | • After each lot• as required by QCprocedures |
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510(k) Summary, Continued
Substantial equivalence differences
The following table compares the Tina-quant Apolipoprotein B ver.2 Assay with the predicate device.
| Feature | Tina-quant ApolipoproteinB ver.2 | Apolipoprotein B(predicate) |
|---|---|---|
| Sample Type | Serum and plasma (heparin,EDTA) | Serum |
| ReagentStability | Store at 2-8°C,unopened.42 days opened andrefrigerated on analyzer. | Store at 2-8°C,unopened.Use within 4 weeks, ifdirectly after use if vialsare stopped, capped andstored at 2-8°C.Do not use remainingantiserum if left open onnephelometer for longerthan 5 days at 8 hoursdaily or comparableperiod of time.Do not freeze. |
| Calibrator | C.f.a.s. Lipids | N Apoliporprotein StandardSerum (human) |
| Controls | Precinorm L, Precipath L | Apolipoprotein ControlSerum CHD (human) |
| ExpectedValues | Females: 60 - 117 mg/dLMales: 66 - 133 mg/dL | Females: 0.66 - 1.25 g/LMales: 0.65 - 1.40 g/L |
| Instrument | Roche/Hitachi ClinicalChemistry Analyzers | Dade BehringNephelometers |
| MeasuringRange | 20 - 400 mg/dL | Not provided in insert |
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510(k) Summary, Continued
Substantial equivalence performance characteristics The performance characteristics of the Tina-quant Apolipoprotein B ver.2 Assay and the predicate device are compared in the table below.
| Feature | Tina-quant ApolipoproteinB ver.2 | Apolipoprotein B(predicate) |
|---|---|---|
| Precision | Within run CV | Inter-assay Precision |
| 1.5% @ 29 mg/dL (serum) | 1.9% CV @ 1.04 g/L | |
| 0.5% @ 112 mg/dL (serum) | Intra-assay Precision | |
| 0.8% @ 69 mg/dL (control) | ||
| 0.5% @ 152 mg/dL (control) | 2.4% CV @ 1.08 g/L | |
| Between Day CV | ||
| 2.5% @ 26 mg/dL (serum) | ||
| 1.1% @ 127 mg/dL (serum) | ||
| 1.0% @ 80 mg/dL (control) | ||
| 1.9% @ 155 mg/dL (control) | ||
| MethodComparison | Bablok/Passing:Tina-quant Apolipoprotein Bver.2 (Y) / Nephelometricmethod (X).$y = 1.127 - 2.849$ mg/dL$r = 0.884$ | Dade Behring N AntiseraApo B (Y) /radioimmunodiffusioncommerical method (X):$y(BN)= 0.94(RID) - 0.004$ g/L$r= 0.99$ |
| Hook Effect | No effect up to 600 mg/dL | NA |
| Analyticalsensitivity (LDL) | 1.5 mg/dL | Established by the lowerlimit of the referencecurve and dependstherefore upon theconcentration of theproteins in the NApolipoprotein StandardSerum |
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510(k) Summary, Continued
Substantial equivalence performance characteristics, cont.
The performance characteristics of the Tina-quant Apolipoprotein B ver.2 Assay and the predicate device are compared in the table below.
| Feature | Tina-quant ApolipoproteinB ver.2 | Apolipoprotein B |
|---|---|---|
| Limitations | Icterus: No significant interference up to an I index of 60 mg/dL (conjugated and unconjugated) Hemolysis: No significant interference up to an H index of 1000. Lipemia: No significant interference up to an L index of 1000. Anti-human apolipoprotein B antibodies from sheep show no cross-reactivity with apolipoprotein A-I or A-II. | Turbidity and particles in the sample can interfere with the test. Therefore particulates resulting from incompleted coagulation or denaturation of proteins should be removed prior to assay by centrifugation. In isolated cases excessive concentrations of triglycerides or hyperlipemic samples may disturb the Apo B assay. In such cases the effect of the disturbance can be reduced by retesting the sample in a higher dilution. |
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Kay A. Taylor Regulatory Submissions, Centralized Diagnostics Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457
Re: K013206
Trade/Device Name: Tina-quant Apolipoprotein B ver.2 Regulation Number: 21 CFR 866.5600 Regulation Name: Low-density lipoprotein immunological test system Regulatory Class: Class II Product Code: DFC Dated: September 24, 2001 Received: September 25, 2001
NOV 1 6 2001
Dear Ms. Taylor:
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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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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 1 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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/dsma/dsmamain.html".
Sincerely yours,
Steven Sutman
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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Indications for Use Statement NOV 1 6 2001
K013206 510(k) Number (if known): N/A
Device Name: Tina-quant Apolipoprotein B ver.2
Indications For Use:
Immunoturbidmetric assay for the in vitro quantitative determination of apolipoprotein B in human serum and plasma on automated clinical chemistry analyzers.
A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders and atherosclerosis.
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use _
(Optional Format 1-2-96)
Jean Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K013206
§ 866.5600 Low-density lipoprotein immunological test system.
(a)
Identification. A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein in serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young persons at risk from cardiovascular diseases.(b)
Classification. Class II (performance standards).