(49 days)
Immunoturbidmetric assay for the in vitro quantitative determination of apolipoprotein A-1 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 A-1 in serum or plasma. Anti-apolipoprotein A-1 antibodies react with the antigen in the sample to form antigen/antibody complexes which, following agglutination, are measured turbidimetrically.
This document describes the Tina-quant Apolipoprotein A-1 ver.2 assay and its equivalence to a predicate device, but it does not detail a study with specific acceptance criteria that the device had to meet and prove. Instead, it describes a "substantial equivalence" comparison to an existing, legally marketed device.
Therefore, many of the requested sections (e.g., sample size for test set, number of experts, adjudication method, MRMC study, standalone performance, ground truth for test set, training set details) are not applicable or cannot be extracted from the provided text, as this type of information is typically associated with studies demonstrating performance against a defined statistical endpoint, not substantial equivalence.
Here's an analysis based on the provided text, focusing on the available information:
Description of Acceptance Criteria and the Study:
The "study" described in the provided text is a substantial equivalence comparison between the Tina-quant Apolipoprotein A-1 ver.2 assay and a predicate device (Dade Behring N Antisera to Human Apolipoprotein A-1 and Apolipoprotein B assay, K860894). The acceptance criteria for substantial equivalence are implicitly that the new device performs comparably to the predicate device across various characteristics, demonstrating similar safety and effectiveness.
The comparison focuses on:
- Intended Use and Indications for Use: Ensuring they are the same or very similar.
- Assay Protocol: Both are immunoturbidometric.
- Traceability/Standardization: The new device is standardized to IFCC reference preparation SP1-01.
- Calibration Interval: Similar.
- Performance Characteristics: Comparing precision, method comparison, hook effect, analytical sensitivity, and limitations.
The device meets the acceptance criteria by demonstrating performance characteristics that are comparable to or better than the predicate device, or within acceptable clinical ranges where direct comparison might not be feasible (e.g., analytical sensitivity).
1. Table of Acceptance Criteria and Reported Device Performance
Since this is a substantial equivalence claim, the "acceptance criteria" are implicitly the performance of the predicate device, and the "reported device performance" is how the new device compares. No explicit numerical acceptance criteria (e.g., "CV must be < X%") are stated, but rather a direct comparison to the predicate.
| Feature | Acceptance Criteria (Predicate Device Performance) | Reported Device Performance (Tina-quant Apolipoprotein A-1 ver.2) |
|---|---|---|
| Intended Use | Immunoturbidmetric assay for in vitro quantitative determination of apolipoprotein A-1 in human serum with Behring nephelometers. | Immunoturbidmetric assay for in vitro quantitative determination of apolipoprotein A-1 in human serum and plasma on automated clinical chemistry analyzers. (Adds plasma, specific analyzers) |
| Indication for Use | For quantitative determination of apolipoprotein A-1 in serum and plasma. Used in diagnosis/treatment of lipid disorders and atherosclerosis. | For quantitative determination of apolipoprotein A-1 in serum and plasma. Used in diagnosis/treatment of lipid disorders and atherosclerosis. (Identical) |
| Assay Protocol | Immunoturbidometric | Immunoturbidometric (Identical) |
| Traceability / Standardization | Not provided in insert | Standardized with regard to the IFCC reference preparation SP1-01. (New device provides this, predicate did not specify) |
| Calibration Interval | • After each lot• as required by QC procedures | • After each lot• as required by QC procedures (Identical) |
| Sample Type | Serum | Serum and plasma (heparin, EDTA) (Expanded sample type) |
| Reagent Stability | • Store at 2-8°C, unopened.• Use within 4 weeks (if vials stopped, capped, stored at 2-8°C) or 5 days (if on nephelometer for 8 hrs/daily).• Do not freeze. | • Store at 2-8°C, unopened.• 42 days opened and refrigerated on analyzer. (Improved opened stability) |
| Calibrator | N Apolipoprotein Standard Serum (human) | C.f.a.s. Lipids (Different calibrator) |
| Controls | Apolipoprotein Control Serum CHD (human) | Precinorm L, Precipath L (Different controls) |
| Expected Values | Females: 1.25 - 2.15 g/LMales: 1.10-2.05 g/L | Females: 108 - 225 mg/dLMales: 104 - 202 mg/dL (Values provided in different units, but generally comparable ranges) |
| Instrument | Dade Behring Nephelometers | Roche/Hitachi Clinical Chemistry Analyzers (Different, specific to new device) |
| Measuring Range | Not provided in insert | 20 - 400 mg/dL (Provided for new device) |
| Precision | Inter-assay Precision: 2.2% CV @ 1.58 g/LIntra-assay Precision: 5.7% CV @ 1.45 g/L | Within run CV:1.0% @ 40 mg/dL (serum)0.6% @ 176 mg/dL (serum)1.0% @ 157 mg/dL (control)1.2% @ 83 mg/dL (control)Between Day CV:2.4% @ 47 mg/dL (serum)1.6% @ 179 mg/dL (serum)1.2% @ 171 mg/dL (control)2.4% @ 84 mg/dL (control) (Comparable or better) |
| Method Comparison | Y (BN) = 1.0 (RID) – 0.04 g/Lr = 0.98. (Compared to radioimmunodiffusion) | Y (Tina-quant) = 2.45 + 1.073X (Nephelometric method)r = 0.781 (Compared to a nephelometric method, correlation lower but context not fully provided for equivalency analysis) |
| Hook Effect | NA | No effect up to 600 mg/dL (Provided, predicate did not specify) |
| Analytical Sensitivity | Established by the lower limit of the reference curve (depends on N Apolipoprotein Standard Serum). | 0.6 mg/dL (Specific value provided for new device) |
| Limitations | Turbidity and particles can interfere. High triglycerides/lipemia may disturb Apo B assay (can retest in higher dilution). | Icterus: No significant interference up to I index of 60 mg/dL.Hemolysis: No significant interference up to H index of 1000.Lipemia: No significant interference up to L index of 1000.No cross-reactivity with Apo B or A-II. (Detailed interference studies) |
Regarding items that cannot be extracted or are not applicable for this type of submission:
- Sample size used for the test set and the data provenance: Not explicitly stated. The method comparison data implies a comparison using patient samples, but the number of samples or their origin is not specified. It's typical for method comparison studies to use a range of patient samples.
- Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This is a quantitative assay, not an interpretation task requiring expert consensus. The "ground truth" would be the measurement from another validated method.
- Adjudication method for the test set: Not applicable for a quantitative assay comparison.
- 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 a laboratory diagnostic assay, not an imaging interpretation device involving human readers or AI assistance.
- If a standalone (i.e. algorithm only without human-in-the loop performance) was done: The device itself is a standalone in-vitro diagnostic device (an "algorithm" in a sense, as it performs a quantitative measurement). Its performance is evaluated purely based on its analytical characteristics.
- The type of ground truth used: For the method comparison, the "ground truth" for the new device was a "Nephelometric method". For the predicate, it was "radioimmunodiffusion (RID)". For other performance characteristics (precision, sensitivity), "ground truth" is established through standardized reference materials and internal quality control.
- The sample size for the training set: Not applicable. This is a laboratory reagent, not a machine learning algorithm that requires a "training set" in the conventional sense. Its performance is characterized through typical analytical validation studies.
- How the ground truth for the training set was established: Not applicable. (See point 8).
In summary, the provided text details a comparison of analytical performance characteristics to establish substantial equivalence, rather than a clinical study against predefined acceptance criteria for a new clinical endpoint.
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NOV 1 6 2001
| 510(k) Summary | K.013249 |
|---|---|
| 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 Corporation9115 Hague RoadIndianapolis, IN 46250(317) 521 - 3544Contact Person: Helen T. TorneyDate Prepared: September 25, 2001 |
| Device Name | Proprietary name: Tina-quant Apolipoprotein ver.2Common name: Apolipoprotein A-1Classification name: Alpha-1- lipoprotein immunological test system |
| Device Description | A device for the measurement of human apolipoprotein A-1 in serum or plasma. Anti-apolipoprotein A-1 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 A-1 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 The Tina-quant Apolipoprotein A-1 ver.2 is substantially equivalent to other devices legally marketed in the United States. We claim equivalence to the Equivalence 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 A-1 ver.2 Assay with the predicate device.
| Feature | Tina-quantApolipoprotein A-1 ver.2 | Apolipoprotein A-1(predicate) |
|---|---|---|
| Intended Use | Immunoturbidmetric assayfor the in vitro quantitativedetermination ofapolipoprotein A-1 inhuman serum and plasmaon automated clinicalchemistry analyzers. | In vitro diagnostic reagent forthe quantitative determinationof apolipoprotein A-1 inhuman serum with theBehring nephelometers. |
| Indication forUse | For the quantitativedetermination ofapolipoprotein A-1 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 A-1 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 SP1-01. | Not provided in insert |
| CalibrationInterval | • After each lot• as required by QCprocedures | • After each lot• as required by QCprocedures |
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Substantial equivalence differences
The following table compares the Tina-quant Apolipoprotein A-1 ver.2 Assay with the predicate device.
| Feature | Tina-quant ApolipoproteinA-1 ver.2 | Apolipoprotein A-1(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: 108 - 225 mg/dLMales: 104 - 202 mg/dL | Females: 1.25 - 2.15 g/LMales: 1.10-2.05 g/L |
| Instrument | Roche/Hitachi ClinicalChemistry Analyzers | Dade BehringNephelometers |
| MeasuringRange | 20 - 400 mg/dL | Not provided in insert |
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Substantial equivalence performance characteristics The performance characteristics of the Tina-quant Apolipoprotein A-1 ver.2 Assay and the predicate device are compared in the table below.
| Feature | Tina-quant ApolipoproteinA-1 ver.2 | Apolipoprotein A-1(predicate) |
|---|---|---|
| Precision | Within run CV1.0% @ 40 mg/dL (serum)0.6% @ 176 mg/dL (serum)1.0% @ 157 mg/dL (control)1.2% @ 83 mg/dL (control)Between Day CV2.4% @ 47 mg/dL (serum)1.6% @ 179 mg/dL (serum)1.2% @ 171 mg/dL (control)2.4% @ 84 mg/dL (control) | Inter-assay Precision2.2% CV @ 1.58 g/LIntra-assay Precision5.7% CV @ 1.45 g/L |
| MethodComparison | Bablok/Passing:Tina-quant Apolipoprotein A-1ver.2 (Y) / Nephelometricmethod (X).y = 2.45+1.073 mg/dLr = 0.781 | Dade Behring N AntiseraApo A-1 (Y) /radioimmunodiffusioncommerical method (X):y(BN)= 1.0 (RID) – 0.04g/Lr= 0.98 |
| Hook Effect | No effect up to 600 mg/dL | NA |
| Analyticalsensitivity(LDL) | 0.6 mg/dL | Established by the lowerlimit of the reference curveand depends thereforeupon the concentration ofthe proteins in the NApolipoprotein StandardSerum. |
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Substantial equivalence performance characteristics, cont.
The performance characteristics of the Tina-quant Apolipoprotein A-1 ver.2 Assay and the predicate device are compared in the table below.
| Feature | Tina-quant ApolipoproteinA-1 ver.2 | Apolipoprotein A-1 |
|---|---|---|
| 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 A-1 antibodies from sheep show no cross-reactivity with apolipoprotein B 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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DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Helen T. Torney Regulatory Submissions, Centralized Diagnostics Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457
NOV 1 6 2001
Re: K013249
Trade/Device Name: Tina-quant Apolipoprotein A-1 ver.2 Regulation Number: 21 CFR 866.5580 Regulation Name: Alpha-1-lipoprotein immunological test system Regulatory Class: Class II Product Code: DER Dated: September 25, 2001 Received: September 28, 2001
Dear Ms. Torney:
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 (OS) 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, (1) = 1 = 1 = 1 = 1 = 1 = 1 = 1 = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = 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/cdrb/dsma/dsmamain.html".
Sincerely yours,
Steven Gutman
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
Ko13249 510(k) Number (if known): N/A
Device Name: Tina-quant Apolipoprotein A-1 ver.2
Indications For Use:
Immunoturbidmetric assay for the in vitro quantitative determination of apolipoprotein A-1 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)
(Division Sign-Off)
Division of Clinical Laboratory Levices
510(k) Number.
vision of Clinical Laboratory Devices
510(k) Number K013249
§ 866.5580
Alpha -1-lipoprotein immunological test system.(a)
Identification. Analpha -1-lipoprotein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques thealpha- 1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement ofalpha- 1-lipoprotein may aid in the diagnosis of Tangier disease (a hereditary disorder of fat metabolism).(b)
Classification. Class II (performance standards).