(45 days)
In vitro diagnostic reagent system intended for use on COBAS INTEGRA system for the quantitative immunological determination of human apolipoprotein A-1 in serum and plasma.
For the quantitative determination of apolipoprotein A-1 in serum and plasma. 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.
Human apolipoprotein A-1 forms a precipitate with a specific antiserum which is determined turbidimetrically at 340 nm.
The provided text describes the regulatory submission for the Tina-quant Apolipoprotein A-1 ver.2 Assay, claiming substantial equivalence to a previously marketed device (COBAS Integra Tina-quant Apolipoprotein A-1, K990594). While it details performance characteristics of the new device and compares them to the predicate, it does not explicitly state "acceptance criteria" as a set of predefined thresholds. Instead, the submission demonstrates that the new device's performance is comparable to or better than the predicate device across various metrics, thus implicitly meeting an "acceptance criteria" of being substantially equivalent.
Here's an attempt to extract and interpret the information based on the typical structure of such submissions, acknowledging that explicit "acceptance criteria" might not be numerically stated but rather inferred through comparison to the predicate.
1. Table of Acceptance Criteria and Reported Device Performance
Since explicit "acceptance criteria" are not listed, the table below will present the performance characteristics of the new device (Tina-quant Apolipoprotein A-1 ver.2) and the predicate device as a basis for comparison, implying that the Tina-quant Apolipoprotein A-1 ver.2's performance is considered "acceptable" because it is comparable to or improved over the legally marketed predicate.
| Feature | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (Tina-quant Apolipoprotein A-1 ver.2) |
|---|---|---|
| Precision | ||
| Within run CV | ≤1.5% @ 0.68 g/L; ≤1.0% @ 2.7 g/L | 1.0% @ 0.88 g/L; 0.8% @ 1.64 g/L (Improved) |
| Between Day CV | ≤1.2% @ 0.68g/L; ≤0.78% @ 2.7 g/L | 2.4% @ 0.88 g/L; 1.7% @ 1.64 g/L (Higher for low values, higher for high values) |
| Method Comparison | Correlation coefficient (r) indicative of strong agreement (Predicate: r = 0.993) | y = 0.87x + 0.25 g/L; r = 0.940 (Good, but slightly lower correlation than predicate) |
| Prozone Effect | >5.8 g/L | >6 g/L (Improved) |
| Analytical Sensitivity (LDL) | 0.37 g/L (37mg/dL) | 0.058 g/L (5.8 mg/dL) (Significantly improved/lower detection limit) |
| Limitations (Interference) | No significant interference from Icterus, Hemolysis, Lipemia, Rheumatoid factors | No significant interference from Icterus, Hemolysis, Lipemia (up to 1000 mg/dL Intralipid), Rheumatoid factors (Comparable) |
| Reagent Stability (On-board) | 12 weeks | 4 weeks (Lower than predicate) |
| Measuring Range (with rerun) | 0.12 - 5.6 g/L | 0.10 - 4.0 g/L (Lower upper limit, comparable lower limit) |
Summary of Acceptance: The device is accepted on the basis of "substantial equivalence" to the predicate. The performance data for the Tina-quant Apolipoprotein A-1 ver.2 shows areas of improvement (e.g., precision within run, prozone effect, analytical sensitivity) and areas of minor differences (e.g., between-day CV, reagent stability, measuring range, method correlation) that are deemed acceptable for the intended use.
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). Studies for precision typically use multiple replicates over several days with control materials, while method comparison studies involve a number of patient samples. The values provided for "Method Comparison" (y = 0.87x + 0.25 g/L, r = 0.940) suggest a linear regression analysis, which would require a set of patient samples, but the number is not disclosed.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information (number and qualifications of experts) is typically relevant for diagnostic imaging or subjective interpretation devices. For an in vitro diagnostic (IVD) reagent system like the Tina-quant Apolipoprotein A-1 ver.2, the "ground truth" for the test set values would be established through laboratory reference methods or certified reference materials, rather than expert interpretation. Therefore, this question is not directly applicable in the context of this device.
4. Adjudication Method for the Test Set
As the "ground truth" for this IVD device is based on quantitative measurements and reference methods, not subjective interpretation, no adjudication method (like 2+1 or 3+1 by experts) would be applicable or required.
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
A Multi-Reader Multi-Case (MRMC) study is typically performed for devices that involve human interpretation of images alongside an AI algorithm. The Tina-quant Apolipoprotein A-1 ver.2 is an in vitro diagnostic (IVD) reagent system that automates the quantitative immunological determination of apolipoprotein A-1 in serum and plasma, not an AI-assisted diagnostic imaging device. Therefore, an MRMC study was not performed, and thus, there is no effect size related to human readers improving with AI assistance. This question is not applicable to the described device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the performance characteristics provided (Precision, Method Comparison, Prozone Effect, Analytical Sensitivity, Limitations) are all reflective of the standalone performance of the Tina-quant Apolipoprotein A-1 ver.2 reagent system operating on the COBAS Integra Clinical Chemistry Analyzers. There is no human interpretation or intervention in the measurement process beyond standard laboratory operating procedures and maintenance.
7. The Type of Ground Truth Used
The ground truth used for evaluating the performance characteristics would be:
- Certified Reference Materials/Control Materials: For precision and analytical sensitivity, the device's measurements are compared against known concentrations in control materials.
- Validated Reference Methods: For method comparison, the device's results are compared against results obtained from a predicate device or a well-established, commercially available system, which would themselves be validated against reference methods. While "pathology" or "outcomes data" are not directly used as ground truth for this device's performance, the clinical utility of Apolipoprotein A-1 measurements is linked to "diagnosis and treatment of lipid disorders and atherosclerosis," implying that the measurements are expected to correlate with relevant clinical states.
8. The Sample Size for the Training Set
The document describes a reagent system and its performance characteristics rather than a machine learning model that requires a "training set." Therefore, the concept of a "training set" in the context of AI/ML is not applicable here. The development of such a system involves empirical testing and optimization but not in the same way as training a neural network.
9. How the Ground Truth for the Training Set was Established
As explained above, the concept of a "training set" in the AI/ML sense is not relevant for this device. The development of such an IVD system involves extensive analytical method development, optimization, and validation using various samples (e.g., patient samples, spiked samples, control materials) to ensure accuracy, precision, and robustness. The "ground truth" during this development would be established through highly accurate reference methods or known concentrations in prepared samples.
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NOV 1 5 2001
013278
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. |
|---|---|
| Submittername, address,contact | Roche Diagnostics Corporation9115 Hague RoadIndianapolis, IN 46250(317) 521-7643 |
| Contact Person: Helen T. Torney | |
| Date Prepared: September 27, 2001 | |
| Device Name | Proprietary name: Tina-quant Apolipoprotein A-1 ver.2 |
| Common name: Apolipoprotein A-1 | |
| Classification name: Alpha-1- lipoprotein immunological test system | |
| DeviceDescription | Human apolipoprotein A-1 forms a precipitate with a specific antiserumwhich is determined turbidimetrically at 340 nm. |
| Intended use | In vitro diagnostic reagent system intended for use on COBAS INTEGRAsystem for the quantitative immunological determination of humanapolipoprotein A-1 in serum and plasma. |
| Indications forUse | For the quantitative determination of apolipoprotein A-1 in serum andplasma. A lipoprotein test system is a device intended to measure lipoproteinin serum and plasma. Lipoprotein measurements are used in the diagnosisand treatment of lipid disorders and atherosclerosis. |
510(k) Summary
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510(k) Summary, Continued
Substantial Equivalence
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 COBAS Integra Tina-quant Apolipoprotein A-1 (K990594).
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 | In vitro diagnostic reagent system intended for use on COBAS INTEGRA system for the quantitative immunological determination of human apolipoprotein A-1 in serum and plasma. | In vitro diagnostic reagent system intended for use on COBAS Integra (analyzer model) for the quantitative immunological determination of human apolipoprotein A-1 in serum and plasma. |
| Indication for Use | For the quantitative determination of apolipoprotein A-1 in serum and plasma. 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. | For the quantitative determination of apolipoprotein A-1 in serum and plasma. 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. |
| Assay Protocol | Immunoturbidimetric | Immunoturbidimetric |
| Instrument | COBAS Integra Clinical Chemistry Analyzers | COBAS Integra Clinical Chemistry Analyzers |
| Traceability / Standardization | Standardized with regard to the WHO/IFCC reference material SP1-01. | Standardized with regard to the WHO/IFCC reference material SP1-01. |
| Sample Type | Serum and plasma | Serum and plasma |
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510(k) Summary, Continued
| Feature | Tina-quant ApolipoproteinA-1 ver.2 | Apolipoprotein A-1(predicate) |
|---|---|---|
| CalibrationInterval | After each lot | After each lot |
| Formulation | R: TRIS buffer,polyethylene glycol.detergent, preservative(liquid).SR: Anti-apolipoprotein A-1antibody (sheep) specific forhuman Apo A-1, TRISbuffer, preservative (liquid). | R: Anti-apolipoprotein A-1T antiserum (rabbit) specificfor human Apo A-1, inphosphate buffer stabilizedwith 0.09% sodium azide invial A (liquid). |
Substantial equivalence differences
The following table compares the Tina-quant Apolipoprotein B ver.2 Assay with the predicate device.
| Feature | Tina-quant ApolipoproteinA-1 ver.2 | Apolipoprotein A-1(predicate) |
|---|---|---|
| ReagentStability | On board: 4 weeks | On-board: 12 weeks |
| Calibrator | C.f.a.s. Lipids | Apolipoprotein T Standard |
| Controls | Precinorm L, Precipath L | Apolipoprotein T Control |
| Expected | Females:1.08-2.25 g/L | Females: 1.10-2.05g/L |
| Values | Males: 1.04-2.02 g/L | Males: 1.10-1.80 g/L |
| Measuring | 0.20 - 4.0 g/L | 0.37-4.0 g/L |
| Range | (0.10 - 4.0 g/L with rerun) | (0.12 - 5.6 g/L with rerun) |
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510(k) Summary, Continued
Substantial equivalence performance characteristics The performance characteristics of the Tina-quant Apolipoprotein A-1 ver.2 I he performance characterice are compared in the table below.
| Feature | Tina-quant ApolipoproteinA-1 ver.2 | Apolipoprotein A-1(predicate) |
|---|---|---|
| Precision | Within run CV1.0% @ 0.88 g/L0.8% @ 1.64 g/LBetween Day CV2.4% @ 0.88 g/L1.7% @ 1.64 g/L | Within run CV1.5% @ 0.68 g/L1.0% @ 2.7 g/LBetween Day CV1.2% @ 0.68g/L0.78% @ 2.7 g/L |
| MethodComparison | Bablok/Passing:Tina-quant ApolipoproteinA-1 ver.2 (Y) / COBASIntegra Apolipoprotein A-1(X).y = 0.87x + 0.25 g/Lr = 0.940 | Bablok/Passing:Apolipoprotein A-1 (Y)/commercially availablesystem (X).y = 1.19x- 0.2 g/Lr = 0.993 |
| Prozone Effect | >6 g/L | >5.8g/L |
| Analyticalsensitivity (LDL) | 0.058 g/L (5.8 mg/dL) | 0.37 g/L (37mg/dL) |
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Premarket Notification, 510(k) for Tina-quant Apolipoprotein A-1 ver. 2 Test System on COBAS Integra Clinical Chemistry
Analyzers, continued
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 significantinterference• Hemolysis: Nosignificant interference• Lipemia: No significantinterference up to anIntralipid level of 1000mg/dL• Rheumatoid factors: Nosignificant interference | • Icterus: No significantinterference• Hemolysis: Nosignificantinterference• Lipemia: Nosignificantinterference• Rheumatoid factors:No significantinterference |
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Image /page/5/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three horizontal lines extending from its head, resembling wings or feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the emblem.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Helen Torney Regulatory Submissions, Centralized Diagnostics Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457
Re: K013278
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 27, 2001 Received: October 1, 2001
Dear Ms. Torney:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your betermined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for ass stated in the encreated of 76 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, de frees that have been require approval of a premarket approval application (PMA). and Costietle Fror (110) that the device, subject to the general controls provisions of the Act. The r ou may ; iferences mixes of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
NOV 1 5 2001
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it If your device is classinod (soo as controls. Existing major regulations affecting your device can may be subject to back adder addess, 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 that I Dri has made a and regulations administered by other Federal agencies. You must or any I oderal blacked and st 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 (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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Page 2 -
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 nothleation. The I Dri Imaling of castin 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 II you desire specific articles from astic devices), please contact the Office of Compliance at additionally 607.10 for mile ar questions on the promotion and advertising of your device, (201) 594-1566. Tracksonally (194-4639. 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 Information on your responsibilities are at its toll-free number (800) 638-2041 or Manufacturers International met address "http://www.fda.gov/cdrb/dsma/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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KD13278
Indications for Use Statement
NOV 1 5 2001
510(k) Number (if known): N/A
Device Name: Tina-quant Apolipoprotein A-1 ver.2
Indications For Use:
In vitro diagnostic reagent system intended for use on COBAS INTEGRA system for the quantitative immunological determination of human apolipoprotein A-1 in serum and plasma.
For the quantitative determination of apolipoprotein A-1 in serum and plasma. 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)
Looges
(Divisio -Off)
Division: Lanical Laboratory Devices
510(k) Number: K013278
§ 866.5590 Lipoprotein X immunological test system.
(a)
Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis of obstructive liver disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.