(64 days)
The Tinaquant Rheumatoid Factor assay is an immunoturbidometric assay for the quantitative determination of rheumatoid factor (antibodies to immunoglobulins) in human serum or plasma using automated clinical chemistry analyzers. Measurement of rheumatoid factor may be used as an aid in the diagnosis of rheumatoid arthritis.
The Rheumatoid Factor determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing rheumatoid factor is transferred into a buffer solution (R1 reagent). In the second step, an aliquot of solution containing fine latex particles coated with polyclonal human IgG (anti-human rheumatoid factor antibodies - R2 reagent) is added to mixture of the first step. The antibody-coated particles will bind to the rheumatoid factor in the sample to form "aggregates" such that the amount of aggregate formed is proportionate to the amount of rheumatoid factor 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 rheumatoid factor in the sample is directly proportional to the amount of turbidity formed.
The provided document, K971379, describes the Tina-quant® Rheumatoid Factor Assay, an immunoturbidometric assay for the quantitative determination of rheumatoid factor in human serum or plasma.
The document primarily focuses on demonstrating substantial equivalence to a predicate device, the Behring Laser Rf Test - Rheumatoid Factor (S) Reagents (K850296), by comparing performance characteristics. This is typical for 510(k) submissions, which aim to show that a new device is as safe and effective as a legally marketed predicate device, rather than establishing de novo clinical utility or fulfilling pre-defined acceptance criteria in the same way a novel high-risk device might.
Here's an analysis based on the structure provided in the request:
1. A table of acceptance criteria and the reported device performance
For a 510(k) submission, "acceptance criteria" are typically implied by demonstrating performance comparable to a predicate device across various metrics. The document does not explicitly state pre-defined acceptance criteria with pass/fail values. Instead, it presents performance characteristics of the Tina-quant® Rheumatoid Factor Assay and compares them directly to the predicate device.
| Feature | Predicate Device: Laser Rf Test - Rheumatoid Factor (S) Reagents | Tina-quant® Rheumatoid Factor Assay (Reported Performance) |
|---|---|---|
| Precision - Intra-Assay | Low: 52 IU/mL (4.2-6.1% CV) | Sample 1: 31.9 IU/mL (3.8% CV) |
| Mid: 201 IU/mL (4.2-6.1% CV) | Sample 2: 144.4 IU/mL (1.4% CV) | |
| High: 510 IU/mL (4.2-6.1% CV) | Sample 3: 645.1 IU/mL (1.1% CV) | |
| Precision - Inter-Assay | 92 IU/mL (9.3% CV) | Sample 1: 76.4 IU/mL (2.6% CV) |
| 155 IU/mL (6.2% CV) | Sample 2: 347.4 IU/mL (2.2% CV) | |
| 306 IU/mL (6.6% CV) | ||
| Lower Detection Limit | 10 IU/mL | 7.5 IU/mL |
| Linearity | 10 - 600 IU/mL | 7.5 - 140 IU/mL |
| Method Comparison | Vs NA Latex RF Kit: | Vs Behring Laser Nephelometer RF: |
| (Regression Analysis) | y = 0.90x - 20, r=0.975, SEE = 44.9, N=72 | Passing/Bablok: y=1.01x-2.30, r=0.880, SEE=11.20, N=35 |
| Least Squares: y = 0.90x + 5.11, r = 0.880, SEE = 15.32, N = 35 | ||
| Interfering Substances | Bilirubin: not tested | Bilirubin: 30 mg/dL (≤ 10% error) |
| Hemoglobin: 2 g/dL | Hemoglobin: 20 g/L (≤ 10% error) | |
| Lipemia: not tested | Lipemia: 2000 mg/dL (≤ 10% error) |
2. Sample size used for the test set and the data provenance
- Precision (Intra & Inter-Assay):
- Intra-Assay: N=21 for each of 3 samples.
- Inter-Assay: Sample N is not explicitly stated for inter-assay precision, but "Level Sample 1 Sample 2" suggests 2 samples were tested. The "N" value (21, 21, 21) under Intra-Assay likely refers to replicates per run, not separate patient samples in the context of clinical validation.
- Method Comparison: N=35 samples were used for the comparison against the Behring Laser Nephelometer RF.
- Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given the nature of an immunoassay, the samples would typically be clinical specimens.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The Tina-quant® Rheumatoid Factor Assay is a quantitative in-vitro diagnostic device that measures Rheumatoid Factor levels. Its performance is evaluated through analytical studies (precision, linearity, method comparison, interference), not by human expert interpretation of images or clinical cases that would require expert-established ground truth. Therefore, this section is not applicable. The "ground truth" for this device is the actual concentration of rheumatoid factor, determined by a reference method or known concentrations in control materials.
4. Adjudication method for the test set
Not applicable, as this device performs quantitative measurements and does not involve human interpretation or adjudication for its analytical performance evaluation.
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 assay for measuring a biomarker, not an AI-assisted diagnostic imaging device that involves human readers.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
This refers to the performance of the analytical instrument and reagents (the "device") by itself, without human interpretation for making a diagnostic decision. The entire performance characteristic section (precision, lower detection limit, linearity, method comparison, interfering substances) is essentially a standalone performance study. The device provides a quantitative result (IU/mL) directly.
7. The type of ground truth used
For analytical performance studies:
- Precision: Based on repeated measurements of control materials or patient samples with stable concentrations. The "ground truth" here is the expected mean value of the control or sample.
- Lower Detection Limit: Established through statistical methods using known low-concentration samples or blank samples.
- Linearity: Assessed by analyzing samples with serially diluted or spiked known concentrations across the claimed range, comparing measured values to expected values.
- Method Comparison: The "ground truth" is established by the results obtained from a legally marketed predicate device or a recognized reference method (in this case, the Behring Laser Nephelometer RF).
8. The sample size for the training set
This document does not describe a "training set" in the context of machine learning or AI development. For an in-vitro diagnostic assay, the development and verification typically involve:
- Reagent formulation and optimization: This involves numerous experiments with various reagents and concentrations.
- Assay parameter optimization: Determining optimal reaction conditions for the instrument.
- Validation studies: The studies described in the performance characteristics section (precision, linearity, etc.) serve as the validation of the finalized assay.
Therefore, a specific "training set" sample size as understood in AI/ML is not applicable.
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" in the AI/ML sense for this type of IVD device. The development process relies on established chemical and immunological principles, and the analytical performance is validated against known concentrations or reference methods.
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JUN 17 1997
| 510(k) Summary | Image: boehringer logo | |
|---|---|---|
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. | |
| 1.Submittername,address,contact | Boehringer Mannheim Corporation2400 Bisso LaneP.O. Box 4117Concord, CA 94524-4117(510) 674 - 0690, extension 8413Fax: (510) 687-1850Contact Person: Yvette LloydDate Prepared: April 8, 1997 | |
| 2.Device name | Proprietary name: Tina-quant® Rheumatoid Factor AssayCommon name: Immunoturbidometric assay for the determination ofRheumatoid Factor.Classification name: Rheumatoid Factor immunological test system | |
| 3.Predicatedevice | The Boehringer Mannheim Tina-quant® Rheumatoid Factor assay issubstantially equivalent to other products in commercial distribution intendedfor similar use. Most notably it is substantially equivalent to the currentlymarketed Behring Laser Rf Test - Rheumatoid Factor (S) Reagents(K850296). |
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10(k) Summary, Continued BOEHRING
Image /page/1/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo consists of a black square with a white circle inside. The word "boehringer" is written in white inside the circle. The word "mannheim" is written vertically in white on the left side of the black square.
The Rheumatoid Factor determination is based upon turbidimetric 4. immunoinhibition (TINIA) using a serum or plasma blood sample. The Device Description sample containing rheumatoid factor is transferred into a buffer solution (R1 reagent). In the second step, an aliquot of solution containing fine latex particles coated with polyclonal human IgG (anti-human rheumatoid factor antibodies - R2 reagent) is added to mixture of the first step. The antibody-参 coated particles will bind to the rheumatoid factor in the sample to form "aggregates" such that the amount of aggregate formed is proportionate to the amount of rheumatoid factor 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 rheumatoid factor in the sample is directly proportional to the amount of turbidity formed. Immunoturbidometric assay for the quantitative in-vitro determination of ડ. Intended use rheumatoid factor. The Boehringer Mannheim Tina-quant® Rheumatoid Factor assay is 6. Comparison substantially equivalent to other products in commercial distribution intended to predicate for similar use. Most notably it is substantially equivalent to the currently device marketed Behring Laser Rf Test - Rheumatoid Factor (S) Reagents (K850296).
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0(k) Summary, Continued
Image /page/2/Picture/1 description: The image shows a logo with the word "boehringer" inside a circle. To the left of the circle, the word "mannheim" is written vertically. The logo is black and white and appears to be a company logo.
- Comparison to predicate device cont.
参
The following table compares the Tina-quant® Rheumatoid Factor with the predicate device, Behring Laser Rf Test - Rheumatoid Factor (S) Reagents. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device is provided in attachment 6.
Similarities:
•Intended Use: Immunoassay for the in vitro quantitative determination of Rheumatoid Factor.
·Sample type: Serum and plasma
Differences:
| Feature | Tina-quant® RheumatoidFactor | Laser Rf Test - RheumatoidFactor (S) Reagents |
|---|---|---|
| Reaction testprinciple | Immunoturbidimetric | Laser Nephelometry |
| Instrumentrequired | Hitachi 717 | Behring Laser Nephelometer |
Performance Characteristics:
| Feature | Tina-quant® RheumatoidFactor | Laser Rf Test - RheumatoidFactor (S) Reagents |
|---|---|---|
| Precision | Intra and InterAssay (IU/mL): | Intra and Interassay (IU/mL): |
| Level | Sample 1 Sample 2 Sample 3 | Low Mid High |
| N | 21 21 21 | 20 20 20 |
| Intra-Assay Mean | 31.9 144.4 645.1 | 52 201 510 |
| %CV | 3.8 1.4 1.1 | range 4.2 to 6.1% |
| Level | Sample 1 Sample 2 | |
| Inter-Assay Mean | 76.4 347.4 | 92 155 306 |
| %CV | 2.6 2.2 | 9.3 6.2 6.6 |
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BOEHRINGERO(k) Summary, Continued MANNHEIM CORPORATION
Image /page/3/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo is a black square with the word "mannheim" written vertically on the left side. Inside the square is a white circle with the word "boehringer" written horizontally inside the circle.
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Performance Characteristics:
Comparison to predicate device, (cont.)
| Feature | Tina-quant® RheumatoidFactor | Laser Rf Test -Rheumatoid Factor (S)Reagents |
|---|---|---|
| Lower DetectionLimit | 7.5 IU/mL | 10 IU/mL |
| Linearity | 7.5 - 140 IU/mL | 10 - 600 IU/mL |
| MethodComparison | Vs Behring LaserNephelometer RFPassing/Bablok$y=1.01x-2.30$$r=0.880$SEE=11.20N=35Least Squares:$y = 0.90x + 5.11$$r = 0.880$SEE = 15.32N = 35 | Vs NA Latex RF KitRegression:$y =0.90x - 20$$r=0.975$SEE =44.9N=72 |
参
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BOEHRINGER O(k) Summary, Continued MANNHEIM CORPORATION
Image /page/4/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo consists of a black square with a white circle inside. The word "boehringer" is written in black inside the white circle. The word "mannheim" is written vertically on the left side of the black square.
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Comparison to predicate device, (cont.)
参
Performance Characteristics:
| Feature | Tina-quant® RheumatoidFactor | Laser Rf Test - RheumatoidFactor (S) Reagents |
|---|---|---|
| Interferingsubstances | No interference at:(≤ 10% error) | No interference at: |
| BilirubinHemoglobinLipemia | 30 mg/dL20 g/L2000 mg/dL | not tested2 g/dLnot tested |
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Image /page/5/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 words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling a stylized caduceus or a representation of the human form, composed of three curved lines.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUN | 7 1997
Ms. Yvette Lloyd Regulatory Affairs Specialist Boehringer Mannheim Corporation 2400 Bisso Lane ………………………… Concord, California 94524-4117
K971379 Re:
Trade Name: Tina-quant® Rheumatoid Factor Reagents 编 Regulatory Class: II Product Code: DHR Dated: April 8, 1997 Received: April 14, 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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP 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 annovacements 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.
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.
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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 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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510(k) Number (if known): N/A
Device Name: Tina-quant® Rheumatoid Factor Assay
Indications For Use:
ું કુંદર
The Tinaquant Rheumatoid Factor assay is an immunoturbidometric assay for the quantitative determination of rheumatoid factor (antibodies to immunoglobulins) in human serum or plasma using automated clinical chemistry analyzers. Measurement of rheumatoid factor may be used as an aid in the diagnosis of rheumatoid arthritis.
Peter S. Magrini
| Concurrence of CDRH, Office of Device Evaluation (ODE) | |
|---|---|
| Prescription Use(Per 21 CFR 801.109) | OR Over-The-Counter Use |
(Optional Format 1-2-96)
§ 866.5775 Rheumatoid factor immunological test system.
(a)
Identification. A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.(b)
Classification. Class II (performance standards).