(178 days)
Immunoturbidometric assay for the quantitative in-vitro determination of Haptoglobin.
Immunological latex agglutination test for the in vitro quantitative determination of haptoglobin in human scrum and plasma.
Mcasurement of haptoglobin may aid in the diagnosis of hemolytic discases in which the red blood cells rupture and release hemoglobin) related to the formation of hemoglobinhaptoglohin complexes and ccrtain kidncy discascs.
The Haptoglobin determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing Haptoglobin is transferred into a TRIS buffer solution (R₁ reagent). In the second step, an aliquot of solution of polyclonal anti-human Haptoglobin antibodies (R₂ reagent) is added to mixture of the first step. The antibody will bind to the Haptoglobin in the sample to form “aggregates” such that the amount of aggregate formed is proportionate to the amount of Haptoglobin 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 Haptoglobin in the sample is directly proportional to the amount of turbidity formed.
The provided document describes the Tina-quant® Haptoglobin Assay, an immunoturbidimetric assay for the quantitative in-vitro determination of Haptoglobin. The document focuses on demonstrating substantial equivalence to a predicate device, the Behring BN® Haptoglobin assay, rather than presenting a standalone study with defined acceptance criteria and subsequent proof.
Therefore, much of the requested information cannot be directly extracted as it pertains to a typical new device validation study with specific acceptance criteria. However, I can provide the available information in the requested format, clearly indicating where data is not available or not applicable based on the provided text.
1. Table of Acceptance Criteria and Reported Device Performance
Note: The document does not explicitly state "acceptance criteria" for the Tina-quant® Haptoglobin Assay in the way a new, independent validation study would. Instead, it presents performance characteristics and compares them to a predicate device to demonstrate substantial equivalence. The "acceptance criteria" are implied to be the comparable performance to the predicate device.
| Feature | Implicit Acceptance Criteria (based on predicate device) | Reported Tina-quant® Haptoglobin Performance |
|---|---|---|
| Precision | Comparable Intra and InterAssay %CV to predicate. | Intra-Assay: |
| - Pool (N=21): Mean 167.1, %CV 2.5 | ||
| Inter-Assay: | ||
| - Sample 1 (N=21): Mean 27.9, %CV 2.0 | ||
| Lower Detection Limit | No specific predicate value provided. | 5 mg/dL |
| Linearity | No specific predicate value provided. | 20 - 570 mg/dL |
| Method Comparison (vs. Behring BN® Haptoglobin) | Should show strong correlation (r close to 1) and agreement (slope near 1, intercept near 0). | Deming's: |
| - y = 0.998x + 2.7 | ||
| - r = 0.982 | ||
| - SEE = 10.97 | ||
| - N = 98 | ||
| Least Squares: | ||
| - y = 0.981x + 5.5 | ||
| - r = 0.982 | ||
| - SEE = 15.36 | ||
| - N = 98 | ||
| Interfering Substances | No interference with common substances at clinically relevant levels. | No interference (≤ 10% error) at: |
| - Bilirubin 60 mg/dL | ||
| - Hemoglobin 500 mg/dL | ||
| - Lipemia 1500 mg/dL | ||
| - Rheumatoid Factor 2000 IU/mL | ||
| Specificity | Specific for haptoglobin. | Specific for haptoglobin |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Precision (Intra-Assay): N=21 for both Pool (low) and Pool (high). The document mentions "N=21" for the Tina-quant® Intra-Assay; for the Behring BN®, it states "N=30", implying 30 replicates.
- Precision (Inter-Assay): N=21 for Sample 1, N/A for Sample 2 for Tina-quant®. The Behring BN® reports "N=10" for Sample 1 and 2. It's unclear if Sample 1 and Sample 2 for Tina-quant® represent independent samples or duplicates run over 21 days for example.
- Method Comparison: N=98 for the comparison between Tina-quant® Haptoglobin and Behring BN® Haptoglobin.
- Data Provenance: Not explicitly stated. Given the manufacturer's location in the USA and the FDA submission, it's highly likely the studies were conducted in the USA, but no specific country of origin is mentioned. The studies appear to be prospective for the purpose of this submission (i.e., data was collected specifically to demonstrate device performance).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
Not applicable. This is an in-vitro diagnostic assay that measures a specific analyte (Haptoglobin) quantitatively. The "ground truth" for such devices is typically established through reference methods or highly accurate comparative methods, not expert consensus. The comparison is made against existing commercial devices (Behring BN® Haptoglobin and Partigen® Haptoglobin).
4. Adjudication Method for the Test Set
Not applicable. As this is an in-vitro diagnostic assay measuring an analyte, there is no expert adjudication process in the traditional sense. The "adjudication" is essentially the statistical analysis comparing the new device's results to the predicate device's results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. This is an automated in-vitro diagnostic assay, not an imaging device or a diagnostic tool requiring human interpretation of cases. Therefore, an MRMC study is not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this is a standalone device. The performance characteristics (precision, linearity, method comparison, interfering substances, specificity) are reported for the Tina-quant® Haptoglobin Assay itself, without human-in-the-loop performance influencing the quantitative result. The device automates the measurement process.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" for the performance evaluation is established by:
- Comparison to a legally marketed predicate device: Behring BN® Haptoglobin assay.
- Comparison to another established method: Partigen® Haptoglobin (for linear regression).
- Internal validation metrics: Precision, linearity, interfering substances, and specificity are evaluated against internal standards or clinically accepted ranges/thresholds for these parameters.
8. The Sample Size for the Training Set
Not applicable. This document describes an in-vitro diagnostic assay, which is a chemical/biological reaction-based system, not a machine learning algorithm that requires a "training set" in the context of AI.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of device.
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Boehringer Mannheim Corporation Laboratory Diagnostics 2400 Bisso Lane
PO Box 4117
PO Box 4117
Concord CA 94524-4117 USA
Telephone: +1 (510) 674 0667 Fax: +1 (510) 674 1680
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JAN - 9 1000
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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 Corporation135 Sandberg StreetThousand Oaks, CA 91360(805) 241 - 7575Contact Person: Mary KoningDate Prepared: July 13, 1997 |
|---|---|
| ---------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
| 2.Device name | Proprietary name: Tina-quant® Haptoglobin AssayCommon name: Immunoturbidometric assay for the determination of Haptoglobin.Classification name: Haptoglobin immunological test system |
|---|---|
| ------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| 3.Predicate device | The Boehringer Mannheim Tina-quant® Haptoglobin is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Behring BN® Haptoglobin assay. |
|---|---|
| ------------------------ | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
Continued on next page
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510(k) Summary, Continued
| 4.DeviceDescription | The Haptoglobin determination is based upon turbidimetric immunoinhibition(TINIA) using a serum or plasma blood sample. The sample containingHaptoglobin is transferred into a TRIS buffer solution (R₁ reagent). In thesecond step, an aliquot of solution of polyclonal anti-human Haptoglobinantibodies (R₂ reagent) is added to mixture of the first step. The antibody willbind to the Haptoglobin in the sample to form “aggregates” such that theamount of aggregate formed is proportionate to the amount of Haptoglobinpresent in the sample.The resulting agglutination complex is measured turbidimetrically wherebyincreased turbidity is reflected through an increase in optical density.Therefore, the amount of Haptoglobin in the sample is directly proportionalto the amount of turbidity formed. |
|---|---|
| 5.Intended use | Immunoturbidometric assay for the quantitative in-vitro determination ofHaptoglobin. |
| 6.Comparisonto predicatedevice | The Boehringer Mannheim Tina-quant® Haptoglobin is substantiallyequivalent to other products in commercial distribution intended for similaruse. Most notably it is substantially equivalent to the currently marketedBehring BN® Haptoglobin assay. |
| Continued on next page |
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510(k) Summary, Continued
- Comparison to predicate device cont.
The following table compares the Tina-quant® Haptoglobin with the The following table compares the Tima quain o suy. Specific data on the predicate device, Deliming DNG Traptograted into the draft labeling in performance of the test have occh moorporated in attachment 6.
Similarities:
•Intended Use: Immunoassay for the in vitro quantitative determination of Haptoglobin
•Sample type: Serum and plasma
| Differences: | ||
|---|---|---|
| Feature | Tina-quant® Haptoglobin | Behring BN® Haptoglobin |
| Reaction testprinciple | Immunoturbidimetric | Latex bound antigen/antibodycausing visible agglutinationthrough large immune complexformation. |
| Instrumentrequired | Hitachi | Behring Nephelometer (BN) |
The Co
Performance Characteristics:
| Feature | Tina-quant® Haptoglobin | Behring BN® Haptoglobin |
|---|---|---|
| Precision | Intra and InterAssay (ng/ml): | Intra and InterAssay (mg/dL): |
| Level | Pool | |
| Low | ||
| High | ||
| N | 21 | 30 |
| Intra-Assay Mean | 167.1 | 188 |
| %CV | 2.5 | 2.5 |
| Level | Sample 1 | |
| Sample 2 | ||
| N | 21 | 10 |
| Inter-Assay Mean | 27.9 | 185 |
| %CV | 2.0 | 3.0 |
| Lower Detection Limit | 5 mg/dL | --- |
Continued on next page
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510(k) Summary, Continued
Performance Characteristics:
Comparison to predicate device, (cont.)
| Feature | Tina-quant® Haptoglobin | Behring BN®Haptoglobin |
|---|---|---|
| Linearity | 20 - 570 mg/dL | --- |
| MethodComparison | Vs Behring BN®HaptoglobinDeming's$y =0.998x + 2.7$$r=0.982$$SEE=10.97$$N=98$Least Squares:$y = 0.981x + 5.5$$r = 0.982$$SEE = 15.36$$N = 98$ | Vs Partigen® HaptoglobinLinear Regression$y =1.01x - 11$$r=0.96$$N=30$ |
| Interferingsubstances | No interference at:(≤ 10% error)Bilirubin 60 mg/dLHemoglobin 500 mg/dLLipemia 1500 mg/dLRheumatoidFactor 2000 IU/mL | --- |
| Specificity | Specific for haptoglobin | Specific for haptoglobin |
Continued on next page
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JAN - 9 1998
Ms. Mary Koning Regulatory Affairs Specialist Boehringer Mannheim Corporation 135 Sandberg Street Thousand Oaks, California 91360
Re : K972639/S1 Trade Name: Tina-quant® Haptoglobin Assay Requlatory Class: II Product Code: DAD Dated: October 20, 1997 Received: October 22, 1997
Dear Ms. Koning:
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 Requlation (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 requlation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. 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 Requlations.
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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 requlation 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): K972639
Device Name: Tina-quant® Haptoglobin Assay
Indications For Usc:
Intendcd usc
Immunological latex agglutination test for the in vitro quantitative determination of haptoglobin in human scrum and plasma.
Mcasurement of haptoglobin may aid in the diagnosis of hemolytic discases in which the red blood cells rupture and release hemoglobin) related to the formation of hemoglobinhaptoglohin complexes and ccrtain kidncy discascs.
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) |
Peter E. Maksim
(Line Sign-Off) ratory Devices KA72639
(Division Sign-Off)
Division of Clinical Labor
510(k) Number
§ 866.5460 Haptoglobin immunological test system.
(a)
Identification. A haptoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the haptoglobin (a protein that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and release hemoglobin) related to the formation of hemoglobin-haptoglobin complexes and certain kidney diseases.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.