(75 days)
This test system is for in vitro diagnostic use for the detection of antineutrophil cytoplasmic antibody in human serum. This test system is to be used as an aid in the detection of antibodies associated with autoimmune vasculitis, Wegener's granulomatosis, microscopic polyarteritis, and idiopathic crescentic glomerulonephritis.
This is an indirect fluorescent antibody test for the semi-quantitative detection of antineutrophil cytoplasmic antibody in human serum
This document describes the Immuno Concepts Antineutrophil Cytoplasmic Antibody (ANCA) Test System with Ethanol Fixed Human Neutrophils. The study aims to demonstrate substantial equivalence to a legally marketed predicate device, the NOVA Lite™ ANCA test system (K961340).
Here's an analysis of the provided information:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to a predicate device and the desired performance metrics for an ANCA test system. While explicit pass/fail criteria are not stated as numerical cut-offs, the goal is to show the new device performs comparably or better than the predicate, especially when a more definitive "reference method" (ELISA for MPO/PR3 antibodies) is considered.
| Metric (vs. Predicate Device, without reference method) | Acceptance Criteria (Implied: Comparable to Predicate) | Immuno Concepts ANCA Performance |
|---|---|---|
| Relative Sensitivity | N/A | 72.3% |
| Relative Specificity | N/A | 77.1% |
| Overall Agreement | N/A | 74.6% |
| Metric (vs. Reference Method) | Acceptance Criteria (Implied: High Sensitivity & Specificity) | Immuno Concepts ANCA Performance | NOVA Lite™ ANCA Performance (Predicate) |
|---|---|---|---|
| Relative Sensitivity | N/A | 98.4% | 85.8% |
| Relative Specificity | N/A | 93.1% | 74.9% |
| Overall Agreement | N/A | 95.5% | 79.8% |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set 1 (Normal Blood Donors): 497 serum samples. Retrospective. Provenance not explicitly stated, but implies general population.
- Test Set 2 (Previously Determined ANCA Positive): 383 serum samples. Retrospective. Provenance: Reference laboratories in the USA, the United Kingdom, and Australia.
- Test Set 3 (Patients with Known Vasculitides): 102 samples. Retrospective. Provenance: Not explicitly stated, but implies clinical settings where vasculitis diagnoses are made.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly state the number of experts or their qualifications for establishing the initial ANCA positivity for the "Previously Determined ANCA Positive" samples. However, it mentions samples were obtained from "reference laboratories," implying that these labs, with their inherent expertise, had already categorized the ANCA status using "in-house IFA assays."
For the "Patients with Known Vasculitides" set, the ground truth was "clinically characterized vasculitides," which would involve diagnosis by medical specialists (e.g., rheumatologists, nephrologists) based on clinical presentation, laboratory findings, and potentially biopsy results. The number and specific qualifications of these clinicians are not provided.
4. Adjudication Method for the Test Set
- Discrepant Samples in Normal Blood Donor Set: For initial discrepancies between the subject device and predicate device, a "referee method" was used: ELISA for MPO and PR3 antibodies and Immuno Concepts HEp-2 ANA Test System for ANA.
- Discrepant Samples in Previously Determined ANCA Positive Set: For discrepancies between the subject device and predicate device, the "referee method" was ELISA for MPO and PR3 antibodies.
This indicates a form of adjudication where a third, more specific test (ELISA/ANA) was used to resolve disagreements or clarify the true status of samples, thereby refining the "ground truth" for those specific samples.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No multi-reader multi-case (MRMC) comparative effectiveness study was mentioned. The study compares the performance of the device and a predicate device (and a reference method) on a set of samples. It does not evaluate the improvement of human readers with AI assistance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, this was a standalone study. The device, an indirect fluorescent antibody test system, is evaluated for its ability to detect ANCA antibodies. It's an assay performed in a laboratory, and the results are interpreted directly from the test system's output (fluorescence patterns and intensity). There is no "human-in-the-loop" AI component described; the device is the diagnostic tool being assessed.
7. Type of Ground Truth Used
Multiple types of "ground truth" were used and evolved:
- Initial Classification:
- Normal Blood Donors: Implied negative status based on donor population.
- Previously Determined ANCA Positive: "In-house IFA assays" from reference laboratories.
- Patients with Known Vasculitides: "Clinically characterized vasculitides" (clinical diagnosis).
- Refined Ground Truth / Reference Method: For discrepant samples, ELISA for Myeloperoxidase (MPO) and Proteinase 3 (PR3) antibodies, and Immuno Concepts HEp-2 ANA Test System for Antinuclear Antibodies (ANA) were used as a more definitive "reference method" to establish the true ANCA status. The final performance metrics are presented against this refined reference method.
8. Sample Size for the Training Set
The document does not provide any information about a "training set." This type of 510(k) submission, typical for in vitro diagnostic (IVD) devices that are not based on machine learning or AI algorithms, focuses on analytical and clinical performance studies for device validation rather than algorithm training.
9. How the Ground Truth for the Training Set Was Established
Since no training set is discussed, the method for establishing its ground truth is not applicable.
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Image /page/0/Picture/1 description: The image shows the logo for Immuno Concepts. The logo consists of two horizontal lines on the left, followed by the letters "IC" in a stylized font. To the right of the "IC" is the word "immuno" stacked on top of the word "concepts", both in a bold, sans-serif font. The logo is black and white.
FEB - 9 1998
- 510(k) SUMMARY *
Date Prepared: November 24, 1997 Contact Person: Eric S. Hoy, Ph.D. Name of Device:
- Trade Name Immuno Concepts Antineutrophil Cytoplasmic Antibody Test System with Ethanol Fixed Human Neutrophils
- · Common Name Immuno Concepts ANCA Test System with Ethanol Fixed Human Neutrophils
- · Classification Name Antineutrophil Cytoplasmic Antibody (21 CFR 866.5660)
Legally marketed device with which this device has been shown to be equivalent: NOVA Lite™ ANCA, INOVA Diagnostics, San Diego, CA, K961340
Description:
This is an indirect fluorescent antibody test for the semi-quantitative detection of antineutrophil cytoplasmic antibody in human serum
Intended Use:
This test system is for in vitro diagnostic use for the detection of antineutrophil cytoplasmic antibody in human serum. This test system is to be used as an aid in the detection of antibodies associated with autoimmune vasculitis, Wegener's granulomatosis, microscopic polyarteritis, and idiopathic crescentic glomerulonephritis.
Summary of Technological Characteristics Compared to the Predicate Device:
Both the predicate device and this device are fluorescent antibody tests for the detection of antineutrophil cytoplasmic antibody in human serum.
Description of Laboratory Data That Indicate Substantial Equivalence: Serum Samples Obtained from Normal Blood Donors
Serum samples from 497 blood donors (247 males and 250 females) were tested using the subject device and the predicate device. The results of this comparison are shown in the following Table:
| Predicate Device | |||
|---|---|---|---|
| Positive | Positive | Negative | |
| Immuno Concepts ANCA | Negative | 47 | 23 |
| Negative | 124 | 303 |
The large number of ANCA positive samples in these otherwise normal individuals was troubling, so we tested all positive sera for antibodies (ANA) using Immuno Concepts HEp-2 ANA Test System, and for antibodies to MPO and PR3 using ELISA kits obtained from elias usa, inc. Twenty-two samples were found to have antinuclear antibodies and were considered uninterpretable for ANCA. Excluding these samples, we obtained the following data for the normal blood donor samples:
| Predicate Device | ||
|---|---|---|
| Positive | Negative | |
| Immuno Concepts ANCA | 41 | 18 |
| 113 | 303 |
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Among the remaining discrepant samples, only one was found to be positive for MPO and PR3 antibodies. This sample and the samples that were IFA positive on both the predicate device and the antibodies. This sample and the samplos that were in A positive of the IFA kits. The remaining samples in the l subject define were considered that positive assays. Thus, when the referee method is taken into account, the comparisons look like this:
| Reference Method | |||
|---|---|---|---|
| Positive | Negative | ||
| Immuno Concepts ANCA | Positive | 42 | 17 |
| Immuno Concepts ANCA | Negative | 0 | 416 |
| NOVA Lite™ ANCA | Positive | 42 | 112 |
| NOVA Lite™ ANCA | Negative | 0 | 321 |
Serum Samples Previously Determined to be Positive for ANCA by Indirect Immunofluorescence
Serum samples which had been judged to be positive for ANCA using in-house IFA assays were obtained from reference laboratories in the USA, the United Kingdom, and Australia. A total of 383 sera, which we expected to be positive for ANCA, were examined in this part of the study. These samples were tested on the predicate device and the subject device with the following results:
| Predicate Device | |||
|---|---|---|---|
| Positive | Positive | Negative | |
| Immuno Concepts ANCA | Negative | 283 | 76 |
| 11 | 13 |
The discrepant samples were tested for MPO and PR3 antibodies by ELISA. When this referee method was taken into account, the comparisons showed the following data:
| Reference Method | |||
|---|---|---|---|
| Positive | Negative | ||
| Immuno Concepts ANCA | Positive | 338 | 15* |
| Negative | 6 | 18 | |
| Reference Method | |||
| Positive | Negative | ||
| NOVA Lite TM ANCA | Positive | 289 | 5 |
| Negative | 55 | 28* |
- Six samples were atypical pANCA patterns from patients with inflammatory bowel disease, and were excluded from these data.
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Combining the data from the normal blood donor population and the expected positive samples, we Ombining the bata from the normal blood doner population and the site and the predicate device:
| Predicate Device | |||
|---|---|---|---|
| Positive | Positive | Negative | |
| Immuno Concepts ANCA | Negative | 124 | 316 |
Relative sensitivity : 72.3% Relative specificity: 77.1% Overall agreement: 74.6%
Taking into account the results of the specific MPO and PR-3 testing, the two tests yield the following data:
| Reference Method | |||
|---|---|---|---|
| Positive | Negative | ||
| Immuno Concepts ANCA | Positive | 380 | 32 |
| Negative | 6 | 434 | |
| Reference Method | |||
| Positive | Negative | ||
| NOVA Lite™ ANCA | Positive | 331 | 117 |
| Negative | 55 | 349 |
count: T For NOVA Lite™ ANCA: For Immuno Concepts ANCA: Relative sensitivity : 85.8% Relative sensitivity : 98.4% Relative specificity: 74.9% Relative specificity: 93.1% Overall agreement: 79.8% Overall agreement: 95.5%
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Serum Samples From Patients With Known Vasculitides
.
Samples obtained from 102 patients with clinically chracterized vasculitides were tested using the Immuno Concepts ethanol fixed neutrophils. The results of this comparison are shown in the following Table:
| Clinical Diagnosis | Number | Positive | Staining Pattern (Ethanol Fixed) |
|---|---|---|---|
| Wegener'sgranulomatosis | 30 | 26 (86.7%) | all cANCA |
| Polyarteritisnodosa | 12 | 8 (66.7%) | all pANCA |
| Microscopicpolyarteritis | 20 | 18 (90.0%) | all pANCA |
| Churg-StraussSyndrome | 3 | 2 (66.7%) | one pANCA; one both pANCA andcANCA |
| Immune ComplexCrescentic Glomerulonephritis | 15 | 10 (66.7%) | all pANCA |
| Inflammatory BowelDisease | 22 | 17 (77.3%) | all atypical pANCA |
In accordance with 21 CFR 807.92(b)(3), we conclude from these data that the present device is
substantially ocuivelopt to the prodicate dovice substantially equivalent to the predicate device.
..
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle head with three curved lines forming the head and beak. The eagle faces right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
FFR - 9
Eric S. Hoy, Ph.D. Chief Scientific Officer Immuno Concepts Incorporated 9779 "I" Business Park Drive Sacramento, California 95827
Re : K974478 Immuno Concepts ANCA Test System with Ethanol Trade Name: Fixed Human Neutrophils Regulatory Class: II Product Code: мов November 24, 1997 Dated: Received: November 26, 1997
Dear Dr. Hoy:
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 reqistration, 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 Regulation (QS) for Medical Devices: General requlation (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 requlatory action. In addition, FDA may publish further announcements 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 Requlations.
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Page 2
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 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 Butman
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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Page of
510(k) Number (if known):_19974478
Device Name:Immuno_Concepts_ANCA_Test System with Ethanol fixed Human Neutrophils Indications For Use:
This is an in vitro diagnostic test system for the detection and semi-quantitation of antineutrophil cytonlasmic antibodies in human serum. This test system is to be used as an aid in the detection of antibodies associated with autoimmune vasculitis, Wegener's granulomatosis, microscopic polyarteritis, and idionathic crescentic glomerulonephritis.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
| Concurrence of CDRH, Office of Device Evaluation (ODE) | |
|---|---|
| (Division Sign-Off) | |
| Division of Clinical Laboratory Devices | |
| 510(k) Number |
Prescription Use ✓ (Per 21 CFR 801.109)
OR
Over-The-Counter Use __
(Optional Format 1-2-96)
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).