(253 days)
No
The summary describes a traditional immunofluorescence assay kit and its performance characteristics, with no mention of AI or ML in the device description, intended use, or performance studies. The evaluation is based on visual fluorescence microscopy performed by technicians.
No.
The device is described as an "indirect immunofluorescence antibody test" used "as an aid in the diagnosis of systemic rheumatic diseases," which classifies it as an in vitro diagnostic (IVD) device, not a therapeutic device.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is "used as an aid in the diagnosis of systemic rheumatic diseases."
No
The device description explicitly lists physical components such as BIOCHIPs, reagents, and other materials, indicating it is a hardware-based test system, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is an "indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of antibodies against cell nuclei (ANA) in human serum." This clearly indicates that the device is intended to be used in vitro (outside the body) to examine a sample (human serum) for diagnostic purposes (as an aid in the diagnosis of systemic rheumatic diseases).
- Sample Type: The test is performed on "human serum," which is a biological sample taken from the body.
- Diagnostic Purpose: The test is used "as an aid in the diagnosis of systemic rheumatic diseases." This directly aligns with the definition of an IVD, which is used to provide information for the diagnosis, prevention, or treatment of a disease or condition.
N/A
Intended Use / Indications for Use
The EUROIMMUN IFA 40: HEp-20-10 is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of antibodies against cell nuclei (ANA) in human serum. This test system is used as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other laboratory and clinical findings.
Product codes
DHN
Device Description
The test system consists of BIOCHIPs coated with HEp-20-10 cells. It includes a fluorescein-labeled goat anti-human IgG, a positive and negative control, salt for PBS, Tween 20, embedding medium, cover glasses and instruction booklet. Reagent trays for the TITERPLANE technique are required but ordered separately.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
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Intended User / Care Setting
For Prescription Use Only.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
1. Analytical performance:
a. Precision/Reproducibility:
- Intra-Assay Reproducibility: 10-fold repeated measurements in one run. The results did not exceed the acceptable deviation of fluorescence intensity of +/- 1 intensity level, positive samples were not found negative and vice versa, and the observed patterns did not change.
- Inter-Assay Reproducibility: 20 repeated measurements on 5 different days with 2 runs per day and 2 replicates per run. The results did not exceed the acceptable deviation of fluorescence intensity of +/- 1 intensity level, positive samples were not found negative and vice versa, and the observed patterns did not change.
- Inter-Lot Reproducibility: 6 repeated measurements with 3 different lots, 1 run per lot, 2 replicates per run. The results did not exceed the acceptable deviation of fluorescence intensity of +/- 1 intensity level, positive samples were not found negative and vice versa, and the observed patterns did not change.
- Inter-Observer Reproducibility: Separate independent reading of the Inter-Assay slides by a 2nd technician. The results did not exceed acceptable deviation of fluorescence intensity of +/- 1 intensity level, positive samples were not found negative and vice versa, and the observed patterns did not change. Performed in a US Laboratory setting.
- Semi-quantitative Reproducibility: Measurements of dilutions (1:40 up to 1:40960) of 14 positive samples and a negative sample, covering 7 main patterns. Samples/dilutions were assayed in 4 different runs, with 3 different lots, in duplicates, and evaluated by two different technicians. Results did not exceed +/- 1 intensity level deviation, endpoint titer did not deviate more than +/- 1 titer level, and observed patterns did not change.
b. Linearity/assay reportable range:
- Assayed 6 samples with different combinations of mixed staining patterns serially diluted.
- Mixed patterns were distinguishable in every dilution, and samples showed a decrease in fluorescence intensity with increasing dilution. Pattern did not change with dilution. Acceptable deviation of fluorescence intensity: +/- 1 intensity level.
c. Traceability, Stability, Expected values (controls, calibrators or methods):
- No recognized standard or reference material for Anti-Nuclear Antibodies available.
- Kit includes negative and positive controls. Negative control: 1+ (3-4+) fluorescence intensity.
- Kit stable for 18 months after manufacture if stored properly.
d. Limit of detection:
- Not applicable.
e. Analytical specificity:
- Cross-reactivity: Verified using CDC ANA reference panel. Results align with CDC characterization, except for CDC sample No. 12, which was negative with all three test systems (subject device, K070763, K972145). No significant cross-reactivity with clinical samples positive for ANCA-associated vasculitis, Crohn's disease, ulcerative colitis, celiac disease, and infectious diseases (Chlamydia pneumoniae and Epstein-Barr virus) (10 samples each).
- Interfering substances: Tested spiking 20 clinical samples with hemoglobin (0, 250 & 500 mg/dL), bilirubin (0, 10 & 40 mg/dL), and triglycerides (0, 500 & 2000 mg/dL). Also tested Human Anti-Mouse Antibodies (HAMA) and Rheumatoid Factor (RF). Deviation in fluorescence intensity did not exceed +/- 1. No significant interference observed up to tested concentrations (hemoglobin 1000 mg/dL, bilirubin 40 mg/dL, triglyceride 2000 mg/dL, HAMA, RF).
f. Assay cut-off:
- Recommended starting dilution for positive result is 1:40.
- Prospective study: 138 samples (53 men, 85 women, age range 0-89 years, average 51 years) from routine health screenings. 16/138 samples found positive for ANA, prevalence 11.6% (95% C.I.: 6.8% - 18.6%).
2. Comparison studies:
a. Method comparison with predicate device:
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Qualitative: Cohort of 200 blinded prospective samples (59 men, 141 women, age range 19-89 years, average 52 years) from routine ANA screening. Tested with subject device and predicate (ImmunoConcepts® HEp-2000 ANA-Ro IFA (K972145)) at 1:40 dilution. Visual fluorescence microscopy evaluation by two independent technicians, with a 3rd decisive in case of discrepancy.
- Negative Agreement: 95.5% (128/134); 95% C.I.: 90.5% - 98.3%
- Positive Agreement: 92.4% (61/66); 95% C.I.: 83.2% - 97.5%
- Overall Agreement: 94.5% (189/200); 95% C.I.: 90.4% - 97.2%
- Discrepant results confirmed using FDA cleared assays.
-
Semi-Quantitative/Quantitative: Cohort of 156 blinded prospective samples (62 men, 94 women, age range 19-90 years, average 52 years) from routine ANA screening. Tested with subject device and predicate (ImmunoConcepts® HEp-2000 ANA-Ro IFA (K972145)). Visual fluorescence microscopy evaluation by two independent technicians, with a 3rd decisive in case of discrepancy.
- Negative Agreement: 100.0% (46/46); 95% C.I.: 92.3% - 100.0%
- Positive Agreement: 100.0% (110/110); 95% C.I.: 96.7% - 100.0%
- Overall Agreement: 100.0% (156/156); 95% C.I.: 97.7% - 100.0%
- Overall % Agreement for Observed Patterns: 91.4%
b. Matrix comparison:
- Not applicable.
3. Clinical studies:
- Not Applicable
4. Clinical cut-off:
- See Assay cut-off.
5. Expected values/Reference range:
- A panel of 200 sera from normal healthy adult blood donors (155 men, 45 women, mean age 38 years, age range 18-68 years) from University hospital Lübeck, Germany. Assayed by three technicians.
- Prevalence of ANA was about 3.5%.
- Reference range determined as titer
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).
0
EUROIMMUN:::::US
K1317el1
FEB 2 6 2014
PREMARKET NOTIFICATION 210(K) SAFETY AND EFFECTIVENESS SUMMARY (as required by 21 CFR § 807.92)
A. 510(k)Number: K131791
- B. Purpose for Submission: New device
- C. Measurand: Anti-nuclear autoantibodies (ANA)
- D. Type of Test: Qualitative and/or Semi-Quantitative, indirect immunofluorescence
- E. Applicant: EUROIMMUN US INC.
- F. Proprietary and Established Names: EUROIMMUN IFA 40: HEp-20-10
G. Requlatory Information:
-
- Regulation: 21 CFR 866.5100 - Antinuclear antibody immunological test system
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- Classification: Class II
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- Product code: DHN
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- Panel: Immunology
H. Intended Use:
-
- Intended Use(s):
The EUROIMMUN IFA 40: HEp-20-10 is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of antibodies against cell nuclei (ANA) in human serum. This test system is used as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other laboratory and clinical findings.
- Intended Use(s):
-
- Indication(s) for use: Same as Intended Use.
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- Special conditions for the use statement(s): For Prescription Use Only.
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Special instrument requirements: ব : Fluorescent Microscope: Equipped with a 488 nm excitation filter; 510 nm color separator; & 520 nm blocking filter with a 100 W mercury vapour lamp light source or LED bluelight.
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l. Device Description:
ット ミイスタブ ランドウェスタイル ----------------------------------------------------------------------------------------------------------------------------------------------------------
The test system consists of BIOCHIPs coated with HEp-20-10 cells. It includes a fluorescein-labeled goat anti-human IgG, a positive and negative control, salt for PBS, Tween 20, embedding medium, cover
1.890
PM
N
1
EUROIMMUN
glasses and instruction booklet. Reagent trays for the TITERPLANE technique are required but ordered separately.
Substantial Equivalence Information: J.
- Predicate device name (s): 1. ImmunoConcepts® Hep-2000 ANA-Ro IFA
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- Predicate 510(k) number(s): K972145
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- Comparison with predicate:
Similarities
| Item | New device | Predicate device |
|---|---|---|
| Intended use | Qualitative or semi-quantitative detection of antibodies | |
| against cell nuclei (ANA). The test system is used as an | ||
| aid in the diagnosis of systemic rheumatic diseases, in | ||
| conjunction with other laboratory and clinical findings. | Same | |
| Samples | Serum | |
| 1:40 dilution | Same | |
| Technology | IFA | Same |
| Reagents | Fluorescein | |
| HEp-20-10 cultured cells | Fluorescein | |
| HEp-2000 cultured cells | ||
| Procedure | Standard IFA technique; serum incubation with cells, | |
| followed by a wash step, incubation with fluorescein- | ||
| labelled anti-human globulin, wash step, embedding | ||
| and reading fluorescence with a fluorescence | ||
| microscope. | Same | |
| Cut off level | 1:40 dilution | Same |
| Reported results | qualitative, Titer | Same |
Difforoncos
| Differences | ||
|---|---|---|
| Item | New device | Predicate device |
| Technology | BIOCHIP TITERPLANE technology | |
| HEp-20-10 cells are bound to the BIOCHIPs | Standard IFA technology | |
| HEp-2000 cells are bound to the test wells | ||
| Controls | 1 Positive control | |
| 1 Negative control | 5 Positive controls (one each for the following | |
| patterns: SSA/Ro, homogeneous, speckled, | ||
| nucleolar, centromere) | ||
| 1 Titratable control serum | ||
| 1 Negative control serum | ||
| . |
K. Standard/Guidance Document Referenced (if applicable):
11 - 2014 - 2017 - 2011 - 2011 - 2017 - 2011 - 2011 - 2011 - 2011 - 2011 - 2011 - 2011 - 201
Guidance for Industry and FDA Staff: Recommendations for Antibody (ANA) Test System Premarket (510(k)) Submissions (January 22, 2009)
L. Test Principle:
The principle follows the TITERPLANE technique. Patient samples, controls and in separate steps conjugate and embedding medium are applied to the reaction fields of a reagent tray. The BIOCHIP Slides are then placed into the recesses of the reagent tray, where all BIOCHIPs of the slide come into contact with the fluids, and the individual reactions commence simultaneously. The fluids are confined to the recessed wells eliminating the need to use a conventional "humidity chamber".
Patient samples are diluted 1:40 in PBS-Tween, 30 µl of each diluted patient sample are added to each reaction field of the reagent tray. Reactions are started by fitting the BIOCHIP Slides containing the sections from the substrate (HEp-20-10 cells) into the corresponding recesses of the reagent tray and incubated for 30 minutes at room temperature. Specific antibodies attach to the HEp-20-10 antigens. After incubation the BIOCHIP Slides are washed with PBS-Tween to remove unbound antibodies. In the meantime, 25 ul of fluorescein-labelled anti-human globulin are added to each reaction field of a clean reagent tray and the BIOCHIP Slides placed into the recesses of the tray. After a 30 minutes incubation at room temperature, the BIOCHIPs are again washed with PBS-Tween to remove any unbound fluorescein-labelled reagent. 10 ul of Embedding medium are placed for each reaction field on a cover glass and the BIOCHIP Slides, with the BIOCHIPs facing downwards, placed onto the prepared cover glass. Fluorescence is read with a fluorescence microscope.
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M. Performance Characteristics (where applicable):
-
- Analytical performance:
General: The fluorescence intensity level is the intensity of the specific fluorescence expressed as a numeric value. These values can vary from "0" (no specific fluorescence) to "4+" (strong specific fluorescence). The evaluation of the fluorescence intensity is performed according to the following table:
- Analytical performance:
| Intensity | Evaluation |
|---|---|
| 0 | Negative: No specific fluorescence. |
| 1+ | Positive: weak visible reaction; dim subdued fluorescence. (Cut-off) |
| 2+ | Positive: Moderate visible reaction; green fluorescence. |
| 3+ | Positive: Strong visible reaction; brilliant green fluorescence |
| 4+ | High Positive: Very strong visible reaction; brilliant green (maximal fluorescence). |
A serum dilution is considered negative for ANA antibodies if the cells exhibit 1+ (3-4+). The homogenous pattern of the positive control was confirmed via testing. EUROIMMUN Inc. recommends using the positive and negative controls as stated within the labeling (Instructions for Use).
The EUROIMMUN IFA 40: HEp-20-10 kit is stable for a period of 18 months after the date of manufacture if stored properly. As the composition of the EUROIMMUN IFA 40: HED-20-10 kit is very similar to the EUROIMMUN ANA IFA: Hep-20-10 kit, stability of most components have already been demonstrated in the K070763 510(k) process. Real time stability tests of the "new" component (conjugate) as well as for the entire kit are conducted in accordance with the international standard DIN EN 13640:2002: Stability testing of in vitro diagnostics reagents. Three production lots of all kit reagents are tested.
- d. Limit of detection: Not applicable.
- Analytical specificity: e.
Cross-reactivity: The specificity of the EUROIMMUN IFA 40: HEb-20-10 was verified using the ANA reference panel of the CDC Centers for Disease Control and Prevention, Atlanta, USA. The CDC samples were assaved according to the package insert by the same technician at the same day. The results are in line with the characterization by the CDC with the exception of CDC sample No. 12. This sample was also tested using the EUROIMMUN ANA IFA: HEp-20-10 (K070763) and the ImmunoConcepts® HEp-2000 ANA-Ro IFA (K972145). The sample was found negative with all three test systems.
In addition to the CDC panel, clinical samples positive for ANCA-associated vasculitis, Crohn's disease, ulcerative colitis, celiac disease and infectious diseases (Chlamydia pneumoniae and Epstein-Barr virus) (each 10 samples) were investigated. The results do not indicate any significant cross reactivity.
Interfering substances: The effect of interfering substances on assay results were tested by spiking 20 clinical samples with hemoglobin (0, 250 & 500 mg/dL), bilirubin (0, 10 & 40 mg/dL) and triglycerides (0. 500 & 2000 mg/dL). The samples consisted of negative (1:160; 1 nucleolar, 1:320; & 1 granular, 1:80 [SS-A+ Blot]).
Of the 5 discrepant negative samples: 1 sample was confirmed by blot as negative; 3 samples were reported by Univ. of Penn. as negative; and 1 sample was reported by Univ. of Penn. as speckled/granular and confirmed SS-A positive by blot.
Confirmations were done using FDA cleared assays.
REAL PRODUCTION SERVER FOR AND FOR
Semi-Quantitative/Quantitative: A comparison study was performed using a cohort of 156 blinded prospective samples obtained from patients sent for routine ANA screening, where at minimum age and sex was available. The samples were tested with EUROIMMUN HEP-20-10 IFA 40 concurrently with ImmunoConcepts® HED-2000 ANA-Ro IFA (K972145) (predicate). The panel consisted 62 men and 94 women, average age of 52 yrs, age
5
EUROIMMI
ranged from 19 to 90 yrs. The tests were performed according to the package insert in single determinations. Visual fluorescence microscopy evaluation was performed by two different technicians independently. In case of a discrepant result a 3rd technician would have been decisive.
| | n = 156 | | | ImmunoConcepts®
HEp-2000 ANA-Ro IFA | | |
|--|--------------------------------|------------------|-----------|----------------------------------------|-----|--------|
| | | Positive | Negative | Total | | |
| | EUROIMMUN
IFA 40: HEp-20-10 | Positive | 110 | 0 | 110 | |
| | | Negative | 0 | 46 | 46 | |
| | | Total | 110 | 46 | 156 | |
| | % Negative Agreement | 46/46 = 100.0% | 95% C.I.: | 92.3% | - | 100.0% |
| | % Positive Agreement | 110/110 = 100.0% | 95% C.I.: | 96.7% | - | 100.0% |
| | % Overall Agreement | 156/156 = 100.0% | 95% C.I.: | 97.7% | - | 100.0% |
Pattern agreement is tabulated below. A single staining pattern was seen with 79 samples, and mixed patterns were seen with 31 samples. For the table each was reported individually.
| Observed Patterns | ||||
|---|---|---|---|---|
| Pattern | n | EUROIMMUN | ||
| IFA 40: HEp-20-10 | ImmunoConcepts® | |||
| Hep-2000 Fluorescent ANA-Ro | % Agreement | |||
| Homogenous | 41 | 41 | 41 | 100.0 |
| Granular/Speckled | 28 | 28 | 26 | 92.9 |
| Nucleolar | 24 | 22 | 23 | 87.5 |
| Centromere | 15 | 15 | 15 | 100.0 |
| Nuclear Dot | 9 | 9 | 9 | 100.0 |
| Nuc. Membrane | 3 | 3 | 2 | 66.7 |
| Cytoplasmic | 28 | 26 | 28 | 92.9 |
| Overall % Agreement: | 91.4 |
Comparison of reciprocal titers between the predicate and the new assay is shown below. If multiple patterns were reported, those titers are reported separately:
| |