The EUROIMMUN ANA Screen ELISA (IgG) is intended for the qualitative determination of IgG class antibodies against nuclear antigens (mixture of dsDNA, histones, ribosomal P-proteins, rRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1 and centromeres) in human serum and plasma (EDTA, Li-heparin, Citrate). It is used as an aid in the diagnosis of mixed connective tissue diseases (MCTD), systemic lupus erythematosus, Sjögren's syndrome, progressive systemic sclerosis and polymyositis and dermatomyositis, in conjunction with other laboratory and clinical findings.

Device Description

The EUROIMMUN ANA Screen ELISA (IgG) consists of a microwell ELISA plate coated with a mixture of dsDNA, histones, ribosomal P proteins, nRNP/Sm, Sm, SS-A, SS-B, Scl-70. Jo-1 and centromeres antigens, calibrator, positive and negative control, peroxidaselabeled anti-human IgG conjugate, sample buffer, wash buffer concentrate, TMB chromogen/substrate solution and stop solution.

AI/ML Overview

The EUROIMMUN ANA Screen ELISA (IgG) is a qualitative enzyme immunoassay used to detect IgG class antibodies against nuclear antigens. This device is intended as an aid in diagnosing various connective tissue diseases.

Here's an analysis of its acceptance criteria and supporting studies:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the EUROIMMUN ANA Screen ELISA (IgG) are demonstrated through its analytical performance (precision/reproducibility, analytical specificity) and comparison studies (method comparison with predicate device, matrix comparison, and clinical studies for sensitivity and specificity). The reported device performance meets these criteria, supporting its substantial equivalence to a legally marketed predicate device.

Acceptance Criteria Category	Specific Metric	Acceptance Criteria (Implied by Study Results)	Reported Device Performance
Precision/Reproducibility	Intra-Assay Reproducibility (% positive/% negative)	Consistent qualitative results (100% positive or 100% negative) for samples across 20 determinations.	Achieved 100% positive or 100% negative calls for all 22 samples tested.
	Inter-Assay Reproducibility (% positive/% negative)	Consistent qualitative results (100% positive or 100% negative) for samples across 30 determinations in 10 runs over 5 days.	Achieved 100% positive or 100% negative calls for all 22 samples tested.
	Lot-to-Lot Reproducibility (% positive/% negative)	Consistent qualitative results (100% positive or 100% negative) for samples across different lots.	Achieved 100% positive or 100% negative calls for all 19 QC samples across different lots, with ranges like 0.1-2.0 for a negative sample (mean 0.15) and 2.7-3.2 for a positive sample (mean 2.9).
Analytical Specificity	Cross-reactivity (Celiac, Wegener's, RA, Infectious)	No significant cross-reactivity (implying very few positive results in known negative samples).	All but 2 out of 82 samples (10 celiac disease, 17 Wegener's granulomatosis, 39 rheumatoid arthritis, 16 infectious diseases) were negative. This demonstrates high specificity.
	Interference (Hemoglobin, Triglycerides, Bilirubin, RF)	Recovery of 90-110% for positive/borderline samples when spiked with interfering substances.	Recoveries for positive/borderline samples were within 92-107% for hemoglobin (up to 1000 mg/dl), triglycerides (up to 2000 mg/dl), and bilirubin (up to 40 mg/dl). Recoveries were 100-110% for rheumatoid factor (up to 500 IU/ml). No significant interference observed.
Method Comparison (vs. Predicate)	Overall Agreement	High overall agreement with the predicate device (Aesku Aeskulisa ANA Hep-2).	Overall Agreement: 97.2% (282/290) with 95% C.I.: 94.6% - 98.8%.
	Positive Agreement	High positive agreement with the predicate device.	Positive Agreement: 96.5% (137/142) with 95% C.I.: 92.0% - 98.8%.
	Negative Agreement	High negative agreement with the predicate device.	Negative Agreement: 98.0% (145/148) with 95% C.I.: 94.2% - 99.6%.
Matrix Comparison	Equivalence of serum and plasma	Regression equation near ideal (intercept 0; slope 1.0) and coefficient of determination (R2) > 0.99, mean %recovery 90-110%.	EDTA plasma: y = 0.04 + 0.99 x, R2 = 0.9988, Mean %recovery = 103% (Range: 98-112%) Li-heparin plasma: y = -0.04 + 1.00 x, R2 = 0.9992, Mean %recovery = 99% (Range: 90-109%) Citrate plasma: y = -0.00 + 0.99 x, R2 = 0.9990, Mean %recovery = 98% (Range: 95-104%) (All within acceptable limits).
Clinical Performance	Overall Clinical Sensitivity	Overall clinical sensitivity for various connective tissue diseases, with specific ranges for each disease, demonstrating the test's ability to detect antibodies in affected patients.	Overall Sensitivity: 72.5% (311/429) With 95% C.I.: 68.0 - 76.7%. Specific sensitivities: MCTD (95.2%), SLE (73.2%), Polymyositis/Dermatomyositis (15.4%), Systemic Sclerosis (72.8%), Sjögren's Syndrome (81.8%). The lower sensitivity for Poly-/dermatomyositis might be noted but isn't explicitly an "acceptance criteria failure" as overall sensitivity is presented.
	Overall Clinical Specificity	High overall clinical specificity across different control/non-ANA disease groups, showing the test's ability to correctly identify unaffected individuals.	Overall Specificity: 95.8% (296/309) with 95% C.I.: 92.9 - 97.7%. Specific specificities: Celiac disease (100.0%), Wegener's granulomatosis (94.1%), Rheumatoid arthritis (94.1%), Other autoimmune diseases (100.0%), Bacterial/viral infections (100.0%).

2. Sample Size Used for the Test Set and Data Provenance

Method Comparison Study (vs. Predicate):
- Sample Size: 290 clinically characterized samples (158 from patients with connective tissue diseases and 132 from control groups).
- Data Provenance: The origin of the data (e.g., country) is not explicitly stated. The study used samples from "different sources," and given it's a 510(k) submission to the FDA, it is likely that parts of the study, especially clinical correlation, would involve US data or data from regions with equivalent clinical standards. It is explicitly indicated as retrospective as the samples were "obtained from different sources".
Clinical Sensitivity and Specificity Studies:
- Sample Size:
  - Clinical Sensitivity: 429 samples from patients with various connective tissue diseases.
  - Clinical Specificity: 309 samples from control groups (celiac disease, Wegener's granulomatosis, rheumatoid arthritis, other autoimmune diseases, bacterial/viral infections).
  - Total: 738 clinically characterized samples.
- Data Provenance: Clinical studies were performed "in cooperation with different sites." The specific countries are not mentioned. This part of the study is retrospective, as it used "clinically characterized samples" which implies they were collected and characterized prior to the study.
Analytical Specificity (Cross-reactivity):
- Sample Size: 82 clinically and serologically characterized samples (10 celiac, 17 Wegener's, 39 RA, 16 infectious diseases).
- Data Provenance: Not specified, but these are identified as "clinically and serologically characterized samples," suggesting retrospective collection.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not explicitly state the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") used to establish the "ground truth" for the test set.

Instead, the ground truth for the clinical studies relies on:

"clinically characterized samples from patients" for patients with mixed connective tissue diseases, systemic lupus erythematosus, Sjögren's syndrome, progressive systemic sclerosis, and polymyositis/dermatomyositis.
"clinically characterized samples" for various control groups.

This implies that the samples were classified based on established clinical diagnostic criteria, likely involving a consensus of medical specialists (e.g., rheumatologists) and potentially other laboratory findings, but the process of "ground truthing" itself is not detailed as an expert review process for each case.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1, none) for discrepancies in the test set.

For the method comparison study, it notes that "The discrepant samples were from controls and one MCTD sample in the cut-off range." It does not specify how these discrepancies were resolved or adjudicated beyond this observation.
For clinical sensitivity and specificity, the samples were "clinically characterized," suggesting their diagnostic status was pre-established, rather than determined by a real-time adjudication process during the study.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This submission is for an in vitro diagnostic device (ELISA kit), which is a laboratory test, not an imaging diagnostic device that typically involves human readers interpreting images. Therefore, the concept of human readers improving with AI vs. without AI assistance is not applicable here.

6. Standalone Performance Study

Yes, a standalone performance study was done.
The entire submission details the standalone performance of the EUROIMMUN ANA Screen ELISA (IgG) through its analytical performance characteristics (precision, analytical specificity, interference) and clinical performance (sensitivity and specificity) when run as an algorithm-only (kit-only) test. The results are reported as the device's inherent capability to detect ANA antibodies and correlate with clinical disease.

7. Type of Ground Truth Used

The ground truth used for both the method comparison and clinical studies was based on:

Clinical Characterization: Samples were derived from "clinically characterized patients" and "control groups." This means the diagnosis of the patients (e.g., systemic lupus erythematosus, Sjögren's syndrome) and the health status of controls were established through standard clinical diagnostic procedures, likely involving a combination of clinical symptoms, physical examination, and other laboratory or imaging tests, according to medical guidelines.
Serological Characterization: For the cross-reactivity study, samples were "clinically and serologically characterized," indicating that their antibody status for other conditions (e.g., celiac disease, ANCA, anti-CCP) was already known.
Predicate Device Comparison: For the method comparison, the predicate device's results served as a comparison point, but the ultimate ground truth for the samples themselves was still their clinical status.

It does not rely on pathology, expert consensus on images (as it's not an imaging device), or direct patient outcomes data as the primary ground truth, but rather on established clinical diagnoses.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI development. This device is an ELISA kit, which is a chemical assay, not an AI/ML algorithm that requires a training set in the conventional sense. The performance characteristics are established through validation studies using defined sample cohorts, not through an iterative training process.

9. How the Ground Truth for the Training Set Was Established

As noted above, the concept of a "training set" is not applicable to this type of device. The ground truth for the samples used in the validation studies was established through:

Clinical Characterization: As described in point 7, samples were from patients with established clinical diagnoses and controls, determined through standard medical practice.
External Reference Panels/Characterized Samples: The reproducibility studies used samples with "expected results" (negative or positive), and analytical specificity studies used "clinically and serologically characterized samples" or CDC ANA reference panels. This indicates that these samples were pre-defined with known characteristics based on previous clinical and/or laboratory evaluations.

Summary

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510(k) SUMMARY

A. 510(k) Number:

K131185

B. Purpose for Submission:

New device

C. Measurand:

Anti-Nuclear Antibodies

D. Type of Test:

Qualitative enzyme immunoassay

E. Applicant:

EUROIMMUN US INC.

F. Proprietary and Established Names:

EUROIMMUN ANA Screen ELISA (IgG)

G. Regulatory Information:

1. Regulation section:
  21 CFR 866.5100 – Anti-Nuclear Antibody immunological test system
1. Classification:
  Class II
1. Product code:
  LJM
1. Panel:
  Immunology

JUL 1 5 2013

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H. Intended Use:

1.Intended use(s):

The EUROIMMUN ANA Screen ELISA (IgG) is intended for the qualitative determination of IgG class antibodies against nuclear antigens (mixture of dsDNA, histones, ribosomal P-proteins, rRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1 and centromeres) in human serum and plasma (EDTA, Liheparin, Citrate). It is used as an aid in the diagnosis of mixed connective tissue diseases (MCTD), systemic lupus erythematosus, Sjögren's syndrome, progressive systemic sclerosis and polymyositis and dermatomyositis, in conjunction with other laboratory and clinical findings.

1. Indication(s) for use:
  Same as intended use.

3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

Microwell plate reader capable of measuring OD at 450nm and at 620nm for dual wavelength readings.

I. Device Description:

J. Substantial Equivalence Information:

1. Predicate device name(s): Aesku Aeskulisa ANA Hep-2
1. Predicate 510(k) number(s): K081104
1. Comparison with predicate:

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Similarities
Item	Device	Predicate
Intended Use	Detection of IgG antibodies to nuclear antigens	Same
Assay Format	Qualitative	Same
Technology	ELISA	Same
Assay Platform	96-well microtiter plates	Same
Calibration	Relative evaluation	Same
Conjugate	Anti-human IgG labeled with horseradish peroxidase	Same
Substrate	TMB	Same
Procedure	Sample incubation with micro-well antigen coated plate, followed by a wash step, incubation with an anti-human IgG enzyme conjugate; wash step, incubation with substrate; then the addition of a stop solution and reading at 450nm.	Same
Reported Results	OD Ratio	Same
Cut-Off Level	Ratio 1.0	Same

Item	Device	Predicate
Antigen Mixture	dsDNA, histones, ribosomal P proteins, nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, centromeres	dsDNA, histones, SS-A (Ro), SS-B (La), Sm, snRNP/Sm, Scl-70, Jo-1 and centromeric antigens and lysed HEp-2 cells
Calibrators & Controls	1 calibrator2 controls: 1 positive, 1 negative	3 controls: 1 positive, 1 cut-off (used for calculation of results), 1 negative
Sample Buffer	Ready for use	5x concentrate
Wash Buffer	10x concentrate	50x concentrate
Stop Solution	0.5 M sulphuric acid	1 M hydrochloric acid
Sample Types	Serum or plasma (EDTA, Li-heparin, Citrate)	Serum
Sample Dilution	1:201	1:101

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K. Standard/Guidance Document Referenced (if applicable):
Guidance for Industry and FDA Staff: Recommendations for Anti-Nuclear Antibody (ANA) Test System Premarket (510(k)) Submissions (January 22, 2009)

L. Test Principle:

Patient samples are diluted 1:201 in sample buffer, 100 µl of each diluted patient sample and pre-diluted controls and calibrator are added to the antigen mixture coated microtiter wells and incubated for 30 minutes at room temperature. After incubation the microtiter well strips are washed with wash buffer to remove unbound antibodies and 100 µl of the anti-human IgG enzyme conjugate reagent is added to each microtiter well. After an additional 30minutes incubation at room temperature, the microtiter wells are again washed 3 times with 300 ul of wash buffer to remove any unbound enzyme conjugate and 100 µl of the chromogen substrate is added. The strips are incubated for 15 minutes at room temperature and 100 ul stop solution is added. The microtiter plates are placed in an ELISA reader and read at a wavelength of 450 nm and a reference wavelength of between 620 nm and 650 nm within 30 minutes.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

The reproducibility of the test was investigated using sera with different concentrations. Intra-assay reproducibility is based on 20 determinations and interassay reproducibility on 30 determinations performed in 10 different runs on 5 days with 2 runs per day, each run performed with 3 replicates according to the package insert. The following results were obtained:

n = 16 - 20	ANA Screen ELISA (IgG) Ratio
	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Sample 6	Sample 7	Sample 8
Mean Value (x):	0.3	0.9	1.1	2.5	6.1	7.4	0.1	2.4
Range of Values:	0.2 - 0.3	0.8 - 0.9	1.0 - 1.2	2.3 - 2.6	5.8 - 6.3	7.1 - 7.7	0.1 - 0.2	2.0 - 2.8
Expected Result:	Negative	Negative	Positive	Positive	Positive	Positive	Negative	Positive
% positive:	0%	0%	100%	100%	100%	100%	0%	100%
% negative:	100%	100%	0%	0%	0%	0%	100%	0%
	Sample 9	Sample 10	Sample 11	Sample 12	Sample 13	Sample 14	Sample 15	Sample 16
Mean Value (x):	4.3	1.0	3.2	2.2	5.6	2.3	2.2	4.3
Range of Values:	3.9 - 4.6	0.9 - 1.0	3.0 - 3.5	2.0 - 2.5	4.9 - 6.2	2.1 - 2.5	2.0 - 2.5	4.0 - 4.8
Expected Result:	Positive	Positive	Positive	Positive	Positive	Positive	Positive	Positive
% positive:	100%	100%	100%	100%	100%	100%	100%	100%
% negative:	0%	0%	0%	0%	0%	0%	0%	0%
	Sample 17	Sample 18	Sample 19	Sample 20	Sample 21	Sample 22
Mean Value (x):	1.6	7.4	2.0	4.6	2.0	8.1
Range of Values:	1.4 - 1.8	6.8 - 7.8	1.8-2.2	4.2 - 5.0	1.9-2.1	7.4-8.8
Expected Result:	Positive	Positive	Positive	Positive	Positive	Positive

Intra-Assay Reproducibility

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n = 16 - 20	ANA Screen ELISA (IgG) Ratio
	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Sample 6	Sample 7	Sample 8
% positive:	100%	100%	100%	100%	100%	100%
% negative:	0%	0%	0%	0%	0%	0%

n = 30	ANA Screen ELISA (IgG) Ratio
	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Sample 6	Sample 7	Sample 8
Mean Value (x):	0.6	0.9	1.1	2.7	6.0	7.6	0.2	2.4
Range of Values:	0.5 - 0.7	0.7 - 1.0	1.0 - 1.2	2.5 - 3.0	5.4 - 6.4	7.2 - 8.0	0.1 - 0.3	1.6 - 3.1
Expected Result:	Negative	Negative	Positive	Positive	Positive	Positive	Negative	Positive
% positive:	0%	0%	100%	100%	100%	100%	0%	100%
% negative:	100%	100%	0%	0%	0%	0%	100%	0%
	Sample 9	Sample 10	Sample 11	Sample 12	Sample 13	Sample 14	Sample 15	Sample 16
Mean Value (x):	4.1	1.0	2.8	1.7	4.7	1.9	1.7	4.0
Range of Values:	3.3 - 4.9	0.8 - 1.2	2.0 - 3.5	1.1 - 2.2	4.2 - 5.6	1.1 - 3.3	1.1 - 2.2	3.4 - 4.8
Expected Result:	Positive	Positive	Positive	Positive	Positive	Positive	Positive	Positive
% positive:	100%	100%	100%	100%	100%	100%	100%	100%
% negative:	0%	0%	0%	0%	0%	0%	0%	0%
	Sample 17	Sample 18	Sample 19	Sample 20	Sample 21	Sample 22
Mean Value (x):	1.4	6.9	2.3	5.2	2.1	8.5
Range of Values:	1.1 - 2.0	5.7 - 8.0	1.6 - 2.7	3.0 - 6.6	1.8 - 2.6	6.9 - 9.8
Expected Result:	Positive	Positive	Positive	Positive	Positive	Positive
% positive:	100%	100%	100%	100%	100%	100%
% negative:	0%	0%	0%	0%	0%	0%

Inter-Assay Reproducibility

The lot to lot reproducibility was investigated during the validation and quality control of the kit using different lots with QC samples distributed over the measurement range. The following results were obtained:

*3 lots x 2 runs	ANA Screen ELISA (IgG) Ratio
** n lots x 1 run
	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Sample 6	Sample 7	Sample 8
n:	11**	11**	11**	6*	6*	6*	6*	6*
Mean Value (x):	0.15	2.9	7.1	0.2	2.1	3.7	1.1	3.1
Range of Values:	0.1-2.0	2.7-3.2	6.8-7.8	0.1-0.2	1.9-2.4	3.4-4.3	1.0-1.2	3.0-3.2
Expected Result:	negative	positive	positive	negative	positive	positive	positive	positive
% positive:	0%	100%	100%	0%	100%	100%	100%	100%
% negative:	100%	0%	0%	100%	0%	0%	0%	0%
	Sample 9	Sample 10	Sample 11	Sample 12	Sample 13	Sample 14	Sample 15	Sample 16
n:	6*	6*	6*	6*	6*	6*	6*	6*
Mean Value (x):	2.0	4.8	2.3	2.0	3.9	1.5	6.0	2.0
Range of Values:	1.5-2.3	4.4-5.7	1.9-2.7	1.5-2.2	3.7-4.2	1.4-1.5	5.3-7.4	1.9-2.1
Expected Result:	positive	positive	positive	positive	positive	positive	positive	positive
% positive:	100%	100%	100%	100%	100%	100%	100%	100%
% negative:	0%	0%	0%	0%	0%	0%	0%	0%
	Sample 17	Sample 18	Sample 19
n:	6*	6*	6*
Mean Value (x):	6.0	1.9	8.5
Range of Values:	4.4-6.8	1.8-2.0	8.1-8.7
Expected Result:	positive	positive	positive
% positive:	100%	100%	100%

Lot to Lot Reproducibility

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3 lots x 2 runs* n lots x 1 run	ANA Screen ELISA (IgG) Ratio
	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Sample 6	Sample 7	Sample 8
% negative:	0%	0%	0%

b. Linearity/assay reportable range:
Not applicable.
c. High Dose Hook Effect
Potential for a high dose Hook effect is a phenomenon that is inherent with one step "sandwich" assay designs: Very high concentrations of antigen in the patient sample bind to all available sites - saturating them - on both the antibody-solid phase and the antibody-labeled conjugate and thereby prevent the "sandwich" formation. Under these conditions, the measured level of analyte may be significantly lower than the actual level present in the sample. The two-step immunoassay design of the ANA Screen ELISA (IgG) eliminates the adverse contribution of binding proteins, endogenous interfering substances and general matrix effects due to the extra wash step.
d. Traceability, Stability, Expected values (controls, calibrators, or methods):
A recognized standard or reference material for anti-nuclear antibodies is not available. Results of this assay are given in ratios. The reactivity of the ANA Screen ELISA (IgG) was verified using the CDC ANA reference panel.
Detection limit: e.
Not applicable.
Analytical specificity: f.
Cross-reactivity: The quality of the antigen mixture coated on the plates (containing the antigens nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, dsDNA, histones, ribosomal P-proteins and centromeres) ensures a high specificity of the ELISA. Cross reactivity was investigated using a total of 82 clinically and serologically characterized samples (10 celiac disease for antibodies against gliadin and tissue transglutaminase, 17 Wegener's granulomatosis for ANCA, 39 rheumatoid arthritis for antibodies against CCP and 16 infectious diseases antibody positive samples). All except of 2 samples were negative in the ANA Screen ELISA (IgG), so no cross reactivity is expected.

Interference: To investigate the influence from hemoglobin, triglycerides and bilirubin, 4 different specimens at different ANA concentrations (ratio 0.5 - 7.3) were spiked with potential interfering substances and were incubated with the test system. The recovery in relation to the unspiked sample without interferent was calculated. The individual recovery of the positive or borderline samples was within the range of

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92 - 107 %. No significant interference was observed for concentrations of up to 1000 mg/dl for hemoglobin, 2000 mg/dl for triglyceride and 40 mg/dl for bilirubin. Furthermore, the influence from rheumatoid factor was investigated by spiking of 6 different speciments with a rheumatoid factor positive material (characterized nephelometrically). The recovery in relation to the original sample (not spiked) was calculated. The recoveries were found within 100 - 110%. No interference was observed with rheumatoid factor up to 500 IU/ml.

Assay cut-off: f.
Ratio 1.0
1. Comparison studies:
- Method comparison with predicate device: a.

A comparison study was performed using 158 clinically characterized samples from patients (49 MCTD, 37 systemic lupus erythematosus, 37 Sjögren's syndrome, 19 systemic sclerosis, 16 myositis) and 132 from control groups (10 celiac disease, 17 Wegener's granulomatosis, 39 rheumatoid arthritis, 16 infectious disease and 50 healthy), obtained from different sources. The panel consisted of 101 men and 174 women (and 14 unknown). Age ranged from 7 to 87 years with an average age of 46 years (15 unknown). The samples were tested with the EUROIMMUN ANA Screen ELISA (IgG) and with the Aesku Aeskulisa ANA Hep-2 as the predicate device. The results are shown in the table below. The discrepant samples were from controls and one MCTD sample in the cut-off range.

n = 290
	Predicate ELISA
	positive	negative
EUROIMMUNANA Screen ELISA(IgG)	positive	137	3
	negative	5	145

Negative Agreement	145	/	148	=	98.0%	95% C.I.:	94.2%	-	99.6%
Positive Agreement	137	/	142	=	96.5%	95% C.I.:	92.0%	-	98.8%
Overall Agreement	282	/	290	=	97.2%	95% C.I.:	94.6%	-	98.8%

Matrix comparison: b.
The usability of plasma was investigated using sample pairs each of serum and corresponding plasma (EDTA, Li-heparin, Citrate). Passing-Bablok regression was calculated for the comparison of serum to plasma. The regression equation is near the ideal correlation (intercept 0; slope 1.0) indicating equivalence of concentrations between serum and the corresponding plasma matrices. Coefficients of determination were found to be above 0.99 and %recovery compared to serum was in the range of 90 to 112 % (serum = 100 %).

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	EDTA plasma	Li-heparin plasma	Citrate plasma
n	12	12	12
Regression Equation: (y = plasma, x = serum)	y = 0.04 + 0.99 x	y = -0.04 + 1.00 x	y = -0.00 + 0.99 x
95% C.I. of intercept	-0.02 - 0.13	-0.10 - 0.01	-0.02 - 0.05
95% C.I. of slope	0.96 - 1.02	0.98 - 1.03	0.95 - 1.00
Coefficient of determination R2	0.9988	0.9992	0.9990
Mean %recovery	103 %	99 %	98 %
Range of %recovery	98 - 112 %	90 - 109 %	95 - 104 %

3. Clinical studies:

a. Clinical Sensitivity:

Clinical studies were performed in cooperation with different sites. In total 738 clinically characterized samples were investigated for anti-nuclear antibodies (IgG). The EUROIMMUN ANA Screen ELISA (IgG) showed an overall sensitivity of 72.5% (95% C.I.: 68.0 - 76.7%) and a specificity of 95.8% (95% C.I.: 92.9 - 97.7%). The results are shown in the table below. 95% C.I. are calculated by the exact method.

No.	Panel	n	positive	%	95% C.I.
1	Mixed connective tissue diseases	21	20	95.2%	76.2 - 99.9%
2	Systemic lupus erythematosus	213	156	73.2%	66.8 - 79.1%
3	Poly-/dermatomyositis	26	4	15.4%	4.4 - 34.9%
4	Systemic sclerosis	81	59	72.8%	61.8-82.1%
5	Sjögren's syndrome	88	72	81.8%	72.2 - 89.2%
	Total	429	311	72.5%	68.0 – 76.7%

Clinical specificity: b.
.

No.	Panel	n	ANA Screen ELISA (IgG)
			negative	%	95% C.I.
6	Celiac disease	10	10	100.0%	69.2-100.0%
7	Wegener's granulomatosis	17	16	94.1%	71.3-99.9%
8	Rheumatoid arthritis	203	191	94.1%	89.9-96.9%
9	Other autoimmune diseases*	63	63	100.0%	94.3 -100.0%
10	Bacterial/viral infections	16	16	100.0%	79.4-100.0%
	Total	309	296	95.8%	92.9-97.7%

*from the following groups: AlH (n = 8), PBC (n = 9), Grave's disease (n = 12), Hashimoto (n = 11), celiac disease (n = 11), Diabetes Type I (n = 12)

c. Other clinical supportive data (when a. and b. are not applicable):

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Not applicable.

1. Clinical cut-off:
  See Assay Cut-Off.

5. Expected values/Reference range:

The levels of ANA (IgG) were analyzed in a panel of 200 samples from apparently healthy blood donors (120 men and 80 women with an average age of 40 y; age range: 19 - 68 y). The results are shown in the table below.

n	200
Positives	6
Negatives	194
Prevalence	3.0%
	Ratio
Lowest Value	0.1
Highest Value	4.5
Mean Value	0.2

Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Michael Locke

Signature

July 15, 2013 Michael Locke/Director of Regulatory Affairs Date Printed Name/Title

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Image /page/9/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Bambshire Avenue Document Control Center - WO66-G60 Silver Spring, MI) 20993-0002

EUROIMMUN US.INC C/O MR. MICHAEL LOCKE DIRECTOR, REGULATORY AFFAIRS 1100 THE AMERICAN ROAD MORRIS PLAINS NJ 07960

July 15, 2013

Re: K131185

Trade/Device Name: ANA Screen ELISA (IgG) Regulation Number: 21 CFR 862.1660 Regulation Name: Antinuclear Antibody Immunological Test System Regulatory Class: II Product Code: LJM Dated: April 24, 2013 Received: April 26, 2013

Dear Mr. Locke:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate 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) that do not require approval of a premarket approval application (PMA). 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. Please note: CDRH docs not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, 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 by Federal statues and regulations administered by other Federal agencies. You must or any with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Scctions 531-542 of the Act); 21 CFR 1000-1050.

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Page 2-Mr. Michael Locke

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.hum. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resources/or You/Industry/default.htm.

Sincerely yours,

Maria M. Chan -S

Maria M. Chan, Ph. D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K131185

EUROIMMUN ANA-Screen ELISA (IgG) Device Name:

Indications For Use:

The EUROIMMUN ANA Screen ELISA (IgG) is intended for the qualitative determination of IgG class antibodies against nuclear antigens (mixture of dsDNA, histones, ribosomal P-proteins, rRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1 and centromeres) in human serum and plasma (EDTA, Li-heparin, Citrate). It is used as an aid in the diagnosis of mixed connective tissue diseases (MCTD), systemic lupus erythematosus, Sjögren's syndrome, progressive systemic sclerosis and poly-/dermatomyositis, in conjunction with other laboratory and clinical findings.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(Please Do NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH; Office of In Vitro Diagnostics and Radiological Health (OIR)

Maria M. Chan -S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

K131185 510(k):

Regulation Number and Section

§ 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).