The EUROIMMUN Anti-M2-3E ELISA (IgG) test kit is intended for the qualitative or semi-quantitative determination of IgG class autoantibodies against the mitochondrial antigens M2 in human serum and plasma. It is used as an aid in the diagnosis of primary billary cirrhosis (PBC), in conjunction with other laboratory and clinical findings.

Device Description

The EUROIMMUN Anti-M2-3E ELISA (IgG) consists of a microwell ELISA plate coated with M2-3E antigen, 3 calibrators, positive and negative control, peroxidase-labelled anti-human IgG conjugate, sample buffer, wash buffer concentrate, TMB chromogen/substrate solution and stop solution.

AI/ML Overview

The provided text describes the performance characteristics of the EUROIMMUN Anti-M2-3E ELISA (IgG) test kit and its comparison to a predicate device and clinical studies. However, it does not explicitly define "acceptance criteria" in a separate section with specific numerical thresholds for each performance metric before presenting the study results. Instead, the "Performance Characteristics" section M presents the study results for analytical and clinical performance.

Based on the information provided, I will infer what constitutes "acceptance criteria" from the reported performance, especially for the "Method comparison with predicate device" and "Clinical studies" sections, where the device needs to show substantial equivalence or good diagnostic accuracy.

1. Table of Acceptance Criteria and Reported Device Performance

Inferred Acceptance Criteria:

Precision/Reproducibility: Intra-assay and Inter-assay CVs < 12% for positive samples. Lot to lot CV < 12% for positive samples.
Linearity/Assay Reportable Range: Observed/Expected (O/E) values in the cut-off should be within 0.8 to 1.2.
Interference: Recovery in relation to unspiked sample should be within 98-123%.
Method Comparison (with predicate): High positive and negative agreement, and high overall agreement with the predicate device. For the 127 samples, overall agreement > 90%
Clinical Sensitivity (for PBC): High sensitivity (e.g., >90%).
Clinical Specificity: High specificity (e.g., >90%) across various control groups.

Reported Device Performance:

Performance Metric	Inferred Acceptance Criteria	Reported Device Performance
Precision/Reproducibility	Intra-assay CVs < 12% for positive samples. Inter-assay CVs < 12% for positive samples. Lot to lot CV < 12% for positive samples.	Intra-assay CV: Mean CV = 4.3% (range 1.6-10.5%). All samples (including positive and low positive/negative) were < 12%. Inter-assay CV: Mean CV = 7.2% (range 3.0-10.3%). All samples (including positive and low positive/negative) were < 12%. Lot-to-lot CV: Mean CV = 6.6% (range 4.5-9.6%). All positive samples were < 12%.
Linearity/Assay Reportable Range	Observed/Expected (O/E) values in the cut-off within 0.8 to 1.2.	Most O/E values were within 0.8 - 1.2. Some values fell below 0.8 (e.g., Sample 3 at 1/32 dilution: 0.7, Sample 1 at 1/32: 0.9, Sample 2 at 1/32: 0.8, Sample 4 at 1/32: 0.8, Sample 5 at 1/32: 0.8). Values highlighted in grey (in the original table) were considered "out of specification," although it's not explicitly stated if this means they failed the acceptance criteria. Given the "up to 1/32" dilution, these might be acceptable for the working range.
Detection Limit	Not explicitly stated as acceptance, but reported as a characteristic.	1.1 RU/ml (determined from 20 replicate determinations of sample buffer). Lowest quantified concentration: 2 RU/ml (lowest calibrator).
Analytical Specificity (Cross-reactivity)	No cross-reactivity with PCA, GBM, LKM positive samples.	29 sera (10 PCA, 10 GBM, 9 LKM positive) were all negative in the Anti-M2-3E ELISA (IgG). No cross-reactivity observed.
Interference	Recovery in relation to unspiked sample within 98-123%.	Individual recovery was within 98 - 123%. No significant interference for hemoglobin (up to 1000 mg/dl), triglyceride (2000 mg/dl), and bilirubin (40 mg/dl).
Method Comparison (Predicate Device)	Overall agreement with predicate > 90%.	Overall agreement: 91.9% (95% C.I.: 85.6% - 96.0%) for 127 samples. Positive agreement: 98.7% (95% C.I.: 93.1% - 100.0%). Negative agreement: 79.5% (95% C.I.: 64.7% - 90.2%).
Matrix Comparison (Serum vs. Plasma)	95% C.I. of slope contains 1.0; 95% C.I. of intercept contains 0.	EDTA plasma: slope 0.98-1.04 (contains 1.0), intercept -1.30-2.75 (contains 0). Heparin plasma: slope 0.96-1.01 (contains 1.0), intercept -1.32-1.11 (contains 0). Citrate plasma: slope 0.98-1.06 (contains 1.0), intercept -1.02-3.18 (contains 0). All conditions satisfied.
Clinical Sensitivity (for PBC)	High sensitivity (e.g., >90%) for PBC.	92.8% (for PBC patients). For PBC/AIH overlap syndrome patients, 100.0%.
Clinical Specificity	High specificity (e.g., >90%) across various control groups.	Overall specificity: 97.4% (95% C.I.: 96.2% - 98.3%) for 929 control samples. (Ranges from 92.0% for SLE to 100.0% for Viral Hepatitis, PSC, and Asymptomatic Blood Donors).
Expected Values (Healthy Donors)	All healthy blood donors negative at cutoff.	200 apparently healthy blood donors were all negative (0 positives) with the 20 RU/ml cutoff.

2. Sample sizes used for the test set and the data provenance

Precision/Reproducibility:
- Intra-assay: 12 unique samples, each tested 20 times.
- Inter-assay: 12 unique samples, each tested 4 times over 6 days (total 24 determinations per sample).
- Lot to Lot: 8 unique samples, each tested across 3 different lots and 2 runs (total 6 determinations per sample).
Linearity: 5 patient sera, each serially diluted up to 1/32, with single determinations.
Analytical Specificity (Cross-reactivity): 29 sera (10 PCA, 10 GBM, 9 LKM positive).
Interference: 5 different specimens at varying Anti-M2-3E concentrations, spiked with potential interfering substances.
Method Comparison with Predicate Device: 127 clinically characterized samples (39 AIH, 49 PBC, 32 AIH/PBC overlap, and 7 created "borderline" samples by mixing) collected at EUROIMMUN UK Ltd. This data appears to be retrospective as samples were already "clinically characterized."
Matrix Comparison: 21 sample pairs of serum and corresponding plasma.
Clinical Studies: 1180 clinically characterized samples (251 from PBC patients and 929 from control groups). The text mentions "performed in cooperation with several university hospitals," suggesting retrospective collection of already diagnosed patient samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not specify the number of experts used to establish the ground truth, nor their qualifications for any of the studies (method comparison or clinical studies). It states samples were "clinically characterized" for the method comparison and "clinically characterized" for the clinical study, but does not detail the process or who performed it.

4. Adjudication method for the test set

The document does not describe any adjudication method for establishing the ground truth for either the method comparison or the clinical studies. Ground truth appears to be based on "clinical characterization" which typically implies diagnosis based on multiple clinical and laboratory findings, but the specific process for confirming these diagnoses is not elaborated.

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

This is not applicable to the provided document. The device is an in vitro diagnostic ELISA test kit, not an AI-assisted diagnostic tool that would involve human readers interpreting images or data with and without AI assistance. The performance is based on the assay's ability to detect autoantibodies.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

Yes, the studies presented are all standalone performance evaluations of the EUROIMMUN Anti-M2-3E ELISA (IgG) test kit. The performance characteristics (analytical and clinical) measure the device's ability to detect specific autoantibodies directly, without human interpretation of the assay's output other than reading the optical density and interpreting the result against the established cutoff.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the clinical studies appears to be based on clinical diagnosis of Primary Biliary Cirrhosis (PBC) and various control conditions. The phrase "clinically characterized samples" implies that these diagnoses were established through a combination of clinical findings, patient history, other laboratory tests, and possibly biopsy/pathology results, as part of routine medical practice at the "several university hospitals." However, specific details like "expert consensus" or "pathology" are not explicitly mentioned as the sole or primary ground truth source.

8. The sample size for the training set

The document does not mention a distinct "training set" in the context of machine learning or algorithm development. The ELISA test kit is a biochemical assay. The "calibrators" are used to establish a calibration curve for quantitative or semi-quantitative results, and "controls" are used for quality assurance, but these are not a "training set" in the AI/ML sense. The product development would involve internal validation and optimization, but specific "training set sizes" are not provided.

9. How the ground truth for the training set was established

As there is no "training set" in the context of an algorithm, this question is not applicable. For the calibrators and controls included in the kit, their "ground truth" (i.e., their known concentration or reactivity level) is established during the manufacturing and quality control processes of the diagnostic kit.

Summary

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EUROIMMUN US INC.

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K092736 ATTACHMENT 1

PREMARKET NOTIFICATION 510(K) SAFETY AND EFFECTIVENESS SUMMARY (as required by 21 CFR § 807.92)

SEP 2 2010

A. 510(k)Number: K092736
B. Purpose for Submission: New device
C. Measurand: Anti-M2-3E autoantibodies
D. Type of Test: Qualitative or semi-quantitative enzyme immunoassay
E. Applicant: EUROIMMUN US INC.
ட் Proprietary and Established Names: EUROIMMUN Anti-M2-3E ELISA (IgG)

Requlatory Information: G.

Requlation: 1.
- 21 CFR 866. 5090- Antimitochondrial antibody immunological test system
Classification: 2. Class II
Product code: 3.
- DBM

Panel:
Immunology
H. Intended Use:
- Intended use(s): 1.

1. Indication(s) for use: Same as intended use.
1. Special conditions for the use statement(s): For prescription use only.
Special instrument requirements: 4.

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

l. Device Description:

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EUROIMMUN US INC.

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J. Substantial Equivalence Information:

1. Predicate device name (s): Inova Quanta Lite M2 EP (MIT3) ELISA
1. Predicate 510(k) number(s): K052262
1. Comparison with predicate:

Similarities

SimilaritiesItem	New Device	Predicate Device
Intended use	Detection of IgG antibodies tomitochondrial antigens as an aid indiagnosis of primary biliary cirrhosis (PBC)and overlap syndrome with autoimmunehepatitis.	Detection of IgG antibodies tomitochondrial antigens as an aid indiagnosis of primary biliary cirrhosis.
Technology	ELISA	Same
Assay platform	96-well microtiter plates	Same
Calibration	Relative units	Same
Conjugate	Rabbit anti-human IgG labeled withhorseradish peroxidase	Goat anti-human IgG labeled withhorseradish peroxidase
Substrate	TMB	Same
Reagentpreparation	All reagents, calibrators and controls areready to use, except for the wash buffer.	Same
Procedure	Sample incubation with micro-well antigencoated plate, followed by a wash step,incubation with an anti-human IgG enzymeconjugate; wash step, incubation withsubstrate; then the addition of a stopsolution and reading at 450nm.	Same

Differences

Item	New Device	Predicate Device
Assay format	Qualitative or semi-quantitative (usingeither the 3 calibrators or 1 calibrator only)	Semi-quantitative
Antigen	Mixture of pyruvate dehydrogenase(isolated from porcine heart) and arecombinant fusion protein. Therecombinant protein was produced in E.coliand comprises the immunogenic domainsof the E2 subunits from branched-chain 2-oxo-acid dehydrogenase (BCOADH),pyruvate dehydrogenase (PDH) and 2-oxoglutarate dehydrogenase (OGDH),together called BPO.	Affinity purified recombinant M2 EP MIT3
Calibrators	3 calibrators2, 20 and 200 RU/ml
Controls	2 controls1 positive, 1 negative	3 controls1 high positive, 1 low positive, 1 negative
Stop solution	0.5 M sulphuric acid
Samples	Serum or plasma	Serum
	1:101 dilution	1:101 dilution
Reported units	RU/ml or Ratio	Units
Cut Off level	20 RU/ml	25 Units

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K. Standard/Guidance Document Referenced (if applicable):

None referenced.

L. Test Principle:

Patient samples are diluted 1:101 in sample buffer, 100 µl of each diluted patient sample and pre-diluted controls and calibrators are added to the antigen coated microtiter wells and incubated for 30 minutes at room temperature. After incubation the microtier well strips are washed with wash buffer to remove unbound antibodies and 100 ul of the anti-human IgG enzyme conjugate reagent is added to each microtiter well. After an additional 30-minutes 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 microtier 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 (where applicable):

1. Analytical performance:
- a. Precision/Reproducibility:

The reproducibility of the test was investigated by determining the intra- and inter-assay coefficients of variation (CV) using sera with values at different points on the calibration curve. The intra-assay CVs are based on 20 determinations and the inter-assay CVs on 4 determinations performed on 6 different days. Neither inter-assay variation nor intra-assay variation should show results over CV = 12% for positive samples. The following results were obtained:

n = 20	Anti-M2-3E ELISA (IgG)RU/ml
	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Sample 6	Sample 7	Sample 8
Mean value (x):	144	101	70	30	101	10	45	19
Standard deviation (SD):	2.26	2.23	1.60	1.01	2.34	1.05	1.37	0.69
Coefficient of variation (CV, %):	1.6	2.2	2.3	3.4	2.3	10.5	3.1	3.7
n = 20	Anti-M2-3E ELISA (IgG)RU/ml
	Sample 9	Sample 10	Sample 11	Sample 12
Mean value (x):	5.5	5.0	16.1	21.8
Standard deviation (SD):	0.34	0.29	0.68	1.21
Coefficient of variation (CV, %):	6.2	5.9	4.3	5.5
Mean CV (%):	4.3

Intra-assay reproducibility

Inter-assay reproducibility

	Anti-M2-3E ELISA (IgG)RU/ml
n = 4 tests / 6 days = 24	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Sample 6	Sample 7	Sample 8
Mean value (x):	158	103	67	43	80	10	39	27
Standard deviation (SD):	4.69	6.20	5.77	4.42	6.30	0.85	2.52	1.95
Coefficient of variation (CV, %):	3.0	6.0	8.6	10.3	7.9	8.4	6.5	7.2
Mean CV (%):	7.2

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		PARKERS SANE SHEER DE LE SEREE -- A S MERCELLA A S

1-----	- 4 46 -- 4 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------1	44-444-44

	Anti-M2-3E ELISA (IgG)RU/ml
n = 20	Sample9	Sample10	Sample11	Sample12
Mean value (x):	5.6	4.9	18.2	24.9
Standard deviation (SD):	0.66	0.39	1.91	2.31
Coefficient of variation (CV, %):	11.9	8.0	10.5	9.3
Mean CV (%):	8.1

The Lot to Lot reproducibility is checked during the kit. 3 different lots are incubated with different QC samples each. For each sample the coefficient of variation (CV) is calculated. Interlot variation should show results below CV = 12% for positive samples. The following results were obtained:

Lot to lot reproducibility

	Anti-M2-3E ELISA (IgG)RU/ml
n = 3 lots x 2 runs = 6	Sample 1	Sample 2	Sample 3	Sample 4	Sample 5	Sample 6	Sample 7	Sample 8
Mean value (x):	14	26	19	27	56	90	98	164
Standard deviation (SD):	1.33	1.33	1.38	1.86	2.51	5.01	7.73	8.96
Coefficient of variation (CV, %):	9.6	5.1	7.5	7.0	4.5	5.6	7.9	5.5
Mean CV (%):	6.6

b. Linearity/assay reportable range:

The linearity of the test was investigated using serial dilutions of patient sera with high antibody concentrations. Each patient serum was diluted up to 1/32. The dilutions were measured with the Anti-M2-3E ELISA (IgG) according to the package insert in single determinations and the results calculated in RU/ml. The observed/expected (O/E) values in the cut-off were within the specifications (0.8 > O/E > 1.2 - out of specification values are highlighted in grey).

	Sample 1			Sample 2			Sample 3			Sample 4			Sample 5
Dilution	Exp.RU/ml	Obs.RU/ml	O/E	Exp.RU/ml	Obs.RU/ml	O/E	Exp.RU/ml	Obs.RU/ml	O/E	Exp.RU/ml	Obs.RU/ml	O/E	Exp.RU/ml	Obs.RU/ml	O/E
1/1	199	199	1.0	161	161	1.0	159	159	1.0	140	140	1.0	198	198	1.0
1/2	99	98	1.0	80	110	1.4	79	99	1.2	70	73	1.0	99	103	1.0
1/4	49	57	1.2	55	61	1.1	49	53	1.1	36	41	1.1	51	61	1.2
1/8	28	26	0.9	31	28	0.9	27	21	0.8	21	17	0.8	30	30	1.0
1/16	13	12	0.9	14	11	0.8	10	9	0.9	9	8	0.9	15	12	0.8
1/32	6	6	0.9	6	5	0.8	4	3	0.7	4	3	0.8	6	5	0.8

Traceability, Stability, Expected values (controls, calibrators or methods). C.

There is no recognized standard or reference material for anti-mitochondrial antibodies. Arbitrary units are used in the assay.

Detection limit: d.
The limit of blank is the lowest arbitrary concentration from a replicate series of samples without analyte. It is defined for this assay as a value of three times the standard deviation of the sample buffer. The detection limit of the Anti-M2-3E ELISA (IgG) is 1.1 RU/ml, determined from 20 replicate determinations of sample buffer only. Due to the high dilution factor of the samples, no influence of the sample material (serum or plasma) is expected. The lowest quantified concentration is the lowest calibrator used in the assay (2 RU/ml).

Analytical specificity: e.

Cross-reactivity: The quality of the antigen used and the antigen source a high specificity of the ELISA. Cross reactivity was investigated using a panel of 29 sera serologically positive for antibodies against PCA (n = 10), GBM (n = 10) and LKM (n = 9). All 29 sera were negative in the Anti-M2-3E ELISA (IgG), so no cross reactivity is expected.

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Interference: To investigate the influence from hemoglobin, triglycerides and bilirubin, 5 different specimens at different anti-M2-3E concentrations (4 - 186 RU/ml) 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 was within the range of 98 - 123 %. 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.

f. Assay cut-off: Qualitative evaluation: Ratio 1.0 Semi-quantitative evaluation: 20 RU/ml
1. Comparison studies:
- Method comparison with predicate device: a.

An external clinical study was performed with 120 clinically characterized samples (39 from AlH patients, 49 from PBC patients and 32 from patients with AIH/PBC overlap syndrome) collected at EUROIMMUN UK Ltd. The samples were tested with the EUROIMMUN Anti-M2-3E ELISA (igG) and with the Inova Quanta Lite M2 EP (MIT3) ELISA as the predicate device. The panel consisted of 18 men and 100 women (2 unknown). The age ranged from 1 - 87 years (2 unknown) with an average age of 50 years. To cover the range around the cut-off with more samples, additional 7 samples with concentrations near the cut-off were created by mixing of positive and negative samples and the results included in the comparison. The results are shown in the table below.

Of the 9 discrepant samples negative in the Inova test and positive in the EUROIMMUN assay, 2 were from patients with AIH/PBC overlap syndrome, 3 were from AIH-1 patients, one from a PBC patient and 3 from an antibody-positive patient diluted with negative material to fit the borderline range. The discrepant sample positive in the Inova test and negative in the EUROIMMUN assay also was a created sample.

n = 127	Inova Quanta Lite M2 EP (MIT3)ELISA
	positive	borderline	negative
EUROIMMUNAnti-M2-3E ELISA (IgG)	positive	78	2	9
	negative	1	2	35
Positive agreement $78 / 79 = 98.7%$ 95% C.I.: 93.1% - 100.0
Negative agreement $35 / 44 = 79.5%$ 95% C.I.: 64.7% - 90.2
Overall agreement $113 / 123 = 91.9%$ 95% C.I.: 85.6% - 96.0

Results of samples within the measurement range (2-200 RU/ml) only (including mixed samples)

n = 46			Inova Quanta Lite M2 EP (MIT3)ELISA
	positive	borderline	negative
EUROIMMUNAnti-M2-3E ELISA (IgG)	positive	2	9	24
	negative	1	1	9
Positive agreement	$24 / 25 =$	96.0%	95% C.I.: 79.6% - 99.9
Negative agreement	$9 / 18 =$	50.0%	95% C.I.: 26.0% - 74.0%
Overall agreement	$33 / 43 =$	76.7%	95% C.I.: 61.4% - 88.2%

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b. Matrix comparison:

The usability of plasma was investigated using 21 sample pairs each of serum and corresponding plasma. The samples cover concentrations in the diagnostically important range, i.e. the lower area of the calibration curve and the cut-off. Passing-Bablok regression was calculated for the comparison

of serum to plasma. The results are shown in the table below.

	EDTA plasma	Heparin plasma	Citrate plasma
Regression equation(y = plasma, x = serum)	$y = 0.09 + 1.01 x$	$y = -0.10 + 0.98 x$	$y = 0.56 + 1.02 x$
95% C.I. of intercept	-1.30 - 2.75	-1.32 - 1.11	-1.02 - 3.18
95% C.I. of slope	0.98 - 1.04	0.96 - 1.01	0.98 - 1.06

A comparison in which the 95% C.I. of the slope contains 1.0 and the 95% C.I. of the intercept contains 0 indicates equivalence of concentration between serum and the corresponding plasma matrices. The comparisons above satisfy this condition.

Coefficients of determination were found to be above 0.99 and %BIAS from serum was in the range of 82 to 112 % (serum = 100 %).

3. Clinical studies:

In a clinical study, performed in cooperation with several university hospitals (see below), in total 1180 clinically characterized samples (251 from PBC patients and 929 from control groups) were investigated for anti-mitochondrial antibodies (lgG). The EUROIMMUN Anti-M2-3E ELISA (lgG) showed a sensitivity for PBC of 92.8% and a specificity of 97.4%. The results are shown in the table below. 95% C.I. are calculated by the exact method.

No.	Panel	n(men, women)	Mean age(age range)	Anti-M2-3E ELISA (IgG)
1	Primary biliary liver cirrhosis	251(20, 229,2 unknown)	55 y(22 - 85 y)	positive	%	95% C.I.
2	PBC/AIH overlap syndrome	15(1, 14)	55 y(32 - 87 y)	15	100.0%	78.2 - 100.0%

Sensitivity: a.

b. Clinical specificity:

No.	Panel	n(men, women)	Mean age(age range)	Anti-M2-3E ELISA (IgG)
				negative	%	95% C.I.
3	Autoimmune hepatitis	131(20, 65,46 unknown)	40 y(1 - 86 y, 46unknown)	125	95.4%	90.3 - 98.3%
4	Viral hepatitis	239(16, 23,200 unknown)	48 y(25 - 84 y;200unknown)	239	100.0%	98.5 - 100.0%
5	Primary sclerosing cholangitis	19(12, 7)	48 y(21 - 73 y)	19	100.0%	82.4 - 100.0%
6	Systemic lupus erythematosus	100(9, 91)	42 y(18 - 79 y)	92	92.0%	84.8 - 96.5%
7	Sjogren's syndrome	120(8, 112)	52 y(18-81)	112	93.3%	87.3 - 97.1%
8	Rheumatoid arthritis	120(33, 87)	54 y(23 - 80)	118	98.3%	94.1 - 99.8%
9	Asymptomatic blood donors	200(131, 69)	40 y(19 - 69 y)	200	100.0%	98.2 - 100.0%
	Total	929		905	97.4%	96.2 - 98.3%

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Other clinical supportive data (when a. and b. are not applicable): C. Not applicable.
1. Clinical cut-off:

See Assay cut-off.

ട്. Expected values/Reference range:
The levels of anti-mitochondrial antibodies (IgG) were analyzed with the EUROIMMUN Anti-M2-3E ELISA (IgG) in a panel of 200 apparently healthy blood donors, consisting of 120 men and 80 women with an age range of 19-69 years (average age: 40 years). With a cut-off of 20 RU/ml, all blood donors were found negative.

Positives	0
Negatives	200
Lowest value	0.35 RU/ml
Highest value	14.50 RU/ml
Mean value	3.81 RU/ml
Std dev. (SD)	2.944 RU/ml

N. Proposed Labeling:

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

o Conclusion:

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

Date

Signature

Kathryn Kohl, Managing Director Typed Name, Title

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

EUROIMMUN US INC. c/o Ms. Kathryn Kohl Managing Director 429 Rockaway Valley Road Unit 1200 Boonton Township, NJ 07005

SEP 0 2 2010

Re: K092736

Trade/Device Name: EURQIMMUN Anti-M2-3E ELISA (IgG) Regulation Number: 21 CFR§866.5090 Regulation Name: Antimitochondrial Antibody Immunological Test System Regulatory Class: Class II Product Code: DBM Dated: July 22, 2010 Received: July 30, 2010

Dear Ms. Kohl:

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.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 or any Federal statutes and regulations administered by other Federal agencies. You must

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Page 2 - Ms. Kathryn Kohl

comply 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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/ReportaProblem/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/cdrh/industry/support/index.html.

Sincerely yours,

Maria M. Chan

Maria M. Chan; Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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EUROIMMUN US INC.

ATTACHMENT 2

INDICATIONS FOR USE STATEMENT

K09 2736

SEP 0 2 2010

510(k) Number (if known): K092736

Device Name: Anti-M2-3E ELISA (IgG)

Indications For Use:

The EUROIMMUN Anti-M2-3E ELISA (IgG) test kit is intended for the qualitative determination of IgG class autoantibodies against the mitochondrial antigens M2 in human serum and plasma. It is used as an aid in the diagnosis of primary biliary cirrhosis (PBC), in conjunction with other laboratory and clinical findings.

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

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (OIVD)

Reena Philip

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510K k 092736

Regulation Number and Section

§ 866.5090 Antimitochondrial antibody immunological test system.

(a)
Identification. An antimitochondrial antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's own tissue), such as primary biliary cirrhosis (degeneration of liver tissue) and chronic active hepatitis (inflammation of the liver).(b)
Classification. Class II (performance standards).