Predicate Devices

K052262, K050662, K040885, K000535, K021482

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a traditional immunoassay kit (line-blot strip test) for detecting antibodies. There is no mention of AI, ML, image processing, or any computational analysis beyond standard laboratory procedures. The evaluation protocol and reaction control card suggest manual or semi-automated interpretation, not AI/ML-driven analysis.

Therapeutic

No
The device is an in vitro diagnostic test used to aid in the diagnosis of autoimmune liver diseases by detecting specific antibodies. It does not provide treatment or therapy.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that "Detection of these antibodies is used as an aid in the diagnosis of autoimmune liver diseases."

SaMD (Software as a Medical Device)

No

The device description clearly lists physical components such as antigen coated test strips, controls, conjugates, buffers, and substrate solution, indicating it is a hardware-based in vitro diagnostic kit, not software only.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The description explicitly states it's "intended for the qualitative detection of IgG class antibodies against 8 different antigens... in human serum and plasma." This is a classic definition of an in vitro diagnostic test, as it analyzes biological samples outside of the body to provide information about a patient's health status.
Purpose: The intended use also states that the detection of these antibodies is used "as an aid in the diagnosis of autoimmune liver diseases." This directly relates to diagnosing a medical condition, which is a primary function of IVDs.
Sample Type: It uses "human serum and plasma," which are biological specimens commonly used in IVD testing.
Care Setting: It is intended for use in a "clinical, reference or hospital laboratory," which are typical settings for performing IVD tests.
Prescription Use: The mention of "For prescription use only" further indicates it's a medical device intended for use under the direction of a healthcare professional, a common characteristic of IVDs.
Performance Studies: The document details various performance studies (analytical and clinical) including sensitivity and specificity, which are standard evaluations for IVD devices to demonstrate their accuracy and reliability.
Predicate Devices: The listing of predicate devices (other IVD tests) further confirms its classification as an IVD.

All these factors align with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) kit is an immune lineblot strip test intended for the qualitative detection of IgG class antibodies against 8 different antigens: AMA-M2, M2-3E (BPO), Sp100, PML, gp210, LKM-1, LC-1 and SLA/LP in human serum and plasma (EDTA, Li-heparin, Citrate). Detection of these antibodies is used as an aid in the diagnosis of autoimmune liver diseases in conjunction with other laboratory and clinical findings.

Product codes (comma separated list FDA assigned to the subject device)

NBS, DBM, NIY, NUM, NRI

Device Description

The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) consists of antigen coated test strips, a positive control, alkaline phosphatase-labelled anti-human 1gG conjugate, sample buffer, wash buffer concentrate, NBT/BCIP substrate solution tray, test instruction, evaluation protocol and reaction control card.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Liver

Indicated Patient Age Range

Not Found

Intended User / Care Setting

The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) test kit is intended to be used in a clinical, reference or hospital laboratory. This kit is not designed for point-of-care testing. For prescription use only.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Analytical performance:

Precision/Reproducibility: Reproducibility was investigated by repeated determinations of different samples covering the whole range of antigens of the EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG). The samples were tested for intra-assay reproducibility in 20 replicates on one day using the same kit lot. Inter-assay reproducibility was investigated in 20 different runs, each run performed by the same technician with a single determination on a different day using the same kit lot. Inter-lot reproducibility was tested in 3 different runs using 3 different kit lots, each run performed with a single determination. Reproducibility was found to be sufficient as no positive sample was found negative and vice versa.
To investigate the influence of different individuals reading the intensity of the bands, different samples covering the whole range of antigens were evaluated by three different technicians and under 3 different light conditions (sunlight, Neon light and electric bulb light), each run performed with a single determination. No deviation was observed between the individual readings and from the light conditions.
Linearity/assay reportable range: Not applicable.
Traceability, Stability, Expected values (controls, calibrators or methods): A recognized standard or reference material for antibodies against AMA-M2, M2-3E, Sp100, PML, gp210, LKM-1, LC-1 and SLA/LP is not available.
Detection limit: Not applicable.
Analytical specificity / Cross-reactivity: The quality of the antigen substrates and the antigen source assure a high level of specificity for the EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG). The test system allows specific detection of IgG class antibodies against AMA-M2, M2-3E, sp100, PML, gp210, LKM-1, LC-1 and SLA/LP. Cross reactivity was investigated using serologically characterized panels from the following groups: Autoantibodies against granulocyte cytoplasm (ANCA; n = 10), autoantibodies against thyroid gland antigens (n = 10) and autoantibodies against islet cell antigens (ICA; n = 10), autoantibodies against cardiolipid syndrome (APS; n = 5) and the CDC ANA reference panel (n = 12) as well as clinical panels from the following groups: Autoimmune hepatitis type 1 (AIH-1; n = 84), primary sclerosing cholangitis (PSC; n = 19), systemic lupus erythematosus (SLE; n = 10), rheumatoid arthritis (RA; n = 50), celiac disease (n = 7), non-alcoholic steatohepatitis (n = 30) and viral hepatitis (HBV, HCV; n = 39). Only 9 samples of these 286 total samples were found positive with the EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) for a few antigens only.
3 AIH tested positive for SLA/LP these three samples should not be considered cross-reactive as SLA/LP is associated with AIH-1.
Interference: Different samples were spiked with potential interfering substances in 3 different concentrations. No interference was observed with haemolytic, lipaemic or icteric samples for concentrations of up to 500 mg/dl for haemoglobin, 2000 mg/dl for triglycerides and 40 mg/dl for bilirubin.

Comparison studies:

Method comparison with predicate device: A clinical study was performed with 295 clinically characterized samples (99 from patients with autoimmune hepatitis (AIH), 104 from patients with primary biliary cirrhosis as well as 42 from patients with viral hepatitis and 50 from patients with rheumatoid arthritis (RA) obtained from different sources. AlH cases were defined on the criteria of the International Autoimmune Hepatitis Group (IAIHG) and the recent recommendations for AIH issued by the American Association for the Study of the Liver Diseases (AASLD). PBC cases were defined on the basis of the consensus statements of both, the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL): the presence of disease-related autoantibodies, more specifically AMA, is one of three criteria required for a definite diagnosis of PBC.
The samples were tested with the EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) and with the Inova ELISA kits as the predicate devices. To investigate the range close to the cut-off , 6 to 29 artificial samples for each antigen were created by mixing positive samples with negative samples of the same matrix as diluent- these samples were tested with the relevant reference ELISAs only, resulting in different total numbers. The results of the study are shown in the table below. Borderline results (Inova) were not included in the agreement calculations. 95% C.I.'s were calculated by the exact method.
The EUROLINE was slightly more sensitive for the detection of gp210 than the predicate assay.
Matrix comparison: The use of EDTA, heparin (Li) and citrate plasma samples was confirmed for each antigen band by a correlation of 8 to 11 sample pairs of serum and corresponding plasma. The sample pairs were selected to cover the complete range of results (negative, positive and close to cut-off). The results of the plasma samples and the corresponding serum sample were compared and found to be sufficient as no positive sample was found negative and vice versa.

Clinical studies:

Sensitivity and specificity: The EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) was validated using several panels with a total of 734 samples, obtained from different sites. The results of these studies are summarized in the tables provided in the original document.

Expected values/Reference range: The levels of IgG antibodies against the antigens AMA-M2, M2-3E, Sp100, PML, gp210 LKM-1, LC-1 and SLA/LP, were analyzed in a panel of 150 healthy blood donors. None of these samples were found positive.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

See tables under "Summary of Performance Studies".

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K052262, K050662, K040885, K000535, K021482

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 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).

Summary

0

EUROIMMUN US INC.

Image /page/0/Picture/1 description: The image shows a black and white pattern. The pattern consists of a series of black shapes that are separated by white spaces. The black shapes are arranged in a row, and they are all the same size and shape. The white spaces are also arranged in a row, and they are all the same size and shape. The pattern is symmetrical, and it is repeated several times.

APR 1 2 2013

PREMARKET NOTIFICATION 210(K) SAFETY AND EFFECTIVENESS SUMMARY (as required by 21 CFR § 807.92)

A.	510(k)Number:
	K113439
B.	Purpose for Submission:
	New device
C.	Measurand:
	Autoantibodies against AMA-M2, M2-3E (BPO), Sp100, PML, gp210, LKM-1, LC-1 and SLA/LP
D.	Type of Test:
	Qualitative immunoblot (solid phase ELISA)
E.	Applicant:
	EUROIMMUN US INC.
F.	Proprietary and Established Names:
	EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG)
G.	Regulatory Information:
	1. Regulation:
	21 CFR §866.5090 - Antimitochondrial antibody immunological test system
	21 CFR §866.5660 - Multiple autoantibodies immunological test system.
	2. Classification:
	Class II
	3. Product code:
	NBS Multiple autoantibodies immunological test system. LKM-1:
	Subsequent Product Codes:
	DBM Antimitochondrial antibody immunological test system. (AMA-M2/M2-3E (BPO))
	NIY Multiple autoantibodies immunological test system. (SLA/LP)
	NUM Antimitochondrial antibody immunological test system. (Sp100)
	NRI Antimitochondrial antibody immunological test system. (gp210)
(PML)
(LC-1)
	4. Panel:
	Immunology
H.	Intended Use:

1. Intended use(s):
  The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) kit is an immune lineblot strip test intended for the qualitative detection of IgG class antibodies against 8 different antigens: AMA-M2, M2-3E (BPO), Sp100, PML, gp210, LKM-1, LC-1 and SLA/LP in human serum and plasma (EDTA, Li-heparin, Citrate). Detection of these antibodies is used as an aid in the diagnosis of autoimmune liver diseases in conjunction with other laboratory and clinical findings.

1

Image /page/1/Picture/1 description: The image shows a close-up of what appears to be a row of electrical components or connectors. There are four dark, rounded shapes that are evenly spaced and connected by a horizontal bar at the bottom. There is also a horizontal bar at the top, creating a channel-like structure. The image is high contrast, with the components appearing black against a white background.

1. Indication(s) for use: Same as intended use.
1. Special conditions for the use statement(s):

The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) test kit is intended to be used in a clinical, reference or hospital laboratory. This kit is not designed for point-of-care testing. For prescription use only.

1. Special instrument requirements: Not applicable.

l. Device Description:

The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) consists of antigen coated test strips, a positive control, alkaline phosphatase-labelled anti-human 1gG conjugate, sample buffer, wash buffer concentrate, NBT/BCIP substrate solution tray, test instruction, evaluation protocol and reaction control card.

J. Substantial Equivalence Information:

1. Predicate device name (s):
  Inova Quanta Lite ELISAs (see table below).
1. Predicate 510(k) number(s):

| EUROIMMUN EUROLINE
Profile Autoimmune Liver

Disease 8 Ag (IgG) Antigens	Predicate device	510(k) number
M2 / M2-3E (BPO)	Quanta Lite M2 EP (MIT3) ELISA	K052262
Sp100	Quanta Lite Sp100 ELISA	K050662
PML	Quanta Lite Sp100 ELISA*	K050662
gp210	Quanta Lite gp210 ELISA	K040885
LKM-1	Quanta Lite LKM-1 ELISA	K000535
LC-1	Quanta Lite LKM-1 ELISA*	K000535
SLA/LP	Quanta Lite SLA ELISA	K021482

As no FDA cleared test systems were available for two of the 8 antigens the Inova Sp100 ELISA was used as the predicate device for PML and the Inova LKM-1 ELISA as the predicate device for LC-1. D. A description of the relationship of these antigens is included in Bogdanos et al., World J Gastroenterol, 2008, 14(21), 3374-3387..

3. Comparison with predicate:

Similarities
Item	Device	Predicates
Intended
Use	Qualitative detection of IgG class antibodies against 8 different
antigens: AMA-M2, M2-3E (BPO), Sp100, PML, gp210, LKM-1,
LC-1 and SLA/LP in human serum and plasma (EDTA, Li-
heparin, Citrate).	Same (when combined)
Reaction
principle	Enzyme immunoassay: enzyme labeled bound patient
antibodies are detected with a chromogenic substrate that is
converted to a visible colored product at the reaction site.	Same

Differences Device Predicate Item Assay format Qualitative Semi-quantitative Technology/ Standard ELISA technique (solid phase ELISA): serum Standard ELISA technique (solid phase ELISA): serum incubation with antigen Procedure incubation with antigen coated strips, followed by a wash step, incubation with an anti-human IgG enzyme conjugate; wash coated wells, followed by a wash step, incubation with an anti-human IgG enzyme step, incubation with substrate, wash step, air drying and conjugate; wash step, incubation with evaluation. substrate, stopping of the reaction with stop solution, photometric reading.

2

EUROIMMUN US INC.

Image /page/2/Picture/1 description: The image shows a pattern of alternating black and white shapes. There are two horizontal black bars running across the top and bottom of the image. Between the bars are a series of black, oval shapes separated by white space.

Differences
Item	Device		Predicate
Antigens	AMA-
M2	Natively purified from bovine heart, containing the 74
kDa E2 subunit of the pyruvate dehydrogenase
complex (PDH) as the main component.	Affinity purified recombinant M2 EP MIT3.
	M2-3E
(BPO)	Recombinant fusion protein, produced in E. coli,
comprising the immunogenic domains of the E2
subunits of the branched-chain 2-oxoacid
dehydrogenase (BCOADH), pyruvate dehydrogenase
(PDH) and 2-oxoglutarate dehydrogenase (OGDH),
together called M2-3E (synonyme: BPO).
	Sp100	Recombinant Sp100, expressed by cloning the
corresponding human cDNA in E. coli.	Purified Sp100 peptide.
	PML	Recombinant PML, expressed by cloning the
corresponding human cDNA in E. coli.
	gp210	Recombinant gp210, expressed by cloning the
corresponding human cDNA in E. coli.	Purified gp210 peptide.
	LKM-1	Recombinant cytochrome P450 IID6, expressed by
cloning the corresponding human cDNA in insect cells
using a baculovirus vector.	Recombinant human cytochrome P450
IID6 antigen.
	LC-1	Recombinant LC-1 (formiminotransferase
cyclodeaminase), expressed by cloning the
corresponding human cDNA in insect cells using a
baculovirus vector.
	SLA/LP	Recombinant SLA/LP (a UGA suppressor tRNA-
associated protein), expressed by cloning the
corresponding human cDNA in E. coli.	Recombinant SLA antigen.
Samples	Serum or plasma (EDTA, Li-heparin, Citrate)
1:101 dilution		Serum
1:101 dilution
Controls	Positive control		3 controls (high positive, low positive,
negative)
Conjugate	Alkaline phosphatase-labeled anti-human IgG (goat)		Goat anti-human IgG labeled with
horseradish peroxidase
Substrate	BCIP/NBT		TMB
Reported
results	positive/negative (qualitative)		Units (qualitative)

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

None referenced.

ட. Test Principle:

The EUROLINE uses different purfied antigens that have been coated and applied in easy to read lines onto a membrane. Antibodies are detected via a secondary antibody linked to an enzyme. The principle of the EUROLINE is that of an enzyme linked immunosorbent assay (ELISA), using a membrane as the solid phase instead of microtiter wells.

Patient samples are diluted 1.101 in sample buffer, 1.5 ml of diluted patient sample are added to the test strip lying in the incubation channel and incubated for 30 minutes at room temperature. After incubation the test strips are washed with diluted wash buffer to remove unbound antibodies and 1.5 ml of the diluted anti-human IgG enzyme conjugate reagent is added to each channel. After an additional 30-minutes incubation at room temperature, the test strips are again washed with wash buffer to remove any unbound enzyme conjugate and 1.5 ml of the substrate solution is added. The strips are incubated for 10 minutes at room temperature and then aspirated and washed with dist. water. The test strips can be evaluated visually by comparison of the band intensity with the reaction control card.

The control band on the strips contains (non-specific) anti-human IgG, which reacts with the sample IgG to show a strong color reaction if the incubation was performed correctly and so represents a function test on each single strip. If the control band is negative, the test is invalid and should be repeated.

The positive control contains a mixture of the targeted antibodies which bind to the antigen coated on the blot strips. A strip incubated with the positive control shows a positive control is negative control is negative, the test results are invalid and should be repeated.

3

The qualitative results are reported for each individual antibody separately. The interpretation of the test results does not include a combined score or diagnosis.

Note: The EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) does not contain all antigens necessary for a complete diagnosis of autoimmune liver diseases. Especially in autoimmune hepatitis type 1, antibodies against smooth muscle and nuclear antigens are relevant. Testing for the presence of these antibodies should be investigated by the laboratory in addition to the antigens contained in this test. In the studies contained in this submission, only the antigen spectrum of the EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) was investigated.

M. Performance Characteristics (where applicable):

Analytical performance:

a. Precision/Reproducibility:
Reproducibility was investigated by repeated determinations of different samples covering the whole range of antigens of the EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG). The samples were tested for intra-assay reproducibility in 20 replicates on one day using the same kit lot. Interassay reproducibility was investigated in 20 different runs, each run performed by the same technician with a single determination on a different day using the same kit lot. Inter-lot reproducibility was tested in 3 different runs using 3 different kit lots, each run performed with a single determination. Reproducibility was found to be sufficient as no positive sample was found negative and vice versa.

To investigate the influence of different individuals reading the intensity of the bands, different samples covering the whole range of antigens were evaluated by three different technicians and under 3 different light conditions (sunlight, Neon light and electric bulb light), each run performed with a single determination. No deviation was observed between the individual readings and from the light conditions.

b. Linearity/assay reportable range:
Not applicable.
Traceability, Stability, Expected values (controls, calibrators or methods): C.
A recognized standard or reference material for antibodies against AMA-M2, M2-3E, Sp100, PML, gp210, LKM-1, LC-1 and SLA/LP is not available.
d. Detection limit:
Not applicable.
Analytical specificity: e.
Cross-reactivity: The quality of the antigen substrates and the antigen source assure a high level of specificity for the EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG). The test system allows specific detection of IgG class antibodies against AMA-M2, M2-3E, sp100, PML, gp210, LKM-1, LC-1 and SLA/LP. Cross reactivity was investigated using serologically characterized panels from the following groups: Autoantibodies against granulocyte cytoplasm (ANCA; n = 10), autoantibodies against thyroid gland antigens (n = 10) and autoantibodies against islet cell antigens (ICA; n = 10), autoantibodies against cardiolipid syndrome (APS; n = 5) and the CDC ANA reference panel (n = 12) as well as clinical panels from the following groups: Autoimmune hepatitis type 1 (AIH-1; n = 84), primary sclerosing cholangitis (PSC; n = 19), systemic lupus erythematosus (SLE; n = 10), rheumatoid arthritis (RA; n = 50), celiac disease (n = 7), non-alcoholic steatohepatitis (n = 30) and viral hepatitis (HBV, HCV; n = 39). Only 9 samples of these 286 total samples were found positive with the EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) for a few antigens only.

3 AIH tested positive for SLA/LP these three samples should not be considered cross-reactive as SLA/LP is associated with AIH-1.

Interference: Different samples were spiked with potential interfering substances in 3 different concentrations. No interference was observed with haemolytic, lipaemic or icteric samples for concentrations of up to 500 mg/dl for haemoglobin, 2000 mg/dl for triglycerides and 40 mg/dl for bilirubin.

f. Assay cut-off:
The cut-off intensity is defined as the lowest limit of a clearly visible band.

4

Image /page/4/Picture/1 description: The image shows a close-up of a series of dark, rounded shapes arranged in a row. The shapes are separated by thin, vertical white lines, and they appear to be resting on a dark horizontal line. The background is white, which contrasts with the dark shapes and lines.

2. Comparison studies:

Method comparison with predicate device: a.
A clinical study was performed with 295 clinically characterized samples (99 from patients with autoimmune hepatitis (AIH), 104 from patients with primary biliary cirrhosis as well as 42 from patients with viral hepatitis and 50 from patients with rheumatoid arthritis (RA) obtained from different sources. AlH cases were defined on the criteria of the International Autoimmune Hepatitis Group (IAIHG) and the recent recommendations for AIH issued by the American Association for the Study of the Liver Diseases (AASLD). PBC cases were defined on the basis of the consensus statements of both, the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL): the presence of disease-related autoantibodies, more specifically AMA, is one of three criteria required for a definite diagnosis of PBC.

The samples were tested with the EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) and with the Inova ELISA kits as the predicate devices. To investigate the range close to the cut-off , 6 to 29 artificial samples for each antigen were created by mixing positive samples with negative samples of the same matrix as diluent- these samples were tested with the relevant reference ELISAs only, resulting in different total numbers. The results of the study are shown in the table below. Borderline results (Inova) were not included in the agreement calculations. 95% C.I.'s were calculated by the exact method.

The EUROLINE was slightly more sensitive for the detection of gp210 than the predicate assay assay. The predicate assay uses a synthetic peptide corresponding to a 25 amino acid stretch in the C-terminal cytosolic domain of gp210. In contrast, the EUROLINE utilizes a recombinant polypeptide corresponding to the 15 kDa C-terminal portion of the perinuclear domain fused to the whole cytosolic domain of gp210. The "discrepant" samples in the comparison study are mainly from PBC patients.

| | Negative agreement |---------|--------- | | | n = 281 | AMA-M2 and/or
M2-3E | 97 98.9% (95.9 – 99.9%) | 2 PBC 2 AIH |
| n = 293 | negative | | Sp100 | | positive 1 artificial | | negative | n = 296 | gp210 | | positive 7 AIH,
6 AIH/PBC,
1 RA | none |
| | negative | n = 325 | LKM-1 | | positive 1 artificial | | negative | n = 298 | SLA/LP | | positive | | negative | Inova Quanta Lite ELISA | | | Positive agreement
| Discrepant samples | |
---------------|-------------------------|------------|----------|----------------------------------------------|-----------------------------------------|----------------------|
| positive | borderline | negative | % (95% C.I.) | positive | negative |
| 0 | 2 | 95.1% (88.9 – 98.4%)
| 3 controls,
| 5 | 4 | 173 | | | |
| Sp100 | | | | | |
| 34 | 1 | 2 | 94.4% (81.3 – 99.3%) | 1 PBC,
| 2 artificial |
| 2 | 2 | 252 | 99.2% (97.2 – 99.9%) | | |
| gp210 | | | | | |
| 33 | 2 | 30 | 100.0% (89.4 – 100.0%) | 16 PBC,
| 0 | 0 | 231 | 88.5% (84.0 – 92.1%) | | |
| LKM-1 | | | | | |
| 50 | 0 | 3 | 92.6% (82.1 – 97.9%) | 3 AIH,
| 3 artificial |
| 4 | 1 | 267 | 98.9% (96.8 – 99.8%) | | |
| SLA | | | | | |
| 30 | 0 | 1 | 100.0% (88.4 – 100.0%) | 1 artificial | none |
| 0 | 1 | 266 | 99.6% (97.9 – 100.0%) | none | |

Matrix comparison: b.

The use of EDTA, heparin (Li) and citrate plasma samples was confirmed for each antigen band by a correlation of 8 to 11 sample pairs of serum and corresponding plasma. The sample pairs were selected to cover the complete range of results (negative, positive and close to cut-off). The results of the plasma samples and the corresponding serum sample were compared and found to be sufficient as no positive sample was found negative and vice versa.

5

Image /page/5/Picture/1 description: The image shows a close-up of what appears to be a row of raised pavement markers, also known as Botts' dots. These markers are black and are evenly spaced along a dark surface, likely a road or pavement. The background is lighter, creating a high contrast that makes the markers stand out.

3. Clinical studies:

Sensitivity and specificity: a.

The EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) was validated using several panels with a total of 7 34 samples, obtained from different sites. The results of these studies are summarized below.

Sensitivity for Primary biliary liver cirrhosis (PBC)

| Panel | n
(men,
women) | Mean
age
(age range) | EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG)
positive (% positive)
(95% C.I.) | | | | |
|------------------------------------|----------------------|----------------------------|---------------------------------------------------------------------------------------------|-----------------------------|------------------------------|------------------------------|------------------------------|
| | | | AMA-M2 | M2-3E | Sp100 | PML | gp210 |
| Primary biliary liver
cirrhosis | 205
(20, 185) | 58 y
(22-90 y) | 175 (85.4%)
(79.8 - 89.9%) | 160 (78.0%)
(71.8-83.5%) | 54 (26.3%)
(20.5 - 32.9%) | 58 (28.3%)
(22.2 - 35.0%) | 68 (33.2%)
(26.8 - 40.1%) |

Specificity for Primary biliary liver cirrhosis (PBC)

| Panel | n
(men,
women) | Mean
age
(age range) | EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG)
negative (% negative)
(95% C.I.) | | | | |
|-----------------------------------|-------------------------------|-------------------------------|---------------------------------------------------------------------------------------------|--------------------------------|--------------------------------|-------------------------------|-------------------------------|
| | | | AMA-M2 | M2-3E | Sp100 | PML | gp210 |
| Autoimmune hepatitis | 163
(20, 59,
84 unkn.) | 38 y
(1-86 y,
84 unkn.) | 162 (99.4%) | 162 (99.4%) | 162 (99.4%) | 163 (100.0%) | 154 (94.5%) |
| Viral hepatitis | 39
(16, 23) | 48 y
(25-84 y) | 39 (100.0%) | 39 (100.0%) | 39 (100.0%) | 39 (100.0%) | 39 (100.0%) |
| Primary sclerosing
cholangitis | 19
(12, 7) | 48 y
(21-73 y) | 19 (100.0%) | 19 (100.0%) | 19 (100.0%) | 19 (100.0%) | 19 (100.0%) |
| Further controls* | 308
(140, 167,
1 unkn.) | 18 y
(0-83 y) | 304 (98.7%) | 307 (99.7%) | 308 (100.0%) | 304 (98.7%) | 302 (98.1%) |
| Total | 529 | | 524 (99.1%)
(97.8 - 99.7%) | 527 (99.6%)
(98.6 - 100.0%) | 528 (99.8%)
(99.0 - 100.0%) | 525 (99.2%)
(98.1 - 99.8%) | 514 (97.2%)
(95.4 - 98.4%) |

Sensitivity for Autoimmune hepatitis (AIH)
Panel	n
(men,
women)	Mean
age
(age range)	EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG)
positive (% positive)
(95% C.I.)
		LKM-1	LC-1	SLA/LP
Autoimmune hepatitis	163
(20, 59,
84 unkn.)	38 y
(1-86 y,
84 unkn.)	20 (12.3%)
(7.7 - 18.3%)	15 (9.2%)
(5.2 - 14.7%)	15 (9.2%)
(5.2 - 14.7%)
Type 1	142
(16, 42,
84 unkn.)	48 y
(20-86 y
84 unkn.)	2 (1.4%)
(0.2 - 5.0%)	1 (0.7%)
(0.0 - 3.9%)	15 (10.6%)
(6.0 - 16.8%)
Type 2	21
(4, 17)	12 y
(1-45 y)	18 (85.7%)
(63.7 - 97.0%)	14 (66.7%)
(43.0 - 85.4%)	0 (0.0%)
(0.0 - 16.1%)

Specificity for Autoimmune hepatitis (AIH)

| Panel | n
(men, women) | Mean age
(age range) | EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG)
negative (% negative)
(95% C.I.) | | |
|------------------------------------|-------------------------------|-------------------------|---------------------------------------------------------------------------------------------|--------------------------------|-------------------------------|
| | | | LKM-1 | LC-1 | SLA/LP |
| Primary biliary liver
cirrhosis | 205
(20, 185) | 58 y
(22-90 y) | 204 (99.5%) | 205 (100.0%) | 199 (97.1%) |
| Viral hepatitis | 39
(16, 23) | 48 y
(25-84 y) | 39 (100.0%) | 39 (100.0%) | 39 (100.0%) |
| Primary sclerosing
cholangitis | 19
(12, 7) | 48 y
(21-73 y) | 19 (100.0%) | 19 (100.0%) | 19 (100.0%) |
| Further controls* | 308
(140, 167,
1 unkn.) | 18 y
(0-83 y) | 308 (100.0%) | 306 (99.4%) | 307 (99.7%) |
| Total | 571 | | 570 (99.8%)
(99.0 - 100.0%) | 569 (99.6%)
(98.7 - 100.0%) | 564 (98.8%)
(97.5 - 99.5%) |

ffom the following groups: systemic lupus enthematosus (n = 10), Sjögren's syndrome (n = 5), myositis (n = 4), rheumatoid arthriis (n = 50), diabeles (n = 7), A1 antitrypsin deficiency (n = 30), Alagille syndrome (n = 29), bilary atresia (n = 35), giant cell hepatiis (n = 16), non-alcoholis (n = 30), haemochromatosis (n = 17), progressive familial intrahepatic cholestatis (n = 31), Wilson's disease (n = 30)

6

EUROIMMUN US INC.

Other clinical supportive data (when a. and b. are not applicable): b. Not applicable.
Clinical cut-off: 4.

See Assay cut-off.

ર . Expected values/Reference range:
The levels of IgG antibodies against the antigens AMA-M2, M2-3E, Sp100, PML, gp210 LKM-1, LC-1 and SLA/LP, were analyzed in a panel of 150 healthy blood donors. None of these samples were found positive.

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.

04.09.2013 Date

Michael Locke/Dir. Of Regulatory Affairs

Name:Title

Michael Locke

Signature

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7

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the left side of the emblem.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

April 12, 2013

EUROIMMUN US INC. c/o Ms. Kathryn Kohl Managing Director 1100 The American Road Morris Plains, NJ 07950

Re: K113439

Trade/Device Name: EUROLINE Profile Autoimmune Liver Disease 8 Ag (1gG) Kit Regulation Numbers: 21CFR§866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Codes: DBM, NUM, NRI, NIY, NIY, NBS Dated: April 10, 2013 Received: April 11, 2013

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. Please note: CDRH does 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 or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

8

Page 2 - Ms. Kathryn Kohl

forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH0ffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/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/MedicalDevices/ResourcesforYou/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

9

Indications for Use Form

510(k) Number (if Known): K113439

Device Name: EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) Kit

Indications for Use:

The EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) Kit is an immune line-blot strip test intended for the qualitative detection of IgG class antibodies against 8 different antigens: AMA-M2, M2-3E (BPO), Sp100, PML, gp210, LKM-1, LC-1 and SLA/LP in human serum and plasma (EDTA, Li-heparin, Citrate). Detection of these antibodies is used as an aid in the diagnosis of autoimmune liver diseases in conjunction with other laboratory and clinical findings.

Prescription Use X (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 In Vitro Diagnostics and Radiological Health (OIR)

Maria Miy @han -S

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

510(k) K113439