The Eu-tTG® IgA is an in vitro diagnostic enzyme immunoassay for the semi-quantitative detection of IgA specific antibodies directed against tissue transglutaminase (tTG) in human serum. It is an aid in the diagnosis of celiac disease and should be used in conjunction with other serological tests and clinical findings.

The Eu-tTG® IgG is an in vitro diagnostic enzyme immunoassay for the semi-quantitative detection of IgG specific antibodies directed against tissue transglutaminase (tTG) in human serum. It is an aid in the diagnosis of celiac disease and should be used in conjunction with other serological tests and clinical findings.

Device Description

Each test kit for Eu-tTG® IgA & Eu-tTG® IgG consists of one (1) microtiter plate (12 strips with 8 microwells coated with the human recombinant tTG antigen), assay controls (positive and negative), a ready-to-use set of five (5) calibrators, Horseradish Peroxidase (HRP) goat anti-human IgA or IgG conjugate, serum diluent, Tetramethylbenzidine (TMB) enzyme substrate, stop solution, and washing solution required for the assay.

AI/ML Overview

The provided text describes two diagnostic devices, Eu-tTG® IgA and Eu-tTG® IgG, both intended as aids in the diagnosis of celiac disease. The study described focuses on their analytical and clinical performance.

Here's the breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve a sensitivity of at least X%"). Instead, it presents the results of method comparison and clinical studies, implying that the achieved performance was deemed sufficient for substantial equivalence to predicate devices. The comparator devices' performance would implicitly serve as a benchmark for acceptability.

However, based on the provided data, we can infer performance metrics. For this response, I will list the observed performance from the clinical studies as the "Reported Device Performance." Since no explicit "acceptance criteria" are given for these values, they serve as the performance characteristics that were reviewed for market clearance.

Eu-tTG® IgA

Performance Metric	Reported Device Performance (with Borderline Samples Considered Positive, Cut-off 9 AU/mL)	Reported Device Performance (with Borderline Samples Considered Negative, Cut-off 16 AU/mL)
Sensitivity (95% C.I.)	97.5% (92.9% - 99.5%)	85.1% (77.5% - 90.9%)
Specificity (95% C.I.)	98.3% (95.8% - 99.5%)	99.2% (97.0% - 99.9%)
Positive Predictive Value (PPV) (95% C.I.)	96.7% (91.8% - 99.1%)	98.1% (93.3% - 99.8%)
Negative Predictive Value (NPV) (95% C.I.)	98.8% (96.4% - 99.7%)	93.0% (89.2% - 95.8%)

Eu-tTG® IgG

Performance Metric	Reported Device Performance (Cut-off 20 AU/mL)
Sensitivity (95% C.I.)	57% (49% - 64.6%)
Specificity (95% C.I.)	94.2% (90.5% - 96.8%)
Positive Predictive Value (PPV) (95% C.I.)	87.0% (79.2% - 92.7%)
Negative Predictive Value (NPV) (95% C.I.)	76.3% (71.0% - 81.0%)

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

Eu-tTG® IgA Clinical Study Test Set: 363 clinical samples (121 positive celiac patients, 242 negative samples).
Eu-tTG® IgG Clinical Study Test Set: 407 clinical samples (165 positive celiac patients, 242 negative samples).
Data Provenance: The document does not explicitly state the country of origin. It indicates that samples were from "clinically diagnosed celiac positive" and "negative samples... from healthy blood donors, IBD patients, patients affected by food intolerances and patients with autoimmune or infectious diseases." This suggests the samples are retrospective, sourced from clinical settings or blood banks, and are clinical samples, not necessarily from a controlled prospective study for this submission.

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

The document states that "The positive celiac patient samples were diagnosed with clinical findings and/or confirmed with biopsy." It does not specify the number of experts or their qualifications involved in establishing this ground truth (e.g., gastroenterologists, pathologists, etc.).

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth. It relies on existing clinical diagnoses and biopsy confirmations.

In the method comparison studies, the "comparator test" results served as the reference for agreement calculations, but this is not an adjudication of ground truth for the clinical diagnosis itself.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study focuses on the performance of a diagnostic immunoassay, not on human readers' interpretation of images or other data, with or without AI assistance.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done

Yes, the studies presented are for the standalone performance of the Eu-tTG® IgA and Eu-tTG® IgG immunoassay kits. These are in vitro diagnostic devices that directly analyze human serum samples; they do not involve a human-in-the-loop for interpreting the assay's output to render a diagnosis. The results (AU/mL values) are generated solely by the device.

7. The Type of Ground Truth Used

The ground truth for the clinical studies was established by:

Clinical findings: This implies a physician's assessment of symptoms, medical history, and other diagnostic indicators.
Biopsy confirmation: This refers to histological examination of intestinal tissue, which is the gold standard for diagnosing celiac disease.
For negative samples, the ground truth was based on being "healthy subjects and patients with autoimmune disorders, infectious disease and IBD" without celiac disease.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" in the context of machine learning or AI development. These are immunoassay kits, which are typically developed and optimized through laboratory procedures, rather than being "trained" on data in the AI sense.

However, the "Assay Cut-off" section refers to testing "153 samples" (103 healthy subjects and 50 non-celiac controls) to establish the normal range and cut-off values. While not a "training set" in the AI sense, these samples were used to define parameters of the assay.

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

As explained above, there isn't a "training set" in the typical AI sense. However, for the 153 samples used to establish cut-off values:

Healthy subjects: Presumed to be healthy without celiac disease.
Non-celiac controls (IBD patients): Diagnosed with IBD but implicitly confirmed not to have celiac disease.

The exact methods for establishing the "ground truth" (e.g., confirmation of health status, specific IBD diagnosis without co-occurring celiac disease) for these 153 samples are not detailed in the provided text.

Summary

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GRIFOLS

K102964

Grifols USA, Inc 2410 Lillyvale Avenue Los Angeles, CA 90032-3548 Tel. (323) 225-2221 (800) 421-0008 www.grifols.com

MAR - 7 2011

Page 1

510(k) Summary

Date 510(k) Summary Prepared: 4 March 2011 1.

Grifols USA, LLC 510(k) Owner:

Grifols USA, LLC 3. Submitter:

Submitter Name:	Grifols USA, LLC.
Contact Person:	Catherine L. Wong
Address:	2410 Lillyvale Avenue
	Los Angeles, CA 90032-3514
Telephone:	(323) 227-7280
Fax No .:	(323) 441-7902

4.

Proprietary and Established Names:	Eu-tTG® IgA & Eu-tTG® IgG
Common Names:	Human Tissue Transglutaminase IgA &
	IgG

5. Regulatory Information:

21 CFR § 866.5660 Regulation No .: Multiple autoantibodies immunological test system Regulation Section: Classification: Class II MVM, Autoantibodies, Endomysial (Tissue Transglutaminase) Product Code: Immunology (82) Panel:

Predicate Devices: 6.

Eu-tTG® IgA umana (K010625), predicate for Eu-tTG® IgA Aeskulisa tTG G (K042644), predicate for Eu-tTG® IgG

Device Information

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7. Device Description

Intended Use 8.

Summary of Comparison with Predicate Device 9.

The proposed devices (Eu-tTG® IgA & Eu-tTG® IgG) have been compared with their predicate devices (Eu-tTG® IgA umana, K010625 & Aeskulisa tTG G, K042644, respectively), and found to be substantially equivalent.

The design, features, technological characteristics, specifications and performance of the proposed devices have been compared with those of the predicate devices, as shown in Tables 1, 2, 3 and 4.

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SIMILARITIES
	Device	Predicate
Item	Eu-tTG® IgA	Eu-tTG® IgA umana (K010625)
Intended Use	The Eu-tTG® IgA is an in vitrodiagnostic enzyme immunoassay forthe semi-quantitative detection of IgAspecific antibodies directed againsttissue transglutaminase (tTG) inhuman serum. It is an aid in thediagnosis of celiac disease and shouldbe used in conjunction with otherserological tests and clinical findings.	Eu-tTG® IgA Umana Assay is aqualitative ELISA test for the in vitrodiagnostic detection of IgA antibodyagainst the recombinant enzymetissue transglutaminase (tTG) inhuman serum. This test is designedfor use as an aid in the diagnosis ofCeliac Disease.
Methodology	ELISA	Same
Analyte	Anti-human tissue transglutaminase(tTG) IgA antibodies	Same
Capture Antigen	Human recombinant tTG	Same
Detection Antibody	Goat anti-human IgA conjugate	Same
Enzyme Conjugate	Horseradish peroxidase (HRP)	Same
Substrate/Chromogen	TMB	Same
OD Reading	450 nm on spectrophotometer	Same
Positive Control	Human serum positive for tTG IgAAntibodies	Same
Negative Control	Human serum	Same
Controls	One positive controlOne negative control	Same
Storage	2-8° C	Same
Sample VolumeRequired	100 μL	Same
Sample Diluent	Ready-to-use	Same
Wash Solution/Buffer	20 X concentrated	Same

Table 1 Device Similarity Between Eu-tTG® IgA and Predicate (Eu-tTG® IgA umana, K010625)

Table 2 Device Differences Between Eu-1TG® IgA and Predicate (Eu-1TG® IgA umana K010625)

DIFFERENCES

DIFFERENCES
	Device	Predicate
Item	Eu-tTG® IgA	Eu-tTG® IgA Umana Assay (K010625
Assay Format	Semi-quantitative	Qualitative
Cutoff	9 AU/mL	7 AU/mL (Ages 2 to Adult);5 AU/mL (Children < 2 years)
Calibrators	Set of 5, Values in AU/mL:Calibrator S1: 0Calibrator S2: 10Calibrator S3: 20Calibrator S4: 50Calibrator S5: 100	One calibrator: 16 AU/mL
Incubation Times	45-30-15 minutes	60-30-30 minutes
Screening Dilution	1:101	1:26
Linear Range	4.2-99.9 AU/mL	NA
Limit of Detection	1.6 AU/mL	NA

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SIMILARITIES
	Device	Predicate
Item	Eu-tTG® IgG	Aeskulisa tTG G (K042644)
Intended Use	The Eu-tTG® IgG is an in vitrodiagnostic enzyme immunoassay forthe semi-quantitative detection of IgGspecific antibodies directed againsttissue transglutaminase (tTG) inhuman serum. It is an aid in thediagnosis of celiac disease and shouldbe used in conjunction with otherserological tests and clinical findings.	The AESKULISA tTG G is a solidphase enzyme immunoassay for thesemi-quantitative and qualitativedetection of IgG antibodies againsttissue transglutaminase (tTG) inhuman serum. The assay is an aid inthe diagnosis of celiac disease(gluten-sensitive enteropathy) andshould be used in conjunction withother serological tests and clinicalfindings. For in vitro diagnostic useonly.
Methodology	ELISA	Same
Analyte	Anti-human tissue transglutaminase(tTG) IgG antibodies	Same
Capture Antigen	Human recombinant tTG	Same
Detection Antibody	Goat anti-human IgG conjugate	Same
Enzyme Conjugate	Horseradish peroxidase (HRP)	Same
Substrate/Chromogen	TMB	Same
Screening Dilution	1:101	Same
OD Reading	450 nm on spectrophotometer	Same
Positive Control	Human serum positive for tTG IgGAntibodies	Same
Negative Control	Human serum	Same
Storage	2-8° C	Same
Sample VolumeRequired	100 µL	Same

Table 3 Device Similarity Between Eu-tTG® IgG and Predicate (Aeskulisa tTG G, K042644)

Table 4 Device Differences Between Eu-tTG® IgG and Predicate (Aeskulisa tTG G, K042644)

DIFFERENCES
Device	Predicate
Item	Eu-tTG® IgG	Aeskulisa tTG G (K042644)
Assay Format	Semi-quantitative	Qualitative or Semi-quantitative
Cutoff	20 AU/mL	15 U/mL
Calibrators	Set of 5, Values in AU/mL:Calibrator S1: 2Calibrator S2: 10Calibrator S3: 20Calibrator S4: 50Calibrator S5: 100	Set of 6, Values in U/mLCalibrator F: 0Calibrator E: 3Calibrator D: 10Calibrator C: 30Calibrator B: 100Calibrator A: 300
IncubationTimes	45-30-15 minutes	Protocol A: 30-15-15 minutesProtocol B: 30-30-30 minutes
Controls	One positive controlOne negative control	One positive controlOne negative controlOne cut-off control

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	Device	Predicate
Linear Range	4.1-99.8 AU/mL	1-100 U/mL
Limit of Detection	1.5 AU/mL	1.0 U/mL
Sample Diluent	Ready-to-use	5x concentrated
Wash Solution/Buffer	20x concentrated	50x concentrated

10. Standard/Guidance Document Referenced

The following standards were referenced in the submission:

CLSI EP5-A2, "Evaluation of Precision Performance of Quantitative . Measurement Methods"
CLSI EP6-A, "Evaluation of the Linearity of Quantitative Measurement . Procedures; A Statistical Approach"
CLSI EP7-A2, "Interference Testing in Clinical Chemistry" .
CLSI EP17-A, "Protocols for Determination of Limits of Detection and . Limits of Quantitation"
CLSI C28-A2, "How to Define and Determine Reference Intervals in the . Clinical Laboratory"
. CLSI EP9-A2, "Method Comparison and Bias Estimation Using Patient Samples"

Performance Characteristics 11.

11.1 Analytical Performance

11.1.1 Precision Study

The intra-run precision studies were each performed in one (1) assay run. Results are summarized in Tables 5 and 6.

Sample No.	1	2	3	4	5	6	7	8	9	10
Mean (AU/mL)	86.4	59.4	38.5	37.6	28.0	13.2	6.6	4.2	2.9	2.5
SD	3.8	4.0	1.3	0.8	1.2	1.1	0.3	0.2	0.1	0.1
CV%	4.4	6.7	3.3	2.1	4.4	8.6	3.9	3.7	2.6	4.0

Table 5 Intra-run Precision Results for Eu-tTG® IgA

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Sample No.	1	2	3	4	5	6	7	8	9	10
Mean (AU/mL)	87.0	63.9	58.5	53.8	42.9	39.9	39.8	33.1	9.9	8.9
SD	3.32	2.96	5.07	4.37	3.14	2.28	3.61	2.95	0.27	0.56
CV%	3.8	4.6	8.7	8.1	7.3	5.7	9.1	8.9	2.7	6.3

Table 6 Intra-run Precision Results for Eu-tTG® IgG

The inter-run (between days) precision study results are summarized in Table 7 and 8.

Sample No.	1	2	3	4	5	6	7	8	9	10
Mean (AU/mL)	85.1	59.9	38.2	32.6	28.2	11.4	7.1	4.0	2.7	2.7
SD	2.70	2.3	0.9	3.0	2.0	0.6	0.7	0.4	0.3	0.2
CV%	3.2	3.8	2.4	9.2	7.2	5.6	10.2	10.2	9.7	8.0

Table 7 Inter-run Precision Results for Eu-tTG® IgA

Table 8 Inter-run Precision Results for Eu-tTG® IgG
Sample	Mean (U/mL)	SD (U/mL)	CV (%)
Low	10.4	0.8	7.7
Medium	41.9	2.4	5.7
High	141.4	6.8	4.8

Sample No.	1	2	3	4	5	6	7	8	9	10
Mean (AU/mL)	89.5	68.4	52.5	45.2	39.8	37.1	36.2	36.2	9.6	8.3
SD	3.03	4.74	1.82	3.24	1.60	3.07	1.85	2.24	0.44	0.66
CV%	3.4	6.9	3.5	7.2	4.0	8.3	5.1	6.2	4.6	7.9

The inter-lot precision study results are summarized in Table 9 and 10.

Table 9 Inter-lot Precision Results for Eu-tTG IgA
Serum Sample No.	1	2	3	4	5	6	7
Mean (AU/mL)	92.2	68.5	62.0	26.1	15.1	4.5	2.5
S.D.	5.6	2.0	6.6	1.3	0.2	0.3	0.1
C.V. (%)	6.1	2.9	10.6	5.0	1.0	5.6	5.4

Table 9 Inter-lot Precision Results for Eu-tTG® IgA

Table 10 Inter-lot Precision Results for Eu-tTG® IgG

Serum Sample No.	1	2	3	4	5	6	7
Mean (AU/mL)	89.4	67.0	42.3	19.3	17.6	14.6	10.3
S.D.	3.75	4.73	0.88	0.78	0.27	1.55	0.68
C.V. (%)	4.2	7.1	2.1	4.0	1.5	10.6	6.6

Linearity/Assay Reportable Range 11.1.2

Linearity was studied using three (3) positive serum samples each for the Eu-tTG® IgA and Eu-tTG® IgG. Each sample was diluted with a low concentration serum sample at around the limit of detection (LoD), 1.6 AU/mL for Eu-tTG® IgA and 1.5 AU/mL for

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Eu-tTG® IgG, respectively, using a dilution scheme. The results of one (1) representative sample for Eu-tTG® IgA show a slope of 0.968 (95% C.I. 0.899 - 1.037), Y-intercept of -1.616 (95% C.I. -5.763 - 2.531) and R2 of 0.9925. The results of one (1) representative sample for Eu-tTG® IgG show a slope of 0.917 (95% C.I. 0.860 - 0.974), Y-intercept of -1.407 (95% C.I. -4.831 - 2.016) and R2 of 0.9933.

The results of the study support a linear range of 4.1-99.8 AU/mL for Eu-tTG® IgA, and 4.2-99.9 AU/mL for Eu-tTG® IgG. The claimed assay range is 1.6 (LoD) to 100 AU/mL for Eu-tTG® IgA, and 1.5 (LoD) to 100 AU/mL for Eu-tTG® IgG.

Traceability, Stability and Expected Values (Controls and Calibrators) 11.1.3

. Traceability

Calibrators are not traceable to any recognized standards. Calibrators are dilutions of the pooled serum of tTG antibody from patients with Celiac disease. The new calibrator and control lots are formulated from an array of tTG antibody positive sera obtained from various commercial plasma centers stored at -70°C. The calibrators and controls are taken from different pooled sera. As new lots of calibrators are developed, studies are performed to calibrate values against original calibrators. Each lot of calibrator is also tested in comparison with normal human sera, clinical samples and internal standards. The concentration values of the calibrators are as follows:

Calibrator	IgA Assay Value	IgG Assay Value
Cal S5	100 AU/mL	100 AU/mL
Cal S4	50 AU/mL	50 AU/mL
Cal S3	20 AU/mL	20 AU/mL
Cal S2	10 AU/mL	10 AU/mL
Cal S1	0 AU/mL	2 AU/mL

. Stability

Stability studies support the expiration date claims of 12 months at 2-8ºC for both Eu-tTG® IgA and Eu-tTG® IgG.

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. Sample Stability

Specimens should be stored at 2-8°C for no longer than five (5) days. For longer storage, serum specimens should be frozen at -20°C. Repeated freezing and thawing of samples should be avoided.

Detection Limit 11.1.4

The limits of blank (LoB) and the limits of detection (LoD) were calculated for both Eu-tTG® IgA and Eu-tTG® IgG, as shown in Table 11.

Table 11 Limits of Blank and Limits of Detection for Eu-tTG® IgA and Eu-tTG® IgG

	LoB (AU/mL)	LoD (AU/mL)
Eu-tTG® IgA	0.05	1.6
Eu-tTG® IgG	0.02	1.5

11.1.5 Analytical Specificity and Interference

A cross reactivity study was performed for both Eu-tTG® IgA and Eu-tTG® IgG using 73 characterized clinical patient samples from individuals with autoimmune disorders, such as: Hashimoto's Thyroiditis, Graves' Disease, Antinuclear Antibodies/Systemic Lupus Erythematosus (ANA/SLE) positive and Cyclic Citrullinated Peptide (CCP) positive; patients with IBD and H. pylori infection. One (1) CCP positive, two (2) Hashimoto's Thyroiditis and one (1) Graves' Disease out of 73 samples (4/73, 5.5%) were tested positive for Eu-tTG® IgA. One (1) Hashimoto's Thyroiditis and two (2) Graves' Disease out of 73 samples were tested positive with the Eu-tTG® IgG (3/73, 4.1%).

Interference was studied by mixing the serum samples with known tTG antibody levels with potentially interfering substances. The study results demonstrated that hemoglobin (up to 2 g/L), bilirubin (up to 342 umol/L), rheumatoid factor (up to 100 AU/mL) or lipids (triglycerides up to 130 mg/dL) does not significantly interfere with the performance of the Eu-tTG® IgA and Eu-tTG® IgG.

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Assay Cut-off 11.1.6

The normal range of the assay was established by testing 153 samples, of which 103 are healthy subjects and 50 non-celiac controls (IBD patients), on each assay.

The assay cut-off values for Eu-tTG® IgA was determined as follows: Negative <9 AU/mL Borderline 9-16 AU/mL Positive >16 AU/mL

The assay cut-off value for Eu-tTG® IgG was determined as follows: Negative <20 AU/mL ≥20 AU/mL Positive

11.2 Method Comparison Studies

Eu-tTG® IgA 11.2.1

A method comparison study was performed which compared the Eu-tTG® IgA to a comparator test using 179 clinical samples. These samples consist of clinically diagnosed celiac positive (clinical history and/or biopsy) and negative samples. The negative samples were obtained from healthy blood donors, IBD patients, patients affected by food intolerances and patients with autoimmune or infectious diseases. All samples were tested using Eu-tTG® IgA and the comparator test kit. The results of the studies are summarized in Tables 12 and 13.

Table 12 Results of Method Comparison Study (Eu-tTG® IgA with Borderline Samples Considered Positive Using Cut-off of 9 AU/mL)

		Eu-tTG® IgA umana Test (K010625)(Cut-off = 7 AU/mL)
		Positive	Negative	Total
Eu-tTG® IgA	Positive	70	2	72
	Negative	4	103	107
	Total	74	105	179

Positive % Agreement = 94.6% (95% CI 86.7% - 98.5%) Negative % Agreement = 98.1% (95% CI 93.3% - 99.8%) Overall % Agreement = 96.6% (95% CI 92.8% - 98.8%)

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		Eu-tTG® IgA umana Test (K010625)(Cut-off = 7 AU/mL)
		Positive	Negative	Total
Eu-tTG® IgA	Positive	61	0	61
	Negative	13	105	118
	Total	74	105	179

Table 13 Results of Method Comparison Study (Eu-tTG® IgA with Borderline Samples Considered Negative Using Cut-off of 16 AU/mL)

Positive % Agreement = 82.4% (95% CI 71.8% - 90.3%) Negative % Agreement = 100.0% (95% CI 96.5% - 100.0%) Overall % Agreement = 92.7% (95% CI 87.9% - 96.1%)

Eu-tTG® IgG 11.2.2

A method comparison study was performed which compared the Eu-tTG® IgG to a comparator test using 178 clinical samples. These samples consist of 51 clinically diagnosed Celiac positive (clinical history and/or biopsy), which include 8 total IgA deficient celiac patients, and 127 negative samples. The negative samples were obtained from healthy blood donors, IBD patients, patients affected by food intolerances and patients with autoimmune or infectious diseases. All samples were tested using Eu-tTG® IgG and the comparator test kit. The results of the studies are summarized in Table 14.

		Aeskulisa tTG G (K042644)(Cut-off = 15 AU/mL)
		Positive	Negative	Total
Eu-tTG® IgG(Cut-off = 20 AU/mL)	Positive	48	7	55
	Negative	6	117	123
	Total	54	124	178

Table 14 Results of Method Comparison Study

Positive % Agreement = 88.9% (95% CI 77.4% - 95.8%) Negative % Agreement = 94.4% (95% CI 88.7% - 97.7%) Overall % Agreement = 92.7% (95% CI 87.8% - 96.1%)

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11.3 Clinical Studies

Eu-tTG® IgA 11.3.1

For the Eu-tTG® IgA assay, the clinical study included 363 clinical samples, of which 121 are positive celiac patients and 242 are negative samples from healthy subjects and patients with autoimmune disorders, infectious disease and IBD. The positive celiac patient samples were diagnosed with clinical findings and/or confirmed with biopsy. Tables 15 and 16 demonstrate the clinical performance of the Eu-tTG® IgA assay.

Table 15 Clinical Performance Results for Eu-tTG® IgA (Borderline Samples Considered Positive Using Cut-off of 9 AU/mL)

		Celiac Disease
		Positive	Negative	Total
Eu-tTG® IgA	Positive	118	4	122
	Negative	3	238	241
	Total	121	242	363

Sensitivity = 97.5% (95% C.I. 92.9% - 99.5%) Specificity = 98.3% (95% C.I. 95.8% - 99.5%) Positive Predicative Value (PPV) = 96.7% (95% C.I. 91.8% - 99.1%) Negative Predicative Value (NPV) = 98.8% (95% C.I. 96.4% - 99.7%)

Table 16 Clinical Performance Results for Eu-tTG® IgA (Borderline Samples Considered Negative Using Cut-off of 16 AU/mL)

		Celiac Disease
		Positive	Negative	Total
Eu-tTG® IgA	Positive	103	2	105
	Negative	18	240	258
	Total	121	242	363

Sensitivity = 85.1% (95% C.I. 77.5% - 90.9%) Specificity = 99.2% (95% C.I. 97.0% - 99.9%) PPV = 98.1% (95% C.I. 93.3% - 99.8%) NPV = 93.0% (95% C.I. 89.2% - 95.8%)

Eu-tTG® IgG 11.3.2

For the Eu-tTG® IgG assay, the clinical study included 407 clinical samples, of which 165 are positive celiac patients, and 242 are

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negative samples from healthy subjects, and patients with autoimmune disorders, infectious disease and IBD. The positive celiac patient samples were diagnosed with clinical findings and/or confirmed with biopsy. Table 17 demonstrates the clinical performance of the Eu-tTG® IgG assay.

Table 17 Clinical Performance Results for Eu-tTG® IgG

		Celiac Disease
		Positive	Negative	Total
Eu-tTG® IgG	Positive	94	14	108
	Negative	71	228	299
	Total	165	242	407

Sensitivity = 57% (95% C.I. 49% - 64.6%) Specificity = 94.2% (95% C.I. 90.5% - 96.8%) PPV = 87.0% (95% C.I. 79.2% - 92.7%) NPV = 76.3% (95% C.I. 71.0% - 81.0%)

Expected Values 11.4

The expected value in the normal population is negative. However, the incidence of celiac disease in the normal population is about 1%, some apparently healthy, asymptomatic individuals may test positive for the tTG antibodies.

Conclusion 12

The submitted material in this 510(k) Premarket Notification is sufficient to support a substantial equivalence decision with the legally marketed predicate devices.

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Image /page/12/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol of a bird-like figure, which is the department's official emblem.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Grifols USA. LLC c/o Ms. Catherine L. Wong Director, Regulatory Affairs 2410 Lillyvale Avenue Los Angeles, California 90032

MAR 0 7 2011

Re: K102964

Trade/Device Name:	Eu-tTG® IgAEu-tTG® IgG
Regulation Number:	21 CFR§866.5660
Regulation Name:	Multiple autoantibodies immunological test system
Regulatory Class:	Class II
Product Code:	MVM
Dated:	February 7, 2011
Received:	February 8, 2011

Dear Ms. Wong:

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. Iisting 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 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 (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice

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Page 2 - Ms. Catherine Wong

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/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/cdrh/industry/support/index.html.

Sincerely yours,

Maria Mchan

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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Indication for Use Statement for Eu-tTG® IgG 4.2

510(k) Number (if known): K102964

Device Name: Eu-tTG® IgG

Indication for Use:

Prescription Use __ X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Leena Philip

Division Sign-Off > Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K102964

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Indication for Use Statement for Eu-tTG® IgA 4.1

510(k) Number (if known): K 102964

Device Name: Eu-tTG® IgA

Indication for Use:

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Reena Philip

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K102964

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).