EU-TTG IGA AND EU-TTG IGG
Device Facts
| Record ID | K102964 |
|---|---|
| Device Name | EU-TTG IGA AND EU-TTG IGG |
| Applicant | Grifols USA, Inc. |
| Product Code | MVM · Immunology |
| Decision Date | Mar 7, 2011 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5660 |
| Device Class | Class 2 |
Intended Use
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 Story
Eu-tTG® IgA and Eu-tTG® IgG are ELISA-based in vitro diagnostic kits for detecting anti-tTG antibodies in human serum. The device utilizes microtiter plates coated with human recombinant tTG antigen. Patient serum is added; if specific antibodies are present, they bind to the antigen. After washing, a goat anti-human IgA or IgG conjugate labeled with horseradish peroxidase (HRP) is added, followed by a TMB substrate. The resulting color change is measured via spectrophotometer at 450 nm. The intensity of the color is proportional to the concentration of tTG antibodies in the sample. The assay is performed in a clinical laboratory setting by trained personnel. Results are semi-quantitative, reported in AU/mL, and used by clinicians alongside other diagnostic data to support a celiac disease diagnosis. The device provides a standardized method for antibody quantification, aiding in the identification of patients requiring further clinical evaluation.
Clinical Evidence
Clinical performance was evaluated using 363 samples for IgA and 407 samples for IgG. For IgA (9 AU/mL cutoff), sensitivity was 97.5% and specificity 98.3%. For IgG, sensitivity was 57% and specificity 94.2%. Method comparison studies against predicate devices showed overall agreement of 92.7% to 96.6%. Analytical performance included precision (intra-run CV% 2.1-9.1%, inter-run CV% 2.4-10.2%), linearity (R2 > 0.99), and interference testing (no significant interference from hemoglobin, bilirubin, rheumatoid factor, or lipids).
Technological Characteristics
Sandwich ELISA; microtiter plate coated with human recombinant tTG antigen; HRP-conjugated goat anti-human IgA/IgG detection; TMB substrate; 450 nm spectrophotometric detection. Requires microtiter plate reader. Storage 2-8°C. Analytical performance validated per CLSI guidelines (EP5-A2, EP6-A, EP7-A2, EP17-A, C28-A2, EP9-A2).
Indications for Use
Indicated for the semi-quantitative detection of IgA or IgG specific antibodies against tissue transglutaminase (tTG) in human serum as an aid in the diagnosis of celiac disease in patients suspected of having the condition. For prescription use only.
Regulatory Classification
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).
Predicate Devices
- Eu-tTG® IgA umana (k010625)
- AESKULISA® tTg G (k042644)
Submission Summary (Full Text)
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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.
2. 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
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.
#### Intended Use 8.
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.
#### 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 <i>in vitro</i><br>diagnostic enzyme immunoassay for<br>the semi-quantitative detection of IgA<br>specific antibodies directed against<br>tissue transglutaminase (tTG) in<br>human serum. It is an aid in the<br>diagnosis of celiac disease and should<br>be used in conjunction with other<br>serological tests and clinical findings. | Eu-tTG® IgA Umana Assay is a<br>qualitative ELISA test for the <i>in vitro</i><br>diagnostic detection of IgA antibody<br>against the recombinant enzyme<br>tissue transglutaminase (tTG) in<br>human serum. This test is designed<br>for use as an aid in the diagnosis of<br>Celiac Disease. |
| Methodology | ELISA | Same |
| Analyte | Anti-human tissue transglutaminase<br>(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 IgA<br>Antibodies | Same |
| Negative Control | Human serum | Same |
| Controls | One positive control<br>One negative control | Same |
| Storage | 2-8° C | Same |
| Sample Volume<br>Required | 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);<br>5 AU/mL (Children < 2 years) |
| Calibrators | Set of 5, Values in AU/mL:<br>Calibrator S1: 0<br>Calibrator S2: 10<br>Calibrator S3: 20<br>Calibrator S4: 50<br>Calibrator 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 vitro<br>diagnostic enzyme immunoassay for<br>the semi-quantitative detection of IgG<br>specific antibodies directed against<br>tissue transglutaminase (tTG) in<br>human serum. It is an aid in the<br>diagnosis of celiac disease and should<br>be used in conjunction with other<br>serological tests and clinical findings. | The AESKULISA tTG G is a solid<br>phase enzyme immunoassay for the<br>semi-quantitative and qualitative<br>detection of IgG antibodies against<br>tissue transglutaminase (tTG) in<br>human serum. The assay is an aid in<br>the diagnosis of celiac disease<br>(gluten-sensitive enteropathy) and<br>should be used in conjunction with<br>other serological tests and clinical<br>findings. For in vitro diagnostic use<br>only. |
| Methodology | ELISA | Same |
| Analyte | Anti-human tissue transglutaminase<br>(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 IgG<br>Antibodies | Same |
| Negative Control | Human serum | Same |
| Storage | 2-8° C | Same |
| Sample Volume<br>Required | 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:<br>Calibrator S1: 2<br>Calibrator S2: 10<br>Calibrator S3: 20<br>Calibrator S4: 50<br>Calibrator S5: 100 | Set of 6, Values in U/mL<br>Calibrator F: 0<br>Calibrator E: 3<br>Calibrator D: 10<br>Calibrator C: 30<br>Calibrator B: 100<br>Calibrator A: 300 |
| Incubation<br>Times | 45-30-15 minutes | Protocol A: 30-15-15 minutes<br>Protocol B: 30-30-30 minutes |
| Controls | One positive control<br>One negative control | One positive control<br>One negative control<br>One 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)<br>(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)<br>(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)<br>(Cut-off = 15 AU/mL) | | |
|-------------------------------------|----------|---------------------------------------------------|----------|-------|
| | | Positive | Negative | Total |
| Eu-tTG® IgG<br>(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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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® IgA<br>Eu-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:
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.
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:
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.
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
