EliA Celikey IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to tissue transglutaminase (tTG) in human serum and EDTA-plasma. EliA Celikey IgG is based on recombinant human tissue transglutaminase as antigen and is useful as an aid in the clinical diagnosis of patients with celiac disease in conjunction with other laboratory and clinical findings. EliA Celikey IgG uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA GliadinDP IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to gliadin in human serum or plasma (Li-heparin, EDTA) to aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings. EliA GliadinDP IgA uses the EliA IgA method on the instrument Phadia 2500/5000.

EliA GliadinDP IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to gliadin in human serum or plasma (Li-heparin, EDTA) to aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings. EliA GliadinDP IgG uses the EliA IgG method on the instrument Phadia 2500/5000.

Device Description

The method-specific reagents are identical with K062583 (EliA Celikey IgG) and K093459 (EliA Gliadin® IgA and EliA Gliadin® IgG), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of: Test Wells (EliA Celikey IgG Wells, EliA GliadinDP IgA Wells, EliA GliadinDP IgG Wells), EliA Sample Diluent, EliA IgG reagents (EliA IgG Conjugate, EliA IgG Calibrator Strips, EliA IgG Curve Control Strips, EliA IgG Calibrator Well), and EliA IgA reagents (EliA IgA Conjugate, EliA IgA Calibrator Strips, EliA IgA Curve Control Strips, EliA IgA Calibrator Well). The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages are required to carry out EliA Celikey IgG and EliA GliadinDP IgA and EliA GliadinDP IgG tests.

AI/ML Overview

The provided document is a 510(k) Premarket Notification from the FDA, detailing the substantial equivalence determination for the Phadia AB EliA Immunoassays (Celikey IgG, GliadinDP IgA, GliadinDP IgG) for use on the Phadia 2500/5000 instrument. The document primarily focuses on demonstrating that the performance of these assays on the new instrument platform is substantially equivalent to their performance on a previously cleared instrument (Phadia 250).

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly present a single table outlining "acceptance criteria" alongside "reported device performance" for the overall substantial equivalence determination. Instead, it details performance characteristics for various analytical aspects, and the acceptance criteria are implied by the ranges and thresholds specified for these studies. The primary "acceptance criteria" for the overall submission appear to be demonstrating equivalence to the predicate device and meeting specific statistical thresholds for precision and linearity.

However, based on the sections "M. Performance Characteristics (if/when applicable)" and "2. Comparison studies: - Instrument comparison C.", we can construct a table for the analytical performance and comparative study results:

Table: Acceptance Criteria (Implied) and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied from stated goals or predicate performance)	Reported Device Performance (Phadia 2500/5000)
Precision	Variability assessed across 21 runs (3 instruments x 7 runs) for each assay. (No explicit %CV targets given, but comparison to typical acceptable analytical variation in such assays is implied). CLSI EP05-A3 guidelines followed.	EliA Celikey IgG: Total Imprecision (%CV): 27.9% (at 1.6 EliA U/mL), 5.9% (at 7.6), 6.6% (at 9.6), 5.1% (at 104.4), 5.3% (at 274.6).EliA GliadinDP IgA: Total Imprecision (%CV): 18.2% (at 0.8), 3.6% (at 7.4), 4.5% (at 8.7), 5.0% (at 42.8), 9.3% (at 135.3).EliA GliadinDP IgG: Total Imprecision (%CV): 13.0% (at 3.6), 7.0% (at 7.2), 5.9% (at 9.3), 8.1% (at 73.7), 7.7% (at 219.6).
Linearity/Reportable Range	Assays should demonstrate linearity across their measurement range. CLSI EP06-A guidelines followed. "Slope for the regression lines should be 0.9 - 1.1... and intercept close to 0."	EliA Celikey IgG: Slope: 1.01-1.04, Intercept: 0.49-2.48, R2: 0.99-1.00.EliA GliadinDP IgA: Slope: 0.99-1.00, Intercept: -1.69-0.79, R2: 1.00.EliA GliadinDP IgG: Slope: 0.98-1.00, Intercept: -5.65-1.02, R2: 0.99-1.00.All R2 values are very close to 1, indicating strong linearity.
Limit of Detection (LoD), Limit of Quantitation (LoQ)	Determined consistent with CLSI EP17-A2 guidelines; proportions of false positives (α) < 5%, false negatives (β) < 5% (for LoD); target uncertainty goal of 20% (for LoQ).	EliA Celikey IgG: LoD: 0.6 EliA U/mL, LoQ: 1.7 EliA U/mL.EliA GliadinDP IgA: LoD: 0.2 EliA U/mL, LoQ: 0.4 EliA U/mL.EliA GliadinDP IgG: LoD: 0.6 EliA U/mL, LoQ: 1.4 EliA U/mL.
Method Comparison (Instrument Comparison)	Slope for regression lines should be 0.9-1.1 for single replicate to single replicate, and intercept close to 0. (Comparing Phadia 2500/5000 to Phadia 250). Additionally, PPA, NPA, and TPA are reported. No explicit acceptance criteria for PPA/NPA/TPA are stated, but high percentages are implied to demonstrate substantial equivalence.	EliA Celikey IgG: Slopes 0.93-0.98, Intercepts -0.28-0.49. PPA: 94.0-97.4%, NPA: 82.6-91.3%, TPA: 94.0-95.0% (equivocal positive); PPA: 94.0-97.0%, NPA: 100.0%, TPA: 96.0-98.0% (equivocal negative).EliA GliadinDP IgA: Slopes 0.95-1.09, Intercepts -0.24-0.60. PPA: 100.0%, NPA: 85.7-90.5%, TPA: 97.1-98.1% (equivocal positive); PPA: 98.7-100.0%, NPA: 96.2%, TPA: 98.1-99.0% (equivocal negative).EliA GliadinDP IgG: Slopes 0.99-1.08, Intercepts -0.14-0.43. PPA: 100.0%, NPA: 89.5-100.0%, TPA: 98.1-100.0% (equivocal positive); PPA: 98.8-100.0%, NPA: 91.7-100.0%, TPA: 98.1-99.0% (equivocal negative).

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Precision Test Set: The study used "a total of 21 runs (3 instruments x 7 runs)". Each sample was tested in "four replicates/run giving in total 84 replicates per sample." The number of distinct samples for precision is not explicitly stated, but multiple samples covering various concentrations are typically used (e.g., 5 samples in the EliA Celikey IgG table).
Linearity Test Set: "Four patient serum samples (five for Celikey IgG)" were diluted and tested.
Detection Limit Test Set: "One blank sample and three low level samples were measured in thirty-three and eleven replicates, respectively, in each of two runs." For Celikey IgG LoD, "6 low level samples and a total of 132 determinations" were used. For LoQ, "66 determinations of 3 low level samples."
Method Comparison Test Set: "More than 100 samples (≥20% of the samples within ±25% of the medical decision point)" were run for each of the three EliA tests.
Expected Values/Reference Range: 400 "apparently healthy subjects ... from a Caucasian population obtained from a blood bank."

Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. It is a 510(k) submission for a device, and the focus is on analytical performance and comparison to a predicate device, not primary clinical trial data of patient outcomes. The "Expected Values/Reference Range" suggests the use of existing blood bank samples, which typically implies retrospective use of collected samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not applicable to this type of device and study. The EliA Immunoassays measure specific antibodies (tTG IgG, Gliadin IgA, Gliadin IgG) in patient samples. The "ground truth" for the analytical studies (precision, linearity, detection limits, method comparison) is based on the quantitative concentration of these analytes as measured by the predicate device or a reference method, rather than subjective expert interpretation (like in imaging studies). For the reference range, the "ground truth" is simply the measured values in a defined healthy population.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not applicable. Adjudication methods (like 2+1 or 3+1 for resolving discrepancies) are typically used in clinical studies where expert readers independently interpret data (e.g., medical images) and their interpretations need to be reconciled to establish a "ground truth" or reference standard. This document describes analytical and comparative studies for an in vitro diagnostic immunoassay, where quantitative measurements are the primary data.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This information is not applicable. MRMC studies are primarily relevant for AI-powered diagnostic devices, particularly in medical imaging, where multiple human readers interpret cases, and the AI's impact on their diagnostic performance is assessed. This document pertains to an in vitro diagnostic immunoassay, not an AI-assisted diagnostic tool that aids human "readers."

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

Yes, this can be considered a standalone performance evaluation in the context of an immunoassay. The device (EliA Immunoassays on Phadia 2500/5000) operates as an automated system to semi-quantitatively measure antibody levels. The analytical performance studies (precision, linearity, LoD/LoQ) and the instrument comparison are essentially the "standalone" performance of the assay on the new platform. It's not an "algorithm only" in the sense of a software-only device, but the analytical steps are automated, and the reported values are direct outputs of the system. Human intervention relates to sample loading and equipment maintenance, not interpretation of raw data for diagnosis.

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

The "ground truth" for the performance studies described is primarily:

Quantitative Analytical Values: For precision, linearity, LoD/LoQ, the ground truth is derived from the inherent nature of the samples at known or measured concentrations, often established by reference methods or highly characterized materials.
Predicate Device Measurements: For the "Instrument Comparison," the results obtained from the previously cleared Phadia 250 instrument serve as the reference or "ground truth" against which the new Phadia 2500/5000 is compared to demonstrate substantial equivalence.
Clinically Defined Healthy Population: For "Expected Values/Reference Range," the ground truth is simply the distribution of the analyte in a healthy population.

It's important to note that this 510(k) is for "adding previously cleared assays on a new instrument platform." This means the clinical utility and diagnostic performance (e.g., clinical sensitivity/specificity for celiac disease) of the assays themselves were already established and reviewed in the original 510(k) clearances (K062583 and K093459). The current submission leverages that prior clinical validation by demonstrating that the new instrument maintains equivalent analytical performance. Thus, the "clinical ground truth" for celiac disease diagnosis (e.g., biopsy confirmation, clinical outcomes) was established in those prior studies, not detailed here. The current submission's focus is on bridging the analytical performance to the new instrument.

8. The sample size for the training set

This document describes a 510(k) submission for an IVD immunoassay, not a machine learning or AI model. Therefore, there is no "training set" in the context of artificial intelligence/machine learning. The assays are based on established biochemical principles (antigen-antibody reactions, fluorescence detection), not on training data to learn patterns or parameters.

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

As there is no "training set" for an AI/ML model, this question is not applicable. The methods for establishing the performance characteristics are described in point 7 above.

Summary

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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

March 1, 2019

Phadia AB % Sheryl Skinner Regulatory Director, RA/QA Phadia US Inc. 4169 Commercial Avenue Portage, Michigan 49002

Re: K181871

Trade/Device Name: EliA Celikey IgG Immunoassay; EliA GliadinDP IgA Immunoassay; EliA GliadinDP IgG Immunoassay Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MVM, MST Dated: July 10, 2018 Received: July 12, 2018

Dear Sheryl Skinner:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

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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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Douglas A. Jeffery -S

Doug Jeffery, Ph.D. Branch Chief Immunology and Flow Cytometry Branch Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K181871

Device Name

EliA Celikey IgG Immunoassay, EliA GliadinDP IgA Immunoassay, EliA GliadinDP IgG Immunoassay

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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A.6 510(k) Summary of Safety and Effectiveness per 21CFR 807.92(c).

This summary of safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR Part 807.92.

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number: K181871

B. Purpose for Submission:

Adding previously cleared assays on a new instrument platform (Phadia® 2500/5000)

C. Measurands:

Anti-tissue transglutaminase (tTG) IgG antibody Anti-gliadin IgA and anti-gliadin IgG autoantibodies

D. Type of Test:

Semi-quantitative measurement immunoassays

E. Applicant:

Phadia AB Rapsgatan 7P P.O. Box 6460 SE-751 37 Uppsala, Sweden Tel: +46-18-16 50 60

510(k) Contact Person: Sheryl Skinner Associate Director, RA/QA ImmunoDiagnostics US Thermo Fisher Scientific Phadia US Inc. 4169 Commercial Avenue Portage, Mi 49002, USA Tel. 269.568.3603 sheryl.skinner@thermofisher.com

Date of Summary Preparation:

February 28, 2019

F. Proprietary and Established Names:

EliA Celikey IgG Immunoassay EliA Gliadin®º IgA Immunoassay EliA Gliadin®º IgG Immunoassay

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G. Regulatory Information:

1. Requlation section:
- 21 CFR §866.5660 Multiple autoantibodies immunological test system 21 CFR §866.5750 – Radioallergosorbent (RAST) Immunological Test System
1. Classification:

Class II

1. Product code:
  MVM Autoantibodies, endomysial (tissue transqlutaminase) autoantibodies, gliadin MST
1. Panel: Immunology (82)

H. Intended use(s):

Intended use(s):

EliA Celikey IqG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to tissue transglutaminase (tTG) in human serum and EDTAplasma. EliA Celikey IgG is based on recombinant human tissue transqlutaminase as antigen and is useful as an aid in the clinical diagnosis of patients with celiac disease in conjunction with other laboratory and clinical findings. EliA Celikey IqG uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA Gliadin®° IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to gliadin in human serum or plasma (Li-heparin, EDTA) to aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings. EliA Gliadin® IgA uses the EliA IgA method on the instrument Phadia 2500/5000.

EliA Gliadin®P IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to gliadin in human serum or plasma (Li-heparin, EDTA) to aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings. EliA Gliadin® IgG uses the EliA IgG method on the instrument Phadia 2500/5000.

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

For prescription use only

Special instrument requirements: ধ
Performance studies were obtained from the Phadia® 2500/5000 instrument This device is not for point-of-care use.

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. Device Description:

EliA Celikey IgG Wells are coated with human recombinant tissue transglutaminase (tTG) - 2 carriers (12 wells each), ready to use;
EliA Gliadin®° IgA Wells are coated with synthetic deamidated gliadin peptides -- 4 carriers (12 wells each), ready to use;
-EliA Gliadin®° IgG Wells are coated with synthetic deamidated gliadin peptides - 4 carriers (12 wells each), ready to use;

EliA Sample Diluent:

EliA Sample Diluent: PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
EliA IgG reagents (required for EliA Celikey IgG and EliA Gliadin®º IgG):
EliA IgG Coniugate 50 or 200: ß-Galactosidase labeled anti-laG (mouse monoclonal antibodies) in PBS containing BSA and 0.06% (w/v) sodium azide – 6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
EliA IgG Calibrator Strips: Human IgG (0, 4, 10, 20, 100, 600 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 singleuse vials per strip, 0.3 mL each, ready to use;
EliA IgG Curve Control Strips: Human IgG (20 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide – 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
EliA IgG Calibrator Well: Coated with mouse monoclonal antibodies 4 carriers (12 wells each), ready to use.

EliA IgA reagents (required for EliA Gliadin®º IgA):

EliA IgA Conjugate 50 or 200: ß-Galactosidase labeled anti-IgA (mouse monoclonal antibodies) in PBS containing BSA and 0.06% (w/v) sodium azide -6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
-EliA IgA Calibrator Strips: Human IgA (0, 0.3, 1.5, 5, 15, 80 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 singleuse vials per strip, 0.3 mL each, ready to use;
-EliA IgA Curve Control Strips: Human IgA (20 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
-EliA IgA Calibrator Well: Coated with mouse monoclonal antibodies - 4 carriers (12 wells each), ready to use.

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The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages are required to carry out EliA Celikey IgG and EliA Gliadin®º IgA and EliA Gliadinºº IgG tests.

J. Substantial Equivalence Information:

Predicate device name(s) and 510(k) number(s): EliA Celikey IgG on Phadia 250 instrument, K062583 EliA Gliadin®P IgA on Phadia 250 instrument, K093459 EliA Gliadin®° IgG on Phadia 250 instrument, K093459

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2. Comparison with predicate device:

EliA Celiac Immunoassays on Phadia 250 and Phadia 2500/5000 instruments – Similarities to predicate devices

Feature	Predicate DevicePhadia 250	New DevicePhadia 2500/5000
Intended UseEliA Celikey IgG	EliA Celikey IgG is intended forthe in vitro semi-quantitativemeasurement of IgG antibodiesdirected to tissuetransglutaminase (tTG) in humanserum and plasma. EliA CelikeyIgG is based on recombinanthuman tissue transglutaminaseas antigen and is useful as anaid in the clinical diagnosis ofpatients with Celiac disease. EliACelikey IgG uses the EliA IgGmethod on the instrumentImmunoCAP 250.( Former name of Phadia 250)	EliA Celikey IgG is intended forthe in vitro semi-quantitativemeasurement of IgG antibodiesdirected to tissuetransglutaminase (tTG) in humanserum and EDTA-plasma. EliACelikey IgG is based onrecombinant human tissuetransglutaminase as antigen andis useful as an aid in the clinicaldiagnosis of patients with celiacdisease in conjunction with otherlaboratory and clinical findings.EliA Celikey IgG uses the EliAIgG method on the instrumentPhadia 2500/5000.
Intended UseEliA GliadinDP IgA	EliA GliadinDP IgA is intended forthe in vitro semi-quantitativemeasurement of IgA antibodiesdirected to gliadin in humanserum and plasma (heparin,EDTA, citrate) to aid in thediagnosis of celiac disease inconjunction with other laboratoryand clinical findings. EliAGliadinDP IgA uses the EliA IgAmethod on the instrumentPhadia 250.	EliA GliadinDP IgA is intended forthe in vitro semi-quantitativemeasurement of IgA antibodiesdirected to gliadin in humanserum or plasma (Li-heparin,EDTA) to aid in the diagnosis ofceliac disease in conjunctionwith other laboratory and clinicalfindings. EliA GliadinDP IgA usesthe EliA IgA method on theinstrument Phadia 2500/5000.
Intended UseEliA GliadinDP IgG	EliA GliadinDP IgG is intended forthe in vitro semi-quantitativemeasurement of IgG antibodiesdirected to gliadin in humanserum and plasma (heparin,EDTA, citrate) to aid in thediagnosis of celiac disease inconjunction with other laboratoryand clinical findings. EliAGliadinDP IgG uses the EliA IgGmethod on the instrumentPhadia 250.	EliA GliadinDP IgG is intended forthe in vitro semi-quantitativemeasurement of IgG antibodiesdirected to gliadin in humanserum or plasma (Li-heparin,EDTA) to aid in the diagnosis ofceliac disease in conjunctionwith other laboratory and clinicalfindings. EliA GliadinDP IgG usesthe EliA IgG method on theinstrument Phadia 2500/5000.
Analyticaltechnology:Immuno-fluorescencemeasurement	Same	Same
Assay process	Same	Same
Common, dedicatedPhadia reagents	Same	SameIntroduction of new articlenumbers for DevelopmentSolution, Stop Solution andWashing Solution is only due tolarger filling volumes which arerequired for the biggerinstruments Phadia 2500/5000
Result calculationsoftware; PhadiaInformation DataManager (IDM)	Same	Same
Sample volume	90 µL (20 µL of non-dilutedsample)	90 µL (20 µL of non-dilutedsample)
Incubationtemperature	37°C	37°C
Conjugate volume	90 µL	90 µL
DevelopmentSolution Volume	90 µL	90 µL
Stop SolutionVolume	200 µL	200 µL
Assay set-up	Random access	Random access
Reagent packagingsize	Various/Common	Various/CommonIntroduction of new articlenumber for EliA Sample Diluent(83-1071-01) is only due tolarger filling volume.
Onboard storage ofreagents	Yes	Yes
Feature	Predicate DevicePhadia 250	New DevicePhadia 2500/5000
Sample matrix;Serum or plasmatype as indicated inthe DFU dependenton assay	For EliA Celikey IgG: Serum orplasma (EDTA, citrate)For EliA GliadinDP IgA and IgG:Serum or plasma (heparin,EDTA, citrate)	For EliA Celikey IgG: serum orEDTA-plasmaFor EliA GliadinDP IgA and IgG:Serum or plasma (Li-heparin,EDTA)
Daily throughput	~250 tests	~2500/5000 tests
Sample Dilution	Phadia 250 uses a steel pipetteto dilute the samples in DilutionPlates (Art.No. 12-3907-08)	Phadia 2500/5000 usesdisposable Pipette Tips in Racks(Art No. 12-3805-04) forpipetting samples in DilutionWell (Art.No. 12-4005-69)
Risk for carry-over	The warning “DO NOT REUSE”in the Phadia 250 DFU for EliAConjugates is due to the fact thata low risk of conjugatecontamination by carry-over fromsamples was identified. In orderto reduce the risk, the single usestatement for the conjugate wasincluded in the Phadia 250 DFU.	When running EliA tests on thePhadia 2500/5000 instruments,there is no need for this warningstatement because theseinstruments use disposable tipsfor pipetting samples and aseparate pipette for theconjugate, and carry-over fromsamples to conjugate isimpossible.
Loading of EliACarriers	EliA carriers are loaded manuallyon the Loading Tray from wherethey can be processed directly ortransferred to the cooled storagecompartment.	The Phadia 2500/5000instruments do not have such aLoading Tray. The EliA carriersare loaded into racks which aredirectly transferred to the cooledstorage compartment
Barcode reader	The Phadia 250 instrument hasa built-in barcode reader at thefront of the instrument, but theoperator needs to scan thebarcodes manually by showingthe reagents to the barcodereader. Alternatively, theoperator can also enter thecharacters below the barcodemanually.	The Phadia 2500/5000instruments dispose of a built-inbarcode reader, and thereagents are on a moving beltwhich conveys them past thebarcode reader. The lot-specificinformation will be readautomatically by the instrumentduring loading.
Process time / Timeto patient result	Phadia 250 needs 1 minute toprocess one Well.Phadia 250 provides the resultsat a one minute interval.	Phadia 2500/5000 instrumentsprocess two Wells in parallel in48 seconds.Phadia 2500/5000 provides theresults at a 24 seconds interval.

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EliA Celiac Immunoassays on Phadia 250 and Phadia 2500/5000 instruments – Differences to predicate device

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

CLSI EP05-A3; Evaluation of Precision Performance of Quantitative Measurement Methods: September 2014

CLSI EP06-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: April 2003

CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantification: October 2004.

CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples

L. Test Principle:

The EliA wells are molded cups comparable to excised wells from a microtiter plate. They are made of polystyrene and are coated with the respective antigen. The wells are at the same time a holder of the coupled antigen for convenient automation and a reaction chamber with reaction/washing solution handling based on pipetting to add and aspiration to remove liquids.

The EliA wells are coated with human recombinant tissue transglutaminase, or with synthetic deamidated gliadin peptides. If present in the patient's specimen, antibodies to these proteins bind to the specific antigen. After washing away nonbound antibodies, enzyme-labeled antibodies against human IgA or IgG antibodies (EliA IgA Conjugate or EliA IgG Conjugate) are added to form an antibody-conjugate complex. After incubation, non-bound conjugate is washed away and the bound complex is incubated with a Development Solution. After stopping the reaction, the fluorescence in the reaction mixture is measured. The higher the response value, the more specific IgA or IgG is present in the specimen. To evaluate test results, the response for patient samples is compared directly to the response for calibrators.

M. Performance Characteristics (if/when applicable):

Analytical performance:

a. Precision/Reproducibility:
To determine the precision of the assay, the variability was assessed in a study with a total of 21 runs (3 instruments x 7 runs).

The study was performed with 1 run/dav over a period of 7 days. Each sample was tested in four replicates/run giving in total 84 replicates per sample. The data was calculated against the calibration curve from Day 1.

The results are summarized in the table below:

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Mean(EliA U/mL)	Within-Run		Between-Run		Between-Instrument		Total Imprecision
	SD	%CV	SD	%CV	SD	%CV	SD	%CV
1.6	0.2	10.0	0.1	7.2	0.4	25.0	0.4	27.9
7.6	0.2	2.8	0.2	3.1	0.3	4.2	0.4	5.9
9.6	0.3	2.7	0.3	2.6	0.5	5.4	0.6	6.6
104.4	2.7	2.6	3.1	3.0	3.4	3.3	5.3	5.1
274.6	8.4	3.1	6.9	2.5	9.5	3.5	14.5	5.3

EliA Celikey IgG on Phadia 2500/5000

EliA Gliadin®º IgA on Phadia 2500/5000

Mean(EliAU/mL)	Within-Run	Between-Run		Between-Instrument		TotalImprecision
	SD	%CV	SD	%CV	SD	%CV	SD	%CV
0.8	0.1	8.9	0.0	5.7	0.1	14.9	0.1	18.2
7.4	0.2	3.0	0.1	1.5	0.1	1.3	0.3	3.6
8.7	0.2	2.8	0.2	2.6	0.2	2.3	0.4	4.5
42.8	1.5	3.6	0.9	2.1	1.2	2.8	2.1	5.0
135.3	5.8	4.3	3.8	2.8	10.4	7.7	12.5	9.3

EliA Gliadin®º IgG on Phadia 2500/5000

Mean		Within-Run	Between-Run		Between-Instrument		TotalImprecision
(EliAU/mL)	SD	%CV	SD	%CV	SD	%CV	SD	%CV
3.6	0.3	8.2	0.2	5.2	0.3	8.6	0.5	13.0
7.2	0.2	3.3	0.4	5.4	0.2	3.1	0.5	7.0
9.3	0.3	2.8	0.5	5.2	0.0	0.0	0.5	5.9
73.7	2.6	3.5	4.9	6.7	2.2	3.0	6.0	8.1
219.6	8.2	3.7	13.2	6.0	6.8	3.1	17.0	7.7

b. Linearity/assay reportable range:

Four patient serum samples (five for Celikey IgG) were diluted in sample diluent and tested with one batch of EliA Celikey IgG, EliA Gliadin®° IgA and EliA Gliadin®° IgG Immunoassays and one set of system reagents on Phadia 2500/5000. The results of the regression analysis are summarized below:

Dilution range(EliA U/mL)	Slope	Intercept	R2
1.3 – 35.5	1.03	0.49	0.99
1.8 – 32.9	1.02	0.69	0.99
2.2 – 196.6	1.02	1.68	1.00
7.1 – 174.0	1.01	2.26	1.00
2.8 – 227.8	1.04	2.48	0.99

EliA Celikev IgG on Phadia 2500/5000

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The reportable range (Limit of Detection, upper limit) for EliA Celikey IgG is from 0.6 to 227 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 1.7 to 227 EliA U/mL.

Dilution range(EliA U/mL)	Slope	Intercept	R2
0.4 – 28.5	1.00	-0.04	1.00
1.3 – 137.8	0.99	-1.69	1.00
0.6 – 26.9	1.00	-0.30	1.00
2.1 – 162.0	0.99	0.79	1.00

EliA Gliadin®º IgA on Phadia 2500/5000

The reportable range (Limit of Detection, upper limit) for EliA Gliadin® IgA is from 0.2 to 142 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 0.4 to 142 EliA U/mL. Please note that concentration values between LoD and LoQ may show a higher uncertainty.

EliA Gliadin®º IgG on Phadia 2500/5000

Dilution range(EliA U/mL)	Slope	Intercept	R2
0.6 - 26.3	0.99	-0.32	1.00
0.8 – 54.4	1.00	-0.50	1.00
7.0 - 334.9	0.98	-5.65	0.99
7.3 – 288.3	1.00	1.02	1.00

The reportable range (Limit of Detection, upper limit) for EliA Gliadin® IgG is from 0.6 to 302 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 1.4 to 302 EliA U/mL.

Statements included in the package inserts: "Please note that concentration values between LoD and LoQ may show a higher uncertainty." "Please note that due to differing binding characteristics of the antibodies in patient samples, not all sera can be diluted linearly within the measuring range."

Traceability, Stability, Expected values (controls, calibrators, or methods): C. The EliA IgG method was previously reviewed in K061165. The EliA IgA method was previously reviewed in K062787.
d. Detection limit:

The limit of blank (LoB), limit of detection (LoD), and limit of quantitation studies were performed on the Phadia 2500/5000 instrument. One blank sample and three low level samples were measured in thirty-three and eleven replicates, respectively, in each of two runs.

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EliA Celikey IgG:

The LoD for EliA Celikey IgG is 0.6 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2 and with proportions of false positives (a) less than 5% and false negatives (β) less than 5%; based on 132 determinations with 66 blank and 66 low level replicates; and LoB of 0.0 EliA U/mL. Since none of those low level samples met the target level for the CV% of 20% a requirement for the LoQ estimation - 3 additional low level samples were measured.

All low level samples were included in the LoD estimation (6 low level samples and a total of 132 determinations).

The LoQ for EliA Celikey IgG is 1.7 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2, based on 66 determinations of 3 low level samples that are different from the ones for the determination of the LoD, and a target uncertainty goal of 20%.

The results are summarized in the table below:

EliA Celikey IgG (EliA U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.0	0.6	1.7

EliA Gliadin®º IqA:

The LoD for EliA Gliadin®° IgA is 0.2 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2 and with proportions of false positives (α) less than 5% and false negatives (β) less than 5%; based on 132 determinations with 66 blank and 66 low level replicates; and LoB of 0.0 ELiA U/mL.

The LoQ for Gliadin®º IgA is 0.4 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2, based on 66 determinations, and a target uncertainty goal of 20%.

The results are summarized in the table below:

EliA GliadinDP IgA (EliA U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.0	0.2	0.4

EliA Gliadin®º IgG:

The LoD for EliA Gliadinºº IgG is 0.6 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2 and with proportions of false positives (α) less than 5% and false negatives (β) less than 5%; based on 132 determinations with 66 blank and 66 low level replicates; and LoB of 0.3 EliA U/mL.

The LoQ for EliA Gliadinºº IgG is 1.4 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2, based on 66 determinations, and a target uncertainty goal of 20%.

The results are summarized in the table below:

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EliA GliadinDP IgG (EliA U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.3	0.6	1.4

e. Analytical specificity:

Interference: Previously reviewed in K062583 and K093459. Carry-over: Phadia 2500/5000 instruments use disposable tips for pipetting samples and a separate pipette for the conjugate, therefore carry-over from samples to conjugate is impossible.

f. Assay cut-off:

The ranges (negative, equivocal, positive) recommended for the evaluation of the test results were derived from the clinical studies (s. K062583 and K093459).

EliA Celikey IqG Well

< 7 EliA U/mL	Negative
7 – 10 EliA U/mL	Equivocal
> 10 EliA U/mL	Positive

EliA Gliadin®º IgA Well

< 7 EliA U/mL	Negative
7 – 10 EliA U/mL	Equivocal
> 10 EliA U/mL	Positive

EliA Gliadin®º IgG Well

< 7 EliA U/mL	Negative
7 – 10 EliA U/mL	Equivocal
> 10 EliA U/mL	Positive

2. Comparison studies:

Method comparison with predicate device (Instrument comparison): a. See 2c Instrument Comparison below
b. Matrix comparison:

Previously reviewed under K062583 and K093459.

Instrument comparison C.

In the Method Comparison studies for the three EliA tests included in this submission, more than 100 samples (≥20% of the samples within ±25% of the medical decision point) were run in single replicates on one Phadia 250 and three Phadia 2500/5000 instruments. The acceptance criteria for the method comparison (the slope for the regression lines should be 0.9 - 1.1 for single replicate to single replicate and intercept close to 0) were met for EliA Celikey IgG, EliA Gliadin®º IgA and EliA Gliadin®º IgG.

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EliA Celikey lgG:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	0.49	0.26 to 0.73	0.93	0.91 to 0.94
PH2500/5000 B	0.14	-0.19 to 0.46	0.96	0.93 to 1.00
PH2500/5000 C	-0.28	-0.55 to -0.00	0.98	0.97 to 1.00

equivocal results considered positive

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	97.4%	97.4%	96.1%
95% CI	90.9% - 99.7%	90.9% - 99.7%	89.0% - 99.2%
NPA	82.6%	87.0%	91.3%
95% CI	61.2% - 95.0%	66.4% - 97.2%	72.0% - 98.9%
TPA	94.0%	95.0%	95.0%
95% CI	87.4% - 97.8%	88.7% - 98.4%	88.7% - 98.4%

equivocal results considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	95.5%	97.0%	94.0%
95% CI	87.5% - 99.1%	89.6% - 99.6%	85.4% - 98.3%
NPA	100.0%	100.0%	100.0%
95% CI	89.4% - 100.0%	89.4% - 100.0%	89.4% - 100.0%
TPA	97.0%	98.0%	96.0%
95% CI	91.5% - 99.4%	93.0% - 99.8%	90.1% - 98.9%

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EliA Gliadin®° IgA:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	0.60	0.40 to 0.93	0.95	0.92 to 0.98
PH2500/5000 B	0.55	0.28 to 0.83	0.97	0.95 to 1.00
PH2500/5000 C	-0.24	-0.71 to -0.06	1.09	1.06 to 1.11

equivocal results considered positive

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	100.0%	100.0%	100.0%
95% CI	95.7% - 100.0%	95.7% - 100.0%	95.7% - 100.0%
NPA	90.5%	85.7%	90.5%
95% CI	69.6% - 98.8%	63.7% - 97.0%	69.6% - 98.8%
TPA	98.1%	97.1%	98.1%
95% CI	93.3% - 99.8%	91.9% - 99.4%	93.3% - 99.8%

equivocal results considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.7%	100.0%	98.7%
95% CI	93.2% - 100.0%	95.4% - 100.0%	93.2% - 100.0%
NPA	96.2%	96.2%	96.2%
95% CI	80.4% - 99.9%	80.4% - 99.9%	80.4% - 99.9%
TPA	98.1%	99.0%	98.1%
95% CI	93.3% - 99.8%	94.8% - 100.0%	93.3% - 99.8%

EliA Gliadin® IgG:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	-0.14	-0.41 to 0.13	1.06	1.04 to 1.09
PH2500/5000 B	0.43	0.13 to 1.16	0.99	0.94 to 1.02
PH2500/5000 C	-0.06	-0.20 to 0.20	1.08	1.07 to 1.10

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criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	100.0%	100.0%	100.0%
95% CI	95.8% - 100.0%	95.8% - 100.0%	95.8% - 100.0%
NPA	89.5%	100.0%	94.7%
95% CI	66.9% - 98.7%	82.4% - 100.0%	74.0% - 99.9%
TPA	98.1%	100.0%	99.0%
95% CI	93.2% - 99.8%	96.5% - 100.0%	94.8% - 100.0%

equivocal results considered positive

equivocal results considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.8%	100.0%	100.0%
95% CI	93.2% - 100.0%	95.5% - 100.0%	95.5% - 100.0%
NPA	100.0%	95.8%	91.7%
95% CI	85.8% - 100.0%	78.9% - 99.9%	73.0% - 99.0%
TPA	99.0%	99.0%	98.1%
95% CI	94.8% - 100.0%	94.8% - 100.0%	93.2% - 99.8%

1. Clinical studies:
a. Clinical sensitivity: Not applicable.
Clinical specificity: b. Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable): Clinical performance values were reviewed in K062583 and K093459.
1. Clinical cut-off: Same as assay cut-off.
Expected values/Reference range: 5.

The frequency distribution for anti-tTG IgG and anti-gliadin IgA and IqG antibodies was investigated in a group of apparently healthy subjects equally distributed by age and gender, using sera from a Caucasian population obtained from a blood bank.

The results are given in the table below:

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Test	n =	Median(EliA U/mL)	95thpercentile	99thpercentile
EliA Celikey IgG onPhadia 2500/5000	400	2.3	3.3	3.9
EliA GliadinDP IgA onPhadia 2500/5000	400	1.4	3.8	7.1
EliA GliadinDP IgG onPhadia 2500/5000	400	0.9	2.7	13.3

N. Proposed Labeling:

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

O. Conclusion:

All available data support that both instrument platforms, Phadia 250 and Phadia 2500/5000 perform substantially equivalent when using the EliA Celikey IgG, EliA Gliadin®º IgA and EliA Gliadinºº IgG immunoassays.

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

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).