EliA CENP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to CENP in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (CREST Syndrome) in conjunction with other laboratory and clinical findings. EliA CENP uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA U1RNP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to U1RNP in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA U1RNP uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA RNP70 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to RNP70 in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA RNP70 uses the EliA IgG method on the instrument Phadia 2500/5000.

Device Description

The method-specific reagents are identical with K082759 (EliA CENP and EliA U1RNP) and K083117 (EliA RNP70), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of: Test Wells:

EliA CENP Wells are coated with human recombinant centromere protein B 2 carriers (12 wells each), ready to use;
-EliA U1RNP Wells are coated with human recombinant RNP (RNP70, A. C) proteins- 4 carriers (12 wells each), ready to use;
-EliA RNP70 Wells are coated with human recombinant RNP (70 kDa) protein-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:

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.

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 CENP, EliA U1RNP and EliA RNP70 tests.

AI/ML Overview

The provided FDA 510(k) summary for the EliA CENP, EliA U1RNP, and EliA RNP70 Immunoassays on the Phadia 2500/5000 instrument describes analytical performance studies, not typically studies involving human readers or expert adjudication in the context of AI/ML devices. Therefore, several of the requested sections below are marked as "Not Applicable (N/A)" because this document pertains to an in vitro diagnostic (IVD) assay and instrument combination, not an AI/ML-driven imaging or diagnostic device requiring human reader studies or expert adjudication of image-based ground truth.

Here's the breakdown based on the provided document:

Acceptance Criteria and Device Performance for EliA CENP, EliA U1RNP, and EliA RNP70 Immunoassays on Phadia 2500/5000

The acceptance criteria for this device are demonstrated through various analytical performance metrics, primarily comparing the new instrument platform (Phadia 2500/5000) to a predicate device (Phadia 250). The performance data below focuses on precision, linearity, detection limits, and method comparison.

1. Table of Acceptance Criteria and Reported Device Performance

The document defines "acceptance criteria" through the results of pre-specified analytical performance studies (precision, linearity, and method comparison), demonstrating the new device's equivalence to the predicate. The "acceptance criteria" are explicitly stated for the method comparison as "the slope for the regression lines should be 0.9 - 1.1 for single replicate to single replicate and intercept close to 0." For Other performance characteristics, the "acceptance" is implied by the presentation of the results, indicating they met the manufacturer's internal standards for demonstrating substantial equivalence.

Performance Characteristic	Acceptance Criteria (as implied or stated)	Reported Device Performance (Phadia 2500/5000)
Precision (Total %CV)	Not explicitly stated; likely internal target for reproducibility.	EliA CENP: Ranging from 6.0% to 19.6% (depending on mean concentration). EliA U1RNP: Ranging from 6.4% to 24.4% (depending on mean concentration). EliA RNP70: Ranging from 8.1% to 18.4% (depending on mean concentration).
Linearity (Slope)	Implied excellent correlation (R² close to 1.00) and slope near 1.00.	EliA CENP: Slopes from 0.99 to 1.04, R² 0.99 to 1.00. EliA U1RNP: Slopes from 1.00 to 1.04, R² 0.99 to 1.00. EliA RNP70: Slopes from 1.00 to 1.02, R² 1.00. (All 95% CIs for slope include 1.00 or are very close).
Detection Limits	Not explicitly stated; based on CLSI EP17-A guidelines for LoB, LoD, LoQ.	EliA CENP: LoB 0.2 EliA U/mL, LoD 0.4 EliA U/mL, LoQ 0.7 EliA U/mL. EliA U1RNP: LoB 0.2 EliA U/mL, LoD 0.5 EliA U/mL, LoQ 1.1 EliA U/mL. EliA RNP70: LoB 0.2 EliA U/mL, LoD 0.3 EliA U/mL, LoQ 0.9 EliA U/mL.
Method Comparison (Slope vs. Predicate)	Slope 0.9 - 1.1. Intercept close to 0.	EliA CENP: Slopes 0.98 to 1.04; Intercepts -0.40 to 0.44. EliA U1RNP: Slopes 0.92 to 1.02; Intercepts 0.03 to 0.98. EliA RNP70: Slopes 1.00 to 1.04; Intercepts 0.29 to 0.35. (All met the acceptance criteria).
Method Comparison (Agreement vs. Predicate)	Not explicitly stated, but high Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) values.	EliA CENP: PPA 98.6-100%, NPA 88.2-100%. EliA U1RNP: PPA 96.8-100%, NPA 94.1-100%. EliA RNP70: PPA 98.6-100%, NPA 80.8-97.4%. (Ranges depend on equivocal results consideration).

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

Sample Size (Method Comparison): More than 100 samples for each EliA test (CENP, U1RNP, RNP70).
Sample Size (Precision): 5 different samples were tested for each immunoassay. Each sample was tested in four replicates/run, over 21 runs (3 instruments x 7 runs), resulting in 84 replicates per sample.
Sample Size (Linearity): Four patient serum samples were diluted for each immunoassay.
Sample Size (Detection Limit): One blank sample (66 determinations) and three low-level samples (66 determinations) were used for LoD/LoQ studies for each immunoassay.
Sample Size (Expected Values/Reference Range): 400 serum samples from an apparently healthy Caucasian population for each immunoassay.
Data Provenance: The document does not explicitly state the country of origin for the patient samples, but the reference populations for "Expected Values" are described as "Caucasian population obtained from a blood bank." The studies described appear to be prospective analytical studies conducted by the manufacturer to support the 510(k) submission for the new instrument platform.

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

N/A. This is an IVD device measuring antibody levels, not an AI/ML device that requires expert human interpretation of images or clinical data for ground truth. The "ground truth" for these tests is the value measured by the predicate device and the analytical standards (e.g., linearity standards, controls).

4. Adjudication Method for the Test Set

N/A. No expert adjudication process is described as this is an IVD device.

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

N/A. This is an IVD device, not an AI-assisted diagnostic tool involving human readers of images or other complex data. The comparison is between an older instrument (Phadia 250) and a new instrument (Phadia 2500/5000) running the same assays.

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

N/A. This is an IVD device, not an AI algorithm. The performance described is the standalone analytical performance of the instrument/assay combination.

7. The Type of Ground Truth Used

For the method comparison studies, the "ground truth" or reference method was the predicate device (Phadia 250 instrument) running the same assays. The goal was to show substantial equivalence between the new and predicate instruments.
For analytical performance characteristics (precision, linearity, detection limits), the ground truth is established through standard laboratory practices using calibrators, controls, and reference materials as per CLSI guidelines, which are themselves traceable to established measurement procedures.

8. The Sample Size for the Training Set

N/A. This document describes performance validation of an IVD assay/instrument system, not the training of an AI/ML model. Therefore, there is no "training set" in the AI/ML sense. The device is a measurement system; it does not "learn" from data.

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

N/A. As there is no AI/ML training set, this question is not applicable. The device's "ground truth" (its measurement accuracy) is established through rigorous analytical validation studies using controls, calibrators, and comparison to validated predicate methods, not through a "training set" of patient data.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

November 27, 2018

Phadia AB Sheryl Skinner Associate Director Phadia US Inc. 4169 Commercial Avenue Portage, Michigan 49002

Re: K182353

Trade/Device Name: EliA CENP Immunoassay EliA U1RNP Immunoassay EliA RNP70 Immunoassay Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LJM, LKO Dated: August 28, 2018 Received: August 29, 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,

Leonthena R. Carrington -S

Lea Carrington Director 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) K182353

Device Name

EliA(TM) CENP Immunoassay, EliA(TM) U1RNP Immunoassay, EliA(TM) RNP70 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:

K182353

B. Purpose for Submission:

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

C. Measurands:

CENP, U1RNP and RNP70 anti-nuclear antibodies

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: Martin Mann Regulatory Affairs Manager Phadia US Inc. 4169 Commercial Avenue Portage, Mi 49002, USA +1 (-269-492) -1957 (Phone) +1 (-269-492) -7541 (Fax) martin.mann@thermofisher.com

Date of Summary Preparation:

November 5, 2018

F. Proprietary and Established Names:

EliA CENP Immunoassay EliA U1RNP Immunoassay EliA RNP70 Immunoassay

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G. Regulatory Information:

1. Regulation section: 21 CFR§ 866.5100, Antinuclear Antibody Immunological Test System
1. Classification: Class II

Product code: ဒေ

LJM Antinuclear antibody (enzyme-labeled), antigen, controls LKO Anti-RNP antibody, antigen and control

1. Panel: Immunology (82)

H. Intended use(s):

Intended use(s):

Indication(s) for use: Same as intended use

Special conditions for use statement(s): 3. For prescription use only

Special instrument requirements: ব

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 CENP Wells are coated with human recombinant centromere protein B 2 carriers (12 wells each), ready to use;
-EliA U1RNP Wells are coated with human recombinant RNP (RNP70, A. C) proteins- 4 carriers (12 wells each), ready to use;
-EliA RNP70 Wells are coated with human recombinant RNP (70 kDa) protein-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:
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.

J. Substantial Equivalence Information:

Predicate device name(s) and 510(k) number(s): EliA CENP on Phadia 250 instrument, K082759 EliA U1RNP on Phadia 250 instrument, K082759 EliA RNP70 on Phadia 250 instrument, K083117

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2. Comparison with predicate device:

EliA CENP, EliA U1RNP and EliA RNP70 Immunoassays on Phadia 250 and Phadia 2500/5000 instruments – Similarities to predicate devices

Feature	Predicate DevicePhadia 250	New DevicePhadia 2500/5000
Intended UseEliA CENP	EliA CENP is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to CENP in human serumand plasma (heparin, EDTA,citrate) as an aid in the clinicaldiagnosis of scleroderma (CRESTSyndrome) in conjunction withother laboratory and clinicalfindings. EliA CENP uses the EliAIgG method on the instrumentImmunoCAP 250.	EliA CENP is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to CENP in humanserum and plasma (Li-heparin,EDTA) as an aid in the clinicaldiagnosis of scleroderma(CREST Syndrome) inconjunction with other laboratoryand clinical findings. EliA CENPuses the EliA IgG method on theinstrument Phadia 2500/5000.
Intended UseEliA U1RNP	EliA U1RNP is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to U1RNP in humanserum and plasma (heparin,EDTA, citrate) as an aid in theclinical diagnosis of mixedconnective tissue disease (MCTD)and systemic lupuserythematosus (SLE) inconjunction with other laboratoryand clinical findings. EliA U1RNPuses the EliA IgG method on theinstrument ImmunoCAP 250.	EliA U1RNP is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to U1RNP in humanserum and plasma (Li-heparin,EDTA) as an aid in the clinicaldiagnosis of mixed connectivetissue disease (MCTD) andsystemic lupus erythematosus(SLE) in conjunction with otherlaboratory and clinical findings.EliA U1RNP uses the EliA IgGmethod on the instrumentPhadia 2500/5000.
Intended UseEliA RNP70	EliA RNP70 is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to RNP70 in humanserum and plasma (heparin,EDTA) as an aid in the clinicaldiagnosis of mixed connectivetissue disease (MCTD) andsystemic lupus erythematosus(SLE) in conjunction with otherlaboratory and clinical findings.EliA RNP70 is to be used togetherwith the EliA IgG method on theinstrument ImmunoCAP 250	EliA RNP70 is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to RNP70 in humanserum and plasma (Li-heparin,EDTA) as an aid in the clinicaldiagnosis of mixed connectivetissue disease (MCTD) andsystemic lupus erythematosus(SLE) in conjunction with otherlaboratory and clinical findings.EliA RNP70 uses the EliA IgGmethod on the instrumentPhadia 2500/5000
Analytical	Same	Same
technology:
Immuno-
fluorescence
measurement
Assay process	Same	Same
Common,dedicated Phadia	Same	SameIntroduction of new article
reagents		numbers for DevelopmentSolution, Stop Solution and
		Washing Solution is only due tolarger filling volumes which are
		required for the biggerinstruments Phadia 2500/5000
Result calculation	Same	Same
software; Phadia
Information Data
Manager (IDM)
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
Development	90 µL	90 µL
Solution Volume
Stop SolutionVolume	200 µL	200 µL
Assay set-up	Random access	Random access
Reagentpackaging size	Various/Common	Various/CommonIntroduction of new article
		number for EliA Sample Diluent
		(83-1071-01) is only due tolarger filling volume.
Onboard storage	Yes	Yes
of reagents

Feature	Predicate DevicePhadia 250	New DevicePhadia 2500/5000
Sample matrix;Serum or plasmatype as indicated inthe DFU dependenton assay	Human serum or plasma(heparin, EDTA, citrate)	Human serum or plasma (Li-heparin, EDTA); i.e. citrateplasma is omitted for all tests
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 CENP, EliA U1RNP and EliA RNP70 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 centromere protein B, human recombinant RNP (RNP70, A, C) or with human recombinant RNP (70 kDa) protein. If present in the patient's specimen, antibodies to these proteins bind to the specific antigen. After washing away non-bound antibodies, enzyme-labeled antibodies against human IgG antibodies (EliA IgG Conjugate) are added to form an antibodyconjugate 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 assay directly measures the amount of antibody of interest bound to the antigen coating the EliA well, therefore the higher the value of fluorescent signal detected by the instrument, the higher the amount of antibody bound and detected in the sample tested. 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/day 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.

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The results are summarized in the table below:

Mean	Within-Run		Between-Run		Between-Instrument		TotalImprecision
(EliAU/mL)	SD	%CV	SD	%CV	SD	%CV	SD	%CV
1.1	0.1	9.9	0.1	6.1	0.2	15.8	0.2	19.6
7.1	0.4	5.8	0.3	4.9	0.3	3.9	0.6	8.6
11.4	0.4	3.5	0.4	3.9	0.5	4.2	0.8	6.7
129.8	4.3	3.3	5.1	3.9	3.9	3.0	7.7	6.0
229.7	9.8	4.3	15.7	6.8	10.1	4.4	21.1	9.2

EliA CENP on Phadia 2500/5000

EliA U1RNP on Phadia 2500/5000

Mean(EliAU/mL)	Within-Run		Between-Run		Between-Instrument		TotalImprecision
	SD	%CV	SD	%CV	SD	%CV	SD	%CV
2.2	0.4	17.9	0.3	12.5	0.2	11.0	0.5	24.4
5.7	0.3	5.4	0.2	2.8	0.1	1.8	0.4	6.4
10.4	0.5	4.7	0.4	4.2	0.6	5.6	0.9	8.5
135.4	5.2	3.8	7.2	5.3	6.5	4.8	11.0	8.1
231.7	9.1	3.9	9.0	3.9	10.7	4.6	16.7	7.2

EliA RNP70 on Phadia 2500/5000

Mean(EliAU/mL)	Within-Run		Between-Run		Between-Instrument		TotalImprecision
	SD	%CV	SD	%CV	SD	%CV	SD	%CV
1.4	0.1	5.4	0.1	4.4	0.2	17.0	0.3	18.4
7.9	0.2	2.9	0.3	4.4	0.5	6.2	0.6	8.1
8.9	0.5	5.2	0.5	5.5	0.5	5.2	0.8	9.2
93.1	5.1	5.5	5.5	5.9	2.9	3.1	8.0	8.6
190.2	9.4	5.0	10.3	5.4	10.6	5.6	17.5	9.2

b. Linearity/assay reportable range:

Four patient serum samples were diluted in sample diluent and tested with one batch of EliA CENP, EliA U1RNP and EliA RNP70 Immunoassays and one set of system reagents on Phadia 2500/5000. The results of the regression analysis are summarized below:

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Dilution range(EliA U/mL)	Slope	95% CI	Intercept	95% CI	R2
0.5 – 24.3	1.00	0.99 – 1.01	0.17	0.02 – 0.31	1.00
2.1 – 180.3	1.01	0.99 – 1.02	0.10	-0.83 – 1.03	1.00
3.8 – 305.0	1.04	0.99 – 1.10	2.70	-4.21 – 9.62	0.99
0.4 – 18.8	0.99	0.97 – 1.02	-0.22	-0.44 – -0.00	1.00

EliA CENP on Phadia 2500/5000

The reportable range (Limit of Detection, upper limit) for EliA CENP is from 0.4 to 240 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 0.7 to 240 EliA U/mL.

EliA U1RNP on Phadia 2500/5000

Dilution range(EliA U/mL)	Slope	95% CI	Intercept	95% CI	R2
0.5 – 18.0	1.01	0.99 - 1.02	0.08	-0.04 - 0.20	1.00
0.6 – 51.3	1.01	0.99 – 1.02	0.04	-0.20 - 0.27	1.00
0.6 – 15.8	1.00	0.96 - 1.04	0.28	0.01 - 0.56	1.00
4.7 – 284.7	1.04	0.98 - 1.10	1.86	-4.75 - 8.47	0.99

The reportable range (Limit of Detection, upper limit) for EliA U1RNP is from 0.5 to 240 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 1.1 to 240 EliA U/mL.

Dilution range(EliA U/mL)	Slope	95% CI	Intercept	95% CI	R2
0.6 - 62.5	1.02	1.00 – 1.04	0.07	-0.47 - 0.49	1.00
0.4 - 38.7	1.01	0.98 – 1.04	-0.42	-0.87 - 0.02	1.00
6.9 - 251.8	1.00	0.97 – 1.03	3.07	0.05 - 6.09	1.00
3.7 - 294.6	1.01	0.98 – 1.03	3.38	0.39 - 6.38	1.00

EliA RNP70 on Phadia 2500/5000

The reportable range (Limit of Detection, upper limit) for EliA RNP70 is from 0.3 to 240 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 0.9 to 240 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.

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d. Detection limit:

The limit of blank (LoB) and limit of detection (LoD) 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.

EliA CENP:

The LoD for EliA CENP is 0.4 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A 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 0.2 EliA U/mL.

The LoQ for EliA CENP is 0.7 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A, based on 66 determinations, and a target uncertainty goal of 20%.

The results are summarized in the table below:

EliA CENP (EliA U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.2	0.4	0.7

EIiA U1RNP:

The LoD for EliA U1RNP is 0.5 EliA U/mL, determined consistent with the quidelines in CLSI document EP17-A 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 0.2 EliA U/mL.

The LoQ for EliA U1RNP is 1.1 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A, based on 66 determinations, and a target uncertainty goal of 20%.

The results are summarized in the table below:

EliA U1RNP (EliA U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.2	0.5	1.1

EliA RNP70:

The LoD for EliA RNP70 is 0.3 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A 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 0.2 EliA U/mL.

The LoQ for EliA RNP70 is 0.9 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A, based on 66 determinations, and a target uncertainty goal of 20%.

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The results are summarized in the table below:

EliA RNP70 (EliA U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.2	0.3	0.9

e. Analytical specificity:
Interference: Previously reviewed in K082759 and K083117.

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. K082759 and K083117).

EliA CENP Well

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

EliA U1RNP Well

< 5 EliA U/mL	Negative
5 - 10 EliA U/mL	Equivocal
> 10 EliA U/mL	Positive

EliA RNP70 Well

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

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

Previously reviewed under K082759 and K083117.

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 CENP, EliA U1RNP and EliA RNP70.

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EliA CENP:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	-0.30	-0.55 to -0.07	1.02	1.00 to 1.03
PH2500/5000 B	0.44	0.07 to 0.78	0.98	0.95 to 1.00
PH2500/5000 C	-0.40	-0.91 to -0.09	1.04	1.03 to 1.07

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%	95.5% - 100.0%
NPA	94.1%	88.2%	88.2%
95% CI	71.3% - 99.9%	63.6% - 98.5%	63.6% - 98.5%
TPA	99.0%	98.0%	97.9%
95% CI	94.6% - 100.0%	93.0% - 99.8%	92.7% - 99.7%

equivocal results considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.7%	98.7%	98.6%
95% CI	92.8% - 100.0%	92.8% - 100.0%	92.5% - 100.0%
NPA	100.0%	92.0%	96.0%
95% CI	86.3% - 100.0%	74.0% - 99.0%	79.6% - 99.9%
TPA	99.0%	97.0%	97.9%
95% CI	94.6% - 100.0%	91.5% - 99.4%	92.7% - 99.7%

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EliA U1RNP:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	0.68	0.34 to 1.02	0.92	0.90 to 0.95
PH2500/5000 B	0.03	-0.36 to 0.65	1.02	0.98 to 1.05
PH2500/5000 C	0.98	0.43 to 1.26	0.92	0.90 to 0.94

equivocal results considered positive

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	100.0%	98.9%	96.8%
95% CI	96.2% - 100.0%	94.3% - 100.0%	91.0% - 99.3%
NPA	100.0%	94.1%	100.0%
95% CI	80.5% - 100.0%	71.3% - 99.9%	80.5% - 100.0%
TPA	100.0%	98.2%	97.3%
95% CI	96.8% - 100.0%	93.7% - 99.8%	92.4%- 99.4%

equivocal results considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.7%	97.4%	100.0%
95% CI	93.0% - 100.0%	90.9% - 99.7%	95.3% - 100.0%
NPA	97.1%	97.1%	97.1%
95% CI	85.1% - 99.9%	85.1% - 99.9%	85.1% - 99.9%
TPA	98.2%	97.3%	99.1%
95% CI	93.7% - 99.8%	92.4% - 99.4%	95.1% - 100.0%

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EliA RNP70:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	0.35	0.17 to 0.52	1.00	0.98 to 1.02
PH2500/5000 B	0.29	0.17 to 0.48	1.04	1.01 to 1.06
PH2500/5000 C	0.33	0.16 to 0.69	1.03	1.01 to 1.06

equivocal results considered positive

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	88.5%	80.8%	84.6%
95% CI	69.8% - 97.6%	60.6% - 93.4%	65.1% - 95.6%
TPA	97.3%	95.5%	96.4%
95% CI	92.3% - 99.4%	89.8% - 98.5%	91.1% - 99.0%

equivocal results considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.6%	100.0%	98.6%
95% CI	92.6% - 100.0%	95.1% - 100.0%	92.7% - 100.0%
NPA	97.4%	92.1%	92.1%
95% CI	86.2% - 99.9%	78.6% - 98.3%	78.6% - 98.3%
TPA	98.2%	97.3%	96.4%
95% CI	93.6% - 99.8%	92.3% - 99.4%	91.1% - 99.0%

3. Clinical studies:

Clinical sensitivity: a. Not applicable.
b. Clinical specificity: Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable): Clinical performance values were reviewed in K082759 and K083117.
1. Clinical cut-off:

Same as assay cut-off.

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5. Expected values/Reference range:

The frequency distribution for CENP, U1RNP and RNP70 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.

Test	n =	Median(EliA U/mL)	95thpercentile	99thpercentile
EliA CENP on Phadia2500/5000	400	0.7	1.0	1.3
EliA U1RNP onPhadia 2500/5000	400	1.5	2.2	3.0
EliA RNP70 onPhadia 2500/5000	400	1.4	2.2	2.5

The results are given in the table below:

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 CENP, EliA U1RNP and EliA RNP70 immunoassays.

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

Regulation Number and Section

§ 866.5100 Antinuclear antibody immunological test system.

(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).