EliA SmDP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Sm in human serum and EDTA-plasma to aid in the clinical diagnosis of systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA SmDP uses the EliA IgG method on the instrument Phadia 2500/5000.

Device Description

The method-specific reagents are identical with K132631 (EliA SmDº on Phadia 250), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:

Test Wells: -EliA SmDP Wells are coated with a synthetic SmD3 peptide – 4 carriers (12 wells each), ready to use;
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 Conjugate 50 or 200: ß-Galactosidase labeled anti-IgG (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 SmDP tests.

AI/ML Overview

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

1. Table of Acceptance Criteria and Reported Device Performance

The device under review is the EliA SmDP Immunoassay on the Phadia 2500/5000 instrument. The study primarily evaluated the performance of this new instrument platform compared to a previously cleared device (EliA SmDP on Phadia 250, K132631). The acceptance criteria for the new device's performance are largely demonstrated through its equivalence to the predicate device.

Performance Metric	Acceptance Criteria (typically from predicate or internal)	Reported Device Performance (EliA SmDP on Phadia 2500/5000)
Precision/Reproducibility	Not explicitly stated as a specific numerical range for the new device, but implied to be acceptable if similar to the predicate and overall low variability. The previous submission (K132631) likely established this.	Total Imprecision (%CV): - 24.8% at 2.2 EliA U/mL - 8.8% at 10.0 EliA U/mL - 6.5% at 146.6 EliA U/mL - 8.8% at 408.1 EliA U/mL (within acceptable limits for immunoassays of this type)
Linearity/Reportable Range	Implied to be linear across the measuring range, with slopes close to 1 and R2 values close to 1.	Linearity (Slope, 95% CI): - 1.04 (0.95-1.12) - 0.98 (0.94-1.02) - 1.01 (0.97-1.05) - 1.01 (0.99-1.02) R2 values: All 0.99 or 1.00 Linear Range: 1.6 EliA U/mL (LoQ) to 480 EliA U/mL (upper limit) Reportable Range: 0.8 EliA U/mL (LoD) to 480 EliA U/mL (upper limit)
Detection Limit (LoD)	Not explicitly stated as a specific numerical value. The study aimed to determine it.	LoD: 0.8 EliA U/mL (with <5% false positives and false negatives)
Quantification Limit (LoQ)	Not explicitly stated as a specific numerical value. The study aimed to determine it.	LoQ: 1.6 EliA U/mL (with a target uncertainty of 20%)
Assay Cut-Off Performance	The medical decision points for "Negative", "Equivocal", "Positive" were previously established in K132631. The comparison study aimed to show consistent performance around these cut-offs between the new and predicate instruments. Acceptance Criteria for Method Comparison (Regression): Slope for regression lines should be 0.9 – 1.1 (for single replicate to single replicate) and intercept close to 0.	Method Comparison (Regression) - EliA SmDP: - Instrument PH2500/5000 A: Intercept 0.07 (-0.38 to 0.53), Slope 1.00 (0.98 to 1.04) - Instrument PH2500/5000 B: Intercept 0.06 (-0.39 to 0.24), Slope 1.03 (1.01 to 1.05) - Instrument PH2500/5000 C: Intercept -0.34 (-0.70 to -0.08), Slope 1.06 (1.03 to 1.09) All meet acceptance criteria.
Percentage Agreement with Predicate (Cut-off)	Not explicitly stated as numerical values, but implied to demonstrate high agreement for positive and negative cases.	Positive Percent Agreement (PPA) (equivocal considered positive): 98.9% - 100.0% Negative Percent Agreement (NPA) (equivocal considered positive): 93.3% - 100.0% Total Percent Agreement (TPA) (equivocal considered positive): 98.1% - 100.0% Positive Percent Agreement (PPA) (equivocal considered negative): 98.7% - 100.0% Negative Percent Agreement (NPA) (equivocal considered negative): 86.7% - 93.3% Total Percent Agreement (TPA) (equivocal considered negative): 95.2% - 98.1% (All values are high, indicating strong agreement.)
Carry-over	"No carry-over" or "negligible carry-over." The predicate device had a warning about low risk of conjugate contamination by carry-over, indicating a desire to eliminate this.	Reported Performance: "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." (Meets expectations by design).

2. Sample Size and Data Provenance for the Test Set

Precision/Reproducibility:
- Sample Size: Multiple samples tested in 84 replicates per sample (7 days x 3 instruments x 4 replicates/run). The specific number of distinct samples for the precision study is not explicitly stated beyond "The study was performed with 1 run/day over a period of 7 days."
- Data Provenance: Not explicitly stated, but typically these types of analytical validation studies are conducted in-house by the manufacturer. No indication of specific country or retrospective/prospective outside of the internal lab setting.
Linearity/Reportable Range:
- Sample Size: Four patient serum samples.
- Data Provenance: Not explicitly stated, likely internal lab testing using patient samples.
Detection Limit (LoD) and Quantification Limit (LoQ):
- Sample Size: One blank sample and five low-level samples measured in 12 replicates in each of 6 runs (total 72 blank determinations, 360 low-level determinations).
- Data Provenance: Internal lab testing.
Method Comparison (Instrument Comparison):
- Sample Size: More than 100 samples (specifically, "≥10% of the samples within ±25% of the medical decision point").
- Data Provenance: Not explicitly stated, but these are patient samples run on both the predicate and new instruments. The text mentions "patient serum samples" for linearity, suggesting these would also be patient samples. Given the device is for SLE diagnosis, these would be relevant clinical samples. No information on country of origin or retrospective/prospective.

3. Number of Experts and their Qualifications for Ground Truth of Test Set

This type of immunoassay (EliA SmDP Immunoassay) directly measures the concentration of antibodies. The "ground truth" for the test set in this context refers to the actual concentration of the analyte or the true clinical status, which is not typically established by human experts interpreting images, but rather by reference methods or clinical diagnosis.

For analytical performance (precision, linearity, detection limits), the "ground truth" samples are often characterized by their known concentrations or by being truly "blank" (zero concentration). This is determined by the assay itself or by careful preparation and measurement in a lab setting, not by human experts.
For method comparison and demonstrating agreement around cut-offs, the "ground truth" for the samples is usually established by the predicate device's measurement or the clinical diagnosis of the patient. The clinical performance (sensitivity/specificity for SLE) was reviewed in the predicate device's submission (K132631) and relies on the clinical diagnosis of SLE. Therefore, for the present submission, human experts (clinicians) would have been involved in the original clinical diagnosis of SLE patients used to establish the cut-off values for the predicate device, but their specific number, qualifications, or adjudication methods are not part of this submission's detailed test set information because it refers back to the predicate.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1, 3+1) are typically used when subjective interpretations by multiple human experts are compared to establish a "ground truth" for diagnostic imaging or similar scenarios.

For this immunoassay, where the output is a semi-quantitative measurement (EliA U/mL), there is no mention or need for an adjudication method by human experts for the analytical performance studies. The measurements are objective.
For the original clinical studies that established the assay's clinical utility and cut-offs (referenced from K132631), clinical diagnosis of SLE would have served as the "ground truth." The adjudication method for establishing those clinical diagnoses is not provided in this document, as it refers to a prior submission.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.

MRMC studies are typically used to assess how human readers perform with and without AI assistance, especially in radiology or pathology.
This submission is for an in-vitro diagnostic (IVD) immunoassay, which does not involve human readers interpreting images or data in the same way that would necessitate an MRMC study. The comparison is between two automated instrument platforms.

6. If a Standalone (Algorithm Only) Performance Study was Done

Yes, the analytical and method comparison studies described are essentially standalone performance studies for the new Phadia 2500/5000 instrument platform operating the EliA SmDP Immunoassay.

The device (the assay and instrument combination) operates autonomously to measure antibody concentrations. There is no "human-in-the-loop" component for the measurement process itself that would differentiate between standalone and assisted performance in this context. The instrument runs the assay and generates a numerical result, which is then interpreted by a clinician in conjunction with other findings.

7. Type of Ground Truth Used

For analytical performance (precision, linearity, LoD/LoQ): Controlled reference materials, blank samples, and carefully characterized patient samples with known dilution factors were used.
For method comparison: The measurements obtained from the predicate device (EliA SmDP on Phadia 250) served as the comparative "ground truth" as the intent was to show substantial equivalence between the two instrument platforms running the same assay reagents.
For clinical cut-offs and performance: The document states that clinical performance values were reviewed in K132631, and the assay cut-offs were derived from clinical studies. This implies that the ultimate ground truth for establishing clinical utility and cut-offs was based on clinical diagnosis of systemic lupus erythematosus (SLE), likely established by expert clinicians using a combination of clinical findings, pathology, and other laboratory tests.

8. Sample Size for the Training Set

The provided document describes a 510(k) submission for adding a previously cleared assay to a new instrument platform. It does not explicitly mention a "training set" in the context of an AI/machine learning model.

For an immunoassay like EliA SmDP, the "training" analogous to an AI model would be the initial development and optimization of the assay itself and the establishment of calibration curves. This process typically involves a large number of samples used during the R&D phase to define parameters and ensure robust performance, but these are not explicitly termed "training sets" in this document.
The document primarily focuses on validation testing (analytical and method comparison) of the new instrument platform.

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

As there is no distinct "training set" described for a machine learning algorithm in this document, the question of how its ground truth was established is not applicable in the AI/ML sense.

However, if we consider the development of the original EliA SmDP assay (from the predicate K132631), the "ground truth" for calibrators and controls would be established metrologically, through dilutions of highly characterized human IgG standards. For the clinical cut-offs, as mentioned in point 7, this would have been established through extensive clinical studies where the ground truth was the definitive diagnosis of SLE based on established criteria and expert clinical judgment.

Summary

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Image /page/0/Picture/0 description: The image shows 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. Underneath the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

December 24, 2018

Phadia AB Shervl Skinner Associate Director RA/QA Phadia US Inc. 4169 Commercial Avenue Portage, Michigan 49002

Re: K183007

Trade/Device Name: EliA SmDP Immunoassay Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LKP Dated: October 31, 2018 Received: October 31, 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.

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

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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) K183007

Device Name EliA(TM) SmDP 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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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:

K183007

B. Purpose for Submission:

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

C. Measurand:

lgG antibodies specific for Sm protein

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:

October 30, 2018

F. Proprietary and Established Names:

EliA™ SmDP Immunoassay

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G. Regulatory Information:

1. Regulation section: 21 CFR §866.5100 Antinuclear Antibody Immunological Test System
1. Classification: Class II
1. Product code: LKP, Anti-Sm 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): 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: .

The method-specific reagents are identical with K132631 (EliA SmDº on Phadia 250), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:

Test Wells: -EliA SmDP Wells are coated with a synthetic SmD3 peptide – 4 carriers (12 wells each), ready to use;
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 Conjugate 50 or 200: ß-Galactosidase labeled anti-IgG (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): 1. EliA SmDP on Phadia 250 instrument, K132631

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2. Comparison with predicate device:

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

Feature	Predicate DevicePhadia 250	New DevicePhadia 2500/5000
Intended UseEliA SmDP	EliA SmDP is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to Sm in human serumand plasma (EDTA, citrate) asan aid in the clinical diagnosis ofsystemic lupus erythematosus(SLE) in conjunction with otherlaboratory and clinical findings.EliA SmDP uses the EliA IgGmethod on the instrumentPhadia 250.	EliA SmDP is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to Sm in human serumand EDTA-plasma to aid in theclinical diagnosis of systemiclupus erythematosus (SLE) inconjunction with other laboratoryand clinical findings. EliA SmDPuses the 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
Time to 1st result	~2 h	~2 h
Feature	Predicate DevicePhadia 250	New DevicePhadia 2500/5000
Sample matrix;Serum or plasmatype as indicated inthe DFU dependenton assay	Human serum and plasma(EDTA, citrate)	Human serum or EDTA- plasma,i.e. citrate plasma is omitted asfor all EliA 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 SmD² 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 a synthetic SmD3 peptide. If present in the patient's specimen, antibodies to SmD3 peptide 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 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 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.

We included only one lot of EliA SmDP Well on the Phadia 2500/5000 instrument, as data for inter-lot-variation has already been shown in K132631. The results are summarized in the table below:

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Mean(EliAU/mL)	n	Within-Run		Between-Run		Between-Instrument		TotalImprecision
		SD	%CV	SD	%CV	SD	%CV	SD	%CV
2.2	84	0.2	8.7	0.2	11.0	0.4	20.5	0.5	24.8
7.1	84	0.3	3.6	0.2	2.8	0.3	4.7	0.5	6.5
10.0	84	0.4	3.7	0.2	1.9	0.8	7.7	0.9	8.8
146.6	84	5.1	3.5	3.7	2.5	7.2	4.9	9.5	6.5
408.1	84	15.5	3.8	9.8	2.4	31.1	7.6	36.1	8.8

EliA SmDP on Phadia 2500/5000

b. Linearity/assay reportable range:

Four patient serum samples were diluted in EliA Sample Diluent and tested with one batch of EliA SmDP Immunoassay and one set of system reagents on Phadia 2500/5000. The ratios of observed/expected values were calculated. The results are summarized below:

EliA SmDP on Phadia 2500/5000
PAUL 20

Dilutionrange(EliA U/mL)	Slope	95% Cl	Intercept	95% Cl	R2
6.5 – 285.5	1.04	0.95 – 1.12	4.21	4.21 – -5.70	0.99
8.7 – 392.8	0.98	0.94 – 1.02	-0.56	-0.56 – -7.29	1.00
27.1 – 537.4	1.01	0.97 – 1.05	-10.58	-21.14 – -0.03	1.00
0.9 - 11.4	1.01	0.99 – 1.02	-0.09	-0.19 – 0.01	1.00

The linear range and the measuring range are set to 1.6 EliA U/mL (LoQ) to 480 EliA U/mL (upper limit of measuring range),

The reportable range (Limit of Detection, upper limit of measuring range) for EliA SmDP is from 0.8 to 480 EliA U/mL. Concentration values between LoD and LoQ may show a higher uncertainty.

Traceability, Stability, Expected values (controls, calibrators, or methods): C. The EliA IgG method was previously reviewed in K061165.
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 five low level samples were measured in twelve replicates in each of six runs spread over six different days.

The LoD for EliA SmDP is 0.8 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 (ß) less than 5%: based on 432 determinations with 72 blank and 360 low level replicates; and LoB of 0.3 EliA U/mL.

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The LoQ for EliA SmDP is 1.6 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A, based on 360 determinations; and a target uncertainty goal of 20%.

The results are summarized in the table below:

EliA SmDP (EliA U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.3	0.8	1.6

e. Analytical specificity:
Interference: Previously reviewed in K132631

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.

Assay cut-off: f.
The ranges (negative, equivocal, positive) recommended for the evaluation of the test results were derived from the clinical studies (s. K132631).

EliA SmD® Well

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

1. Comparison studies:
Method comparison with predicate device (Instrument comparison): a. See 2c Instrument Comparison below
b. Matrix comparison: Previously reviewed under K132631.
Instrument comparison C.

In the Method Comparison studies for EliA SmDP, more than 100 samples (≥10% of the samples within ±25% of the medical decision point) were run in sinqle replicates on one Phadia 250 and one Phadia 2500/5000 instrument. 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 SmDP.

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A.6-10

EliA SmDº:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	0.07	-0.38 to 0.53	1.00	0.98 to 1.04
PH2500/5000 B	0.06	-0.39 to 0.24	1.03	1.01 to 1.05
PH2500/5000 C	-0.34	-0.70 to -0.08	1.06	1.03 to 1.09

equivocal results considered positive

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.9%	98.9%	100.0%
95% CI	94.0% - 100.0%	94.0% - 100.0%	96.0% - 100.0%
NPA	93.3%	100.0%	100.0%
95% CI	68.1% - 99.8%	73.5% - 100.0%	78.2% - 100.0%
TPA	98.1%	99.0%	100.0%
95% CI	93.3% - 99.8%	94.7% - 100.0%	96.5% - 100.0%

equivocal results considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.7%	100.0%	100.0%
95% CI	92.8% - 100.0%	95.2% - 100.0%	95.2% - 100.0%
NPA	86.7%	88.9%	93.3%
95% CI	69.3% - 96.2%	70.8% - 97.6%	77.9% - 99.2%
TPA	95.2%	97.1%	98.1%
95% CI	89.2% - 98.4%	91.6% - 99.4%	93.3% - 99.8%

1. Clinical studies:
a. Clinical sensitivity: 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 K132631.
Clinical cut-off: 4. Same as assay cut-off.

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5. Expected values/Reference range:

The frequency distribution for Sm 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:

Test	n =	Median(EliA U/mL)	95thpercentile	99thpercentile
EliA SmDP on Phadia2500/5000	400	1.1	2.2	4.2

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 SmDP 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).