Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard immunoassay kit and automated system for measuring antibodies. There is no mention of AI or ML in the intended use, device description, or performance studies. The analysis focuses on traditional analytical performance metrics.

Therapeutic

No
This device is for in vitro semi-quantitative measurement of antibodies to aid in the diagnosis of systemic lupus erythematosus (SLE), not for treating or preventing disease.

Diagnostic

Yes

The "Intended Use / Indications for Use" section states that the device is intended "to aid in the clinical diagnosis of systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings." This indicates its use in diagnosing a medical condition.

SaMD (Software as a Medical Device)

No

The device description explicitly lists multiple physical components including test wells, sample diluent, conjugate, calibrator strips, curve control strips, and a calibrator well. It also mentions the use of the Phadia EliA Immunodiagnostic System, which is an automated hardware system.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is intended for "in vitro semi-quantitative measurement of IgG antibodies directed to Sm in human serum and EDTA-plasma". The term "in vitro" is a key indicator of an IVD.
Device Description: The description details reagents and components used to perform a test on biological samples (human serum and EDTA-plasma) outside of the body.
Performance Studies: The document describes analytical performance studies conducted to validate the device's ability to accurately measure the target analyte in biological samples.
Predicate Device: The mention of a predicate device (K132631) which is also an EliA product, further supports its classification as an IVD, as predicate devices are typically other legally marketed IVDs.

All these elements align with the definition of an In Vitro Diagnostic device, which is used to examine specimens derived from the human body to provide information for diagnostic purposes.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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.

Product codes

LKP

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

For prescription use only.
This device is not for point-of-care use.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies

Precision/Reproducibility:

Study type: Precision/Reproducibility
Sample size: 21 runs (3 instruments x 7 runs), 4 replicates per sample per run, total 84 replicates per sample.
Key results:
| Mean (EliA U/mL) | n | Within-Run SD | Within-Run %CV | Between-Run SD | Between-Run %CV | Between-Instrument SD | Between-Instrument %CV | Total Imprecision SD | Total Imprecision %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 |

Linearity/assay reportable range:

Study type: Linearity
Sample size: Four patient serum samples
Key results:
| Dilution range (EliA U/mL) | Slope | 95% Cl (Slope) | Intercept | 95% Cl (Intercept) | 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 |

Detection limit:

Study type: Limit of Blank (LoB) and Limit of Detection (LoD), Limit of Quantitation (LoQ)
Sample size: One blank sample and five low level samples measured in twelve replicates in each of six runs spread over six different days.
Key results: LoD for EliA SmDP is 0.8 EliA U/mL, LoB of 0.3 EliA U/mL. LoQ for EliA SmDP is 1.6 EliA U/mL.

Method comparison with predicate device (Instrument comparison):

Study type: Method Comparison
Sample size: More than 100 samples
Key results: 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.
| Instrument | Intercept | 95% Cl (Intercept) | Slope | 95% Cl (Slope) |
|---|---|---|---|---|
| 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 |

Key Metrics

Method comparison with predicate device (Instrument comparison) considering equivocal results 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%

Method comparison with predicate device (Instrument comparison) considering equivocal results 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%

Predicate Device(s)

K132631

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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).

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

1

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)

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.

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):

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.

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.

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.

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 Device
Phadia 250 | New Device
Phadia 2500/5000 |
|--------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use
EliA SmDP | EliA SmDP is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to Sm in human serum
and plasma (EDTA, citrate) as
an 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 250. | 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. |
| Analytical
technology:
Immuno-
fluorescence
measurement | Same | Same |
| Assay process | Same | Same |
| Common, dedicated
Phadia reagents | Same | Same
Introduction of new article
numbers for Development
Solution, Stop Solution and
Washing Solution is only due to
larger filling volumes which are
required for the bigger
instruments Phadia 2500/5000 |
| Result calculation
software; Phadia
Information Data
Manager (IDM) | Same | Same |
| Sample volume | 90 µL (20 µL of non-diluted
sample) | 90 µL (20 µL of non-diluted
sample) |
| Incubation
temperature | 37°C | 37°C |
| Conjugate volume | 90 µL | 90 µL |
| Development
Solution Volume | 90 µL | 90 µL |
| Stop Solution
Volume | 200 µL | 200 µL |
| Assay set-up | Random access | Random access |
| Reagent packaging
size | Various/Common | Various/Common
Introduction of new article
number for EliA Sample Diluent
(83-1071-01) is only due to
larger filling volume. |
| Onboard storage of
reagents | Yes | Yes |
| Time to 1st result | ~2 h | ~2 h |
| Feature | Predicate Device
Phadia 250 | New Device
Phadia 2500/5000 |
| Sample matrix;
Serum or plasma
type as indicated in
the DFU dependent
on assay | Human serum and plasma
(EDTA, citrate) | Human serum or EDTA- plasma,
i.e. citrate plasma is omitted as
for all EliA tests |
| Daily throughput | ~250 tests | ~2500/5000 tests |
| Sample Dilution | Phadia 250 uses a steel pipette
to dilute the samples in Dilution
Plates (Art.No. 12-3907-08) | Phadia 2500/5000 uses
disposable Pipette Tips in Racks
(Art No. 12-3805-04) for
pipetting samples in Dilution
Well (Art.No. 12-4005-69) |
| Risk for carry-over | The warning "DO NOT REUSE"
in the Phadia 250 DFU for EliA
Conjugates is due to the fact that
a low risk of conjugate
contamination by carry-over from
samples was identified. In order
to reduce the risk, the single use
statement for the conjugate was
included in the Phadia 250 DFU. | When running EliA tests on the
Phadia 2500/5000 instruments,
there is no need for this warning
statement because these
instruments use disposable tips
for pipetting samples and a
separate pipette for the
conjugate, and carry-over from
samples to conjugate is
impossible. |
| Loading of EliA
Carriers | EliA carriers are loaded manually
on the Loading Tray from where
they can be processed directly or
transferred to the cooled storage
compartment. | The Phadia 2500/5000
instruments do not have such a
Loading Tray. The EliA carriers
are loaded into racks which are
directly transferred to the cooled
storage compartment |
| Barcode reader | The Phadia 250 instrument has
a built-in barcode reader at the
front of the instrument, but the
operator needs to scan the
barcodes manually by showing
the reagents to the barcode
reader. Alternatively, the
operator can also enter the
characters below the barcode
manually. | The Phadia 2500/5000
instruments dispose of a built-in
barcode reader, and the
reagents are on a moving belt
which conveys them past the
barcode reader. The lot-specific
information will be read
automatically by the instrument
during loading. |
| Process time / Time
to patient result | Phadia 250 needs 1 minute to
process one Well.
Phadia 250 provides the results
at a one minute interval. | Phadia 2500/5000 instruments
process two Wells in parallel in
48 seconds.
Phadia 2500/5000 provides the
results at a 24 seconds interval. |

7

8

EliA SmD² Immunoassays on Phadia 250 and Phadia 2500/5000 instruments – Differences to predicate device

9

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
(EliA
U/mL) | n | Within-Run | | Between-
Run | | Between-
Instrument | | Total
Imprecision | |
|------------------------|----|------------|-----|-----------------|------|------------------------|------|----------------------|------|
| | | 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

| Dilution
range

(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

| 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) | 95th
percentile | 99th
percentile |
|----------------------------------|-----|-----------------------|--------------------|--------------------|
| EliA SmDP on Phadia
2500/5000 | 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.