EliA RF IgM is intended for the in vitro quantitative measurement of IgM class rheumatoid factor antibodies in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of rheumatoid arthritis in conjunction with other laboratory and clinical findings. EliA RF IgM uses the EliA IgM method on the instrument Phadia 2500/5000.

Device Description

The method-specific reagents are identical with K102673, but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of: Test Wells: EliA RF IqM Wells are coated with aggregated rabbit IgG 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 IgM Method Reagents: EliA IgM Conjugate 50 or 200: ß-Galactosidase labeled anti-IgM (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 IgM Calibrator Strips: Human IgM (0, 10, 35, 80, 500, 1000 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 IgM Curve Control Strips: Human IgM (80 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 IgM 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 an EliA RF IgM test.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the EliA RF IgM Immunoassay on the Phadia 2500/5000 instruments, based on the provided FDA 510(k) summary:

1. Acceptance Criteria and Reported Device Performance

The core of this submission is to demonstrate that the EliA RF IgM Immunoassay, previously cleared on the Phadia 250 instrument (K102673), performs substantially equivalently when used on the new Phadia 2500/5000 instrument platform. Therefore, the acceptance criteria are primarily focused on method comparison and analytical performance to show this equivalence. No explicit "acceptance criteria" are provided as a single table within this document for each performance characteristic, but they are implied by the statistical analyses and cut-offs used.

Here's an organized table presenting the relevant acceptance criteria (implied or stated) and the reported device performance:

Performance Characteristic	Acceptance Criteria (Implied/Stated)	Reported Device Performance
Precision	Not explicitly stated for each concentration, but typically CV% should be within acceptable clinical limits for diagnostic assays.	EliA RF IgM on Phadia 2500/5000:
Linearity	Slope for regression lines should be close to 1, intercept close to 0, R² close to 1.	EliA RF IgM on Phadia 2500/5000:
Reportable Range	Defined by LoD and upper limit (200 IU/mL).	EliA RF IgM on Phadia 2500/5000:Reportable range: 0.6 to 200 IU/mL.Measuring range (LoQ to upper limit): 1.0 to 200 IU/mL. (Section 10b)
Detection Limit (LoD)	Determined consistent with CLSI EP17-A; proportions of false positives (α) < 5% and false negatives (β) < 5%.	EliA RF IgM on Phadia 2500/5000:LoD: 0.6 IU/mL (based on 132 determinations with 66 blank and 66 low-level replicates).LoB: 0.2 IU/mL. (Section 10d)
Quantitation Limit (LoQ)	Determined consistent with CLSI EP17-A2; target uncertainty goal of 20%.	EliA RF IgM on Phadia 2500/5000:LoQ: 1.0 IU/mL (based on 66 determinations). (Section 10d)
Method Comparison	Slope for regression lines should be 0.9 - 1.1 for single replicate to single replicate, and intercept close to 0. (For predicate vs. new instrument performance).	EliA RF IgM on Phadia 2500/5000 vs. Phadia 250:
PPA/NPA (Equivocal results considered positive)	Not explicitly stated, but typically high agreement with predicate is expected for substantial equivalence.	EliA RF IgM on Phadia 2500/5000 vs. Phadia 250:Instrument A: PPA 100.0%, NPA 82.4%Instrument B: PPA 100.0%, NPA 88.9%Instrument C: PPA 100.0%, NPA 77.8% (Table from Section 12c)
PPA/NPA (Equivocal results considered negative)	Not explicitly stated, but typically high agreement with predicate is expected for substantial equivalence.	EliA RF IgM on Phadia 2500/5000 vs. Phadia 250:Instrument A: PPA 98.7%, NPA 96.3%Instrument B: PPA 100.0%, NPA 100.0%Instrument C: PPA 100.0%, NPA 96.4% (Table from Section 12c)

2. Sample Sizes and Data Provenance

Precision Test Set Sample Size: Five samples (at various concentrations: 1.6, 3.9, 7.0, 73.7, 169.6 IU/mL). Each sample tested in four replicates/run, over 21 runs (3 instruments x 7 runs), totaling 84 replicates per sample.
Linearity Test Set Sample Size: Four patient serum samples.
Detection Limit (LoD/LoB) Test Set Sample Size: One blank sample (measured in 33 replicates in each of two runs) and three low-level samples (measured in 11 replicates in each of two runs). Total 66 blank determinations and 66 low-level determinations for LoD. 66 determinations for LoQ.
Method Comparison Test Set Sample Size: More than 100 samples (with ≥20% of the samples within ±25% of the medical decision point).
Expected Values/Reference Range Test Set Sample Size: n = 400 apparently healthy subjects.
Data Provenance: Not explicitly stated for specific sample origins (e.g., country of origin, retrospective/prospective). The reference range study mentions "sera from a Caucasian population obtained from a blood bank," which implies a prospective collection for that specific study, but the overall patient samples used in other analytical studies are not detailed.

3. Number of Experts and Qualifications (Ground Truth Establishment for Test Set)

Not Applicable: This submission is for an immunoassay, which detects specific antibodies in patient samples. The "ground truth" for such devices is established by the assay's ability to accurately measure the analyte (IgM class rheumatoid factor antibodies) and correlate with clinical diagnosis of rheumatoid arthritis, as per established medical criteria for the disease itself, not by expert consensus on image interpretation or similar qualitative assessments. For method comparison studies, the "ground truth" is essentially the result obtained by the predicate device (EliA RF IgM on Phadia 250).

4. Adjudication Method (for Test Set)

Not Applicable: Adjudication methods (like 2+1 or 3+1) are typically used for qualitative assessments, such as image interpretation, where multiple experts provide independent reads that may then be reconciled. This device is a quantitative immunoassay.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No: An MRMC study is not relevant for this type of in vitro diagnostic device (immunoassay). MRMC studies are used to assess the comparative effectiveness of different diagnostic methods (e.g., AI-assisted vs. unassisted human readers) using multiple readers and multiple cases, typically for image-based diagnostics.

6. Standalone Performance Study (Algorithm Only)

Yes, implicitly: The entire submission describes the standalone performance of the device (EliA RF IgM Immunoassay on the Phadia 2500/5000 instrument) in terms of its analytical characteristics (precision, linearity, detection limits, method comparison to the predicate). There is no "human-in-the-loop" for this automated immunoassay; the result is generated by the instrument and its associated software based on the specimen's reaction.

7. Type of Ground Truth Used

For Analytical Performance:
- Predicate Device Results: For method comparison, the results obtained from the predicate device (EliA RF IgM on Phadia 250) served as the comparative "ground truth" against which the new instrument's results were evaluated for substantial equivalence.
- Expected Values/Spiked Samples/Known Standards: For studies like linearity and precision, the "ground truth" is based on samples with known or expected concentrations, or samples created through controlled dilutions.
For Clinical Relevance: While the direct analytical studies here used the predicate as a reference, the original clinical performance values for the EliA RF IgM immunoassay were "reviewed in K102673," which would have established its "aid in diagnosis" claim against clinical findings of rheumatoid arthritis.

8. Sample Size for the Training Set

Not Applicable in the traditional sense: This device is an immunoassay, not an AI/ML algorithm that undergoes a distinct "training phase" on a dataset in the way an imaging algorithm would. The development of an immunoassay involves optimization of reagents and protocols, which is a different process than "training" an algorithm. The 510(k) process focuses on demonstrating analytical and clinical performance for regulatory clearance.

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

Not Applicable: As explained above, there is no traditional "training set" or "ground truth for a training set" as it would apply to an AI/ML device. The "ground truth" related to the assay's development (optimization, reagent formulation, etc.) would stem from biochemical principles, manufacturing specifications, and initial performance evaluations to ensure the assay functions as intended before formal validation studies.

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, there is a symbol of the Department of Health & Human Services. To the right of the symbol, the text "FDA U.S. FOOD & DRUG" is displayed in a bold, sans-serif font, with "FDA" in a blue square. Below that, the word "ADMINISTRATION" is written in a smaller font size, also in blue.

December 18, 2018

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

Re: K182747

Trade/Device Name: EliA RF IgM Immunoassay Regulation Number: 21 CFR 866.5775 Regulation Name: Rheumatoid factor immunological test system Regulatory Class: Class II Product Code: DHR Dated: September 27, 2018 Received: September 28, 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) K182747

Device Name EliA(TM) RF IgM Immunoassay

Indications for Use (Describe)

EliA RF IgM is intended for the in vitro quantitative measurement of IgM class rheumatoid factor antibodies in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of theumatoid arthritis in conjunction with other laboratory and clinical findings. EliA RF IgM uses the EliA IgM 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:

B. Purpose for Submission:
Adding a previously cleared assay on a new instrument platform (Phadia® 2500/5000)
C. Measurands: Rheumatoid Factor IgM
D. Type of Test: Quantitative measurement immunoassay
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:

September 27, 2018

F. Proprietary and Established Names:

EliA™ RF IgM Immunoassay

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G. Regulatory Information:

1. Regulation section: 21 CFR§866.5775 - Rheumatoid Factor Immunological Test System
1. Classification: Class II
1. Product code: DHR System, Test, Rheumatoid Factor (RF)
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 K102673, but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:

Test Wells:

EliA RF IqM Wells are coated with aggregated rabbit IgG 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 IgM Method Reagents:
EliA IgM Conjugate 50 or 200: ß-Galactosidase labeled anti-IgM (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 IgM Calibrator Strips: Human IgM (0, 10, 35, 80, 500, 1000 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 IgM Curve Control Strips: Human IgM (80 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 IgM 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 an EliA RF IgM test.

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J. Substantial Equivalence Information:

Predicate device name(s) and 510(k) number(s): EliA RF IgM on Phadia 250 instrument, K102673

2. Comparison with predicate device:

EliA RF IgM Immunoassay on Phadia 250 and Phadia 2500/5000 instruments – Similarities to predicate devices

Feature	Predicate DevicePhadia 250	New DevicePhadia 2500/5000
Intended UseEliA RF IgM	EliA RF IgM is intended for the invitro quantitative measurementof IgM class rheumatoid factorantibodies in serum and plasma(Li-heparin, EDTA, citrate) to aidin the diagnosis of rheumatoidarthritis in conjunction with otherlaboratory and clinical findings.EliA RF IgM uses the EliA IgMmethod on the instrumentPhadia 250.	EliA RF IgM is intended for the invitro quantitative measurementof IgM class rheumatoid factorantibodies in human serum andplasma (Li-heparin, EDTA) to aidin the diagnosis of rheumatoidarthritis in conjunction with otherlaboratory and clinical findings.EliA RF IgM uses the EliA IgMmethod on the instrumentPhadia 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
Development	90 µL	90 µL
Solution Volume
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 or plasma (Li-heparin, EDTA, citrate)	Human serum or plasma (Li-heparin, EDTA), i.e. citrateplasma is omitted in both 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 RF IgM Immunoassay 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 aggregated rabbit IgG antigen. 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 IgM antibodies (EliA IgM 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 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):

1. 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 RF IgM Well on the Phadia 2500/5000 instrument, as data for inter-lot-variation has already been shown in K102673. The results are summarized in the table below:

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Mean(IU/mL)	Within-Run		Between-Run		Between-Instrument		Total Imprecision
	SD	%CV	SD	%CV	SD	%CV	SD	%CV
1.6	0.2	12.7	0.1	7.1	0.1	4.2	0.2	15.2
3.9	0.2	5.0	0.2	4.5	0.2	6.0	0.3	9.0
7.0	0.3	4.8	0.2	3.1	0.4	5.3	0.5	7.8
73.7	1.8	2.5	3.1	4.2	5.3	7.2	6.4	8.7
169.6	7.3	4.3	7.9	4.6	10.8	6.4	15.2	9.0

EliA RF IgM on Phadia 2500/5000

b. Linearity/assay reportable range:

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

Dilution range(IU/mL)	Slope	Intercept	R2
0.9 - 41.0	1.02	0.37	1.00
0.9 - 29.2	1.02	0.18	1.00
2.2 - 195.5	0.96	-1.11	0.99
0.8 - 71.5	1.01	0.24	1.00

EliA RF IgM on Phadia 2500/5000

The reportable range (Limit of Detection, upper limit) for EliA RF IgM is from 0.6 to 200 IU/mL. The measuring range (Limit of Quantitation, upper limit) is from 1.0 to 200 IU/mL.

Statements included in the package insert: "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 IgM method was previously reviewed in K091845.
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 RF IgM:

The LoD for EliA RF IgM is 0.6 IU/mL, determined consistent with the guidelines in CLSI document EP17-A and with proportions of false positives (a) less than 5% and false negatives (B) less than 5%; based on 132 determinations with 66 blank and 66 low level replicates; and LoB of 0.2 IU/mL.

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The LoQ for EliA RF IgM is 1.0 IU/mL, determined consistent with the guidelines in CLSI document EP17-A2, based on 66 determinations, and a target uncertainty goal of 20%.

The results are summarized in the table below:

EliA RF IgM (IU/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.2	0.6	1.0

e. Analytical specificity:
Interference: Previously reviewed in K102673.

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. K102673).

EliA RF IgM Well

< 3.5 IU/mL	Negative
3.5 - 5.0 IU/mL	Equivocal
> 5.0 IU/mL	Positive

1. Comparison studies:
Method comparison with predicate device (Instrument comparison): a. See 2c Instrument Comparison below
b. Matrix comparison: Previously reviewed under K102673.

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Instrument comparison C.

In the Method Comparison studies for EliA RF IgM, 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.

EliA RF IgM:

Instrument	Intercept	95% CI	Slope	95% CI
PH2500/5000 A	0.068	-0.097 – 0.447	0.996	0.969 – 1.012
PH2500/5000 B	0.421	0.188 – 0.755	0.983	0.953 – 1.017
PH2500/5000 C	-0.023	-0.264 – 0.210	1.061	1.044 – 1.078

equivocal results considered positive

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	100.0%	100.0%	100.0%
95% CI	95.9% - 100%	95.9% - 100%	95.7% - 100%
NPA	82.4%	88.9%	77.8%
95% CI	56.6% - 96.2%	65.3% - 98.6%	52.4% - 93.6%

equivocal results considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.7%	100.0%	100.0%
95% CI	93.0% - 100%	95.3% - 100%	95.1% - 100%
NPA	96.3%	100.0%	96.4%
95% CI	81.0% - 99.9%	87.7% - 100%	81.7% - 99.9%

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 K102673.

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Clinical cut-off: 4.
Same as assay cut-off.

5. Expected values/Reference range:

The frequency distribution for IgM rheumatoid factor 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(IU/mL)	95thpercentile	99thpercentile
EliA RF IgM onPhadia 2500/5000	400	<0.6	2.9	19.2

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 RF IgM immunoassay.

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

Regulation Number and Section

§ 866.5775 Rheumatoid factor immunological test system.

(a)
Identification. A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.(b)
Classification. Class II (performance standards).