Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard in vitro diagnostic immunoassay kit and automated instrument system. There is no mention of AI, ML, or any computational analysis beyond standard data processing for quantitative measurement and performance metrics.

Therapeutic

No
This device is for in vitro diagnostic (IVD) use to aid in the diagnosis of rheumatoid arthritis by measuring antibodies, not for therapeutic purposes.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the in vitro quantitative measurement of IgM class rheumatoid factor antibodies in human serum and plasma... to aid in the diagnosis of rheumatoid arthritis." This directly indicates its role in diagnosis.

SaMD (Software as a Medical Device)

No

The device description clearly outlines multiple physical components, including test wells, sample diluent, method reagents, calibrator strips, and curve control strips. These are tangible, physical items used in the in vitro diagnostic process, not solely software.

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 the in vitro quantitative measurement of IgM class rheumatoid factor antibodies in human serum and plasma... to aid in the diagnosis of rheumatoid arthritis". The phrase "in vitro" (meaning "in glass" or "in the lab") and the measurement of analytes in human samples for diagnostic purposes are key characteristics of an IVD.
Device Description: The description details reagents and components used to perform a test on biological samples (serum and plasma).
Care Setting: While it states "For prescription use only" and "This device is not for point-of-care use," this describes the intended use environment and user, not whether it's an IVD. IVDs can be used in various settings, including clinical laboratories.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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.

Product codes

DHR

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 IgM 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.

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 study
Sample size: Each sample tested in four replicates/run, total 84 replicates per sample for 21 runs (3 instruments x 7 runs).
Key results:

Mean (IU/mL)	Within-Run SD	Within-Run %CV	Between-Run SD	Between-Run %CV	Between-Instrument SD	Between-Instrument %CV	Total Imprecision SD	Total Imprecision %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

Linearity/Assay Reportable Range:
Study type: Linearity study
Sample size: Four patient serum samples
Key results:

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
Reportable range: 0.6 to 200 IU/mL. Measuring range: 1.0 to 200 IU/mL.

Detection Limit:
Study type: LoB and LoD studies
Sample size: One blank sample and three low level samples measured in thirty-three and eleven replicates, respectively, in each of two runs.
Key results: LoD for EliA RF IgM is 0.6 IU/mL, LoB of 0.2 IU/mL. LoQ for EliA RF IgM is 1.0 IU/mL.

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

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.

Method Comparison with Predicate Device (Instrument comparison):
Study type: Method Comparison studies
Sample size: More than 100 samples (≥20% of the samples within ±25% of the medical decision point)
Key results: Slope for the regression lines should be 0.9 - 1.1 for single replicate to single replicate and intercept close to 0 were met.

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

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Assay Cut-off:


5.0 IU/mL	Positive

Instrument Comparison with 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%

Instrument Comparison with 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%

Expected Values/Reference Range:
Frequency distribution for IgM rheumatoid factor in apparently healthy subjects.

Test	n =	Median (IU/mL)	95th percentile	99th percentile
EliA RF IgM on Phadia 2500/5000	400

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).

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.

1

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):

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.

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 Device
Phadia 250 | New Device
Phadia 2500/5000 |
|--------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use
EliA RF IgM | EliA RF IgM is intended for the in
vitro quantitative measurement
of IgM class rheumatoid factor
antibodies in serum and plasma
(Li-heparin, EDTA, citrate) 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 250. | 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. |
| 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 | 90 µL | 90 µL |
| Solution Volume | | |
| 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 or plasma (Li-
heparin, EDTA, citrate) | Human serum or plasma (Li-
heparin, EDTA), i.e. citrate
plasma is omitted in both 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. |

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8

EliA RF IgM Immunoassay 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 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

| 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.

13

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) | 95th
percentile | 99th
percentile |
|------------------------------------|-----|-------------------|--------------------|--------------------|
| EliA RF IgM on
Phadia 2500/5000 | 400 |