Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard immunoassay system and its reagents, focusing on analytical performance and comparison to a predicate device. There is no mention of AI or ML in the device description, intended use, or performance studies.

Therapeutic

No
The device is an in vitro diagnostic (IVD) device intended for semi-quantitative measurement of antibodies to aid in diagnosis, not for treating any condition.

Diagnostic

Yes

The device is intended for the "in vitro semi-quantitative measurement of IgG antibodies directed to M2 in human serum and plasma...to aid in the clinical diagnosis of primary biliary cirrhosis in conjunction with other laboratory and clinical findings." This explicitly states its use in aiding diagnosis.

SaMD (Software as a Medical Device)

No

The device description clearly outlines multiple physical components including test wells, sample diluent, conjugate, calibrator strips, and calibrator wells, which are all reagents and consumables used in an in vitro diagnostic test. It also mentions the use of the Phadia 2500/5000 instrument, which is a hardware system. While there is likely software controlling the instrument and processing the results, the device itself is 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 semi-quantitative measurement of IgG antibodies directed to M2 in human serum and plasma... to aid in the clinical diagnosis of primary biliary cirrhosis". The phrase "in vitro" (meaning "in glass" or "in the lab") and the purpose of measuring analytes in human samples for diagnostic aid are key characteristics of an IVD.
Device Description: The description details reagents and components used to perform a test on human samples (serum and plasma). This aligns with the nature of IVD devices.
Performance Studies: The document describes analytical performance studies (Precision, Linearity, Detection limit, Analytical specificity) and comparison studies (Instrument comparison, Matrix comparison) conducted to validate the performance of the device when used with human samples. This is standard practice for IVD devices.
Predicate Device: The mention of a predicate device (K141375) which is also an EliA M2 on a different instrument, further indicates that this device is being compared to an existing IVD.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

EliA M2 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to M2 in human serum and plasma (Li-heparin, EDTA) to aid in the clinical diagnosis of primary biliary cirrhosis in conjunction with other laboratory and clinical findings. EliA M2 uses the EliA IgG method on the instrument Phadia 2500/5000.

Product codes (comma separated list FDA assigned to the subject device)

DBM

Device Description

The method-specific reagents are identical with K141375 (EliA M2 on Phadia 250), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:

Test Wells: -EliA M2 Wells are coated with native pyruvate dehydrogenase complex from mitochondria and recombinant M2-antigen - 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 ug/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 M2 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 (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision/Reproducibility: A study with a total of 21 runs (3 instruments x 7 runs) was performed. Each sample was tested in four replicates/run, giving 84 replicates per sample. The data was calculated against the calibration curve from Day 1. Only one lot of EliA M2 Well on the Phadia 2500/5000 instrument was included.
Results:

Mean (U/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
1.7	0.1	7.3	0.1	4.8	0.2	13.1	0.3	15.8
4.0	0.2	4.3	0.1	2.9	0.3	6.6	0.3	8.4
5.9	0.2	3.7	0.1	2.5	0.3	4.2	0.4	6.2
74.8	2.3	3.1	1.7	2.2	4.0	5.3	4.9	6.5
175.9	8.0	4.5	6.8	3.9	12.1	6.9	16.0	9.1

Linearity/Assay Reportable Range: Four patient serum samples were diluted in EliA Sample Diluent and tested.
Results:

Dilution range (U/mL)	Slope	Intercept	R2
0.7 - 48.3	0.99	-0.32	1.00
2.1 - 211.3	1.02	1.90	1.00
5.7 - 253.2	1.03	2.36	1.00
0.5 - 16.6	1.02	0.13	1.00
The linear range and the measuring range are set to 0.8 U/mL (LoQ) to 220 U/mL (upper limit of measuring range). The reportable range (Limit of Detection, upper limit of measuring range) for EliA M2 is from 0.5 to 220 U/mL.

Detection Limit: LoB and 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.
Results:

EliA M2 (U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.3	0.5	0.8
The LoD for EliA M2 is 0.5 U/mL. The LoQ for EliA M2 is 0.8 U/mL.

Method Comparison with Predicate Device (Instrument comparison): More than 100 samples (≥10% of the samples within ±25% of the medical decision point) were run in single 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 M2.
Results:

Instrument	Intercept	95% CI	Slope	95% CI
PH2500/5000	-0.14	-0.46 to 0.03	1.04	1.02 to 1.06

Clinical studies: Not applicable. Clinical performance values were reviewed in K141375.

Expected values/Reference range: The frequency distribution for anti-M2 antibodies was investigated in a group of 400 apparently healthy subjects equally distributed by age and gender, using sera from a Caucasian population obtained from a blood bank.
Results:

Test	n =	Median (U/mL)	95th percentile	99th percentile
EliA M2 on Phadia 2500/5000	400	0.9	1.9	5.2

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

equivocal results considered positive:

criteria	PH2500/5000
PPA	100.0%
95% CI	96.0% – 100%
NPA	93.3%
95% CI	68.1% – 99.8%
TPA	99.1%
95% CI	94.9% – 100%

equivocal results considered negative:

criteria	PH2500/5000
PPA	100.0%
95% CI	95.7% - 100%
NPA	95.5%
95% CI	77.2% - 99.9%
TPA	99.1%
95% CI	94.9% - 100%

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K141375

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

K061165

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.5090 Antimitochondrial antibody immunological test system.

(a)
Identification. An antimitochondrial antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's own tissue), such as primary biliary cirrhosis (degeneration of liver tissue) and chronic active hepatitis (inflammation of the liver).(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 is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

July 13, 2018

Phadia AB % Martin Mann Senior Regulatory Affairs Manager Phadia US Inc. 4169 Commercial Avenue Portage, Michigan 49002

Re: K181556

Trade/Device Name: EliA M2 Immunoassay Regulation Number: 21 CFR 866.5090 Regulation Name: Antimitochondrial antibody immunological test system Regulatory Class: Class II Product Code: DBM Dated: June 12, 2018 Received: June 13, 2018

Dear Martin Mann:

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. 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 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

1

803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); 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,

Douglas A. Jeffery -S

For 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)

Device Name EliA(TM) M2 Immunoassay

Indications for Use (Describe)

EliA M2 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to M2 in human serum and plasma (Li-heparin, EDTA) to aid in the clinical diagnosis of primary biliary cirrhosis in conjunction with other laboratory and clinical findings. EliA M2 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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A.6 510(k) Summary of Safety and Effectiveness per 21CFR 807.92(c).

This summary of safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR Part 807.92.

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:

B. Purpose for Submission:

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

C. Measurand:

lqG antibodies specific for M2 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: Martin Mann Requlatory Affairs Manager Phadia US Inc. 4169 Commercial Avenue Portage, Mi 49002, USA +1 (-269-492) -1957 (Phone) +1 (-269-492) -7541 (Fax) martin.mann@thermofisher.com

Date of Summary Preparation: June 12, 2018

F. Proprietary and Established Names:

EliA™ M2 Immunoassay

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G. Regulatory Information:

1. Requlation section: 21 CFR §866.5090, Antimitochondrial antibody immunological test system
1. Classification: Class II
1. Product code: DBM, Antimitochondrial Antibody, Indirect Immunofluorescent, Antigen, Control
1. Panel: Immunology (82)

H. Intended use(s):

Intended use(s):

EliA M2 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to M2 in human serum and plasma (Li-heparin, EDTA) to aid in the clinical diagnosis of primary biliary cirrhosis in conjunction with other laboratory and clinical findings. EliA M2 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 K141375 (EliA M2 on Phadia 250), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:

Test Wells: -EliA M2 Wells are coated with native pyruvate dehydrogenase complex from mitochondria and recombinant M2-antigen - 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 ug/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 M2 tests.

J. Substantial Equivalence Information:

Predicate device name(s) and 510(k) number(s): 1. EliA M2 on Phadia 250 instrument, K141375

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2. Comparison with predicate device:

EliA M2 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 M2 | EliA M2 is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to M2 in human serum
and plasma (heparin, EDTA) to
aid in the clinical diagnosis of
primary biliary cirrhosis in
conjunction with other laboratory
and clinical findings. EliA M2
uses the EliA IgG method on the
instrument Phadia 250. | EliA M2 is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to M2 in human serum
and plasma (Li-heparin, EDTA) to
aid in the clinical diagnosis of
primary biliary cirrhosis in
conjunction with other laboratory
and clinical findings. EliA M2
uses the EliA IgG method on the
instrument Phadia 2500/5000. |
| Sample matrix;
Serum or plasma
type as indicated in
the DFU dependent
on assay | human serum and plasma
(heparin, EDTA) | human serum and plasma (Li-
heparin, EDTA) |
| Analytical
technology:
Immuno-
fluorescence
measurement | Same | Same |
| Assay process | Same | Same |
| Common, dedicated
Phadia reagents | 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 |
| 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 M2 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 native pyruvate dehydrogenase complex from mitochondria and recombinant M2-antigen. If present in the patient's specimen, antibodies to M2 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, nonbound coniugate 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 more specific IgG is present in the specimen. 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/dav 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 M2 Well on the Phadia 2500/5000 instrument, as data for inter-lot-variation has already been shown in K141375. The results are summarized in the table below:

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| Mean
(U/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 |
|----------------|----------------------|-----------------------|-------------------|--------------------|--------------------------|---------------------------|-------------------------|--------------------------|
| 1.7 | 0.1 | 7.3 | 0.1 | 4.8 | 0.2 | 13.1 | 0.3 | 15.8 |
| 4.0 | 0.2 | 4.3 | 0.1 | 2.9 | 0.3 | 6.6 | 0.3 | 8.4 |
| 5.9 | 0.2 | 3.7 | 0.1 | 2.5 | 0.3 | 4.2 | 0.4 | 6.2 |
| 74.8 | 2.3 | 3.1 | 1.7 | 2.2 | 4.0 | 5.3 | 4.9 | 6.5 |
| 175.9 | 8.0 | 4.5 | 6.8 | 3.9 | 12.1 | 6.9 | 16.0 | 9.1 |

EliA M2 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 M2 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 M2 on Phadia 2500/5000

| Dilution range

(U/mL)	Slope	Intercept	R2
0.7 - 48.3	0.99	-0.32	1.00
2.1 - 211.3	1.02	1.90	1.00
5.7 - 253.2	1.03	2.36	1.00
0.5 - 16.6	1.02	0.13	1.00

The linear range and the measuring range are set to 0.8 U/mL (LoQ) to 220 U/mL (upper limit of measuring range).

The reportable range (Limit of Detection, upper limit of measuring range) for EliA M2 is from 0.5 to 220 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 M2 is 0.5 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 U/mL.

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The LoQ for EliA M2 is 0.8 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 M2 (U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.3	0.5	0.8

e. Analytical specificity:
Interference: Previously reviewed in K141375

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. K141375).

EliA M2 Well

| 6 U/mL | Positive |

Comparison studies: 2.
Method comparison with predicate device (Instrument comparison): a. See 2c Instrument Comparison below
Matrix comparison: b. Previously reviewed under K141375.
Instrument comparison C.

In the Method Comparison studies for EliA M2, more than 100 samples (≥10% of the samples within ±25% of the medical decision point) were run in single 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 M2.

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EliA M2:

Instrument	Intercept	95% CI	Slope	95% CI
PH2500/5000	-0.14	-0.46 to 0.03	1.04	1.02 to 1.06

equivocal results considered positive

criteria	PH2500/5000
PPA	100.0%
95% CI	96.0% – 100%
NPA	93.3%
95% CI	68.1% – 99.8%
TPA	99.1%
95% CI	94.9% – 100%

equivocal results considered negative

criteria	PH2500/5000
PPA	100.0%
95% CI	95.7% - 100%
NPA	95.5%
95% CI	77.2% - 99.9%
TPA	99.1%
95% CI	94.9% - 100%

ဒေ 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 K141375.
Clinical cut-off: 4. Same as assay cut-off.
Expected values/Reference range: 5.

The frequency distribution for anti-M2 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.

13

The results are given in the table below:

| Test | n = | Median
(U/mL) | 95th
percentile | 99th
percentile |
|--------------------------------|-----|------------------|--------------------|--------------------|
| EliA M2 on Phadia
2500/5000 | 400 | 0.9 | 1.9 | 5.2 |

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 M2 immunoassays.

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