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.

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.

AI/ML Overview

The provided text describes the 510(k) premarket notification for the EliA™ M2 Immunoassay, specifically focusing on its performance on new instrument platforms (Phadia® 2500/5000) compared to a previously cleared device (EliA M2 on Phadia 250 instrument, K141375).

This document is for an in vitro diagnostic (IVD) device, which measures IgG antibodies to M2 to aid in the clinical diagnosis of primary biliary cirrhosis. The "device" in this context is the immunoassay system, which includes the reagents and the instrument platforms.

Therefore, the acceptance criteria and study details discussed pertain to the analytical performance of this IVD device. The concepts of "human readers," "expert consensus for image interpretation," "MRMC," and "standalone algorithm performance" are not applicable here, as this is not an AI/ML imaging device or a device requiring human interpretation of complex visual data. The "ground truth" for an IVD diagnostic test is typically established through reference methods, established clinical diagnoses, or highly characterized samples.

Here's a breakdown of the acceptance criteria and study proof based on the provided text, focusing on the analytical performance of the immunoassay system.

Acceptance Criteria and Reported Device Performance

The core of the "acceptance criteria" for this 510(k) submission is demonstrating substantial equivalence to the predicate device. This is achieved by showing that the analytical performance characteristics of the EliA M2 immunoassay on the Phadia 2500/5000 instruments are comparable and acceptable. The document highlights various analytical performance parameters with their respective results.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is an IVD device, the "acceptance criteria" aren't explicitly stated as pass/fail thresholds in a table, but rather implied by the data presented for substantial equivalence. The document presents the study results for various analytical performance metrics.

Performance Characteristic	Implicit Acceptance Criteria (Comparative)	Reported Device Performance (EliA M2 on Phadia 2500/5000)
Precision/Reproducibility	Low variability across runs, instruments, and within-run. CVs should be acceptable for diagnostic assays.	Total Imprecision %CV: 1.7 U/mL: 15.8% 4.0 U/mL: 8.4% 5.9 U/mL: 6.2% 74.8 U/mL: 6.5% 175.9 U/mL: 9.1%
Linearity/Reportable Range	Observed/Expected ratios for linearity close to 1, strong correlation (R² close to 1). Linear range and measuring range should be clearly defined.	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 Measuring Range: 0.8 U/mL (LoQ) to 220 U/mL
Detection Limit (LoD)	LoD should be adequately determined and clinically acceptable.	LoD: 0.5 U/mL (determined based on CLSI EP17-A guidelines)
Limit of Quantitation (LoQ)	LoQ should be adequately determined for quantitative measurements.	LoQ: 0.8 U/mL (determined based on CLSI EP17-A guidelines, target uncertainty 20%)
Analytical Specificity (Interference)	Should be free from significant interference from common substances.	"Previously reviewed in K141375" (implies no new interference studies needed if the chemistry is the same).
Analytical Specificity (Carry-over)	Should be no significant carry-over between samples/reagents.	No carry-over from samples to conjugate due to disposable tips and separate pipettes.
Method Comparison (vs. Predicate)	Strong correlation (slope close to 1, intercept close to 0) between new and predicate instruments.	Slope: 1.04 (95% CI: 1.02 to 1.06) Intercept: -0.14 (95% CI: -0.46 to 0.03)
PPA, NPA, TPA (Equivocal Positive)	High agreement (e.g., >90%) with predicate based on clinical classification.	PPA: 100.0% (96.0% – 100%) NPA: 93.3% (68.1% – 99.8%) TPA: 99.1% (94.9% – 100%)
PPA, NPA, TPA (Equivocal Negative)	High agreement (e.g., >90%) with predicate based on clinical classification.	PPA: 100.0% (95.7% - 100%) NPA: 95.5% (77.2% - 99.9%) TPA: 99.1% (94.9% - 100%)

2. Sample Size Used for the Test Set and Data Provenance

Precision/Reproducibility:
- Sample Size: Each sample was tested in four replicates/run, over 7 days, on 3 instruments. This totals 84 replicates per sample (4 replicates * 7 days * 3 instruments = 84 replicates). The document doesn't specify the number of distinct "samples" (control materials or patient samples) used to establish precision at different concentration levels, but it shows results for 5 different mean concentration levels (1.7, 4.0, 5.9, 74.8, 175.9 U/mL). Typically, these would be control materials or pooled patient samples.
- Data Provenance: Not explicitly stated, but clinical studies for cut-off determination (K141375) and reference ranges mentioned a "Caucasian population obtained from a blood bank." For analytical studies like precision, standard reference materials or well-characterized internal controls are commonly used. The study was performed over 7 days.
Linearity/Assay Reportable Range:
- Sample Size: Four patient serum samples were diluted.
- Data Provenance: Not explicitly stated regarding country of origin or retrospective/prospective nature for these specific samples.
Detection Limit (LoB, LoD, LoQ):
- Sample Size:
  - LoB: One blank sample, measured in twelve replicates in each of six runs (72 determinations total).
  - LoD: Five low-level samples, measured in twelve replicates in each of six runs (360 low level replicates total).
  - LoQ: 360 determinations.
- Data Provenance: Not explicitly stated.
Method Comparison (Instrument Comparison):
- Sample Size: More than 100 samples.
- Data Provenance: Not explicitly stated regarding country of origin or retrospective/prospective nature. Samples were run in "single replicates" on one Phadia 250 and one Phadia 2500/5000 instrument.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Not applicable. This is an in vitro diagnostic (IVD) immunoassay system, not an AI/ML imaging device that requires human expert interpretation of visual data. The "ground truth" for IVD laboratory tests is typically established by:
- Quantitative values: Directly measured by reference methods or highly characterized (e.g., gravimetric, spectrophotometric) standards traceability.
- Qualitative results (positive/negative): Defined by cut-off values derived from clinical studies, often comparing against a gold standard diagnostic method (e.g., biopsy, established clinical diagnosis of PBC).

4. Adjudication Method for the Test Set

Not applicable. This concept (e.g., 2+1, 3+1) relates to consensus reading in imaging studies. For an IVD assay, results are quantitative values or interpreted based on pre-defined cut-offs.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

Not applicable. This is an IVD immunoassay device, not an AI-assisted diagnostic imaging system. There are no "human readers" in the context of image interpretation improving with AI assistance. The device directly measures antibody levels.

6. If a Standalone (i.e. Algorithm Only Without Human-in-the Loop Performance) Was Done

Partially applicable, but in a different sense. The device itself performs the measurement and provides a quantitative result. The "performance" demonstrated (precision, linearity, LoD, method comparison) is inherently "standalone" in that it's the instrument and reagents producing the values. The "human-in-the-loop" would be the clinician interpreting the numerical result in conjunction with other clinical findings for diagnosis. There isn't an "algorithm" making a diagnostic call independently like in an imaging AI; rather, it's a measurement system.

7. The Type of Ground Truth Used

Analytical Performance:
- Reference materials and statistical methods: For precision, linearity, and detection limit, the ground truth is based on highly characterized control materials, serial dilutions, and established statistical methodologies (e.g., CLSI guidelines EP05-A3, EP06-A, EP17-A).
Clinical Performance (Cut-off determination and comparison):
- Clinical diagnosis and predicate device comparison: The clinical cut-off values for "Negative," "Equivocal," and "Positive" were "derived from the clinical studies (s. K141375)." This implies that the cut-offs were established using patient samples with confirmed clinical diagnoses of primary biliary cirrhosis (or healthy controls) as the ground truth in the predicate device's original studies.
- For the current submission, the "ground truth" for the method comparison study (comparing Phadia 2500/5000 to Phadia 250) is the result generated by the predicate device (EliA M2 on Phadia 250 instrument). The goal is to show the new instrument produces substantially equivalent results to the established predicate.

8. The Sample Size for the Training Set

Not applicable in the AI/ML sense. This is an immunoassay system; it does not have a "training set" in the context of machine learning model development. The development process would involve formulation optimization, reagent stability testing, and calibration studies, but not "training data" for an algorithm that learns patterns. The calibration curve is established using calibrators provided with the kit.

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

Not applicable. See point 8. For IVDs, the "ground truth" for establishing a calibration curve (which is somewhat analogous to "training" the system to interpret raw signals into quantitative units) is defined by the known concentrations of the calibrator materials provided in the kit. These calibrators are rigorously manufactured and assigned values traceable to reference 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

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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)

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):

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 DevicePhadia 250	New DevicePhadia 2500/5000
Intended UseEliA M2	EliA M2 is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to M2 in human serumand plasma (heparin, EDTA) toaid in the clinical diagnosis ofprimary biliary cirrhosis inconjunction with other laboratoryand clinical findings. EliA M2uses the EliA IgG method on theinstrument Phadia 250.	EliA M2 is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to M2 in human serumand plasma (Li-heparin, EDTA) toaid in the clinical diagnosis ofprimary biliary cirrhosis inconjunction with other laboratoryand clinical findings. EliA M2uses the EliA IgG method on theinstrument Phadia 2500/5000.
Sample matrix;Serum or plasmatype as indicated inthe DFU dependenton assay	human serum and plasma(heparin, EDTA)	human serum and plasma (Li-heparin, EDTA)
Analyticaltechnology:Immuno-fluorescencemeasurement	Same	Same
Assay process	Same	Same
Common, dedicatedPhadia reagents	Same	Introduction 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
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 M2 Immunoassays on Phadia 250 and Phadia 2500/5000 instruments – Differences to predicate device

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K. Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3; Evaluation of Precision Performance of Quantitative Measurement Methods: September 2014

CLSI EP06-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: April 2003

CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantification: October 2004.

CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples

L. Test Principle:

The EliA wells are molded cups comparable to excised wells from a microtiter plate. They are made of polystyrene and are coated with the respective antigen. The wells are at the same time a holder of the coupled antigen for convenient automation and a reaction chamber with reaction/washing solution handling based on pipetting to add and aspiration to remove liquids.

The EliA wells are coated with 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-RunSD	Within-Run%CV	Between-RunSD	Between-Run%CV	Between-InstrumentSD	Between-Instrument%CV	Total ImprecisionSD	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

< 4 U/mL	Negative
4 – 6 U/mL	Equivocal
> 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)	95thpercentile	99thpercentile
EliA M2 on Phadia2500/5000	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.

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).