EliA PR3s is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to proteinase 3 (PR3) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of Granulomatosis with Polyangiitis (GPA, formerly called Wegener's Granulomatosis) in conjunction with other laboratory and clinical findings. EliA PR3s uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA MPOs is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to myeloperoxidase (MPO) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of microscopic polyangiitis (MPA) in conjunction with other laboratory and clinical findings. EliA IgG method on the instrument Phadia 2500/5000.

EliA GBM is intended for the in vitro semi-quantitative measurement of IgG antibodies to a3 chain of collagen IV in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of Goodpasture syndrome in conjunction with other laboratory and clinical findings. EliA GBM uses the EliA IgG method on the instrument Phadia 2500/5000.

Device Description

The method-specific reagents are identical with K140225, but are filled in containers specific for the Phadia® 2500/5000 instrument. Each device consists of:

Test Wells: -
EliA PR3S Wells are coated with human PR3 protein – 4 carriers (12 wells each), ready to use:

EliA MPOS Wells are coated with human MPO protein – 4 carriers (12 wells each), ready to use;

EliA GBM Wells are coated with human recombinant α3 chain of collagen IV – 2 carriers (12 wells each), ready to use;

EliA Sample Diluent: PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use:
-EliA IgG Conjugate 50 or 200: ß-Galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA and 0.06% (w/v) sodium azide – 6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
-EliA IgG Calibrator Strips: Human IgG (0, 4, 10, 20, 100, 600 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 singleuse vials per strip, 0.3 mL each, ready to use;
EliA IgG Curve Control Strips: Human IgG (20 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide – 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
EliA IgG Calibrator Well: Coated with mouse monoclonal antibodies 4 carriers (12 wells each), ready to use.
-EliA ANCA/GBM Positive Control 2500/5000: Human serum containing IgG antibodies to PR3, MPO and GBM in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 single use vials, 0.3 mL each, ready to use;
-EliA IgG/IqM/IgA Negative Control 2500/5000: Human sera from healthy donors in PBS containing BSA, detergent and 0.095% (w/v) sodium azide -6 single-use vials, 0.3 mL 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. Apart from the EliA ANCA/GBM Positive Control 2500/5000 and the EliA IgG/ IgM/IgA Negative Control 2500/5000, all packages listed above are required to carry out an EliA PR3°, EliA MPOS and EliA GBM tests.

AI/ML Overview

The provided text describes the acceptance criteria and study results for the EliA PR3s, EliA MPOs, and EliA GBM immunoassays when used on the Phadia 2500/5000 instrument. This submission is to add these previously cleared assays to a new instrument platform, so the focus is on method comparison rather than clinical studies.

Here's the breakdown of the requested information:

1. Table of acceptance criteria and reported device performance for Instrument Comparison (Method Comparison):

The acceptance criteria for method comparison (comparing Phadia 2500/5000 to the predicate Phadia 250) were:

Slope for the regression lines should be between 0.9 and 1.1 for single replicate to single replicate.
Intercept close to 0.

The performance is reported for each immunoassay (EliA PR3s, EliA MPO®, EliA GBM) and for each of the three Phadia 2500/5000 instruments (A, B, C) tested against the Phadia 250.

EliA PR3s on Phadia 2500/5000 (vs. Phadia 250):

Instrument	Intercept (95% CI)	Slope (95% CI)	PPA (95% CI) - Equivocal considered Positive	NPA (95% CI) - Equivocal considered Positive	TPA (95% CI) - Equivocal considered Positive	PPA (95% CI) - Equivocal considered Negative	NPA (95% CI) - Equivocal considered Negative	TPA (95% CI) - Equivocal considered Negative
PH2500/5000 A	0.15 (-0.07 to 0.33)	0.99 (0.94 to 1.03)	98.8% (93.7% - 100%)	76.5% (50.1% - 93.2%)	95.1% (89.0% - 98.4%)	98.6% (92.5% – 100%)	96.8% (83.3% – 99.9%)	98.1% (93.2% – 99.8%)
PH2500/5000 B	0.10 (-0.07 to 0.28)	1.00 (0.96 to 1.04)	100.0% (95.8% - 100%)	76.5% (50.1% - 93.2%)	96.1% (90.4% - 98.9%)	97.2% (90.3% – 99.7%)	96.8% (83.3% – 99.9%)	97.1% (91.7% – 99.4%)
PH2500/5000 C	-0.01 (-0.12 to 0.14)	1.00 (0.96 to 1.04)	98.8% (93.7% - 100%)	76.5% (50.1% - 93.2%)	95.1% (89.0% - 98.4%)	98.6% (92.5% – 100%)	93.5% (78.6% – 99.2%)	97.1% (91.7% – 99.4%)

EliA MPO® on Phadia 2500/5000 (vs. Phadia 250):

Instrument	Intercept (95% CI)	Slope (95% CI)	PPA (95% CI) - Equivocal considered Positive	NPA (95% CI) - Equivocal considered Positive	TPA (95% CI) - Equivocal considered Positive	PPA (95% CI) - Equivocal considered Negative	NPA (95% CI) - Equivocal considered Negative	TPA (95% CI) - Equivocal considered Negative
PH2500/5000 A	-0.02 (-0.27 to 0.09)	0.98 (0.95 to 1.00)	97.8% (92.2% - 99.7%)	87.5% (61.7% – 98.4%)	96.2% (90.6% - 99.0%)	97.5% (91.2% – 99.7%)	100.0% (87.2% – 100%)	98.1% (93.4% - 99.8%)
PH2500/5000 B	-0.02 (-0.24 to 0.10)	0.98 (0.96 to 1.01)	98.9% (93.8% – 100%)	88.2% (63.6% - 98.5%)	97.1% (91.9% - 99.4%)	97.4% (90.9% – 99.7%)	100.0% (87.7% – 100%)	98.1% (93.3% - 99.8%)
PH2500/5000 C	-0.09 (-0.34 to -0.02)	0.99 (0.96 to 1.02)	98.9% (93.9% – 100%)	88.2% (63.6% - 98.5%)	97.2% (92.0% - 99.4%)	97.4% (91.0% – 99.7%)	100.0% (87.7% – 100%)	98.1% (93.4% - 99.8%)

EliA GBM on Phadia 2500/5000 (vs. Phadia 250):

Instrument	Intercept (95% CI)	Slope (95% CI)	PPA (95% CI) - Equivocal considered Positive	NPA (95% CI) - Equivocal considered Positive	TPA (95% CI) - Equivocal considered Positive	PPA (95% CI) - Equivocal considered Negative	NPA (95% CI) - Equivocal considered Negative	TPA (95% CI) - Equivocal considered Negative
PH2500/5000 A	0.85 (0.56 to 1.21)	0.94 (0.92 to 0.96)	100.0% (95.5% - 100%)	84.2% (60.4% - 96.6%)	97.0% (91.5% - 99.4%)	98.6% (92.6% – 100%)	92.6% (75.7% – 99.1%)	97.0% (91.5% – 99.4%)
PH2500/5000 B	1.04 (0.73 to 1.39)	0.95 (0.91 to 0.99)	100.0% (95.5% - 100%)	84.2% (60.4% - 96.6%)	97.0% (91.4% - 99.4%)	98.6% (92.5% – 100%)	92.6% (75.7% – 99.1%)	97.0% (91.4% – 99.4%)
PH2500/5000 C	0.34 (0.04 to 0.63)	0.98 (0.95 to 1.00)	100.0% (95.5% - 100%)	89.5% (66.9% - 98.7%)	98.0% (93.0% - 99.8%)	98.6% (92.6% – 100%)	100.0% (87.2% – 100%)	99.0% (94.6% – 100%)

2. Sample size used for the test set and the data provenance:

Sample Size: More than 100 samples for each EliA test (PR3s, MPO®, GBM). The submission also specifies "≥20% of the samples within ±25% of the medical decision point."
Data Provenance: Not explicitly stated as "country of origin," but implies clinical samples used for method comparison. The samples are referred to as "patient serum samples." It is a prospective study as the comparison aims to show equivalence of the new instrument platform with the predicate.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This information is not provided in the given text. The study is a method comparison between two instruments (Phadia 250 and Phadia 2500/5000) using the same assays, not a clinical study to establish diagnostic accuracy against a clinical gold standard determined by experts. The "ground truth" for the method comparison is the measurement value obtained from the predicate Phadia 250 instrument.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

This information is not applicable as the study is a method comparison of quantitative measurements, not a diagnostic study requiring expert adjudication of cases. The comparison is based on numerical results from two instruments.

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:

This is not applicable. The device described is an immunoassay system for semi-quantitative measurement of antibodies, not an AI-assisted diagnostic imaging device used by human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

The device (EliA immunoassays on Phadia 2500/5000) operates as a standalone automated system for measuring antibody levels. The results are semi-quantitative measurements that are an aid in clinical diagnosis, meaning a human clinician interprets the results in conjunction with other findings. However, the performance data presented (precision, linearity, detection limits, method comparison) is reflective of the standalone performance of the algorithm/instrument system. Therefore, the analytical performance studies (precision, linearity, detection limit) and method comparison effectively represent standalone algorithmic performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

For the method comparison study, the "ground truth" for evaluating the performance of the EliA assays on the Phadia 2500/5000 instrument was the results obtained from the predicate device, Phadia 250 instrument.

8. The sample size for the training set:

This information is not applicable as the devices are immunoassays, not machine learning algorithms that require a specific training set in the typical sense. The underlying EliA IgG method and its associated reagents were previously reviewed (K140225), implying that analytical performance of the assay itself was established in prior submissions. This current submission focuses on instrument equivalence.

9. How the ground truth for the training set was established:

This is not applicable for the same reasons as point 8. The assays do not involve machine learning with a distinct training set. The "ground truth" for establishing the analytical parameters and clinical performance of the immunoassays themselves would have been established through extensive analytical validation (e.g., against reference methods, known positive/negative samples, clinical samples with confirmed diagnoses) in their original clearance (K140225).

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and then the word "ADMINISTRATION" in a smaller font size below that.

March 13, 2018

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

Re: K173792

Trade/Device Name: EliA PR3s Immunoassay; EliA MPOs Immunoassay; EliA GBM Immunoassav Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MOB, MVJ Dated: December 12, 2017 Received: December 14, 2017

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 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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,

Kelly Oliner-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) K173792

Device Name

EliA(TM) PR3s Immunoassay, EliA(TM) MPOs Immunoassay, EliA(TM) GBM 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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N.1 510(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:
K173792

B. Purpose for Submission:

Adding previously cleared assays on the Phadia 2500/5000 instrument platform

C. Measurands:

Anti-PR3 autoantibodies Anti-MPO autoantibodies Anti-GBM autoantibodies

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:

March 9, 2018

F. Proprietary and Established Names:

EliA™ PR3S Immunoassay EliA™ MPOS Immunoassay EliA™ GBM Immunoassay

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G. Regulatory Information:

1. Requlation section: 21 CFR §866.5660 Multiple autoantibodies immunological test system
Classification: 2. Class II (Assays)
1. Product code:

MOB Antineutrophil cytoplasmic antibodies (ANCA) MVJ Antibodies to glomerular basement membrane (GBM)

1. Panel: Immunology (82)

H. Intended Use:

Intended use(s):

EliA PR3S is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to proteinase 3 (PR3) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of Granulomatosis with Polyangiitis (GPA, formerly called Wegener's Granulomatosis) in conjunction with other laboratory and clinical findings. EliA PR3S uses the EliA lgG method on the instrument Phadia 2500/5000.

EliA MPOS is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to myeloperoxidase (MPO) in human serum and plasma (Liheparin, EDTA) as an aid in the clinical diagnosis of microscopic polyangiitis (MPA) in conjunction with other laboratory and clinical findings. EliA MPO® uses the EliA lgG method on the instrument Phadia 2500/5000.

EliA GBM is intended for the in vitro semi-quantitative measurement of lgG antibodies to a3 chain of collagen IV in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of Goodpasture syndrome in conjunction with other laboratory and clinical findings. EliA GBM uses the EliA IgG method on the instrument Phadia 2500/5000.

2. 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: l.

The method-specific reagents are identical with K140225, but are filled in containers specific for the Phadia® 2500/5000 instrument. Each device consists of:

Test Wells: -
EliA PR3S Wells are coated with human PR3 protein – 4 carriers (12 wells each), ready to use:

EliA MPOS Wells are coated with human MPO protein – 4 carriers (12 wells each), ready to use;

EliA GBM Wells are coated with human recombinant α3 chain of collagen IV – 2 carriers (12 wells each), ready to use;

EliA Sample Diluent: PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use:
-EliA IgG Conjugate 50 or 200: ß-Galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA and 0.06% (w/v) sodium azide – 6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
-EliA IgG Calibrator Strips: Human IgG (0, 4, 10, 20, 100, 600 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 singleuse vials per strip, 0.3 mL each, ready to use;
EliA IgG Curve Control Strips: Human IgG (20 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide – 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
EliA IgG Calibrator Well: Coated with mouse monoclonal antibodies 4 carriers (12 wells each), ready to use.
-EliA ANCA/GBM Positive Control 2500/5000: Human serum containing IgG antibodies to PR3, MPO and GBM in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 single use vials, 0.3 mL each, ready to use;
-EliA IgG/IqM/IgA Negative Control 2500/5000: Human sera from healthy donors in PBS containing BSA, detergent and 0.095% (w/v) sodium azide -6 single-use vials, 0.3 mL each, ready to use;

J. Substantial Equivalence Information:

Predicate device name(s) and 510(k) number(s): EliA PR3S on Phadia 250 instrument, K140225 EliA MPOS on Phadia 250 instrument, K140225 EliA GBM on Phadia 250 instrument, K140225

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2. Comparison with predicate device:

EliA ANCA/GBM Immunoassays on Phadia 250 and Phadia 2500/5000 instruments – Similarities to predicate devices

Feature	Predicate DevicePhadia 250	New DevicePhadia 2500/5000
Intended UseEliA PR3S	EliA PR3S is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to proteinase 3 (PR3) inhuman serum and plasma(heparin, EDTA, citrate) as anaid in the clinical diagnosis ofGranulomatosis with Polyangiitis(GPA, formerly called Wegener'sGranulomatosis) in conjunctionwith other laboratory and clinicalfindings. EliA PR3S uses the EliAIgG method on the instrumentPhadia 250.	EliA PR3S is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to proteinase 3 (PR3) inhuman serum and plasma (Li-heparin, EDTA) as an aid in theclinical diagnosis ofGranulomatosis with Polyangiitis(GPA, formerly called Wegener'sGranulomatosis) in conjunctionwith other laboratory and clinicalfindings. EliA PR3S uses the EliAIgG method on the instrumentPhadia 2500/5000.
Intended UseEliA MPOS	EliA MPOS is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to myeloperoxidase(MPO) in human serum andplasma (heparin, EDTA, citrate)as an aid in the clinical diagnosisof microscopic polyangiitis(MPA) in conjunction with otherlaboratory and clinical findings.EliA MPOS uses the EliA IgGmethod on the instrumentPhadia 250.	EliA MPOS is intended for the invitro semi-quantitativemeasurement of IgG antibodiesdirected to myeloperoxidase(MPO) in human serum andplasma (Li-heparin, EDTA) as anaid in the clinical diagnosis ofmicroscopic polyangiitis (MPA) inconjunction with other laboratoryand clinical findings. EliA MPOSuses the EliA IgG method on theinstrument Phadia 2500/5000.
Intended UseEliA GBM	EliA GBM is intended for the invitro semi-quantitativemeasurement of IgG antibodiesto α3 chain of collagen IV inhuman serum and plasma(heparin, EDTA, citrate) as anaid in the clinical diagnosis ofGoodpasture syndrome inconjunction with other laboratoryand clinical findings. EliA GBMuses the EliA IgG method on theinstrument Phadia 250.	EliA GBM is intended for the invitro semi-quantitativemeasurement of IgG antibodiesto α3 chain of collagen IV inhuman serum and plasma (Li-heparin, EDTA) as an aid in theclinical diagnosis of Goodpasturesyndrome in conjunction withother laboratory and clinicalfindings. EliA GBM uses the EliAIgG method 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
DevelopmentSolution Volume	90 µL	90 µL
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 Directions for Use(DFU) dependent onassay	Serum or plasma (heparin,EDTA, citrate)	Serum or plasma (Li-heparin,EDTA)
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) for pipettingsamples in Dilution Well (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 tips forpipetting samples and a separatepipette for the conjugate, andcarry-over from samples toconjugate is impossible.
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 carriers areloaded 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 the reagentsare on a moving belt whichconveys them past the barcodereader. The lot-specific informationwill be read automatically by theinstrument during 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 in 48seconds.Phadia 2500/5000 provides theresults at a 24 seconds interval.

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EliA ANCA/GBM 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 human PR3 protein, or human MPO protein, or human recombinant a3 chain of collagen IV. If present in the patient's specimen, antibodies to these proteins bind to the specific antigen. After washing away nonbound antibodies, enzyme-labeled antibodies against human IgG antibodies (EliA IgG Conjugate) are added to form an antibody-conjugate complex. After incubation, non-bound conjugate is washed away and the bound complex is incubated with a Development Solution. After stopping the reaction, the fluorescence in the reaction mixture is measured. The higher the response value, the 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):

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 PR3S, EliA MPOS and EliA GBM on the Phadia 2500/5000 instrument, as data for inter-lot-variation was reviewed in K140225. The results are summarized in the tables below:

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EliA PR3§ on Phadia 2500/5000

	Within-Run		Between-Run		Between-Instrument		TotalImprecision
Mean(U/mL)	SD	%CV	SD	%CV	SD	%CV	SD	%CV
1.6	0.1	7.7	0.1	4.6	0.1	4.1	0.2	9.9
2.3	0.1	5.0	0.1	6.3	0.0	0.0	0.2	8.0
2.7	0.1	3.8	0.1	4.8	0.2	6.1	0.2	8.6
70.0	2.6	3.7	3.0	4.4	1.5	2.2	4.3	6.1
170.0	8.3	4.9	9.1	5.4	4.1	2.4	13.0	7.7

EliA MPO® on Phadia 2500/5000

Mean(U/mL)	Within-Run		Between-Run		Between-Instrument		TotalImprecision
	SD	%CV	SD	%CV	SD	%CV	SD	%CV
1.3	0.1	5.5	0.0	3.3	0.1	4.7	0.1	8.0
3.6	0.2	4.2	0.2	4.4	0.1	3.9	0.3	7.3
4.9	0.3	5.2	0.3	6.2	0.2	4.8	0.5	9.4
71.5	3.4	4.7	3.8	5.3	4.8	6.7	7.0	9.7
117.8	5.4	4.6	6.5	5.5	7.0	5.9	11.0	9.3

EliA GBM on Phadia 2500/5000

Mean(U/mL)	Within-Run		Between-Run		Between-Instrument		TotalImprecision
	SD	%CV	SD	%CV	SD	%CV	SD	%CV
4.0	0.4	10.0	0.3	8.0	0.6	14.8	0.8	19.5
7.8	0.5	6.0	0.5	6.2	0.3	4.2	0.7	9.6
9.6	0.4	3.7	0.4	4.7	0.0	0.4	0.6	6.0
191.0	6.7	3.5	12.4	6.5	3.5	1.8	14.5	7.6
522.0	22.2	4.2	25.4	4.9	0.0	0.0	33.7	6.5

b. Linearity/assay reportable range:

Four patient serum samples were diluted in sample diluent and tested with one batch of EliA PR3§, EliA MPO§ and EliA GBM Immunoassays and one set of system reagents on the Phadia 2500/5000 instrument. The ratios of observed/expected values were calculated. The results are summarized below:

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Dilution range(U/mL)	Slope	Intercept	R²
0.7 - 22.9	1.02	0.30	1.00
1.3 - 106.9	0.99	0.24	1.00
1.4 - 125.9	1.00	-0.09	1.00
2.0 - 203.5	1.00	-1.88	1.00

EliA PR3S on Phadia 2500/5000

The linear range and the measuring range are set to 1.0 U/mL (LoQ) to 177 U/mL (upper limit of measuring range).

The reportable range (Limit of Detection, upper limit of measuring range) for EliA PR3S is from 0.6 to 177 U/mL. Concentration values between LoD and LoQ may show a higher uncertainty.

EliA MPO® on Phadia 2500/5000

Dilution range(U/mL)	Slope	Intercept	R2
0.2 - 8.7	1.01	0.01	1.00
0.5 - 8.2	1.01	0.00	1.00
0.2 - 10.3	0.99	0.13	1.00
1.8 - 143.2	1.01	0.07	1.00

The linear range and the measuring range are set to 0.3 U/mL (LoQ) to 134 U/mL (upper limit of measuring range).

The reportable range (Limit of Detection, upper limit of measuring range) for EliA MPOS is from 0.2 to 134 U/mL. Concentration values between LoD and LoQ may show a higher uncertainty.

EliA GBM on Phadia 2500/5000

Dilution range(EliA U/mL)	Slope	Intercept	R2
8.1 - 527.3	1.04	-2.18	1.00
1.6 - 31.5	1.00	-0.57	1.00
3.9 - 262.8	1.01	0.83	1.00
352.0 - 808.8	0.98	31.91	0.99

The linear range and the measuring range are set to 2.4 EliA U/mL (LoQ) to 680 EliA U/mL (upper limit of measuring range).

The reportable range (Limit of Detection, upper limit of measuring range) for EliA GBM is from 1.5 to 680 EliA U/mL. Concentration values between LoD and LoQ may show a higher uncertainty.

Traceability, Stability, Expected values (controls, calibrators, or methods): C. The EliA IgG method was previously reviewed in K140225.

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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.

EliA PR3S:

The LoD for EliA PR3S is 0.6 U/mL, determined consistent with the quidelines in CLSI document EP17-A2 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.

The LoQ for EliA PR3S is 1.0 U/mL, determined consistent with the quidelines in CLSI document EP17-A2, based on 360 determinations; and a target uncertainty goal of 20%.

The results are summarized in the table below:

EliA PR3S (U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.3	0.6	1.0

EliA MPOS:

The LoD for EliA MPO§ is 0.2 U/mL, determined consistent with the guidelines in CLSI document EP17-A2 and with proportions of false positives (g) 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 0.1 U/mL.

The LoQ for EliA MPO§ is 0.3 U/mL, determined consistent with the guidelines in CLSI document EP17-A2, based on 360 determinations; and a target uncertainty goal of 20%.

The results are summarized in the table below:

EliA MPOS (U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.1	0.2	0.3

EliA GBM:

The LoD for EliA GBM is 1.5 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2 and with proportions of false positives (a) less than 5% and false negatives (β) less than 5%; based on 432 determinations with 72 blank and 360 low level replicates; and LoB of 0.7 EliA U/mL.

The LoQ for EliA GBM is 2.4 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2, based on 360 determinations; and a target uncertainty goal of 20%.

The results are summarized in the table below:

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N.1-11

EliA GBM (EliA U/mL)	LoB	LoD	LoQ
Phadia 2500/5000	0.7	1.5	2.4

Analytical specificity: e.
Interference: Previously reviewed in K140225

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 (neqative, equivocal, positive) recommended for the evaluation of the test results were derived from the clinical studies (s. K140225).

EliA PR3§ Well

< 2.0 U/ml	Negative
2.0 - 3.0 U/ml	Equivocal
> 3.0 U/ml	Positive

EliA MPOS Well

< 3.5 U/ml	Negative
3.5 – 5.0 U/ml	Equivocal
> 5.0 U/ml	Positive

EliA GBM Well

< 7 EliA U/ml	Negative
7 - 10 EliA U/ml	Equivocal
> 10 EliA U/ml	Positive

1. Comparison studies:
Method comparison with predicate device (Instrument comparison): a. See 2c Instrument Comparison below
b. Matrix comparison: Previously reviewed under K140225.
C. Instrument comparison

In the Method Comparison studies for the three EliA tests included in this submission, 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 for EliA PR3-, EliA MPOS and EliA GBM.

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N.1-12

EliA PR36:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	0.15	-0.07 to 0.33	0.99	0.94 to 1.03
PH2500/5000 B	0.10	-0.07 to 0.28	1.00	0.96 to 1.04
PH2500/5000 C	-0.01	-0.12 to 0.14	1.00	0.96 to 1.04

equivocal considered positive

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.8%	100.0%	98.8%
95% CI	93.7% - 100%	95.8% - 100%	93.7% - 100%
NPA	76.5%	76.5%	76.5%
95% CI	50.1% - 93.2%	50.1% - 93.2%	50.1% - 93.2%
TPA	95.1%	96.1%	95.1%
95% CI	89.0% - 98.4%	90.4% - 98.9%	89.0% - 98.4%

equivocal considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.6%	97.2%	98.6%
95% CI	92.5% – 100%	90.3% – 99.7%	92.5% – 100%
NPA	96.8%	96.8%	93.5%
95% CI	83.3% – 99.9%	83.3% – 99.9%	78.6% – 99.2%
TPA	98.1%	97.1%	97.1%
95% CI	93.2% – 99.8%	91.7% – 99.4%	91.7% – 99.4%

EliA MPO®:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	-0.02	-0.27 to 0.09	0.98	0.95 to 1.00
PH2500/5000 B	-0.02	-0.24 to 0.10	0.98	0.96 to 1.01
PH2500/5000 C	-0.09	-0.34 to -0.02	0.99	0.96 to 1.02

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criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	97.8%	98.9%	98.9%
95% CI	92.2% - 99.7%	93.8% – 100%	93.9% – 100%
NPA	87.5%	88.2%	88.2%
95% CI	61.7% – 98.4%	63.6% - 98.5%	63.6% - 98.5%
TPA	96.2%	97.1%	97.2%
95% CI	90.6% - 99.0%	91.9% - 99.4%	92.0% - 99.4%

equivocal considered positive

equivocal considered negative

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	97.5%	97.4%	97.4%
95% CI	91.2% – 99.7%	90.9% – 99.7%	91.0% – 99.7%
NPA	100.0%	100.0%	100.0%
95% CI	87.2% – 100%	87.7% – 100%	87.7% – 100%
TPA	98.1%	98.1%	98.1%
95% CI	93.4% - 99.8%	93.3% - 99.8%	93.4% - 99.8%

EliA GBM:

Instrument	Intercept	95% Cl	Slope	95% Cl
PH2500/5000 A	0.85	0.56 to 1.21	0.94	0.92 to 0.96
PH2500/5000 B	1.04	0.73 to 1.39	0.95	0.91 to 0.99
PH2500/5000 C	0.34	0.04 to 0.63	0.98	0.95 to 1.00

equivocal considered positive

criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	100.0%	100.0%	100.0%
95% CI	95.5% - 100%	95.5% - 100%	95.5% - 100%
NPA	84.2%	84.2%	89.5%
95% CI	60.4% - 96.6%	60.4% - 96.6%	66.9% - 98.7%
TPA	97.0%	97.0%	98.0%
95% CI	91.5% - 99.4%	91.4% - 99.4%	93.0% - 99.8%

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criteria	PH2500/5000 A	PH2500/5000 B	PH2500/5000 C
PPA	98.6%	98.6%	98.6%
95% CI	92.6% – 100%	92.5% – 100%	92.6% – 100%
NPA	92.6%	92.6%	100.0%
95% CI	75.7% – 99.1%	75.7% – 99.1%	87.2% – 100%
TPA	97.0%	97.0%	99.0%
95% CI	91.5% – 99.4%	91.4% – 99.4%	94.6% – 100%

equivocal considered negative

1. 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 K140225.
বা Clinical cut-off: Same as assay cut-off.
1. Expected values/Reference range:

The frequency distribution for PR3, MPO and GBM antibodies was investigated in a group of apparently healthy subjects equally distributed by age and gender, using sera from a Caucasian population obtained from a blood bank. The results are given in the table below:

Test	n =	Median(EliA U/mL)	95thpercentile	99thpercentile
EliA PR3S on Phadia2500/5000	400	0.7	1.1	1.5
EliA MPOS on Phadia2500/5000	400	0.3	0.5	0.8
EliA GBM on Phadia2500/5000	400	1.9	2.7	3.2

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

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O. Conclusion:

All available data support that both instrument platforms, Phadia 250 and Phadia 2500/5000 perform substantially equivalent when using the EliA PR3S, EliA MPOS, and EliA GBM immunoassays.

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

Regulation Number and Section

§ 866.5660 Multiple autoantibodies immunological test system.

(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).