Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard in vitro diagnostic assay and automated instrument system. There is no mention of AI or ML in the intended use, device description, or performance studies. The performance studies focus on traditional analytical and clinical validation metrics.

Therapeutic

No.
This device is an in vitro diagnostic (IVD) device intended for the semi-quantitative measurement of antibodies as an aid in clinical diagnosis, not for therapeutic purposes.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the in vitro semi-quantitative measurement of IgG antibodies... as an aid in the clinical diagnosis of..." several conditions. This clearly indicates its role in diagnosis.

SaMD (Software as a Medical Device)

No

The device description clearly outlines multiple physical components including test wells, sample diluent, conjugate, calibrator strips, control strips, calibrator wells, and positive/negative controls. While it interacts with an automated system (Phadia 2500/5000), the device itself is a collection of physical reagents and components, 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 devices are intended for "in vitro semi-quantitative measurement" of specific antibodies in human serum and plasma. This is a key characteristic of IVDs, which are used to examine specimens taken from the human body.
Purpose: The intended use also states that the measurements are "as an aid in the clinical diagnosis" of specific conditions (Granulomatosis with Polyangiitis, microscopic polyangiitis, and Goodpasture syndrome). IVDs are used to provide information for diagnostic purposes.
Device Description: The description details the components of the device, which are reagents and test wells designed for laboratory testing of biological samples.
Performance Studies: The document includes a summary of performance studies, which are typically conducted for IVDs to demonstrate their analytical and clinical performance.
Predicate Device: The mention of predicate devices with K numbers indicates that this device is being compared to previously cleared IVDs.

All of these factors strongly indicate that this device falls under the definition of an In Vitro Diagnostic.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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.

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

MOB, MVJ

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.

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.

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:
Study with a total of 21 runs (3 instruments x 7 runs) for EliA PR3S, EliA MPOS, and EliA GBM on Phadia 2500/5000 instrument. Each sample was tested in four replicates/run, totaling 84 replicates per sample.

EliA PR3S: Total Imprecision %CV ranged from 7.7% to 9.9%.
EliA MPOS: Total Imprecision %CV ranged from 7.3% to 9.7%.
EliA GBM: Total Imprecision %CV ranged from 6.0% to 19.5%.

Linearity/Reportable Range:
Four patient serum samples were diluted and tested.

EliA PR3S: Linear range and measuring range from 1.0 U/mL (LoQ) to 177 U/mL. Reportable range from 0.6 to 177 U/mL.
EliA MPOS: Linear range and measuring range from 0.3 U/mL (LoQ) to 134 U/mL. Reportable range from 0.2 to 134 U/mL.
EliA GBM: Linear range and measuring range from 2.4 EliA U/mL (LoQ) to 680 EliA U/mL. Reportable range from 1.5 to 680 EliA U/mL.

Detection Limits:
LoB and LoD studies performed on Phadia 2500/5000 instrument with 12 replicates in each of 6 runs for one blank and five low-level samples.

EliA PR3S: LoB 0.3 U/mL, LoD 0.6 U/mL, LoQ 1.0 U/mL.
EliA MPOS: LoB 0.1 U/mL, LoD 0.2 U/mL, LoQ 0.3 U/mL.
EliA GBM: LoB 0.7 EliA U/mL, LoD 1.5 EliA U/mL, LoQ 2.4 EliA U/mL.

Carry-over: Not possible due to disposable tips for samples and separate pipette for conjugate.

Method Comparison with predicate device (Instrument comparison):
More than 100 samples (≥20% of samples within ±25% of medical decision point) run in single replicates on one Phadia 250 and three Phadia 2500/5000 instruments.
Acceptance criteria for slope (0.9 - 1.1) and intercept (close to 0) were met.

EliA PR3S: Slopes ranged from 0.99 to 1.00. Intercepts ranged from -0.01 to 0.15.
EliA MPOS: Slopes ranged from 0.98 to 0.99. Intercepts ranged from -0.09 to -0.02.
EliA GBM: Slopes ranged from 0.94 to 0.98. Intercepts ranged from 0.34 to 1.04.

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

Instrument comparison results for EliA PR3S, EliA MPOS, and EliA GBM show:
EliA PR3S:

Equivocal considered positive: PPA 98.8% - 100.0%, NPA 76.5%, TPA 95.1% - 96.1%.
Equivocal considered negative: PPA 97.2% - 98.6%, NPA 93.5% - 96.8%, TPA 97.1% - 98.1%.
EliA MPOS:
Equivocal considered positive: PPA 97.8% - 98.9%, NPA 87.5% - 88.2%, TPA 96.2% - 97.2%.
Equivocal considered negative: PPA 97.4% - 97.5%, NPA 100.0%, TPA 98.1%.
EliA GBM:
Equivocal considered positive: PPA 100.0%, NPA 84.2% - 89.5%, TPA 97.0% - 98.0%.
Equivocal considered negative: PPA 98.6%, NPA 92.6% - 100.0%, TPA 97.0% - 99.0%.

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.

K140225, K140225, K140225

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.

Not Found

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

§ 866.5660 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).

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

1

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)

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.

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;

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.

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 Device
Phadia 250 | New Device
Phadia 2500/5000 |
|--------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use
EliA PR3S | EliA PR3S is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to proteinase 3 (PR3) in
human serum and plasma
(heparin, EDTA, citrate) 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 250. | 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. |
| Intended Use
EliA MPOS | EliA MPOS is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to myeloperoxidase
(MPO) in human serum and
plasma (heparin, EDTA, citrate)
as an aid in the clinical diagnosis
of microscopic polyangiitis
(MPA) in conjunction with other
laboratory and clinical findings.
EliA MPOS uses the EliA IgG
method on the instrument
Phadia 250. | 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 MPOS
uses the EliA IgG method on the
instrument Phadia 2500/5000. |
| Intended Use
EliA GBM | EliA GBM is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
to α3 chain of collagen IV in
human serum and plasma
(heparin, EDTA, citrate) 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 250. | EliA GBM is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
to α3 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. |
| Analytical
technology:
Immuno-
fluorescence
measurement | | |
| | Same | Same |
| Assay process | Same | Same |
| Common, dedicated
Phadia reagents | Same | Same
Introduction of new article
numbers for Development
Solution, Stop Solution and
Washing Solution is only due to
larger filling volumes which are
required for the bigger
instruments Phadia 2500/5000 |
| Result calculation
software; Phadia
Information Data
Manager (IDM) | Same | Same |
| Sample volume | 90 µl (20 µL of non-diluted
sample) | 90 µl (20 µL of non-diluted
sample) |
| Incubation
temperature | 37°C | 37°C |
| Conjugate volume | 90 µL | 90 µL |
| Development
Solution Volume | 90 µL | 90 µL |
| Stop Solution
Volume | 200 µL | 200 µL |
| Assay set-up | Random access | Random access |
| Reagent packaging
size | Various/Common | Various/Common
Introduction of new article
number for EliA Sample Diluent
(83-1071-01) is only due to
larger filling volume. |
| Onboard storage of
reagents | Yes | Yes |
| Time to 1st result | ~2 h | ~2 h |
| Feature | Predicate Device
Phadia 250 | New Device
Phadia 2500/5000 |
| Sample matrix;
Serum or plasma
type as indicated in
the Directions for Use
(DFU) dependent on
assay | 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 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 ANCA/GBM 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 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 | | Total
Imprecision | |
|----------------|----------------|-----|-----------------|-----|------------------------|-----|----------------------|-----|
| 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 | | Total
Imprecision | |
|----------------|----------------|-----|-----------------|-----|------------------------|-----|----------------------|-----|
| | 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 | | Total
Imprecision | |
|----------------|------------|------|-----------------|-----|------------------------|------|----------------------|------|
| | 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

| 3.0 U/ml | Positive |

EliA MPOS Well

| 5.0 U/ml | Positive |

EliA GBM Well

| 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) | 95th
percentile | 99th
percentile |
|----------------------------------|-----|-----------------------|--------------------|--------------------|
| EliA PR3S on Phadia
2500/5000 | 400 | 0.7 | 1.1 | 1.5 |
| EliA MPOS on Phadia
2500/5000 | 400 | 0.3 | 0.5 | 0.8 |
| EliA GBM on Phadia
2500/5000 | 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.