EliA PR3s Immunoassay; EliA MPOs Immunoassay; EliA GBM Immunoassay

K173792 · Phadia AB · MOB · Mar 13, 2018 · Immunology

Device Facts

• Record ID: K173792
• Device Name: EliA PR3s Immunoassay; EliA MPOs Immunoassay; EliA GBM Immunoassay
• Applicant: Phadia AB
• Product Code: MOB · Immunology
• Decision Date: Mar 13, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5660
• Device Class: Class 2

Intended 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 MPOs uses the EliA IgG method on the instrument Phadia 2500/5000. 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.

Device Story

Automated solid-phase fluoroimmunoassay system; detects human IgG autoantibodies to PR3, MPO, or collagen IV-α3 (GBM). Input: human serum/plasma samples. Process: samples incubated in antigen-coated wells; unbound antibodies washed; enzyme-labeled anti-human IgG conjugate added; fluorogenic substrate (MUG) added; fluorescence measured. Output: semi-quantitative concentration (U/mL) compared to calibrators. Used in clinical laboratories; operated by trained personnel. Results aid clinicians in diagnosing GPA, MPA, or Goodpasture syndrome. Phadia 2500/5000 platforms provide high-throughput automated processing.

Clinical Evidence

Bench testing only. Precision/reproducibility assessed over 7 days (21 runs). Linearity, LoB, LoD, and LoQ established per CLSI guidelines. Method comparison study (>100 samples) between Phadia 250 and Phadia 2500/5000 showed high agreement (slopes 0.94-1.00). Clinical performance values and interference data were previously reviewed in K140225.

Technological Characteristics

Solid-phase fluoroimmunoassay. Components: polystyrene wells coated with human PR3, MPO, or recombinant collagen IV α3; β-galactosidase labeled anti-human IgG conjugate; 4-Methylumbelliferyl-β-D-galactoside (MUG) substrate. Automated platform (Phadia 2500/5000) performs sample handling, incubation at 37°C, washing, and fluorescence detection. Connectivity: onboard instrument software (ISW) and Information Data Manager (IDM).

Indications for Use

Indicated for in vitro semi-quantitative measurement of IgG autoantibodies to PR3, MPO, or GBM in human serum/plasma to aid clinical diagnosis of Granulomatosis with Polyangiitis (GPA), microscopic polyangiitis (MPA), or Goodpasture syndrome, respectively, in conjunction with other clinical findings. For prescription use only.

Regulatory Classification

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).

Predicate Devices

• EliA PR3S, EliA MPOS, and EliA GBM on Phadia 250 (K140225)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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)

| <span></span> | Prescription Use (Part 21 CFR 801 Subpart D) |
|---------------|----------------------------------------------|
| <span></span> | 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: [phone]

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) [e-mail]

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)
- 3. Product code:

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

- 4. Panel: Immunology (82)
# H. Intended Use:

1. 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

3. 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:

1. 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<br>Phadia 250 | New Device<br>Phadia 2500/5000 |
|--------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use<br>EliA PR3S | EliA PR3S is intended for the in<br>vitro semi-quantitative<br>measurement of IgG antibodies<br>directed to proteinase 3 (PR3) in<br>human serum and plasma<br>(heparin, EDTA, citrate) as an<br>aid in the clinical diagnosis of<br>Granulomatosis with Polyangiitis<br>(GPA, formerly called Wegener's<br>Granulomatosis) in conjunction<br>with other laboratory and clinical<br>findings. EliA PR3S uses the EliA<br>IgG method on the instrument<br>Phadia 250. | EliA PR3S is intended for the in<br>vitro semi-quantitative<br>measurement of IgG antibodies<br>directed to proteinase 3 (PR3) in<br>human serum and plasma (Li-<br>heparin, EDTA) as an aid in the<br>clinical diagnosis of<br>Granulomatosis with Polyangiitis<br>(GPA, formerly called Wegener's<br>Granulomatosis) in conjunction<br>with other laboratory and clinical<br>findings. EliA PR3S uses the EliA<br>IgG method on the instrument<br>Phadia 2500/5000. |
| Intended Use<br>EliA MPOS | EliA MPOS is intended for the in<br>vitro semi-quantitative<br>measurement of IgG antibodies<br>directed to myeloperoxidase<br>(MPO) in human serum and<br>plasma (heparin, EDTA, citrate)<br>as an aid in the clinical diagnosis<br>of microscopic polyangiitis<br>(MPA) in conjunction with other<br>laboratory and clinical findings.<br>EliA MPOS uses the EliA IgG<br>method on the instrument<br>Phadia 250. | EliA MPOS is intended for the in<br>vitro semi-quantitative<br>measurement of IgG antibodies<br>directed to myeloperoxidase<br>(MPO) in human serum and<br>plasma (Li-heparin, EDTA) as an<br>aid in the clinical diagnosis of<br>microscopic polyangiitis (MPA) in<br>conjunction with other laboratory<br>and clinical findings. EliA MPOS<br>uses the EliA IgG method on the<br>instrument Phadia 2500/5000. |
| Intended Use<br>EliA GBM | EliA GBM is intended for the in<br>vitro semi-quantitative<br>measurement of IgG antibodies<br>to α3 chain of collagen IV in<br>human serum and plasma<br>(heparin, EDTA, citrate) as an<br>aid in the clinical diagnosis of<br>Goodpasture syndrome in<br>conjunction with other laboratory<br>and clinical findings. EliA GBM<br>uses the EliA IgG method on the<br>instrument Phadia 250. | EliA GBM is intended for the in<br>vitro semi-quantitative<br>measurement of IgG antibodies<br>to α3 chain of collagen IV in<br>human serum and plasma (Li-<br>heparin, EDTA) as an aid in the<br>clinical diagnosis of Goodpasture<br>syndrome in conjunction with<br>other laboratory and clinical<br>findings. EliA GBM uses the EliA<br>IgG method on the instrument<br>Phadia 2500/5000. |
| Analytical<br>technology:<br>Immuno-<br>fluorescence<br>measurement | | |
| | Same | Same |
| Assay process | Same | Same |
| Common, dedicated<br>Phadia reagents | Same | Same<br>Introduction of new article<br>numbers for Development<br>Solution, Stop Solution and<br>Washing Solution is only due to<br>larger filling volumes which are<br>required for the bigger<br>instruments Phadia 2500/5000 |
| Result calculation<br>software; Phadia<br>Information Data<br>Manager (IDM) | Same | Same |
| Sample volume | 90 µl (20 µL of non-diluted<br>sample) | 90 µl (20 µL of non-diluted<br>sample) |
| Incubation<br>temperature | 37°C | 37°C |
| Conjugate volume | 90 µL | 90 µL |
| Development<br>Solution Volume | 90 µL | 90 µL |
| Stop Solution<br>Volume | 200 µL | 200 µL |
| Assay set-up | Random access | Random access |
| Reagent packaging<br>size | Various/Common | Various/Common<br>Introduction of new article<br>number for EliA Sample Diluent<br>(83-1071-01) is only due to<br>larger filling volume. |
| Onboard storage of<br>reagents | Yes | Yes |
| Time to 1st result | ~2 h | ~2 h |
| Feature | Predicate Device<br>Phadia 250 | New Device<br>Phadia 2500/5000 |
| Sample matrix;<br>Serum or plasma<br>type as indicated in<br>the Directions for Use<br>(DFU) dependent on<br>assay | Serum or plasma (heparin,<br>EDTA, citrate) | Serum or plasma (Li-heparin,<br>EDTA) |
| Daily throughput | ~250 tests | ~2500/5000 tests |
| Sample Dilution | Phadia 250 uses a steel pipette<br>to dilute the samples in Dilution<br>Plates (Art.No. 12-3907-08) | Phadia 2500/5000 uses<br>disposable Pipette Tips in Racks<br>(Art No. 12-3805-04) for pipetting<br>samples in Dilution Well (Art.No.<br>12-4005-69) |
| Risk for carry-over | The warning “DO NOT REUSE”<br>in the Phadia 250 DFU for EliA<br>Conjugates is due to the fact that<br>a low risk of conjugate<br>contamination by carry-over from<br>samples was identified. In order<br>to reduce the risk, the single use<br>statement for the conjugate was<br>included in the Phadia 250 DFU. | When running EliA tests on the<br>Phadia 2500/5000 instruments,<br>there is no need for this warning<br>statement because these<br>instruments use disposable tips for<br>pipetting samples and a separate<br>pipette for the conjugate, and<br>carry-over from samples to<br>conjugate is impossible. |
| Loading of EliA<br>Carriers | EliA carriers are loaded manually<br>on the Loading Tray from where<br>they can be processed directly or<br>transferred to the cooled storage<br>compartment. | The Phadia 2500/5000<br>instruments do not have such a<br>Loading Tray. The EliA carriers are<br>loaded into racks which are<br>directly transferred to the cooled<br>storage compartment |
| Barcode reader | The Phadia 250 instrument has<br>a built-in barcode reader at the<br>front of the instrument, but the<br>operator needs to scan the<br>barcodes manually by showing<br>the reagents to the barcode<br>reader. Alternatively, the<br>operator can also enter the<br>characters below the barcode<br>manually. | The Phadia 2500/5000<br>instruments dispose of a built-in<br>barcode reader, and the reagents<br>are on a moving belt which<br>conveys them past the barcode<br>reader. The lot-specific information<br>will be read automatically by the<br>instrument during loading. |
| Process time / Time<br>to patient result | Phadia 250 needs 1 minute to<br>process one Well.<br>Phadia 250 provides the results<br>at a one minute interval. | Phadia 2500/5000 instruments<br>process two Wells in parallel in 48<br>seconds.<br>Phadia 2500/5000 provides the<br>results 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-<br>Run | | Between-<br>Run | | Between-<br>Instrument | | Total<br>Imprecision | |
|----------------|----------------|-----|-----------------|-----|------------------------|-----|----------------------|-----|
| Mean<br>(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<br>(U/mL) | Within-<br>Run | | Between-<br>Run | | Between-<br>Instrument | | Total<br>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<br>(U/mL) | Within-Run | | Between-<br>Run | | Between-<br>Instrument | | Total<br>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<br>(U/mL) | Slope | Intercept | R² |
|--------------------------|-------|-----------|------|
| <b>0.7</b> - 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 - <b>203.5</b> | 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<br>(U/mL) | Slope | Intercept | R2 |
|--------------------------|-------|-----------|------|
| <b>0.2</b> - 8.7 | 1.01 | 0.01 | 1.00 |
| 0.5 - 8.2 | 1.01 | 0.00 | 1.00 |
| <b>0.2</b> - 10.3 | 0.99 | 0.13 | 1.00 |
| 1.8 - <b>143.2</b> | 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<br>(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 |

- 2. 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 |

{15}------------------------------------------------

| 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% |

{16}------------------------------------------------

| 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

- 3. Clinical studies:
- Clinical sensitivity: a. Not applicable.
- b. Clinical specificity: Not applicable.
- c. Other clinical supportive data (when a. and b. are not applicable): Clinical performance values were reviewed in K140225.
- বা Clinical cut-off: Same as assay cut-off.
- 5. 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<br>(EliA U/mL) | 95th<br>percentile | 99th<br>percentile |
|----------------------------------|-----|-----------------------|--------------------|--------------------|
| EliA PR3S on Phadia<br>2500/5000 | 400 | 0.7 | 1.1 | 1.5 |
| EliA MPOS on Phadia<br>2500/5000 | 400 | 0.3 | 0.5 | 0.8 |
| EliA GBM on Phadia<br>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.

{17}------------------------------------------------

#### 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.