Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes an immunoassay system and its components for quantitative measurement of antibodies. There is no mention of AI or ML in the intended use, device description, or performance studies. The analysis focuses on standard immunoassay performance metrics.

Therapeutic

No

Explanation: This device is for in vitro diagnostic use, specifically for measuring antibodies to aid in the diagnosis of certain thyroid conditions. It is not intended for treating or preventing disease.

Diagnostic

Yes.

The "Intended Use / Indications for Use" section explicitly states that the device is intended "as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings." This directly indicates a diagnostic purpose.

SaMD (Software as a Medical Device)

No

The device description clearly outlines physical components such as wells coated with antigens, sample diluent bottles, conjugate bottles, control vials, calibrator strips, and calibrator wells. These are tangible reagents and consumables used in an in vitro diagnostic assay, not solely software. The device also relies on the Phadia EliA Immunodiagnostic System instrument for operation.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The intended use statement explicitly states: "EliA anti-TG Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroglobulin (TG) in human serum and plasma... as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease..." and similarly for the EliA anti-TPO Immunoassay.

The device description also details reagents and controls used for testing human serum and plasma samples, which are typical components of an in vitro diagnostic assay. The performance studies further describe testing human serum and plasma samples to evaluate the device's performance.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

EliA anti-TG is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroglobulin (TG) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TG uses the EliA IgG method on the instruments Phadia 250 and Phadia 2500/5000.

EliA anti-TPO is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroid peroxidase (TPO) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TPO uses the EliA IgG method on the instruments Phadia 250 and Phadia 2500/5000.

EliA Thyroid Positive Control 250 and EliA Thyroid Positive Control 2500/5000 is intended for laboratory use in monitoring the performance of in vitro measurement of antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) with Phadia 250 and Phadia 2500/5000 using the EliA IgG method.

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

JZO, JJY

Device Description

The method specific reagents on Phadia® 250 and Phadia® 2500/5000 are identical: they are only filled in different containers. Each device consists of:

EliA anti-TG wells are coated with a human thyroglobulin antigen 4 carriers (16 wells each), ready to use; or EliA anti-TPO wells are coated with a human recombinant thyroid peroxidase
antigen 4 carriers (16 wells each), ready to use; EliA Sample Diluent: PBS containing BSA, detergent and 0.095% 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% sodium azide - 6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
-EliA Thyroid Positive Control 250 or 2500/5000: Human serum containing IqG antibodies to TG and TPO in PBS containing BSA, detergent and 0.095% sodium azide - 6 single use vials, 0.3 mL each, ready to use;
EliA Negative Control 250 or 2500/5000: Human sera from healthy donors in -PBS containing BSA, detergent and 0.095% sodium azide - 6 single-use vials, 0.3 mL each, ready to use;
-EliA IgG Calibrator Strips: Human IqG (0, 4, 10, 20, 100, 600 µq/L) in PBS containing BSA, detergent and 0.095% sodium azide - 5 strips, 6 single-use 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% sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
-EliA IqG Calibrator Well: Coated with mouse monoclonal antibodies - 4 carriers (12 wells each), ready to use.

The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages except the positive and negative controls are required to carry out an EliA anti-TG or anti-TPO test.

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

Laboratory use. 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:

To determine the precision of the assays on Phadia 250 and Phadia 2500/5000 instrument, the variability was assessed on 8 samples.
Two batches were used to determine the precision of the assays on Phadia 250 and on Phadia 2500/5000.
For EliA anti-TG Immunoassay on Phadia 250: 21 runs (3 instruments x 7 runs each) over 7 days, 252 replicate determinations per sample.
For EliA anti-TG Immunoassay on Phadia 2500/5000: 21 runs (3 instruments x 7 runs each) over 7 days, 252 replicate determinations per sample.
For EliA anti-TPO Immunoassay on Phadia 250: 21 runs (3 instruments x 7 runs each) over 7 days, 252 replicate determinations per sample.
For EliA anti-TPO Immunoassay on Phadia 2500/5000: 21 runs (3 instruments x 7 runs each) over 7 days, 252 replicate determinations per sample.

Linearity/assay reportable range:

6-7 patient serum samples were diluted in sample diluent and tested with one batch of EliA anti-TG Immunoassay and EliA anti-TPO Immunoassay and one set of system reagents on Phadia 250 or Phadia 2500/5000.
The claimed linear range for anti-TG is 12 – 4794 IU/mL.
The claimed linear range for anti-TPO is 4 – 1542 IU/mL.

Hook Effect/Over the Range Results:

Hook effect was investigated by using five serum samples above the upper limit of the measuring range.
Five high positive samples were diluted and the dilutions were measured in two replicates and compared to the upper limit of the technical measuring range (4794 IU/ml for EliA anti-TG and 1542 IU/ml for TPO EliA anti-TPO).
No hook effect was observed for EliA anti-TG (up to 27.7 times above the upper limit).
No hook effect was observed for EliA anti-TPO (up to 13.4 times above the upper limit).

Traceability, Stability, Expected values (controls, calibrators, or methods):

IgG calibrators are traceable to IRP 67/86 of Human Serum Immunoqlobulins A. G and M from WHO.
Shelf life for EliA anti-TG wells and EliA anti-TPO wells determined to be 18 months via accelerated study and confirmed by real-time stability.
On-board stability for Phadia 250 instrument was 28 days at 2-8°C, tested with 3 positive and 2 negative samples. Results applicable to Phadia 2500/5000 due to similar storage conditions.
Open stability of foilbag determined to be 9 months at 2-8°C.

Detection limit:

LoB and LoD studies done on both Phadia 250 and Phadia 2500/5000.
Four different analyte-free samples and four blood donor samples with low antibody concentration measured in six replicates in each of six runs at six different days (36 replicates per sample).
Each sample run in 6 runs on 2 instruments (3 runs on instrument 1 and 3 runs on instrument 2) with 2 lots of wells and reagents.
LoD for EliA anti-TG is 12.0 IU/mL for both instruments.
LoD for EliA anti-TPO is 4.0 IU/mL for both instruments.

Endogenous Interference:

Study investigated interference from bilirubin, hemoglobin, lipemic factor, rheumatoid factor, thyroxine, and iodide.
Three serum samples were prediluted and spiked with interfering substances or blank solutions, analyzed in triplicates.
No interference observed up to specified concentrations (e.g., Bilirubin F 192 mg/dl, Hemoglobin 4960 mg/dl, Rheumatoid factor 500 IU/ml).

Reference sera:

External Quality Assessment Scheme (QAS) sera from CAP and UK-NEQAS were measured.
The targets of the reference samples were hit.

Carry-over:

Study done on Phadia 250 instrument using EliA Ro test.
A serum sample diluted 1:2 and 1:20.
Negligible carry over effect observed. Phadia 2500/5000 instruments use disposable tips, making carry-over from samples to conjugate impossible.

Assay cut-off:

Study done on 604 apparently healthy blood donor samples (Caucasian, African American, Hispanic, Asian, equally distributed by sex and age).
Samples measured on Phadia 250 instrument for EliA anti-TG and EliA anti-TPO.
90th percentile used for setting cut-off.
EliA anti-TG: 60 IU/mL Positive.
EliA anti-TPO: 35 IU/mL Positive.

Method comparison with predicate device:

EliA anti-TG Immunoassay: 718 serum samples from various diagnostic groups. Samples analyzed with EliA anti-TG and VarelisA TG assays. Values outside overlapping measuring range (12-3000 IU/ml) excluded (n=280).
EliA anti-TPO Immunoassay: 718 serum samples from various diagnostic groups. Samples analyzed with EliA anti-TPO and VarelisA TPO assays. Values outside overlapping measuring range (4-1542 IU/ml) excluded (n=297).

Matrix comparison:

Serum, lithium heparin plasma and EDTA plasma from same patients (n = 57).
Weighted Deming regression analysis performed.
Slopes and R2 for serum vs EDTA and serum vs Li-heparin were close to 1.00, indicating good agreement.

Instrument comparison:

Performance of EliA™ anti-TG and EliA anti-TPO evaluated on Phadia 250 and Phadia 2500/5000 instruments using 30 positive, 8 equivocal and 12 negative samples.
Samples analyzed in six runs in single replicates on three Phadia 250 and three Phadia 2500/5000 instruments (2 runs on each instrument).
Regression analysis results showed slopes close to 1 (0.96 for anti-TG, 0.98 for anti-TPO).

Clinical studies:

EliA anti-TG Immunoassay: Clinical sensitivity and specificity determined using clinically defined AI Thyroiditis samples from method comparison study.
EliA anti-TPO Immunoassay: Clinical sensitivity and specificity determined using clinically defined AI Thyroiditis samples from method comparison study.

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

EliA anti-TG Immunoassay (equivocal results evaluated as negative):

Positive percent agreement: 89.7% (122/136) (95% Cl: 83.3% -94.3%)
Negative percent agreement: 88.7% (268/302) (95% CI: 84.6% -92.1%)
Total percent agreement: 89.0% [(122+268)/438] (95% Cl: 85.7% -91.8%)
Sensitivity (95% CI): 55.8% (48.9% - 62.6%)
Specificity (95% CI): 88.9% (85.8% - 91.5%)

EliA anti-TG Immunoassay (equivocal results evaluated as positive):

Positive percent agreement: 86.3% (170/197) (95% CI: 80.7% - 90.8%)
Negative percent agreement: 91.3% (220/241) (95% CI: 87.0% -94.5%)
Total percent agreement: 89.0% [(170+220)/438] (95% Cl: 85.7% – 91.8%)

EliA anti-TPO Immunoassay (equivocal results evaluated as negative):

Positive percent agreement: 100% (167/167) (95% Cl: 97.8% – 100.0%)
Negative percent agreement: 89.7% (297/331) (95% CI: 85.9% -92.8%)
Total percent agreement: 93.2% [(167+297)/498] (95% Cl: 90.6% -95.2%)
Sensitivity (95% CI): 82.3% (76.6% – 87.2%)
Specificity (95% CI): 90.5% (87.5% – 92.9%)

EliA anti-TPO Immunoassay (equivocal results evaluated as positive):

Positive percent agreement: 100% (213/213) (95% Cl: 98.3% – 100.0%)
Negative percent agreement: 73.7% (210/285) (95% CI: 68.2% -78.7%)
Total percent agreement: 84.9% [(213+210)/498] (95% Cl: 81.5% -88.8%)

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.

K003414, K993585, K091845, K061165

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.

K063775, K072393, K082759

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

§ 866.5870 Thyroid autoantibody immunological test system.

(a)
Identification. A thyroid autoantibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the thyroid autoantibodies (antibodies produced against the body's own tissues). Measurement of thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlargement of thyroid gland), Grave's disease (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid.(b)
Classification. Class II (performance standards).

Summary

0

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized representation of three human profiles facing to the right, stacked on top of each other. The profiles are rendered in black and have a flowing, ribbon-like appearance. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

March 25, 2016

Phadia US Inc. Martin Mann Sr. Regulatory Affairs Manager 4169 Commercial Avenue Portage, MI 49002

Re: K151799 Trade/Device Name: EliATM anti-TG Immunoassay EliA™ anti-TPO Immunoassay EliATM Thyroid Positive Control 250 EliATM Thyroid Positive Control 2500/5000 Regulation Number: 21 CFR §866.5870 Regulation Name: Thyroid autoantibody immunological test system Regulatory Class: II Product Code: JZO, JJY Dated: February 24, 2016 Received: February 25, 2016

Dear Mr. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements

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Page 2-Mr. Martin Mann

as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Leonthena R. Carrington -S

Leonthena R. Carrington, MS, MBA, MT(ASCP) Director

Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

2

Indications for Use

510(k) Number (if known) K151799

Device Name

EliA™ anti-TG Immunoasay, EliA™ anti-TPO Immunoassay, EliA™ Thyroid Positive Control 250, and EliA™ Thyroid Positive Control 2500/5000.

Indications for Use (Describe)

EliA anti-TG Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroglobulin (TG) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TG uses the EliA IgG method on the instrument Phadia 250.

EliA anti-TG Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroglobulin (TG) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TG uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA anti-TPO Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroid peroxidase (TPO) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TPO uses the EliA IgG method on the instrument Phadia 250.

EliA anti-TPO Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroid peroxidase (TPO) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TPO uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA Thyroid Positive Control 250 is intended for laboratory use in monitoring the performance of in vitro measurement of antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) with Phadia 250 using the EliA IgG method.

EliA Thyroid Positive Control 2500/5000 is intended for laboratory use in monitoring the performance of in vitro measurement of antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) with Phadia 2500/5000 using the EliA IgG method.

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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F.1 510k Decision Summary Input

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number: K151799

B. Purpose for Submission: New devices
C. Measurand: lgG Antibodies to TG and TPO

D. Type of Test: Quantitative immunofluorescence assays

E. Applicant: Phadia AB, Sweden

F. Proprietary and Established Names:

EliA™ anti-TG Immunoassay EliA™ anti-TPO Immunoassay EliA™ Thyroid Positive Control 250 EliA™ Thyroid Positive Control 2500/5000

G. Requlatory Information:

1. Regulation section:
  21 CFR §866.5870, Thyroid autoantibody immunological test system 21 CFR §862.1660, Quality control material (assayed and unassayed)
Classification: 2.
Class II (Assays) Class I (Controls)
1. Product code:
  JZO System, Test, Thyroid Autoantibody JJY Multi-Analyte Controls, All Kinds (assayed)
1. Panel:
  Immunology

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H. Intended Use:

Intended use(s):

EliA anti-TG is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroglobulin (TG) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TG uses the EliA IgG method on the instruments Phadia 250 and Phadia 2500/5000.

EliA anti-TPO is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroid peroxidase (TPO) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TPO uses the EliA IgG method on the instruments Phadia 250 and Phadia 2500/5000.

EliA Thyroid Positive Control 250 and EliA Thyroid Positive Control 2500/5000 is intended for laboratory use in monitoring the performance of in vitro measurement of antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) with Phadia 250 and Phadia 2500/5000 using the EliA IgG method.

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2._Indication(s) for use:
Same as intended use

Special conditions for use statement(s): For prescription use only

4.__Special instrument requirements:
Phadia® 250 or Phadia® 2500/5000

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-Device Description:

The method specific reagents on Phadia® 250 and Phadia® 2500/5000 are identical: they are only filled in different containers. Each device consists of:

EliA anti-TG wells are coated with a human thyroglobulin antigen 4 carriers (16 wells each), ready to use; or EliA anti-TPO wells are coated with a human recombinant thyroid peroxidase
antigen 4 carriers (16 wells each), ready to use; EliA Sample Diluent: PBS containing BSA, detergent and 0.095% 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% sodium azide - 6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
-EliA Thyroid Positive Control 250 or 2500/5000: Human serum containing IqG antibodies to TG and TPO in PBS containing BSA, detergent and 0.095% sodium azide - 6 single use vials, 0.3 mL each, ready to use;
EliA Negative Control 250 or 2500/5000: Human sera from healthy donors in -PBS containing BSA, detergent and 0.095% sodium azide - 6 single-use vials, 0.3 mL each, ready to use;
-EliA IgG Calibrator Strips: Human IqG (0, 4, 10, 20, 100, 600 µq/L) in PBS containing BSA, detergent and 0.095% sodium azide - 5 strips, 6 single-use 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% sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
-EliA IqG Calibrator Well: Coated with mouse monoclonal antibodies - 4 carriers (12 wells each), ready to use.

The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages except the positive and negative controls are required to carry out an EliA anti-TG or anti-TPO test.

J. Substantial Equivalence Information:

1. Predicate device name(s) and 510(k) number(s):
VarelisA TG Antibodies, Phadia GmbH	K003414
VarelisA TPO Antibodies, Phadia GmbH	K993585
EliATM IgG/IgM/IgA Negative Control 250	K091845
EliA IgG Calibrator Strips	K061165

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2. Comparison with predicate device:

EliA anti-TG Immunoassay – Similarities to predicate device

| Feature | Predicate Device
VarelisA TG | New Device
EliA anti-TG | |
|-----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| Intended Use | The VarelisA TG (Thyroglobulin)
Antibodies EIA kit is designed for
the quantitative and qualitative
determination of thyroglobulin
antibodies in serum or plasma to
aid in the diagnosis of thyroid
diseases such as autoimmune
thyroiditis and Graves' disease | EliA anti-TG is intended for the in
vitro quantitative measurement
of IgG antibodies directed to
thyroglobulin (TG) in human
serum and plasma (Li-heparin,
EDTA) as an aid in the clinical
diagnosis of autoimmune
thyroiditis and Graves' disease in
conjunction with other laboratory
and clinical findings. EliA anti-TG
uses the EliA IgG method on the
instruments Phadia 250 and
Phadia 2500/5000. | |
| Internal Controls | Positive and Negative Control
included in the kit | Positive and negative Control
provided with the EliA Thyroid
Positive Control 250 / 2500/5000
and EliA IgG/IgM/IgA Negative
Control 250 / 2500/5000,
respectively | |
| Assay Type | ELISA | | |
| Type of test | quantitative | | |
| Reported Unit | IU/ml | | |
| Solid Phase | Microwells | | |
| Antigen | human thyroglobulin antigen | | |
| Feature | Predicate Device
VarelisA TG | New Device
EliA anti-TG | |
| Instrumentation | ELISA-Reader needed | Phadia 250 and 2500/5000 are
fully automated immunoassay
analyzers | |
| Reaction
temperature | Room temperature | 37°C controlled | |
| Incubation times | Positive and negative Controls,
diluted patient samples: 30 min.
Conjugate: 30 min.
Substrate: 10 min (in dark) | Diluted patient samples: 30 min.
Conjugate: 28 min.
Development Solution: 39 min. | |
| Detection antibody
(conjugate) | IgG conjugate: anti-human IgG
horse radish peroxidase (goat) | IgG conjugate: anti-human IgG
ß-Galactosidase (mouse
monoclonal antibodies) | |
| Signal | Optical density (at 450nm) | Fluorescence | |
| Calibration | 6-point Calibration | 6-point total IgG Calibration | |
| Calibrators | 6 vials of TG-specific IgG at
concentrations of
0 - 30 - 100 - 300 - 1000 -
3000 IU/ml | 6 vials of human IgG at
concentrations of
0 - 4 - 10 - 20 - 100 - 600 μg/l | |
| Calibration curve | n.a. | Option to store curve for up to 28
days and run curve controls in
each assay for calibration | |
| Concept | All reagents in a single kit | Modular reagents concept
(test-method specific and
general reagents) | |
| Sample Dilution | 1:101 | 1:100 | |
| Cut-off | 100 IU/ml positive | 60 IU/ml positive | |
| Substrate | TMB Chromogen | Development Solution 0.01 %
4-Methylumbelliferyl-β-D-
galactoside & in vitro quantitative
measurement of IgG antibodies
directed to thyroid peroxidase
(TPO) in human serum and
plasma (Li-heparin, EDTA) as an
aid in the clinical diagnosis of
autoimmune thyroiditis and
Graves' disease in conjunction
with other laboratory and clinical
findings. EliA anti-TPO uses the
EliA IgG method on the
instruments Phadia 250 and
Phadia 2500/5000. | |
| Internal Controls | Positive and Negative Control
included in the kit | Positive and negative Control
provided with the EliA Thyroid
Positive Control 250 / 2500/5000
and EliA IgG/IgM/IgA Negative
Control 250 / 2500/5000,
respectively | |
| Assay Type | ELISA | | |
| Type of test | quantitative | | |
| Reported Unit | IU/ml | | |
| Solid Phase | Microwells | | |
| Antigen | human recombinant TPO antigen | | |
| Feature | Predicate Device
VarelisA TPO | New Device
EliA anti-TPO | |
| Instrumentation | ELISA-Reader needed | Phadia 250 and 2500/5000 are
fully automated immunoassay
analyzers | |
| Reaction
temperature | Room temperature | 37°C controlled | |
| Incubation times | Positive and negative Controls,
diluted patient samples: 30 min.
Conjugate: 30 min.
Substrate: 10 min (in dark) | Diluted patient samples: 30 min.
Conjugate: 28 min.
Development Solution: 39 min. | |
| Detection antibody
(conjugate) | IgG conjugate: anti-human IgG
horse radish peroxidase (goat) | IgG conjugate: anti-human IgG
ß-Galactosidase (mouse
monoclonal antibodies) | |
| Signal | Optical density (at 450nm) | Fluorescence | |
| Calibration | 6-point antigen-specific
Calibration | 6-point total IgG Calibration | |
| Calibrators | 6 vials of TPO-specific IgG at
concentrations of
0 - 30 - 100 - 300 - 1000 -
3000 IU/ml | 6 vials of human IgG at
concentrations of
0 - 4 - 10 - 20 - 100 - 600 μg/l | |
| Calibration curve | n.a. | Option to store curve for up to 28
days and run curve controls in
each assay for calibration | |
| Concept | All reagents in a single kit | Modular reagents concept
(test-method specific and
general reagents) | |
| Sample Dilution | 1:101 | 1:200 | |
| Cut-off | 100 IU/ml positive | 35 IU/ml positive | |
| Substrate | TMB Chromogen | Development Solution 0.01 %
4-Methylumbelliferyl-ß-D-
galactoside & 80% consensus of all participants could be reached. For UK-NEQAS the target is set by the provider based on all responses; an equivocal target means that positive and negative responses are acceptable. The targets of the reference samples were hit.

| Sample No. | Sample ID
supplier | Institution | Target | EliA anti-TG (IU/ml) | |
|------------|-----------------------|-------------|--------|---------------------------------|----|
| | | | | Neg 60 | |
| 1 | S2-03 | CAP | Pos | 4511.7 | OK |
| 2 | S2-11 | CAP | Pos | 5979.9 | OK |
| 3 | S2-19 | CAP | Neg | 0.7 | OK |
| 4 | S2-11 | CAP | Pos | 4650.7 | OK |
| 5 | S2-19 | CAP | Pos | 6083.5 | OK |
| 6 | S2-02 | CAP | Pos | 5333.6 | OK |
| 7 | S2-10 | CAP | Neg | 0.8 | OK |
| 8 | S2-18 | CAP | Pos | 3612.1 | OK |

Evaluation of QAS sera on EliA anti-TG

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Sample No.	Sample ID supplier	Institution	Target	EliA anti-TPO (IU/ml)
				Neg 35
1	S2-03	CAP	Pos	150.1	OK
2	S2-11	CAP	Pos	171.3	OK
3	S2-19	CAP	Neg	0.0	OK
4	S2-11	CAP	Pos	97.0	OK
5	S2-19	CAP	Pos	164.4	OK
6	S2-02	CAP	Pos	155.6	OK
7	S2-10	CAP	Neg	0.0	OK
8	S2-18	CAP	Pos	89.6	OK
9	1012	NEQAS	Equ	41.4	OK
10	1032	NEQAS	Pos	102.1	OK
11	1042	NEQAS	Pos	136.5	OK
12	1052	NEQAS	Pos	98.3	OK
13	1062	NEQAS	Pos	87.5	OK
14	111-2	NEQAS	Pos	132.3	OK
15	112-2	NEQAS	Equ	21.8	OK
16	114-2	NEQAS	Pos	174.5	OK
17	116-2	NEQAS	Pos	90.4	OK
18	122-2	NEQAS	Pos	84.9	OK
19	123-2	NEQAS	Equ	1.6	OK
20	124-2	NEQAS	Pos	107.6	OK

Evaluation of QAS sera on EliA anti-TPO

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Carry-over: A study was carried out on a Phadia 250 instrument using the test EliA Ro, cleared under K082759. A serum sample was diluted 1:2 and 1:20 using instrument dilution and manual dilution. A lower dilution factor than the default one (1:100) was chosen to challenge the system. Only a few RUs difference compared to the reference pipetting could be seen, which is too low to be expressed in U/mL. The observed carry over effect is therefore negligible without any influence to assay results.

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:
A study was done on 604 apparently healthy blood donor samples from Caucasian, African American, Hispanic and Asian individuals almost equally distributed by sex and age in order to evaluate expected values for each of the antigens in the submission in the normal population and to confirm the defined cut-off. The samples were measured on the Phadia 250 instrument for EliA anti-TG and EliA anti-TPO. The 90t" and 95th percentile of the 604 samples were calculated and the 90th percentile was taken into account for setting the cut-off. The following values were selected for the cut-off:

EliA anti-TG
60 IU/mL	Positive

In case of equivocal results, it is recommended to retest the patient after 8-12 weeks.

EliA anti-TPO
35 IU/mL	Positive

In case of equivocal results, it is recommended to retest the patient after 8-12 weeks.

1. Comparison studies:
Method comparison with predicate device: a.

EliA anti-TG Immunoassay:

A total of 718 serum samples were collected with a diagnosis from patients with Graves' disease (n = 100), autoimmune thyroiditis (n = 100), non-Al thyroid disease (n = 48), connective tissue disease (n = 15), Crohn`s disease (n = 20), ulcerative colitis (n = 20), primary biliary cirrhosis (n = 10), HIV infection (n = 20), HCV infection (n = 20), HBV infection (n = 20), other infection (n = 20), cancer (n = 56), rheumatoid arthritis (n = 12), hypergamma-globulinemia (n = 15),

23

systemic lupus erythematosus (n = 24), Sjögren's syndrome (n = 14), celiac disease (n = 15), type 1 diabetes mellitus (n = 15), type II diabetes mellitus (n = 15), pregnant women of all trimesters (n = 90), pre-eclampsia (n = 5), miscarriage (n=9), thyroid cancer (n = 21), myasthenia gravis (n = 7), pernicious anemia (n = 8), chronic lymphocytic thyroiditis (n = 10), sub-acute thyroiditis (n = 5), multi-nodular goiter (n = 4).

Samples were analyzed with the EliA anti-TG and VarelisA TG assays. The test was run in single determination and values outside the overlapping measuring range for both tests (12-3000 IU/ml) were excluded from statistical analyses (n=280). The results are summarized in the tables below:

	VarelisA TG (IU/mL)
	Positive >100	Negative 60	122
Negative ≤60	14	268	282
Total	136	302	438

EliA anti-TG - Equivocal results evaluated as negative:

Positive percent agreement: 89.7% (122/136) (95% Cl: 83.3% -94.3%)

Negative percent agreement: 88.7% (268/302) (95% CI: 84.6% -92.1%)

Total percent agreement: 89.0% [(122+268)/438] (95% Cl: 85.7% -91.8%)

EliA anti-TG - Equivocal results evaluated as positive:

		VarelisA TG (IU/mL)
		Positive >60	Negative 100	Negative 100
Negative test ≤60.0 IU/mL	95	447	542
Total	215	503	718

Sensitivity (95% CI): 55.8% (48.9% - 62.6%) Specificity (95% CI): 88.9% (85.8% - 91.5%)

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The table below shows the results for each clinical subgroup:

| Condition of
samples | No (%)
pos. on
EliA anti-
TG | No (%)
pos. on
Predicate
VarelisA
TG |
|-------------------------- | Graves' Disease | Autoimmune thyroiditis | Non-AI Thyroid Disease | Connective Tissue Disease | Crohn's disease | Ulcerative colitis | Primary Biliary Cirrhosis | HIV infection | HCV infection | HBV infection | Other infection | Cancer | Rheumatoid arthritis | Hypergammaglobulinemia | Systemic lupus erythematosus | Sjögren's syndrome | Celiac disease | Type I diabetes mellitus | Type II diabetes mellitus | Pregnant women (all trimesters) | 90 | Pre-eclampsia | Miscarriage | Thyroid cancer | Myasthenia gravis | Pernicious anemia | Multi-nodular goiter | Number
-------|-------------------------|---------------------------------------|--------------------------------------------------|
| 100 | 48 (48%) | 48 (48%) |
| 115 | 72 (62.6%) | 69 (60%) |
| 48 | 7 (14.6%) | 9 (18.8%) |
| 15 | 2 (13.3%) | 2 (13.3%) |
| 20 | 1 (5%) | 0 (0%) |
| 20 | 1 (5%) | 0 (0%) |
| 10 | 0 (0%) | 0 (0%) |
| 20 | 0 (0%) | 3 (15%) |
| 20 | 1 (5%) | 2 (10%) |
| 20 | 1 (5%) | 2 (10%) |
| 20 | 1 (5%) | 1 (5%) |
| 56 | 13 (23.2%) | 7 (12.5%) |
| 12 | 2 (16.7%) | 1 (8.3%) |
| 15 | 1 (6.7%) | 1 (6.7%) |
| 24 | 5 (20.8%) | 3 (12.5%) |
| 14 | 2 (14.3%) | 2 (14.3%) |
| 15 | 3 (20%) | 2 (13.3%) |
| 15 | 2 (13.3%) | 2 (13.3%) |
| 15 | 1 (6.7%) | 1 (6.7%) |
| 5 (5.6%) | 2 (2.2%) |
| 5 | 0 (0%) | 0 (0%) |
| 9 | 6 (66.7%) | 1 (11.1%) |
| 21 | 0 (0%) | 0 (0%) |
| 7 | 0 (0%) | 0 (0%) |
| 8 | 2 (25%) | 2 (25%) |
| 4 | 0 (0%) | 0 (0%) |

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EliA anti-TPO Immunoassay:

The clinically defined AI Thyroiditis samples that were used for the method comparison were also used to determine sensitivity and specificity of the assay. The results are summarized in the tables below.

EliA anti-TPO - diagnostic group Al Thyroiditis - equivocal results evaluated as negative:

Diagnostic Group - Al Thyroiditis
	+	-	total
Positive test >35.0 IU/mL	177	48	225
Negative test ≤35.0 IU/mL	38	455	493
Total	215	503	718

Sensitivity (95% CI): 82.3% (76.6% – 87.2%) Specificity (95% CI): 90.5% (87.5% – 92.9%)

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The table below shows the results for each clinical subgroup:

| Condition | Number
of
samples | No (%)
pos. on
EliA anti-
TPO | No (%)
pos. on
Predicate
VarelisA
TPO |
|---------------------------------|-------------------------|----------------------------------------|---------------------------------------------------|
| Graves' Disease | 100 | 81 (81%) | 68 (68%) |
| Autoimmune thyroiditis | 115 | 96 (83.5%) | 88 (76.5%) |
| Non-AI Thyroid Disease | 48 | 5 (10.4%) | 5 (10.4%) |
| Connective Tissue Disease | 15 | 1 (6.7%) | 1 (6.7%) |
| Crohn's disease | 20 | 0 (0%) | 0 (0%) |
| Ulcerative colitis | 20 | 0 (0%) | 0 (0%) |
| Primary Biliary Cirrhosis | 10 | 0 (0%) | 0 (0%) |
| HIV infection | 20 | 1 (5%) | 0 (0%) |
| HCV infection | 20 | 1 (5%) | 1 (5%) |
| HBV infection | 20 | 0 (0%) | 0 (0%) |
| Other infection | 20 | 0 (0%) | 0 (0%) |
| Cancer | 56 | 11 (19.6%) | 5 (8.9%) |
| Rheumatoid arthritis | 12 | 1 (8.3%) | 1 (8.3%) |
| Hypergammaglobulinemia | 15 | 0 (0%) | 0 (0%) |
| Systemic lupus erythematosus | 24 | 1 (4.2%) | 0 (0%) |
| Sjögren's syndrome | 14 | 1 (7.1%) | 1 (7.1%) |
| Celiac disease | 15 | 2 (13.3%) | 2 (13.3%) |
| Type I diabetes mellitus | 15 | 2 (13.3%) | 2 (13.3%) |
| Type II diabetes mellitus | 15 | 2 (13.3%) | 2 (13.3%) |
| Pregnant women (all trimesters) | 90 | 10 (11.1%) | 10 (11.1%) |
| Pre-eclampsia | 5 | 4 (80%) | 3 (60%) |
| Miscarriage | 9 | 2 (22.2%) | 1 (11.1%) |
| Thyroid cancer | 21 | 2 (9.5%) | 1 (4.8%) |
| Myasthenia gravis | 7 | 1 (14.3%) | 0 (0%) |
| Pernicious anemia | 8 | 1 (12.5%) | 0 (0%) |
| Multi-nodular goiter | 4 | 0 (0%) | 0 (0%) |

b. Other clinical supportive data: Not applicable
Clinical cut-off: 4.

Same as assay cut-off

5. Expected values/Reference range:

EliA anti-TG Immunoassay:

Antibody prevalence in autoimmune patients varies widely depending on disease area. A significant percentage (>10%) of healthy subjects was reported to have anti-thyroglobulin antibodies. Expected values may vary depending on the population tested.

30

The 5th percentile of the tested normal samples was calculated as 5.4 IU/ml, the 95th percentile as 97.9 IU/ml.

EliA anti-TPO Immunoassay:

Antibody prevalence in autoimmune patients varies widely depending on disease area. A significant percentage (>10%) of healthy subjects was reported to have anti-thyroid peroxidase antibodies. Expected values may vary depending on the population tested.

The 5th percentile of the tested normal samples was calculated as 1.7 IU/ml, the 95th percentile as 59.9 IU/ml.