(488 days)
No
The summary describes a standard immunoassay test and does not mention any AI or ML components.
No
This device is an in vitro diagnostic test for measuring antibodies in human serum to aid in the diagnosis of certain conditions, not a device used for therapy.
Yes
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 diagnosis of Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM)". This clearly indicates its diagnostic purpose.
No
The device description explicitly states it is a "fully integrated and automated system composed of assay-specific reagents, EliA method-specific reagents, and general reagents," indicating it includes hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro52 in human serum" and "intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro60 in human serum". The term "in vitro" is a key indicator of an in vitro diagnostic device, meaning it is used to test samples taken from the human body, such as blood or serum, outside of the body.
Furthermore, the device is described as an "Immunoassay" which is a common type of in vitro diagnostic test. The purpose of the test is to aid in the diagnosis of specific diseases (Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myopathies) by measuring specific antibodies in the serum. This aligns with the definition and purpose of an IVD.
N/A
Intended Use / Indications for Use
EliA Ro52 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro52 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM) in conjunction with other laboratory and clinical findings. EliA Ro52 uses the EliA IgG method.
EliA Ro60 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro60 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Ro60 uses the EliA IgG method.
Product codes (comma separated list FDA assigned to the subject device)
LKJ
Device Description
The EliA Ro52 and EliA Ro60 Immunoassays are semi-quantitative solid-phase fluoroenzyme immunoassays, for the determination of autoantibodies against SS-A/Ro 52 kDa and 60 kDa proteins. The EliA Ro52 and EliA Ro60 test System is a fully integrated and automated system composed of assay-specific reagents, EliA method-specific reagents, and general reagents.
Assay-Specific Reagents include:
- . EliA Ro52 Wells: coated with human recombinant SS-A/Ro (52 kDa) protein - 2 carriers (12 wells each), ready to use.
- EliA Ro60 Wells: coated with human recombinant SS-A/Ro (60 kDa) protein ■ - 4 carriers (12 wells each), ready to use.
- . EliA ANA Positive Control 250 or 2500/5000: Human serum in PBS containing IgG antibodies to dsDNA, RNP, Sm, Ro. La, Scl-70, CENP, and Jo-1 - 6 single use vials, 0.3 mL each, ready to use.
- . EliA ANA 3 Positive Control 250 or 2500/5000: Human monoclonal antibodies in PBS containing BSA, detergent and sodium azide (0.095% (w/v)) containing IgG antibodies to Ro52, Rib-P and RNA Pol III - 6 single use vials, 0.3 mL each, ready to use.
- . EliA IgG/IgM/IgA Negative Control 250 or 2500/5000: Human blood preparation from healthy donors in PBS containing BSA, detergent and 0.095% sodium azide - 6 singleuse vials, 0.3 mL each, ready to use.
EliA Method-Specific Reagents include:
- I 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.
- I 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.
- 트 EliA IgG Calibrator Strips: Human IgG (0, 4, 10, 20, 100, 600 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.
- I 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.
- I EliA IgG Calibrator Well: coated with mouse monoclonal antibodies - 4 carriers (12 wells each), ready to use.
General Reagents include:
- Development Solution: 0.01% 4-Methylumbelliferyl-B-D-galactoside, 110, 6x >170, or 6x >1165 determinations.
- I Stop Solution: 4% Sodium Carbonate - 6 bottles (65 mL, 119 mL, or 2800 mL each), sufficient for 6x >292, 6x >560, or 6x >13100 determinations.
- I Washing Solution Additive: detergent, preservative 10 EliA U/mL.
2. Comparison Studies:
a) Method Comparison with Predicate Device:
Study Type: Agreement study comparing EliA Ro52/Ro60 with QUANTA Flash Ro52/Ro60.
Sample Size: EliA Ro52: 181 patient serum samples. EliA Ro60: 104 patient serum samples.
Key Results:
EliA Ro52 (equivocal results considered negative): PPA 80.8%, NPA 98.4%, TPA 93.4%.
EliA Ro52 (equivocal results considered positive): PPA 92.3%, NPA 90.7%, TPA 91.2%.
EliA Ro60 (equivocal results considered negative): PPA 93.9%, NPA 92.1%, TPA 93.3%.
EliA Ro60 (equivocal results considered positive): PPA 97.0%, NPA 81.6%, TPA 91.3%.
b) Instrument Comparison:
EliA Ro52: Compared performance on Phadia 250 and Phadia 2500E using 57 positive, 6 equivocal and 30 negative samples. Regression analysis: Intercept 0.91 (0.46-1.14), Slope 0.94 (0.93-0.97).
EliA Ro60: Compared performance on Phadia 250 and Phadia 2500E using 42 positive, 9 equivocal and 39 negative samples. Regression analysis: Intercept 0.24 (0.15-0.48), Slope 1.01 (0.97-1.04).
3. Clinical Studies
c) Clinical Sensitivity and Specificity:
EliA Ro52:
Sample Size: 755 clinically and ethnically defined serum samples (120 SLE, 60 SS, 94 IIM, 91 SSc as diagnostic group; 390 disease control group).
Key Results (equivocal = negative):
For SLE: Sensitivity 47.5% (95% CI 38.3-56.8), Specificity 96.9% (95% CI 94.7-98.4).
For SS: Sensitivity 50.0% (95% CI 36.8-63.2), Specificity 96.9% (95% CI 94.7-98.4).
For IIM: Sensitivity 36.2% (95% CI 26.5-46.7), Specificity 96.9% (95% CI 94.7-98.4).
For SSc: Sensitivity 20.9% (95% CI 13.1-30.7), Specificity 96.9% (95% CI 94.7-98.4).
EliA Ro60:
Sample Size: 713 clinically and ethnically defined serum samples (120 SLE, 60 SS as diagnostic group; 533 disease control group).
Key Results (equivocal = negative):
For SLE: Sensitivity 48.3% (95% CI 39.1-57.6), Specificity 98.6% (95% CI 97.1-99.5).
For SS: Sensitivity 68.3% (95% CI 55-79.7), Specificity 98.6% (95% CI 97.1-99.5).
d) Other Clinical Supportive Data: Not applicable.
Expected Values/Reference Range: Antibody prevalence in autoimmune patients varies. Proportion of sera from a normal population found positive for the antinuclear antibodies covered by the EliA Ro52 and EliA Ro60 test is below 1%.
Frequency distribution in apparently healthy subjects (n=638):
EliA Ro52: Median 1.0 EliA U/mL, 95th percentile 1.8 EliA U/mL, 99th percentile 2.6 EliA U/mL.
EliA Ro60: Median 0.5 EliA U/mL, 95th percentile 0.9 EliA U/mL, 99th percentile 7.4 EliA U/mL.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
EliA Ro52 (equivocal results considered negative):
PPA: 80.8% (95% CI 67.5 - 90.4)
NPA: 98.4% (95% CI 94.5 - 99.8)
TPA: 93.4% (95% CI 88.8 - 96.5)
EliA Ro52 (equivocal results considered positive):
PPA: 92.3% (95% CI 81.5 – 97.9)
NPA: 90.7% (95% CI 84.3 – 95.1)
TPA: 91.2% (95% CI 86.1 – 94.9)
EliA Ro60 (equivocal results considered negative):
PPA: 93.9% (95% CI 85.2 - 98.3)
NPA: 92.1% (95% CI 78.6 - 98.3)
TPA: 93.3% (95% CI 86.6 - 97.3)
EliA Ro60 (equivocal results considered positive):
PPA: 97.0% (95% CI 89.5 - 99.6)
NPA: 81.6% (95% CI 65.7 - 92.3)
TPA: 91.3% (95% CI 84.2 - 96.0)
Clinical Sensitivity and Specificity:
EliA Ro52:
For SLE (equivocal = negative): Sensitivity 47.5% (95% CI 38.3 - 56.8), Specificity 96.9% (95% CI 94.7 - 98.4)
For SS (equivocal = negative): Sensitivity 50.0% (95% CI 36.8 - 63.2), Specificity 96.9% (95% CI 94.7 - 98.4)
For IIM (equivocal = negative): Sensitivity 36.2% (95% CI 26.5 - 46.7), Specificity 96.9% (95% CI 94.7 - 98.4)
For SSc (equivocal = negative): Sensitivity 20.9% (95% CI 13.1 - 30.7), Specificity 96.9% (95% CI 94.7 - 98.4)
EliA Ro60:
For SLE (equivocal = negative): Sensitivity 48.3% (95% CI 39.1 - 57.6), Specificity 98.6% (95% CI 97.1 - 99.5)
For SS (equivocal = negative): Sensitivity 68.3% (95% CI 55 - 79.7), Specificity 98.6% (95% CI 97.1 - 99.5)
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.
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.
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
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the FDA name and title on the right. The symbol on the left is a stylized representation of a human figure, while the text on the right reads "FDA U.S. FOOD & DRUG ADMINISTRATION" in blue letters.
July 27, 2022
Phadia AB % Jane Anthony Senior Manager, Quality Systems and Compliance Phadia US Inc. 4169 Commercial Avenue Portage, Michigan 49002
Re: K210902
Trade/Device Name: EliA Ro52 EliA Ro60 Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear Antibody Immunological Test System Regulatory Class: Class II Product Code: LKJ Dated: April 4, 2022 Received: April 6, 2022
Dear Jane Anthony:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
542 of the Act); 21 CFR 1000-1050.
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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name
EliA Ro52
Indications for Use (Describe)
EliA Ro52 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro52 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM) in conjunction with other laboratory and clinical findings. EliA Ro52 uses the EliA IgG method.
| 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) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
3
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
4
Indications for Use
510(k) Number (if known)
Device Name
EliA Ro60
Indications for Use (Describe)
EliA Ro60 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro60 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Ro60 uses the EliA IgG method.
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) | ☐ |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
5
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
6
510(K) DECISION SUMMARY
This 510(k) Summary is prepared in accordance with the requirements of 21 CFR Part 807.92.
Premarket Notification 510(k) No: K210902
| Date of Summary Preparation: | July 25, 2022 |
|---|---|
| Manufacturer: | Phadia AB |
| Rapsgatan 7P | |
| P.O. Box 6460 | |
| 751 37 Uppsala, Sweden | |
| Distributor: | Phadia US Inc. |
| 4169 Commercial Avenue | |
| Portage, MI 49002 | |
| Company Contact Person: | Jane Anthony |
| Senior Manager, Quality Systems and Compliance | |
| Phadia US Inc. | |
| 4169 Commercial Avenue, Portage, MI 49002 | |
| 269-254-6833 | |
| jane.anthony@thermofisher.com |
Proprietary and Established Device Name:
EliA Ro52 EliA Ro60
Regulatory Information:
| Product Code: | LKJ |
|---|---|
| Classification: | Class II |
| Regulation: | 21 CFR 866.5100 – Antinuclear Antibody Immunological Test |
| System | |
| Panel: | Immunology |
Purpose of Submission:
New Device
7
Measurand:
IgG autoantibodies specific to SS-A/Ro proteins (52 kDa and 60 kDa)
Type of Test:
Automated semi-quantitative solid phase fluoroenzymeimmunoassay.
Intended Use:
EliA Ro52 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro52 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM) in conjunction with other laboratory and clinical findings. EliA Ro52 uses the EliA IgG method.
EliA Ro60 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Ro60 in human serum as an aid in the diagnosis of Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Ro60 uses the EliA IgG method.
Indication(s) for Use:
Same as intended use
Special Conditions for Use:
Rx - For Prescription Use Only
Special Instrument Requirements:
For use on the Phadia 250 instrument and the Phadia 5000 instrument series (E-modules).
Device Description:
The EliA Ro52 and EliA Ro60 Immunoassays are semi-quantitative solid-phase fluoroenzyme immunoassays, for the determination of autoantibodies against SS-A/Ro 52 kDa and 60 kDa proteins. The EliA Ro52 and EliA Ro60 test System is a fully integrated and automated system composed of assay-specific reagents, EliA method-specific reagents, and general reagents.
Assay-Specific Reagents include:
- . EliA Ro52 Wells: coated with human recombinant SS-A/Ro (52 kDa) protein - 2 carriers (12 wells each), ready to use.
- EliA Ro60 Wells: coated with human recombinant SS-A/Ro (60 kDa) protein ■ - 4 carriers (12 wells each), ready to use.
Phadia AB, Rapsgatan 7P, P.O. Box 6460, 751 37 Uppsala, Sweden
Confidential Page 2 (26)
8
- . EliA ANA Positive Control 250 or 2500/5000: Human serum in PBS containing IgG antibodies to dsDNA, RNP, Sm, Ro. La, Scl-70, CENP, and Jo-1 - 6 single use vials, 0.3 mL each, ready to use.
- . EliA ANA 3 Positive Control 250 or 2500/5000: Human monoclonal antibodies in PBS containing BSA, detergent and sodium azide (0.095% (w/v)) containing IgG antibodies to Ro52, Rib-P and RNA Pol III - 6 single use vials, 0.3 mL each, ready to use.
- . EliA IgG/IgM/IgA Negative Control 250 or 2500/5000: Human blood preparation from healthy donors in PBS containing BSA, detergent and 0.095% sodium azide - 6 singleuse vials, 0.3 mL each, ready to use.
EliA Method-Specific Reagents include:
- I 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.
- I 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.
- 트 EliA IgG Calibrator Strips: Human IgG (0, 4, 10, 20, 100, 600 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.
- I 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.
- I EliA IgG Calibrator Well: coated with mouse monoclonal antibodies - 4 carriers (12 wells each), ready to use.
General Reagents include:
- Development Solution: 0.01% 4-Methylumbelliferyl-B-D-galactoside, 110, 6x >170, or 6x >1165 determinations.
- I Stop Solution: 4% Sodium Carbonate - 6 bottles (65 mL, 119 mL, or 2800 mL each), sufficient for 6x >292, 6x >560, or 6x >13100 determinations.
- I Washing Solution Additive: detergent, preservative 10 EliA U/mL | Negative: 20
CU |
| Substrate | Development Solution 0.01 %
4-Methylumbelliferyl-ß-D-
galactoside,
10 EliA U/mL | Negative: 20 CU |
| Substrate | Development Solution 0.01 %
4-Methylumbelliferyl-β-D-
galactoside,
240" for both assays. No recommendations are made for dilution of samples outside measuring range in the Directions for Use.
18
c) Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Traceability:
The IgG calibrators are traceable (via unbroken chain of calibrations) to the International Reference Preparation (IRP) 67/86 of Human Serum Immunoglobulins A. G and M from WHO. New batches of IgG calibrators are compared to a secondary standard (standardized with the IRP) or the IRP directly and adjusted accordingly to meet the correct concentration.
The instrument measures specific IgG concentrations in ug/L. By using a conversion factor given by the lot-specific code of the EliA test well. the results are automatically converted to EliA U/mL.
Stabilitv:
Data for open and closed real-time stability and on-board stability of EliA IgG reagents and general EliA reagents on Phadia 250 as well as on the E-module of the Phadia 2500 and Phadia 5000 series were already cleared with several other EliA tests, e.g., under K141375 (EliA M2 on Phadia 250). For the Phadia 2500 and Phadia 5000 instrument series, they were already cleared under K061165/A003 (EliA CCP).
Shelf-life:
The stability of EliA Ro52 and EliA Ro60 Wells was evaluated with a real-time study. The results support stability of the test under the recommended storage of 2 – 8°C for up to 24 months for EliA Ro52 and 18 months for EliA Ro60.
On-board stability:
The on-board stability EliA Ro52 and EliA Ro60 carriers (containing the antigen coated wells) was tested over 8 weeks using 3 positive and 2 negative samples only on the Phadia 250 instrument. As the storage conditions in the E-module of the Phadia 2500 and Phadia 5000 series are similar to the Phadia 250, the results can also be used for stability claims for these instruments. The on-board stability for the Phadia 250 was determined to be 28 days at 2-8°C.
Open Stability:
Stability after first opening of the foil bag containing the EliA Ro52 and EliA Ro60 wells was tested with a real-time study. According to the accelerated stability study, a shelf-life of 9 months at 2-8°C after first opening can be assigned to EliA Ro52 and EliA Ro60 wells.
d) Detection Limit:
Four blank and four low level samples were measured with two different reagent sets (two lots of antigen wells). The four blank samples were created from depleted IgG sera, each diluted with EliA Sample Diluent. The blank samples and the low-
19
level samples were assayed in three runs using two different sets of EliA Ro52 and EliA Ro60 Well lots over three different days on a Phadia 250 and Phadia 2500E each in 5-fold determination. For each instrument type, the total number of combined observations for blank and low-level samples is 120 (60 per reagent set, 15 per sample and reagent set).
The results are summarized in the tables below.
EliA Ro52:
| Instrument | LoB | LoD | LoQ |
|---|---|---|---|
| EliA U/mL | EliA U/mL | EliA U/mL | |
| Phadia 250 | 0.0 | 0.2 | 0.6 |
| E-module of the Phadia 2500 and | |||
| Phadia 5000 series | 0.1 | 0.3 | 0.7 |
The LoD for EliA Ro52 is 0.3 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 (B) less than 5%; based on 240 determinations with 120 blank and 120 low-level replicates per instrument type; and LoB of 0.1 EliA U/mL.
A harmonized LoB of 0.1 EliA U/mL, LoD of 0.3 EliA U/mL, and LoQ of 0.7 EliA U/mL for the immunoassay was used.
EliA Ro60:
| Instrument | LoB
EliA U/mL | LoD
EliA U/mL | LoQ
EliA U/mL |
|-------------------------------------------------------|------------------|------------------|------------------|
| Phadia 250 | 0.1 | 0.2 | 0.4 |
| E-module of the Phadia 2500 and
Phadia 5000 series | 0.1 | 0.2 | 0.5 |
The LoD for EliA Ro60 is 0.4 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 (ß) less than 5%; based on 240 determinations with 120 blank and 120 low-level replicates per instrument type; and LoB of 0.1 EliA U/mL.
As the LoB, LoD and LoQ were harmonized over both instrument types, the LoB was set to 0.1 EliA U/mL, the LoD to 0.2 EliA U/mL, and the LoQ to 0.5 EliA U/mL. The DfU states our current worldwide harmonized LoD of 0.4 EliA U/mL for both instrument types as the lower limit of the measuring range.
20
e) Analytical specificity:
Endogenous and Exogenous Interference:
A study was run to investigate whether high concentrations of potentially interfering substances in serum, like bilirubin, hemoglobin, lipemic factor, rheumatoid factor, human IgG, Ibuprofen, Losartan, Hydroxychloroquine, Azathioprine, Prednisone, Rituximab, Infliximab, Diltiazem and Omeprazole adversely affect the results of the new device.
Three serum samples (one negative sample, one sample with a concentration within the equivocal range, and one high positive sample) were spiked with the different interfering substances or blank solution. The samples were tested in triplicates. A calibration curve was run in duplicate. The runs were repeated twice. One batch of EliA antigen wells and one batch of system reagents were used throughout the studies.
The ratio of blank/spiked sample ranged from 0.90 – 1.10 for EliA Ro52 and EliA Ro60. No interference was observed up to the concentrations listed in the table below:
| Potential Interfering | Concentration in |
|---|---|
| Compound | undiluted sample |
| Bilirubin F | 40 mg/dL |
| Bilirubin C | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Lipemic factor | 2000 mg/dL |
| Rheumatoid factor | 500 IU/mL |
| Human IgG | 3500 mg/dL |
| Ibuprofen | 21.9 mg/dL |
| Losartan | 1.14 mg/dL |
| Hydroxychloroquine | 0.23 mg/dL |
| Azathioprine | 0.26 mg/dL |
| Prednisone | 0.01 mg/dL |
| Rituximab | 109 mg/dL |
| Infliximab | 26.4 mg/dL |
| Omeprazole | 0.84 mg/dL |
| Diltiazem | 0.09 mg/dL |
Reference Sera:
The panel of CDC ANA human reference sera #1 - #12 was tested with EliA Ro52 and EliA Ro60.
Confidential Page 15 (26)
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In the EliA Ro52 test, CDC ANA #2 (speckled pattern in FANA), CDC ANA #7 (SS-A/Ro) and CDC ANA #10 (Jo-1) showed positive results with 13.9 EliA U/mL, 19.5 EliA U/mL and 247.4 EliA U/mL, respectively. CDC ANA #3 (RNP-Sm, SS-A/Ro, SS-B/La) showed an equivocal result with 7.4 EliA U/mL. All other CDC ANA samples remained negative.
In the EliA Ro60 test, CDC ANA #2 (speckled pattern in FANA), CDC ANA #3 (RNP-Sm, SS-A/Ro, SS-B/La), and CDC ANA #7 (SS-A/Ro) showed positive results with 143.0 EliA U/mL, 146.2 EliA U/mL and 207.2 EliA U/mL, respectively. All other CDC ANA samples remained negative.
f) Assay Cut-Off:
EliA Ro52:
To define the cut-off, a study was performed using a cohort consisting of 69 apparently healthy blood donors, 19 samples from SLE patients and 9 samples from Sjögren's syndrome (SS) patients. The samples were measured on a Phadia 250 instrument.
The cut-off value of EliA Ro52 that was initially set with the intended use target diseases SLE and SS could be verified for the additional intended use groups using 10 IIM and 14 SSc patient sera.
EliA Ro60:
To define the cut-off, a study was performed using a cohort consisting of 70 apparently healthy blood donors, 22 samples from SLE patients and 6 samples from Sjögren's syndrome patients. The samples were measured on a Phadia 250 instrument
The cut-off was set as follows for EliA Ro52 and EliA Ro60:
| 10 EliA U/mL | Positive |
In case of equivocal results, it is recommended to retest the patient after 8-12 weeks.
2. Comparison Studies:
- a) Method Comparison with Predicate Device:
A total of 208 patient serum samples with concentrations covering the measuring range were tested with EliA Ro52, EliA Ro60 and QUANTA Flash Ro52 and QUANTA Flash Ro60 assays. Observed concentrations of samples outside the measuring intervals of the EliA and/or QUANTA Flash tests were disregarded in the agreement calculations.
22
The tests were run in single determination and evaluated according to their Directions for Use. The results are summarized in the tables below:
| n = 181 | QUANTA Flash Ro52
positive: ≥ 20 CU | QUANTA Flash Ro52
negative: 10 EliA U/mL | 42 | 2 | 44 |
| EliA Ro52
negative: 7 EliA U/mL | 48 | 12 | 60 |
| EliA Ro52
negative: 10 EliA U/mL | 62 | 3 | 65 |
| EliA Ro60 negative: 7 EliA U/mL | 64 | 7 | 71 |
| EliA Ro60
negative: Results of clinically defined samples. IIM samples represented the "target disease", SLE, SS, and SSc samples were excluded, other autoimmune diseases and infectious diseases were used as "control disease". Equivocal results were either judged as negative or positive.
| Equivocal = negative | |||
|---|---|---|---|
| Result | IIM | Controls | Total |
| Positive | 34 | 12 | 46 |
| Negative | 60 | 378 | 438 |
| Total | 94 | 390 | 484 |
| Equivocal = positive | |||
|---|---|---|---|
| Result | IIM | Controls | Total |
| Positive | 35 | 17 | 52 |
| Negative | 59 | 373 | 432 |
| Total | 94 | 390 | 484 |
| Value | 95% CI | |
|---|---|---|
| Sensitivity | 36.2% | 26.5 - 46.7 |
| Specificity | 96.9% | 94.7 - 98.4 |
| Value | 95% CI | |
|---|---|---|
| Sensitivity | 37.2% | 27.5 - 47.8 |
| Specificity | 95.6% | 93.1 - 97.4 |
Results of clinically defined samples. SSc samples represented the "target disease", SLE, SS and IIM samples were excluded, other autoimmune diseases and infectious diseases were used as "control disease". Equivocal results were either judged as negative or positive.
| Equivocal = negative | |||
|---|---|---|---|
| CC | C | A | T |
| Result | SSC | Controls | Total |
|---|---|---|---|
| Positive | 19 | 12 | 31 |
| Negative | 72 | 378 | 450 |
| Total | 91 | 390 | 481 |
| Equivocal = positive | |
|---|---|
| -- | ---------------------- |
| Result | SSc | Controls | Total |
|---|---|---|---|
| Positive | 24 | 17 | 41 |
| Negative | 67 | 373 | 440 |
| Total | 91 | 390 | 481 |
| Value | 95% CI | |
|---|---|---|
| Sensitivity | 20.9% | 13.1 - 30.7 |
| Specificity | 96.9% | 94.7 - 98.4 |
| Value | 95% CI | |
|---|---|---|
| Sensitivity | 26.4% | 17.7 - 36.7 |
| Specificity | 95.6% | 93.1 - 97.4 |
The table below shows the results for each clinical subgroup:
26
SCIENTIF
Traditional 510(k) for EliA Ro52 and EliA Ro60, Amendment to K210902 A.7 510(k) Decision Summary_V4
| Diagnosis | total
n | Positive
n | Equivocal
n | Negative
n |
|--------------------------------------------------|------------|---------------|----------------|---------------|
| Systemic lupus erythematosus | 120 | 57 | 4 | 59 |
| Primary Sjögren's syndrome | 60 | 30 | 3 | 27 |
| Idiopathic inflammatory myopathies (IIM) [total] | 94 | 34 | 1 | 59 |
| IIM PM | 40 | 7 | 0 | 33 |
| IIM DM | 13 | 3 | 1 | 9 |
| IIM Myositis/CTD-overlap | 18 | 3 | 0 | 15 |
| IIM Overlap / MCTD | 9 | 9 | 0 | 0 |
| IIM Jo-1 Positive | 10 | 9 | 0 | 1 |
| IIM Sporadic inclusion body myositis (sIBM) | 4 | 3 | 0 | 1 |
| Systemic sclerosis (SSc) [total] | 91 | 19 | 5 | 67 |
| SSc, diffuse | 56 | 11 | 3 | 42 |
| SSc, limited | 27 | 8 | 2 | 17 |
| SSc, various* | 8 | 0 | 0 | 8 |
| Celiac disease | 13 | 0 | 0 | 13 |
| Crohn's disease | 12 | 0 | 0 | 12 |
| CTD overlap Non-MCTD | 10 | 0 | 1 | 9 |
| Graves' disease | 12 | 0 | 0 | 12 |
| Primary antiphospholipid syndrome | 12 | 1 | 0 | 11 |
| Primary Biliary Cholangitis | 25 | 1 | 2 | 22 |
| Primary Sclerosing Cholangitis | 24 | 0 | 0 | 24 |
| Type 1 Diabetes | 12 | 0 | 0 | 12 |
| Diagnosis | total
n | Positive
n | Equivocal
n | Negative
n |
| Ulcerative colitis | 35 | 0 | 1 | 34 |
| Lymphoma | 21 | 0 | 0 | 21 |
| Leukemia | 20 | 0 | 0 | 20 |
| Varied Cancer | 9 | 0 | 0 | 9 |
| Mixed connective tissue disease | 10 | 2 | 0 | 8 |
| Rheumatoid arthritis | 35 | 2 | 0 | 33 |
| Bacterial infections [total] | 17 | 1 | 0 | 16 |
| Bacterial infections (Mycoplasma) | 3 | 0 | 0 | 3 |
| Bacterial infections (Borrelia) | 7 | 0 | 0 | 7 |
| Bacterial infections (var. Staphylococcus) | 3 | 1 | 0 | 2 |
| Bacterial infections (various) | 4 | 0 | 0 | 4 |
| Viral infections [total] | 80 | 4 | 1 | 75 |
| Viral infections (Dengue) | 4 | 0 | 0 | 4 |
| Viral infections (EBV) | 3 | 0 | 0 | 3 |
| Viral infections (HBV) | 11 | 1 | 0 | 10 |
| Viral infections (HCV) | 31 | 2 | 1 | 28 |
| Viral infections (HIV) | 24 | 1 | 0 | 23 |
| Viral infections (various) | 7 | 0 | 0 | 7 |
| Hashimoto's disease | 10 | 1 | 0 | 9 |
| Vasculitis [total] | 33 | 0 | 0 | 33 |
| Granulomatosis with Polyangiitis | 10 | 0 | 0 | 10 |
| Eosinophilic granulomatosis with
polyangiitis | 4 | 0 | 0 | 4 |
| Microscopic polyangiitis | 13 | 0 | 0 | 13 |
| Polyarteritis nodosa | 3 | 0 | 0 | 3 |
| Giant cell arteritis | 3 | 0 | 0 | 3 |
| Target diseases | 365 | 140 | 13 | 212 |
| Control disease | 390 | 12 | 5 | 373 |
| Total | 755 | 152 | 18 | 585 |
27
*"SSc various" group is composed of the patients having SSc, classified according to the ACR/EULAR van den Hoogen 2013 criterion. The patients were not further sub-grouped.
28
EliA Ro60:
In total, 713 clinically and ethnically defined serum samples, including those of US origin, were used to determine sensitivity and specificity of the assay. Samples with a diagnosis of systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) represent the diagnostic group (target diseases: SLE n=120 + Sjögren's syndrome n=60). Samples with various autoimmune and infectious disease diagnoses represent the disease control group (n=533). The results are summarized in the tables below.
Results of clinically defined samples. SLE samples represented the "target disease" Sjögren's syndrome samples were excluded, other autoimmune diseases and infectious diseases were used as "control disease", but without control group SSc since these patients may have Ro antibodies. Equivocal results were either judged as negative or positive.
| Equivocal = negative |
|---|
| Result | SLE | Controls | Total |
|---|---|---|---|
| Positive | 58 | 6 | 64 |
| Negative | 62 | 436 | 498 |
| Total | 120 | 442 | 562 |
| Value | 95% CI | |
|---|---|---|
| Sensitivity | 48.3% | 39.1 - 57.6 |
| Specificity | 98.6% | 97.1 - 99.5 |
| Equivocal = positive | |||
|---|---|---|---|
| Result | SLE | Controls | Total |
| Positive | 61 | 7 | 68 |
| Negative | 59 | 435 | 494 |
| Total | 120 | 442 | 562 |
Larring onl - mostition
| Value | 95% CI | |
|---|---|---|
| Sensitivity | 50.8% | 41.6 - 60.1 |
| Specificity | 98.4% | 96.8 - 99.4 |
Results of clinically defined samples. Sjögren's syndrome samples represented the "target disease", SLE samples were excluded, other autoimmune diseases and infectious diseases were used as "control disease", but without control group SSc since these patients may have Ro antibodies. Equivocal results were either judged as negative or positive.
| Equivocal = negative | |||
|---|---|---|---|
| Result | SS | Controls | Total |
| Positive | 41 | 6 | 47 |
| Negative | 19 | 436 | 455 |
| Total | 60 | 442 | 502 |
| Value | 95% CI | |
|---|---|---|
| Sensitivity | 68.3% | 55 - 79.7 |
| Specificity | 98.6% | 97.1 - 99.5 |
| Equivocal = positive | |||||
|---|---|---|---|---|---|
| Result | ટેટ | Controls | Total | ||
| Positive | 43 | રે રેણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં મુખ્યત્વે ખેત-ઉપયોગ વિદ્યારત તેમ જ દૂધની ડેર | |||
| Negative | 17 | 435 | 452 | ||
| Total | 60 | 442 | 502 |
| Value | 95% CI | |
|---|---|---|
| Sensitivity | 71.7% | 58.6 - 82.5 |
| Specificity | 98.4% | 96.8 - 99.4 |
29
I E N
Traditional 510(k) for EliA Ro52 and EliA Ro60, Amendment to K210902 A.7 510(k) Decision Summary_V4
| Diagnosis | total n | positive n | equivocal n | negative n |
|---|---|---|---|---|
| Systemic lupus erythematosus (SLE) | 120 | 58 | 3 | 59 |
| Sjögren's syndrome (SS) | 60 | 41 | 2 | 17 |
| Idiopathic inflammatory myopathies (IIM) | 10 | 0 | 0 | 10 |
| Systemic sclerosis (SSc) [total] | 91 | 21 | 0 | 70 |
| SSc, diffuse | 56 | 11 | 0 | 45 |
| SSc, limited | 27 | 10 | 0 | 17 |
| SSc, various* | 8 | 0 | 0 | 8 |
| Celiac disease | 13 | 0 | 0 | 13 |
| Crohn's disease | 12 | 0 | 0 | 12 |
| CTD overlap Non-MCTD | 10 | 1 | 0 | 9 |
| Graves' disease | 12 | 0 | 0 | 12 |
| Primary antiphospholipid syndrome | 12 | 1 | 0 | 11 |
| Primary Biliary Cholangitis | 25 | 0 | 0 | 25 |
| Primary Sclerosing Cholangitis | 24 | 0 | 0 | 24 |
| Type 1 Diabetes | 12 | 0 | 0 | 12 |
| Ulcerative colitis | 35 | 1 | 0 | 34 |
| Lymphoma | 21 | 0 | 0 | 21 |
| Leukemia | 20 | 0 | 0 | 20 |
| Varied Cancer | 9 | 0 | 0 | 9 |
| Mixed connective tissue disease | 10 | 0 | 0 | 10 |
| Rheumatoid arthritis | 77 | 1 | 1 | 75 |
| Bacterial infections [total] | 17 | 0 | 0 | 17 |
| Bacterial infections (Mycoplasma) | 3 | 0 | 0 | 3 |
| Bacterial infections (Borrelia) | 7 | 0 | 0 | 7 |
| Bacterial infections (var. Staphylococcus) | 3 | 0 | 0 | 3 |
| Bacterial infections (various) | 4 | 0 | 0 | 4 |
| Viral infections [total] | 80 | 1 | 0 | 79 |
| Viral infections (Dengue) | 4 | 0 | 0 | 4 |
| Viral infections (EBV) | 3 | 0 | 0 | 3 |
| Viral infections (HBV) | 11 | 0 | 0 | 11 |
| Viral infections (HCV) | 31 | 1 | 0 | 30 |
| Viral infections (HIV) | 24 | 0 | 0 | 24 |
| Viral infections (various) | 7 | 0 | 0 | 7 |
| Diagnosis | total | |||
| n | positive | |||
| n | equivocal | |||
| n | negative | |||
| n | ||||
| Hashimoto's disease | 10 | 1 | 0 | 9 |
| Vasculitis [total] | 33 | 0 | 0 | 33 |
| Granulomatosis with Polyangiitis | 10 | 0 | 0 | 10 |
| Eosinophilic granulomatosis with | ||||
| polyangiitis | 4 | 0 | 0 | 4 |
| Microscopic polyangiitis | 13 | 0 | 0 | 13 |
| Polyarteritis nodosa | 3 | 0 | 0 | 3 |
| Giant cell arteritis | 3 | 0 | 0 | 3 |
| Target diseases | 180 | 99 | 5 | 76 |
| Control disease | 533 | 27 | 1 | 505 |
| Total | 713 | 126 | 6 | 581 |
The table below shows the results for each clinical subgroup:
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*"SSc various" group is composed of the patients having SSc, classified according to the ACR/EULAR van den Hoogen 2013 criterion. The patients were not further sub-grouped.
d) Other Clinical Supportive Data:
Not applicable.
Clinical Cut-Off: Same as assay cut-off.
Expected Values/Reference Range:
Antibody prevalence in autoimmune patients varies widely depending on disease area. The proportion of sera from a normal population found positive for the antinuclear antibodies covered by the EliA Ro52 and EliA Ro60 test is below 1%. Expected values may vary depending on the population tested.
The frequency distribution for antinuclear antibodies was investigated in a group of apparently healthy subjects equally distributed by age and gender, using sera from Caucasian, African American, Hispanic and Asian population obtained from a blood bank.
The results are given in the table below:
| Test | n | Median
EliA U/mL | 95th percentile
EliA U/mL | 99th percentile
EliA U/mL |
|-----------|-----|---------------------|------------------------------|------------------------------|
| Elia Ro52 | 638 | 1.0 | 1.8 | 2.6 |
| Elia Ro60 | 638 | 0.5 | 0.9 | 7.4 |
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Proposed Labeling
The labeling is drafted in accordance with the requirements of 21 CFR Part 809.10.
Conclusion
All available data support that both immunoassays, the new devices EliA Ro52 and EliA Ro60 and their proposed predicate devices QUANTA Flash Ro52 and QUANTA Flash Ro60 perform substantially equivalent.
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.