(90 days)
No
The summary describes a standard in vitro diagnostic immunoassay system and reagents, with no mention of AI or ML in the intended use, device description, or performance studies. The focus is on the chemical and biological components and the automated instrument for performing the assays.
No
This device is for in vitro diagnostic (IVD) use, specifically for the semi-quantitative measurement of antibodies as an aid in diagnosis. It does not directly treat or alleviate a disease, which is the function of a therapeutic device.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the in vitro semi-quantitative measurement of IgG antibodies... as an aid in the clinical diagnosis of scleroderma (CREST Syndrome)" and "as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings." This directly indicates its use in aiding diagnosis.
No
The device description clearly outlines physical components such as test wells, sample diluent, and IgG reagents, which are tangible materials used in the in vitro diagnostic process. It also mentions the use of the Phadia EliA Immunodiagnostic System, an automated instrument, indicating hardware is involved.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the devices are "intended for the in vitro semi-quantitative measurement of IgG antibodies..." This clearly indicates that the tests are performed outside of the body using biological samples (serum and plasma).
- Device Description: The description details reagents and components used to perform laboratory tests on patient samples.
- Performance Studies: The document describes analytical and method comparison studies, which are typical for IVD devices to demonstrate their performance characteristics.
- Predicate Devices: The mention of predicate devices with K numbers (K082759 and K083117) indicates that these devices have gone through the FDA's premarket notification (510(k)) process, which is required for many IVD devices.
- Intended User / Care Setting: The statement "For prescription use only. This device is not for point-of-care use" further supports that this is a laboratory-based diagnostic test.
N/A
Intended Use / Indications for Use
EliA CENP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to CENP in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (CREST Syndrome) in conjunction with other laboratory and clinical findings. EliA CENP uses the EliA IgG method on the instrument Phadia 2500/5000.
EliA U1RNP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to U1RNP in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA U1RNP uses the EliA IgG method on the instrument Phadia 2500/5000.
EliA RNP70 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to RNP70 in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA RNP70 uses the EliA IgG method on the instrument Phadia 2500/5000.
Product codes (comma separated list FDA assigned to the subject device)
LJM, LKO
Device Description
The method-specific reagents are identical with K082759 (EliA CENP and EliA U1RNP) and K083117 (EliA RNP70), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:
Test Wells:
- EliA CENP Wells are coated with human recombinant centromere protein B 2 carriers (12 wells each), ready to use;
- -EliA U1RNP Wells are coated with human recombinant RNP (RNP70, A. C) proteins- 4 carriers (12 wells each), ready to use;
- -EliA RNP70 Wells are coated with human recombinant RNP (70 kDa) protein-4 carriers (12 wells each), ready to use;
EliA Sample Diluent:
- -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 reagents:
- EliA IgG Coniugate 50 or 200: ß-Galactosidase labeled anti-laG (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.
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 are required to carry out EliA CENP, EliA U1RNP and EliA RNP70 tests.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use
Not for point-of-care use.
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)
Analytical Performance:
-
Precision/Reproducibility: A study was performed with 3 instruments over 7 days (1 run/day), testing each sample in 4 replicates/run, yielding 84 replicates per sample. The data was calculated against the calibration curve from Day 1. The results are summarized in tables for EliA CENP, EliA U1RNP, and EliA RNP70 on Phadia 2500/5000, showing Within-Run, Between-Run, Between-Instrument, and Total Imprecision (SD and %CV) for various mean EliA U/mL concentrations.
-
Linearity/Assay Reportable Range: Four patient serum samples were diluted and tested. Regression analysis results for EliA CENP, EliA U1RNP, and EliA RNP70 on Phadia 2500/5000 are provided, showing Slope, 95% CI for Slope, Intercept, 95% CI for Intercept, and R2 for various dilution ranges. The reportable range (LoD to upper limit) and measuring range (LoQ to upper limit) are stated for each assay (EliA CENP: 0.4 to 240 EliA U/mL and 0.7 to 240 EliA U/mL respectively; EliA U1RNP: 0.5 to 240 EliA U/mL and 1.1 to 240 EliA U/mL respectively; EliA RNP70: 0.3 to 240 EliA U/mL and 0.9 to 240 EliA U/mL respectively).
-
Detection Limit: LoB, LoD, and LoQ were determined on the Phadia 2500/5000 instrument. LoB and LoD studies used one blank sample and three low-level samples measured in thirty-three and eleven replicates respectively, in two runs (total 132 determinations with 66 blank and 66 low level replicates for LoD). LoQ was based on 66 determinations with a target uncertainty goal of 20%. Specific values are reported for each assay.
-
Analytical Specificity: Interference was previously reviewed in K082759 and K083117. Carry-over is impossible due to disposable tips for samples and a separate pipette for conjugate.
-
Assay Cut-off: Ranges (negative, equivocal, positive) derived from clinical studies (K082759 and K083117) are provided for EliA CENP (10 EliA U/mL), EliA U1RNP (10 EliA U/mL), and EliA RNP70 (10 EliA U/mL).
Instrument Comparison:
- More than 100 samples (≥20% within ±25% of medical decision point) were run in single replicates on one Phadia 250 and three Phadia 2500/5000 instruments. Acceptance criteria for method comparison (slope 0.9-1.1, intercept close to 0) were met.
- EliA CENP: Tables show Intercept, 95% CI, Slope, and 95% CI for each Phadia 2500/5000 instrument (A, B, C) compared to Phadia 250. PPA (Positive Percent Agreement), NPA (Negative Percent Agreement), and TPA (Total Percent Agreement) with 95% CI are provided for equivocal results considered positive and equivocal results considered negative.
- EliA U1RNP: Similar tables are provided for EliA U1RNP.
- EliA RNP70: Similar tables are provided for EliA RNP70.
Clinical Studies:
- Clinical sensitivity: Not applicable.
- Clinical specificity: Not applicable.
- Other clinical supportive data: Clinical performance values were reviewed in K082759 and K083117.
Clinical Cut-off: Same as assay cut-off.
Expected Values/Reference Range:
- Frequency distribution for CENP, U1RNP, and RNP70 antibodies investigated in 400 apparently healthy Caucasian subjects (equal age/gender distribution). Median, 95th, and 99th percentile EliA U/mL values are provided for each assay.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
PPA, NPA, TPA. Specific values for each assay and instrument are provided in the "Summary of Performance Studies" section.
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.
EliA CENP on Phadia 250 instrument, K082759, EliA U1RNP on Phadia 250 instrument, K082759, EliA RNP70 on Phadia 250 instrument, K083117
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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 contains 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 is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 27, 2018
Phadia AB Sheryl Skinner Associate Director Phadia US Inc. 4169 Commercial Avenue Portage, Michigan 49002
Re: K182353
Trade/Device Name: EliA CENP Immunoassay EliA U1RNP Immunoassay EliA RNP70 Immunoassay Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LJM, LKO Dated: August 28, 2018 Received: August 29, 2018
Dear Sheryl Skinner:
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.
1
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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 531-542 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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Leonthena R. Carrington -S
Lea Carrington 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) K182353
Device Name
EliA(TM) CENP Immunoassay, EliA(TM) U1RNP Immunoassay, EliA(TM) RNP70 Immunoassay
Indications for Use (Describe)
EliA CENP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to CENP in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (CREST Syndrome) in conjunction with other laboratory and clinical findings. EliA IgG method on the instrument Phadia 2500/5000.
EliA U1RNP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to U1RNP in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA U1RNP uses the EliA IgG method on the instrument Phadia 2500/5000.
EliA RNP70 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to RNP70 in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA RNP70 uses the EliA IgG method on the instrument Phadia 2500/5000.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
A.6 510(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:
B. Purpose for Submission:
Adding previously cleared assays on a new instrument platform (Phadia® 2500/5000)
C. Measurands:
CENP, U1RNP and RNP70 anti-nuclear antibodies
D. Type of Test:
Semi-quantitative measurement immunoassays
E. Applicant:
Phadia AB Rapsgatan 7P P.O. Box 6460 SE-751 37 Uppsala, Sweden Tel: +46-18-16 50 60
510(k) Contact Person: Martin Mann Regulatory Affairs Manager Phadia US Inc. 4169 Commercial Avenue Portage, Mi 49002, USA +1 (-269-492) -1957 (Phone) +1 (-269-492) -7541 (Fax) martin.mann@thermofisher.com
Date of Summary Preparation:
November 5, 2018
F. Proprietary and Established Names:
EliA CENP Immunoassay EliA U1RNP Immunoassay EliA RNP70 Immunoassay
4
G. Regulatory Information:
-
- Regulation section: 21 CFR§ 866.5100, Antinuclear Antibody Immunological Test System
-
- Classification: Class II
Product code: ဒေ
LJM Antinuclear antibody (enzyme-labeled), antigen, controls LKO Anti-RNP antibody, antigen and control
-
- Panel: Immunology (82)
H. Intended use(s):
- Intended use(s):
EliA CENP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to CENP in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (CREST Syndrome) in conjunction with other laboratory and clinical findings. EliA CENP uses the EliA IgG method on the instrument Phadia 2500/5000.
EliA U1RNP is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to U1RNP in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA U1RNP uses the EliA IgG method on the instrument Phadia 2500/5000.
EliA RNP70 is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to RNP70 in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA RNP70 uses the EliA IgG method on the instrument Phadia 2500/5000.
- Indication(s) for use: Same as intended use
Special conditions for use statement(s): 3. 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.
5
-Device Description:
The method-specific reagents are identical with K082759 (EliA CENP and EliA U1RNP) and K083117 (EliA RNP70), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of: Test Wells:
- EliA CENP Wells are coated with human recombinant centromere protein B 2 carriers (12 wells each), ready to use;
- -EliA U1RNP Wells are coated with human recombinant RNP (RNP70, A. C) proteins- 4 carriers (12 wells each), ready to use;
- -EliA RNP70 Wells are coated with human recombinant RNP (70 kDa) protein-4 carriers (12 wells each), ready to use;
EliA Sample Diluent:
-
-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 reagents: -
EliA IgG Coniugate 50 or 200: ß-Galactosidase labeled anti-laG (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.
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 are required to carry out EliA CENP, EliA U1RNP and EliA RNP70 tests.
J. Substantial Equivalence Information:
- Predicate device name(s) and 510(k) number(s): EliA CENP on Phadia 250 instrument, K082759 EliA U1RNP on Phadia 250 instrument, K082759 EliA RNP70 on Phadia 250 instrument, K083117
6
2. Comparison with predicate device:
EliA CENP, EliA U1RNP and EliA RNP70 Immunoassays on Phadia 250 and Phadia 2500/5000 instruments – Similarities to predicate devices
| Feature | Predicate Device
Phadia 250 | New Device
Phadia 2500/5000 |
|--------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use
EliA CENP | EliA CENP is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to CENP in human serum
and plasma (heparin, EDTA,
citrate) as an aid in the clinical
diagnosis of scleroderma (CREST
Syndrome) in conjunction with
other laboratory and clinical
findings. EliA CENP uses the EliA
IgG method on the instrument
ImmunoCAP 250. | EliA CENP is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to CENP in human
serum and plasma (Li-heparin,
EDTA) as an aid in the clinical
diagnosis of scleroderma
(CREST Syndrome) in
conjunction with other laboratory
and clinical findings. EliA CENP
uses the EliA IgG method on the
instrument Phadia 2500/5000. |
| Intended Use
EliA U1RNP | EliA U1RNP is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to U1RNP in human
serum and plasma (heparin,
EDTA, citrate) as an aid in the
clinical diagnosis of mixed
connective tissue disease (MCTD)
and systemic lupus
erythematosus (SLE) in
conjunction with other laboratory
and clinical findings. EliA U1RNP
uses the EliA IgG method on the
instrument ImmunoCAP 250. | EliA U1RNP is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to U1RNP in human
serum and plasma (Li-heparin,
EDTA) as an aid in the clinical
diagnosis of mixed connective
tissue disease (MCTD) and
systemic lupus erythematosus
(SLE) in conjunction with other
laboratory and clinical findings.
EliA U1RNP uses the EliA IgG
method on the instrument
Phadia 2500/5000. |
| Intended Use
EliA RNP70 | EliA RNP70 is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to RNP70 in human
serum and plasma (heparin,
EDTA) as an aid in the clinical
diagnosis of mixed connective
tissue disease (MCTD) and
systemic lupus erythematosus
(SLE) in conjunction with other
laboratory and clinical findings.
EliA RNP70 is to be used together
with the EliA IgG method on the
instrument ImmunoCAP 250 | EliA RNP70 is intended for the in
vitro semi-quantitative
measurement of IgG antibodies
directed to RNP70 in human
serum and plasma (Li-heparin,
EDTA) as an aid in the clinical
diagnosis of mixed connective
tissue disease (MCTD) and
systemic lupus erythematosus
(SLE) in conjunction with other
laboratory and clinical findings.
EliA RNP70 uses the EliA IgG
method on the instrument
Phadia 2500/5000 |
| Analytical | Same | Same |
| technology: | | |
| Immuno- | | |
| fluorescence | | |
| measurement | | |
| Assay process | Same | Same |
| Common,
dedicated Phadia | Same | Same
Introduction of new article |
| reagents | | numbers for Development
Solution, Stop Solution and |
| | | Washing Solution is only due to
larger filling volumes which are |
| | | required for the bigger
instruments Phadia 2500/5000 |
| Result calculation | Same | Same |
| software; Phadia | | |
| Information Data | | |
| Manager (IDM) | | |
| Sample volume | 90 µL (20 µL of non-diluted
sample) | 90 µL (20 µL of non-diluted
sample) |
| Incubation
temperature | 37°C | 37°C |
| Conjugate volume | 90 µL | 90 µL |
| Development | 90 µL | 90 µL |
| Solution Volume | | |
| Stop Solution
Volume | 200 µL | 200 µL |
| Assay set-up | Random access | Random access |
| Reagent
packaging size | Various/Common | Various/Common
Introduction of new article |
| | | number for EliA Sample Diluent |
| | | (83-1071-01) is only due to
larger filling volume. |
| Onboard storage | Yes | Yes |
| of reagents | | |
| | | |
| Feature | Predicate Device
Phadia 250 | New Device
Phadia 2500/5000 |
| Sample matrix;
Serum or plasma
type as indicated in
the DFU dependent
on assay | Human serum or plasma
(heparin, EDTA, citrate) | Human serum or plasma (Li-
heparin, EDTA); i.e. citrate
plasma is omitted for all tests |
| Daily throughput | ~250 tests | ~2500/5000 tests |
| Sample Dilution | Phadia 250 uses a steel pipette
to dilute the samples in Dilution
Plates (Art.No. 12-3907-08) | Phadia 2500/5000 uses
disposable Pipette Tips in Racks
(Art No. 12-3805-04) for
pipetting samples in Dilution
Well (Art.No. 12-4005-69) |
| Risk for carry-over | The warning “DO NOT REUSE”
in the Phadia 250 DFU for EliA
Conjugates is due to the fact that
a low risk of conjugate
contamination by carry-over from
samples was identified. In order
to reduce the risk, the single use
statement for the conjugate was
included in the Phadia 250 DFU. | When running EliA tests on the
Phadia 2500/5000 instruments,
there is no need for this warning
statement because these
instruments use disposable tips
for pipetting samples and a
separate pipette for the
conjugate, and carry-over from
samples to conjugate is
impossible. |
| Loading of EliA
Carriers | EliA carriers are loaded manually
on the Loading Tray from where
they can be processed directly or
transferred to the cooled storage
compartment. | The Phadia 2500/5000
instruments do not have such a
Loading Tray. The EliA carriers
are loaded into racks which are
directly transferred to the cooled
storage compartment |
| Barcode reader | The Phadia 250 instrument has
a built-in barcode reader at the
front of the instrument, but the
operator needs to scan the
barcodes manually by showing
the reagents to the barcode
reader. Alternatively, the
operator can also enter the
characters below the barcode
manually. | The Phadia 2500/5000
instruments dispose of a built-in
barcode reader, and the
reagents are on a moving belt
which conveys them past the
barcode reader. The lot-specific
information will be read
automatically by the instrument
during loading. |
| Process time / Time
to patient result | Phadia 250 needs 1 minute to
process one Well.
Phadia 250 provides the results
at a one minute interval. | Phadia 2500/5000 instruments
process two Wells in parallel in
48 seconds.
Phadia 2500/5000 provides the
results at a 24 seconds interval. |
7
8
EliA CENP, EliA U1RNP and EliA RNP70 Immunoassays on Phadia 250 and Phadia 2500/5000 instruments – Differences to predicate device
9
K. Standard/Guidance Document Referenced (if applicable):
CLSI EP05-A3; Evaluation of Precision Performance of Quantitative Measurement Methods: September 2014 CLSI EP06-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: April 2003 CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantification; October 2004.
CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples
L. Test Principle:
The EliA wells are molded cups comparable to excised wells from a microtiter plate. They are made of polystyrene and are coated with the respective antigen. The wells are at the same time a holder of the coupled antigen for convenient automation and a reaction chamber with reaction/washing solution handling based on pipetting to add and aspiration to remove liquids.
The EliA wells are coated with human recombinant centromere protein B, human recombinant RNP (RNP70, A, C) or with human recombinant RNP (70 kDa) protein. If present in the patient's specimen, antibodies to these proteins bind to the specific antigen. After washing away non-bound antibodies, enzyme-labeled antibodies against human IgG antibodies (EliA IgG Conjugate) are added to form an antibodyconjugate 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 assay directly measures the amount of antibody of interest bound to the antigen coating the EliA well, therefore the higher the value of fluorescent signal detected by the instrument, the higher the amount of antibody bound and detected in the sample tested. To evaluate test results, the response for patient samples is compared directly to the response for calibrators.
M. Performance Characteristics (if/when applicable):
- 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.
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The results are summarized in the table below:
| Mean | Within-Run | | Between-
Run | | Between-
Instrument | | Total
Imprecision | |
|----------------|------------|-----|-----------------|-----|------------------------|------|----------------------|------|
| (EliA
U/mL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1.1 | 0.1 | 9.9 | 0.1 | 6.1 | 0.2 | 15.8 | 0.2 | 19.6 |
| 7.1 | 0.4 | 5.8 | 0.3 | 4.9 | 0.3 | 3.9 | 0.6 | 8.6 |
| 11.4 | 0.4 | 3.5 | 0.4 | 3.9 | 0.5 | 4.2 | 0.8 | 6.7 |
| 129.8 | 4.3 | 3.3 | 5.1 | 3.9 | 3.9 | 3.0 | 7.7 | 6.0 |
| 229.7 | 9.8 | 4.3 | 15.7 | 6.8 | 10.1 | 4.4 | 21.1 | 9.2 |
EliA CENP on Phadia 2500/5000
EliA U1RNP on Phadia 2500/5000
| Mean
(EliA
U/mL) | Within-Run | | Between-Run | | Between-Instrument | | Total
Imprecision | |
|------------------------|------------|------|-------------|------|--------------------|------|----------------------|------|
| | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 2.2 | 0.4 | 17.9 | 0.3 | 12.5 | 0.2 | 11.0 | 0.5 | 24.4 |
| 5.7 | 0.3 | 5.4 | 0.2 | 2.8 | 0.1 | 1.8 | 0.4 | 6.4 |
| 10.4 | 0.5 | 4.7 | 0.4 | 4.2 | 0.6 | 5.6 | 0.9 | 8.5 |
| 135.4 | 5.2 | 3.8 | 7.2 | 5.3 | 6.5 | 4.8 | 11.0 | 8.1 |
| 231.7 | 9.1 | 3.9 | 9.0 | 3.9 | 10.7 | 4.6 | 16.7 | 7.2 |
EliA RNP70 on Phadia 2500/5000
| Mean
(EliA
U/mL) | Within-Run | | Between-
Run | | Between-
Instrument | | Total
Imprecision | |
|------------------------|------------|-----|-----------------|-----|------------------------|------|----------------------|------|
| | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1.4 | 0.1 | 5.4 | 0.1 | 4.4 | 0.2 | 17.0 | 0.3 | 18.4 |
| 7.9 | 0.2 | 2.9 | 0.3 | 4.4 | 0.5 | 6.2 | 0.6 | 8.1 |
| 8.9 | 0.5 | 5.2 | 0.5 | 5.5 | 0.5 | 5.2 | 0.8 | 9.2 |
| 93.1 | 5.1 | 5.5 | 5.5 | 5.9 | 2.9 | 3.1 | 8.0 | 8.6 |
| 190.2 | 9.4 | 5.0 | 10.3 | 5.4 | 10.6 | 5.6 | 17.5 | 9.2 |
b. Linearity/assay reportable range:
Four patient serum samples were diluted in sample diluent and tested with one batch of EliA CENP, EliA U1RNP and EliA RNP70 Immunoassays and one set of system reagents on Phadia 2500/5000. The results of the regression analysis are summarized below:
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| Dilution range
| (EliA U/mL) | Slope | 95% CI | Intercept | 95% CI | R2 |
|---|---|---|---|---|---|
| 0.5 – 24.3 | 1.00 | 0.99 – 1.01 | 0.17 | 0.02 – 0.31 | 1.00 |
| 2.1 – 180.3 | 1.01 | 0.99 – 1.02 | 0.10 | -0.83 – 1.03 | 1.00 |
| 3.8 – 305.0 | 1.04 | 0.99 – 1.10 | 2.70 | -4.21 – 9.62 | 0.99 |
| 0.4 – 18.8 | 0.99 | 0.97 – 1.02 | -0.22 | -0.44 – -0.00 | 1.00 |
EliA CENP on Phadia 2500/5000
The reportable range (Limit of Detection, upper limit) for EliA CENP is from 0.4 to 240 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 0.7 to 240 EliA U/mL.
EliA U1RNP on Phadia 2500/5000
| Dilution range
| (EliA U/mL) | Slope | 95% CI | Intercept | 95% CI | R2 |
|---|---|---|---|---|---|
| 0.5 – 18.0 | 1.01 | 0.99 - 1.02 | 0.08 | -0.04 - 0.20 | 1.00 |
| 0.6 – 51.3 | 1.01 | 0.99 – 1.02 | 0.04 | -0.20 - 0.27 | 1.00 |
| 0.6 – 15.8 | 1.00 | 0.96 - 1.04 | 0.28 | 0.01 - 0.56 | 1.00 |
| 4.7 – 284.7 | 1.04 | 0.98 - 1.10 | 1.86 | -4.75 - 8.47 | 0.99 |
The reportable range (Limit of Detection, upper limit) for EliA U1RNP is from 0.5 to 240 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 1.1 to 240 EliA U/mL.
| Dilution range
| (EliA U/mL) | Slope | 95% CI | Intercept | 95% CI | R2 |
|---|---|---|---|---|---|
| 0.6 - 62.5 | 1.02 | 1.00 – 1.04 | 0.07 | -0.47 - 0.49 | 1.00 |
| 0.4 - 38.7 | 1.01 | 0.98 – 1.04 | -0.42 | -0.87 - 0.02 | 1.00 |
| 6.9 - 251.8 | 1.00 | 0.97 – 1.03 | 3.07 | 0.05 - 6.09 | 1.00 |
| 3.7 - 294.6 | 1.01 | 0.98 – 1.03 | 3.38 | 0.39 - 6.38 | 1.00 |
EliA RNP70 on Phadia 2500/5000
The reportable range (Limit of Detection, upper limit) for EliA RNP70 is from 0.3 to 240 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 0.9 to 240 EliA U/mL.
Statements included in the package inserts: "Please note that concentration values between LoD and LoQ may show a higher uncertainty." "Please note that due to differing binding characteristics of the antibodies in patient samples, not all sera can be diluted linearly within the measuring range."
- Traceability, Stability, Expected values (controls, calibrators, or methods): C. The EliA IgG method was previously reviewed in K061165.
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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 three low level samples were measured in thirty-three and eleven replicates, respectively, in each of two runs.
EliA CENP:
The LoD for EliA CENP is 0.4 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A and with proportions of false positives (a) less than 5% and false negatives (β) less than 5%; based on 132 determinations with 66 blank and 66 low level replicates; and LoB of 0.2 EliA U/mL.
The LoQ for EliA CENP is 0.7 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A, based on 66 determinations, and a target uncertainty goal of 20%.
The results are summarized in the table below:
| EliA CENP (EliA U/mL) | LoB | LoD | LoQ |
|---|---|---|---|
| Phadia 2500/5000 | 0.2 | 0.4 | 0.7 |
EIiA U1RNP:
The LoD for EliA U1RNP is 0.5 EliA U/mL, determined consistent with the quidelines in CLSI document EP17-A and with proportions of false positives (a) less than 5% and false negatives (β) less than 5%; based on 132 determinations with 66 blank and 66 low level replicates; and LoB of 0.2 EliA U/mL.
The LoQ for EliA U1RNP is 1.1 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A, based on 66 determinations, and a target uncertainty goal of 20%.
The results are summarized in the table below:
| EliA U1RNP (EliA U/mL) | LoB | LoD | LoQ |
|---|---|---|---|
| Phadia 2500/5000 | 0.2 | 0.5 | 1.1 |
EliA RNP70:
The LoD for EliA RNP70 is 0.3 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A and with proportions of false positives (a) less than 5% and false negatives (β) less than 5%; based on 132 determinations with 66 blank and 66 low level replicates; and LoB of 0.2 EliA U/mL.
The LoQ for EliA RNP70 is 0.9 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A, based on 66 determinations, and a target uncertainty goal of 20%.
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The results are summarized in the table below:
| EliA RNP70 (EliA U/mL) | LoB | LoD | LoQ |
|---|---|---|---|
| Phadia 2500/5000 | 0.2 | 0.3 | 0.9 |
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 (negative, equivocal, positive) recommended for the evaluation of the test results were derived from the clinical studies (s. K082759 and K083117).
EliA CENP Well
| 10 EliA U/mL | Positive |
EliA U1RNP Well
| 10 EliA U/mL | Positive |
EliA RNP70 Well
| 10 EliA U/mL | Positive |
- Comparison studies: 2.
- Method comparison with predicate device (Instrument comparison): a. See 2c Instrument Comparison below
- b. Matrix comparison:
Previously reviewed under K082759 and K083117.
- Instrument comparison C.
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 CENP, EliA U1RNP and EliA RNP70.
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EliA CENP:
| Instrument | Intercept | 95% Cl | Slope | 95% Cl |
|---|---|---|---|---|
| PH2500/5000 A | -0.30 | -0.55 to -0.07 | 1.02 | 1.00 to 1.03 |
| PH2500/5000 B | 0.44 | 0.07 to 0.78 | 0.98 | 0.95 to 1.00 |
| PH2500/5000 C | -0.40 | -0.91 to -0.09 | 1.04 | 1.03 to 1.07 |
equivocal results considered positive
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 100.0% | 100.0% | 100.0% |
| 95% CI | 95.7% - 100.0% | 95.7% - 100.0% | 95.5% - 100.0% |
| NPA | 94.1% | 88.2% | 88.2% |
| 95% CI | 71.3% - 99.9% | 63.6% - 98.5% | 63.6% - 98.5% |
| TPA | 99.0% | 98.0% | 97.9% |
| 95% CI | 94.6% - 100.0% | 93.0% - 99.8% | 92.7% - 99.7% |
equivocal results considered negative
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 98.7% | 98.7% | 98.6% |
| 95% CI | 92.8% - 100.0% | 92.8% - 100.0% | 92.5% - 100.0% |
| NPA | 100.0% | 92.0% | 96.0% |
| 95% CI | 86.3% - 100.0% | 74.0% - 99.0% | 79.6% - 99.9% |
| TPA | 99.0% | 97.0% | 97.9% |
| 95% CI | 94.6% - 100.0% | 91.5% - 99.4% | 92.7% - 99.7% |
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EliA U1RNP:
| Instrument | Intercept | 95% Cl | Slope | 95% Cl |
|---|---|---|---|---|
| PH2500/5000 A | 0.68 | 0.34 to 1.02 | 0.92 | 0.90 to 0.95 |
| PH2500/5000 B | 0.03 | -0.36 to 0.65 | 1.02 | 0.98 to 1.05 |
| PH2500/5000 C | 0.98 | 0.43 to 1.26 | 0.92 | 0.90 to 0.94 |
equivocal results considered positive
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 100.0% | 98.9% | 96.8% |
| 95% CI | 96.2% - 100.0% | 94.3% - 100.0% | 91.0% - 99.3% |
| NPA | 100.0% | 94.1% | 100.0% |
| 95% CI | 80.5% - 100.0% | 71.3% - 99.9% | 80.5% - 100.0% |
| TPA | 100.0% | 98.2% | 97.3% |
| 95% CI | 96.8% - 100.0% | 93.7% - 99.8% | 92.4%- 99.4% |
equivocal results considered negative
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 98.7% | 97.4% | 100.0% |
| 95% CI | 93.0% - 100.0% | 90.9% - 99.7% | 95.3% - 100.0% |
| NPA | 97.1% | 97.1% | 97.1% |
| 95% CI | 85.1% - 99.9% | 85.1% - 99.9% | 85.1% - 99.9% |
| TPA | 98.2% | 97.3% | 99.1% |
| 95% CI | 93.7% - 99.8% | 92.4% - 99.4% | 95.1% - 100.0% |
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EliA RNP70:
| Instrument | Intercept | 95% Cl | Slope | 95% Cl |
|---|---|---|---|---|
| PH2500/5000 A | 0.35 | 0.17 to 0.52 | 1.00 | 0.98 to 1.02 |
| PH2500/5000 B | 0.29 | 0.17 to 0.48 | 1.04 | 1.01 to 1.06 |
| PH2500/5000 C | 0.33 | 0.16 to 0.69 | 1.03 | 1.01 to 1.06 |
equivocal results considered positive
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 100.0% | 100.0% | 100.0% |
| 95% CI | 95.8% - 100.0% | 95.8% - 100.0% | 95.8% - 100.0% |
| NPA | 88.5% | 80.8% | 84.6% |
| 95% CI | 69.8% - 97.6% | 60.6% - 93.4% | 65.1% - 95.6% |
| TPA | 97.3% | 95.5% | 96.4% |
| 95% CI | 92.3% - 99.4% | 89.8% - 98.5% | 91.1% - 99.0% |
equivocal results considered negative
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 98.6% | 100.0% | 98.6% |
| 95% CI | 92.6% - 100.0% | 95.1% - 100.0% | 92.7% - 100.0% |
| NPA | 97.4% | 92.1% | 92.1% |
| 95% CI | 86.2% - 99.9% | 78.6% - 98.3% | 78.6% - 98.3% |
| TPA | 98.2% | 97.3% | 96.4% |
| 95% CI | 93.6% - 99.8% | 92.3% - 99.4% | 91.1% - 99.0% |
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 K082759 and K083117.
-
- Clinical cut-off:
Same as assay cut-off.
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5. Expected values/Reference range:
The frequency distribution for CENP, U1RNP and RNP70 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.
| Test | n = | Median
(EliA U/mL) | 95th
percentile | 99th
percentile |
|-----------------------------------|-----|-----------------------|--------------------|--------------------|
| EliA CENP on Phadia
2500/5000 | 400 | 0.7 | 1.0 | 1.3 |
| EliA U1RNP on
Phadia 2500/5000 | 400 | 1.5 | 2.2 | 3.0 |
| EliA RNP70 on
Phadia 2500/5000 | 400 | 1.4 | 2.2 | 2.5 |
The results are given in the table below:
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
All available data support that both instrument platforms, Phadia 250 and Phadia 2500/5000 perform substantially equivalent when using the EliA CENP, EliA U1RNP and EliA RNP70 immunoassays.
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.