(38 days)
No
The summary describes a laboratory immunoassay kit and an automated instrument for performing the assay. There is no mention of AI or ML in the intended use, device description, or performance studies. The performance studies focus on standard analytical validation metrics for laboratory tests.
No.
This device is an in vitro diagnostic (IVD) device intended for the semi-quantitative measurement of specific antibodies to aid in the diagnosis of certain conditions, not for treating or preventing disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the in vitro semi-quantitative measurement of IgA antibodies... to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE)."
No
The device description clearly outlines physical components such as "Test Wells," "Sample Diluent," "Conjugate," "Calibrator Strips," "Curve Control Strips," and "Calibrator Well." These are tangible reagents and consumables, not software. The device also relies on the "Phadia EliA Immunodiagnostic System," which is an automated instrument, indicating a hardware component is essential for the device's function.
Based on the provided information, 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 IgA antibodies..." in human serum and plasma. The term "in vitro" is a key indicator of an IVD.
- Purpose: The purpose of the measurement is "to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings." This clearly indicates a diagnostic purpose performed outside of the body.
- Sample Type: The devices analyze "human serum and plasma," which are biological samples commonly used in in vitro diagnostic testing.
- Device Description: The description details reagents and components used to perform a laboratory test on these samples.
- Performance Studies: The document includes details about performance studies like precision, linearity, detection limit, and instrument comparison, which are standard evaluations for IVD devices.
- Predicate Devices: The mention of predicate devices (K112414 and K131821) which are also IVDs further supports the classification of this device as an IVD.
The information provided aligns perfectly with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
EliA ß2-Glycoprotein I IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to ß2-Glycoprotein I in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA ß2-Glycoprotein I IgA uses the EliA IgA method on the instrument Phadia 2500/5000.
EliA Cardiolipin IgA is intended for the in vitro sem-quantitative measurement of IgA antibodies directed to cardiolipin in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgA uses the EliA IgA method on the instrument Phadia 2500/5000.
Product codes
MSV, MID
Device Description
The method-specific reagents are identical with K112414 (EliA B2-Glycoprotein I IqA) and K131821 (EliA Cardiolipin IqA), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:
- -Test Wells: EliA ß2-Glycoprotein I IqA Wells are coated with human ß2-Glycoprotein I antigen - 2 carriers (12 wells each), ready to use;
- EliA Cardiolipin IgA Wells are coated with bovine cardiolipin antigen and boyine ß2-glycoprotein I as co-factor - 2 carriers (12 wells each), ready to use;
- -EliA Sample Diluent: PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
- -EliA IqA Conjuqate 50 or 200: ß-Galactosidase labeled anti-IgA (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 IgA Calibrator Strips: Human IgA (0, 0.3, 1.5, 5, 15, 80 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 IgA Curve Control Strips: Human IgA (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 IgA 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 ß2-Glycoprotein I IgA and EliA Cardiolipin IgA tests.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
For prescription use only
This device is 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
Analytical performance studies include Precision/Reproducibility and Linearity/assay reportable range studies.
Precision/Reproducibility:
- Study type: Variability assessment with five serum samples.
- Sample size: 21 runs (3 instruments x 7 runs) for five serum samples. Each serum sample was tested in four replicates/run, totaling 84 replicates per serum sample.
- Key results:
- EliA β2-Glycoprotein I IgA on Phadia 2500/5000:
- Mean (EliA U/mL): 1.6, 8.0, 10.4, 42.8, 136.6
- Total Imprecision %CV: 26.2, 6.6, 7.1, 6.7, 9.7
- EliA Cardiolipin IgA on Phadia 2500/5000:
- Mean (APL-U/mL): 2.1, 13.5, 19.4, 93.0, 153.0
- Total Imprecision %CV: 18.5, 6.2, 7.4, 7.9, 11.9
- EliA β2-Glycoprotein I IgA on Phadia 2500/5000:
Linearity/assay reportable range:
- Study type: Linearity study using diluted patient serum samples.
- Sample size: Four patient serum samples.
- Key results:
- EliA β2-Glycoprotein I IgA on Phadia 2500/5000:
- Dilution range (EliA U/mL): 0.4 — 66.6, 5.2 — 205.2, 6.4 – 242.8, 5.5 – 198.8
- R2 values: All 1.00
- Reportable range: 0.3 to 183 EliA U/mL
- Measuring range: 1.1 to 183 EliA U/mL
- EliA Cardiolipin IgA on Phadia 2500/5000:
- Dilution range (APL-U/mL): 0.5 – 49.5, 1.8 – 91.3, 2.4 - 147.0, 4.4 – 221.6
- R2 values: All 1.00
- Reportable range: 0.3 to 181 APL-U/mL
- Measuring range: 1.0 to 181 APL-U/mL
- EliA β2-Glycoprotein I IgA on Phadia 2500/5000:
Detection limit studies (LoB, LoD, LoQ) were performed on the Phadia 2500/5000 instrument.
- EliA ß2-Glycoprotein I IgA: LoD is 0.3 EliA U/mL, LoQ is 1.1 EliA U/mL.
- EliA Cardiolipin IgA: LoD is 0.3 APL-U/mL, LoQ is 1.0 APL-U/mL.
Method comparison with predicate device (Instrument comparison):
- Study type: Comparison of more than 100 serum samples between one Phadia 250 and three Phadia 2500/5000 instruments.
- Sample size: More than 100 serum samples (≥20% of the samples within ±25% of the medical decision point).
- Key results:
- EliA β2-Glycoprotein I IgA: Slopes for PH2500/5000 A, B, C were 0.98, 1.02, 1.01, respectively.
- Equivocal results considered positive: PPA ranging from 97.3% to 98.7%, NPA ranging from 80.0% to 88.0%.
- Equivocal results considered negative: PPA 100.0%, NPA ranging from 94.6% to 100.0%.
- EliA Cardiolipin IgA: Slopes for PH2500/5000 A, B, C were 0.98, 0.99, 1.06, respectively.
- Equivocal results considered positive: PPA 100.0%, NPA ranging from 88.4% to 97.7%.
- Equivocal results considered negative: PPA ranging from 93.3% to 97.8%, NPA 94.6%.
- EliA β2-Glycoprotein I IgA: Slopes for PH2500/5000 A, B, C were 0.98, 1.02, 1.01, respectively.
Key Metrics
- Precision: Total Imprecision %CV for EliA β2-Glycoprotein I IgA ranged from 6.6% to 26.2%. Total Imprecision %CV for EliA Cardiolipin IgA ranged from 6.2% to 18.5%.
- Linearity: R2 values of 1.00 for all tested dilution ranges for both EliA β2-Glycoprotein I IgA and EliA Cardiolipin IgA.
- Detection Limit:
- EliA β2-Glycoprotein I IgA: LoD = 0.3 EliA U/mL, LoQ = 1.1 EliA U/mL.
- EliA Cardiolipin IgA: LoD = 0.3 APL-U/mL, LoQ = 1.0 APL-U/mL.
- Method Comparison:
- EliA β2-Glycoprotein I IgA (equivocal considered positive): PPA 97.3% - 98.7%, NPA 80.0% - 88.0%.
- EliA β2-Glycoprotein I IgA (equivocal considered negative): PPA 100.0%, NPA 94.6% - 100.0%.
- EliA Cardiolipin IgA (equivocal considered positive): PPA 100.0%, NPA 88.4% - 97.7%.
- EliA Cardiolipin IgA (equivocal considered negative): PPA 93.3% - 97.8%, NPA 94.6%.
Predicate Device(s)
EliA ß2-Glycoprotein I IgA on Phadia 250 instrument, K112414, EliA Cardiolipin IgA on Phadia 250 instrument, K131821
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym followed by the full name of the agency, "U.S. Food & Drug Administration," on the right. The FDA part of the logo is in blue, with the acronym in a solid blue square and the agency's name in a lighter shade of blue.
June 25, 2018
Phadia AB Martin Mann Senior Regulatory Affairs Manager Phadia US Inc. 4169 Commercial Avenue Portage, Michigan 49002
Re: K181329
Trade/Device Name: EliA B2-Glycoprotein I IgA Immunoassay, EliA Cardiolipin IgA Immunoassay Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MSV, MID Dated: May 14, 2018 Received: May 18, 2018
Dear Martin Mann:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
1
Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For 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).
Sincerelv.
Kelly Oliner -S
For Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name
EliA(TM) ß2-Glycoprotein I IgA Immunoassay, EliA(TM) Cardiolipin IgA Immunoassay
Indications for Use (Describe)
EliA ß2-Glycoprotein I IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to ß2-Glycoprotein I in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA B2-Glycoprotein I IgA uses the EliA IgA method on the instrument Phadia 2500/5000.
EliA Cardiolipin IgA is intended for the in vitro sem-quantitative measurement of IgA antibodies directed to cardiolipin in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgA uses the EliA IgA 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.1 510(k) Summary of Safety and Effectiveness per 21CFR 807.92(c).
This summary of safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR Part 807.92.
510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE
A. 510(k) Number: K181329
B. Purpose for Submission:
Adding previously cleared assays on a new instrument platform (Phadia® 2500/5000)
C. Measurands:
Anti-ß2-qlycoprotein | IgA autoantibodies Anti-cardiolipin IgA autoantibodies
D. Type of Test:
Semi-quantitative measurement immunoassays
E. Applicant:
Phadia AB Rapsgatan 7P P.O. Box 6460 SE-751 37 Uppsala, Sweden Tel: +46-18-16 50 60
510(k) Contact Person: Martin Mann Requlatory Affairs Manager Phadia US Inc. 4169 Commercial Avenue Portage, Mi 49002, USA +1 (-269-492) -1957 (Phone) +1 (-269-492) -7541 (Fax) martin.mann@thermofisher.com
Date of Summary Preparation: Mav 15, 2018
F. Proprietary and Established Names: EliA™ ß2-Glycoprotein I IgA Immunoassay EliA™ Cardiolipin IgA Immunoassay
4
G. Regulatory Information:
-
- Requlation section: 21 CFR §866.5660 Multiple autoantibodies immunological test system
-
- Classification: Class II
-
- Product code:
MSV System, Test, Antibodies, ß2-Glycoprotein I (ß2-GPI) MID System, Test, Anti-Cardiolipin Immunological
-
- Panel: Immunology (82)
H. Intended use(s):
- Intended use(s):
EliA ß2-Glycoprotein I IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to ß2-Glycoprotein I in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA ß2-Glycoprotein I IgA uses the EliA IgA method on the instrument Phadia 2500/5000.
EliA Cardiolipin IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to cardiolipin in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgA uses the EliA IgA method on the instrument Phadia 2500/5000.
-
Indication(s) for use: Same as intended use
-
Special conditions for use statement(s): For prescription use only
- Special instrument requirements: ব
Performance studies were obtained from the Phadia® 2500/5000 instrument This device is not for point-of-care use.
5
. Device Description:
The method-specific reagents are identical with K112414 (EliA B2-Glycoprotein I IqA) and K131821 (EliA Cardiolipin IqA), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:
- -Test Wells: EliA ß2-Glycoprotein I IqA Wells are coated with human ß2-Glycoprotein I antigen - 2 carriers (12 wells each), ready to use;
- EliA Cardiolipin IgA Wells are coated with bovine cardiolipin antigen and boyine ß2-glycoprotein I as co-factor - 2 carriers (12 wells each), ready to use;
- -EliA Sample Diluent: PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
- -EliA IqA Conjuqate 50 or 200: ß-Galactosidase labeled anti-IgA (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 IgA Calibrator Strips: Human IgA (0, 0.3, 1.5, 5, 15, 80 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 IgA Curve Control Strips: Human IgA (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 IgA 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 ß2-Glycoprotein I IgA and EliA Cardiolipin IgA tests.
J. Substantial Equivalence Information:
- Predicate device name(s) and 510(k) number(s): EliA ß2-Glycoprotein I IgA on Phadia 250 instrument, K112414 EliA Cardiolipin IgA on Phadia 250 instrument, K131821
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2. Comparison with predicate device:
EliA APS IgA 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 Cardiolipin IgA | EliA Cardiolipin IgA is intended
for the in vitro semi-quantitative
measurement of IgA antibodies
directed to cardiolipin in human
serum and plasma (heparin,
EDTA, citrate) to aid in the
diagnosis of antiphospholipid
syndrome (APS) as well as
thrombotic disorders related to
systemic lupus erythematosus
(SLE) in conjunction with other
laboratory and clinical findings.
EliA Cardiolipin IgA uses the EliA
IgA method on the instrument
Phadia 250. | EliA Cardiolipin IgA is intended
for the in vitro semi-quantitative
measurement of IgA antibodies
directed to cardiolipin in human
serum and plasma (Li-heparin,
EDTA) to aid in the diagnosis of
antiphospholipid syndrome
(APS) as well as thrombotic
disorders related to systemic
lupus erythematosus (SLE) in
conjunction with other laboratory
and clinical findings. EliA
Cardiolipin IgA uses the EliA IgA
method on the instrument
Phadia 2500/5000. |
| Intended Use
EliA β2-Glycoprotein
I IgA | EliA β2-Glycoprotein I IgA is
intended for the in vitro semi-
quantitative measurement of IgA
antibodies directed to β2-
Glycoprotein I in human serum
and plasma (heparin, EDTA,
citrate) to aid in the diagnosis of
antiphospholipid syndrome
(APS) as well as thrombotic
disorders related to systemic
lupus erythematosus (SLE) in
conjunction with other laboratory
and clinical findings. EliA β2-
Glycoprotein I IgA uses the EliA
IgA method on the instrument
Phadia 250. | EliA β2-Glycoprotein I IgA is
intended for the in vitro semi-
quantitative measurement of IgA
antibodies directed to β2-
Glycoprotein I in human serum
and plasma (Li-heparin, EDTA)
to aid in the diagnosis of
antiphospholipid syndrome
(APS) as well as thrombotic
disorders related to systemic
lupus erythematosus (SLE) in
conjunction with other laboratory
and clinical findings. EliA β2-
Glycoprotein I IgA uses the EliA
IgA method on the instrument
Phadia 2500/5000. |
| Analytical
technology:
Immuno-
fluorescence
measurement | Same | Same |
| Assay process | Same | Same |
| Common, dedicated
Phadia reagents | Same | Introduction of new article
numbers for Development |
| | | Solution, Stop Solution and
Washing Solution is only due to
larger filling volumes which are
required for the bigger
instruments Phadia 2500/5000 |
| Result calculation
software; Phadia
Information Data
Manager (IDM) | Same | Same |
| Sample volume | 90 µL (20 µL of non-diluted
sample) | 90 µL (20 µL of non-diluted
sample) |
| Incubation
temperature | 37°C | 37°C |
| Conjugate volume | 90 µL | 90 µL |
| Development
Solution Volume | 90 µL | 90 µL |
| Stop Solution
Volume | 200 µL | 200 µL |
| Assay set-up | Random access | Random access |
| Reagent packaging
size | Various/Common | Various/Common
Introduction of new article
number for EliA Sample Diluent
(83-1071-01) is only due to
larger filling volume. |
| Onboard storage of
reagents | Yes | Yes |
| Time to 1st result | ~2 h | ~2 h |
| Feature | Predicate Device
Phadia 250 | New Device
Phadia 2500/5000 |
| Sample matrix;
Serum or plasma
type as indicated in
the DFU dependent
on assay | Serum or plasma (heparin,
EDTA, citrate) | Serum or plasma (Li-heparin,
EDTA) |
| Daily throughput | ~250 tests | ~2500/5000 tests |
| Sample Dilution | Phadia 250 uses a steel pipette
to dilute the samples in Dilution
Plates (Art.No. 12-3907-08) | Phadia 2500/5000 uses
disposable Pipette Tips in Racks
(Art No. 12-3805-04) for
pipetting samples in Dilution
Well (Art.No. 12-4005-69) |
| Risk for carry-over | The warning "DO NOT REUSE"
in the Phadia 250 DFU for EliA
Conjugates is due to the fact that
a low risk of conjugate
contamination by carry-over from
samples was identified. In order
to reduce the risk, the single use
statement for the conjugate was
included in the Phadia 250 DFU. | When running EliA tests on the
Phadia 2500/5000 instruments,
there is no need for this warning
statement because these
instruments use disposable tips
for pipetting samples and a
separate pipette for the
conjugate, and carry-over from
samples to conjugate is
impossible. |
| Loading of EliA
Carriers | EliA carriers are loaded manually
on the Loading Tray from where
they can be processed directly or
transferred to the cooled storage
compartment. | The Phadia 2500/5000
instruments do not have such a
Loading Tray. The EliA carriers
are loaded into racks which are
directly transferred to the cooled
storage compartment |
| Barcode reader | The Phadia 250 instrument has
a built-in barcode reader at the
front of the instrument, but the
operator needs to scan the
barcodes manually by showing
the reagents to the barcode
reader. Alternatively, the
operator can also enter the
characters below the barcode
manually. | The Phadia 2500/5000
instruments dispose of a built-in
barcode reader, and the
reagents are on a moving belt
which conveys them past the
barcode reader. The lot-specific
information will be read
automatically by the instrument
during loading. |
| Process time / Time
to patient result | Phadia 250 needs 1 minute to
process one Well.
Phadia 250 provides the results
at a one minute interval. | Phadia 2500/5000 instruments
process two Wells in parallel in
48 seconds.
Phadia 2500/5000 provides the
results at a 24 seconds interval. |
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8
EliA APS IgA 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 bovine cardiolipin antigen, or with human β2-Glycoprotein I antigen. 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 IgA antibodies (EliA IgA Conjugate) are added to form an antibody-conjugate complex. After incubation, non-bound conjugate is washed away and the bound complex is incubated with a Development Solution. After stopping the reaction, the fluorescence in the reaction mixture is measured. The higher the response value, the more specific IgA is present in the specimen. To evaluate test results, the response for patient samples is compared directly to the response for calibrators.
M. Performance Characteristics (if/when applicable):
- Analytical performance:
a. Precision/Reproducibility:
To determine the precision of the assay, the variability was assessed in a study with five serum samples totaling in 21 runs (3 instruments x 7 runs). The study was performed with 1 run/day over a period of 7 days. Each serum sample was tested in four replicates/run giving in total 84 replicates per serum sample. The data was calculated against the calibration curve from Day 1.
We included only one lot of EliA ß2-Glycoprotein I IgA Well and EliA Cardiolipin IgA Well on the Phadia 2500/5000 instrument, as data for inter-lot-variation has already been shown in K112414 and K131821.
The results are summarized in the table below:
10
| Mean
(EliA
U/mL) | Within-
Run | | Between-
Run | | Between-
Instrument | | Total
Imprecision | |
|------------------------|----------------|-----|-----------------|-----|------------------------|------|----------------------|------|
| | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1.6 | 0.1 | 8.0 | 0.2 | 9.8 | 0.4 | 23.0 | 0.4 | 26.2 |
| 8.0 | 0.3 | 3.7 | 0.3 | 3.5 | 0.3 | 4.2 | 0.5 | 6.6 |
| 10.4 | 0.4 | 3.7 | 0.5 | 5.0 | 0.4 | 3.4 | 0.7 | 7.1 |
| 42.8 | 1.4 | 3.3 | 2.2 | 5.2 | 1.2 | 2.8 | 2.9 | 6.7 |
| 136.6 | 6.6 | 4.8 | 10.3 | 7.5 | 5.1 | 3.7 | 13.2 | 9.7 |
EliA β2-Glycoprotein I IgA on Phadia 2500/5000
EliA Cardiolipin IgA on Phadia 2500/5000
| Mean
(APL- | Within-Run | | Between-
Run | | Between-
Instrument | | Total
Imprecision | |
|---------------|------------|-----|-----------------|-----|------------------------|------|----------------------|------|
| U/mL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 2.1 | 0.2 | 7.2 | 0.2 | 7.9 | 0.3 | 15.1 | 0.4 | 18.5 |
| 13.5 | 0.8 | 5.6 | 0.3 | 2.3 | 0.2 | 1.4 | 0.8 | 6.2 |
| 19.4 | 0.7 | 3.9 | 1.1 | 5.5 | 0.6 | 3.0 | 1.4 | 7.4 |
| 93.0 | 5.4 | 5.8 | 1.4 | 1.5 | 4.8 | 5.2 | 7.4 | 7.9 |
| 153.0 | 10.7 | 7.0 | 12.0 | 7.9 | 8.5 | 5.5 | 18.2 | 11.9 |
b. Linearity/assay reportable range:
Four patient serum samples were diluted in sample diluent and tested with one batch of EliA ß2-Glycoprotein I IgA and EliA Cardiolipin IgA Immunoassays and one set of system reagents on Phadia 2500/5000. The results of the regression analysis are summarized below:
EliA β2-Glycoprotein I IgA on Phadia 2500/5000
| Dilution range
| (EliA U/mL) | Slope | Intercept | R2 |
|---|---|---|---|
| 0.4 — 66.6 | 1.00 | 0.24 | 1.00 |
| 5.2 — 205.2 | 1.03 | -0.12 | 1.00 |
| 6.4 – 242.8 | 1.02 | -0.46 | 1.00 |
| 5.5 – 198.8 | 1.02 | 1.80 | 1.00 |
The reportable range (Limit of Detection, upper limit) for EliA $2-Glycoprotein I IgA is from 0.3 to 183 EliA U/mL. The measuring range (Limit of Quantitation, upper limit) is from 1.1 to 183 EliA U/mL.
11
| Dilution range
| (APL-U/mL) | Slope | Intercept | R2 |
|---|---|---|---|
| 0.5 – 49.5 | 1.01 | 0.40 | 1.00 |
| 1.8 – 91.3 | 0.98 | -0.25 | 1.00 |
| 2.4 - 147.0 | 0.98 | -1.45 | 1.00 |
| 4.4 – 221.6 | 1.00 | 3.76 | 1.00 |
EliA Cardiolipin IgA on Phadia 2500/5000
The reportable range (Limit of Detection, upper limit) for EliA Cardiolipin IgA is from 0.3 to 181 APL-U/mL. The measuring range (Limit of Quantitation, upper limit) is from 1.0 to 181 APL-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 IqA method was previously reviewed in K062787.
- 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 serum samples were measured in thirty-three and eleven replicates, respectively, in each of two runs.
EliA ß2-Glycoprotein I IqA:
The LoD for EliA ß2-Glycoprotein I IgA is 0.3 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2 and with proportions of false positives (α) 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 0.1 EliA U/mL.
The LoQ for EliA ß2-Glycoprotein I IgA is 1.1 EliA U/mL, determined consistent with the guidelines in CLSI document EP17-A2, based on 66 determinations, and a target uncertainty goal of 20%.
The results are summarized in the table below:
| EliA β2-Glycoprotein I IgA (EliA U/mL) | LoB | LoD | LoQ |
|---|---|---|---|
| Phadia 2500/5000 | 0.1 | 0.3 | 1.1 |
12
EliA Cardiolipin IgA:
The LoD for EliA Cardiolipin IgA is 0.3 APL-U/mL, determined consistent with the guidelines in CLSI document EP17-A2 and with proportions of false positives (a) less than 5% and false negatives (β) less than 5%; based on 132 determinations with 66 blank and 66 low level replicates; and LoB of 0.1 APL-U/mL.
The LoQ for EliA Cardiolipin IgA is 1.0 APL-U/mL, determined consistent with the quidelines in CLSI document EP17-A2, based on 66 determinations, and a target uncertainty goal of 20%.
The results are summarized in the table below:
| EliA Cardiolipin IgA (APL-U/mL) | LoB | LoD | LoQ |
|---|---|---|---|
| Phadia 2500/5000 | 0.1 | 0.3 | 1.0 |
Analytical specificity: e.
Interference: Previously reviewed in K112414 and K131821 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. K112414 and K131821).
EliA ß2-Glvcoprotein | IgA Well
| 10 EliA U/mL | Positive |
EliA Cardiolipin IgA Well
| 20 APL-U/mL | Positive |
-
- Comparison studies:
- Method comparison with predicate device (Instrument comparison): a. See 2c Instrument Comparison below
Matrix comparison: b.
Previously reviewed under K112414 and K131821.
13
Instrument comparison C.
In the Method Comparison studies for the two EliA tests included in this submission, more than 100 serum 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 ß2-Glycoprotein I IgA and EliA Cardiolipin IgA.
EliA β2-Glycoprotein | IgA:
| Instrument | Intercept | 95% Cl | Slope | 95% Cl |
|---|---|---|---|---|
| PH2500/5000 A | 0.85 | 0.58 to 1.26 | 0.98 | 0.95 to 1.01 |
| PH2500/5000 B | 0.44 | -0.20 to 0.76 | 1.02 | 0.99 to 1.04 |
| PH2500/5000 C | 0.22 | -0.06 to 0.53 | 1.01 | 0.98 to 1.05 |
equivocal results considered positive
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 98.7% | 97.3% | 98.7% |
| 95% CI | 92.8% – 100% | 90.6% – 99.7% | 92.8% – 100% |
| NPA | 80.0% | 88.0% | 84.0% |
| 95% CI | 59.3% – 93.2% | 68.8% – 97.5% | 63.9% – 95.5% |
| TPA | 94.0% | 94.9% | 95.0% |
| 95% CI | 87.4% – 97.8% | 88.6% – 98.3% | 88.7% – 98.4% |
equivocal results considered negative
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 100.0% | 100.0% | 100.0% |
| 95% CI | 94.3% – 100% | 94.2% – 100% | 94.3% – 100% |
| NPA | 94.6% | 97.3% | 100.0% |
| 95% CI | 81.8% – 99.3% | 85.8% – 99.9% | 90.5% – 100% |
| TPA | 98.0% | 99.0% | 100.0% |
| 95% CI | 93.0% – 99.8% | 94.5% – 100% | 96.4% – 100% |
14
EliA Cardiolipin IgA:
| Instrument | Intercept | 95% Cl | Slope | 95% Cl |
|---|---|---|---|---|
| PH2500/5000 A | 0.30 | -0.01 to 0.56 | 0.98 | 0.96 to 1.01 |
| PH2500/5000 B | -0.27 | -0.64 to 0.01 | 0.99 | 0.95 to 1.02 |
| PH2500/5000 C | -0.40 | -0.90 to -0.15 | 1.06 | 1.04 to 1.10 |
equivocal results considered positive
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 100.0% | 100.0% | 100.0% |
| 95% CI | 93.8% – 100% | 93.8% – 100% | 93.8% – 100% |
| NPA | 88.4% | 97.7% | 95.3% |
| 95% CI | 74.9% – 96.1% | 87.7% – 99.9% | 84.2% – 99.4% |
| TPA | 95.0% | 99.0% | 98.0% |
| 95% CI | 88.8% – 98.4% | 94.6% – 100% | 93.0% – 99.8% |
equivocal results considered negative
| criteria | PH2500/5000 A | PH2500/5000 B | PH2500/5000 C |
|---|---|---|---|
| PPA | 95.6% | 93.3% | 97.8% |
| 95% CI | 84.9% – 99.5% | 81.7% – 98.6% | 88.2% – 99.9% |
| NPA | 94.6% | 94.6% | 94.6% |
| 95% CI | 85.1% – 98.9% | 85.1% – 98.9% | 85.1% – 98.9% |
| TPA | 95.0% | 94.1% | 96.0% |
| 95% CI | 88.8% – 98.4% | 87.5% – 97.8% | 90.2% – 98.9% |
- ဒေ.
က 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 K112414 and K131821.
- Clinical cut-off: 4. Same as assay cut-off.
15
Expected values/Reference range: 5.
The frequency distribution for anti-ß2-Glycoprotein I IgA and anti-cardiolipin IgA antibodies was investigated in a group of apparently healthy subjects equally distributed by age and gender, using sera from a Caucasian population obtained from a blood bank.
The results are given in the table below:
| Test | n = | Median
(EliA U/mL;
APL-U/mL) | 95th
percentile | 99th
percentile |
|------------------------------------------------------|-----|------------------------------------|--------------------|--------------------|
| EliA ß2-Glycoprotein I
IgA on Phadia
2500/5000 | 400 | 1.8 | 4.1 | 9.5 |
| EliA Cardiolipin IgA
on Phadia 2500/5000 | 400 | 2.8 | 6.6 | 16.5 |
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 ß2-Glycoprotein I IgA and EliA Cardiolipin IgA immunoassays.
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.