(245 days)
No
The summary describes a standard automated immunodiagnostic system and assay for measuring antibodies. There is no mention of AI, ML, or any related technologies in the device description, intended use, or performance studies. The performance metrics are standard for an immunoassay.
No
The device is intended for in vitro semi-quantitative measurement of IgG antibodies to aid in the clinical diagnosis of scleroderma. It is a diagnostic device, not a therapeutic one.
Yes
The "Intended Use / Indications for Use" states that the device is "intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma... as an aid in the clinical diagnosis of scleroderma." This clearly indicates its role in diagnosing a medical condition.
No
The device is described as an in vitro diagnostic (IVD) test that uses reagents and an automated instrument (Phadia 100/250) to measure antibodies in human samples. This involves physical components and chemical processes, not solely software.
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 device is "intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma... as an aid in the clinical diagnosis of scleroderma". The term "in vitro" is a key indicator of an IVD, meaning it's used to test samples outside of the living body.
- Device Description: The description refers to it as an "immunodiagnostic system" and mentions "reagents," which are typical components of IVD tests.
- Clinical Diagnosis: The intended use clearly states its purpose is to aid in clinical diagnosis.
- Sample Type: It specifies the use of human serum and plasma, which are biological samples tested by IVDs.
- Performance Studies: The document details various performance studies (precision, linearity, analytical specificity, method comparison, clinical sensitivity and specificity) which are required for the validation of IVD devices.
- Predicate Device: The mention of a "Predicate Device" (INOVA QuantaLite™ Scl-70 ELISA) is common in regulatory submissions for IVDs, where a new device is compared to an already cleared device.
All of these points strongly indicate that the EliA Scl-70s is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
EliA Scl-70s is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma (heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (diffuse form) in conjunction with other laboratory and clinical findings. EliA Scl-70s uses the EliA IgG method on the instrument Phadia 100.
EliA Scl-70s is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma (heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (diffuse form) in conjunction with other laboratory and clinical findings. EliA Scl-70s uses the EliA IgG method on the instrument Phadia 250.
Product codes (comma separated list FDA assigned to the subject device)
LJM
Device Description
EliA Scl-70 Wells (14-5637-01) are coated with a human recombinant Scl-70 protein -4 carriers, (12 wells each), ready to use. The method-specific reagents on Phadia 250 are identical; they are only filled in different containers.
Needed reagents for Phadia 100:
- EliA Sample Diluent, method-specific, PBS containing BSA, detergent and 0.095% sodium azide . - ready to use: (83-1003-01)
- EliA IgG Conjugate, β-galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA, detergent and 0.06% sodium azide - ready to use; (83-1002-01, 83-1005-01)
- EliA ANA Positive Control 100: 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; (83-1038-01)
- EliA IgG/IgM/IgA Negative Control 100: containing normal human serum from healthy donors -. 6 single-use vials, 0.3 mL each, ready to use; (83-1042-01)
- EliA IgG Calibrators, human IgG in PBS (0, 4, 10, 20, 100, 600 µg/L) 6 single-use vials, 0.3 mL . each, ready to use; (83-1000-01)
- EliA IgG Curve Control, human IgG (20 µg/L) in PBS, 6 single-use vials, 0.3 mL each, ready to . use; (83-1001-01)
- EliA IgG Calibrator Wells are coated with mouse monoclonal antibodies 4 carriers. (12 wells . each), ready to use; (14-5509-01)
Needed reagents for Phadia 250:
- EliA Sample Diluent, method-specific, PBS containing BSA, detergent and 0.095% sodium azide . - ready to use; (83-1023-01)
- EliA IgG Conjugate, β-galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA, detergent and 0.06% sodium azide - ready to use; (83-1017-01, 83-1018-01)
- . EliA ANA Positive Control 250: 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; (83-1033-01)
- EliA IgG/IgM/IgA Negative Control 250: containing normal human serum from healthy donors -. 6 single-use vials, 0.3 mL each, ready to use; (83-1037-01)
- EliA IgG Calibrator Strips, human IgG in PBS (0, 4, 10, 20, 100, 600 µg/L) 6 single-use vials, . 0.3 mL each, ready to use; (83-1015-01)
- EliA IgG Curve Control Strips, human IgG (20 µg/L) in PBS, 6 single-use vials, 0.3 mL each, . ready to use; (83-1016-01)
- EliA IgG Calibrator Wells are coated with mouse monoclonal antibodies 4 carriers, (12 wells each), ready to use; (14-5509-01)
The Phadia EliA immunodiagnostic system is automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages except the positive and negative controls are required to carry out an EliA Scl-70° test.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
For prescription use only
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A study was done on 400 apparently healthy blood donor samples from Caucasian individuals equally distributed by sex and age in order to evaluate expected values in the normal population and to confirm the defined cut-off. The samples were measured on the Phadia 250 instrument for EliA Scl-70°. The 99th percentile of the 400 samples were calculated and taken into account for setting of the cut-off.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision/Reproducibility:
- EliA Scl-70 on Phadia 100 (n=84): Mean values of 8.8, 30.2, 193.0 EliA U/ml with Total %CVs of 3.55, 4.01, 6.03 respectively.
- EliA Scl-70 on Phadia 250 (n = 252): Mean values of 7.5, 28.2, 200.1 EliA U/ml with Total %CVs of 3.33, 3.53, 5.40 respectively.
Linearity/assay reportable range:
- For EliA Scl-70 on Phadia 100 and Phadia 250, R2 values for linearity were 1.00 across various dilution ranges. The claimed linear range for EliA Scl-70 is 0.6 - 297.1 EliA U/ml. No hook effect observed.
Detection limit:
- LoB and LoD studies performed on Phadia 100 and Phadia 250.
- Phadia 100: LoB = 0.25, LoD = 0.36
- Phadia 250: LoB = 0.31, LoD = 0.52
- A single LoD of 0.6 U/mL was decided for both instruments.
Analytical specificity:
- Endogenous Interference: No interference observed for Bilirubin F (19.2 mg/dl), Bilirubin C (20.1 mg/dl), Hemoglobin (496 mg/dl), Chyle (1%), Rheumatoid factor (500 IU/ml).
- Carry-over: Negligible.
Assay cut-off:
- Based on 400 healthy blood donor samples, the cut-off values are: 10 EliA U/mL (Positive).
Method comparison with predicate device:
- Comparison between EliA Scl-70 and INOVA QuantaLite™ Scl-70 ELISA using 390 serum samples.
- Positive percent agreement: 89.5% (95% CI: 77.8 – 95.6%)
- Negative percent agreement: 97.2% (95% CI: 94.5 – 98.6%)
- Total percent agreement: 95.9% (95% CI: 93.3 – 97.7%)
- When equivocal results were evaluated as positive for EliA Scl-70:
- Positive percent agreement: 93.0% (95% CI: 82.2 – 97.8%)
- Negative percent agreement: 93.4% (95% Cl: 89.9 - 95.8%)
- Total percent agreement: 93.3% (95% CI: 90.2 - 95.5%)
Matrix comparison:
- Comparison of serum, lithium heparin plasma, and EDTA plasma (n=50).
- Serum vs heparin plasma: Slope = 1.05 (1.03 to 1.07), Intercept = -0.08 (-0.24 to +0.17), R2 = 1.00.
- Serum vs EDTA plasma: Slope = 1.00 (0.99 to 1.02), Intercept = -0.05 (-0.29 to +0.21), R2 = 1.00.
Instrument comparison:
- Performance on Phadia 250 instruments using 24 positive, 8 equivocal and 4 negative samples.
- Estimate for Intercept = -0.07 (95% Cl: -0.52 – 0.14), Estimate for Slope = 0.96 (95% Cl: 0.94 – 0.99).
Clinical studies:
- 336 clinically defined sera from patients with scleroderma or other connective tissue diseases, bacterial or viral infections, cancer or rheumatoid arthritis were tested.
- Sensitivity: 30.7% (95% CI: 22.1% - 40.8%)
- Specificity: 98.7% (95% CI: 96.0% - 99.7%)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity: 30.7% (95% CI: 22.1% - 40.8%)
Specificity: 98.7% (95% CI: 96.0% - 99.7%)
Positive percent agreement between EliA Scl-70 and predicate: 89.5% (95% CI: 77.8 – 95.6%)
Negative percent agreement between EliA Scl-70 and predicate: 97.2% (95% CI: 94.5 – 98.6%)
Total percent agreement between EliA Scl-70 and predicate: 95.9% (95% CI: 93.3 – 97.7%)
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.
QuantaLite™ Scl-70 ELISA, INOVÀ K924988
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
K063775, K072393, K091845, K082759
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 30, 2014
PHADIA US, INC. C/O MR. MARTIN ROBERT MANN SENIOR REGULATORY AFFAIRS MANAGER 4169 COMMERCIAL AVENUE PORTAGE, MI 49002
Re: K140493
Trade/Device Name: EliA™ Scl-708 Immunoassay Regulation Number: 21 CFR §866.5100 Regulation Name: Antinuclear Antibody Immunological Test System Regulatory Class: Class II Product Code: LJM Dated: September 24, 2014 Received: September 26, 2014
Dear Mr. Mann:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (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 Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely vours.
Maria M. Chan -S
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K140493
Device Name EliA™ Scl-70s
Indications for Use (Describe)
EliA Scl-70s is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma (heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (diffuse form) in conjunction with other laboratory and clinical findings. EliA Scl-70s uses the EliA IgG method on the instrument Phadia 100.
EliA Scl-70s is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma (heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (diffuse form) in conjunction with other laboratory and clinical findings. EliA Scl-70s uses the EliA IgG method on the instrument Phadia 250.
| 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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510k Summary long EliA Scl-70S D.1
510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION SUMMARY
- A. 510(k) Number: K140493
- B. Purpose for Submission: New devices
- C. Measurand: lgG Antibodies to Scl-70
- D. Type of Test: Semi-quantitative immunofluorescence assay
- E. Applicant: Phadia US Inc.
- F. Proprietary and Established Names: EliA™ Scl-708 Well
- G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100, Antinuclear antibody immunological test system
- 2. Classification: Class II (Assay)
-
- Product code: LJM Antinuclear Antibody (Enzyme-Labeled), Antigen, Controls|
-
- Panel: Immunology
4
H. Intended Use:
1. Intended use(s):
EliA Scl-70° is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma (heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (diffuse form) in conjunction with other laboratory and clinical findings. EliA Scl-70 uses the EliA IgG method on the instrument Phadia 100.
EliA Scl-70° is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma (heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (diffuse form) in conjunction with other laboratory and clinical findings. EliA Scl-70 uses the EliA IgG method on the instrument Phadia 250.
-
- Indication(s) for use: Same as intended use
-
- Special conditions for use statement(s): For prescription use only
-
- Special instrument requirements: Phadia® 100, Phadia® 250
5
l. Device Description:
- EliA Scl-70 Wells (14-5637-01) are coated with a human recombinant Scl-70 protein -4 carriers, (12 wells each), ready to use
The method-specific reagents on Phadia 250 are identical; they are only filled in different containers.
Needed reagents for Phadia 100:
- EliA Sample Diluent, method-specific, PBS containing BSA, detergent and 0.095% sodium azide . - ready to use: (83-1003-01)
- EliA IgG Conjugate, ß-galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA, detergent and 0.06% sodium azide - ready to use; (83-1002-01, 83-1005-01)
- EliA ANA Positive Control 100: 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; (83-1038-01)
- EliA IgG/IgM/IgA Negative Control 100: containing normal human serum from healthy donors -. 6 single-use vials, 0.3 mL each, ready to use; (83-1042-01)
- EliA IgG Calibrators, human IgG in PBS (0, 4, 10, 20, 100, 600 µg/L) 6 single-use vials, 0.3 mL . each, ready to use; (83-1000-01)
- EliA IgG Curve Control, human IgG (20 µg/L) in PBS, 6 single-use vials, 0.3 mL each, ready to . use; (83-1001-01)
- EliA IgG Calibrator Wells are coated with mouse monoclonal antibodies 4 carriers. (12 wells . each), ready to use; (14-5509-01)
Needed reagents for Phadia 250:
- EliA Sample Diluent, method-specific, PBS containing BSA, detergent and 0.095% sodium azide . - ready to use; (83-1023-01)
- EliA IgG Conjugate, ß-galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA, detergent and 0.06% sodium azide - ready to use; (83-1017-01, 83-1018-01)
- . EliA ANA Positive Control 250: 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; (83-1033-01)
- EliA IgG/IgM/IgA Negative Control 250: containing normal human serum from healthy donors -. 6 single-use vials, 0.3 mL each, ready to use; (83-1037-01)
- EliA IgG Calibrator Strips, human IgG in PBS (0, 4, 10, 20, 100, 600 µg/L) 6 single-use vials, . 0.3 mL each, ready to use; (83-1015-01)
- EliA IgG Curve Control Strips, human IgG (20 µg/L) in PBS, 6 single-use vials, 0.3 mL each, . ready to use; (83-1016-01)
- EliA IgG Calibrator Wells are coated with mouse monoclonal antibodies 4 carriers, (12 wells each), ready to use; (14-5509-01)
The Phadia EliA immunodiagnostic system is automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages except the positive and neqative controls are required to carry out an EliA Scl-70° test.
J. Substantial Equivalence Information:
-
- Predicate device name(s) and 510(k) number(s): QuantaLite™ Scl-70 ELISA, INOVÀ K924988
6
2. Comparison with predicate:
Similarities to predicate device
| Feature | Predicate Device | New Device |
|---|---|---|
| INOVA QuantaLite Scl-70 ELISA | EliA Scl-70S | |
| Intended Use | QUANTALite Scl-70 is an en- | |
| zyme-linked immunosorbent as- | ||
| say (ELISA) for the semi- | ||
| quantitative detection of Scl-70 | ||
| antibodies in human serum. The | ||
| presence of Scl-70 antibodies | ||
| can be used in conjunction with | ||
| clinical findings and other labora- | ||
| tory tests to aid in the diagnosis | ||
| of scleroderma. | EliA Scl-70S is intended for the in | |
| vitro semi-quantitative measure- | ||
| ment of IgG antibodies directed | ||
| to Scl-70 in human serum and | ||
| plasma (heparin, EDTA) as an | ||
| aid in the clinical diagnosis of | ||
| scleroderma (diffuse form) in | ||
| conjunction with other laboratory | ||
| and clinical findings. EliA Scl-70S | ||
| uses the EliA IgG method on the | ||
| instruments Phadia 100 or Pha- | ||
| dia 250. | ||
| Internal Controls | Low Positive, High Positive and | |
| Negative Control | ||
| included in the kit | Positive and negative Control | |
| provided with the EliA ANA Posi- | ||
| tive Control 100 / 250 and EliA | ||
| IgG/IgM/IgA Negative Control | ||
| 100 / 250, respectively | ||
| Assay Type | ELISA | |
| Type of test | Semi-quantitative | |
| Solid Phase | Microwells |
Differences to predicate device
| Differences to predicate device | ||
|---|---|---|
| Feature | Predicate Device | |
| INOVA QuantaLite Scl-70 ELISA | New Device | |
| EliA Scl-70S | ||
| Antigen used | purified Scl-70 antigen | Human recombinant Scl-70 pro- |
| tein | ||
| Instrumentation | ELISA-Reader needed | Phadia 100, Phadia 250 are fully |
| automated immunoassay ana- | ||
| lyzers | ||
| Reaction tempera- | ||
| ture | Room temperature, 20-26°C | 37°C controlled |
| Incubation times | High positive, low positive and | |
| negative Controls, diluted patient | ||
| samples: 30 min. | ||
| Conjugate: 30 min. | ||
| Substrate: 30 min (in dark). | Diluted patient samples: 30 min. | |
| Conjugate: 28 min. | ||
| Development Solution: 39 min. | ||
| Detection antibody | ||
| (conjugate) | IgG conjugate: anti-human IgG | |
| horse radish peroxidase (goat) | IgG conjugate: anti-human IgG | |
| β-Galactosidase (mouse mono- | ||
| clonal antibodies) | ||
| Signal | Optical density (at 450nm) | Fluorescence |
| Calibration | 1-point Calibration | Total IgG Calibration |
| Calibrators | n.a. | 6 vials of human IgG at concen- |
| trations of | ||
| 0 - 4 - 10 - 20 - 100 - 600 µg/l | ||
| Calibration curve | n.a. | Option to store curve for up to 28 |
| days and run curve controls in | ||
| each assay for calibration | ||
| Concept | All reagents in a single kit | Modular reagents concept |
| (test-method specific and general |
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| Feature | Predicate Device
INOVA QuantaLite Scl-70 ELISA | New Device
EliA Scl-70S
reagents) |
|-----------------|-----------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Sample Dilution | 1:101 | 1:100 |
| Reported Unit | Units | EliA U/ml |
| Cut-off | 80 Units strong positive | 10.0 EliA U/ml positive |
| Substrate | TMB Chromogen | Development Solution 0.01 %
4-Methylumbelliferyl-β-D-
galactoside & 10 EliA U/mL | Positive |
In case of equivocal results, it is recommended to retest the patient after 8-12 weeks.
2. Comparison studies:
Method comparison with predicate device: a.
A total of 390 serum samples were collected from patients with diagnosis of Scleroderma (SSc. n = 101), limited cutaneous form of systemic sclerosis (CREST, n = 33), Mixed connective tissue disease (MCTD, n = 37), Systemic lupus erythematodes (SLE, n = 34), Sjögren's syndrome (SS, n = 26), Poly/Dermatomyositis (PM/DM, n = 5), Rheumatoid arthritis (RA, n = 30), various cancers (n = 20), various bacterial infections (n = 24), various viral infections (n = 26), technical samples positive or equivocal for EliA Scl-70° (n = 54).
Samples were analyzed with the EliA Scl-70° and INOVA QuantaLite™ Scl-70 ELISA assays. The test was run in single determination and values outside the linear measuring range (n=16) were excluded from statistical analyses for the technical agreement. The results are summarized in the tables below:
| QuantaLite Scl-70 ELISA (Units) | ||||
|---|---|---|---|---|
| Positive >20 | Negative 10 | 51 | 9 | |
| Negative ≤10 | 6 | 308 | 314 | |
| Total | 57 | 317 | 374 | |
| Positive percent agreement: 89.5% (95% CI: 77.8 – 95.6%) | ||||
| Negative percent agreement: 97.2% (95% CI: 94.5 – 98.6%) | ||||
| Total percent agreement: 95.9% (95% CI: 93.3 – 97.7%) |
Equivocal results evaluated as negative:
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Equivocal results evaluated as positive:
| QuantaLite Scl-70 ELISA (Units) | ||||
|---|---|---|---|---|
| Positive >20 | Negative 10 | 53 | ||
| Negative ≤10 | 4 | 296 | 300 | |
| Total | 57 | 317 | 374 | |
| Positive percent agreement: | ||||
| 93.0% (95% CI: 82.2 – 97.8%) |
Negative percent agreement: 93.4% (95% Cl: 89.9 - 95.8%) Total percent agreement: 93.3% (95% CI: 90.2 - 95.5%)
b. Matrix comparison:
Serum, lithium heparin plasma, and EDTA plasma were collected from the same patients (n = 50) to demonstrate that the plasma results do not deviate from the corresponding serum results and are within the pre-defined specifications.
Samples were spiked with a serum sample of high antibody titer to cover the measuring range. Samples were tested in duplicates. Passing & Bablok regression plots were generated using the first replicate only and by plotting the concentration observed from the control tube (serum) versus the concentration for each test collection tube. The corresponding slopes of regression and coefficient determination are summarized in the tables below:
| | Range tested
(EliA U/mL) | Slope
(95% CI) | Intercept
(95% CI) | R2 |
|----------------------------|-----------------------------|------------------------|---------------------------|------|
| Serum vs heparin
plasma | 0.6 — 278.9 | 1.05
(1.03 to 1.07) | -0.08
(-0.24 to +0.17) | 1.00 |
| Serum vs EDTA
plasma | 0.6 — 264.2 | 1.00
(0.99 to 1.02) | -0.05
(-0.29 to +0.21) | 1.00 |
C. Instrument comparison
Performance of EliA Scl-70° was evaluated on the Phadia 250 instruments using 24 positive, 8 equivocal and 4 negative samples were analyzed in six runs in single replicates on three Phadia 250 instruments, with 2 runs on each instrument. The regression analysis results are summarized as follows:
| Intercept | Slope | |
|---|---|---|
| Estimate | -0.07 | 0.96 |
| 95% Cl | -0.52 – 0.14 | 0.94 – 0.99 |
3. Clinical studies:
Clinical Sensitivity and specificity: a.
336 clinically defined sera from patients with scleroderma or other connective tissue diseases, bacterial or viral infections, cancer or rheumatoid arthritis were tested on EliA Scl-70° as laid out in the respective Directions for Use
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Test results of EliA Scl-70 with 336 clinically defined samples. The diagnostic group of Scleroderma diagnosed patients (SSc) is the positive target group. Equivocal results evaluated as negative:
| Diagnostic Group - SSc | |||
|---|---|---|---|
| + / SSc | - / Controls* | total | |
| Positive test >10 EliA U/mL | 31 | 3 | 34 |
| Negative test ≤10 EliA U/mL | 70 | 232 | 302 |
| Total | 101 | 235 | 336 |
Sensitivity: 30.7% (95% CI: 22.1% - 40.8%) Specificity: 98.7% (95% CI: 96.0% - 99.7%)
The table below shows the positive results for each clinical subgroup. Equivocal results evaluated as negative:
| Disease | Total number
of samples | Number & percentage of positive samples
QuantaLite Scl-70 | | Elia Scl-70s | |
|------------|----------------------------|--------------------------------------------------------------|-----|--------------|-----|
| SSc | 101 | 29 | 29% | 31 | 31% |
| CREST | 33 | 2 | 6% | 2 | 6% |
| MCTD | 37 | 0 | 0% | 0 | 0% |
| SLE | 34 | 1 | 3% | 0 | 0% |
| SS | 26 | 1 | 4% | 1 | 4% |
| PM/DM | 5 | 0 | 0% | 0 | 0% |
| RA | 30 | 0 | 0% | 0 | 0% |
| Cancer | 20 | 0 | 0% | 0 | 0% |
| Infections | 50 | 2 | 4% | 0 | 0% |
SSc: Scleroderma, CREST: limited cutaneous form of systemic sclerosis, MCTD: Mixed connective tissue disease, SLE: Systemic Lupus Erythematosus, SS: Sjögren's syndrome- systemic sclerosis, PM/DM: Poly-/Dermatomyositis, RA: Rheumatoid arthritis, Cancer: various cancers, Infections: various bacterial and viral infections.
Other clinical supportive data (when a. is not applicable): b. Not applicable
-
- Clinical cut-off:
Same as assay cut-off
- Clinical 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 Scl-70 antibodies covered by the EliA Scl-70 test is below 1 %. Expected values may vary depending on the population tested.
- Expected values/Reference range: