(273 days)
Not Found
No
The device description details a standard automated immunoassay system that measures light units and converts them to chemiluminescent units based on a predefined master curve and calibrators. There is no mention of algorithms that learn or adapt from data, which are characteristic of AI/ML.
No
The device is an in vitro diagnostic immunoassay used for the semi-quantitative determination of IgG autoantibodies to ß2GP1-Domain1 in human serum, aiding in the diagnosis of antiphospholipid syndrome. It is not designed to treat, cure, or prevent any disease.
Yes
The device is described as an "aid in the diagnosis of antiphospholipid syndrome," which directly indicates its use in the diagnostic process.
No
The device description explicitly states that the system includes "liquid handling hardware, luminometer and computer with software-user interface" and utilizes a "reagent cartridge format." This indicates the device is a complex system involving both hardware and software components, 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 an "in vitro chemiluminescent immunoassay (CIA) for the semi-quantitative determination of IgG autoantibodies to ß2GP1-Domain1 in human serum." This clearly indicates that the test is performed outside of the body using a biological sample (human serum).
- Purpose: The intended use also states that the results are used "as an aid in the diagnosis of antiphospholipid syndrome." This aligns with the definition of an IVD, which is used to diagnose or aid in the diagnosis of a condition.
- Device Description: The description details a laboratory-based assay using reagents and an automated instrument to analyze a biological sample. This is characteristic of an IVD.
The information provided strongly supports the classification of this device as an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
The QUANTA Flash® ß2GP1-Domain1 is an in vitro chemiluminescent immunoassay (CIA) for the semi-quantitative determination of IgG autoantibodies to ß2GP1-Domain1 in human serum. The presence of anti-B2GP1- Domain1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The OUANTA Flash® B2GP1-Domain1 is not intended to replace assays for antibodies against the whole ß2GP1 molecule. Testing for antibodies to the whole is required according to the classification criteria for antiphospholipid syndrome.
The QUANTA Flash ß2GP1-Domain1 Controls are intended for quality control purposes of the QUANTA Flash ß2GP1-Domain1 chemiluminescent immunoassay (CIA) kit.
The HemosIL® AcuStar Anti-S2GPI Domain 1 is an in vitro chemiluminescent immunoassay (CIA) for the semiquantitative determination of IgG autoantibodies to B2GPI Domain 1 in human serum. The presence of anti-R2GPI Domain 1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The HemosIL® AcuStar Anti-ß2GPI Domain 1 is not intended to replace assays for antibodies against the whole ß2GPI molecule. Testing for antibodies to the whole ß₂GPI molecule is required according to the classification criteria for antiphospholipid syndrome.
The HemosIL AcuStar Anti-B2GPI Domain 1 Controls are intended for quality control purposes of the HemosIL AcuStar Anti-ß2GPI Domain 1 chemiluminescent immunoassay (CIA) kit.
Product codes (comma separated list FDA assigned to the subject device)
MSV, JJX
Device Description
The QUANTA Flash® ß2GP1-Domain1 assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash® ß2GP1-Domain1 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.
The assays included in this submission, the QUANTA Flash ß2GP1-Domain1 marketed by Inova Diagnostics Inc. (9900 Old Grove Road, San Diego, CA 92131) and HemoslL AcuStar Anti-ß-GPI Domain 1 marketed by Instrumentation Laboratory (180 Hartwell Road Bedford, MA 01730), are equivalent assays. Therefore all data stated hereafter and referred to as: QUANTA Flash §2GP1-Domain1 data is equivalently also valid for HemosIL "AcuStar Anti-ß₂GPI Domain 1.
Recombinant ß2GP1-Domain1 protein is coated onto paramagnetic beads, which are stored lyophilized in the reagent cartridge. The reagent pack is prepared for use in the BIO-FLASH system by pressing down on the grey lid of the reagent pack to pierce the induction seals on the reagent tubes. Once the seals are broken, the beads are rehydrated by adding the entire contents of the vial of resuspension buffer to the bead reagent tube using the transfer pipette supplied with the kit. Only the hole above the bead reagent tube is accessible at this point. The beads are then mixed with the resuspension buffer by pipetting up and down 30 times. This amount of mixing ensures complete resuspension of the beads. The label covering the remaining three reagent holes is now removed, and the reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in sample racks. A patient serum sample is prediluted 1:10 by the BIO-FLASH with system rinse in a small disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are all combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. Isoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(III) coproporphyrin in sodium hydroxide solution) and Trigger 2 (urea-hydrogen peroxide in sodium chloride solution) are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti- ß2GP1-Domain1 antibodies bound to the corresponding ß2GP1-Domain1 on the beads.
The QUANTA Flash® ß2GP1-Domain1 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash® ß2GP1-Domain1 Calibrators. Based on the results obtained with the two Calibrators included in the reagent kit, an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU) from the instrument signal (RLU) obtained for each sample.
The QUANTA Flash® ß2GP1-Domain1 kit contains the following materials:
One (1) QUANTA Flash ß2GP1-Domain1 Reagent Cartridge, containing the following reagents for 50 determinations:
a. ß2GP1-Domain1 antigen coated paramagnetic beads in a suspension.
b. Assay Buffer - buffer containing protein stabilizers and preservatives.
C. Tracer IgG - Isoluminol labeled anti-human IgG antibodies in buffer, containing protein stabilizers and preservative.
d. Resuspension Buffer 3 - buffer containing protein stabilizers and preservatives.
e. QUANTA Flash ß2GP1-Domain1 Calibrator 1: One (1) barcode labeled tube containing 1.0 mL prediluted, ready to use reagent. Calibrators contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
f. QUANTA Flash ß2GP1-Domain1 Calibrator 2: One (1) barcode labeled tube containing 1.0 mL prediluted, ready to use reagent. Calibrators contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
The QUANTA Flash 12GP1-Domain1 Controls kit contains three vials of Low Control and three vials of High Control.
Low Control: Three (3) barcode labeled tubes containing 1.0 mL, ready to use reagent. Controls contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
High Control: Three (3) barcode labeled tubes containing 1.0 mL, ready to use reagent. Controls contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
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
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision:
Study Type: Precision study according to CLSI EP5-A2 guideline.
Sample Size: 80 measurements for each of 8 samples.
Key Results: Total %CV values were within the acceptance limit (15%), ranging from 5.6-10.6% for β2GP1-Domain1 samples.
Limit of Blank (LoB) and Limit of Detection (LoD):
Study Type: LoD and LoB determination consistent with CLSI EP17-A guideline.
Sample Size: 264 determinations (144 measurements on blank samples, 120 measurements of low level samples).
Key Results: LoD = 1296 RLU, LoB = 425.7 RLU.
Auto-rerun function validation:
Study Type: Performance validation of Auto-rerun function.
Sample Size: 3 high positive specimens.
Key Results: % recovery values for auto-rerun results compared to manual dilution were between 91.9% and 99% (average 94%), within the ± 20% acceptance limit.
High concentration hook effect:
Study Type: Hook effect assessment.
Key Results: No hook effect observed up to 435,000 RLU for high positive specimens.
Linearity:
Study Type: Linearity evaluation according to CLSI EP6-A.
Sample Size: 5 serum samples.
Key Results: Percent recovery for all 100 data points ranged from 83.9% to 113.9%, or less than 4 CU. Linear regression for β2GP1-Domain1 showed a slope of 1.01 (95% CI: 0.99 to 1.02), Y-intercept of -3.18 (-9.20 to 2.83), R of 1.00.
Interference:
Study Type: Interference study.
Key Results: No interference detected with bilirubin up to 100 mg/dL (recovery: 92.9% to 97.6%), hemoglobin up to 200 mg/dL (recovery: 95.6% to 97.2%), triglycerides up to 1000 mg/dL (recovery: 92.5% to 100%), cholesterol up to 224.3 mg/dL (recovery: 92.5% to 100%), and RF IgM up to 500 IU/mL (recovery: 86.2% to 98.3%).
Cross-reactivity:
Study Type: Evaluation of potential cross-reactivity.
Sample Size: 111 clinical samples.
Key Results: Only 2 out of 111 samples showed reactivity with QUANTA Flash ß2GP1 Domain1 CIA despite high levels of other autoantibodies. Fisher test revealed no significant association, indicating no significant cross-reactivity.
Stability (Shelf life):
Study Type: Accelerated stability studies.
Key Results: All components fulfilled acceptance criteria for one year preliminary expiration dating.
Stability (In-use/onboard stability of Calibrators):
Study Type: Onboard stability assessment.
Key Results: Calibrators were stable for up to 4 calibrations over an 8-hour period, with RLU values within 90-110% range.
Stability (In-use/onboard stability of Controls):
Study Type: Onboard stability assessment.
Key Results: Controls remained within their acceptable range for all 20 runs, with linear regression line remaining between 85% and 115% at run 15. The controls were given a maximum of 15 uses with a maximum of 10 minutes onboard per use.
Stability (In-use/onboard stability of Reagent Cartridge):
Study Type: In-use stability assessment.
Key Results: The in-use (onboard) stability of the reagent cartridge was set at 60 days.
Cut-off, reference range:
Study Type: Reference interval establishment.
Sample Size: 30 subjects (healthy, viral hepatitis, SLE without thrombotic events, syphilis, HIV).
Key Results: Cut-off established at 7880 RLU, defined as 20 CU.
Clinical sensitivity, specificity:
Study Type: Clinical performance validation.
Sample Size: 1090 samples (270 APS patients, 820 control population).
Sensitivity: 51.1% (45.0-57.2%).
Specificity: 99.6% (98.9-99.9%).
ROC Analysis AUC: 0.84 (95% CI: 0.81 to 0.86).
Expected values:
Study Type: Evaluation of anti-ß2GP1-Domain1 antibody levels in healthy blood donors.
Sample Size: 400 apparently healthy blood donors.
Key Results: With a cut-off of 20 CU, one sample (0.2%) was positive (34.2 CU). Mean concentration was 3.8 CU, range
§ 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).
0
Image /page/0/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird symbol.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
FEB 1 8 2015
INOVA DIAGNOSTICS, INC. C/O ROGER ALBESA SUPERVISOR, RESEARCH AND DEVELOPMENT 9900 OLD GROVE ROAD SAN DIEGO CA 92131-1638
Re: K141274
Trade/Device Name: QUANTA Flash® B2GP1-Domain1 QUANTA Flash® ß2GP1-Domain1 Controls HemosIL® Acustar Anti-B2GPI-Domain 1 HemosIL® Acustar Anti-B2GPI-Domain 1 Controls Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MSV, JJX Dated: January 12, 2015 Received: January 14, 2015
Dear Mr. Albesa,
This letter corrects our substantially equivalent letter of February 13, 2015.
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.
1
Page 2 - Mr. Roger Albesa
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.
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/ResourcesforYou/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 yours.
Leonthena R. Carrington -A
Leonthena Carrington, MS, MBA, MT(ASCP) Director (Acting) 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) K141274
Device Name
QUANTA Flash® ß2GP1-Domain1, QUANTA Flash® ß2GP1-Domain1 Controls, HemosIL® AcuStar Anti-ß2GPI Domain1 and HemosIL® AcuStar Anti-ß2GPI Domain 1 Controls.
Indications for Use (Describe)
The QUANTA Flash® ß2GP1-Domain1 is an in vitro chemiluminescent immunoassay (CIA) for the semi-quantitative determination of IgG autoantibodies to ß2GP1-Domain1 in human serum. The presence of anti-B2GP1- Domain1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The OUANTA Flash® B2GP1-Domain1 is not intended to replace assays for antibodies against the whole ß2GP1 molecule. Testing for antibodies to the whole is required according to the classification criteria for antiphospholipid syndrome.
The QUANTA Flash ß2GP1-Domain1 Controls are intended for quality control purposes of the QUANTA Flash ß2GP1-Domain1 chemiluminescent immunoassay (CIA) kit.
The HemosIL® AcuStar Anti-S2GPI Domain 1 is an in vitro chemiluminescent immunoassay (CIA) for the semiquantitative determination of IgG autoantibodies to B2GPI Domain 1 in human serum. The presence of anti-R2GPI Domain 1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The HemosIL® AcuStar Anti-ß2GPI Domain 1 is not intended to replace assays for antibodies against the whole ß2GPI molecule. Testing for antibodies to the whole is required according to the classification criteria for antiphospholipid syndrome.
The HemosIL AcuStar Anti-B2GPI Domain 1 Controls are intended for quality control purposes of the HemosIL AcuStar Anti-ß2GPI Domain 1 chemiluminescent immunoassay (CIA) kit.
| 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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510(k) Summary
This summary of the 510(k) (ref. K141274) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| Submitter: | Inova Diagnostics, Inc.
9900 Old Grove Road,
San Diego, CA, 92131 | |
|------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| Purpose of submission: | New device(s) | |
| Devices in the submission: | QUANTA Flash® β2GP1-Domain1
QUANTA Flash® β2GP1-Domain1 Controls
HemosIL® AcuStar Anti-β₂GPI Domain 1
HemosIL® AcuStar Anti-β₂GPI Domain 1 Controls | |
| Scientific contact: | Roger Albesa, M.S.
Supervisor of Research and Development
Inova Diagnostics, Inc.
9900 Old Grove Road, San Diego, CA 92131
e-mail: ralbesa@inovadx.com
Tel. (858) 586-9900/1394 | |
| Quality Systems contact: | Ronda Elliott, Vice President, Quality and Regulatory
Inova Diagnostics, Inc.
9900 Old Grove Road, San Diego, CA, 92131
e-mail: relliott@inovadx.com
Tel. (858) 586-9900
Fax: 858-863-0025/1381 | |
| Preparation date: | 01/09/2015 | |
| Device name (assay kit): | Proprietary names: QUANTA Flash® β2GP1-Domain1,
HemosIL® AcuStar Anti-β₂GPI Domain 1 | |
| | Common name: Anti-β2GPI Domain 1 Chemiluminescent immunoassay
Classification name: Anti-β2GPI Domain 1 antibody, antigen and control | |
| Regulation Description | Multiple autoantibodies immunological test system | |
| Regulation Medical Specialty | Immunology | |
| Review Panel | Immunology | |
| Product Code | System, Test, Antibodies,B2-Glycoprotein I (B2-GPI) (MSV) | |
| Regulation Number | 866.5660 (Reagent Kit) | |
| Regulation Number | 862.1660 (Controls) | |
| Device Class | 2 | |
| Predicate device: | QUANTA Lite® β2GPI IgG ELISA, 510(k) number: K970551 | |
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Device description:
The QUANTA Flash® ß2GP1-Domain1 assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash® ß2GP1-Domain1 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.
The assays included in this submission, the QUANTA Flash ß2GP1-Domain1 marketed by Inova Diagnostics Inc. (9900 Old Grove Road, San Diego, CA 92131) and HemoslL AcuStar Anti-ß-GPI Domain 1 marketed by Instrumentation Laboratory (180 Hartwell Road Bedford, MA 01730), are equivalent assays. Therefore all data stated hereafter and referred to as: QUANTA Flash §2GP1-Domain1 data is equivalently also valid for HemosIL "AcuStar Anti-ß₂GPI Domain 1.
Recombinant ß2GP1-Domain1 protein is coated onto paramagnetic beads, which are stored lyophilized in the reagent cartridge. The reagent pack is prepared for use in the BIO-FLASH system by pressing down on the grey lid of the reagent pack to pierce the induction seals on the reagent tubes. Once the seals are broken, the beads are rehydrated by adding the entire contents of the vial of resuspension buffer to the bead reagent tube using the transfer pipette supplied with the kit. Only the hole above the bead reagent tube is accessible at this point. The beads are then mixed with the resuspension buffer by pipetting up and down 30 times. This amount of mixing ensures complete resuspension of the beads. The label covering the remaining three reagent holes is now removed, and the reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in sample racks. A patient serum sample is prediluted 1:10 by the BIO-FLASH with system rinse in a small disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are all combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. Isoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(III) coproporphyrin in sodium hydroxide solution) and Trigger 2 (urea-hydrogen peroxide in sodium chloride solution) are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti- ß2GP1-Domain1 antibodies bound to the corresponding ß2GP1-Domain1 on the beads.
The QUANTA Flash® ß2GP1-Domain1 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash® ß2GP1-Domain1 Calibrators. Based on the results obtained with the two Calibrators included in the reagent kit, an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU) from the instrument signal (RLU) obtained for each sample.
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The QUANTA Flash® ß2GP1-Domain1 kit contains the following materials:
One (1) QUANTA Flash ß2GP1-Domain1 Reagent Cartridge, containing the following reagents for 50 determinations:
- a. ß2GP1-Domain1 antigen coated paramagnetic beads in a suspension.
- b. Assay Buffer - buffer containing protein stabilizers and preservatives.
- C. Tracer IgG - Isoluminol labeled anti-human IgG antibodies in buffer, containing protein stabilizers and preservative.
- d. Resuspension Buffer 3 - buffer containing protein stabilizers and preservatives.
- QUANTA Flash ß2GP1-Domain1 Calibrator 1: One (1) barcode labeled tube containing e. 1.0 mL prediluted, ready to use reagent. Calibrators contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
- f. QUANTA Flash ß2GP1-Domain1 Calibrator 2: One (1) barcode labeled tube containing 1.0 mL prediluted, ready to use reagent. Calibrators contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
The QUANTA Flash 12GP1-Domain1 Controls kit contains three vials of Low Control and three vials of High Control.
- । QUANTA Flash ß2GP1-Domain1 Low Control: Three (3) barcode labeled tubes containing 1.0 mL, ready to use reagent. Controls contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
- । QUANTA Flash ß2GP1-Domain1 High Control: Three (3) barcode labeled tubes containing 1.0 mL, ready to use reagent. Controls contain human antibodies to ß2GP1-Domain1 in stabilizers and preservatives.
Intended use(s):
QUANTA Flash ß2GP1-Domain1
The QUANTA Flash 82GP1-Domain1 is an in vitro chemiluminescent immunoassay (CIA) for the semiquantitative determination of IgG autoantibodies to ß2GP1-Domain1 in human serum. The presence of anti-ß2GP1-Domain1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The QUANTA Flash ß2GP1-Domain1 is not intended to replace assays for antibodies against the whole ß2GP1 molecule. Testing for antibodies to the whole ß2GP1 molecule is required according to the classification criteria for antiphospholipid syndrome.
QUANTA Flash ß2GP1-Domain1 Controls
The QUANTA Flash ß2GP1-Domain1 Controls are intended for quality control purposes of the QUANTA Flash ß2GP1-Domain1 chemiluminescent immunoassay (CIA) kit.
HemosIL AcuStar Anti-ß,GPI Domain 1
The HemosIL " AcuStar Anti-R2GPI Domain 1 is an in vitro chemiluminescent immunoassay (CIA) for the semi-quantitative determination of IgG autoantibodies to ß3GPI Domain 1 in human serum. The presence of anti-ß-GPI Domain 1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of antiphospholipid syndrome. The Hemosl ® AcuStar Anti-ß,GPI Domain 1 is not intended to replace assays for antibodies against the whole ß₂GPI molecule. Testing for
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antibodies to the whole ß₂GPI molecule is required according to the classification criteria for antiphospholipid syndrome.
HemosIL AcuStar Anti-ß₂GPI Domain 1 Controls
The HemosIL AcuStar Anti-ß2GPI Domain 1 Controls are intended for quality control purposes of the HemosIL Anti-ß2GPI Domain 1 chemiluminescent immunoassay (CIA) kit.
Substantial equivalence: The QUANTA Flash ß2GP1-Domain1 and the QUANTA Flash ß2GP1-Domain1 Controls have a similar intended use and assay principle as the predicate device.
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Comparison to predicate device:
| QUANTA Flash ® β2GP1-Domain1 reagent kit | |
|---|---|
| -- | ------------------------------------------ |
| Similarities | ||
|---|---|---|
| Item | Applicant | Predicate Device |
| QUANTA Flash ® β2GP1-Domain1 | QUANTA Lite® β2 GPI IgG ELISA | |
| Intended use | The QUANTA Flash ® β2GP1-Domain1 is | |
| an in vitro chemiluminescent | ||
| immunoassay (CIA) for the semi- | ||
| quantitative determination of IgG | ||
| autoantibodies to β2GP1-Domain1 in | ||
| human serum. The presence of anti- | ||
| β2GP1-Domain1 autoantibodies is | ||
| used in conjunction with clinical and | ||
| other laboratory findings as an aid in | ||
| the diagnosis of antiphospholipid | ||
| syndrome. The QUANTA Flash ® β2GP1- | ||
| Domain1 is not intended to replace | ||
| assays for antibodies against the | ||
| whole β2GP1 molecule. Testing for | ||
| antibodies to the whole β2GP1 | ||
| molecule is required according to the | ||
| classification criteria for | ||
| antiphospholipid syndrome. | QUANTA Lite® β2 GPI IgG is an enzyme | |
| linked immunoassay (ELISA) for the | ||
| semi-quantitative detection of β2 GPI | ||
| IgG antibodies in human serum. The | ||
| presence of β₂ GPI IgG antibodies can | ||
| be used in conjunction with clinical | ||
| findings and other laboratory tests to | ||
| aid in the diagnosis of certain | ||
| autoimmune disease thrombotic | ||
| disorders such as those secondary to | ||
| systemic lupus erythematosus (SLE) or | ||
| other lupus-like thrombotic diseases. | ||
| Assay methodology | Solid phase (heterogeneous) | |
| immunoassay | Solid phase (heterogeneous) | |
| immunoassay | ||
| Shelf life | One year | One year |
| Sample type | Serum | Serum |
| Differences | ||
| Item | QUANTA Flash β2GP1-Domain1 | Predicate Device |
| Detection/ | ||
| Operating principle | Chemiluminescent immunoassay | Enzyme-linked immunosorbent assay |
| Solid phase | Paramagnetic microparticles (beads) | 96-well plate |
| Antigen | Recombinant domain1 of β2- | |
| Glycoprotein1 | purified β2-Glycoprotein1 | |
| Conjugate | Isoluminol conjugated anti-human IgG | HRP conjugated anti-human IgG |
| Calibration | Lot specific Master Curve + two | |
| Calibrators (included in kit) | Five lot specific calibrators | |
| (Included in the kit) | ||
| Units | 1380.4 CU by further diluting it by a factor specified in the assay definition file (10 fold), thereby bringing the measured value within the AMR. The final result will be calculated by the software by taking into account the additional dilution factor. As the highest value that can be measured is 1380.4 CU, the highest value that can be reported is 13804 CU. |
To validate the Auto-rerun function, three high positive specimens with results above the analytical measuring range were selected. The samples were run with the Auto-rerun function enabled on the BIO-FLASH. Then the specimens were manually diluted the same way as it happens in the Auto-rerun function (10 fold), and tested on the BIO-FLASH. The results were within the analytical measuring range after auto-rerun or manual dilution for all specimens. The % recovery values for results obtained with the auto-rerun results compared to the results obtained by manual dilution were between 91.9% and 99% (average 94%) and are within the ± 20% acceptance limit.
High concentration hook effect
To assess hook effect, the measurement signal (relative light units, RLU) was examined for the above mentioned four high positive specimens, before and after automatic or manual dilution. All sera produced significantly higher RLU values (above the AMR) when used "as is" compared to the manually or automatically diluted ones, thereby confirming that high positive specimens above the analytical measuring range do not show hook effect up to 435,000 RLU.
Linearity
The linearity of the AMR was evaluated by a study according to CLSI EP6-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline. Five serum samples with various ß2GP1-Domain1 antibody concentrations were diluted with assay buffer to obtain values that cover the AMR. Percent recovery for all 100 data points ranged from 83.9% to 113.9%, or less than 4 CU. All specimens showed dilution linearity individually, and the combined data yielded the following results with linear regression:
| Assay | Test Range (CU) | Slope (95% CI) | Y-intercept (95% CI) | R | Percent Recovery |
|---|---|---|---|---|---|
| ß2GP1-Domain1 | 1.0 to 1640.7 | 1.01 (0.99 to 1.02) | -3.18 (-9.20 to 2.83) | 1.00 | 83.9-113.9% |
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Interference
Interfering substances were spiked into every specimen at three different concentrations in 10% of total specimen volume, and the resulting samples were assessed in triplicates with the ß2GP1-Domain1 assay. Recovery of the unit values was calculated compared to control samples spiked with the same volume of diluents (10% of total). Acceptance criteria for the interference studies were 85%-115% recovery, or ±4 CU difference, whichever is greater.
No interference was detected with bilirubin up to 100 mg/dL (recovery: 92.9% to 97.6%), hemoglobin up to 200 mg/dL (recovery: 95.6% to 97.2%), triglycerides up to 1000 mg/dL (recovery: 92.5% to 100%), cholesterol up to 224.3 mg/dL (recovery: 92.5% to 100%), and RF IgM up to 500 IU/mL (recovery: 86.2% to 98.3%).
Cross-reactivity
A potential cross-reactivity of the QUANTA Flash ß2GP1 Domain1 CIA with other autoantibodies was evaluated with 111 clinical samples with unknown disease states, most having high levels of various other autoantibodies. These samples were tested for various autoantibodies using other QUANTA Flash immunoassays: Sm, RNP, SS-A/Ro60, Ro52, SS-B, Jo-1, Scl-70, CENP, Ribosomal P, DFS70 and the QUANTA Flash 12GP1-Domain1 ClA. These are autoantibodies found in individuals with autoimmune diseases such as SLE, Sjögren's Syndrome, scleroderma, and polymyositis patients. All except for two samples were negative for QUANTA Flash ß2GP1 Domain1 CIA.
Fisher test revealed no significant association between the other positive reactivities and Domain1. This verified that there is no significant cross-reactivity on the QUANTA Flash 182GP1 Domain1 ClA.
| # of Samples tested = 111 | # of Positives (%) | # of Domain1 Positives (%) |
|---|---|---|
| Sm | 6 (5.4%) | 0 (0.0%) |
| RNP | 10 (9.0%) | 0 (0.0%) |
| Ro60 | 11 (9.9%) | 0 (0.0%) |
| Ro52 | 20 (18.0%) | 0 (0.0%) |
| SSB | 8 (7.2%) | 0 (0.0%) |
| Jo-1 | 1 (0.9%) | 0 (0.0%) |
| Scl-70 | 25 (22.5%) | 2 (1.8%) |
| CENP | 0 (0.0%) | 0 (0.0%) |
| Ribosomal P | 5 (4.5%) | 0 (0.0%) |
| DFS70 | 5 (4.5%) | 0 (0.0%) |
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Stability
Shelf life
To establish the initial claim for shelf life, accelerated stability studies were performed for 4 weeks at 37 °C.
Accelerated stability testing was performed on each of the following sealed components of the QUANTA Flash® ß2GP1-Domain1 to establish initial stability claim:
| • QUANTA Flash® β2GP1-Domain1 Reagent Kit | (1 Lot) |
|---|---|
| • β2GP1-Domain1 beads | (3 Lots) |
| • Resuspension Buffer | (3 Lots) |
| • Calibrators 1 and 2 | (3 Lots) |
| • Low and High controls | (3 Lots) |
Each week a new sealed component was placed in the incubator, and all components were tested at the end of the experiment together with the one that was stored at 5 ± 3°C. The recovery of the measured values was calculated for each time point (compared to those obtained with 5 ± 3°C stored reagent). All calculations were performed by comparing results of sealed components stored at 5 ± 3℃ (control) to those stored at 37 ± 3℃ (test) for 1, 2, 3, and 4 weeks, where one week is equal to six months at 5 ± 3℃. Linear regression analysis was performed between recovery values and the number of days.
Acceptance criteria for one year preliminary expiration dating were:
-Microparticles (beads), Resuspension Buffer, and Reagent Kit:
With regression analysis, the lower 95% Cl interval of the regression line is ≥ 85% at 2 weeks, and no individual data point has ≤ 75% recovery at 2 weeks.
- Controls and Calibrators:
With regression analysis, the lower 95% Cl interval of the regression line is ≥ 90% at 2 weeks, and no individual data point has ≤ 80% recovery at 2 weeks.
All components tested fulfilled the acceptance criteria above, so one year expiration dating was assigned to each component
In-use (onboard) stability
Calibrators
During assessing on-board stability, Calibrators were placed, uncapped, onboard the instrument, and calibration was performed altogether five times, then a panel of characterized patient specimens were run on each calibration curve.
Acceptance criteria were: Calibrators are considered stable if all five calibrations performed in the 8.5 hour period are successful, and Calibrator average RLU recovery values are between 90% and 110% compared to the first use.
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A total of 5 successful calibrations were performed over an 8.5 hour period. Calibrator RLU values remained within the 90-110% range. Moreover, all characterized patient samples ran within their expected range. This supports the claim that calibrators can be used for up to 4 calibrations over an 8 hour period.
Controls
During assessing on-board stability, Low and high Controls were assayed for a total of 20 runs, over 9 days. The controls were left uncapped, onboard the instrument for 15 minutes per run. When not in use, the controls were capped, and stored at 5 ± 3°C for at least 2 hours between runs.
Acceptance criteria: Controls are considered stable when all replicates run within their established range, moreover, the linear regression line obtained by plotting %recovery values against the number of runs stays between 85% and 115% at run 15.
Low and high controls ran within their respective acceptable range for all 20 runs. The linear regression line obtained by plotting %recovery values against the number of runs was within 85% and 115% at run 15 for both Controls. The controls were given a maximum of 15 uses with a maximum of 10 minutes onboard per use.
Reagent Cartridge
To determine the in-use stability of the QUANTA Flash® ß2GP1-Domain1 reagent cartridge, four serum specimens (with different reactivity levels) along with the Low and high Control were tested. The specimens were tested periodically for 64 days. Recoveries were calculated compared to the day zero average values, and linear regression analysis was performed. The claim was established using the following criteria (using the one that is fulfilled first):
a) The stability claim is established at the day where the 95% confidence interval of the regression line reaches 85% or 115% recovery, or b) When 2 data points or ≥2% of the recovery data (whichever is greater) is ≤ 75% or ≥ 125%.
The onboard study was ended at 64 days, where all three lots of Reagent Cartridge tested still fulfill the acceptance criteria. The in-use (onboard) stability of the reagent cartridge was set at 60 days.
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Cut-off, reference range
The reference population for establishing the reference interval for the ß2GP1-Domain1 assay consisted of 30 subjects:
| Apparently healthy blood donors | 5 |
|---|---|
| Viral hepatitis | 4 |
| Systemic Lupus erythematosus (without history of thrombotic events) | 10 |
| Syphilis | 10 |
| HIV | 1 |
All specimens were the same matrix as specified in the Intended Use. All specimens were unaltered. The cut-off was established using Analyse-it for Excel, to ensure optimal differentiation between negatives and positives, and found at 7880 RLU. This point was defined as 20 CU. A result below 20 CU is considered negative, and equal or greater than 20 CU is considered positive.
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Clinical performance characteristics
Clinical sensitivity, specificity
A separate set of samples, none of which were used in establishing the reference range, was used to validate the clinical performance of the QUANTA Flash ß2GP1-Domain1 ClA. A total of 1090 samples were included in the Validation Set for the QUANTA Flash ß2GP1-Domain1. This Validation Set includes:
- 270 samples from APS patients
- 71 infectious disease samples (40 syphilis, 10 HCV, 21 HBV)
- 104 samples from Crohn's Disease (CD) patients
- 94 samples from Ulcerative Colitis (UC) patients
- 127 samples from autoimmune scleroderma patients
- . 168 samples from patients with rheumatoid arthritis
- 49 samples from patients with osteoarthritis
- 24 samples from patients with other diseases (Polymyalgia Rheumatica, Degenerative Spine Disease)
- . 183 samples from different conditions "without APS" (Pre-eclampsia/eclampsia, fetal loss, systemic lupus erythematosus (SLE), thrombosis and atopic dermatitis)
Clinical sensitivity and specificity for APS (n=270) using the control population (n=820) is calculated in the table below.
| Cohort 1 (n=938) | Diagnosis | Percent Agreement | |||
|---|---|---|---|---|---|
| APS | Not APS | Total | (95% confidence) | ||
| QUANTA Flash® | |||||
| Domain 1 CIA | Positive | 138 | 3 | 141 | Sensitivity = 51.1% (45.0-57.2%) |
| Negative | 132 | 817 | 949 | Specificity = 99.6% (98.9-99.9%) | |
| Total | 270 | 820 | 1090 |
To assess diagnostic efficiency, ROC analysis was performed on the validation sample pool for APS. The results are below:
| Test | Area | 95% CI | SE | Z | p |
|---|---|---|---|---|---|
| QUANTA Flash B2GP1-Domain1 | |||||
| (CU) | 0.84 | 0.81 to 0.86 | 0.015 | 22.24 |