ImmuLisa Enhanced B2GP1 IgA Antibody ELISA, ImmuLisa Enhanced B2GP1 IgG Antibody ELISA, ImmuLisa Enhanced B2GP1 IgM Antibody ELISA, ImmuLisa Enhanced B2GP1 IgA/IgG/IgM Antibody ELISA
Device Facts
| Record ID | K162788 |
|---|---|
| Device Name | ImmuLisa Enhanced B2GP1 IgA Antibody ELISA, ImmuLisa Enhanced B2GP1 IgG Antibody ELISA, ImmuLisa Enhanced B2GP1 IgM Antibody ELISA, ImmuLisa Enhanced B2GP1 IgA/IgG/IgM Antibody ELISA |
| Applicant | Immco Diagnostics, Inc. |
| Product Code | MSV · Immunology |
| Decision Date | Jun 19, 2017 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5660 |
| Device Class | Class 2 |
Intended Use
ImmuLisa Enhanced™ B2GP1 IgA Antibody ELISA: Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgA antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings. ImmuLisa Enhanced™ B2GP1 IgG Antibody ELISA: Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgG antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings. ImmuLisa Enhanced™ B2GP1 IgM Antibody ELISA: Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings. ImmuLisa Enhanced™ B2GP1 IgA/IgG/IGM Antibody ELISA: Enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of β2-GPI IgA, IgG and IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.
Device Story
Solid-phase ELISA kits for detection of IgA, IgG, IgM, or combined IgA/IgG/IgM autoantibodies against β2-glycoprotein I (β2-GPI) in human serum. Input: patient serum samples; process: manual incubation in β2-GPI antigen-coated microplate wells, washing, addition of HRP-conjugated anti-human antibodies, TMB substrate reaction, and stop solution; output: optical density measured via spectrophotometer at 450 nm. Results expressed in ELISA units/mL (EU/mL). Used in clinical laboratories by technicians; results interpreted by clinicians alongside other laboratory tests (e.g., lupus anticoagulant, anti-cardiolipin) and clinical findings to aid in diagnosis of APS and SLE-associated thrombotic disorders.
Clinical Evidence
Clinical performance evaluated using cohorts of patients with APS, SLE, APS with SLE, and disease controls (autoimmune/infectious). For B2GP1 IgA, sensitivity ranged 9.4-38.3% and specificity 92.0-94.3% depending on diagnosis and indeterminate handling. For B2GP1 IgG, sensitivity 21.4-58.8% and specificity 93.8-95.2%. For B2GP1 IgM, sensitivity 15.8-64.1% and specificity 96.1-97.5%. For combined IgA/IgG/IgM, sensitivity 24.6-84.8% and specificity 91.9%.
Technological Characteristics
Solid-phase ELISA; polystyrene microplate wells; purified human β2-GPI capture antigen; HRP-conjugated goat anti-human IgA/IgG/IgM detection antibodies; TMB substrate; sulfuric acid stop solution. Manual assay format; requires microplate reader (450 nm) and washer. Storage 2–8°C. Results traceable to in-house standards.
Indications for Use
Indicated for qualitative or semi-quantitative detection of β2-GPI IgA, IgG, or IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE).
Regulatory Classification
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).
Predicate Devices
- Inova Quanta Lite® β2GP1 IgA ELISA (K973006)
- Inova Quanta Lite® β2GP1 IgG ELISA (K970551)
- Inova Quanta Lite® β2GP1 IgM ELISA (K973014)
Related Devices
- K013956 — DIAMEDIX IS-ANTI-B2 GLYCOPROTEIN I SCREEN · Diamedix Corp. · Jan 8, 2002
- K013628 — DIAMEDIX IS-ANTI-B2 GLYCOPROTEIN I IGG/IGM TEST SYSTEM · Diamedix Corp. · Dec 21, 2001
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM
A. 510(k) Number:
K162788
B. Purpose for Submission:
New device
C. Measurand:
IgA autoantibodies specific for β₂-GP1
IgG autoantibodies specific for β₂-GP1
IgM autoantibodies specific for β₂-GP1
IgA/IgG/IgM autoantibodies specific for β₂-GP1
D. Type of Test:
Immunoassay, semi-quantitative or qualitative
E. Applicant:
IMMCO Diagnostics, Inc.
F. Proprietary and Established Names:
ImmuLisa Enhanced™ B2GP1 IgA Antibody ELISA
ImmuLisa Enhanced™ B2GP1 IgG Antibody ELISA
ImmuLisa Enhanced™ B2GP1 IgM Antibody ELISA
ImmuLisa Enhanced™ B2GP1 IgA/IgG/IgM Antibody ELISA
G. Regulatory Information:
1. Regulation section:
21 CFR §866.5660, Multiple Autoantibodies Immunological Test System
2. Classification:
Class II
3. Product code:
MSV, System, Test, Antibodies, β₂-Glycoprotein I (β₂-GPI)
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4. Panel:
Immunology (82)
H. Intended Use:
1. Intended uses:
ImmuLisa Enhanced™ B2GP1 IgA Antibody ELISA: Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgA antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.
ImmuLisa Enhanced™ B2GP1 IgG Antibody ELISA: Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgG antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.
ImmuLisa Enhanced™ B2GP1 IgM Antibody ELISA: Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.
ImmuLisa Enhanced™ B2GP1 IgA/IgG/IGM Antibody ELISA: Enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of β2-GPI IgA, IgG and IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings.
2. Indication for use:
Same as intended use
3. Special conditions for use statement:
For prescription use only
4. Special instrument requirements:
An ELISA microplate reader capable of reading absorbance values at 450 nm. If a dual wavelength microplate reader is available, the reference filter should be set at 450/630
2
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nm. An automatic microplate washer capable of accurately dispensing 200 µL of fluid is also required.
I. Device Description:
For ImmuLisa Enhanced™ B2GP1 IgA, or ImmuLisa Enhanced™ B2GP1 IgG, or ImmuLisa Enhanced™ B2GP1 IgM Antibody ELISA:
Each kit consists of 12 x 8 β2-GPI antigen coated microplate with individual break-away microwells; one negative control; three positive controls (one positive for β2-GPI IgA antibodies, one positive for β2-GPI IgG antibodies, and one positive for β2-GPI IgM antibodies); one set of five-level calibrators; three Horse radish peroxidase (HRP) conjugates (HRP goat anti-human IgA conjugate, HRP goat anti-human IgG conjugate and HRP goat anti-human IgM conjugate); TMB enzyme substrate; stop solution; and wash buffer. The results are read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/mL). Semi-quantitative results are reported as: Negative (< 20 EU/mL), Borderline/ Indeterminate (20–25 EU/mL) and Positive (>25 EU/mL).
ImmuLisa Enhanced™ B2GP1 IgA/IgG/IgM Antibody ELISA:
Each kit consists of 12 x 8 β2-GPI antigen coated microplate with individual break-away microwells; negative control; positive control for β2-GPI antibodies; one-level calibrator; Horse radish peroxidase (HRP) goat anti-human IgA/IgG/IgM conjugate; TMB enzyme substrate; stop solution; wash buffer; and diluent. The results are read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/mL). Qualitative results are reported as Negative (< 20 EU/mL) and Positive (≥20 EU/mL).
J. Substantial Equivalence Information:
1. Predicate device name(s) and 510(k) number(s):
Inova Quanta Lite® β2GP1 IgA ELISA, K973006
Inova Quanta Lite® β2GP1 IgG ELISA, K970551
Inova Quanta Lite® β2GP1 IgM ELISA, K973014
2. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | New Device
ImmuLisa Enhanced™ B2GP1 IgA Antibody ELISA | Predicate
Quanta Lite® β2GP1 IgA ELISA |
| Intended Use | Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgA antibodies in human serum to aid in diagnosis of autoimmune thrombotic | Enzyme-linked immunosorbent assay (ELISA) for the semi-quantitative detection of β2-GPI IgA antibodies in human serum. The presence of β2-GPI IgA antibodies |
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| | disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings. | 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 Type | Manual ELISA | Same |
| Solid Phase | Polystyrene microplate wells | Same |
| Capture Antigen | Purified human β2-GPI | Same |
| Sample Type | Serum | Same |
| Kit component set | Includes positive control, negative control, calibrators, conjugate, substrate, diluent, wash buffer, stop solution, microplate well | Same |
| Labeled Detection Antibody (Conjugate) | Goat anti-human IgA conjugated to horseradish peroxidase (HRP) | Same |
| Substrate/ Chromogen | Tetramethylbenzidene (TMB) | Same |
| Stop Solution | Sulfuric Acid | Same |
| Sample Dilution | 1:101 | Same |
| Incubation Times | Positive and negative controls, diluted patient samples: 30 minutes Conjugate: 30 minutes Substrate: 30 minutes (in the dark) | Same |
| Reaction Temperature | Room temperature (20–25°C) | Same |
| Traceability | International Reference Preparation is not available. Results are traceable to in-house standards. | Same |
| Positive Control | β2-GPI IgA antibodies | Same |
| Signal | Optical density | Same |
| Instrumentation | Microwell plate reader (450 nm) | Same |
| Storage | 2–8°C | Same |
| Differences | | |
| --- | --- | --- |
| Item | New Device ImmuLisa Enhanced™ B2GP1 IgA Antibody ELISA | Predicate Quanta Lite® β2 GP1 IgA ELISA |
| Assay Format | Semi-quantitative and qualitative | Semi-quantitative |
| Reported Unit | EU/mL | Standard IgA anti-β2-GPI unit (SAU) |
| Calibrators | Set of 5: Values in EU/mL: 160, 80 40, 20, 1 | Set of 5: Values in SAU: 150, 75, 37.5 18.75 and 9.375 |
| Wash Buffer | Powdered or optional liquid concentrate | Liquid concentrate |
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| Similarities | | |
| --- | --- | --- |
| Item | New Device ImmuLisa Enhanced™ B2GPI IgG Antibody ELISA | Predicate Quanta Lite® β2 GPI IgG ELISA |
| Intended Use | Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgG antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings. | Enzyme-linked immunosorbent assay (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 Type | Manual ELISA | Same |
| Solid Phase | Polystyrene microplate wells | Same |
| Capture Antigen | Purified human β2-GPI | Same |
| Sample Type | Serum | Same |
| Kit Component Set | Includes positive control, negative control, calibrators, conjugate, substrate, diluent, wash buffer, stop solution, microplate well. | Same |
| Labeled Detection Antibody (Conjugate) | Goat anti-human IgG conjugated to HRP | Same |
| Substrate/Chromogen | TMB | Same |
| Stop Solution | Sulfuric Acid | Same |
| Sample Dilution | 1:101 | Same |
| Incubation Times | Positive and negative controls, diluted patient samples: 30 minutes Conjugate: 30 minutes Substrate: 30 minutes (in the dark) | Same |
| Reaction Temperature | Room temperature (20–25°C) | Same |
| Traceability | International Reference Preparation is not available. Results are traceable to | Same |
| | in the dark. | |
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| Differences | | |
| --- | --- | --- |
| Item | New Device ImmuLisa Enhanced™ B2GPI IgG Antibody ELISA | Predicate Quanta Lite® β2 GPI IgG ELISA |
| Assay Format | Semi-quantitative and qualitative | Same |
| Reported Unit | EU/mL | Standard IgG anti-β2-GPI unit (SGU) |
| Calibrators | Set of 5: Values in EU/mL: 160, 80 40, 20, 1 | Set of 5: Values in SGU: 150, 75, 37.5 18.75 and 9.375 |
| Wash Buffer | Powdered or optional liquid concentrate | Liquid concentrate |
| Linear Range | 3.1–160 EU/mL | Not specified |
| Limit of Detection | 3.1 EU/mL | Not specified |
| Results Interpretation | Negative: < 20 EU/mL Borderline: 20–25 EU/mL Positive: > 25 EU/mL | Negative: ≤ 20 SGU Positive: > 20 SGU |
| Similarities | | |
| --- | --- | --- |
| Item | New Device ImmuLisa Enhanced™ B2GPI IgM Antibody ELISA | Predicate Quanta Lite® β2 GPI IgM ELISA |
| Intended Use | Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings. | Enzyme-linked immunosorbent assay (ELISA) for the semi-quantitative detection of β2-GPI IgM antibodies in human serum. The presence of β2-GPI IgM 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 Type | Manual ELISA | Same |
| Solid Phase | Polystyrene microplate wells | Same |
| Capture Antigen | Purified human β2-GPI | Same |
| Sample Type | Serum | Same |
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| Kit Component Set | Includes positive control, negative control, calibrators, conjugate, substrate, diluent, wash buffer, stop solution, microplate well. | Same |
| --- | --- | --- |
| Labeled Detection Antibody Conjugate | Goat anti-human IgM conjugated to HRP | Same |
| Substrate/Chromogen | TMB | Same |
| Stop Solution | Sulfuric Acid | Same |
| Sample Dilution | 1:101 | Same |
| Incubation Times | Positive and negative controls diluted patient samples: 30 min. Conjugate: 30 minutes. Substrate: 30 minutes (in the dark). | Same |
| Reaction Temperature | Room temperature (20–25°C) | Same |
| Traceability | International Reference Preparation is not available. Results are traceable to in-house standards. | Same |
| Positive Control | β2-GPI IgM antibodies | Same |
| Instrumentation | Microwell plate reader (450 nm) | Same |
| Storage | 2–8°C | Same |
| Differences | | |
| --- | --- | --- |
| Item | New Device
ImmuLisa Enhanced™ B2GPI
IgM Antibody ELISA | Predicate
Quanta Lite® β2 GPI
IgM ELISA |
| Assay Format | Semi-quantitative and qualitative | Semi-quantitative |
| Reported Unit | EU/mL | Standard IgM anti-β2-GPI unit
(SMU) |
| Calibrators | Set of 5: Values in EU/mL: 160, 80 40, 20, 1 | Set of 5: Values in SMU: 150, 75, 37.5 18.75 and 9.375 |
| Wash Buffer | Powdered or optional liquid concentrate | Liquid concentrate |
| Linear Range | 2.3–160 EU/mL | Not specified |
| Limit of Detection | 2.3 EU/mL | Not specified |
| Results
Interpretation | Negative: <20 EU/mL
Borderline: 20–25 EU/mL
Positive: >25 EU/mL | Negative: ≤20 SMU
Positive: >20 SMU |
| Similarities | | |
| --- | --- | --- |
| Item | New Device
ImmuLisa Enhanced™ B2GPI
IgA/IgG/IgM Antibody ELISA | Predicates
Quanta Lite® β2 GPI IgA ELISA
Quanta Lite® β2 GPI IgG ELISA
Quanta Lite® β2 GPI IgM ELISA |
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| Intended Use | Enzyme-linked immunosorbent assay (ELISA) for the qualitative or semi-quantitative detection of β2-GPI IgA/IgG/IgM antibodies in human serum to aid in diagnosis of autoimmune thrombotic disorders associated with antiphospholipid syndrome (APS) and APS with systemic lupus erythematosus (SLE) in conjunction with other laboratory tests and clinical findings. | Enzyme-linked immunosorbent assay (ELISA) for the semi-quantitative detection of β2-GPI IgA, IgG or IgM antibodies in human serum. The presence of β2-GPI IgA, IgG or IgM 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 Type | Manual ELISA | Same |
| Solid Phase | Polystyrene microplate wells | Same |
| Capture Antigen | Purified human β2-GPI | Same |
| Sample Type | Serum | Same |
| Kit Component Set | Includes positive control, negative control, calibrators, conjugate, substrate, diluent, wash buffer, stop solution, microplate well. | Same |
| Labeled Detection Antibody(Conjugate) | Goat anti-human IgA conjugated to HRP, Goat anti-human IgG conjugated to HRP and Goat anti-human IgM conjugated to HRP | Same |
| Substrate/Chromogen | TMB | Same |
| Stop Solution | Sulfuric Acid | Same |
| Sample Dilution | 1:101 | Same |
| Incubation Times | Positive and negative controls diluted patient samples: 30 minutes Conjugate: 30 minutes Substrate: 30 minutes (in the dark). | Same |
| Reaction Temperature | Room temperature (20–25°C) | Same |
| Traceability | International Reference Preparation is not available. Results are traceable to in-house standards. | Same |
| Positive Control | β2-GPI IgA/IgG/IgM antibodies | Same |
| Instrumentation | Microwell plate reader (450 nm) | Same |
| Storage | 2–8°C | Same |
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| Differences | | |
| --- | --- | --- |
| Item | New Device
ImmuLisa Enhanced™ B2GPI
IgA/IgG/IgM Antibody ELISA | Predicate
QuantaLite® β2GPI IgA ELISA
QuantaLite® β2GPI IgG ELISA
QuantaLite® β2GPI IgM ELISA |
| Assay Format | Qualitative | Semi-quantitative |
| Reported Unit | EU/mL | SAU, SGU and SMU |
| Calibrators | 30 EU/mL (one-point calibration) | Set of 5: Values in SAU, SGU or SMU: 150, 75, 37.5 18.75 and 9.375 |
| Wash Buffer | Powdered or optional liquid concentrate | Liquid Concentrate |
| Limit of Detection | 2.7 EU/mL | Not specified |
| Results
Interpretation | Negative: < 20 EU/ mL
Positive: ≥ 20 EU/ mL | Negative: ≤ 20 SAU,SGU or SMU
Positive: > 20 SAU,SGU or SMU |
## K. Standard/Guidance Document Referenced:
CLSI guideline EP05-A2, “Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline.”
CLSI guideline EP06-A, “Evaluation of the Linearity of Quantitative Analytical Measurement Procedures: A Statistical Approach.”
CLSI guideline EP07-A2, “Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition.”
CLSI guideline EP09-A2, “Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline.”
CLSI guideline EP12-A2, “User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition.”
CLSI guideline EP17-A, “Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline.”
## L. Test Principle:
The test is performed as a solid phase immunoassay. Controls, calibrators and patient sera are incubated in the β2-GPI antigen coated wells to allow specific antibodies present in the serum to bind to the antigen. Unbound antibodies and other serum proteins are removed by washing the microplate wells. Bound antibodies are detected by adding an enzyme-labeled anti-human IgA, IgG or IgM conjugate or combined anti-human IgA/IgG/IgM conjugate to the microplate wells. Unbound conjugate is removed by washing. Enzyme substrate (TMB) is then added to the wells and the presence of antibodies is
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detected by a color change produced by the conversion of TMB substrate to a colored reaction product. The reaction is stopped and the intensity of the color change, which is proportional to the concentration of antibody, is read by a spectrophotometer at $450~\mathrm{nm}$ . Results are expressed in ELISA units per milliliter (EU/mL) and reported as positive or negative.
Semi-quantitative results are determined from a series of five calibrators (160 EU/mL, 80 EU/mL, 40 EU/mL, 20 EU/mL, and 1 EU/mL). Values less than 20 EU/mL are considered negative results while values greater than 25 EU/mL are considered positive; results between 20 EU/mL and 25 EU/mL are considered 'indeterminate'. The sponsor states the following recommendations in the Package Insert: "Indeterminate results should be retested and evaluated along with other laboratory methods; and when a negative result occurs in the presence of clinical indications or when indeterminate results are obtained, lupus anti-coagulant and anti-cardiolipin antibody testing is recommended as additional testing."
Qualitative results are determined using a ratio of the absorbance of the sample to the absorbance of the cut-off calibrator (20 EU/mL). The ratio is multiplied by the concentration of the cut-off calibrator to give a numerical value. Values greater than or equal to 20 EU/mL are considered positive and $< 20$ EU/mL values are considered negative.
# M. Performance Characteristics:
# 1. Analytical performance:
The results of all studies met the manufacturer's pre-determined acceptance criteria.
# a. Precision/Reproducibility:
# Semi-Quantitative Precision:
Precision performance was evaluated in accordance with CLSI guideline EP05-A2. Native sera from the Intended Use population that cover the analytical measuring range were tested and included samples in the negative range, $\sim 20\%$ below cut-off, around the cut-off, $\sim 20\%$ above cut-off and in the moderate positive range of the assays. All specimens were assayed 12 times on one day to determine intra-assay repeatability. The same five specimens were also assayed across 13 runs with six repetitions in each over a period of four weeks to assess reproducibility at three sites using two sets of equipment. An additional 12 replicates were run on the first set of equipment (total replicates $= 90$ ). Assays were performed by two operators using one reagent lot and different equipment sets. The first operator performed the assay manually with a multi-channel pipettor, microplate washer and microplate reader. The second operator used an automatic system with a liquid handling system including a microplate reader. One assay lot was used for the study. Tabulated below are the precision and reproducibility results:
B2GPI IgA Semi-Quantitative Precision:
| Specimen | Mean (EU/mL) | Repeatability | | Between Days | | Total Imprecision | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | CV% | SD | CV% | SD | CV% |
| B2GPI | 2.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| B2GPI | 2.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
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B2GPI IgG Semi-Quantitative Precision:
| Specimen | Mean (EU/mL) | Total Imprecision Manual/Operator #1 | | Total Imprecision Automated/Operator # 2 | |
| --- | --- | --- | --- | --- | --- |
| | | SD | CV% | SD | %CV |
| 1 | 10.1 | 0.9 | 8.9 | 1.2 | 11.7 |
| 2 | 15.6 | 0.7 | 4.5 | 0.8 | 5.3 |
| 3 | 21.2 | 1.2 | 5.7 | 1.2 | 5.7 |
| 4 | 25.0 | 1.0 | 4.1 | 1.2 | 4.6 |
| 5 | 56.0 | 1.7 | 3.2 | 3.6 | 6.4 |
| 6 | 109.8 | 4.6 | 4.2 | 6.0 | 5.5 |
| 7 | 154.0 | 11.1 | 7.2 | 8.1 | 5.3 |
| Specimen | Mean (EU/mL) | Total Imprecision Manual/Operator #1 | | Total Imprecision Automated/Operator # 2 | |
| --- | --- | --- | --- | --- | --- |
| | | SD | CV% | SD | CV% |
| 1 | 10.1 | 1.01 | 10.0 | 1.22 | 12.1 |
| 2 | 15.6 | 0.89 | 5.7 | 0.70 | 4.5 |
| 3 | 21.2 | 1.10 | 5.2 | 1.23 | 5.8 |
| 4 | 25.0 | 1.24 | 5.0 | 1.09 | 4.4 |
| 5 | 56.0 | 2.69 | 4.8 | 3.41 | 6.1 |
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B2GPI IgM Semi-Quantitative Precision:
| Specimen | Mean (EU/mL) | Repeatability | | Between Days | | Total Imprecision | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | CV% | SD | CV% | SD | CV% |
| 1 | 11.1 | 1.1 | 8.9 | 1.2 | 11.2 | 1.7 | 15.0 |
| 2 | 17.3 | 1.2 | 6.9 | 1.6 | 9.3 | 2.0 | 11.5 |
| 3 | 19.7 | 0.7 | 3.8 | 2.1 | 10.8 | 2.1 | 10.6 |
| 4 | 26.1 | 1.4 | 5.7 | 1.6 | 5.9 | 1.6 | 6.1 |
| 5 | 83.7 | 3.5 | 4.2 | 4.1 | 4.8 | 4.0 | 4.7 |
| 6 | 114.8 | 7.6 | 6.8 | 9.3 | 8.1 | 9.2 | 8.0 |
| 7 | 159.4 | 9.1 | 6.1 | 8.5 | 5.3 | 9.4 | 5.9 |
| Specimen | Mean (EU/mL) | Total Imprecision Manual/Operator #1 | | Total Imprecision Automated/Operator # 2 | |
| --- | --- | --- | --- | --- | --- |
| | | SD | CV% | SD | CV% |
| 1 | 11.1 | 0.98 | 8.8 | 1.35 | 12.2 |
| 2 | 17.3 | 1.93 | 11.2 | 1.36 | 7.9 |
| 3 | 19.7 | 1.88 | 9.6 | 2.18 | 11.1 |
| 4 | 26.1 | 1.20 | 4.6 | 1.60 | 6.1 |
| 5 | 83.7 | 3.74 | 4.5 | 4.07 | 4.9 |
| 6 | 114.8 | 8.51 | 7.4 | 9.51 | 8.3 |
| 7 | 159.4 | 6.42 | 4.0 | 9.00 | 5.6 |
# Qualitative Reproducibility:
Studies were performed under the guidance of CLSI EP12-A2. Ninety replicates each of native sera in the negative range, $\sim 20\%$ below cut-off, at $\sim$ cut-off, $\sim 20\%$ above cut-off and in the moderate positive range of the assays were tested for qualitative reproducibility. These samples were tested in multiple runs same as in semi-quantitative precision study. The results of these studies are presented in the tables below.
# Qualitative Reproducibility:
B2GPI IgA Qualitative Precision:
| Specimen | Mean (EU/mL) | % Negative | % Positive |
| --- | --- | --- | --- |
| Low Negative | 8.3 | 100 | 0 |
| Cut-off -20% | 15.4 | 100 | 0 |
| Low Cut-off -20% | 15.4 | 100 | 0 |
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| Cut-off | 20.9 | 23.3 | 76.7 |
| --- | --- | --- | --- |
| Cut-off +20% | 24.2 | 0 | 100 |
| Moderate Positive | 64.8 | 0 | 100 |
| Moderate to High Pos | 128.6 | 0 | 100 |
B2GPI IgG Qualitative Precision:
| Specimen | Mean (EU/mL) | % Negative | % Positive |
| --- | --- | --- | --- |
| Low Negative | 9.8 | 100 | 0 |
| Cut-off -20% | 14.8 | 100 | 0 |
| Cut-off | 20.8 | 23.3 | 76.7 |
| Cut-off +20% | 24.5 | 0 | 100 |
| Moderate Positive | 59.4 | 0 | 100 |
| Moderate to High Pos | 96.7 | 0 | 100 |
B2GPI IgM Qualitative Precision:
| Specimen | Mean (EU/mL) | % Negative | % Positive |
| --- | --- | --- | --- |
| Low Negative | 10.3 | 100 | 0 |
| Cut-off -20% | 14.5 | 100 | 0 |
| Cut-off | 19.7 | 61.1 | 38.9 |
| Cut-off +20% | 26.1 | 0 | 100 |
| Moderate Positive | 100.5 | 0 | 100 |
| Moderate to High Pos | 151.4 | 0 | 100 |
B2GPI IgA/IgG/IgM Qualitative Precision:
| Specimen | Mean (EU/mL) | % Negative | % Positive |
| --- | --- | --- | --- |
| Low Negative | 8.0 | 100 | 0 |
| Cut-off -20% | 17.4 | 97.8 | 2.2 |
| Cut-off | 19.8 | 50 | 50 |
| Cut-off +20% | 24.8 | 0 | 100 |
| Moderate Positive | 62.7 | 0 | 100 |
| Moderate to High Pos | 135.9 | 0 | 100 |
# Lot-to-Lot Reproducibility:
Lot-to-lot reproducibility was tested by using samples spanning the assay range, similar to the samples used in the precision study, above. Three assay lots were used in the study. Assays were performed by two operators using different equipment sets. The first operator performed the assay manually with a multichannel pipettor, microplate washer and microplate reader. The second
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operator used an automatic system with a liquid handling system including a microplate reader. Each of the seven samples below was tested in three runs with three replicates over three days on each of the three assay lots (81 replicates/sample).
B2GPI IgA Lot-to-Lot Reproducibility:
| Specimen | Mean (EU/mL) | Lot 1 CV% | Lot 2 CV% | Lot 3 CV% | Inter-Lot CV% |
| --- | --- | --- | --- | --- | --- |
| 1 | 10.2 | 9.6 | 8.6 | 10.3 | 12.6 |
| 2 | 16.0 | 7.0 | 6.3 | 6.6 | 9.5 |
| 3 | 20.8 | 6.3 | 4.6 | 4.6 | 7.9 |
| 4 | 25.7 | 6.1 | 7.1 | 5.9 | 8.7 |
| 5 | 56.5 | 3.6 | 4.0 | 3.0 | 6.4 |
| 6 | 114.9 | 2.9 | 2.6 | 4.0 | 5.6 |
| 7 | 168.1 | 3.4 | 4.5 | 5.0 | 8.3 |
B2GPI IgG Lot-to-Lot Reproducibility:
| Specimen | Mean (EU/mL) | Lot 1 CV% | Lot 2 CV% | Lot 3 CV% | Inter-Lot CV% |
| --- | --- | --- | --- | --- | --- |
| 1 | 12.6 | 7.5 | 7.0 | 6.3 | 9.0 |
| 2 | 15.7 | 5.8 | 5.7 | 5.3 | 6.6 |
| 3 | 21.3 | 6.4 | 6.0 | 5.1 | 8.4 |
| 4 | 26.3 | 7.2 | 7.4 | 5.9 | 8.4 |
| 5 | 52.8 | 5.1 | 4.7 | 5.4 | 5.3 |
| 6 | 110.7 | 7.1 | 6.1 | 6.9 | 6.6 |
| 7 | 158.3 | 5.4 | 3.7 | 5.4 | 5.1 |
B2GPI IgM Lot-to-Lot Reproducibility:
| Specimen | Mean (EU/mL) | Lot 1 CV% | Lot 2 CV% | Lot 3 CV% | Inter-Lot CV% |
| --- | --- | --- | --- | --- | --- |
| 1 | 10.5 | 6.6 | 13.0 | 13.8 | 13.7 |
| 2 | 15.3 | 6.1 | 8.8 | 9.5 | 10.1 |
| 3 | 20.7 | 4.8 | 7.3 | 7.1 | 6.8 |
| 4 | 27.2 | 6.8 | 4.4 | 4.5 | 6.3 |
| 5 | 85.3 | 4.9 | 4.0 | 3.9 | 6.0 |
| 6 | 112.7 | 8.5 | 8.2 | 7.8 | 9.2 |
| 7 | 160.6 | 7.0 | 4.0 | 4.2 | 6.3 |
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B2GPI IgA/IgG/IgM Lot-to-Lot Reproducibility:
| Specimen | Mean (EU/mL) | Lot 1 CV% | Lot 2 CV% | Lot 3 CV% | Inter-Lot CV% |
| --- | --- | --- | --- | --- | --- |
| 1 | 8.2 | 9.7 | 12.1 | 11.3 | 12.4 |
| 2 | 16.7 | 7.7 | 5.8 | 8.1 | 7.5 |
| 3 | 18.7 | 6.6 | 5.4 | 7.8 | 7.7 |
| 4 | 24.7 | 8.2 | 4.6 | 4.2 | 7.2 |
| 5 | 63.4 | 6.4 | 8.0 | 9.1 | 8.0 |
| 6 | 132.8 | 6.4 | 5.2 | 5.3 | 6.7 |
# b. Linearity/assay reportable range:
Linearity and recovery were tested by diluting positive specimens with equidistant dilutions across the measuring range and comparing actual vs. expected results. The linear range of the IgA assay was determined to be 3.6–160 EU/ml. The linear range of the IgG assay was determined to be 3.1–160 EU/ml. The linear range of the IgM assay was determined to be 2.3–160 EU/ml. Results of the linear regression analysis are summarized below:
B2GPI IgA:
| Specimen | Dilution Range (EU/mL) | Slope (95% CI) | Y-Intercept (95% CI) | R2 | % Recovery |
| --- | --- | --- | --- | --- | --- |
| 1 | 2.3 to 17.8 | 1.06 (0.89 to 1.21) | -0.59 (-2.4 to 1.2) | 0.9767 | 88% to 112% |
| 2 | 11.0 to 63.9 | 1.05 (0.97 to 1.14) | -0.77 (-4.2 to 2.6) | 0.9934 | 93% to 105% |
| 3 | 59.0 to 168.3 | 1.08 (0.94 to 1.22) | -0.68 (-16.7 to 15.4) | 0.9915 | 90% to 100% |
B2GPI IgG:
| Specimen B | Dilution Range (EU/mL) | Slope (95% CI) | Y-Intercept (95% CI) | R2 | % Recovery |
| --- | --- | --- | --- | --- | --- |
| 1 | 2.1 to 41.4 | 1.04 (0.89 to1.19) | 0.2 (-1.8 to 4.9) | 0.9807 | 82% to 100% |
| 2 | 4.1 to 140.9 | 1.03 (0.93 to 1.13) | 4.13 (-3.9 to 12.1) | 0.9905 | 86% to 100% |
| B2GPI IgM: | 3.3 to 198.1 | 0.99 (0.91 to 1.07) | 7.25 (-1.8 to 16.3) | 0.9936 | 82% to 100% |
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B2GPI IgM:
| Specimen | Dilution Range (EU/mL) | Slope (95% CI) | Y-Intercept (95% CI) | R² | % Recovery |
| --- | --- | --- | --- | --- | --- |
| 1 | 1.7 to 63.4 | 1.00 (0.95 to 1.05) | 1.8 (-0.1 to 3.6) | 0.9974 | 81% to 100% |
| 2 | 5.4 to 87.5 | 1.02 (0.93 to 1.10) | 2.3 (-1.9 to 6.4) | 0.9936 | 89% to 100% |
| 3 | 54.7 to 173.5 | 0.96 (0.82 to 1.09) | 3.1 (-13.1 to 19.4) | 0.9963 | 86% to 100% |
High dose hook effect: High antibody concentrations specimens above 160 EU/mL were tested. No hook effect was demonstrated in dilution sample levels up to 228.6 EU/mL for IgA; 597.6 EU/mL for IgG; and 605.5 EU/mL for IgM.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
i. Traceability:
There are currently no recognized international standards for the measurement of β2-GP1 IgA, β2-GP1 IgG and β2-GP1 IgM antibodies. Calibrator and Control values are directly traceable to in-house standards.
ii. Value Assignment:
Calibrators and Positive Controls are dilutions of pooled β2-GP1 IgA, β2-GP1 IgG or β2-GP1 IgM antibody positive sera. IMMCO formulates new calibrator and control lots from an array of antibody positive sera obtained from various commercial plasma centers. The calibrators and controls are taken from different pooled sera. All source sera have been tested and found negative for infectious disease as stated in the product insert. Manufactured calibrator sets are stored in aliquots frozen at -70°C. As new lots of calibrators are developed, comparison studies are performed to calibrate values against original calibrators.
iii. Stability:
Shelf life stability:
Accelerated and open kit stability studies for each device were performed on three lots of components/reagents. Accelerated studies were conducted with materials incubated at 37°C. In these conditions, one day is considered equivalent to one month stored at 2°–8°C. Materials are removed from the incubator for testing at three-day intervals for a minimum of 21 days.
Data from accelerated stability study support an 18-month shelf life stability claim. Real-time stability testing is on-going.
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# Open Kit Stability:
For open kit stability studies, materials are opened and stored in a dark environment as required for bench-top usage, then assayed at 15, 45 and 90 day intervals. Open vial stability studies demonstrate opened reagents are stable at 45 days, but the sponsor chose a more restrictive one month open kit stability claim.
# d. Detection limit:
The Limit of Blank (LoB) and the Limit of Detection (LoD) were determined by following CLSI EP17-A. Sixty samples of diluent were run as blank samples for LoB and six different normal human sera for LoD were each assayed 10 times. The LoB was determined to be $2.6\mathrm{EU / ml}$ for $\beta 2$ -GP1 IgA, $2.3\mathrm{EU / mL}$ for $\beta 2$ -GP1 IgG, $1.4\mathrm{EU / mL}$ for $\beta 2$ -GP1 IgM and $1.9\mathrm{EU / mL}$ $\beta 2$ -GP1 IgA/IgG/IgM. The LoD was determined to be $3.6\mathrm{EU / mL}$ for $\beta 2$ -GP1 IgA, $3.1\mathrm{EU / mL}$ for $\beta 2$ -GP1 IgG, $2.3\mathrm{EU / mL}$ for $\beta 2$ -GP1 IgM and $2.7$ for $\beta 2$ -GP1 IgA/IgG/IgM.
# e. Analytical specificity:
# Endogenous Interference:
The studies were performed according to CLSI EP07-A2. Interference was studied by mixing sera with known $\beta 2$ -GP1 antibody levels with potentially interfering serum samples and studying deviation from expected results. Known levels of antibodies included negative, around the cut-off and low positive (i.e. 2-5 times the cut-off). No significant interference was demonstrated in for $\beta 2$ -GP1 IgA, $\beta 2$ -GP1 IgG, $\beta 2$ -GP1 IgM or $\beta 2$ -GP1 IgA/IgG/IgM with the following substances at the levels indicated: Hemoglobin (2 g/L), Bilirubin (342 $\mu$ mol/L), Rheumatoid Factor (100 IU/mL), Triglycerides (37 mmol/L), Cholesterol (13 mmol/L), Heparin (3000 U/L), Acetylsalicylic Acid (3.62 mmol/L), Prednisone (0.84 $\mu$ mol/L), Warfarin (32.5 $\mu$ mol/L), Hydroxychloroquine (148 $\mu$ mol/L), Rituximab (75 $\mu$ g/mL) and Atorvastatin (600 $\mu$ g EQ/L).
# Cross-reactivity:
Numerous potentially cross-reactive autoimmune and infectious disease sera were tested for B2GP1 antibodies for $\beta 2$ -GP1 IgA, $\beta 2$ -GP1 IgG, $\beta 2$ -GP1 IgM or $\beta 2$ -GP1 IgA/IgG/IgM. Results for each assay are provided in the following table:
| | ImmuLisa™ B2GP1 Antibody ELISAs | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Condition | B2GP1 IgA | | B2GP1 IgG | | B2GP1 IgM | | B2GP1 IgA/IgG/IgM | |
| | n | % Pos | n | % Pos | n | % Pos | n | % Pos |
| Syphilis | 7/40 | 17.5 | 3/40 | 7.5 | 5/40 | 12.5 | 8/37 | 21.6 |
| HCV | 0/32 | 0.0 | 2/32 | 6.3 | 1/32 | 3.1 | 2/32 | 6.3 |
| Celiac | 0/16 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1/22 | 4.5 |
| Polymyositis | 3/17 | 17.6 | 0/17 | 0.0 | 1/17 | 5.9 | 2/17 | 11.8 |
| Dermatomyositis | 2/12 | 16.7 | 0/12 | 0.0 | 1/12 | 8.3 | 0/12 | 0.0 |
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| Rheumatoid Arthritis | 6/46 | 13.0 | 4/60 | 6.7 | 0/60 | 0.0 | 3/45 | 6.7 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Systemic Sclerosis | 3/31 | 9.7 | 3/23 | 13.0 | 1/23 | 4.3 | 2/23 | 8.7 |
| Sjögren's | 2/37 | 5.4 | 5/37 | 13.5 | 2/37 | 5.4 | 2/37 | 5.4 |
| Stroke | 1/15 | 6.7 | 0/15 | 0.0 | 1/15 | 6.7 | 1/15 | 6.7 |
| Epilepsy | 1/14 | 7.1 | 0/14 | 0.0 | 1/14 | 7.1 | 1/14 | 7.1 |
| Arterial Thrombosis | 1/15 | 6.7 | 2/15 | 13.3 | 1/15 | 6.7 | 3/15 | 20.0 |
| Venous Thrombosis | 0/15 | 0.0 | 0/15 | 0.0 | 0/15 | 0.0 | 1/15 | 6.7 |
| Myocardial Infarction | 3/20 | 15.0 | 0/20 | 0.0 | 1/20 | 5.0 | 4/20 | 20.0 |
| Acute Coronary Syndrome | 1/10 | 10.0 | 0/10 | 0.0 | 0/10 | 0.0 | 1/10 | 10.0 |
| Pre-eclampsia | 0/20 | 0.0 | 3/20 | 15.0 | 0/20 | 0.0 | 0/20 | 0.0 |
| SNHL | 0/0 | 0.0 | 0/10 | 0.0 | 0/0 | 0.0 | 0/7 | 0.0 |
| Hashimoto's | 0/7 | 0.0 | 0/20 | 0.0 | 0/20 | 0.0 | 0/7 | 0.0 |
| Graves | 3/25 | 12.0 | 1/18 | 5.6 | 0/18 | 0.0 | 1/20 | 5.0 |
| Wegener's | 4/45 | 8.9 | 0/34 | 0.0 | 1/34 | 2.9 | 1/42 | 2.4 |
| Churg-Strauss | 3/23 | 13.0 | 1/23 | 4.3 | 0/23 | 0.0 | 2/23 | 8.7 |
| Crohn's | 0/20 | 0.0 | 1/20 | 5.0 | 0/20 | 0.0 | 1/20 | 5.0 |
| Ulcerative Colitis | 1/20 | 5.0 | 2/20 | 10.0 | 2/20 | 10.0 | 2/20 | 10.0 |
| Toxoplasma | 0/10 | 0.0 | 1/10 | 10.0 | 1/10 | 10.0 | 1/10 | 10.0 |
| CMV | 0/10 | 0.0 | 1/10 | 10.0 | 1/10 | 10.0 | 2/10 | 20.0 |
| Rubella | 0/10 | 0.0 | 0/10 | 0.0 | 0/10 | 0.0 | 0/10 | 0.0 |
| Total | 41/623 | 6.5 | 29/534 | 5.4 | 20/515 | 3.8 | 41/581 | 7.0 |
The 'Limitations of Procedure' section of the Package Insert states: "A diagnosis cannot be made on the basis of anti-B2GP1 results alone. The results of other laboratory tests supporting diagnosis of APS, SLE and associated thrombotic conditions in at-risk patients, particularly anticardiolipin antibody and lupus anticoagulant tests, must be considered along with clinical findings."
f. Assay cut-off:
The cutoff was established by testing a population of 62 normal healthy subjects (NHS) for $\beta 2$ -GP1IgA, $\beta 2$ -GP1IgG, $\beta 2$ -GP1IgM and 60 NHS for $\beta 2$ -GP1IgA/IgG/IgM) and calculating the mean of the normal subjects plus 2.5 SD for IgA, mean plus 3 SD for IgG, mean plus 2.5 for IgM and mean plus 2 for IgA/IgG/IgM as supported by receiver operating curve (ROC) analysis. The cutoff was assigned an arbitrary value of $20~\mathrm{EU / mL}$ .
| β2-GP1 | Interpretation |
| --- | --- |
| <20 EU/mL | Negative |
| 20 – 25 EU/mL | Indeterminate (Borderline)* |
| >25 EU/mL | Positive |
*The B2GP1 IgA/IgG/IgM ELISA is qualitative and values greater than or equal to 20 EU/mL are reported as positive.
2. Comparison studies:
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a. Method comparison with predicate devices: ImmuLisa™ B2GP1 Antibody ELISAs were tested in comparison with analogous Quanta Lite kits using sera from patients with autoimmune diseases associated with $\beta 2$ -GP1 antibodies (disease-associated population: APS, SLE, APS with SLE), patients with a suspected diagnosis of APS and SLE submitted for reference laboratory testing and patients with infectious diseases and other autoimmune conditions (disease control population). The number of specimens tested for each ImmuLisa™ B2GP1 Antibody ELISA varies and is indicated in the respective tables.
Only specimens in the linear range of the assays were included in the method comparison. Greater than $15\%$ of the test cases were the cutoff of the assay. Normal human sera were excluded from the method comparison.
The samples used in the method comparison study for the $\beta 2$ -GP1 IgA, $\beta 2$ -GP1 IgG, $\beta 2$ -GP1 IgM and $\beta 2$ -GP1 IgA/IgG/IgM are shown in the table below:
| ImmuLisa™ B2GP1 Antibody ELISAs | B2GP1 IgA | B2GP1 IgG | B2GP1 IgM | B2GP1 IgA/IgG/IgM |
| --- | --- | --- | --- | --- |
| Number and type of clinical samples tested on each ImmuLisa™ B2GP1 Antibody ELISA | | | | |
| Total Specimens | n=328 | n=338 | n=355 | n=331 |
| Disease-associated population | n=153 | n=154 | n=169 | n=176 |
| Antiphospholipid syndrome (APS) | 91 | 82 | 96 | 87 |
| Systemic lupus erythematosus (SLE) | 26 | 26 | 27 | 21 |
| APS with SLE | 36 | 46 | 46 | 68 |
| Suspected diagnosis | n=50 | n=52 | n=52 | n=48 |
| Suspected diagnosis of APS | 31 | 32 | 32 | 28 |
| Suspected diagnosis of SLE | 19 | 20 | 20 | 20 |
| Disease controls | n=125 | n=132 | n=134 | n=107 |
| Autoimmune conditions | n=70 | n=75 | n=81 | n=56 |
| Celiac | 5 | 0 | 0 | 0 |
| Rheumatoid Arthritis | 24 | 23 | 25 | 19 |
| Systemic Sclerosis | 7 | 6 | 7 | 6 |
| Sjögren's | 14 | 14 | 13 | 14 |
| Wegener's granulomatosus | 7 | 0 | 0 | 3 |
| Churg-Strauss | 0 | 8 | 8 | 1 |
| Graves' Disease | 13 | 13 | 12 | 13 |
| Hashimoto's Disease | 0 | 5 | 16 | 0 |
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| ImmuLisa™ B2GP1 Antibody ELISAs | B2GP1 IgA | B2GP1 IgG | B2GP1 IgM | B2GP1 IgA/IgG/IgM |
| --- | --- | --- | --- | --- |
| Sensory Neuronal Hearing Loss | 0 | 6 | 0 | 0 |
| Infectious diseases | n=31 | n=32 | n=28 | n=26 |
| Syphilis | 19 | 20 | 16 | 16 |
| Hepatitis C virus (HCV) | 12 | 12 | 12 | 10 |
| Other conditions | n=24 | n=25 | n=25 | n=25 |
| Thrombocytopenia | 9 | 10 | 10 | 10 |
| Pre-eclampsia | 15 | 15 | 15 | 15 |
The method comparison results between the new devices and the predicates are shown below:
# B2GPI IgA:
# Indeterminate B2GPI IgA Samples Called Positive
| N=328 (Disease-associated: 153, Suspected diagnosis: 50, Disease control: 125) | QuantaLite® β2GP1 IgA ELISA (SAU) | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive: >20 | | Negative: ≤20 |
| ImmuLisa Enhanced™ B2GPI IgA Antibody ELISA (EU/mL) | Positive: ≥20 | 86 | 2 | 88 |
| | Negative: <20 | 29 | 211 | 240 |
| Total | | 115 | 213 | 328 |
Positive percent agreement: $74.8\%$ (86/115) $95\%$ CI: $65.7\% - 82.2\%$
Negative percent agreement: $99.1\%$ (211/213) $95\%$ CI: $96.3\% - 99.8\%$
Total percent agreement: $90.5\%$ (297/328) $95\%$ CI: $87.7\% - 93.4\%$
# Indeterminate B2GPI IgA Samples Called Negative
| N=328 (Disease-associated: 153, Suspected diagnosis: 50, Disease control: 125) | QuantaLite® β2GP1 IgA ELISA (SAU) | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive: >20 | | Negative: ≤20 |
| ImmuLisa Enhanced™ B2GPI IgA Antibody ELISA (EU/mL) | Positive: ≥25 | 84 | 0 | 84 |
| | Negative: <25 | 31 | 213 | 244 |
| Total | | 115 | 213 | 328 |
Positive percent agreement: $73.0\%$ (84/115) $95\%$ CI: $63.8\% - 80.7\%$
Negative percent agreement: $100.0\%$ (213/213) $95\%$ CI: $97.8\% - 100.0\%$
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Total percent agreement: 90.5% (297/328) 95% CI: 86.7% - 93.4%
# B2GPI IgG:
Indeterminate B2GPI IgG Samples Called Positive
| N=338 (Disease-associated: 154, Suspected diagnosis: 52, Disease control: 132) | QuantaLite® β2GP1 IgG ELISA (SGU) | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive: >20 | | Negative: ≤20 |
| ImmuLisa Enhanced™ B2GPI IgG Antibody ELISA (EU/mL) | Positive: ≥20 | 64 | 21 | 85 |
| | Negative: <20 | 13 | 240 | 253 |
| Total | | 77 | 261 | 338 |
| Positive percent agreement: 83.1% (64/77) | | 95% CI: 72.5% – 90.4% | | |
| Negative percent agreement: 92.0% (240/261) | | 95% CI: 87.8% – 94.8% | | |
| Total percent agreement: 89.9% (304/338) | | 95% CI: 86.2% – 92.8% | | |
Indeterminate B2GPI IgG Samples Called Negative
| N=338 (Disease-associated: 154, Suspected diagnosis: 52, Disease control: 132) | QuantaLite® β2GP1 IgG ELISA (SGU) | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive: >20 | | Negative: ≤20 |
| ImmuLisa Enhanced™ B2GPI IgG Antibody ELISA (EU/mL) | Positive: ≥25 | 63 | 15 | 78 |
| | Negative: <25 | 14 | 246 | 260 |
| Total | | 77 | 261 | 338 |
| Positive percent agreement: 81.8% (63/77) | | 95% CI: 71.0% – 89.4% | | |
| Negative percent agreement: 94.3% (246/261) | | 95% CI: 90.5% – 96.6% | | |
| Total percent agreement: 91.4% (309/338) | | 95% CI: 87.8% – 94.0% | | |
# B2GPI IgM:
Indeterminate B2GPI IgM Samples Called Positive
| N=355 (Disease-associated: 169, Suspected diagnosis: 52, Disease control: 134) | QuantaLite® β2GP1 IgM ELISA (SMU) | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive: >20 | | Negative: ≤20 |
| ImmuLisa Enhanced™ B2GPI IgM Antibody ELISA (EU/mL) | Positive: ≥20 | 110 | 2 | 112 |
| | Negative: <20 | 10 | 233 | 243 |
| Total | | 120 | 235 | 355 |
Positive percent agreement: 91.7% (110/120) 95% CI: 84.8% - 95.7%
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Negative percent agreement: 99.1% (233/235) 95% CI: 96.7% - 99.9%
Total percent agreement: 96.6% (343/355) 95% CI: 94.3% - 98.4%
# Indeterminate B2GPI IgM Samples Called Negative
| N=355 (Disease-associated: 169, Suspected diagnosis: 52, Disease control: 134) | QuantaLite® β2GP1 IgM ELISA (SMU) | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive: >20 | | Negative: ≤20 |
| ImmuLisa Enhanced™ B2GPI IgM Antibody ELISA (EU/mL) | Positive: ≥25 | 109 | 2 | 111 |
| | Negative: <25 | 11 | 233 | 244 |
| Total | | 120 | 235 | 355 |
Positive percent agreement: 90.8% (109/120) 95% CI: 83.8% - 95.1%
Negative percent agreement: 99.1% (233/235) 95% CI: 96.7% - 99.9%
Total percent agreement: 96.3% (342/355) 95% CI: 94.0% - 98.2%
# B2GPI IgA/IgG/IgM results
| N=331 (Disease-associated: 176, Suspected diagnosis: 48, Disease control: 107) | QuantaLite® β2GP1 IgA/IgG/IgM (SMU) | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive: >20 | | Negative: ≤20 |
| ImmuLisa Enhanced™ B2GPI IgM Antibody ELISA (EU/mL) | Positive: ≥20 | 142 | 5 | 147 |
| | Negative: <20 | 35 | 149 | 184 |
| Total | | 177 | 154 | 331 |
Positive percent agreement: 80.2% (142/177) 95% CI: 73.4% - 85.7%
Negative percent agreement: 96.8% (149/154) 95% CI: 92.2% - 98.8%
Total percent agreement: 87.9% (291/331) 95% CI: 83.8% - 91.1%
b. Matrix comparison:
Not applicable since human serum is the only claimed specimen matrix.
# 3. Clinical studies:
a. Clinical sensitivity and specificity:
Serum samples from cohorts of patients with the target condition(s) or other autoimmune and infectious conditions expected to be found in the intended use population were tested and each assay performance was assessed against the clinical diagnosis.
The samples used in the clinical study for the β2-GP1 IgA, β2-GP1 IgG, β2-GP1 IgM and β2-GP1 IgA/IgG/IgM are shown in the table below:
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| ImmuLisa™ B2GP1 Antibody ELISAs | B2GP1 IgA | B2GP1 IgG | B2GP1 IgM | B2GP1 IgA/IgG/IgM |
| --- | --- | --- | --- | --- |
| Number and type of clinical samples tested on each ImmuLisa™ B2GP1 Antibody ELISA | | | | |
| Disease-associated population | n= 294 | n= 318 | n= 345 | n= 266 |
| Antiphospholipid syndrome (APS) | 128 | 97 | 145 | 105 |
| Systemic lupus erythematosus (SLE) | 64 | 98 | 101 | 61 |
| APS with SLE | 103 | 123 | 99 | 100 |
| Suspected diagnosis | n= 259 | n= 259 | n= 259 | n= 259 |
| Suspected diagnosis of APS | 88 | 88 | 88 | 85 |
| Suspected diagnosis of SLE | 171 | 171 | 171 | 171 |
| Disease controls | n= 438 | n= 442 | n= 432 | n= 432 |
| Autoimmune conditions | n= 301 | n= 305 | n= 295 | n= 298 |
| Celiac | 16 | 0 | 0 | 22 |
| Polymyositis | 17 | 17 | 17 | 17 |
| Dermatomyositis | 12 | 12 | 12 | 12 |
| Rheumatoid Arthritis | 46 | 60 | 60 | 45 |
| Systemic Sclerosis | 31 | 23 | 23 | 23 |
| Sjögren's | 37 | 37 | 37 | 37 |
| Wegener's granulomatosus | 45 | 45 | 45 | 45 |
| Churg-Strauss | 23 | 23 | 23 | 23 |
| Ulcerative Colitis | 20 | 20 | 20 | 20 |
| Crohn's | 20 | 20 | 20 | 20 |
| Graves' Disease | 27 | 18 | 18 | 20 |
| Hashimoto's Disease | 7 | 20 | 20 | 7 |
| Sensory Neuronal Hearing Loss | 0 | 10 | 0 | 7 |
| Infectious diseases | n= 102 | n=102 | n= 102 | n= 99 |
| Syphilis | 40 | 40 | 40 | 37 |
| Hepatitis C virus (HCV) | 12 | 12 | 12 | 12 |
| HCV | 20 | 20 | 20 | 20 |
| Toxoplasma | 10 | 10 | 10 | 10 |
| Cytomegalovirus (CMV) | 10 | 10 | 10 | 10 |
| Rubella | 10 | 10 | 10 | 10 |
| Other conditions | n= 124 | n= 124 | n= 124 | n= 124 |
| Thrombocytopenia | 15 | 15 | 15 | 15 |
| Pre-eclampsia | 20 | 20 | 20 | 20 |
| Stroke | 15 | 15 | 15 | 15 |
| Epilepsy | 14 | 14 | 14 | 14 |
{23}
The clinical study results are tabulated below:
# B2GP1 IgA:
Results Where Indeterminate Samples Called Positive
| N=653 (Disease-associated: 128, Disease control: 525) | APS Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 49 | 42 | 91 |
| B2GPI IgA Antibody ELISA | Negative | 79 | 483 | 562 |
| Total | | 128 | 525 | 653 |
Clinical sensitivity: $38.3\%$ (49/128) $95\%$ CI: $30.0\% - 47.3\%$
Clinical specificity: $92.0\%$ (483/525) $95\%$ CI: $89.3\% - 94.1\%$
| N=628 (Disease-associated: 103, Disease control: 525) | APS with SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 20 | 42 | 62 |
| B2GPI IgA Antibody ELISA | Negative | 83 | 483 | 566 |
| Total | | 103 | 525 | 628 |
Clinical sensitivity: $19.4\%$ (20/103) $95\%$ CI: $12.5\% - 28.6\%$
Clinical specificity: $92.0\%$ (483/525) $95\%$ CI: $89.3\% - 94.1\%$
| N=589 (Disease-associated: 64, Disease control: 525) | SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 7 | 42 | 49 |
| B2GPI IgA Antibody ELISA | Negative | 57 | 483 | 540 |
| Total | | 64 | 525 | 589 |
Clinical sensitivity: $10.9\%$ (7/64) $95\%$ CI: $4.9\% - 21.8\%$
Clinical specificity: $92.0\%$ (483/525) $95\%$ CI: $89.3\% - 94.1\%$
Results Where Indeterminate Samples Called Negative
| N=653 (Disease-associated: 128, Disease control: 525) | APS Diagnosis | | Total |
| --- | --- | --- | --- |
| | Positive | Negative | |
{24}
| | | | | |
| --- | --- | --- | --- | --- |
| ImmuLisa Enhanced™
B2GPI IgA Antibody ELISA | Positive | 47 | 30 | 77 |
| | Negative | 81 | 495 | 576 |
| Total | | 128 | 525 | 653 |
Clinical sensitivity: 36.7% (49/128) 95% CI: 28.5% – 47.5%
Clinical specificity: 94.3% (583/525) 95% CI: 91.9% – 96.0%
| N=628 (Disease-associated: 103, Disease control: 525) | APS with SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 17 | 30 | 47 |
| B2GPI IgA Antibody ELISA | Negative | 86 | 495 | 581 |
| Total | | 103 | 525 | 628 |
Clinical sensitivity: 16.5% (17/103) 95% CI: 10.2% – 25.4%
Clinical specificity: 94.3% (583/525) 95% CI: 91.9% – 96.0%
| N=589 (Disease-associated: 64, Disease control: 525) | SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 6 | 30 | 36 |
| B2GPI IgA Antibody ELISA | Negative | 58 | 495 | 553 |
| Total | | 64 | 525 | 589 |
Clinical sensitivity: 9.4% (6/64) 95% CI: 3.9% – 19.9%
Clinical specificity: 94.3% (583/525) 95% CI: 91.9% – 96.0%
## B2GP1 IgG:
### Indeterminate B2GPI IgG Samples Called Positive
| N=617 (Disease-associated: 97, Disease control: 520) | APS Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 57 | 32 | 89 |
| B2GPI IgG Antibody ELISA | Negative | 40 | 488 | 528 |
| Total | | 97 | 520 | 617 |
Clinical sensitivity: 58.8% (57/97) 95% CI: 48.3 – 68.5%
Clinical specificity: 93.8% (488/520) 95% CI: 91.3 – 95.7%
| N=643 (Disease-associated: 123, Disease control: 520) | APS with SLE Diagnosis | Total |
| --- | --- | --- |
{25}
| | | Positive | Negative | |
| --- | --- | --- | --- | --- |
| ImmuLisa Enhanced™
B2GPI IgG Antibody ELISA | Positive | 71 | 32 | 103 |
| | Negative | 52 | 488 | 540 |
| Total | | 123 | 520 | 643 |
Clinical sensitivity: 57.7% (71/123) 95% CI: 48.5% – 66.5%
Clinical specificity: 93.8% (488/520) 95% CI: 92% – 96%
| N=618 (Disease-associated: 98, Disease control: 520) | SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™
B2GPI IgG Antibody ELISA | Positive | 26 | 32 | 58 |
| | Negative | 72 | 488 | 560 |
| Total | | 98 | 520 | 618 |
Clinical sensitivity: 26.5% (26/98) 95% CI: 18.4% – 36.6%
Clinical specificity: 93.8% (488/520) 95% CI: 91.3% – 95.7%
## Indeterminate B2GPI IgG Samples Called Negative
| N=617 (Disease-associated: 97, Disease control: 520) | APS Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™
B2GPI IgG Antibody ELISA | Positive | 53 | 25 | 78 |
| | Negative | 44 | 495 | 539 |
| Total | | 97 | 520 | 617 |
Clinical sensitivity: 54.6% (53/97) 95% CI: 44.2 – 64.7%
Clinical specificity: 95.2% (495/520) 95% CI: 92.9 – 96.8%
| N=643 (Disease-associated: 123, Disease control: 520) | APS with SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™
B2GPI IgG Antibody ELISA | Positive | 64 | 25 | 89 |
| | Negative | 59 | 495 | 554 |
| Total | | 123 | 520 | 643 |
Clinical sensitivity: 52.0% (64/123) 95% CI: 42.9% – 61.1%
Clinical specificity: 95.2% (495/520) 95% CI: 92.9 – 96.8%
| N=618 (Disease-associated: 98, Disease control: 520) | SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 21 | 25 | 46 |
{26}
27
| B2GPI IgG Antibody ELISA | Negative | 77 | 495 | 572 |
| --- | --- | --- | --- | --- |
| Total | | 98 | 520 | 618 |
Clinical sensitivity: 21.4% (21/98) 95% CI: 14.0% - 31.1%
Clinical specificity: 95.2% (495/520) 95% CI: 92.9 - 96.8%
# B2GP1 IgM:
Indeterminate B2GPI IgM Samples Called Positive
| N=655 (Disease-associated: 145, Disease control: 510) | APS Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 93 | 20 | 113 |
| B2GPI IgM Antibody ELISA | Negative | 52 | 490 | 542 |
| Total | | 145 | 510 | 655 |
Clinical sensitivity: 64.1% (93/145) 95% CI: 55.7 - 71.8%
Clinical specificity: 96.1% (490/510) 95% CI: 93.9 - 97.5%
| N=609 (Disease-associated: 99, Disease control: 510) | APS with SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 46 | 20 | 66 |
| B2GPI IgM Antibody ELISA | Negative | 53 | 490 | 543 |
| Total | | 99 | 510 | 609 |
Clinical sensitivity: 46.5% (46/99) 95% CI: 36.5 - 56.7%
Clinical specificity: 96.1% (490/510) 95% CI: 93.9 - 97.5%
| N=673 (Disease-associated: 101, Disease control: 510) | SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 19 | 20 | 39 |
| B2GPI IgM Antibody ELISA | Negative | 82 | 490 | 572 |
| Total | | 101 | 510 | 611 |
Clinical sensitivity: 18.8% (19/101) 95% CI: 12.0 - 28.1%
Clinical specificity: 96.1% (490/510) 95% CI: 93.9 - 97.5%
Indeterminate B2GPI IgM Samples Called Negative
{27}
28
| N=655 (Disease-associated: 145, Disease control: 510) | APS Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 89 | 13 | 102 |
| B2GPI IgM Antibody ELISA | Negative | 56 | 497 | 553 |
| Total | | 145 | 510 | 655 |
Clinical sensitivity: 61.4% (89/145) 95% CI: 52.9–69.2%
Clinical specificity: 97.5% (497/510) 95% CI: 95.6 – 98.6%
| N=609 (Disease-associated: 99, Disease control: 510) | APS with SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 42 | 13 | 55 |
| B2GPI IgM Antibody ELISA | Negative | 57 | 497 | 554 |
| Total | | 99 | 510 | 609 |
Clinical sensitivity: 42.4% (42/99) 95% CI: 32.7 – 52.8%
Clinical specificity: 97.5% (497/510) 95% CI: 95.6 – 98.6%
| N=673 (Disease-associated: 101, Disease control: 510) | SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 16 | 13 | 29 |
| B2GPI IgM Antibody ELISA | Negative | 85 | 497 | 582 |
| Total | | 101 | 510 | 611 |
Clinical sensitivity: 15.8% (16/101) 95% CI: 9.6 – 24.8%
Clinical specificity: 97.5% (497/510) 95% CI: 95.6 – 98.6%
# B2GP1 IgA/IgG/IgM:
| N=623 (Disease-associated: 105, Disease control: 518) | APS Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™ | Positive | 89 | 42 | 131 |
| B2GPI IgA/IgG/IgM Antibody ELISA | Negative | 16 | 476 | 492 |
| Total | | 105 | 518 | 623 |
Clinical sensitivity: 84.8% (89/105) 95% CI: 76.1 – 90.8%
Clinical specificity: 91.9% (476/518) 95% CI: 89.1 – 94.0%
| N=618 (Disease-associated: 100, Disease control: 518) | APS with SLE Diagnosis | | Total |
| --- | --- | --- | --- |
| | Positive | Negative | |
{28}
| ImmuLisa Enhanced™
B2GPI IgA/IgG/IgM
Antibody ELISA | Positive | 66 | 42 | 108 |
| --- | --- | --- | --- | --- |
| | Negative | 34 | 476 | 510 |
| Total | | 100 | 518 | 618 |
Clinical sensitivity: 66.0% (66/100) 95% CI: 55.8 – 75.0%
Clinical specificity: 91.9% (476/518) 95% CI: 89.1 – 94.0%
| N=579 (Disease-associated: 61, Disease control: 518) | SLE Diagnosis | | Total | |
| --- | --- | --- | --- | --- |
| | | Positive | | Negative |
| ImmuLisa Enhanced™
B2GPI IgA/IgG/IgM
Antibody ELISA | Positive | 15 | 42 | 57 |
| | Negative | 46 | 476 | 522 |
| Total | | 61 | 518 | 579 |
Clinical sensitivity: 24.6% (15/61) 95% CI: 14.8 – 37.6%
Clinical specificity: 91.9% (476/518) 95% CI: 89.1 – 94.0%
4. Clinical cut-off:
Not applicable
5. Expected values/Reference range:
Test results in a normal population are expected to be negative. A study of 174 normal, apparently disease-free samples tested with the B2GP1 IgA assay yielded seven positive results (4.0%). A study of 151 normal, apparently disease-free samples tested with the B2GP1 IgG yielded five positive results (3.3%). A study of 151 normal, apparently disease-free samples tested with the B2GP1 IgM assay yielded three positive results (2.0%). A study of 206 normal, apparently disease-free samples tested with the B2GP1 IgA/IgG/IgM assay yielded seven positive results (3.4%).
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
