(592 days)
Not Found
No
The description details a standard chemiluminescent immunoassay and the associated reagents and systems, with no mention of AI or ML in the device description, intended use, or performance studies.
No
The device is an in vitro diagnostic (IVD) immunoassay intended for the qualitative detection of IgG antibodies to SARS-CoV-2. It is used as an aid in identifying individuals with an adaptive immune response, not for therapy or treatment.
Yes
The device is described as an "in vitro diagnostic" device and is intended for the "qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma... as an aid in identifying individuals with an adaptive immune response." This clearly indicates its use in diagnosing or aiding in the diagnosis of a medical condition.
No
The device description clearly outlines physical components like reagent packs, calibrators, and controls, which are integral to the device's function as a chemiluminescent immunoassay. It is designed to be used on specific hardware systems (VITROS Systems).
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "For in vitro diagnostic and laboratory professional use." This is the primary indicator that the device is intended for use outside of the body to examine specimens for diagnostic purposes.
Furthermore, the description details a chemiluminescent immunoassay for the detection of antibodies in human serum and plasma samples, which is a typical application of in vitro diagnostics.
N/A
Intended Use / Indications for Use
For in vitro diagnostic and laboratory professional use.
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma (K2-EDTA and K3-EDTA) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.
For use in the calibration of the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma.
Product codes (comma separated list FDA assigned to the subject device)
QVP
Device Description
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiO Immunodiagnostic System, VITROS 3600 Immunodiagnostic System, VITROS 5600 Integrated System and VITROS XT 7600 Integrated System) providing fully automated random-access testing.
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls on the VITROS Systems.
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack is supplied as ready to use and contains:
- 100 wells coated with 100ng/well of recombinant SARS-CoV-2 spike antigen derived from human cells.
- 18.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent).
- 20.4 mL conjugate reagent [anti-human IgG (murine monoclonal) conjugated to horseradish peroxidase, 5ng/mL] in buffer with bovine protein stabilizers and antimicrobial agent.
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator contains:
- 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 1gG Calibrator 0 (anti-SARS-CoV-2 IgG in anti-SARS-CoV-2 IgG negative human serum with antimicrobial agent, 1 mL)
- Lot calibration card.
- Protocol card
- 8 calibrator bar code labels
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls contain:
- 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls 1 and 2 (defibrinated human plasma with anti-microbial agent, 2 mL). Control 1 is non-reactive and Control 2 is reactive
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is designed for use on the VITROS Systems. The VITROS Systems use the following ancillary reagents (general purpose reagents): - VITROS Immunodiagnostic Products Signal Reagent
- VITROS Immunodiagnostic Products Universal Wash Reagent.
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)
A. Analytical Performance:
1. Precision/Reproducibility:
- Within-Laboratory Precision: Evaluated with EDTA plasma pools (PP4, PP5, PP6), negative and positive quality control materials (PP1, PP2), and calibrator (PP3) on VITROS ECi/ECiQ, 3600 Immunodiagnostics Systems, and VITROS 5600, XT7600 Integrated Systems following CLSI EP05-A3.
- Sample Size: 240 observations per sample and lot (2 replicates x 2 runs x 20 days x 3 lots).
- Key Results: Total precision %CV ranged from 3.4% -32.2%, depending on the sample and instrument.
- Reproducibility (Between-Laboratory Precision): Determined with EDTA plasma pools (GRP4, GRP5, GRP6), quality controls (GRP1, GRP2), and customer calibrator (GRP3) using the VITROS ECi/ECiQ, 3600 Immunodiagnostics Systems, and VITROS 5600, XT7600 Integrated Systems. Samples measured in triplicate using 3 reagent lots, in 2 runs per day over 5 days at 3 sites, according to CLSI EP05-A3.
- Sample Size: 270 observations per panel member.
- Key Results: Total reproducibility %CV ranged from 6.1% - 22.8%, depending on the sample and instrument.
3. Analytical Specificity:
- A. Cross-Reactivity: Evaluated by testing serum samples with antibodies to other microorganisms or underlying conditions.
- Key Results: No cross-reactivity observed with any evaluated cross-reactants (Influenza A/B, HCV, HBV, Haemophilus influenzae, ANA, Rheumatoid Factor, HAMA, Adenovirus, Coxsackie B, Echovirus, Poliovirus, RSV, Anti-SARS-coronavirus, Anti-MERS-coronavirus, Human coronavirus HKU1/NL63/OC43/229E, HIV, HPIV, HMPV, Enterovirus, Rhinovirus, EBV, EBVNA, Rubella, Legionella pneumophila, Bordetella pertussis, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Candida albicans, Pneumocystis jirovecii, Pseudomonas aeruginosa, Staphylococcus epidermidis, CMV).
- B. Interference: Evaluated for interference consistent with CLSI EP07.
- Key Results: All endogenous (ANA, Bilirubin conjugated/unconjugated, Cholesterol, Hemoglobin, Human anti-Mouse, Ig (total), Rheumatoid Factor, Total Protein, Triglycerides) and exogenous (Abacavir, Acetaminophen, Amoxicillin, Aspirin, Atorvastatin, Azithromycin, Biotin, Cefoxitin, Ceftriaxone, Dextromethorphan, EDTA, Gentamicin, Guaifenesin, Heparin, Ibuprofen, Intralipid, Levofloxacin, Levothyroxine, Lisinopril, Lopinavir, Loratadine, Losartan, Meropenem, Metformin, Metoprolol, Naproxen, Omeprazole, Oseltamivir, Peramivir, Prednisone, Ritonavir, Theophylline, Vancomycin, Zanamivir) substances showed no interference (=15 days from symptom onset:
* VITROS ECi/ECiQ Immunodiagnostic Systems: PPA 93.86% (95% CI: 90.50%-96.10%)
* VITROS 3600 Immunodiagnostic Systems and VITROS 5600 Integrated Systems: PPA 93.52% (95% CI: 90.10%-95.81%)
* VITROS XT 7600 Integrated Systems: PPA 93.49% (95% CI: 90.10%-95.80%)- Lower PPA observed for earlier time bins (0-7 days and 8-14 days).
- Negative Percent Agreement (NPA):
- Sample Size: 304 presumed SARS-CoV-2 negative samples.
- Key Results:
- VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and VITROS 5600: NPA 99.01% (95% CI: 97.14%-99.66%)
- VITROS XT 7600: NPA 99.01% (95% CI: 97.13%-99.66%)
- Key Results: All endogenous (ANA, Bilirubin conjugated/unconjugated, Cholesterol, Hemoglobin, Human anti-Mouse, Ig (total), Rheumatoid Factor, Total Protein, Triglycerides) and exogenous (Abacavir, Acetaminophen, Amoxicillin, Aspirin, Atorvastatin, Azithromycin, Biotin, Cefoxitin, Ceftriaxone, Dextromethorphan, EDTA, Gentamicin, Guaifenesin, Heparin, Ibuprofen, Intralipid, Levofloxacin, Levothyroxine, Lisinopril, Lopinavir, Loratadine, Losartan, Meropenem, Metformin, Metoprolol, Naproxen, Omeprazole, Oseltamivir, Peramivir, Prednisone, Ritonavir, Theophylline, Vancomycin, Zanamivir) substances showed no interference (=15 days from symptom onset:
F. Other Supportive Performance Characteristics Data:
- Calibration Cycle Stability:
- Study Design: Established calibration interval by testing 6 precision panel samples over time with a single calibration.
- Key Results: Supports a calibration interval stability of 28 days.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement (PPA) for >=15 days post-symptom onset:
- VITROS ECi/ECiQ Immunodiagnostic Systems: 93.86% (95% CI: 90.50%-96.10%)
- VITROS 3600 Immunodiagnostic Systems and VITROS 5600 Integrated Systems: 93.52% (95% CI: 90.10%-95.81%)
- VITROS XT 7600 Integrated Systems: 93.49% (95% CI: 90.10%-95.80%)
Negative Percent Agreement (NPA):
- VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and VITROS 5600: 99.01% (95% CI: 97.14%-99.66%)
- VITROS XT 7600: 99.01% (95% CI: 97.13%-99.66%)
Predicate Device(s)
Not Found
Reference Device(s)
K962919, K083173, K081543, K182063
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
N/A
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food & Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the text "FDA U.S. FOOD & DRUG ADMINISTRATION" on the right. The symbol features a stylized image of an eagle, while the text is written in blue, with "FDA" in a larger, bolder font than the rest of the text.
EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack, VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator DECISION SUMMARY
Background Information: I
A De Novo Number
B Applicant
Ortho-Clinical Diagnostics, Inc.
C Proprietary and Established Names
VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack, VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator
D Regulatory Information
| Product
Code(s) | Classification | Regulation
Section | Panel |
|--------------------|----------------|------------------------------------------------|-------------------|
| QVP | Class II | 21 CFR 866.3983 - SARS-
CoV-2 serology test | MI - Microbiology |
II Submission/Device Overview:
A Purpose for Submission:
De Novo request for evaluation of automatic class II designation for the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test comprised of (1) the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack, (2) the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator, and (3) the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls.
B Measurand:
IgG antibodies to SARS-CoV-2 in human serum, K2-EDTA plasma, and K3-EDTA plasma.
C Type of Test:
Chemiluminescent Immunoassay.
III Indications for Use:
1
A Indication(s) for Use: Rx ONLY
For in vitro diagnostic and laboratory professional use.
VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma (K2-EDTA and K3-EDTA) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.
VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator
For use in the calibration of the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma.
B Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
C Special Instrument Requirements:
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrators uses the following VITROS Systems (instruments):
- VITROS ECi/ECiQ Immunodiagnostic Systems .
- VITROS 3600 Immunodiagnostic Systems .
- . VITROS 5600 Integrated Systems
- . VITROS XT 7600 Integrated Systems
These VITROS systems were cleared previously as part of premarket notifications: K962919, K083173, K081543, and K182063 respectively,
IV Device/System Characteristics:
A Device Description:
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiO Immunodiagnostic System, VITROS 3600 Immunodiagnostic System, VITROS 5600 Integrated
2
System and VITROS XT 7600 Integrated System) providing fully automated random-access testing.
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls on the VITROS Systems.
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack is supplied as ready to use and contains:
- . 100 wells coated with 100ng/well of recombinant SARS-CoV-2 spike antigen derived from human cells.
- 18.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent) .
- . 20.4 mL conjugate reagent [anti-human IgG (murine monoclonal) conjugated to horseradish peroxidase, 5ng/mL] in buffer with bovine protein stabilizers and antimicrobial agent.
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator contains:
- 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 1gG Calibrator 0 (anti-SARS-CoV-2 IgG in anti-SARS-CoV-2 IgG negative human serum with antimicrobial agent, 1 mL)
- Lot calibration card .
- . Protocol card
- . 8 calibrator bar code labels
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls contain:
-
3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls 1 and 2 . (defibrinated human plasma with anti-microbial agent, 2 mL). Control 1 is non-reactive and Control 2 is reactive
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is designed for use on the VITROS Systems. The VITROS Systems use the following ancillary reagents (general purpose reagents): -
. VITROS Immunodiagnostic Products Signal Reagent
-
VITROS Immunodiagnostic Products Universal Wash Reagent .
B Principle of Operation
The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator on the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. An immunometric technique is used; this involves a two- stage reaction. In the first stage antibodies to SARS-CoV-2 present in the sample bind with SARS-CoV-2 spike protein coated on the well. Unbound sample is removed by washing. In the second stage horseradish peroxidase (HRP)-labeled murine monoclonal anti-human IgG antibodies are
3
added in the conjugate reagent. The conjugate binds specifically to the antibody portion of the antigen-antibody complex. If complexes are not present, the unbound conjugate is removed by the subsequent wash step.
The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system.
| Test Type | System | Incubation Time | Time to first result | Test Temperature | Reaction Sample
Volume |
|--------------|----------------------------------|-----------------|----------------------|------------------|---------------------------|
| Immunometric | ECi/ECiQ. 3600.
5600. XT 7600 | 37 minutes | 48 minutes | 37 ℃ | 20 ul |
- Not all products and systems are available in all countries.
Figure 1: Reaction Scheme
Image /page/3/Figure/5 description: The image shows a diagram of a process involving several components. It starts with a recombinant SARS-CoV-2 antigen, followed by Anti-SARS-CoV-2, and then HRP-labeled anti-human IgG murine monoclonal. The process culminates in luminescence, which is achieved using a signal reagent with an enhancer.
C Instrument Description Information
1. Instrument Name:
VITROS Systems (instruments):
- . VITROS ECi/ECiQ Immunodiagnostic System
- . VITROS 3600 Immunodiagnostic System
- VITROS 5600 Integrated System .
- VITROS XT 7600 Integrated System. .
-
- Specimen Identification:
Not applicable
-
- Specimen Sampling and Handling:
Specimen Sampling:
The specimens recommended for this assay are:
- . Serum
- K2-EDTA Plasma
- K3-EDTA Plasma
4
Specimen Handling and Storage:
- . Specimens may be stored for up to 24 hours at room temperature (15-30℃) or 7 days at 2 - 8ºC.
- Specimens may be stored frozen at 8 AI | | | | | |
| Bilirubin, conjugated | 40 mg/dL | 475 umol/L | | | | |
| Bilirubin, unconjugated | 40 mg/dL | 684 umol/L | | | | |
| Cholesterol | 400 mg/dL | 10.3 mmol/L | | | | |
| Hemoglobin | 1000 mg/dL | 10 g/L | | | | |
| Human anti-Mouse | 3600 ng/mL | 0.024 umol/L | | | | |
| Ig (total) | 6 g/dL | 60 g/L | | | | |
10
| Test Concentration | ||
|---|---|---|
| Substance | Conventional | SI Units |
| Rheumatoid Factor | 35.7-61.7 IU/mL | N/A |
| Total Protein | 15 g/dL | 150 g/L |
| Triglycerides | 1500 mg/dL | 16.94 mmol/L |
N/A: Not Applicable (alternative units are not provided)
Table 8. Exogenous interferants evaluated with VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test
| Substance | Test Concentration | |
|---|---|---|
| Conventional | SI Units | |
| Abacavir | 1.27 mg/dL | 44.4 µmol/L |
| Acetaminophen | 15.6 mg/dL | 1.03 mmol/L |
| Amoxicillin | 1.35 mg/dL | 37 µmol/L |
| Aspirin | 3 mg/dL | 0.167 mmol/L |
| Atorvastatin | 75 µg/dL | 1.34 µmol/L |
| Azithromycin | 1.1 mg/dL | 14.8 µmol/L |
| Biotin | 3510 ng/mL | 14.3 µmol/L |
| Cefoxitin | 660 mg/dL | 15.5 mmol/L |
| Ceftriaxone | 84 mg/dL | 1.51 mmol/L |
| Dextromethorphan | 1.56 µg/dL | 0.0575 µmol/L |
| EDTA | 0.099 mg/dL | 3.39 µmol/L |
| Gentamicin | 3.0 mg/dL | 62.8 µmol/L |
| Guaifenesin | 450 µg/dL | 22.7 µmol/L |
| Heparin | 330 units/dL | 330 units/dL |
| Ibuprofen | 21.9 mg/dL | 1.06 mmol/L |
| Intralipid | 2000 mg/dL | N/A |
| Levofloxacin | 3.6 mg/dL | 99.7 µmol/L |
| Levothyroxine | 429 µg/dL | 0.552 µmol/L |
| Lisinopril | 24.6 µg/dL | 0.607 µmol/L |
| Lopinavir | 57.17 µg/mL | 90.89 µmol/L |
| Loratadine | 8.7 µg/dL | 0.271 µmol/L |
| Losartan | 1155 ng/mL | 2.505 µmol/L |
| Meropenem | 33.9 mg/dL | 884 µmol/L |
| Metformin | 1.2 mg/dL | 92.9 µmol/L |
| Metoprolol | 150 µg/dL | 5.61 µmol/L |
| Naproxen | 36.0 mg/dL | 1.56 mmol/L |
| Omeprazole | 840 µg/dL | 24.3 µmol/L |
| Oseltamivir | 39.9 µg/dL | 1.28 µmol/L |
| Peramivir | 183600 ng/mL | 559 µmol/L |
| Prednisone | 10 µg/dL | 0.276 µmol/L |
| Ritonavir | 10.98 mg/dL | 126.42 mmol/L |
| Theophylline | 6.0 mg/dL | 333 µmol/L |
| Vancomycin | 12.0 mg/dL | 82.8 µmol/L |
| Zanamivir | 1089 ng/mL | 3.28 µmol/L |
N/A = Not Applicable (alternative units are not provided)
11
When amlodipine was tested at a concentration of 1.88 ug/dL, a negative bias (-11.1% change of the S/C value) was observed in reactive samples.
-
- Assay Reportable Range:
Not applicable
- Assay Reportable Range:
-
- Traceability. Stability. Expected Values (Controls, Calibrators, or Methods):
Specimen Stability: The stability of SARS-CoV-2 antibodies in serum. K2-EDTA plasma. and K -- EDTA plasma was evaluated with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test after various storage conditions with and without freeze-thawing cycles in the VITROS 5600 Integrated Systems. The storage conditions evaluated were room temperature, 2 - 8°C, and EDTA plasma, and K-EDTA plasma.
- Traceability. Stability. Expected Values (Controls, Calibrators, or Methods):
Figure 4: Weighted Deming linear regression analysis between K2-EDTA plasma and serum
15
C Clinical Studies:
-
- Clinical Sensitivity:
Not applicable
- Clinical Sensitivity:
11. Clinical Specificity:
Not applicable
12. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
16
Clinical Agreement Study:
The clinical performance of VITROS Immunodiagnostic Products anti SARS- CoV-2 IgG test was evaluated at three testing sites using 642 unique retrospective clinical samples acquired from two populations. Population 1 consisted of 338 samples collected from individuals previously infected with SARS-CoV-2 with a prior SARS-CoV-2 positive test result using a comparator that FDA determined is appropriate (RT PCR test). Population 2 consisted of 304 samples collected prior to December 2019 (before the widespread outbreak of COVID-19). Of the 304 samples, 30% of the tested samples were collected from blood donor centers.
Of the 338 samples in Population 1, 24 samples were collected 0 - 7 days from COVID-19 symptom onset, 21 samples collected between 8 - 14 days from symptom onset, and 293 samples were collected >15 days from COVID-19 symptom onset. Table 12 below shows the sample distribution and the respective percentages from the total of samples tested per "Days post-symptoms onset" time bin.
| Time bin
(n= total number
samples tested) | Days post-
symptom
onset | Percent Samples
(per time bin) |
|-------------------------------------------------|--------------------------------|-----------------------------------|
| 0-7 days (n = 24) | 0 - 4 | 70.83% |
| | 5 - 7 | 29.17% |
| 8-14 days (n = 21) | 8 - 11 | 47.62% |
| | 12 - 14 | 52.38% |
| ≥ 15 days (n = 293) | 15 - 21 | 10.58% |
| | 22 - 30 | 10.92% |
| | 31 - 60 | 40.61% |
| | 61 - 90 | 26.62% |
| | 91 - 195 | 11.26% |
Table 12. Sample distribution within each "Days post symptoms onset" time bin.
Tables 13 and 14 below represents sample distribution per matrix tested for each study population (Population 1 and Population 2).
| Table 13. Distribution of Population I samples by matrix and days post-symptom onset. | ||||
|---|---|---|---|---|
| Matrix | Days post-symptom onset | |||
| ≤7 days | 8 - 10 days | ≥15 days | Total | |
| EDTA plasma | (b)(4) | 169 | ||
| Serum | 169 | |||
| Total | 338 |
Table 14. Distribution of Population 2 samples by matrix.
17
| EDTA plasma | 138 |
|---|---|
| Serum | 166 |
| Total | 304 |
Ortho conducted the clinical agreement study at 3 testing sites: one internal site and 2 external sites.
Positive Percent Agreement (PPA)
A total of 338 samples collected from individual patients confirmed to have a prior SARS-CoV-2 positive result by RT-PCR were tested. Blood samples were collected within the United States between April 2020 and March 2021. Samples were tested with the VITROS Immunodiagnostic Products Anti SARS-CoV-2 IgG test in each analyzer (except with the VITROS XT7600 Integrated System where one sample was not tested due to limited volume). Of the 338 samples included in the study, 169 were EDTA plasma samples and 169 were serum samples.
The performance of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test and 95% Confidence Interval for each VITROS analyzer is summarized in the tables below.
PPA performance of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test and 95% Confidence Interval by system:
| Days from
Symptom
Onset | Number of
Subjects Tested
(with prior RT-
PCR Positive) | Reactive | PPA | 95% CI
(Wilson score) |
|-------------------------------|------------------------------------------------------------------|----------|--------|--------------------------|
| 0-7 days | 24 | 11 | 45.83% | 27.89%-64.93% |
| 8-14 days | 21 | 11 | 52.38% | 32.37% - 71.66% |
| ≥15 days | 293 | 275 | 93.86% | 90.50%-96.10% |
| Total | 338 | -- | -- | -- |
Table 15. In the VITROS ECi/ECiO Immunodiagnostic Systems.
Table 16. In the VITROS 3600 Immunodiagnostic Systems and the VITROS 5600 Integrated Systems
| | | VITROS Immunodiagnostic Products
Anti-SARS-CoV-2 IgG test Results | | |
|----------------------------|------------------------------------------------------------------|----------------------------------------------------------------------|--------|--------------------------|
| Days from
Symptom Onset | Number of
Subjects Tested
(with prior RT-
PCR Positive) | Reactive | PPA | 95% CI
(Wilson score) |
| 0-7 days | 24 | 10 | 41.67% | 24.47% - 61.17% |
| 8-14 days | 21 | 11 | 52.38% | 32.37% - 71.66% |
| ≥15 days | 293 | 274 | 93.52% | 90.10% - 95.81% |
| Total | 338 | -- | -- | -- |
18
| Days from
Symptom
Onset | Number of
Subjects Tested
(with prior RT-
PCR Positive) | Reactive | PPA | 95% CI
(Wilson score) |
|-------------------------------|------------------------------------------------------------------|----------|--------|--------------------------|
| 0-7 days | 24 | 10 | 41.67% | 24.47% - 61.17% |
| 8-14 days | 21 | 11 | 52.38% | 32.37% - 71.66% |
| ≥15 days | 292 | 273 | 93.49% | 90.10% - 95.80% |
| Total | 337 | -- | -- | -- |
Table 17. In the VITROS XT 7600 Integrated Systems
Negative Percent Agreement (NPA)
Three hundred and four (304) presumed SARS-CoV-2 negative samples collected prior to the COVID-19 pandemic within the United States were tested. Of the 304 samples, 138 were EDTA plasma samples and 166 serum samples. All samples were tested using VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems "(except the samples that were not tested on one or more analyzers due to limited volume). The performance of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test and 95% Confidence Interval for each VITROS analyzer is summarized in the table below:
Table 18: NPA performance of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test and 95% confidence interval in all VITROS analyzers
| | | VITROS Immunodiagnostic Products
Anti-SARS-CoV-2 IgG test Results | | |
|--------------------------------------------|--------------------------------------------|----------------------------------------------------------------------|--------|--------------------------|
| Analyzer | Presumed Negative
(Collected Pre-COVID) | Non-
Reactive | NPA | 95% CI
(Wilson score) |
| VITROS ECi/ECiQ/VITROS
3600/VITROS 5600 | 304 | 301 | 99.01% | 97.14%-
99.66% |
| VITROS XT 7600 | 303 | 300 | 99.01% | 97.13% -
99.66% |
D Clinical Cut-Off:
Not applicable
E Expected Values/Reference Range:
Not applicable
F Other Supportive Performance Characteristics Data:
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Calibration Cvcle Stability
The purpose of this study was to establish the calibration interval, or how frequently the assay should be calibrated. The calibration interval was established by testing samples on the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test using a single calibration over time.
In the study, Ortho-Clinical Diagnostics included a panel of 6 precision pool samples. Each panel member was prepared as follows:
- Precision Pool 1 (PP1): Control level 1 (Non-Reactive) .
- . Precision Pool 2 (PP2): Control level 2 (Reactive)
- Precision Pool 3 (PP3): Calibrator .
- Precision Pool 4 (PP4): High negative EDTA plasma sample .
- . Precision Pool 5 (PP5): Low Positive EDTA plasma sample
- Precision Pool 6 (PP6): High Positive EDTA plasma sample .
After a single initial calibration on Day samples were tested on Day and up to Day on the VITROS ECi/ECiO, VITROS 3600, VITROS 5600, and VITROS XT7600.
For each positive sample (PP2, PP4, PP5, and PP6) linear regression analysis was conducted. In addition, percent difference from baseline was calculated as follows:
| (b)(4) |
|---|
| -------- |
Percent difference to baseline should be (b)(4).The percent difference to baseline should be
The study results support a calibration interval stability of 28 days for the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test.
VII Proposed Labeling:
The labeling supports the decision to grant the De Novo request for this device.
VIII Identified Risks and Mitigations:
| Risks to Health | Mitigation Measures |
|---|---|
| Risk of false test results | Certain labeling information including |
| limitations, device descriptions, explanations | |
| of procedures and performance information | |
| identified in special controls (1), (3), and (5). | |
| Use of certain specimen collection devices | |
| identified in special control (2). | |
| Certain design verification and validation | |
| including documentation of device | |
| descriptions, certain analytical studies and | |
| clinical studies, and risk analysis strategies | |
| identified in special control (4). | |
| Testing of characterized samples and labeling | |
| information identified in special control (6). |
10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov DEN210038 -
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| Risks to Health | Mitigation Measures |
|---|---|
| Failure to correctly interpret the test results | Certain labeling information including |
| limitations, device descriptions, explanations | |
| of procedures and performance information | |
| identified in special controls (1), (3), and (5). | |
| Use of certain specimen collection devices | |
| identified in special control (2). | |
| Certain design verification and validation | |
| including documentation of device | |
| descriptions, certain analytical studies and | |
| clinical studies, and risk analysis strategies | |
| identified in special control (4). | |
| Testing of characterized samples and labeling | |
| information identified in special control (6). | |
| Failure to correctly operate the device | Certain labeling information including |
| limitations, device descriptions, explanations | |
| of procedures and performance information | |
| identified in special controls (1), (3), and (5). | |
| Use of certain specimen collection devices | |
| identified in special control (2). |
IX Benefit/Risk Assessment:
A Summary of the Assessment of Benefit:
The benefit of the assay is the ability to detect Anti-SARS-CoV-2 IgG antibodies as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. The device could also provide a tool for tracking possible patient exposure.
True positive test results provide additional support for the diagnosis of recent or past SARS-CoV-2 infection. Results could be used in conjunction with clinical and epidemiological information, as well as other laboratory results to guide patient management. The test results may improve infection control measures and may aid in tracking and reducing transmission of infection. There is currently no SARS-CoV-2 antibody test that has undergone full FDA premarket review to most definitively determine clinical truth of the presence or absence of detectable antibodies for the method comparison study, however this uncertainty could be acceptable, particularly because the sponsor used a comparator that FDA determined is appropriate (SARS-CoV-2 RT-PCR devices), which represents the most reasonable alternative to establish clinical truth in the clinical study. This is an acceptable source of uncertainty regarding the benefits of the test.
Summary of the Assessment of Risk: B
The risks associated with the device, when used as intended, are those related to the risk of false test results, which have essentially the same impacts as the risks related to failure to correctly
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interpret the test results and failure to correctly operate the device as all would cause the user to rely on incorrect information.
A false negative result could be interpreted as indicating that a person did not recently have COVID-19, which may lead a person to take fewer necessary precautions against spreading the virus to others if they are still shedding the virus from a recent infection. This may increase the risk of transmission. In the context of the current public health emergency, incorrect serological test results used to guide infection control activities could lead to misallocation of resources used for surveillance and prevention. The positive percent agreement performance point estimate of the device observed in the clinical study indicates that false negative results are not likely to occur when the device is used in the intended use population.
A false positive SARS-CoV-2 antibody result could be interpreted as a diagnosis of recent COVID-19, and a clinician may assume a patient may still be shedding the virus, which may result in unnecessary additional testing, quarantine, or self-isolation to prevent the spread of the virus to others. False positive serology test results can lead to an incorrect assessment that the tested person had an immune response to SARS-CoV-2, which may lead the person to take fewer necessary precautions against virus exposure. This may increase the individual's risk of infection and may lead the person to not seek testing if later infected, likely increasing the spread of the disease. In the context of the current public health emergency, incorrect serological test results used to guide infection control activities could lead to misallocation of resources used for surveillance and prevention.
A positive result could be wrongly interpreted as a diagnosis of acute COVID-19 to explain an individual's symptoms and delay correct diagnosis and initiation of appropriate treatment for the actual cause of patient illness. A positive test result could be wrongly interpreted as indicating that the tested person has immunity to SARS-CoV-2, which may lead the person to take fewer precautions against virus exposure. This may increase the individual's risk of infection and may lead the person to not seek testing if later infected, likely increasing the spread of the disease. A negative result may be misinterpreted as ruling out SARS-CoV-2 infection, with a concomitant delay in the correct diagnosis and treatment.
C Patient Perspectives:
This submission did not include specific information on patient perspectives for this device.
D Summary of the Assessment of Benefit-Risk:
The risks associated with the device (risk of false test results, failure to correctly interpret the results, and failure to correctly operate the device) are mitigated by labeling information, which will assist the operator in correctly performing the test and will assist healthcare providers in understanding the intended use of the test and evaluating the predictive value of a result based on the analytical and clinical performance of the test. In addition, those risks are mitigated by the use of certain validated specimen collection devices. Further, the risk of false test results and failure to correctly interpret the results are mitigated by certain design verification and validation, including analytical and clinical studies and risk analysis strategies to reduce the likelihood of such errors. Finally, the risk of false test results due to a disease or disorder that Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov DEN210038 -
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presents a public health emergency, or a public health emergency that otherwise exists are addressed by special controls requiring certain testing of characterized samples and labeling information in those situations. The special controls help to ensure that errors will be uncommon and will facilitate accurate assay implementation of results. In addition, the device's performance observed in the clinical study suggests that errors will be uncommon and that the assay will provide benefits to patients as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. While general controls alone are insufficient to mitigate the risks associated with the device, the benefits outweigh the risks given the special controls.
Conclusion: X
The De Novo request is granted, and the device is classified under the following regulation and subject to the special controls identified in the letter granting the De Novo request:
| Product Code(s): | QVP |
|---|---|
| Device Type: | SARS-CoV-2 serology test |
| Class: | Class II |
| Regulation: | 21 CFR 866.3983 |