Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard chemiluminescent immunoassay performed on automated laboratory systems. There is no mention of AI, ML, or any computational analysis beyond basic signal processing and cut-off determination.

Therapeutic

No
This device is an in vitro diagnostic (IVD) test intended for the qualitative detection of total antibodies to SARS-CoV-2. It is used as an aid in identifying individuals with an adaptive immune response, not for treating or preventing disease.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is "For in vitro diagnostic and laboratory professional use" and is "intended for the qualitative detection of total antibodies to SARS-CoV-2... an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection." This clearly defines it as an in vitro diagnostic device used to aid in diagnosis.

SaMD (Software as a Medical Device)

No

The device description clearly outlines physical components such as reagent packs, calibrators, and controls, which are used in conjunction with the VITROS Systems hardware. This indicates it is not a software-only device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The very first line explicitly states "For in vitro diagnostic and laboratory professional use." It also describes the device's purpose as the "qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma... using the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems." This clearly indicates it's used to test samples taken from the human body outside of the body (in vitro) to diagnose or aid in the diagnosis of a condition (SARS-CoV-2 infection).
Device Description: The description details the components used to perform the test on human samples (reagent pack, calibrator, controls) and the systems on which the test is run, all of which are typical for IVD devices.
Performance Studies: The document includes detailed information about performance studies such as precision, reproducibility, cross-reactivity, interference, and clinical agreement studies using human samples. These types of studies are required for the validation of IVD devices to demonstrate their accuracy and reliability.
Key Metrics: The inclusion of metrics like Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are standard performance indicators for diagnostic tests.

The information provided strongly aligns with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Rx ONLY

For in vitro diagnostic and laboratory professional use.

VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma (K-EDTA. K-EDTA and lithium heparin) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total 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 Total Calibrator

For use in the calibration of the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of total 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 Total test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiQ 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 Total test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls on the VITROS Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack is supplied as ready to use and contains:

. 100 coated wells (streptavidin, bacterial; binds ≥3 ng biotin per well; biotin recombinant SARS-CoV-2 antigen 0.1 ug/mL)
6.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent) .
. 16.2 mL conjugate reagent (HRP-recombinant SARS-CoV-2 antigen) in buffer with bovine protein stabilizers and antimicrobial agent

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator contains:

. 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator (anti-SARS-CoV-2 in anti-SARS-CoV-2 negative human plasma with antimicrobial agent, 1 mL)
. Lot calibration card
. Protocol card
. 8 calibrator bar code labels

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls contain:

. 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total 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 Total 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

in vitro diagnostic and laboratory professional use.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Description of Clinical Agreement Study used as Supportive Data:
The clinical performance of VITROS Immunodiagnostic Products anti SARS- CoV-2 Total test was evaluated at three testing sites using retrospective clinical samples acquired from two populations.
Population 1: Of the 296 samples in this population, 31 samples were collected 0-7 days from COVID-19 symptom onset, 26 samples collected between 8 - 14 days from symptom onset, and 239 samples were collected >15 days from COVID-19 symptom onset. This population consisted of (b)(4) samples collected from individuals previously infected with SARS-CoV-2 with a prior SARS CoV-2 positive test result using a comparator RT-PCR test determined appropriate by the FDA.
Sample distribution per matrix: 70 EDTA plasma samples, 82 Lithium heparin plasma, 144 Serum.
Blood samples were collected within the United States between April 2020 and April 2021.
Population 2: 513 samples collected prior to December 2019 (before the widespread outbreak of COVID-19). This population consisted of 46 EDTA plasma samples, 333 Lithium heparin plasma samples and 134 serum samples. Samples were presumed SARS-CoV-2 negative and collected within the United States.
Ortho conducted the clinical agreement study at 3 testing sites: one internal site and 2 external sites.
All samples were tested using VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/ XT 7600 Integrated Systems analyzer (except the samples that were not tested on one or more analyzers due to limited volume).

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 controls (PP1, PP2), and calibrator (PP3) on VITROS ECi/ECiQ, 3600, 5600, and XT7600 Immunodiagnostics Systems, following CLSI EP05-A3. Three lots of reagents, calibrators, and controls were used. Operators ran two replicates of each sample on two occasions per day for twenty nonconsecutive days for each reagent lot. Total of 80 observations per sample and lot (2 replicates x 2 runs x 20 days). The study included three reagent lots and was evaluated within a single calibration cycle (2 replicates x 2 runs x 20 days x 3 lots = 240 observations total).
- Key Results: The total precision % CV (from the "total" standard deviation) for the S/C values ranged from 3.8% - 23.2%, depending upon the sample and instrument.
Reproducibility (Between-Laboratory Precision): Determined with EDTA plasma pool samples (TRP4, TRP5, TRP6), quality controls (TRP1, TRP2), and customer calibrator (TRP3) using the same VITROS systems. Samples were measured in triplicate using 3 reagent lots, in 2 runs per day over 5 days at 3 sites, according to CLSI EP05-A3.
- Key Results: The total reproducibility % CV (from the "total" standard deviation) for the S/C values ranged from 7.1% - 14.2%, depending upon the sample and instrument.

2. Linearity: Not applicable.

3. Analytical Specificity:

A. Cross-Reactivity: Evaluated by testing serum samples with antibodies to other microorganisms or underlying conditions that could cause false positive results. Tested in singlicate on the VITROS 5600 Integrated system.
- Key Results: No cross-reactivity was observed with any of the 36 cross-reactants evaluated (e.g., Influenza A, B, HCV, ANA, various coronaviruses, HIV, EBV, SARS coronavirus, MERS coronavirus, etc.).
B. Interference: Evaluated consistent with CLSI EP07. Commonly encountered endogenous substances (e.g., Bilirubin, Cholesterol, Hemoglobin, HAMA, RF, Total Protein, Triglycerides) and exogenous substances (various medications like Acetaminophen, Amlodipine, Amoxicillin, Aspirin, Biotin, etc.) were tested on one lot of reagent using the VITROS 5600 Integrated System in 3 reactive (low positive) and 3 non-reactive (negative) samples.
- Key Results: All substances evaluated did not interfere (

Regulation Number and Section

N/A

Summary

0

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and 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 is a stylized image of a bird, while the text is written in a combination of blue and white colors. The word "FDA" is in a blue box.

EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack, VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator DECISION SUMMARY

I Background Information:

A De Novo Number

DEN210040

B Applicant

Ortho-Clinical Diagnostics, Inc.

C Proprietary and Established Names

VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack, VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total 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 Total test is comprised of (1) the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack, (2) the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator, and (3) the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls.

B Measurand:

Total antibodies to SARS-CoV-2 in human serum, K2-EDTA plasma, K2-EDTA plasma and Lithium heparin plasma.

1

C Type of Test: Chemiluminescent Immunoassay

III Indications for Use:

A Indication(s) for Use:

Rx ONLY

For in vitro diagnostic and laboratory professional use.

VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma (K-EDTA. K-EDTA and lithium heparin) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total 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 Total Calibrator

For use in the calibration of the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of total 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 Total Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrators uses the following VITROS Systems (instruments):

o 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.

2

IV Device/System Characteristics:

A Device Description:

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiQ 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 Total test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls on the VITROS Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack is supplied as ready to use and contains:

. 100 coated wells (streptavidin, bacterial; binds ≥3 ng biotin per well; biotin recombinant SARS-CoV-2 antigen 0.1 ug/mL)
6.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent) .
. 16.2 mL conjugate reagent (HRP-recombinant SARS-CoV-2 antigen) in buffer with bovine protein stabilizers and antimicrobial agent

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator contains:

. 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator (anti-SARS-CoV-2 in anti-SARS-CoV-2 negative human plasma with antimicrobial agent, 1 mL)
. Lot calibration card
. Protocol card
. 8 calibrator bar code labels

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls contain:

. 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total 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 Total 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

3

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator on the VITROS ECi/ECiQ/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 S1 antigen coated on the well. Unbound sample is removed by washing. In the second stage horseradish peroxidase (HRP)- labeled recombinant SARS-CoV-2 spike protein SI antigen is added in the conjugate reagent. The conjugate binds specifically to any anti-SARS-CoV-2 captured on the well in the first stage. 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 °C | 80 μL |

" Not all products and systems are available in all countries

Image /page/3/Figure/4 description: The image is of the text "Figure 1: Reaction Scheme". The text is black and the background is white. The text indicates that the image is of a reaction scheme and is labeled as Figure 1.

Image /page/3/Figure/5 description: This image shows a diagram of a process involving SARS-CoV-2 antigens. The process starts with a Biotinylated recombinant SARS-CoV-2 antigen, followed by Anti-SARS-CoV-2, and then HRP-labeled recombinant SARS-CoV-2 antigen. Finally, a signal reagent with an enhancer is added, resulting in luminescence.

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.
1. Specimen Identification:

4

Not applicable

3. Specimen Sampling and Handling:

Specimen Sampling:

The specimens recommended for this assay are:

. Serum
. K2-EDTA Plasma
. K3-EDTA Plasma
Lithium Heparin Plasma .

Specimen Handling and Storage

Specimens may be stored for up to 24 hours at room temperature (15-30 ℃) or 7 days . at 2 - 8 °C.
Specimens may be stored frozen at ≤ -20 ℃ for ≤ 4 weeks. .
Specimens may be subjected to up to five freeze-thaw cycles. .

4. Calibration:

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator is provided together with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator contains anti-SARS-CoV-2 antibody in human plasma. In addition, the calibrator contains the lot calibration card, protocol card and 8 calibrator bar code labels.

Calibration is lot-specific; reagent packs and calibrators are linked by lot number, Reagent packs from the same lot may use the same calibration. The calibrator is supplied frozen. The analyzer automatically processes the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator in duplicate. Results are calculated as a normalized signal, relative to a cutoff value. During the calibration process a lot-specific parameter is used to determine a valid stored cutoff value for the VITROS Immunodiagnostic and VITROS Integrated Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test should be calibrated:

When the reagent pack and calibrator lot changes. .
Every 28 days. .
After specified service procedures have been performed. .
If quality control results are consistently outside of the acceptable range. .

5. Quality Control:

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls are provided separately from the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and contains:

Control 1: Anti-SARS-CoV-2 Total non-reactive human defibrinated plasma. .

5

. Control 2: Anti-SARS-CoV-2 Total reactive human defibrinated plasma.

Ouality Control Procedure

· To verify system performance, analyze control materials:
- o After calibration
- o If the system is turned off for more than 2 hours
- · After reloading reagent packs that have been removed from the MicroWell Supply and stored for later use
- · According to local regulations or at least once each day that the test is performed
- · After specified service procedures are performed
If controls results fall outside the acceptance range, investigate the cause before . deciding whether to report patient results.

V Standards/Guidance Documents Referenced:

CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition

CLSI EP07 Interference testing in Clinical Chemistry

CLSI EP09 Measurement Procedure Comparison and Bias Estimation Using Patient Samples. Third Edition (2016).

CLSI EP35 Assessment of Equivalence or Suitability of Specimen Type for Medical Laboratory measurement Procedure.

CLSI EP37 Supplemental Tables for Interference Testing in Clinical Chemistry

Performance Characteristics: VI

A Analytical Performance:

1. Precision/Reproducibility:
- A. Within-Laboratory Precision: The within-laboratory precision of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test was evaluated with EDTA plasma pools samples (PP4, PP5, and PP6), negative and positive quality control materials (PP1, PP2), and the calibrator (PP3), on the VITROS ECi/ECiQ and 3600 Immunodiagnostics Systems and the VITROS 5600 and XT7600 Integrated Systems following the CLSI document EP05-A3. A total of 3 lots of reagent packs, calibrators and controls were included in the study. For each reagent lot, operators ran two replicates of each precision panel sample on two occasions per day for twenty nonconsecutive days.

The data presented are a representation of test performance and are provided as a guideline. Variables such as sample handling and storage, reagent handling and storage, laboratory environment, and system maintenance can affect reproducibility of test results.

Each precision panel was tested in duplicate, in two runs per day, on 20 non-consecutive days, on each instrument for a total of 80 observations per sample and lot. The study included three reagent lots and was evaluated within a single calibration cycle (2

6

replicates x 2 runs x 20 days x 3 lots= 240 observations total). The VITROS Anti-SARS-CoV-2 Total's total precision % CV (from the "total" standard deviation) for the S/C values ranged from 3.8% - 23.2%, depending upon the sample and instrument.

| VITROS | Panel | Number
of | Grand
Mean | Repeatability
(Within Run) | Laboratory | |
|----------|--------|---- | System | member | observ | XT 7600 | PP1 | 240 | XT 7600 | PP2 | 240 | XT 7600 | PP3 | 240 | XT 7600 | PP4 | 240 | XT 7600 | PP5 | 240 | XT 7600 | PP6 | 240 | 5600 | PP1 | 240 | 5600 | PP2 | 240 | 5600 | PP3 | 240 | 5600 | PP4 | 240 | 5600 | PP5 | 240 | 5600 | PP6 | 240 | 3600 | PP1 | 240 | 3600 | PP2 | 240 | 3600 | PP3 | 240 | 3600 | PP4 | 240 | 3600 | PP5 | 240 | 3600 | PP6 | 240 | ECi/ECiQ | PP1 | 240 | ECi/ECiQ | PP2 | 240 | ECi/ECiQ | PP3 | 240 | ECi/ECiQ | PP4 | 240 | ECi/ECiQ | PP5 | 240 | ECi/ECiQ | PP6 | 240 | Between-Run | | Between-Day | | Between-Lot | | Within-
----------|---------------|-------------------------------|-------|-------------|-------|-------------|-------|-------------|-------|-----------------------|-------|
| (S/C) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) |
| 0.02 | 0.002 | N/A | 0.004 | N/A | 0.000 | N/A | 0.006 | N/A | 0.008 | N/A |
| 3.45 | 0.054 | 1.6 | 0.076 | 2.2 | 0.069 | 2.0 | 0.324 | 9.4 | 0.344 | 10.0 |
| 1.14 | 0.021 | 1.8 | 0.039 | 3.4 | 0.027 | 2.4 | 0.173 | 15.2 | 0.180 | 15.8 |
| 1.06 | 0.021 | 2.0 | 0.039 | 3.7 | 0.021 | 2.0 | 0.152 | 14.3 | 0.160 | 15.1 |
| 4.00 | 0.069 | 1.7 | 0.090 | 2.3 | 0.062 | 1.6 | 0.346 | 8.7 | 0.370 | 9.3 |
| 11.70 | 0.179 | 1.5 | 0.234 | 2.0 | 0.167 | 1.4 | 0.754 | 6.4 | 0.826 | 7.1 |
| 0.02 | 0.003 | N/A | 0.003 | N/A | 0.000 | N/A | 0.005 | N/A | 0.007 | N/A |
| 3.18 | 0.049 | 1.5 | 0.069 | 2.2 | 0.055 | 1.7 | 0.312 | 9.8 | 0.328 | 10.3 |
| 1.06 | 0.021 | 2.0 | 0.041 | 3.9 | 0.008 | 0.8 | 0.030 | 2.8 | 0.055 | 5.2 |
| 0.98 | 0.021 | 2.1 | 0.037 | 3.8 | 0.013 | 1.3 | 0.032 | 3.3 | 0.055 | 5.6 |
| 3.70 | 0.070 | 1.9 | 0.084 | 2.3 | 0.046 | 1.2 | 0.450 | 12.2 | 0.465 | 12.6 |
| 11.00 | 0.219 | 2.0 | 0.223 | 2.0 | 0.223 | 2.0 | 1.862 | 16.9 | 1.897 | 17.2 |
| 0.02 | 0.002 | N/A | 0.002 | N/A | 0.000 | N/A | 0.002 | N/A | 0.005 | N/A |
| 2.99 | 0.044 | 1.5 | 0.076 | 2.5 | 0.059 | 2.0 | 0.499 | 16.7 | 0.510 | 17.1 |
| 1.00 | 0.021 | 2.1 | 0.031 | 3.1 | 0.031 | 3.1 | 0.134 | 13.4 | 0.142 | 14.2 |
| 0.93 | 0.017 | 1.8 | 0.030 | 3.2 | 0.030 | 3.2 | 0.147 | 15.8 | 0.154 | 16.6 |
| 3.50 | 0.056 | 1.6 | 0.087 | 2.5 | 0.051 | 1.5 | 0.686 | 19.6 | 0.696 | 19.9 |
| 10.40 | 0.156 | 1.5 | 0.147 | 1.4 | 0.189 | 1.8 | 2.397 | 23.0 | 2.414 | 23.2 |
| 0.02 | 0.001 | N/A | 0.001 | N/A | 0.000 | N/A | 0.005 | N/A | 0.005 | N/A |
| 2.83 | 0.059 | 2.1 | 0.060 | 2.1 | 0.049 | 1.7 | 0.150 | 5.3 | 0.179 | 6.3 |
| 0.94 | 0.016 | 1.7 | 0.023 | 2.4 | 0.023 | 2.4 | 0.000 | 0.0 | 0.036 | 3.8 |
| 0.86 | 0.034 | 4.0 | 0.024 | 2.8 | 0.016 | 1.9 | 0.026 | 3.0 | 0.051 | 5.9 |
| 3.27 | 0.048 | 1.5 | 0.074 | 2.3 | 0.031 | 0.9 | 0.250 | 7.6 | 0.267 | 8.2 |
| 9.88 | 0.153 | 1.5 | 0.197 | 2.0 | 0.040 | 6.5 | 0.978 | 9.9 | 1.196 | 12.1 |

Table 1. Within-Laboratory Precision Study- Data Summary (for all 4 VITROS analyzers)

N/A = Not Applicable (alternative units are not provided)

Table 8. Exogenous interferants evaluated with VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test

Substance	Test Concentration
	Conventional Units	SI Units
Acetaminophen	15.6 mg/dL	1.03 mmol/L
Amlodipine	7.5 $\mu$ g/dL	0.183 $\mu$ mol/L
Amoxicillin	5.4 mg/dL	148 $\mu$ mol/L
Aspirin	3 mg/dL	0.167 mmol/L
Atorvastatin	75 $\mu$ g/dL	1.34 $\mu$ mol/L
Azithromycin	1.1 mg/dL	14.8 $\mu$ mol/L
Biotin	3510 ng/mL	14.3 $\mu$ mol/L
Cefoxitin	660 mg/dL	15.5 mmol/L
Ceftriaxone	84 mg/dL	1.51 mmol/L
Dextromethorphan	1.56 $\mu$ g/dL	0.0575 $\mu$ mol/L
EDTA	0.099 mg/dL	3.39 $\mu$ mol/L
Gentamicin	3.0 mg/dL	62.8 $\mu$ mol/L

11

	Test Concentration
Substance	Conventional Units	SI Units
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	0.9 mg/dL	24.9 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)

When Levofloxacin was tested at a concentration of 1.8 mg/dL, a positive bias (+12.03% change of the S/C value) was observed in reactive samples.

4. Assay Reportable Range:

Not applicable

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

Specimen Stability: The stability of SARS-CoV-2 antibodies in serum, K2-EDTA plasma, K 2-EDTA plasma, and Lithium heparin plasma was evaluated with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total 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 ≤-20 °C with 5 freeze-thaw cycles.

Freshly drawn whole blood from ndividual donors was collected. Of the whole blood donors (0) were unaltered and were spiked using a DI47

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The whole blood was distributed among the collection tubes used in the study. Each spiked sample was unique.

After centrifugation, each sample from each collection tube was tested in duplicate using one reagent lot on one VITROS 5600 Integrated System, denoted as the fresh timepoint. Aliquots of each sample were prepared and stored at room temperature, 2-8°C, and 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 = 31) | 0 - 4 | 77.42% |
| 0-7 days (n = 31) | 5 - 7 | 22.58% |
| 8-14 days (n = 26) | 8 - 11 | 42.31% |
| 8-14 days (n = 26) | 12 - 14 | 57.69% |
| ≥ 15 days (n = 239) | 15 - 21 | 11.30% |
| | 22 - 30 | 22.18% |
| | 31 - 60 | 44.77% |
| | 61 - 90 | 8.79% |
| | 91 - 253 | 12.97% |

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 1 samples by matrix and days post-symptom onset.

Matrix	Days post-symptom onset			Total
	≤7 days	8-10 days	≥15 days
EDTA plasma		(b)(4)		70
Lithium heparin plasma				82
Serum				144
Total				396

Table 14. Distribution of Population 2 samples by matrix.

Matrix	Samples tested
EDTA plasma	46
Lithium heparin plasma	333
Serum	134

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Total	513
-------	-----

Ortho conducted the clinical agreement study at 3 testing sites: one internal site and 2 external sites.

Positive Percent Agreement (PPA)

A total of 296 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 April 2021. Samples were tested with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test in each analyzer (except the samples that were not tested on one or more analyzers due to limited volume). Of the 296 samples included in the study, 70 were EDTA plasma samples, 82 were Lithium-Heparin plasma sample and 144 were serum samples.

The performance of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total 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 Total test and 95% Confidence Interval by system:

| Days from
Symptom Onset | Number of
Subjects Tested
(with prior RT-
PCR Positive) | VITROS Immunodiagnostic Products
Anti-SARS-CoV-2 Total Test Results | | |
|----------------------------|------------------------------------------------------------------|------------------------------------------------------------------------|--------|--------------------------|
| | | Reactive | PPA | 95% CI
(Wilson score) |
| 0-7 days | 25 | 9 | 36.00% | 20.24% -55.48% |
| 8-14 days | 19 | 16 | 84.21% | 62.44% - 94.48% |
| ≥15 days | 238 | 224 | 94.12% | 90.37% -96.46% |
| Total | 282 | -- | -- | -- |

Table 15. In the VITROS ECi/ECiQ Immunodiagnostic Systems

Table 16. In the VITROS 3600 Immunodiagnostic Systems

| Days from
Symptom Onset | Number of
Subjects Tested
(with prior RT-
PCR Positive) | VITROS Immunodiagnostic Products
Anti-SARS-CoV-2 Total Test Results | | |
|----------------------------|------------------------------------------------------------------|------------------------------------------------------------------------|--------|--------------------------|
| | | Reactive | PPA | 95% CI
(Wilson score) |
| 0-7 days | 25 | 11 | 44.00% | 26.66% - 62.93% |
| 8-14 days | 22 | 17 | 77.27% | 56.56% - 89.88% |
| ≥15 days | 239 | 225 | 94.14% | 90.41% - 96.48% |
| Total | 286 | -- | -- | -- |

Table 17. In the VITROS 5600 Integrated Systems

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| Days from
Symptom Onset | Number of
Subjects Tested
(with prior RT-
PCR Positive) | VITROS Immunodiagnostic Products
Anti-SARS-CoV-2 Total Test Results | | |
|----------------------------|------------------------------------------------------------------|------------------------------------------------------------------------|--------|--------------------------|
| | | Reactive | PPA | 95% CI
(Wilson score) |
| 0-7 days | 27 | 10 | 37.04% | 21.53% - 55.77% |
| 8-14 days | 19 | 15 | 78.95% | 56.67% - 91.49% |
| ≥15 days | 239 | 225 | 94.14% | 90.41% - 96.48% |
| Total | 285 | -- | -- | -- |

Table 18. In the VITROS XT 7600 Integrated Systems

| Days from
Symptom Onset | Number of
Subjects Tested
(with prior RT-
PCR Positive) | Reactive | PPA | 95% CI
(Wilson score) |
|----------------------------|------------------------------------------------------------------|----------|--------|--------------------------|
| 0-7 days | 25 | 10 | 40.00% | 23.40% - 59.26% |
| 8-14 days | 22 | 17 | 77.27% | 56.56% - 89.88% |
| ≥15 days | 237 | 223 | 94.09% | 90.33% - 96.45% |
| Total | 284 | -- | -- | -- |

Negative Percent Agreement (NPA)

Five hundred and thirteen (513) presumed SARS-CoV-2 negative samples collected prior to the COVID-19 pandemic within the United States were tested. Of the 513 samples, 46 were EDTA plasma samples, 333 were Lithium heparin plasma samples and 134 were serum samples . All samples were tested using VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/ XT 7600 Integrated Systems analyzer (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 Total test and 95% Confidence Interval for each VITROS analyzer is summarized in the table below:

Table 19. NPA performance of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test and 95% confidence interval in all VITROS analyzers

| Analyzer | Presume
Negative
(Collected Pre-
COVID) | VITROS Immunodiagnostic Products
Anti-SARS-CoV-2 Total Test Results | | |
|-----------------|--------------------------------------------------|------------------------------------------------------------------------|--------|-----------------|
| Non-Reactive | NPA | 95% CI
(Wilson score) | | |
| VITROS ECI/ECiQ | 505 | 502 | 99.41% | 98.27% - 99.80% |
| VITROS 3600 | 511 | 509 | 99.61% | 98.58%-99.89% |
| VITROS 5600 | 509 | 508 | 99.80% | 98.90%-99.97% |
| VITROS T-7600 | 505 | 503 | 99.61% | 98.57% - 99.89% |

D Clinical Cut-Off:

20

Not applicable

E Expected Values/Reference Range: Not applicable

F Other Supportive Performance Characteristics Data:

Calibration Cycle 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 Total 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 wand up to Day on the VITROS ECi/ECiQ, 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:

15/143

The percent difference to baseline should be 1014

The study results support a calibration interval stability of 28 days for the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test.

VII Proposed Labeling:

The labeling supports the decision to grant the De Novo request for this device.

Identified Risks and Mitigations: VIII

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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).
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 Total 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

22

most definitively determine clinical truth of the presence 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.

B Summary of the Assessment of Risk:

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 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 mav 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.

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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 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 and interpretation 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.

X Conclusion:

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