Celltrion DiaTrust COVID-19 Ag Home Test Instructions

Celltrion DiaTrust COVID-19 Ag Home Test

For use under the Emergency Use Authorization (EUA) only
For in vitro diagnostic use

INTENDED USE

Celltrion DiaTrustTM COVID-19 Ag Home Test is a lateral flow immunoassay intended for the qualitative detection of nucleocapsid protein and receptor binding domain (RBD) of the SARS-CoV-2 spike proteins in mid-turbinate swabs from the SARS-CoV-2. This test is authorized for non-prescription home use with self-collected and adult-collected direct mid-turbinate swab samples from individuals aged 14 years or older with symptoms of COVID-19 within the first seven days of symptom onset.

This test is also authorized for non-prescription home use with self-collected and adult-collected mid-turbinate swab samples from individuals aged 14 years or older with or without symptoms or other epidemiological reasons to suspect COVID-19 when tested twice over three days with at least 24 hours (and no more than 48 hours) between tests.

The Celltrion DiaTrustTM COVID-19 Ag Home Test does not differentiate between SARS-CoV and SARS-CoV-2.
Results are for the identification of SARS-CoV-2 nucleocapsid protein antigen and/or receptor binding domain (RBD). These antigens are generally detectable in mid-turbinate swabs during the acute phase of infection. Positive results indicate the presence of viral antigens, but clinical correlation with past medical history and other diagnostic information is necessary to determine infection status. Positive results do not rule out bacterial infection or co- infection with other viruses. The agent detected may not be the definite cause of disease. Individuals who test positive with the Celltrion

DiaTrustTM COVID-19 Ag Home Test should self-isolate and seek follow up care with their physician or healthcare provider as additional testing and public health reporting may be necessary.

Negative results are presumptive, do not rule out SARS-CoV-2 infection and should not be used as the sole basis for treatment or patient management decisions, including infection control decisions. Negative results should be considered in the context of an individual’s recent exposures, history and the presence of clinical signs and symptoms consistent with COVID-19 and confirmed with a molecular assay, if necessary, for patient management.
For serial testing programs, additional confirmatory testing with a molecular test for negative results may be necessary, if there is a high likelihood of SARS-CoV-2 infection, such as an individual with a close contact with COVID-19 or with suspected exposure to COVID-19 or in communities with high prevalence of infection. Additional confirmatory testing with a molecular test for positive results may also be necessary, if there is a low likelihood of SARS- CoV-2 infection, such as in individuals without known exposures to COVID-19 or residing in communities with low prevalence of infection.
Individuals who test negative and continue to experience COVID-19 like symptoms of fever, cough and/or shortness of breath may still have SARS-CoV-2 infection and should seek follow up care with their physician or healthcare provider.

Individuals should provide all results obtained with this product to their healthcare provider for public health reporting. All healthcare providers will report all test results they receive from individuals who use the authorized product to relevant public health authorities in accordance with local, state, and federal requirements, using appropriate LOINC and SNOMED codes, as defined by the Laboratory In Vitro Diagnostics (LIVD) Test Code Mapping for SARS-CoV-2 Tests provided by CDC.

The Celltrion DiaTrustTM COVID-19 Ag Home Test is authorized for non- prescription self-use or a lay user testing another person 14 years or older in a non-laboratory setting. The Celltrion DiaTrustTM COVID-19 Ag Home Test is only for use under the Food and Drug Administration’s Emergency Use Authorization.

SUMMARY AND EXPLANATION

Coronavirus is a group of viruses that belongs to the Family Coronaviridae; a type of RNA virus of 27 -32 kb commonly found in birds and mammals including human. Coronavirus is divided into four genera: alpha, beta, gamma and delta. The virus causes illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV).

Coronavirus disease 2019 (COVID-19) is a new strain caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease originated from Wuhan city of China in December 2019. The World Health Organization (WHO) publicly named this virus ‘COVID-19’ and declared it a pandemic and a Public Health Emergency of International Concern. The infection is typically spread from one person to another via direct contact or respiratory droplets from cough or sneeze. Latent period from exposure to onset of symptoms is between one to fourteen days (four to seven days on average). Common symptoms and signs of infection include fever, cough, shortness of breath and breathing difficulties. In severe cases, infections can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death.

Due to the wide variety of symptoms, it is difficult to differentiate COVID-19 from other existing respiratory viruses or bacteria. Diagnosing COVID-19 through isolating the virus or detecting specific genes from the collected respiratory droplet specimens is a challenge in terms of time and accessibility as it requires long hours, a well-equipped laboratory and advanced technology which are often not available to many public. The test is designed to detect antigen to SARS-CoV-2, and it will help assess if an individual has COVID-19 antigen within 15 minutes r.

TEST PRINCIPLE

The Celltrion DiaTrustTM COVID-19 Ag Home Test is a lateral flow immunoassay test. The Celltrion DiaTrustTM COVID-19 Ag Home Test is designed to detect antigens from the SARS-CoV-2 from direct mid-turbinate swab samples from individuals with or without symptoms or other epidemiological reasons to suspect COVID-19 when tested twice over two or three days with at least 24 hours but not more than 48 hours between tests. This test is also authorized to detect antigens from the SARS-CoV-2 from direct mid-turbinate swab samples from individuals aged 14 years or older with symptoms of COVID-19 within the first seven days of symptom onset. This test is authorized for non- prescription home use with mid-turbinate nasal swab specimens from individuals aged 14 years and older. The Celltrion DiaTrustTM COVID-19 Ag Home Test is validated for use from direct specimens testing without transport media.

A nitrocellulose membrane strip in the device having a test line and a control line, wherein the test line is pre-coated with anti-mouse monoclonal antibody to SARS-CoV-2 to detect SARS-CoV-2 nucleocapsid and RBDs from the SARS-CoV-2 spike proteins, and the control line is coated with goat anti-mouse IgG. When the extracted swab specimen is dispensed into to the sample well, the specimen migrates towards the conjugate pad, which contains conjugated antibodies with colloidal gold directed against the SARS-CoV-2 antigen. When the sample contains SARS-CoV-2 antigens, an antigen-antibody-conjugate complex is formed. The sample-conjugate complex then passes over the membrane until it reaches the capture zone (test line). Here, the complex is bound to immobilized antibodies and form visible colored band in the test line. The sample then migrates across the membrane along the strip until it reaches the control line where excess conjugate binds and produces a second visible line on the membrane. This control line indicates that the sample has migrated across the membrane as intended and indicates that the test was correctly performed. This test does not use biotin-Streptavidin/avidin chemistry in any of the steps for coupling reagents.

MATERIALS SUPPLIED

Kit components

| Quantity
---|---
1 Test Kit| 2 Tests Kit| 5 Tests Kit| 25 Tests Kit
Test cassette with test strip| 1 ea/box| 2 ea/box| 5 ea/box| 25 ea/box
Extraction buffer (0.3 mL / test tube)1| ****

1 ea/box

| ****

2 ea/box

| ****

5 ea/box

| ****

25 ea/box

Filter cap| 1 ea/box| 2 ea/box| 5 ea/box| 25 ea/box
Swab| 1 ea/box| 2 ea/box| 5 ea/box| 25 ea/box
Instructions for Use| 1 ea/box| 1 ea/box| 1 ea/box| 1 ea/box

1 Extraction buffer is provided in the sealed test tube.

MATERIALS REQUIRED BUT NOT PROVIDED

• Celltrion DiaTrustTM COVID-19 Ag Home Test Application (Celltrion SafeKey)
• Smartphone for using App, Celltrion SafeKey (Android 10 or newer, iOS 14.2 or newer)
• Compatible computer for web-based App https://celltrion.safekey.tools

PRECAUTIONS AND WARNINGS

• For in vitro diagnostic use only
• This product has not been FDA cleared or approved, but has been authorized by FDA under an Emergency Use Authorization (EUA).
• The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.
• All the results within the United States and its territories are required to be reported to the appropriate public health authorities.
• This product has been authorized only for the detection of proteins from SARS-CoV-2, not for any other viruses or pathogens.
• Do not use the test device beyond the expiration date.
• Keep sealed until usage, and once opened use immediately.
• Test samples immediately after collection.
• Do not use the test device if the pouch is damaged or open.
• Do not re-use the device.
• This test is intended for diagnosis of coronavirus infection by detecting COVID-19 antigen, but should not be used as a sole criterion for the determination of SARS-CoV-2 infection. Other laboratory tests and clinical information (signs and symptoms) should be used and considered for diagnosis.
• Inadequate or inappropriate sample collection may yield false test results.
• To obtain accurate results, the test must be performed as indicated in this Instructions for Use
• Results should be read within 15 minutes. If the test is read before 15 minutes or after 20 minutes, false negative or false positive results may occur.
• Inadequate or improper nasal swab sample collection may result in false negative test results.
• Do not touch the swab head when handling the swab.
• Do not ingest
• Keep out of reach of children
• Avoid contact with skin and eyes
• If contact with the body occurs, rinse with water. If irritation persists, seek medical advice.
• Discard Celltrion DiaTrustTM COVID-19 Ag Home Test in accordance with local, state and federal regulations or accreditation requirements.

LIMITATIONS

• Do not use this test for individuals under 14 years of age. The swab included in the kit is designed for collection of samples from adults and additional safety measures are needed for safe collection in children under 14 years of age.
• Testing for asymptomatic individuals should be performed at least twice over three days, with at least twenty-four hours and no more than 48 hours between tests. You may need to purchase additional tests to perform this serial (repeat) testing.
• There is a higher chance of false negative results with antigen tests than with laboratory-based molecular tests. This means that there is a higher chance this test will give you a negative result when you have a COVID-19.
• Serial testing (i.e., testing every day or every other day) is more likely to detect COVID-19, especially when you do not have any symptoms
• This test detects both viable (live) and non-viable SARS-CoV-2. Test performance depends on the amount of virus (antigens) in the sample and may or may not correlate with viral culture results performed on the same sample.
• A negative test result may occur if the level of antigens in a sample is below the detection limit of the test or if the sample was collected or transported improperly.
• Failure to follow the Test Procedure may adversely affect test performance and/or invalidate the test result.
• Test results must be evaluated in conjunction with other clinical data available to the physician.
• Positive test results do not rule out co-infections with other pathogens.
• Negative test results are not intended to rule in other non-SARS-CoV-2 viral or bacterial infections.
• Negative results should be treated as presumptive and confirmed with an FDA-authorized molecular assay, if necessary, for clinical management.
• Performance of nasal swabs collected from patients without symptoms or other epidemiological reasons to suspect COVID-19 infection or for serial screening, when tested twice over two to three days with at least 24 but not more than 48 hours between tests has not yet been determined; a study to support use will be completed.
• If the differentiation of specific coronaviruses and strains is needed, additional testing, in consultation with state or local public health departments, is required.
• The amount of antigen in a sample may decrease as the duration of illness increases. Specimens collected after seven days are more likely to be negative compared to RT-PCR.
• The performance of this test was established based on the evaluation of a limited number of clinical specimens collected between March and July of 2021. The clinical performance has not been established in all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.
• The Celltrion DiaTrustTM COVID-19 Ag Home Test does not differentiate between SARS-CoV and SARS-CoV-2.

CHEMICAL HAZARD AND SAFETY INFORMATION

Hazardous ingredients for the extraction buffer

Chemical Name (CAS)| Material Safety Data Sheet| GHS Code for each ingredient| Conc.
---|---|---|---
Sodium Azide (26628-22-8)| _Material Safety Data Sheet_| Acute Tox.2 (oral), H300 Acute Tox.1 (dermal), H310|

0.09%

The extraction buffer solution in the extraction buffer tube contains a hazardous ingredient as shown in above table. If the extraction buffer solution contacts the skin or eye, immediately wash with plenty of running water. In case the irritation persists, please seek medical advice at: https://www.poison.org/contact-us or 1-800-222-1222.

STORAGE AND STABILITY
An unopened test device should be stored at 2 – 30°C (36 – 86°F). It is stable until the expiration date marked on the label. Do not open the aluminum pouch until you are ready to use the test device. Use the test device immediately after opening the aluminum pouch. If the tests were refrigerated, keep them at room temperature for 30 minutes prior to use.

QUALITY CONTROL
A procedural internal control is built in the ‘control line (c)’ of the device and is used to ensure that the applied specimen has migrated well into the device. It is coated with goat anti-mouse IgG and a red colored line will always appear when the test is performed properly.
External run controls are not required to use the Celltrion DiaTrustTM COVID-19 Ag Home Test.

TEST PROCEDURE
When opening the test device, download the mobile application (Celltrion SafeKey) using QR code from Instructions for Use provided with the test kit and follow the instructions as described in the mobile application.

1. Test Preparation
   Following the instruction in the mobile application, when you are ready to proceed with the test, tear open the two aluminum pouches.

2. Prepare the aluminum pouch containing the test device and place it on the testing surface along with the reagents from the second aluminum pouch – test tube filled with the extraction buffer and filter cap. In case the tests were refrigerated, keep them ambient for 30 minutes to let it reach the room temperature.

• Testing should be completed within 30-60 minutes of opening the pouch. 2. Remove the test device, test tube and filter cap from the aluminum pouches and place it on a flat surface just prior to starting test. 3. Scan the QR code on the test device through your mobile phone camera. If you are having difficulty scanning the QR on the test device, you may type the serial number into the input box below. The serial number is printed on the test device. 4. Fill out the requested personal information and symptoms about the person who will be tested. 2. Specimen collection (CDC guideline):
  Use only the swabs provided with the test kit (FA/FANAB01 and Miraclean Technology, Item No. 96000) for specimen collection following the instruction on the mobile application.

  1. Make sure extraction buffer tube and filter cap are also readily available before starting sample collection, as the collected swab sample must be immediately inserted into the extraction buffer tube for sample extraction. After swabbing, immediately insert the swab into extraction buffer tube. Do not leave the sampled swab dry in open air as it may result in incorrect test results.
  2. Look for the “PEEL HERE” sign to peel open the swab package halfway. Make sure the soft tip is still covered with the packaging. Identify the breakpoint on the swab and break off the handle. Remove the swab from the package. Do not touch the soft tip or lay it down on any surfaces. You will see two notches on the handle. Make sure to hold the swab at the second notch.
  3. Insert the entire soft end of the swab straight back into your nostril less than one inch (about 2cm) or until resistance is felt. Slowly rotate the swab, gently rubbing it along the insides of your nasal passage several times. Gently remove the swab. Using the same swab, repeat this process in your other nostril with the same end of the swab. Note: The swab included in the kit is designed for collection of samples from adults. Do not collect swabs from children under 14 years of age.
  4. Test method
  5. Put the tip of the swab into the test tube. Move the swab up and down at least 10 times to ensure sufficient sample is extracted.
  6. Remove the swab while pressing against the sides of the tube to ensure maximum amount of liquid has been squeezed from the swab.

• Avoid swabbing and inserting excessive amount of mid-turbinate nasal specimen into the test tube, as it may block the filter cap when dispensing sample extracts.
  Note: False negative results can occur if the specimen is not properly mixed or too vigorously mixed.

  3. Put the filter cap on the opening of the test tube and immediately dispense three drops of sample extracts (100 μL) into the sample well of the device.

• If you have dropped the test device after sample application, please discard the test device and restart the test using a new test device.
  Note: Adding only one drop of solution or the entire vial may result in false negative results.

  4. Click the “Completed” button and the 15 minute timer will start on the mobile application.
  5. Read results 15 minutes after applying the sample. Do not read results after 20 minutes. Click the “YES” or “NO” button on the application for the presence of red colored lines in the device window next to each of the two letters, C (Control) and T (Test). Follow the instructions based on your test result.
     Note: False negative or false positive results can occur if results are read before 15 minutes or after 20 minutes.

• You will be instructed to take a picture of the test device. Please note that the photos are not processed and have no effect on reported results. They are collected for future reference only. 6. Dispose the remainder of the test in general waste.

INTERPRETATION OF RESULTS

• Negative result: If no red colored line appears in the test line (T) and a red colored line is present on the control region (C), then the result is negative. A negative result indicates viral antigens were not detected in the specimen and the individual is presumed negative for COVID-19.

  • Negative results do not rule out COVID-19.
  • In case of negative test result: Continue to follow all social distancing recommendations and take protective measures. If suspicions of infection persist and/or your first test is negative, repeat the test after 1 – 2 days and consult your healthcare provider or local COVID-19 center.
  • Note: A negative result is presumptive and confirmation with a molecular assay, if necessary, for patient management may be performed.
    For serial testing programs, additional confirmatory testing with a molecular test for negative results may be necessary after second negative result for asymptomatic patients, if there is a high likelihood of SARS-CoV-2 infection, such as in an individual with as close contact with COVID-19 or with suspected exposure to COVID-19 or in communities with high prevalence of infection. Additional confirmatory testing with a molecular test for positive results may also be necessary, if there is a low likelihood of SARS-CoV-2 infection, such as in individuals without known exposures to SARS-CoV-2 or residing in communities with low prevalence of infection.

• Positive result: If red colored line is visible in the test line (T) and control line (C), the result is positive. A positive result indicates that viral antigens from COVID-19 were present in the specimen and the individual is positive for COVID-19.

  • Persons who test positive with the Celltrion DiaTrustTM COVID-19 Ag Home Test should self-isolate and seek follow up care with their physician or healthcare provider as additional testing and public health reporting may be necessary.

• Invalid result: If there is no red colored line in the control region (C), the result is invalid.

  • In case of an invalid test result: Repeat the test using new test kit. If the test result is still invalid, contact your doctor or local COVID-19 center. An invalid results does not indicate if the individual did or did not have COVID-19 and should be repeated.These are photos of actual positive results. Please note that the test line can show up faintly. This faint line still indicates a positive result.

PERFORMANCE CHARACTERISTICS

Analytical testing is conducted with the nasopharyngeal swab specimen, and the matrix equivalency study is conducted to support mid-turbinate nasal swab as the specimen type.

1. Limit of detection (LoD)
   LoD studies determine the lowest detectable concentration of SARS-CoV-2. The LoD was determined by limiting dilution studies using SARS-CoV-2 virus inactivated by beta-Propiolactone (BPL).
   Negative sample was prepared by collecting nasopharyngeal swab samples from healthy donors (negative clinical matrix) eluted in PBS.
   The positive standard materials are prepared with the six different concentrations of SARS-CoV-2 inactivated virus (Conc. 6.3 × 105 TCID50/mL, NMC-nCoV02 #24) that is serially diluted in PBS and negative clinical matrix.
   The diluted positive standard materials are applied to the swab tip with 100 μL of approximate absorption volume. The extraction buffer tubes are prepared and each swab samples are inserted into each extraction buffer tubes. The swab was moved up and down inside the tube 10 times and taken out by pressing to remove the extracted liquid. The filter cap was equipped onto the test tube, then three drops of extracts (100 μL) was dispensed into the sample inlet. The result was read 15 minutes after applying the sample.
   Serial dilutions of the inactivated SARS-CoV-2 were tested in 5 replicates. The lowest concentration at which all 5 replicates were positive was treated as the tentative LoD for each test. Based on this testing, the tentative LoD was 3.2 × 101 TCID50/mL.
   The LoD of each test was then confirmed by testing 20 replicates with concentrations near the tentative limit of detection. The final LoD of Celltrion DiaTrustTM COVID-19 Ag Home Test was determined to be the lowest concentration resulting in positive detection more than 95% of the time, which is at least 19 out of 20 replicates.
   In conclusion, the limit of detection (LoD) of Celltrion DiaTrustTM COVID-19 Ag Home Test for NP swab is 3.2 × 101 TCID50/mL.

2. Cross-reactivity (Analytical specificity) and Microbial Interference Studies Wet-testing:
   The study was performed to evaluate the cross-reactivity of the Celltrion DiaTrustTM COVID-19 Ag Home Test.
   Nasopharyngeal swab sample from healthy donors (negative clinical matrix) were collected and eluted in extraction buffer to be used as a negative standard material. For each test, the diluted sample was added to a sterile nasal swab before conducting the test according to the instruction for use. Positive standard materials (NMC-nCoV02 #24, 6.3 × 105 TCID50/mL) were spiked into negative sample and were diluted to make low concentration level (6.3 × 101 TCID50/mL, approx. 2xLoD) for testing.
   Potential cross-reactive organisms listed in the below table were prepared at the concentration of 105 PFU/mL or higher for viruses and 106 CFU/mL or higher for bacteria. They were spiked into the negative and low positive samples and were tested in 3 replicates. A total of 31 pathogens listed in the below table showed no cross-reactivity with the Celltrion DiaTrustTM COVID-19 Ag Home Test.

List of organisms

|

Testing conc.

| Test result
---|---|---
Negative

(No. of negative/ No. of replicates)

| Low Positive (No. of positive/ No. of replicates)

Other high priority pathogens from the same virus family

| Coronavirus OC43| 4.4 × 107 PFU/mL| 3/3| 3/3
Coronavirus 229E| 3 × 106 PFU/mL| 3/3| 3/3
Coronavirus NL63| 1 × 105 TCID50/mL| 3/3| 3/3
MERS-coronavirus| 1.183 × 105

TCID50/mL

| 3/3| 3/3

Other high priority organisms

| Human adenovirus 1| 7 × 107 PFU/mL| 3/3| 3/3
Human adenovirus 3| 2.4 × 106 PFU/mL| 3/3| 3/3
Human adenovirus 5| 4.0 × 107 PFU/mL| 3/3| 3/3
Human adenovirus 7| 2.0 × 108 PFU/mL| 3/3| 3/3
Respiratory syncytial virus A| 8.0 × 105 PFU/mL| 3/3| 3/3
Respiratory syncytial virus B| 2.4 × 106 PFU/mL| 3/3| 3/3
Parainfluenza 1| 2.8 × 105 PFU/mL| 3/3| 3/3
Parainfluenza 2| 2 × 107 PFU/mL| 3/3| 3/3
Parainfluenza 3| 8 × 105 PFU/mL| 3/3| 3/3
Parainfluenza 4a| 1.3 × 108 PFU/mL| 3/3| 3/3
Rhinovirus 1| 1.4 × 105 PFU/mL| 3/3| 3/3
Metapneumovirus| 6 × 105 PFU/mL| 3/3| 3/3
Human enterovirus| 1 × 105 PFU/mL| 3/3| 3/3
Influenza A H1N1| 2 × 105 PFU/mL| 3/3| 3/3
Influenza A H3N2| 4.9 × 106 PFU/mL| 3/3| 3/3
Influenza B| 1 × 106 PFU/mL| 3/3| 3/3
Mycoplasma pneumonia

(whole organism)

| 1 × 107 CFU/mL| 3/3| 3/3
Streptococcus pyogenes| 1 × 106 CFU/mL| 3/3| 3/3
Bordetella pertussis| 1 × 106 CFU/mL| 3/3| 3/3
Streptococcus pneumoniae| 1 × 106 CFU/mL| 3/3| 3/3
Legionella pneumophila| 1 × 106 CFU/mL| 3/3| 3/3
Haemophilus influenzae| 1 × 106 CFU/mL| 3/3| 3/3
Candida albicans| 1 × 106 CFU/mL| 3/3| 3/3
Chlamydia pnuemoniae| 2.0 × 107 TCID50/mL| 3/3| 3/3
Pooled human nasal wash| 100%| 3/3| 3/3
Staphylococcus epidermidis| 1 × 106 CFU/mL| 3/3| 3/3
Staphylococcus aureus| 1 × 106 CFU/mL| 3/3| 3/3

Human coronavirus HKU1 spike protein at the concentration of 10 μg/mL was spiked into negative and positive samples. It was tested in 3 replicates using the Celltrion DiaTrustTM COVID-19 Ag Home Test, and no cross-reactivity was observed.

In-silico:
To estimate the likelihood of cross-reactivity with SARS-CoV-2 virus in the presence of organisms that were not available for wet testing, in silico analysis was used to assess the degree of protein sequence homology.

• Human coronavirus HKU1: 25% homology was found between SARS-CoV-2 Receptor Binding Domain spike proteins and HKU1 spike protein, and 44% homology was found between SARS-CoV-2 Nucleocapsid protein and HKU1 Nucleocapsid protein. Therefore, cross-reactivity cannot be ruled out.
• Pneumocystis jirovecii: No significant similarity was found between SARS-CoV-2 RBD spike protein / nucleocapsid protein and P. jirovecii. But minor similarity was found between some partial proteins of P. jirovecii RU 7and SARS-CoV-2 RBD spike protein / nucleocapsid protein. Therefore, cross-reactivity cannot be ruled out.
• Mycobacterium tuberculosis: No significant similarity was found between M. tuberculosis and SARS-CoV-2 RBD spike protein / nucleocapsid protein despite of increasing expect threshold.
• SARS-CoV: 72% homology was found between SARS-CoV-2 Receptor Binding Domain spike proteins and SARS-CoV spike protein, and 96% homology was found between SARS-CoV-2 Nucleocapsid protein and SARS-CoV Nucleocapsid protein. Therefore, cross-reactivity is highly likely.
• The Celltrion DiaTrustTM COVID-19 Ag Home Test does not differentiate between SARS-CoV and SARS-CoV-2.

Endogenous interference substances study:
Test to evaluate interference of the Celltrion DiaTrustTM COVID-19 Ag Home Test was performed.
Extraction buffer was used as negative sample. Positive standard materials were spiked into negative sample and were diluted to make low concentration level (6.3 × 101 TCID50/mL, approx. 2xLoD) for testing.
Potential interfering substances were added to the negative and positive samples and were tested using the Celltrion DiaTrustTM COVID-19 Ag Home Test in 3 replicates. The test results demonstrated that 48 interfering substances did not affect the performance of Celltrion DiaTrustTM COVID-19 Ag Home Test.

No.

|

Interfering substances

|

Testing conc.

|

Negative

| Negative + Interfering substances| Low positive| Low pos. + Interfering substances
---|---|---|---|---|---|---
1| Whole blood| 4%| 3/3| 3/3| 3/3| 3/3
2| Mucin| 0.5%| 3/3| 3/3| 3/3| 3/3
3| Chloraseptic| 1.5 mg/mL| 3/3| 3/3| 3/3| 3/3
4| NeilMed NasoGel| 5% v/v| 3/3| 3/3| 3/3| 3/3
5| CVS Nasal drops| 15% v/v| 3/3| 3/3| 3/3| 3/3
6| Afrin (Oxymetazoline)| 15% v/v| 3/3| 3/3| 3/3| 3/3
7| Sodium cromoglycate| 15% v/v| 3/3| 3/3| 3/3| 3/3

No.

|

Interfering substances

|

Testing conc.

|

Negative

| Negative + Interfering substances| Low positive| Low pos. + Interfering substances
---|---|---|---|---|---|---
 | (CVS nasal spray, Cromolyn)|  |  |  |  |
8| Zicam| 15% v/v| 3/3| 3/3| 3/3| 3/3
9| Homeopathic (Alkalol)| 1:10 dilution| 3/3| 3/3| 3/3| 3/3
10| Sore throat Phenol Spray| 15% v/v| 3/3| 3/3| 3/3| 3/3
11| Tobramycin| 5 μg/mL| 3/3| 3/3| 3/3| 3/3
12| Mupirocin| 10 mg/mL| 3/3| 3/3| 3/3| 3/3
13| Fluticasone Propionate| 5% v/v| 3/3| 3/3| 3/3| 3/3
14| Tamiflu (Oseltamivir Phosphate)| 5 mg/mL| 3/3| 3/3| 3/3| 3/3
15| Albumin, human| 3000 mg/dL| 3/3| 3/3| 3/3| 3/3
16| Bilirubin| 500 μmol/L| 3/3| 3/3| 3/3| 3/3
17| Hemoglobin| 500 mg/dL| 3/3| 3/3| 3/3| 3/3
18| Cholesterol| 20 μmol/L| 3/3| 3/3| 3/3| 3/3
19| Triglyceride| 1000 mg/dL| 3/3| 3/3| 3/3| 3/3
20| Biotin| 0.75 mg/mL| 3/3| 3/3| 3/3| 3/3
21| Sodium citrate| 25 mg/mL| 3/3| 3/3| 3/3| 3/3
22| Heparin| 100 U/mL| 3/3| 3/3| 3/3| 3/3
23| EDTA| 5 μmol/L| 3/3| 3/3| 3/3| 3/3
24| K3-EDTA| 20 mg/mL| 3/3| 3/3| 3/3| 3/3
25| Diphenhydramine hydrochloride| 5 mg/mL| 3/3| 3/3| 3/3| 3/3
26| Acetaminophen| 199 μmol/L| 3/3| 3/3| 3/3| 3/3
27| Acetylsalicylic acid| 3.62 mmol/L| 3/3| 3/3| 3/3| 3/3
28| Ibuprofen| 2.425 mmol/L| 3/3| 3/3| 3/3| 3/3
29| Olopatadine hydrochloride| 5 mg/mL| 3/3| 3/3| 3/3| 3/3

30

| Hanmi Ko-and-Cool Nasal Spray (Chlorpheniramine Maleate 250 mg/ 100 mL, Xylometazoline Hydrochloride 0.1 g/100

mL)

|

10%(v/v)

|

3/3*

|

3/3*

|

3/3**

|

3/3**

31

| Samchundang Narista-S Nasal Spray (Chlorpheniramine Maleate 2.5 mg/mL, Dipotassium Glycyrrhizinate 3 mg/mL, Naphazoline Hydrochloride 0.5

mg/mL)

|

10%(v/v)

|

3/3*

|

3/3*

|

3/3**

|

3/3**

32| Sodium chloride| 20 mg/mL| 3/3| 3/3| 3/3| 3/3
33| Zanamivir| 5 mg/mL| 3/3| 3/3| 3/3| 3/3

No.

|

Interfering substances

|

Testing conc.

|

Negative

| Negative + Interfering substances| Low positive| Low pos. + Interfering substances
---|---|---|---|---|---|---
34| Oseltamivir| 10 mg/mL| 3/3| 3/3| 3/3| 3/3
35| Artemether- lumefantrine| 50 μmol/L| 3/3| 3/3| 3/3| 3/3
36| Doxycycline hyclate| 70 μmol/L| 3/3| 3/3| 3/3| 3/3
37| Quinine| 150 μmol/L| 3/3| 3/3| 3/3| 3/3
38| Lamivudine| 1 mg/mL| 3/3| 3/3| 3/3| 3/3
39| Erythromycin| 81.6 μmol/L| 3/3| 3/3| 3/3| 3/3
40| Ciprofloxacin| 30.2 μmol/L| 3/3| 3/3| 3/3| 3/3
41| Rheumatoid factor positive plasma| 10%(v/v)| 3/3| 3/3| 3/3| 3/3
42| Neutrogena lotion (glycerin)| 1% (v/v)| 3/3| 3/3| 3/3| 3/3
43| Hand sanitizer (ethyl alcohol)| 1% (v/v)| 3/3| 3/3| 3/3| 3/3
44| Hand soap (benzalkonium chloride)| 1% (v/v)| 3/3| 3/3| 3/3| 3/3

45

| Laundry detergent (C12- 15 pareth-7 and sodium laureth-12 sulfate)|

1% (v/v)

|

3/3*

|

3/3*

|

3/3**

|

3/3**

46| Bleach (sodium hypochlorite)| 1% (v/v)| 3/3| 3/3| 3/3| 3/3
47| Surface sanitizer (citric acid)| 1% (v/v)| 3/3| 3/3| 3/3| 3/3
48| Dish-washing liquid (sodium lauryl sulfate)| 1% (v/v)| 3/3| 3/3| 3/3| 3/3

*: Negative / **: Positive

High-dose Hook effect
Pooled nasopharyngeal specimens were used as clinical matrix, and SARS-CoV-2 virus inactivated by beta-Propiolactone (BPL) was spiked to make various high concentration levels of SARS-CoV-2 antigens. Prepared samples of each concentration levels were tested using Celltrion DiaTrustTM COVID-19 Ag Home Test in 3 replicates following instructions.
No high-dose hook effect was observed up to 6.3 × 105 TCID50/mL, approx. 20,000xLoD.

SARS-CoV-2 inactivated virus

( 6.3 Í 105 TCID50/mL )

TCID 50 /mL

(concentration)

| Test results

(No. of positives/ No. of replicates)

Lot 1| Lot  2
3.2 Í 101 [1xLoD]| 3/3| 3/3
1.3 Í 102 [4xLoD]| 3/3| 3/3
1.5 Í 104 [500xLoD]| 3/3| 3/3
6.3 Í 105 [20,000xLoD]| 3/3| 3/3

Flex study
The robust use of Celltrion DiaTrustTM COVID-19 Ag Home Test was demonstrated by ten (10) Flex studies: temperature and humidity, delay in sample testing, delay in result reading, extraction buffer volume variability, swab mixing expression variability, disturbance during testing, testing on non-level surface, impact of light sources, test device held at 90° angle and disturbance during analysis – receiving a phone call while the mobile app is running.

Clinical performance
The clinical evaluation of the Celltrion DiaTrustTM COVID-19 Ag Home Test was evaluated by testing a total of 492 prospectively collected direct mid- turbinate nasal swab samples, consisted of 45 positive and 447 negative samples from suspected COVID-19 patients in United States, aged 14 years and older at four clinical sites. Mid-turbinate nasal swabs were collected and tested by each study participant, eluted in the extraction buffer and tested with the device immediately, using only the QRI and App. Results of each samples were confirmed by FDA EUA RT-PCR.
According to the test results, clinical performance results of the Celltrion DiaTrustTM COVID-19 Ag Home Test was as follows:

Table 1. Demographic and Clinical Characteristics

Characteristic

| ****

Total number

| Total Positive by RT-PCR| ****

% Positive

---|---|---|---

Age Range

| 14-24| 88| 12| 12/88 (13.6%)
25-64| 381| 31| 31/381 (8.1%)
≥65| 23| 2| 2/23 (8.7%)
Sex|  |  |
Female| 266| 18| 18/266 (6.8%)
Male| 226| 27| 27/226 (11.9%)
Total| 492| 45| 45/492 (9.1%)

Table 2. Observations of All subjects

All Data

| Reference PCR Results
---|---
Positive| Negative| Total

DiaTrustTM COVID-19 Ag Home Test

| Positive| 39| 1| 40
Negative| 6| 446| 452
Total| 45| 447| 492

PPA:86.7 % (95% CI: 73.8%-93.7%) NPA: 99.8 % (95% CI: 98.7%-100.0%)

Table 3. Observations of Symptomatic subjects

Symptomatic Data

| Reference PCR Results
---|---
Positive| Negative| Total

DiaTrustTM COVID-19 Ag Home Test

| Positive| 31| 1| 32
Negative| 5| 174| 179
Total| 36| 175| 211

PPA: 86.1% (95% CI: 71.3% – 93.9%) NPA: 99.4% (95% CI: 96.8% – 99.9%)

Table 4. Observations of Asymptomatic subjects

Asymptomatic Data

| Reference PCR Results
---|---
Positive| Negative| Total

DiaTrustTM COVID-19 Ag Home Test

| Positive| 8| 0| 8
Negative| 1| 272| 273
Total| 9| 272| 281

PPA: 88.9 % (95% CI: 56.8%-98.0%)

NPA: 100.0% (95% CI: 98.6%-100.0%)

Table 5. PPA and NPA by days since onset of symptoms

(95% CI: 56.5% – 98.0%)

| 100% (272/272)

(95% CI: 98.6% – 100.0%)

1

| 75.0% (3/4)

(95% CI: 30.1% – 95.4%)

| 95.8% (23/24)

(95% CI: 79.8% – 99.3%)

2

| 100.0% (8/8)

(95% CI: 67.6% – 100.0%)

| 100.0% (40/40)

(95% CI: 91.2% – 100.0%)

3

| 100.0% (9/9)

(95% CI: 70.1% – 100.0%)

| 100.0% (38/38)

(95% CI: 90.8% – 100.0%)

4

| 85.7% (6/7)

(95% CI: 48.7% – 97.4%)

| 100.0% (30/30)

(95% CI: 88.6% – 100.0%)

5

| 66.7% (2/3)

(95% CI: 20.8% – 93.9%)

| 100.0% (24/24)

(95% CI: 86.2% – 100.0%)

6

| 100.0% (2/2)

(95% CI: 34.2% – 100.0%)

| 100.0% (12/12)

(95% CI: 75.8%-100.0%)

7

| 33.3% (1/3)

(95% CI: 6.1%-79.2%)

| 100.0% (7/7)

(95% CI: 64.6%-100.0%)

ASSISTANCE

If you have any questions regarding the use of this product or if you want to report a test system problem, please contact Humasis Co., Ltd. (via email: [email protected], via phone: +82-31-8085-6284) or Celltrion USA, Inc. (via email: [email protected], or via phone: 201-499-1844). Test system problems may also be reported to the FDA through the MedWatch medical products reporting program (phone: 800.FDA.1088; fax: 800.FDA.0178; http://www.fda.gov/medwatch

REFERENCES

1. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020.
2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020.
3. Kang CK, Song KH, Choe PG, et al. Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea. J Korean Med Sci 2017; 32:744-9.
4. WHO, Novel Coronavirus (2019-nCoV) situation reports. Available at:
   https://www.who.int/emergencies/diseases/novel- coronavirus-2019/situationreports/ (Accessed at 2 Feb, 2020).

Read User Manual Online (PDF format)

Download This Manual (PDF format)

Download this manual  >>