CorDx Tyfast COVID-19 Ag Rapid Test; CorDx COVID-19 Ag Test by CorDx, Inc.

The CorDx Tyfast COVID- 19 Ag Rapid Test is a visually read lateral flow immunoassay device intended for the rapid, qualitative detection of SARS-CoV-2 virus nucleocapsid protein antigen directly in anterior nasal swab specimens from individuals with signs and symptoms of COVID-19.

This test is for non-prescription home use by individuals aged 14 years or older testing themselves, or adults testing individuals aged 2 years or older.

The CorDx Tyfast COVID- 19 Ag Rapid Test does not differentiate between SARS-CoV and SARS-CoV-2.

All negative results are presumptive. Symptomatic individuals with an initial negative test result must be re-tested once between 48 and 72 hours after the first test using an antigen test or a molecular test for SARS-CoV-2. Negative results do not preclude SARS-CoV-2 infections or other pathogens and should not be used as the sole basis for treatment. Positive results do not rule out co-infection with other respiratory pathogens.

This test is not a substitute for visits to a healthcare provider or appropriate follow-up and should not be used to determine any treatments without provider supervision. Individuals who test negative and experience continued or worsening COVID-19 like symptoms, such as fever, cough and/or shortness of breath, should seek follow up care from their healthcare provider.

The performance characteristics for SARS-CoV-2 were established from September, 2023, to December, 2023, when SARS-CoV-2 Omicron was dominant. Test accuracy may change as new SARS-CoV-2 viruses emerge. Additional testing with a lab-based molecular test (e.g., PCR) should be considered in situations where a new virus or variant is suspected.

The CorDx Tyfast COVID-19 Ag Rapid Test is intended for non-prescription self-use and/or as applicable an adult lay user testing another person 2 years of age or older in a nonlaboratory setting.

Device Description

The CorDx Tyfast COVID-19 Ag Rapid Test is a rapid, immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect nucleocapsid protein from SARS-CoV-2 from anterior nasal swab specimens. This test does not differentiate between SARS-CoV and SARS-CoV-2. The test kit includes the: test cassette, swab, tube with sample processing solution, tube holder (back of the box) and the Quick Reference Instructions (QRI).

The test strip enclosed in a cassette housing is comprised of the following components: sample pad, reagent pad, reaction membrane, and absorbing pad. The reagent pad contains colloidal-gold conjugated with a monoclonal antibody against the nucleocapsid protein of SARS-CoV-2; the reaction membrane contains the secondary antibody for the nucleocapsid protein of SARS-CoV-2. The whole strip is fixed inside a plastic cassette.

When the sample extract is added into the sample well, conjugates dried onto the reagent pad are dissolved and migrate along with the sample. If SARS-CoV-2 nucleocapsid antigen is present in the sample, a complex formed between the anti-SARS-2 conjugate and the viral antigen will be captured by the specific anti-SARS-2 monoclonal antibody coated on the test line region (T). Absence of the test line (T) suggests a negative result. To serve as a procedural control, a red line will always appear in the control line region (C) indicating that proper volume of sample has been added and membrane wicking has occurred.

AI/ML Overview

The CorDx Tyfast COVID-19 Ag Rapid Test is a qualitative lateral flow immunoassay intended for the rapid detection of SARS-CoV-2 virus nucleocapsid protein antigen in anterior nasal swab specimens from individuals with signs and symptoms of COVID-19. It is designed for non-prescription home use by individuals aged 14 years or older testing themselves, or adults testing individuals aged 2 years or older.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the device performance are based on the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a highly sensitive 510(k)-cleared SARS-CoV-2 RT-PCR assay.

Metric	Acceptance Criteria (Implicit)	Reported Device Performance (95% CI)
Positive Percent Agreement (PPA)	Not explicitly stated, but typically expected to be high for symptomatic individuals.	85.6% (78.1% to 10.8%) - Note: The upper CI value of 10.8% appears to be a typo in the original text and should likely be a higher value consistent with 85.6% PPA. Assuming it's meant to be 90.8% or similar.
Negative Percent Agreement (NPA)	Not explicitly stated, but typically expected to be very high.	99.5% (98.5% to 99.8%)

2. Sample Sizes and Data Provenance

Test Set Sample Size: 740 individuals were enrolled in the study, with 693 evaluable subjects.
- True Positives: 101 subjects
- True Negatives: 572 subjects
- Discordant Results (Test Negative, Comparator Positive): 17 subjects
- Discordant Results (Test Positive, Comparator Negative): 3 subjects
Data Provenance: The clinical study was prospective, conducted from September 2023 to December 2023 at four (4) sites throughout the United States. This indicates the data is prospective and from the USA.
Training Set Sample Size: The document does not provide specific details on the training set sample size for any machine learning components, as this is a visually read lateral flow immunoassay and not explicitly an AI/ML device in the context of the provided text. The "Precision Study by Lots" used 60 replicates for each of 3 lots (180 total) for negative, 2xLoD, and 4xLoD samples to assess analytical precision and consistency.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts or their specific qualifications (e.g., radiologist with 10 years experience) used to establish ground truth. However, the ground truth was established by a "highly sensitive 510(k)-cleared SARS-CoV-2 RT-PCR assay," which is considered the gold standard for SARS-CoV-2 detection. Therefore, the expertise lies in the validated performance of the comparator RT-PCR assay and its operation in a clinical laboratory setting.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for discordant results in the clinical study beyond simply identifying the discordant cases. The final ground truth was determined by the RT-PCR assay, implying that the RT-PCR result was considered definitive for the purpose of performance calculation.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

A MRMC comparative effectiveness study was not conducted. This device is a visually read rapid antigen test, and the study design focused on the device's performance against a gold standard molecular assay, not on human reader improvement with or without AI assistance.

6. Standalone Performance (Algorithm Only)

Standalone performance (algorithm only) was not explicitly conducted or reported, as this device is a visually read lateral flow immunoassay. Its performance is inherent in its design and the user's interpretation, rather than an independent algorithm.

7. Type of Ground Truth Used

The primary ground truth used for the clinical performance evaluation was a highly sensitive 510(k)-cleared SARS-CoV-2 RT-PCR assay. This is a molecular diagnostic method, considered a definitive reference standard for SARS-CoV-2 infection.

8. Sample Size for the Training Set

As this is a visually read rapid antigen test and not an AI/ML diagnostic system in the conventional sense, a 'training set' for an algorithm is not applicable in the way it would be for an image-based AI system. The analytical performance evaluations would involve internal validation data. For instance, the "Precision Study by Lots" utilized 180 samples in total across three lots for each concentration (negative, 2xLoD, 4xLoD) to demonstrate analytical consistency.

9. How Ground Truth for the Training Set Was Established

Given that this is not an AI/ML device with a distinct 'training set' for an algorithm, the concept of establishing ground truth for a training set in that context is not applicable. For internal analytical studies (like LoD, inclusivity, cross-reactivity, and precision), ground truth was established through:

Spiking known concentrations of SARS-CoV-2 virus: For LoD and inclusivity studies, UV-inactivated or heat-inactivated SARS-CoV-2 virus (USA-WA1/2020 isolate or specific variants) at defined TCID50/mL or IU/mL concentrations were spiked into negative nasal wash or swab matrix.
Testing against known common respiratory pathogens/substances: For cross-reactivity and interference studies, known concentrations of various microorganisms or endogenous/exogenous substances were used, both with and without spiked SARS-CoV-2 (at 3x LoD), to assess their impact on test results.
Use of WHO International Standard: For LoD determination, the WHO International Standard for SARS-CoV-2 Antigen (NIBSC 21/368) was used to ensure traceability.

These methods establish the "ground truth" for the analytical performance characteristics of the device during its development and validation.

Summary

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June 21, 2024

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, with the word "ADMINISTRATION" underneath.

CorDx, Inc. % Jinjie Hu President and Principal Consultant Axteria Biomed Consulting Inc. 8040 Cobble Creek Circle Potomac, Maryland 20854

Re: K240728

Trade/Device Name: CorDx Tyfast COVID-19 Ag Rapid Test; CorDx COVID-19 Ag Test Regulation Number: 21 CFR 866.3984 Regulation Name: Over-the-counter test to detect SARS-CoV-2 from clinical specimens Regulatory Class: Class II Product Code: QYT Dated: March 18, 2024 Received: March 18, 2024

Dear Jinjie Hu:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely, Silke Digitally signed by Silke Schlottmann -S Schlottmann -S Date: 2024.06.21 10:54:26 -04'00 Silke Schlottmann, Ph.D. Deputy Assistant Director Bacteriology Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K240728

Device Name

CorDx Tyfast COVID-19 Ag Rapid Test; CorDx COVID-19 Ag Rapid Test

Indications for Use (Describe)

This test is for non-prescription home use by individuals aged 14 years or older testing themselves, or adults testing individuals aged 2 years or older.

The CorDx Tyfast COVID- 19 Ag Rapid Test does not differentiate between SARS-CoV and SARS-CoV-2.

The performance characteristics for SARS-CoV-2 were established from September, 2023, when SARS-CoV-2 Omicron was dominant. Test accuracy may change as new SARS-CoV-2 viruses emerge. Additional testing with a lab-based molecular test (e.g., PCR) should be considered in situations where a new virus or variant is suspected.

Type of Use (Select one or both, as applicable)
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Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)
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CorDx, Inc.

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

CorDx, Inc. SUBMITTER: 9540 Waples St. # C, San Diego, CA 92121
Contact person: Jinjie Hu, Axteria BioMed Consulting Inc. 8040 Cobble Creek Circle Potomac, MD 20854 Tel: 1-(301)814-4985 Email: jinjie.hu@axteriabiomed.com

Date prepared: March 22, 2024

Purpose of Submission:

To obtain a substantial equivalence for the CorDx Tyfast COVID-19 Ag Rapid Test (also known as CorDx COVID-19 Ag Test in EUA)

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CorDx, Inc.

A. 510(k) Number: K240728
B. Purpose for Submission: New Device
C. Measure: Antigen of SARS-CoV-2

D. Type of Test: Qualitative chromatographic immunoassay

E. Applicant:

CorDx, Inc.

F. Proprietary and Established Names: CorDx Tyfast COVID-19 Ag Rapid Test

G. Regulatory Information:

1. Regulation: 21 CFR 866.3984 - Over-The-Counter Test to Detect SARS-Cov-2 From Clinical Specimens
1. Classification: Class II
1. Product Code: QYT
1. Panel: Microbiology

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CorDx, Inc.

H. Intended Use:

1. Intended use(s):

This test is for non-prescription home use by individuals aged 14 years or older testing themselves, or adults testing individuals aged 2 years or older.

The CorDx Tyfast COVID- 19 Ag Rapid Test does not differentiate between SARS-CoV and SARS-CoV-2.

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CorDx, Inc.

The CorDx Tyfast COVID-19 Ag Rapid Test is intended for non-prescription self-use and/or as applicable an adult lay user testing another person 2 years of age or older in a nonlaboratory setting.

1. Special condition for use statement(s): This device is intended for over-the-counter (OTC) use.
1. Special instrument requirements: None

I. Device Description:

J. Substantial Equivalence Information:

1. Predicate device name(s): ACON Laboratories, Inc. K230828, Flowflex COVID-19 Antigen Home Test
1. Predicate K number(s): K230828
1. Comparison with predicate

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CorDx Tyfast COVID-19 Ag Rapid Test

CorDx, Inc.

Parameter	CorDx Tyfast COVID-19 AgRapid Test	Predicate (K230828)Flowflex COVID-19 AntigenHome Test	SimilarityorDifference
Intended Use	The CorDx Tyfast COVID- 19 AgRapid Test is a visually readlateral flow immunoassay deviceintended for the rapid, qualitativedetection of SARS-CoV-2 virusnucleocapsid protein antigendirectly in anterior nasal swabspecimens from individuals withsigns and symptoms ofCOVID-19.This test is for non-prescriptionhome use by individuals aged 14years or older testing themselves,or adults testing individuals aged2 years or older.The CorDx Tyfast COVID- 19 AgRapid Test does not differentiatebetween SARS-CoV and SARS-CoV-2.All negative results arepresumptive. Symptomaticindividuals with an initial negativetest result must be re-tested oncebetween 48 and 72 hours after thefirst test using an antigen test or amolecular test for SARS-CoV-2.Negative results do not precludeSARS-CoV-2 infections or otherpathogens and should not be usedas the sole basis for treatment.Positive results do not rule out co-infection with other respiratorypathogens.	The Flowflex COVID-19 AntigenHome Test is a visually read lateralflow immunoassay device intendedfor the rapid, qualitative detectionof SARS-CoV-2 virusnucleocapsid protein antigendirectly in anterior nasal swabspecimens from individuals withsigns and symptoms of COVID-19 within the first 6 days ofsymptom onset.This test is for non-prescriptionhome use by individuals aged 14years or older testing themselves,or adults testing individuals aged 2years or older.The Flowflex COVID-19 AntigenHome Test does not differentiatebetween SARS-CoV and SARS-CoV-2.All negative results arepresumptive. Symptomaticindividuals with an initial negativetest result must be re-tested oncebetween 48 and 72 hours after thefirst test using either an antigentest or a molecular test for SARS-CoV-2. Negative results do notpreclude SARS-CoV-2 infectionsor other pathogens and should notbe used as the sole basis fortreatment.Positive results do not rule out co-infection with other respiratorypathogens.	Same
Parameter	CorDx Tyfast COVID-19 AgRapid Test	Predicate (K230828)Flowflex COVID-19 AntigenHome Test	SimilarityorDifference
	This test is not a substitute forvisits to a healthcare provider orappropriate follow-up and shouldnot be used to determine anytreatments without providersupervision. Individuals who testnegative and experience continuedor worsening COVID-19 likesymptoms, such as fever, coughand/or shortness of breath, shouldseek follow up care from theirhealthcare provider.	This test is not a substitute forvisits to a healthcare provider orappropriate follow-up and shouldnot be used to determine anytreatments without providersupervision. Individuals who testnegative and experiencecontinued or worseningCOVID-19 like symptoms, suchas fever, cough and/or shortnessof breath, should seek follow upcare from their healthcareprovider.
	The performance characteristicsfor SARS-CoV-2 were establishedfrom September, 2023, toDecember, 2023, when SARS-CoV-2 Omicron was dominant.Test accuracy may change as newSARS-CoV-2 viruses emerge.Additional testing with a lab-based molecular test (e.g., PCR)should be considered in situationswhere a new virus or variant issuspected.	The performance characteristicsfor SARS-CoV-2 wereestablished from December 2022toMarch 2023 when SARS-CoV-2Omicron was dominant. Testaccuracy may change as newSARS-CoV-2 viruses emerge.Additional testing with a lab-based molecular test (e.g., PCR)should be considered insituations where a new virus orvariant is suspected.
Intended UseEnvironment	Over the counter use/self-testing	Over the counter use/self-testing	Same
Intended Usepopulation	Individuals with symptoms ofCOVID-19	Individuals with symptoms ofCOVID-19	Same
Organismdetected	SARS-CoV-2	SARS-CoV-2	Same
Analyte	Nucleocapsid protein antigen fromSARS-CoV-2	Nucleocapsid protein antigenfrom SARS-CoV-2	Same
Regulationnumber	21 CFR 866.3984	21 CFR 866.3984	Same
Principle of theTechnology	Qualitative lateral flowimmunoassay	Qualitative lateral flowimmunoassay	Same
Sample type	Anterior nasal swab specimens	Anterior nasal swab specimens	Same
Detectionformat	Test cassette, visually read withoutan instrument.	Test cassette, visually readwithout an instrument.	Same
Assay Result	Qualitative (positive, negative,invalid)	Qualitative (positive, negative,invalid)	Same
Parameter	CorDx Tyfast COVID-19 Ag Rapid Test	Predicate (K230828) Flowflex COVID-19 Antigen Home Test	Similarity or Difference
Time to Result	Time to result: 10 minutes after the extracted sample is added to the test cassette sample well.	Time to result: 15 minutes after the extracted sample is added to the test cassette sample well.	Different5 minutes less reading time
Controls	-Internal procedural controls: Each CorDx Tyfast COVID-19 Rapid Ag Test has a built-in "Control" region which serves as an internal procedural control when a colored line appears in the control line region ("C line"). The "C line” should always appear if the test has been performed correctly. If the "C line" does not appear at 10 minutes, the test result is invalid. It is recommended to review the instructions again and repeat the test with a new sample and a new cassette. If the problem persists, please stop using the product and contact CorDx for technical support.-External controls: a separate external control kit is available for purchase from CorDx. The configurations of the CorDx Tyfast COVID-19 Ag Control Swab Kit from CorDx is: 10 positive swabs and 10 negative swabs per box.The COVID-19 antigen positive control swab is composed of SARS-COV-2 recombinant antigen extract dried onto a swab. The COVID-19 antigen negative control swab is composed of negative sample matrix dried onto a swab.	-Internal procedural controls: The Flowflex Plus COVID-19 Home Test has a built-in internal procedural control. The colored biotin labeled particle will bind to streptavidin on nitrocellulose membrane and the colored mouse monoclonal antibody labeled particle will bind to goat anti-mouse antibody on nitrocellulose membrane to form a colored Control line (C) in the control line region. Formation of the Control line serves as an internal control indicating that proper volume of specimen has been added and membrane wicking has occurred.	Different
Reagent Storage	Store at 36~~86°F/2~~30°C in a place out of direct sunlight and out	Store Flowflex COVID-19 Antigen Home Test between 2-30°C (36-86°F) until use.	Same

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CorDx Tyfast COVID-19 Ag Rapid Test

CorDx, Inc.

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CorDx Tyfast COVID-19 Ag Rapid Test

CorDx, Inc.

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CorDx, Inc.

K. Standard/Guidance Document referenced (if applicable):

Document Title	Issued by	Applicable study
Reclassification order for DEN220028 and special controls under 21 CFR 866.3984for Over- the-counter tests to detect SARS-CoV-2 from clinical specimens	FDA	All
ISO11135:2014, Sterilization of health care products - Ethylene oxide -Requirements for development, validation and routine control of a sterilizationprocess for medical devices	ISO	Sterility
ISO 10993-7, Biological Evaluation of Medical Devices - Part 7: Ethylene OxideSterilization Residuals	ISO	Sterility
ISO 10993-1, Biological Evaluation of Medical Devices - Part 1: Evaluation andtesting within a risk management process	ISO	Biocompatibility
EP5-A3 Evaluation of Precision of Quantitative Measurement Procedures	CLSI	Precision
EP12-A2 User Protocol for Evaluation of Qualitative Test Performance	CLSI	Precision
EP25A Evaluation of Stability of In Vitro Diagnostic Reagents	CLSI	Reagent stability
EP37 Supplemental Tables for Interference Testing in Clinical Chemistry	CLSI	Interference

L. Test Principle:

M. Performance Characteristics

1. Analytical performance:

a. Precision Study by Lots

The purpose of the study was to assess lot-to-lot variability of three different lots of the CorDx Tyfast COVID-19 Ag Rapid Test kits. The study included a sample panel consisting of a negative sample, a low positive (2x LoD) sample, and a positive (4x LoD) sample. The positive samples were prepared by spiking UV-inactivated SARS-CoV-2 in pooled negative Nasal Wash Matrix. The study results demonstrated 100% consistent performance of the CorDx Tyfast COVID-19 Ag Rapid Test for the detection of SARS-CoV-2 virus antigen when performed under different conditions of variability (days, runs, operators, kit lots and sample replicates).

	Test result(#Neg/60, # Pos/60)
Lot	NEG	2xLoD	4xLoD
Lot 1	60/60	60/60	60/60
Lot 2	60/60	60/60	60/60

Table 1. Precision Study Results

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CorDx Tyfast COVID-19 Ag Rapid Test

CorDx, Inc.

Lot 3	60/60	60/60	60/60
Total	180/180	180/180	180/180
Agreement	100%	100%	100%

b. Limit of Detection

l ) Limit of Detection in pooled negative Nasal Wash Matrix

UV-inactivated SARS-CoV-2 virus (Isolate: USA-WA1/ 2020) was spiked into pooled negative Nasal Wash Matrix and serially diluted. Each dilution was tested in triplicate on the CorDx Tyfast COVID-19 Ag Rapid Test to find the initial LoD range. The final LoD was confirmed to be 1.25x104 TCID50/mL by testing 20 individual replicates with concentrations at the initial LoD and at concentrations above and below the initial LoD.

2) Limit of Detection in Pooled Negative Swab Matrix

The Limit of Detection (LoD) of the CorDx Tyfast COVID-19 Ag Rapid Test in the Pooled Negative Swab Matrix (PNSM) was established by testing serial dilutions of heat-inactivated SARS-CoV-2 virus (Isolate: USA-WA1/ 2020) spiked in PNSM. The preliminary LoD determined by testing a 10-fold dilution series of five replicates per concentration was confirmed by testing 20 replicates. The confirmed LoD for the CorDx Tyfast COVID-19 Ag Rapid Test in PNSM was 1.00x104 TCID50/mL.

3) Limit of Detection by testing the WHO International Standard for SARS-CoV-2 antigen (NIBSC code: 21/368)

This study was designed to determine the Limit of Detection (LoD) for the CorDx Tyfast COVID-19 Ag Rapid Test using the WHO International Standard for SARS-CoV-2 Antigen (NIBSC 21/368) in Pooled Negative Swab Matrix (PNSM). The preliminary LoD determined by testing a 2-fold dilution series of three replicates per concentration was tested with an additional 17 replicates, for a total of 20 replicates, to confirm the LoD. Concentrations above and below the preliminary LoD were also tested with 20 replicates to further verify the LoD. The LoD for the CorDx Tyfast COVID-19 Ag Rapid Test was 5.00x102 IU/mL.

c. Inclusivity

The inclusivity of the CorDx Tyfast COVID-19 Ag Rapid Test was determined for detecting SARS-CoV-2 Alpha, Beta, Delta and Omicron variants as assessed by its Limit of Detection. Serially diluted Heat-irradiated SARS-CoV-2 Alpha (Lineage B1.1.7), Brazil (Lineage P.1), Beta (Lineage B.1.351), Delta (Lineage B.1.617.2), Omicron (Lineage B.1.1.529, XBB), and B.1595 variants were spiked into Pooled Negative Swab Matrix (PNSM) to determine the LoD for each tested variant using one lot of kit.

Based on the results, the CorDx TyFast COVID-19 Ag Rapid Test detects SARS-CoV-2 variants with LoD at the concentrations as indicated in the table below. The assay can detect

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CorDx, Inc.

these variants near the LoD of the original SARS-CoV-2 virus and thus displays comparable sensitivity and acceptable inclusivity for these variants tested.

SARS-CoV-2Variant	Concentration(TCID50/ mL)	SARS-CoV-2Variant	Concentration(TCID50/ mL)
Alpha B1.1.7	$2.5x10^4$	Omicron B.1.1.529	$3.125x10^3$
Brazil P.1	$2.5x10^4$	Omicron XBB	$2.5x10^4$
Beta B.1.351	$2.5x10^4$	B.1.595	$3.906x10^2$
Delta B.1.617.2	$3.125x10^3$

Table 2. LoD Concentrations of SARS-CoV-2 Variants

d. Linearity/assay reportable range:

Not applicable. This is a qualitative device.

Cross-reactivity and microbial interference study e.

Cross reactivity (analytical specificity) and microbial interference studies were performed to determine if the CorDx Tyfast COVID-19 Ag Rapid Test reacts with non-SARS-CoV-2 respiratory pathogens and other microorganisms that are likely to be encountered in the clinical sample. Each microorganism was evaluated in the absence and presence of inactivated SARS-CoV-2 virus (3x LoD) to see if false positive and false negative test results may occur. Study results showed that no cross reactivity or interference occurs with the following microorganisms at the concentration tested in the table below.

Table 3: Microorganisms and Concentrations Tested in the Study

Microorganisms	Concentration Tested
Human coronavirus 229E (Inactive)	1x105 TCID50/mL
Human coronavirus 229E (Live)	2.81x104 TCID50/mL
Human coronavirus OC43 (Inactive)	1x105 TCID50/mL
Human coronavirus OC43 (Live)	1x105 TCID50/mL
Human coronavirus NL63 (Inactive)	1x105 TCID50/mL
Human coronavirus NL63 (Live)	1x105 TCID50/mL
MERS-coronavirus (Inactive, UV)	1x105 TCID50/mL
MERS-coronavirus (Inactive, Heat)	1x105 TCID50/mL
SARS-coronavirus(Gamma-irradiated virus in Vero E6 cells in DMEM) (Inactive)	1x105 PFU/mL
SARS-coronavirus (Gamma-irradiated virus in PBS) (Inactive)	1x107 PFU/mL
Adenovirus (e.g., C1 Ad. 71) (Live)	1x106 TCID50/mL
Human Metapneumovirus 3 (hMPV-3) Type B1 (Inactive)	1x105 TCID50/mL
Human Metapneumovirus 3 (hMPV-3) Type B1 (Live)	1x105 TCID50/mL
Parainfluenza virus Type 1 (Inactive)	1x107 TCID50/mL
Parainfluenza virus Type 1 (Live)	1x105 TCID50/mL
Parainfluenza virus Type 2 (Inactive)	1x105 TCID50/mL
Parainfluenza virus Type 2 (Live)	1x105 TCID50/mL
Parainfluenza virus Type 3 (Inactive)	1x107 TCID50/mL

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CorDx Tyfast COVID-19 Ag Rapid Test

CorDx, Inc.

Microorganisms	Concentration Tested
Parainfluenza virus Type 3 (Live)	1x106 TCID50/mL
Parainfluenza virus Type 4A (Inactive)	1x105 TCID50/mL
Parainfluenza virus Type 4A (Live)	1x105 TCID50/mL
Influenza A /Perth/16/09 (H3N2) (Inactive)	1x105 TCID50/mL
Influenza A/California/07/09 (H1N1) (Inactive)	1x105 TCID50/mL
Influenza A /Hong Kong/2671/19 (Live)	1x105 TCID50/mL
Influenza A/Indiana/02/ 2020 (H1N1) pdm09 (Live)	1x107 CEID50/mL
Influenza B/Brisbane/60 /08 (Victoria lineage) (Inactive)	For Cross reactivity:4.68 x104 TCID50/mLFor Interference:2.34 x104 TCID50/mL
Influenza B/Wisconsin/01 /10 (Yamagata lineage) (Inactive)	1x105 TCID50/mL
Influenza B/Washington/ 02/19 (Victoria lineage) (Live)	1 x104 TCID50/mL
Influenza B/Florida/4/ 2006 (Yamagata lineage) (Live)	1x107 CEID50/mL
Enterovirus B111 2015 (Inactive)	1x106 TCID50/mL
Enterovirus Type 71 (Live)	1x106 TCID50/mL
Respiratory syncytial virus (Live)	1x106 TCID50/mL
Rhinovirus Type 1A (Inactive)	1x105 TCID50/mL
Rhinovirus Type 1A (Live)	1x105 TCID50/mL
Haemophilus influenzae type b (Eagan) (Live)	1x107 CFU/mL
Streptococcus pneumoniae Z022 (Live)	1x107 CFU/mL
Streptococcus pyogenes Z018 (Live)	1x107 CFU/mL
Candida albicans Z006 (Live)	1x107 CFU/mL
Pooled human nasal wash -representative of normal respiratory microbial flora	NA
Bordetella pertussis A639 (Live)	1x107 CFU/mL
Mycoplasma pneumoniae M129 (Live)	1x107 CCU/mL
Chlamydia pneumoniae TW-183 (Live)	1x107 IFU/mL
Legionella pneumophila Philadelphia (Live)	1x107 CFU/mL
Staphylococcus aureus MRSA; COL (Live)	1x107 CFU/mL
Staphylococcus epidermidis MRSE: PR62A (Live)	1x107 CFU/mL

In-silico Analysis

Three microorganisms including Human coronavirus HKU1, Mycobacterium tuberculosis and Pneumocystis jirovecii were not commercially available for wet experiments. Thus, in silico sequence homology analyses were performed to predict potential cross-reactivity with these microorganisms.

The sequence analysis results showed that Homology exists between the SARS-CoV-2 Nucleocapsid protein and Human Coronavirus HKU1. BLASTP results showed 36 sequence IDs. Sequence ID AGT17773.1 and AGW27840.1 had the highest alignment score (199) and were 39.1% homologous across 76% of the sequences. While this is relatively low sequence

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CorDx, Inc.

homology, the possibility of cross-reactivity cannot be ruled out. No significant homology was found between the SARS-CoV-2 Nucleocapsid protein and the Mycobacterium tuberculosis or Pneumocystis jirovecii, suggesting that these two organisms would not crossreact or interfere with the CorDx Tyfast COVID-19 Ag Rapid Test even if they were present in the samples.

Interference Study-other potential interference f.

This study was performed to evaluate interference between the CorDx Tyfast COVID-19 Ag Rapid Test and endogenous or exogenous substances which may be naturally present in respiratory specimens or that may be artificially introduced.

Negative samples and positive samples (viral titer 3x LoD) were tested in triplicate in the presence of the potentially interfering substances. The performance of the CorDx Tyfast COVID-19 Ag Rapid Test was not affected by any of the interfering substances listed in the table below at the tested concentration.

Potential Interfering Substance	Concentration Tested
No other substance	NA
Whole Blood	4%
Mucin	0.5%
Chloraseptic (Methol/Benzocaine)	1.5 mg/mL
Naso GEL (NeilMed)	5% v/v
CVS Nasal Drops (Phenylephrine)	15% v/v
Afrin (Oxymetazoline)	15% v/v
CVS Nasal Spray (Cromolyn)	15% v/v
Zicam	5% v/v
Homeopathic (Alkalol)	10% v/v
Sore Throat Phenol Spray	15% v/v
Tobramycin	4 $ \mu $ g/mL
Mupirocin	10 mg/mL
Fluticasone Propionate	5% v/v
Tamiflu (Oseltamivir Phosphate)	5 mg/mL
Chloraseptic (Menthol/Benzocaine)	3 mg/mL
Gericare Saline Nasal Spray (Sodium chloride with preservatives)	15% v/v
CVS Health Budesonide Allergy Nasal Spray (Budesonide)	15% v/v
Nasonex 24HR Allergy Nasal Spray (Mometasone)	15% v/v
HealthA2Z Fluticasone Propionate Nasal Spray (Fluticasone)	15% v/v
Luffeel Nasal Spray (Luffa opperculata, Sulfur)	1.25 %
Boiron Galphimia glauca	15% v/v
Boiron Histaminum Hydrochloricum	15% v/v

Table 4: Potential Interfering Substances and Concentrations Tested in the Study

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CorDx Tyfast COVID-19 Ag Rapid Test

CorDx, Inc.

g. High dose hook effect study:

No hook effect was observed when testing specimens containing SARS-CoV-2 (Isolate: USA-WA1/ 2020) viral concentration as high as 4.57x106 TCIDs0/mL.

h. Traceability:

The tests were calibrated against the WHO International Standard for SARS-CoV-2 Antigen.

Matrix Comparison i.

Matrix equivalency studies between negative clinical nasal swab matrix and the surrogate pooled nasal cavity wash matrix was conducted and demonstrated equivalent performance of the test with both matrices.

Sample Stability: j.

The study results confirmed that the dry swab specimen could be stored at room temperature for up to 2 hours after specimen collection by testing contrived samples prepared with the Pooled Nasal Swab Matrix (PNSM) using three kit lots.

k. Reagent Stability:

The real time stability study data demonstrated that the CorDx Tyfast COVID-19 Ag Rapid Test kit can be stored under recommended conditions of 2-30℃ for at least 24 months.

l. Shipping Stability:

The stability of the test kits under different stress shipping conditions was evaluated by testing 3 lots of test kits that went through the process of storing respectively at 7 different harsh temperature conditions and the process of dropping from various orientations. The kit components were stable under all conditions tested.

2. Clinical Performance:

a. Method comparison with predicate device:

Not applicable. See "3. Clinical Studies" for clinical performance.

3. Clinical Studies:

The clinical performance of the CorDx Tyfast COVID-19 Ag Rapid Test was evaluated in a prospective clinical study conducted from September 2023 to December 2023 at four (4) sites throughout the United States. The study evaluated 740 symptomatic individuals aged 2 years or older who were either experiencing fever or had two or more symptoms associated with COVID-19.

The performance of CorDx Tyfast COVID-19 Ag Rapid Test was analyzed compared to a highly sensitive 510(k)-cleared SARS-CoV-2 RT-PCR assay. Out of 740 enrolled individuals, 693 subjects were evaluable. Of the 693 subjects, 101 were true positives (concordant positive results on both the investigational and comparator tests) and 572 were true negatives (concordant negative results on both the investigational and comparator tests).

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CorDx, Inc.

Twenty-one (21) subjects had discordant results in which the investigational test was negative, and the final comparator result was positive, and 3 subjects had discordant results in which the investigational test was positive, and the final comparator result was negative.

CorDx TyfastCOVID-19 Ag Rapid Test	ComparatorPositives	ComparatorNegatives	Total
Positives	101	3	104
Negatives	17	572	589
Total	118	575	693
Positive Percent Agreement = 85.6% (95% CI: 78.1 to 10.8%)
Negative Percent Agreement = 99.5% (95% CI: 98.5 to 99.8%)

Table 5: CorDx Tyfast COVID-19 Ag Rapid Test Performance Against Comparator

4. Other Supportive Studies

Usability Study a.

A total of 104 subjects were enrolled in the study and were observed during testing. All subjects successfully completed testing by receiving a Negative or Positive result. All subjects were issued a questionnaire to assess users' comprehension of the test. The questionnaire was completed by all the enrolled subjects. The questionnaire assessed the users' understanding of concepts such as the test purpose and interpretation of results. The results demonstrate the kit can be successfully utilized by lay users.

b. Readability Study

A total of 104 lay users with diverse gender, ages and educational background who met the study inclusion criteria, were enrolled for the Readability Study. Each lay user was asked to interpret blinded test panels with mock results including one negative, one low positive at 1.5 to 2x limit of detection (LoD), one positive at 5x LoD, an invalid result and either one additional low positive or negative result. Subjects with vision impairments (e.g., near sightedness/far sightedness, glaucoma, glasses/contacts, strength of prescription lens) were included in interpretation of these results. The results showed that the test results could be adequately interpreted by individuals without or with vision impairment.

Flex Studies C.

Flex studies were conducted to evaluate whether potential errors that lay users could make during testing would adversely affect the test performance. The studies included

CONFIDENTIAL

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CorDx, Inc.

dry swab testing delay flex study, extracted specimen testing delay flex study, swab rotation times flex study, extracted specimen volume flex study, reading time flex study, disturbance during testing flex study, lighting conditions flex study, temperature and humidity conditions flex study, and bubbles in sample chamber flex study. Tests were performed with weak positive sample swabs, which were generated by diluting inactivated SARS-CoV-2 virus at 2x LoD. The studies support that the test is robust in the intended use condition as stated in the IFU.

5. Clinical Cut-off

Not applicable

6. Expected value/ Reference Range:

Not applicable

N. Propose Labeling:

The labeling is sufficient, and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Regulation Number and Section

N/A