REA SARA ingzhou Realy Tech Co., Lt Product name: Novel Coronavirus (SARS-Cov-2) Antigen Rapid Test device (saliva) Package Specification: 25 tests/kit Manufacturer: Hangzhou Realy Tech Co., Ltd File No.KS905160 1 Version:L.0 EHfective date:2020-12-10REA BUNA DARA a Hangzhou Realy Tech C: Ad. 1. Clinical validation time ‘This clinical evaluation was conducted from October 2020 to November, 2020. Hl. Background information for clinical evaluation Since December 2019, world has successively discovered multiple cases of patients with new-type coronavirus pneumonia. With the spread of the epidemic, China and abroad have also been found. |AS an acute respiratory infectious disease, the disease has been included in the Class B infectious diseases stipulated in the Law of the People’s Republic of China on the Prevention and Control of Infectious Diseases, and is managed as a Class A infectious disease. Based on the current epidemiological investigation, the incubation period is 1-14 days, mostly 3-7 days. ‘The main manifestations are fever, dry cough, and fatigue. A few patients have symptoms such as nasal congestion, runny nose, sore throat, myalgia and diarrhea. Severe patients usually have ‘dyspnea and / or hypoxemia one week after the onset of symptoms, and severe patients can quickly progress to acute respiratory distress syndrome, septic shock, difficult to correct metabolic acidosis, coagulation dysfunction and multiple organ Functional failure, ete. It is worth noting that in the ‘course of severe and critically il patients, there may be moderate o low fever, even without obvious fever. Mild patients showed only low fever, mild fatigue, and no pneumonia. Judging from the current ‘cases, most patients have a good prognosis, and a few patients are critically ill. The elderly and those with chronic underlying disease have a better prognosis. Symptoms in children are relatively mild. ‘The Novel Coronavirus (SARS-Cov-2) Antigen Rapid Test device (saliva) developed by our company can help diagnose whether patients are infected with the Novel Coronavirus. Ithas further enriched the detection methods of Novel Coronavirus, expanded the supply of detection reagents, and fully served the needs of epidemic prevention and control IIL Test purposes ‘The Novel Coronavirus (SARS-Cov-2) Antigen Rapid Test device (saliva) produced by Hangzhou Realy Technology Co.,Ltd, was used to verify the feasibility of clinical evaluation and the reliability of test results for Chinese subjects. ‘The purpose of research of the clinical test is to calculate the consistency percentage of negative/positive and the total consistency percentage and Kappa coefficient by statistically analyzing test results through comparative experimental research. IV. Test design 1. Test plan selection and reasons In vitro diagnostic reagents for testing and reference reagents were used to conduct comparative research tests on clinically suspected Novel Coronavirus saliva samples, and it was proved that the {in vitro diagnostic reagents used in the test can achieve the expected assistance in infection of the Novel Coronavirus. 2. Sample volume required ‘The total number of clinical tials ofthis product is not less than 100 cases. The samples is classified into the positive group and the negative group as per the test results of the reference product, ‘Meanwhile, the (unfrozen) nasopharyngeal swab samples shall be tested via the RT-PCR from the same patient at same time , then the sativa sample test results of the product tested and the File No.K5905160 2 Version:1.0 EMfective date:2020-12-10REA A Hangzhou Re: h Co., Ltd. nasopharyngeal swab sample RT-PCR test results shall be compared, with statistical analysis being made. 3. Sample inclusion/exclusion eertifieation. ‘The positive group and negative group in this experiment are applicable to the following inclusion/exclusion criteria, Positive group inclusion: PCR Testis posi symptoms are clinically positive; ‘Negative inclusion: PCR testis negative; ‘Sample collection, processing It is applicable to the diagnosis of the Novel coroinavirus from the samples of sativa.Use freshly collected samples for optimal test performance. Inadequate sample collection or improper sample handling may yield a false-negative result Sample collection procedure: The oral fluid specimen should be collected using the saliva collector provided with the kitFollow the detailed Directions for Use refer to product IFU. No other collection cup should be used with this assay. Oral fluid collected at any time of the day may be used. NOTE: Do not place anything in the mouth including food,drink,gum, tobacco,water and mouthwash products for at least 10 minutes prior to collection of oral fluid specimen. Specimen preparation: Take out a sample extraction tube, remove the aluminum foil, Insert the sponge of sample collector with the saliva sample into the tube and twist close the whole cap of sample collector. 4 In vitro diagnostic reagents and reference produets for te LOT: 202010001 Expiry: October,2022(Tentative) ‘Storage Conditions: Store in a dry place at 2-30°C, protected from light. After opening the inner package, the test card will become invalid due to moisture absorption. Please use it within 1 hour. Source:Hangzhou Realy Tech Co.,Ltd 5.2 Reference products Name: Novel Coronavirus(2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing) Manufacturer: Sansure Biotech Inc Storage Conditions: Store in a dry place at 2-8°C, protected from light. \V. Experiment method 1 Open the package with the saliva collector, then remove the saliva collector from the sealed plastic bag 2. Pre-process the saliva samples according to the instructions of the The Novel Coronavirus (SARS-Cov-2) Antigen Rapid Test device (saliva) , and label the samples randomly. Fle No.K5905160 3 Version:1.0 Effective dat:2020-12-10PUN AREA Al wzhou Realy Tech Co., Lte fo the mouth, actively swab the inside ofthe mouth and tongue to collect oral fluid for approximately 10 second until the sponge becomes soft and fully saturated, The sponge will be free from hard spots when fully saturated 2.2, Take out a sample extraction tube, remove the aluminum foil. Remove the collector fom the ‘mouth and put the saturated oral fluid collector into the extraction tube. 2.3 Screw the cap into the extraction tube tightly so that iva is squeezed out of the sponge into the extraction tube. 2.4 Gently shake the extraction tube vertically for about $ seconds to allow saliva mix well with ‘extraction buffer. Take out the saliva collector and discard it 3. ‘The operation steps of the in vitro diagnostic reagents forthe test are as follows. For details, please refer to the product instruction manual: 3.1 Remove the test device from the sealed foil pouch and use it as soon as possible. Best results will be obtained if the assay is performed immediately after opening the foil pouch. Put the test device on a clean and flat surface. 3.2 twist open the small white cap from the extraction tbe transfer 3 drop of sample into the sample well of test device vertically 3.3 Read the result at 10-20 minutes. Don” { interpret the result after 20 minutes. Note: The detection steps need to be completed under protection against infection VI. Statistical methods of statist -al analysis of clinical research data ‘A Methods evaluating clinical performance ‘Whether various indexes can reach the standards of clinical evaluation shall be judged by calculating the consistency percentage of negative/positive and the total consistency percentage in the test results ofthe product tested and the reference produet, to validate the accuracy ‘and applicability of the product in clinical applications, The product tested shall be subject to tests through the sample of different types, with statistics on the results. Meanwhile, different types of sample of the subjects shall be subject to determination by the product tested synchronously, and then the determination results of both shall be compared. The test results recorded shall be subject to statistical analysis upon completion of determination of all clinical samples,to calculate the consistency percentage of negativelpositive and the total consistency percentage. Afterwards, equivalence of both shall be evaluated as per these statistical indexes B Statistical method ‘The products launched on the market shall be subject to comparative study and evaluation. Kappa inspection: each sample shall be tested with the product tested and the reference product respectively, nd then the consistency in statistical results of these two inspection methods shall be compared through Kappa inspection, ‘The data shall be subject to Kappa inspection and analysis and the Kappa coefficient shall be calculated. Favorable consistency can be proven if Kappa is>0.8. The consistency in test results Fle Wo 5905160 4 Verson:1.0 Fffecive date:2020-12-10REA BNR BABAR A A Hangzhou Realy Tech C ‘The coincidence rate shall be calculated by comparing with the reference product whose marketing is approved. The product performance shall meet the following requirements. 1)Coincidence rate of negative: the sample whose test results are negative for both the product tested ‘and the reference product and the proportion in the sample whose test results are negative for the reference product shall be more than 95%. 2)Coincidence rate of positive: the sample whose test results are positive for both the product tested and the reference product and the proportion in the sample whose test results are positive for the reference product shall be more than 85%. 3)Total coincidence rate: the sample whose test results are the same for the produet tested and the reference product and its proportion in the total number of samples shall be more than 90%. 2019-nCoV nucleic acid test kit (RT-PCR) Method Total Results Result sitive | negative ‘The Novel Coronavirus (SARS- " = “ Cov-2) Antigen Rapid Test positive A B AB device (saliva) negative c D cD Total Results AIC BHD | A+B+C+D Clinical sensitivity =AMA*C)*100% Clinical specificity = D(B+D)*100% Accuracy: (A+D)(A*B+C#D)*100%: Ifthe coincidence rate of positivelnegative can meet clinical requirements, two methods or Products are considered as equivalent; Ifthe coincidence rate of positive/negative is greatly different, the clinical scheme should be re-designed. 4)Kappa consistency analysis shall be adopted for statistical analysis of reference reagents ‘The results of the product tested are statistical materials and can be per the table below: 2019-nCaV nucleie acid test kit (RTEPCR) Method ‘Total Results Resul sitive] negative ‘The Novel Coronavirus (SARS- i ost gat Cov-2) Antigen Rapid Test positive A B AB device (saliva) negative c D cD Total Results atc BeD | AsB+C+D. Po. (A#D)A+B+C+D)*100% Pe=((A+BY(A4C) HA+B\BED)) (AHBHCHDY Kappa:( Po-Ps\(1-p.) conducting Kappa consistency analysis for the base data above, high consistency can be judged if the Kappa coefficient is ~0.8,and both systems are considered as equivalent. Consistency is Fle No.5905160 5 Verson:1.0 lective date:2020-12-10R E, /\ DAR HARARE A Hangzhou Realy Tech C: ‘considered if 0.4 99.9% (95%CI* 98.98% to 100%) Accuracy: (62+156)/ (62+0*4+156) *100%-98,20% (95%CT¥ 95.29% t0 99.46%) Pe= (62466462156) 2224222) =0.28 Kappas( Py- Pe)/(1-p,) "0.97 *:95% confidence interview According to the above table, 156 are proven negative of 156 negative specimens, 62 are proven positive of 66 positive specimens. The sensitivity and accuracy are more than 90%, indicating, favorable consistency with the reference product. The Kappa=0.97>0.8,indicating favorable and. high consistency of two methods and equivalence of two such systems. X Analysis on Inconsistency in Test Results NO. | Age | Gender [ Rapid Test REPCR Clinical diagnostic 14 [39 | F[ Negative Positive (N gene) Infection 25 days 250 | east | aR Positive (N gene) Infection 16 days 37 | 36 | M_| Negative Positive (N gene) Infection 28 days 49 [30 | M_ | Negative Positive (RARP gene) Infection 22 days XI Discussion and Conclusions Ldiseussion A Results of comparative analysis of the product tested and the reference product: Test results of saliva specimen tested and the reference result: both the coincidence rate of negative/posit consistency with the reference product. In the analysis results of Kappa inspection, Kappa was fe and the total coincidence rate are larger than 85%, indicating favorable File No.K5905160 6 Version:1.0 Etfetive date:2020-12-10 swan &REA BUNA A Hangzhou ich Co., Ltd, proven >0.8, indicating favorable and high consistency of both methods. Both systems were proven ‘equivalent 2.Test conclu By analyzing the test results of the product tested and the reference product, the consistency percentage of negative/positive and the total consistency percentage are proven high. Moreover, according to the results of statistical analysis, there is no remarkable difference in test results of both, indicating favorable consistency in diagnosis and equivalence of two such systems and can be used for auxiliary diagnosis of those suffering from pneumonia triggered by COVID-19. X. Quality control methods On-site quality control 1) During the course of this study, clinical implementors appointed clinical inspectors to conduct regular on-site supervision visits to the research hospital. Through monitoring visits, it was found that all the contents of the research plan were strictly observed, and the correctness ofthe research data was also guaranteed. Participating researchers have undergone unified training, unified recording methods and judgment standards. The entire clinical trial process is conducted under strict ‘operation, and the test content is complete and authentic, All observations and findings in the clinical trials have been verified and the data are reliable. The conclusions in the clinical trials are derived from the original data, 2) Quality control of clinical experiment process During the evaluation, quality control was performed daily to ensure that the product was under control. Strict quality control is performed for each trial to ensure the quality of clinica trials. XI. Prediction of adverse events Because the Novel Coronavirus (SARS-Cov-2) Antigen Rapid Test device (saliva) is an in vitro diagnostic reagent product, no direct contact with patients is required in clinical trials, no test repor is provided to patients, and the test resulls are only used for comparative studies. It involves personal privacy, does not serve as a basis for auxiliary diagnosis, does not bring any risk to the subject, and does not cause adverse events, References: [The "Technical Review Points for the Registration of New Coronavirus Antigen / Antibody Detection Reagents in 2019 (Trial)" issued by the State Drug Administration Medical Device ‘Technical Evaluation Center on February 25, 2020: 2. *Pneumonitis Diagnosis and Treatment Program for New Coronavirus Infection (Trial Version 7)" issued by the National Health Committee on February 19, 2020. File No:xS905160 7 Version:1.0 Etfectve date:2020-12-10uasu obexoeg: | xouuy "pT "0D Wael Aleoy nOyZBUEH fe 7 A V3uYSUN R ATRL Hangzhou Realy Tech Co., Ltd. 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