FREND PSA Plus_Package insert (V.0.1)
Contents
1. 1 Endogenous Interferents These interference studies on endogenous substances were performed using the FREND PSA Plus on the FREND System according to the recommendations in the CLSI protocol EP7 A Added hemoglobin up to 500 mg dL does not interfere with the assay Average recovery when added to serum containing tPSA at 1 0 and 4 0 ng mL was 97 25 Added unconjugated bilirubin up to 20 mg dL does not interfere with the assay Average recovery when added to serum containing tPSA at 1 0 and 4 0 ng mL was 98 2 Added gamma globulin Total Protein up to 5 0 g dL does not interfere with the assay Average recovery when added to serum containing tPSA at 1 0 and 4 0 ng mL was 106 3 Added triglyceride up to 3 g dL does not interfere with this assay Average recovery when added to serum containing tPSA at 1 0 and 4 0 ng mL was 101 5 18 2 Pharmaceutical Interferents The following chart shows the interference studies performed using the FREND PSA Plus on the FREND system for various drugs that might be found in the serum plasma of men diagnosed with prostate cancer The concentrations of the drugs that were added to the test samples and controls at base concentrations of tPSA of 1 0 ng mL and 4 0 ng mL are shown as are the recoveries on the far right side of the chart It is unlikely since the FREND PSA Plus method uses monoclonal antibodies that any substances without a tertiary structure similar to PSA wo2. MNDO Use by YYYY MM DD Lot number Catalog number cor AN Warning or Caution Manufactured by Authorized representative in the Europe Community Invitro diagnostic medical device 2 C Temperature limitation sc we Contains sufficient for lt n gt tests 23 Nano nfek sales nanoentek com www nanoentekinc com e Manufactured by NanoEnTek Inc HQ 12F 5 Digital ro 26 gil Guro gu Seoul 152 740 Korea Tel 82 2 6220 7940 Fax 82 2 6220 7721 US Branch NanoEnTek USA Inc 5627 Stoneridge Drive Suite 304 Pleasanton CA 94588 USA Tel 1 925 225 0108 1 888 988 0108 Toll free Fax 1 925 225 0109 EC REP MT Promedt Consulting GmbH Altenhofstrasse 80 66386 St Ingbert Germany SK Medical Beijing Co Ltd 26F SK tower No 6 Jia Jianguomenwai Avenue Chaoyang District Beijing 100022 P R China Tel 86 10 5920 7844 Fax 86 10 5920 5697
3. 35 22 TEST3 0 10 4 08 924 12 71 18 22 19 39 27 13 27 12 31 74 TEST4 0 00 4 27 818 13 91 16 07 19 32 26 88 29 51 27 43 TEST5 0 00 4 59 867 12 61 17 56 20 67 24 91 27 36 2832 TEST6 0 10 4 26 7 74 11 58 18 57 22 78 25 93 26 38 40 09 MEAN ng mL 0 033 4 413 8 555 12 740 17 608 21 015 25 675 28 790 33 797 sD 0 241 0 526 0 802 0 972 1 490 1 255 2 913 5 561 CV 55 6 1 63 55 71 49 10 1 165 Expected Value 0 0 43 8 0 128 17 0 21 3 25 5 29 8 34 0 Recovery 103 8 106 9 99 9 103 6 989 100 7 968 99 4 1c Comparative Analysis A group of well characterized serum samples collected with from subjects with pathology verified prostate cancer and stored at 70 C under monitored conditions were analyzed for total PSA Results from the FRE obt RB oversight ND PSA Plus on the FREND System y were compared to those ained using the TOSOH ST AIA PACK PA assay x A total of 160 unique samples were analyzed in the study however only samples with tPSA results wit use 16 Slope 0 9192 95 Cl 0 8369 1 0014 Intercept 0 01179 95 CI 0 2763 0 2527 Correlation Coefficient R 0 9671 95 Cl 0 9545 0 9763 Number of Samples 143 Range of FREND PSA Plus values 0 04 29 99 ng mL Range of ST AIA PACK PA values 0 00 25 86 ng mL hin the linearity of the FREND PSA Plus up to 25 0 ng mL n 143 were d in the comparative analysis 2 Precis
4. available tPSA fluorescent assay Results of this study are shown below Category Other FDA Cleared PSA PSA Plus on FREND Number of Samples n 196 196 Mean x 0 71 ng mL 0 83 ng mL SD 0 38 ng mL 0 43 ng mL Range of Values 0 00 2 03 ng mL 0 02 2 69 ng mL Median 0 66 ng mL 0 77 ng mL 13 Expected Values for Management of Patients with Prostate Cancer Distribution of Serum FREND PSA Plus Concentrations Healthy Benign and Various Malignant Disease States 0 4 0 4 1 10 0 10 1 20 0 20 1 40 0 gt 40 0 N ng mL ng mL ng mL ng mL ng mL Healthy Subjects 196 Men gt 50 yrs 196 100 0 0 0 0 Benign Disease Cond 410 Benign Prostate 104 56 73 25 96 11 54 3 85 1 92 Diabetes 97 95 88 3 09 1 03 0 00 0 00 HTN Heart Disease 102 95 10 4 90 0 00 0 00 0 00 Benign Gl 107 94 4 4 67 0 00 0 93 0 00 Malignant Diseases 302 Prostate Cancer 85 40 00 38 82 12 95 2 35 5 88 Gleason Score 5 6 43 51 16 44 19 2 38 2 38 0 Gleason Score 7 31 35 48 38 72 19 35 0 6 45 Gleason Score 8 9 11 9 09 18 18 36 36 9 09 27 27 Lung Liver Cancer 52 98 08 0 1 92 0 0 GB Gastric Pancreatic 31 100 0 0 0 0 Colorectal Cancer 89 94 38 4 49 1 13 0 0 Other Cancers 45 97 78 2 22 0 0 0 TOTAL Subjects 908 Treated and untreated
5. of 34 kilodaltons 3 As a serine protease with chymotrypsin like activity PSA belongs to the kallikrein family In blood PSA exists as a free or complex form with protease inhibitors such as a 1 antichymotrypsin ACT Total PSA represents the sum of both free and complex forms PSA is uniquely associated with prostate tissues from normal inflamed or cancerous stages Elevated PSA in serum or plasma is found in patients with prostate cancer benign prostatic hypertrophy or inflammatory tissues Studies on a variety of PSA methods have shown that PSA can be useful as an indicator for the diagnosis and management of prostate cancer gt PSA has been found in normal benign hyperplastic and malignant prostatic tissue in metastatic prostatic carcinoma and also in prostatic fluid as well as in seminal fluid PSA is not found in any other tissue in men and it is not produced by cancers originating in the lung colon rectum stomach pancreas or thyroid Though increased concentrations of PSA are found in the serum of patients with benign prostate hyperplasia BPH prostatitis and prostate infections and inflammation they are also found in patients with cancer of the prostate 9 PSA measurement is an essential tool in assessing the status of disease in patients with prostate cancer when serial samples are measured over time The clinical value realized by monitoring tPSA concentrations in patients with prostate cancer regardless of the
6. potential reference material for international standardization of PSA immunoassays Clinical Chemistry 1995 41 9 1273 82 6 Wang M C et al 1981 Prostatic Antigen A New Potential Marker for Prostatic Cancer Prostate 2 89 7 Frankel A G et al 1982 Monoclonal Antibodies to a Human Prostate Antigen Cancer Res 42 3714 8 Papsidero L D et al 1980 A Prostate Antigen in Sera of Prostatic Cancer Patients Cancer Res 40 2428 9 Kuriyama M et al 1980 Quantitation of Prostate Specific Antigen in Serum by a Sensitive Enzyme Immunoassay Cancer Res 40 4658 Killian C S 1985 Prognostic Importance of Prostate Specific Antigen for Monitoring Patients with Stages B2 to D1 Prostate Cancer Cancer Res 45 886 11 Kuriyama M et al 1982 Multiple Marker Evaluation in Human Prostate Cancer with the Use of Tissue Specific Antigens J Nat Canc 68 99 12 Nahm MH and Goffman JW Heteroantibody Phantom of the Immunoassay Clinical Chemistry 1990 36 829 13 Boscato LM Stuart MC Heterophilic Antibodies A Problem for All Immunoassay Compared Clinical Chemistry 1988 33 1916 20 14 Young D 1990 Effects of Drugs on Clinical Laboratory Tests 3rd Edition Washington DC American Association for Clinical Chemistry Press 15 Chan DW Bruzek DJ Oesterling JE et al Human Anti Murine Immunoassays Clinical Chemistry 1997 1916 20 10 22 19 Glossary of Symbols Do not reuse 2 Ep Date OVY
7. 3 that the antibody is reactive If this reference zone signal is missing or lower than threshold the FREND system consider it as an incorrect or failed test not producing a test result but an error message In addition with each cartridge run the system monitors in part for 1 flow of sample 2 speed of sample flow 3 shelf life of cartridge components 4 function of internal barcode scanner and 5 function of scanner s mechanical components External quality control testing Commercially available controls from a variety of manufacturers are available that contain tPSA as a measured analyte It is recommended that a minimum of at least two 2 levels of controls be run at least once per month or once for each new lot whichever comes earlier However Controls should be run with a minimum frequency depending on number of tests run in the laboratory Each laboratory should establish its own criteria based on the following parameters 1 Each new lot 2 Each new shipment even if from the same lot previously received 3 Each new operator an individual who has not run the tests for at least two weeks 4 Monthly as a continued check on storage conditions 5 Whenever problems storage operator or other are identified 6 Or other times as required by your laboratory s standard QC procedures 4 Individual laboratory policy will dictate exactly which control materials and lot numbers should be run the frequen
8. D N i UreriDi Nanos PSA concentration Less than 0 10 ng mL PSA lt 0 10 ng mL Bara Grii Date Time 2012 1 17 11 55 AM PSA concentration User ID Nano Patient ID T10 Not less than 0 10 ng mL BSA and not higher than 25 00 ng mL 9 73 ng mL ee Date Time 2012 1 13 11 30 AM ser ID Nano ji PAID LO PSA concentration Higher than 25 00 ng mL PSA gt 25 00 ng mL 11 12 Limitations of the Procedure When used for diagnostic purposes the results obtained from this assay should be used in conjunction with other data e g symptoms results of other tests clinical impressions medical history therapy etc The FREND System paired with a FREND PSA Plus cartridge is programmed to report 25 0 ng mL as the highest concentration of PSA measurable without dilution The lowest measurable concentration is 0 1 ng mL the assay sensitivity limit Heterophilic antibodies in a sample have the potential to cause interference in immunoassay systems 213 Infrequently PSA levels may appear elevated due to heterophilic antibodies present in the patient s serum or plasma or to nonspecific protein binding If the PSA level is inconsistent with clinical evidence additional PSA testing is suggested to confirm the results Although hemolysis has an insignificant effect on the assay hemolyzed samples may indicate mistreatment of a specimen prior to assay and results should be interpreted with caution Lipemia has an ins
9. FREND PSA Plus on the FREND system The same samples were also measured for tPSA by another FDA cleared method For each point to point in a sample serial set the change in the tPSA concentration was compared to the change in the clinical status of the patients as measured by other laboratory tests patient interviews physical examinations and imaging studies of a variety of types and recorded on a Clinical Report Form These changes in the tPSA marker concentration were defined as significant or not by multiplying the overall CV of the assay at the midrange as determined by the test imprecision study by a factor of 2 5 to define a percentage change different from what would be expected because of assay imprecision For the FREND PSA Plus assay with an overall mid range CV of 8 5 significance was set at a change in excess of 20 Any increase in value from one time period to the next that did not exceed 20 was logged as lt 20 Change For the other FDA cleared method significance was set at a change gt 8 5 This was calculated using that method s published overall mid range CV of 3 4 x 2 5 Physician s impressions regarding subject s disease status at each blood draw were recorded on CRFs for all serial PSA samples The status information at one visit was compared with the status at the next and a change in status was determined for the visit pair The change in clinical status from the physician s impression was then compared to
10. NESPI FRPS O02EN V 0 1 Nano ntlek C Gers FREND PSA Plus Prostate Specific Antigen A Caution The sale and distribution of this device is restricted by United States federal law to by or on the order of a physician In addition the use of this device is restricted to by or on the order of a physician Because of differences in reagent specificity and assay methods the concentration of PSA in a given specimen may vary with devices from different manufacturers Values obtained with different assay methods cannot be used interchangeably It is mandatory that results reported by the laboratory to the physician include the identity of the assay used If the assay method for PSA is changed during the course of monitoring patients with serial PSA levels baseline values for the patients being serially monitored must be confirmed by additional sequential testing 1 2 Name and Intended Use The NanoEnTek FREND PSA Plus is designed for in vitro DIAGNOSTIC USE ONLY for the quantitative measurement of total Prostate Specific Antigen PSA in human serum heparinized plasma and EDTA plasma using the FREND System This device is indicated for the serial measurement of total PSA in serum heparinized plasma and EDTA plasma to be used as an aid in the management of patients with prostate cancer Summary and Explanation of Test Prostate specific antigen PSA is a single chain glycoprotein with molecular weight
11. arations necessary Assay Procedure 1 Prepare the FREND PSA Plus and specimen 2 Record the Sample ID on the cartridge in the designated area 3 Drop the sample 30 uL into the sample inlet on the cartridge using a calibrated micro pipette with a fresh pipette tip 4 Press the Test button on the Main screen of the FREND System 5 The screen of FREND System to the Patient ID screen automatically 6 Type the Patient ID and press the Enter button to begin the test 7 Insert the cartridge into the cartridge slot using the cartridge arrows as a guide A Caution Please check the direction of the cartridge before insertion and assure the insertion is complete 8 When the reaction in the cartridge is complete within 4minutes the FREND System will automatically begin the reading process 9 When the measurements are completed the cartridge will automatically be expelled and the results displayed AN Caution Do not remove power from the FREND System while a cartridge is in the reading chamber This may cause a system error 10 If the FREND System is connected to the optional printer press the Print button and the results will be output on the printer paper 11 For more detailed instructions please refer to the FREND System User Manual 10 Procedural Notes If a specimen Prostate Specific Antigen concentration is found to be greater than the linearity limit of t
12. ckage Insert and User Manual PSA Plus cartridges are disposable single use devices Do not reuse them under any circumstances Keep the cartridge sealed in the pouch until just ready for use Use the cartridge immediately after opening its pouch Wear disposable gloves when handling the cartridges and the samples Wash hands thoroughly and often after handling reagent cartridges or samples For professional use only PSA Plus has been designed so that the high dose hook effect is not a problem for the vast majority of samples Samples with PSA concentrations between 25 and 1 200 ng mL will read gt 25 ng mL The hook effect phenomenon may occur only at PSA concentrations gt 1 200 ng mL Storage and Stability All unopened materials are stable until the expiration date on the label when stored at the specified temperature Cartridge stability has been demonstrated for twelve months from the date of manufacture The expiration date is clearly indicated on the product box and the cartridges Materials Cat No Refrigerator Temperature 2 8 C PSA Plus cartridges FRPS 025 Room Temperature 18 25 C Pipette Tips None Specimen Collection and Handling Serum or plasma heparinized or EDTA only is required for the assay Citrated plasma SHOULD NOT BE USED No special patient preparation is necessary To use serum a blood sample is collected aseptically without additives by venous puncture After allow
13. cy with which controls are to be tested criteria for acceptance of the results and required corrective action to be taken if results do not meet laboratory criteria If any external quality control sample values are out of the acceptable range it will be necessary to investigate the problem before reporting patient results to assure there is not an instrument or software malfunction Do not assay patient samples on the FREND System using the FREND PSA Plus if quality control results do not give expected values Refer to your laboratory policies on how to determine acceptability of external control material results Each laboratory operates under a different set of regulations Every laboratory must follow the standardized procedures acceptable to the regulatory agencies to whom the laboratory is responsible Specimen Processing Preparation Remove from the refrigerator sufficient cartridges of FREND PSA Plus to test the number of patient samples and required external quality control materials Allow the cartridges to come to room temperature for 15 30 minutes prior to the start of the testing sequence f using refrigerated patient samples remove those from the refrigerator and allow to them to come to room temperature prior to testing If frozen samples will be utilized be sure these are removed from the freezer thawed naturally and then mixed gently but thoroughly prior to testing here are no other reagents or sample prep
14. e expected result The FREND PSA Plus cartridge is a single use cartridge that contains all the reagents within the cartridge necessary to support the reactions CV by Material Material Variation Source jones Sea A ERA Som ASi Siteto Site 3 50 1 57 167 3 47 1 61 2 06 Day to Day 0 00 0 99 1 21 0 00 0 00 0 00 Lot to Lot 9 12 3 16 7 01 6 08 4 30 6 00 Inter cartridge 18 45 6 81 7 94 20 03 6 17 7 49 Total 20 87 7 74 10 79 21 22 7 69 9 81 17 3 Specificity The following substances were evaluated for potential cross reactivity with the FREND PSA Plus at the concentrations indicated below Testing was done according to the instructions recommended by CLS protocol EP7 A No significant cross reactivity was found Specificity of FREND PSA Plus No Substrate Concentration 1 PAP Prostate Acid Phosphatase 10 0 ng mL 2 Kallikrein 15 0ng mL 4 Analytical Sensitivity The Limit of Detection LoD for the FREND PSA Plus was determined using the CLSI EP17 A protocol The analytical sensitivity of the FREND PSA Plus was determined to be 0 1 ng mL 16 Interference Interference is defined for purposes of this study to be recovery outside of 15 of the known specimen mean concentration In other words recovery from 85 to 115 of the expected is considered acceptable performance
15. ectronically on the FREND PSA Plus Code chip are prepared gravimetrically and are compared to international reference standards WHO International Prostate Specific Antigen 90 10 NIBSC code 96 670 However for the end user there is no need for calibration as is generally performed on other automated laboratory equipment All calibration statistics and information have been electronically stored on the FREND PSA Plus Code chip included in each box of FREND PSA Plus cartridge The FREND PSA Plus Code chip is specific for that manufactured lot of FREND PSA Plus The appropriateness of the calibration information should always be checked by running sufficient external quality control materials as samples to verify that the results obtained for tPSA on the FREND System using the FREND PSA Plus cartridges of a particular lot meet the laboratory criterion for acceptability FREND PSA Plus Code chip Installation Please refer to the FREND System User Manual for more detailed instructions relative to the Code chip installation Abbreviated instructions follow here 1 Insert the FREND System electrical cord into an appropriate outlet 2 Insert the Code chip into the Code chip slot at the rear of the FREND System following the arrows 3 Press the Setup button on the Main screen 4 Press the Code chip button on the Setup screen 5 The information embedded on the FREND PSA Plu
16. he assay of 25 0 ng mL and a definitive result is required the specimen should be diluted with female sera that has been previously measured on the FREND PSA Plus and found to contain lt 0 1 ng mL tPSA and then re assayed according to the Assay Procedure The recommended dilution for samples with an initial result of gt 25 0 ng mL is 1 10 or 1 50 It is desirable to dilute the sample so that the diluted sample reads between 2 and 20 ng mL Dilutions must be made manually and the final result on the diluted sample calculated manually by multiplying the result obtained on the diluted sample by the dilution factor 10 11 Calculation of Results The FREND System performs all sample and cartridge handling operations automatically within the cartridge once the sample has been manually added to the sample well in the cartridge and the cartridge placed into the FREND System The rate of fluorescence produced by the reaction is read at various intervals during the analysis process blank readings are subtracted after which the net rate is automatically converted to total Prostate Specific Antigen concentration in ng mL based upon information stored on the PSA Code chip This result is then output on the screen and to the optional printer It is also stored in memory on the FREND System Screen Displays for Various Concentration Scenarios Displayed result Description eu ne Date Time 2012 1 13 10 55 AM User I
17. he lot specific FREND PSA Plus Code chip and then is displayed on the FREND System screen A hard copy printout can be obtained if desired A ratio calculated between the Reference zone and the Test zone corrects for test to test variations Total PSA concentration in a sample analyzed with the FREND PSA Plus on the FREND System correlates directly with the fluorescence intensity the higher the tPSA concentration the greater the fluorescence The FREND PSA Plus has a measuring range determined as 0 1 ng mL to 25 0 ng mL The FREND PSA Plus uses single use transparent plastic cartridges in which all required reagents are stored within the cartridge itself All that is added by the user is a 30 uL test sample The cartridge is inserted into the FREND System ina prescribed fashion indicated with a black arrow on the cartridge The reaction is read multiple times as the sample moves via capillary action through the cartridge This type of assay system is sometimes referred to as one which incorporates laminar flow Material Provided FREND PSA Plus Catalog Number FRPS 025 FREND PSA Plus cartridges 25 Disposable pipette tips micro pipettor provided 30 FREND PSA Plus Code chip 1 FREND PSA Plus Package Insert i One Cartridge contains Monoclonal anti PSA1 48 9 6ng Monoclonal anti PSA2 144 28 8ng Fluorescent particle 24 0 48 ug Materials Required But Not Provided The fol
18. ignificant effect on the assay except in the case of gross lipemia where interference with the lateral flow of the sample in the cartridge may occur Specimens from patients who have received preparations of mouse monoclonal antibodies for diagnosis or therapy may contain human anti mouse antibodies HAMA Such specimens may show falsely elevated or decreased PSA values Certain medications may interfere with assay performance All results should be interpreted with respect to the clinical picture of the patient The concentration of tPSA in a given sample determined with assays from different manufacturers can vary due to differences in assay methods calibration and reagent specificity 5 Please refer to the Specimen Collection and Handling Warnings and Precautions Storage and Stability and Procedural Notes sections in this insert sheet Clinical results must be interpreted with regard to medications administered to the patient The ability of the assay to detect both free and complexed forms of total PSA free PSA complexed with alpha 1 antichymotrypsin on an equal molar basis equimolarity has not been established 12 13 Expected Values 14 As with every clinical diagnostic test a reference interval corresponding to the characteristics of the population being tested should be determined by each laboratory The FREND PSA Plus on the FREND System is to be used on serial blood samples to manage patients with p
19. ing the sample to clot for 30 minutes at room temperature the collection tube should be centrifuged for 10 minutes at 3 000 rpm 9 For heparinized or EDTA plasma a venous blood sample is collected aseptically with the designated additive The plasma should be separated from the packed cells as soon as possible Prostatic manipulation has been shown to affect the PSA results so samples should be drawn before any prostatic procedures such as DRE prostatic massage and TRUS are performed Samples may be stored at 2 8 C for up to 6 hours prior to analysis If the analysis is scheduled to be done at some later time the sample should be stored frozen at 20 C or below for future use Repeated freeze thaw cycles should be avoided Turbid serum samples or samples containing particulate matter such as fibrin clots or strands should be centrifuged before being tested Prior to assay slowly bring frozen samples to room temperature 18 25 C and mix gently but thoroughly before testing Procedure 1 Reagent Preparation Cartridges There is no reagent preparation required to measure tPSA using the FREND PSA Plus cartridge on the FREND System However the cartridges needed for a particular run should be removed from the refrigerator and allowed to reach room temperature for 15 30 minutes before they are used 2 Calibration The calibrators used during the cartridge manufacture process to create the information placed el
20. ion 2a Precision Testing Single Lot and Single Site Precision was determined as described in the CLSI protocol EP5 A Four clinical samples across the measuring range were assayed in replicates of two at two separate times per day for twenty days using a single lot of FREND PSA Plus cartridge The findings follow showing repeatability between run between day and within laboratory precision data Sample MeanPSA Repeatability Between run Between day Eeay ngm sD Ia so a sp Tve so Tae 1 0098 0013 1280 0005 55 oo04 37 0014 144 2 4321 o248 570054 12 Joos9 21 o269 62 3 12735 0636 50 0405 32 Jo102 os 0761 60 4 25462 1278 50 06e8 26 o321 13 1477 58 2b Precision Testing Multiple Lots and Multiple Sites Three different lots of FREND P geographically diverse sites Four rep SA Plus were evaluated at three icates each of Material A Material B and Material C and two replicates of QC 1 QC 2 and QC 3 were evaluated in each of two runs performed for five days at each site A total of 40 results on each material were generated at each of the three sites yielding a grand total of 120 replicates of each material The data was analyzed using a CLSI format from EP5 A2 for an ANOVA analysis Instrument to Instrument is the same as Site to Site in this scenario As can be seen from the table below the largest source of variation is the cartridge which would be th
21. lowing materials are not provided with the reagent but are required to perform Prostate Specific Antigen analysis using the FREND PSA Plus on the FREND System They are available separately from NanoEnTek Materials Cat No FREND System F10 Warnings and Precautions The FREND PSA Plus cartridges are intended for in vitro diagnostic use only PSA Plus cartridges are only to be used on the NanoEnTek FREND System Allow cartridges to come to room temperature for 15 30 minutes prior to use Avoid cross contamination between samples by using a new pipette tip for each new specimen Avoid high humidity direct sunlight or heat in the area used for cartridge storage Inaccurate results are possible if the sample used is contaminated in any way Using specimens containing clotted fibrin could result in erroneous results Over or under loading the cartridge with sample may result in inaccurate results Cartridges should not be frozen Human specimens are not used in the preparation of this product however since human specimens will be used for samples and other quality control products in the lab may be derived from human materials please use standard laboratory safety procedures when handling all specimens and controls 4 Do not use the cartridges beyond the expiration date on the pouch Do not use the cartridge if the pouch is damaged or the seal is broken Perform testing as specified in the Pa
22. rostate cancer Testing of ambulatory male subjects fifty years old and older who reported themselves as healthy without any known illnesses diseases or conditions was performed using both the FREND PSA Plus on the FREND System and another commercially available PSA method The currently accepted reference interval for tPSA of up to 4 0 ng mL was validated for both systems As is true for all PSA methods no tPSA results can be interpreted as being definitive for the presence or absence of prostate cancer Patients with levels of PSA within the reference interval found in apparently healthy subjects may have prostate cancer patients with levels exceeding those in the reference interval may be prostate cancer free Results from the FREND PSA Plus on the FREND System should be interpreted in the light of other clinical findings and diagnostic procedures such as DRE various imaging studies etc since certain treatments can cause PSA values to decrease by virtue of the treatment while the cancer is still progressing Reference Ranges The interval given here was determined in serum samples from 196 apparently healthy male subjects from the age of 50 71 years Category Men Number of Samples n 196 Reference Interval 0 4 0 ng mL In this study greater than 99 of the healthy subjects had serum PSA concentrations less than or equal to 4 0 ng mL by FREND PSA Plus on both the FREND System and another commercially
23. rvals there appears to be no differences between the concordances for the FREND PSA Plus assay and the other FDA cleared PSA assay FREND FDA Concordance PSA Plus 95 Cl Cleared PSA 95 CI Positive 77 8 69 8 to 85 3 81 5 73 8 to 88 7 Negative 64 1 55 1 to 71 5 64 1 55 1 to 71 5 Total 70 3 64 1 to 76 9 72 0 66 1 to 77 5 Confidence Intervals are based on 10 000 resamples of the patient data 21 18 References 1 de Koning HJ Liem MK Baan CA Boer R Schr der FH Alexander FE Prostate cancer mortality reduction by screening power and time frame with complete enrollment in the European Randomized Screening for Prostate Cancer ERSPC trial International Journal Cancer 2002 98 268 73 2 Wan Ming Zhang Patrik Finne Jari Leinonen et al Characterization and immunological determination of the complex between prostate specific antigen and a2 macroglobulin Clinical Chemistry 1998 44 12 2471 2479 3 David L Woodrum et al Analytical performance of the Tandem R free PSA immunoassay measuring free prostate specific antigen Clinical Chemistry 1997 43 7 1203 1208 4 Yun Sik Kwak M D Appropriate use of Prostate Specific Antigen in Diagnosing Carcinoma of the Prostate Journal Korean Geriatrics Society 2009 Vol 13 Mar pp 12 17 5 Chen Z Prestigiacomo A et al Purification and characterization of prostate specific antigen PSA complexed to alpha 1 antichymotrypsin
24. s Code chip is automatically saved on the FREND System 6 When the Code chip installation is completed press the OK button to go to the Setup screen 7 Press the Item button on the Setup screen 8 Check the FREND PSA Plus cartridge lot number and the installation date of the Code chip 9 Press the Home button to go to the Main screen to begin running external quality control and patient samples 3 Quality Control FREND System QC Cartridge FREND QC Cartridge contains multiple controls to check optic part of the system By testing QC Cartridge part of analytical components of the system of 1 laser power 2 alignment and 3 mechanical integrity are confirmed For each day of patient testing perform QC Cartridge testing Refer to the Quality Control Procedures section in the User Manual of FREND System In brief perform QC Cartridge testing for the following conditions 1 Upon initial setup of the system 2 Each day of patient testing 3 When the system has been transported or moved 4 Whenever there is uncertainty about the performance of the system 5 Whenever required by your laboratory s quality control requirements Internal procedural controls FREND PSA Plus test cartridge contains built in control features Fluorescence signal in the Reference Zone of each cartridge shows 1 that enough volume is added 2 that proper flow is obtained and
25. significant changes in the PSA concentration of each sample as measured by both the test device FREND PSA Plus and the predicate device FDA Cleared Assay The results of these comparisons are shown below where clinical status was divided into two groups those visit pairs showing progression and those showing no disease progression per the visit to visit status 1 Samples with no Progression Negative Concordance Other FDA Cleared PSA Assay FREND PSA Plus 28 5 lt 8 5 Total 220 31 IS 46 lt 20 15 67 82 Total 46 82 128 NC FREND PSA Plus 0 641 NC AIA PACK PSA 0 641 Different 0 000 There is no difference in the Negative Concordance NC between the two assays 20 2 Samples with Progression Positive Concordance Other FDA Cleared PSA Assay FREND PSA Plus 28 5 lt 8 5 Total 220 83 1 84 lt 20 5 19 24 Total 88 20 108 PC FREND PSA Plus 0 778 PC AIA PACK PSA 0 815 Different 0 037 A McNemar test of the paired data in the above table yields a p value of 0 218 The associated 95 confidence interval for the true difference is 0 0157 to 0 0551 Both estimators agree there are no statistically significant differences in the Positive Concordances PC between the two assays Below is a chart comparing the concordances of the FREND PSA Plus assay and the other FDA cleared PSA assay Based on the 95 confidence inte
26. subjects Serial samples are not included in this cohort 15 Performance Characteristics Performance characteristics were evaluated for the FREND PSA Plus as follows 1 Accuracy 1a Recovery Known samples of PSA were added to a female serum specimen 0 01 ng mL The concentration of PSA was determined before and after the addition of the exogenous PSA and the percent recovery was calculated Spiked Recovery FREND PSA Plus Concentration Observed Recovery Added ng mL Concentration ng mL 1 06 98 3 1 08 1 09 100 7 1 04 96 7 442 101 8 4 34 4 35 100 3 4 27 98 4 13 58 106 0 12 81 12 04 94 0 11 82 92 3 24 26 95 0 25 53 24 67 96 6 26 90 105 4 1b Dilution Linearity Specimens from a high concentration pool 34 ng mL tPSA were diluted with a low concentration pool following instructions in the CLS EP6 A document Correlation with the expected linearity showed R 0 9992 40 y 0 9866x 0 1324 R 0 9992 30 20 FREND PSA Plus ng mL 0 10 20 30 40 Expected value ng mL Dilution Linearity FREND PSA Plus 15 Dilution Linearity Data FREND PSA Plus No Blank 1 2 3 4 5 6 7 High Dilution 0 000 0 125 0 250 0 375 0 500 0 625 0 750 0 875 1 000 TEST 1 0 00 4 63 885 13 30 18 34 21 44 23 78 28 04 39 98 TEST 2 0 00 4 65 865 12 33 16 89 22 49 25 42 3433
27. treatment regimen is well known Since the mid 1980 s there has been a growing body of literature concerning the utility of Prostate Specific Antigen PSA for both the monitoring and detection of prostate cancer CaP 3 Principle of the Assay The FREND PSA Plus is a rapid quantitative sandwich immunoassay using fluorescent nanoparticles which measures the concentration of total PSA Thirty uL of patient serum or plasma heparin or EDTA only is manually presented to the inlet on the individual single unit test cartridge where it is mixed with fluorescent nano particles conjugated with PSA antibodies PSA molecules in the specimen bind to conjugated antibodies to form immune complexes which then move by capillary action through the reagent cartridge channel to the detection area When the specimen reaches the test zone it hydrates dried solid phase anti PSA antibodies PSA fluorescent particle immune complexes in the specimen are grabbed by the capture antibodies to form sandwich immune complexes The residual PSA unbound fluorescent nano particles conjugated with PSA antibodies pass through the test zone and bind to PSA antigens in the reference zone As the sample moves forward to the waste reservoir non specific binding components are washed away The intensity of fluorescence measured by a light source laser is proportional to the amount of total PSA in the original sample The result is calculated using information stored on t
28. uld interfere The testing showed that indeed there was no significant interference from the tested drugs that would affect the interpretation of a tPSA result as assayed on the FREND PSA Plus Interference Study Results for FREND PSA Plus on the FREND System No Substrate Concentration Average Recovery 1 Flutamide 10 pg mL 94 50 2 Diethylstilbestrol DES 5 pg mL 103 80 3 Goserelin 40 ng mL 103 20 4 Tamsulosin 100 ng mL 98 85 5 Acetaminophen 250ng mL 10045 6 Acetylsalicylic acid 600 pg mL 95 85 F Leuprolide 275 ng mL 101 50 8 Ibuprofen 500 pg mL 102 25 9 Finasteride 250 ng mL 93 60 10 Docetaxel 10 pg mL 11445 17 Serial Measurements and Concordance with Medical Status Since the FREND PSA Plus Indication for Use is that the assay results will be used as a tool in managing the care for patients with prostate cancer it is imperative that the changes in the marker are compared to clinical status changes to determine the efficacy of the test Therefore as an important part of the clinical studies performed to characterize the FREND PSA Plus serial samples collected longitudinally from patients previously diagnosed with prostate cancer and treated in a variety of ways over the clinical course of their 19 disease including prostatectomy radioactive seeds external beam radiation chemotherapy hormone therapy alone or in combination were assayed for tPSA with the
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