P0063 ViraQ HCV Check 125 P0063

Transcription

1 P0063 ViraQ HCV Check 125 P0063 The kit insert contains a detailed protocol and should be read carefully before testing the run control to ensure optimal performance

2 Table of contents Intended Use... 3 Key to Symbols Used... 3 Principle of method... 3 Traceability of HCV-RNA concentration in IU/mL and copies/ml... 4 Kit Contents... 5 Storage Instructions... 5 Warning and precautions... 5 Test Procedure... 6 Expected assay response values... 6 Calculation and Interpretation of results... 6 Performance data... 9 Limitations References P0063 ViraQ Ultrio HCV Check 125 2

3 Intended Use P0063 ViraQ HCV Check 125 is intended to be used as external run control for monitoring consistent performance and analytical sensitivity of multiplex nucleic acid test (NAT) blood screening assays for detection of HCV-RNA as defined in Table 1. Table 1. Nucleic acid blood screening kits covered by this run control Manufacturer Equipment Agent Test kits Hologic/Grifols Diagnostic Solutions TIGRIS PANTHER Human Immunodefienc Procleix ULTRIO virus type 1 Procleix ULTRIO Plus Procleix ULTRIO Elite P0063 ViraQ HCV Check 125 is also intended to be used for monitoring precision of commercial and in house viral load assays with a limit of quantification (LOQ) below the HCV RNA run control concentration. P0063 ViraQ HCV Check 125 must not be used to replace the internal kit controls or calibrators required for the release of assay results. The product is intended for performance evaluation only. Key to Symbols Used Manufacturer Lot number Catalogue number Store below -30 C Biological substance Category B Do not re-use Device for performance evaluation Expiry date Contents Caution Read instructions for use Principle of method P0063 ViraQ HCV Check 125 is an external run control to monitor the performance of transcription mediated amplification (TMA) or polymerase chain reaction (PCR) assays for the qualitative or quantitative detection of HCV RNA in plasma or serum samples. The external run control is designed to mimic plasma specimens with a low concentration of HCV RNA. The HCV RNA concentration in the run control is 125 copies/ml (equivalent to 46 International Units (IU)/mL). P0063 ViraQ HCV Check 125 generates a sample to cut-off (S/CO) ratio just in the saturation range of the Ultrio assay versions. A concentration of approximately 5 times the 95% lower limit of detection (LOD) of the Ultrio, Ultrio Plus and Ultrio Elite assays 1-4 is chosen to ensure a reactivity rate above 99.5%. For quantitative NAT methods such as real time PCR or TMA assays P0063 ViraQ HCV Check 125 is suitable for monitoring precision of quantitative values in the low viral load range near the LOQ. The HCV standard used for manufacturing of the run control is chemically inactivated to reduce infectivity and handling risk. To guarantee consistent detection and quantification of the viral load the run control sample should not be re-used. P0063 ViraQ Ultrio HCV Check 125 3

4 Traceability of HCV-RNA concentration in IU/mL and copies/ml Traceability and securing continuous and stable performance of P0063 ViraQ HCV Check 125 is based on three viral standards (figure 1) described below: The primary standard is the 1 st WHO HCV-RNA international standard (96/790) with an assigned value in IU/ml. The secondary VQC-Sanquin HCV-RNA genotype 1 standard was prepared by pooling positive HCV-RNA genotype 1 plasma units, Dept. of Viral Diagnostic Services, Sanquin, Amsterdam, The Netherlands) and quantitated in Siemens Versant bdna The genotype was determined by RFLP analysis 8. A homogeneous pool was aliquoted, snap frozen in liquid nitrogen and stored at -70 C. A 1:100 dilution of S0009 was included in the WHO collaborative studies 5,6. The tertiary chemically inactivated BQC HCV-RNA genotype 3a standard (S0109) originate from a plasma unit positive for HCV-RNA genotype 3a and negative for HCV antibodies (pre-seroconversion stage). S0109 is calibrated against S0009. Subsequently P0063 ViraQ HCV Check125 is manufactured by gravimetrically recorded dilution steps from S0109. Figure 1: Traceability chain of P0063 HCV Check control to 1 st WHO IS (96/790), the VQC-Sanquin HCV-RNA genotype 1 standard and BQC inactivated HCV-RNA genotype 3a standard. BQC has quantified its viral standards in copies/ml using the branched (b) DNA 3.0 test as the reference assay 7. Expression in nucleic acid copies/ml (which is a SI unit) allows comparison between different viruses, genotypes, limiting dilution analysis for estimating NAT efficiency and relation to 50% minimum infectious dose for understanding residual transfusion transmission risk (in which one CID50 equals 8 HCV RNA copies 10 ). P0063 ViraQ Ultrio HCV Check 125 4

5 The HCV RNA concentration in copies/ml (and 95% confidence interval (C.I.)) was originally established in suitable dilutions of the S0009 VQC-Sanquin standard in 27 Siemens bdna 3.0 assays at 6.30 ( ).10 6 copies/ml as was estimated from the results reported in proficiency studies. The secondary S0009 VQC Sanquin standard was calibrated against the International Standard in the WHO collaborative studies 5,6 and internal calibrations. These were analysed together. The result of the meta-analysis 1 IU was found to be equivalent to 2.73 ( ) copies/ml. The S0109 BQC standard has been quantified against the S0009 VQC Sanquin HCV standard in 2 x 6 bdna 3.0 assays on suitable dilutions at a concentration (95%CI) of 6.06.( ).10 6 copies/ml. The accurate calibration of the S0109 BQC inactivated standard against the S0009 VQC-Sanquin standard is repeated by Ct analysis on 13 parallel assays of 2000 copies/ml samples of the two preparations in the TaqScreen 2.0 assay showing a potency (95%C.I.) of the latter standard of 0.82 ( ) 17. The production and quality control methods are designed such that the traceability to the primary and secondary standards as described above is guaranteed and that the virus concentration in consecutive batches of P0063 HCV Check 125 run control (95%CI) is maintained consistently at 125 (92-169) copies/ml or 47 (28-77) IU/mL. Kit Contents 10 Tubes, each containing 1.5 ml run control without preservatives in polypropylene tubes with screw caps. Storage Instructions Store the run controls at or below -30 C for a maximum of two years (reference actual expiry date). Stability experiments showed less than 10% degradation of HCV-RNA after storing samples in liquid format at 2-8 C and at room temperature for 8 hours. Warning and precautions P0063 ViraQ HCV Check 125 contains HCV particles that are chemically inactivated by a procedure guaranteeing considerable reduction, if not eradication, of infectivity. The plasma matrix is prepared from human plasma tested negative for blood borne virus markers (HBV-DNA, HCV-RNA, HIV-RNA, HBsAg, anti-hbc, anti-hiv, anti-hcv and anti- Treponema pallidum). No test method can offer complete assurance that products derived from human blood cannot transmit (unknown) infectious agents. Observe the universal precautions for prevention of transmission of infectious agents when handling these materials 18,19. Do not pipette by mouth. Use personal protective equipment, including lab coats, gloves and safety glasses. Do not eat, drink or smoke in areas where HCV run controls are handled. Disinfect spills using a 0.5% hypochlorite solution (1:10 v/v household bleach) or equivalent disinfectant. Dispose unused or spilled materials according to the normal practices for biological waste disposal in your institution. If precipitates are visible, mix the run controls for 2 minutes thoroughly. P0063 ViraQ Ultrio HCV Check 125 5

6 Test Procedure Thaw the run control quickly in a water bath at 37 C, by gently mixing until frozen contents are just thawed. Remove the run control tube from the water bath immediately. Vortex the run control. Give a short spin in a centrifuge before releasing screw cap from vial. Minimise the time period from thawing until usage of the run control. When not used immediately place in refrigerator. The duration is limited to 8 hours storage until use. The controls should be handled and tested in a manner identical to that of clinical specimens in the assay procedure being evaluated. The external run control tubes are barcoded for automated data-processing. The run controls can be placed at random positions in sample racks of the equipment. After testing discard the remaining run control. Note: To minimize degradation of HCV-RNA in the run control do not leave the run control longer than 8 hours on the NAT equipment before the actual processing of the sample in the assay. Do not refreeze! Expected assay response values Qualitative detection of HCV RNA in Grifols Procleix Ultrio Versions The expected distribution of assay response values on P0063 ViraQ HCV Check 125 Control per 1000 test runs in the Ultrio assay versions is presented in Table 2. Table 2. Expected distribution of S/CO response values in Ultrio Plus assay. Range of assay response values Expected frequency per 1000 runs Test runs Interpretation Saturated: S/CO Positive Dynamic: 1<S/CO<7 63 Positive Non-reactive 1.2 Negative Quantitative HCV-RNA detection by viral load assays The expected viral load (and 95% CI) results on P0063 ViraQ HCV Check 125 in quantitative HCV RNA assays are shown in Table 3. Table 3. Expected viral load in P0063 ViraQ Check 125 (see also limitations) Unitage Average 95 % confidence interval Copies/mL 1 IU/mL Siemens Versant bdna 3.0 assay, only (Figure 1) Calculation and Interpretation of results Qualitative detection of HCV RNA in Grifols Procleix Ultrio Versions P0063 ViraQ HCV Check 125 Control should react positive in more than 99.5% of NAT blood screening test runs. In the Ultrio assay versions it is expected that S/CO ratios are equal to or above 7.0 on the run control samples. Dynamic S/CO ratios below 7.0 may occur in frequencies indicated in table 2. A negative result is rare and is expected to occur in <0.5% of test runs, while low positive results occur in ~ 6 % of all cases. Frequencies of S/CO values out of the observed ranges are indicative of deterioration of reagents or systematic performance errors. Although the S/CO ratios on the run controls are not normally distributed, the Westgard rules 21 provide guidance for the interpretation on frequency of lower or negative S/CO results. P0063 ViraQ Ultrio HCV Check 125 6

7 Quantitative HCV-RNA detection by viral load assays For monitoring the accuracy and precision in viral load assays, the following steps should be taken: 1. Use Levey-Jennings QC chart for trend analysis 2. Monitoring variation in quantitative values between result sets 3. Interpretation: Upon establishing a deviation, identify possible error source. Sub 1 Levey-Jennings QC chart. Test the run control for at least 10 times (this will become the reference period, see below), apply log transformation on IU/mL or copies/ml, estimate the geometric mean, standard deviation (SD) and its confidence interval (CI) as described below. If Ct values are used no log transformation is required and confidence intervals can be calculated from the mean and SD. The Levey-Jennings chart is designed to identify individual aberrant values outside the 95% and 99% confidence intervals (CI).With collecting additional data the chart characteristics may be updated. The quantitative values for [HCV-RNA] are log normal distributed. Calculate from each measurement the log(concentration). Calculate mean and SD on these values: log (mean) and log (SD). Take anti-log of the log (mean), i.e. the geometric mean of the concentration Use table 4 to obtain Student-t-values belonging to the 95% and 99% CI for different number of observations (n). Calculate the log(95% and 99% CI) as follows: Log (99% Lower limit): log (Average) (99%) Student-t-Value x log(sd) Log (95% Lower limit): log (Average) (95%) Student-t-Value x log(sd) Log (95% Upper limit): log (Average) + (95%) Student-t-Value x log(sd) Log (99% Upper limit): log (Average) + (99%) Student-t-Value x log(sd) Table 4. Relation of Student t value and numbers of runs (n) to calculate CI s. Run (n) t-value at 95% C.I. t-value at 99% C.I infinite Figure 3. Example Levey-Jennings chart on HCV-RNA Ct values (Roche TaqScreen 2.0) Sub 2 Monitoring variation in quantitative values between result sets P0063 ViraQ Ultrio HCV Check 125 7

8 The cumulative Chi-square distribution is used to estimate the probability the SD of the test population (s) is different from the SD of reference population ( ): n is number of measurements over the evaluated period Within the set evaluated: calculate SD on the log(concentration) or Ct value(n>10): s Within the reference set: calculate SD on the log(concentration) or Ct value:. Calculate 2 = (n 1) s2 2 Table 5. Chi-square ( 2 ) values for p=0.05 n-1 (df) 2 n-1 (df) 2 n-1 (df) Interpretation: Chi-square: 2 (Calculated) < 2 (P=0.05): precision is not significantly changed. Chi-square: 2 (Calculated) 2 (P=0.05): precision has changed significantly. For the analysis result sets could be defined by reagent batch, laboratory operator, equipment, et cetera. Sub 3. Upon establishing a deviation, identify possible error source. Use the Westgard rules for deviations found in the Levey Jennings trend analysis. Significant differences between result sets can be used for root cause analysis to identify the error source. P0063 ViraQ Ultrio HCV Check 125 8

9 Performance data Qualitative detection of HCV RNA in Grifols Procleix Ultrio Versions Analytical sensitivity of the Ultrio assay versions. The analytical sensitivity of the Ultrio assay versions has been evaluated in different validation studies 1-4,17. Table 6 shows the 95% LODs of the Ultrio, Ultrio Plus and Ultrio Elite on the three WHO (96/790, 96/798 and 06/100) and S0009 HCV genotype 1 standard dilution series. From this table it is concluded that the Ultrio, Ultrio Plus and Ultrio Elite assays have the same analytical sensitivity. Thus, these assays can be monitored with the same run control. Table 6. Analytical sensitivity of Procleix Ultrio versions on Sanquin and BQC HCV-RNA standards and the 2 nd WHO HCV subtype B standard HCV-RNA standard Assay 50% LOD (CI) 95% LOD (CI) n version copies/ml copies/ml Ref 1 st WHO HCV IS All Ultrio (96/790) # tests 48 a 2.3 ( ) 16.7 ( ) 4 2 nd WHO HCV IS All Ultrio (96/798) # tests 593 b 2.4 ( ) 17.1 ( ) 4 3 rd WHO HCV IS All Ultrio (06/100) # tests 750 c 3.1 ( ) 22.3 ( ) 4 S0009 VQC-Sanquin HCV genotype 1 S0109 BQC HCV genotype 3a inactivated Ultrio ( ) 24.7 ( ) Ultrio Plus ( ) 15.0 ( ) Ultrio Elite ( ) 12.9 ( ) Ultrio ( ) 28.1 ( ) 20 # IU/mL LOD values converted to copies per ml using factor of 2.73 copies per IU a) Duplex n=24, Ultrio n=24, b) Duplex n=72, Ultrio n=522, c) Ultrio n=86, Ultrio plus n=419 and Ultrio Elite n=245 The choice for HCV RNA concentration in P0063 ViraQ HCV Check 125 Control is 125 copies/ml. 125 Copies/mL is approximately 5 times the 95% LOD of the Ultrio versions. Thus, a positive result on the run control is guaranteed in more than 99.5% of test runs. Commutability of inactivated standard to the native standard. The results on standard dilution series of S0109 BQC HCV genotype 3a inactivated standard were used to design the P0063 ViraQ HCV Check 125. The analytical sensitivity of Ultrio on the inactivated BQC standard was found to be lower than in other studies on the native VQC-Sanquin standard. This difference is caused by lack of commutability of the inactivated BQC standard between testing in the bdna assay (used for calibration) and the target Ultrio assay versions. Distribution characteristics of S/CO results. Figure 3 shows the S/CO values in 5070 Ultrio Plus Assay runs on P0063 ViraQ HCV Check 125 Control in a histogram which confirm the expected reactivity. Obviously, the S/CO values are not normally distributed. A transformation of S/CO values to obtain normally distributed S/CO values appears not possible. Therefore monitoring S/CO response values in Levey-Jennings charts to identify responses outside confidence limits cannot be applied in a statistically valid manner. Only the proportions of S/CO results in the dynamic and negative range can be used to identify lack of performance. 4 P0063 ViraQ Ultrio HCV Check 125 9

10 Figure 3. S/CO Distribution on P0063 ViraQ HCV Check 125 in Ultrio Plus Assay (n=6047, see also table 7) Predicted and observed reactivity rate in Ultrio versions. The observed reactivity levels in two different ViraQ HCV RNA run controls of 125 and 25 copies/ml in Ultrio Plus (P0063 and P0068) confirm the probit analysis data on BQC standard dilution series (P0026) in Ultrio (Table 7). The results confirm consistency in reactivity of Ultrio versions, Ultrio batches and run controls batches (data not shown). Table 7. Predicted and observed number of non-reactive response values in Ultrio assays BQC product Predicted number Observed number of HCV-RNA Copies of non-reactive non-reactive results level /ml results per 1000 per 1000 # P0026 BQC HCV RNA standard dilution panel 1 x 95% LOD N.A. P0067 Trend control 0.93 x LOD P0063 Check Control 4.45 x LOD #The test results presented in table 7 were collected during 4 years by 3 laboratories on these two run control levels and during 2 months by 5 laboratories on the dilution series of the inactivated BQC standard used for preparation of the run control products. Quantitative HCV-RNA detection by viral load assays Rationale for monitoring quantitative real time PCR or TMA performance with a HCV-RNA run control at 125 copies/ml. 125 copies/ml is high enough to ensure the viral load measurement is within the linear range of viral load assays and will yield a precise result, similar to higher concentrations. The precision of the viral load assays depends on the concentration measured in the sample: The variability increases with decreasing concentration, specifically in the range of low concentrations close to LOQ. For example, the HCV detection in the Roche TaqScreen 1.0 assay using a dilution series of the S0009 VQC-Sanquin HCV genotype 1 standard tested in 12 replicates (Figure 2). Figure 2 shows decrease in precision (i.e. higher variability in Ct values) with decreasing HCV concentrations. Below 125 copies/ml the effect becomes significant. This is in the range of LOQ, LOD and lower. P0063 ViraQ Ultrio HCV Check

11 Figure 4. Variability of Ct values in HCV standard dilutions. To be able to monitor quality of viral load assays over time, it is assumed that decreased assay performance leads to increasing LOD/LOQ and consequently in an increase in variability and lower viral load measurements. The decrease in viral load measurements on the run control can be monitored using a Levey-Jennings chart and is described in section Calculation and Interpretation of results, The increase in variability can be quantified and analyzed for significant differences using cumulative chi-square distribution. The procedure for analyzing, a significant difference is present, is described in section Calculation and Interpretation of results, Monitoring variation in quantitative values over time to which is referred to. Table 8. 2 and p-values comparing several concentrations with the reference 216 copies/ml (same data used as figure 2) copies/ml St.dev. average Ct value 2 p-value The comparison between standard deviations is able to recognise a decline in sensitivity; discriminate between 216 and 72 copies/ml. Table 9 presents an overview of the claimed lower limits of detection (LOD) and quantification (LOQ) of a number of quantitative HCV-RNA assays. P0063 ViraQ HCV Check 125 is supposed to be a suitable run control for these and any other quantitative HCV RNA assay with a proven LOQ below 125 copies/ml. Table 9. LODs and LOQs in some quantitative HCV RNA assays Manufacturer Assay LOD LOQ unit Standard Abbott Real Time HCV 12 12a IU/mL 2 nd WHO I.S. Hologic Aptima HCV Quant Dx n.a. n.a. IU/mL 3 rd WHO I.S. Roche COBAS AmpliPrep/COBAS TaqMan HCV test IU/mL 1 st WHO I.S. P0063 ViraQ Ultrio HCV Check

12 Limitations P0063 ViraQ HCV Check 125 Control is not intended to be used for evaluation of the analytical or diagnostic sensitivity of NAT blood screening assays. P0063 ViraQ HCV Check 125 Control must not be substituted for the mandatory controls or calibrators provided with IVD test kits for calculating the cut off and/or criteria for releasing test results. The Poisson distribution in samples with low HCV concentrations cannot guarantee that 100% reactive results will be found on P0063 ViraQ HCV Check 125 Control in NAT blood screening assays. Therefore nonreactive response values on the run control should not be used for a decision to reject the test run. The expected distributions of assay response values on P0063 ViraQ HCV Check 125 that are presented in this package insert are based on evaluation studies involving a limited number of runs and reagent batches of the Ultrio and Ultrio Plus assays. It cannot be guaranteed that future reagent batches of the Ultrio Plus and Elite assay versions will generate the same reactivity. It cannot be guaranteed that the inactivated BQC standard from which P0063 ViraQ HCV Check 125 is prepared is commutable across different NAT methods. Commutability of lyophilized or heat-inactivated virus in WHO and BQC standards with regard to reported concentrations in IU/mL and copies/ml by different quantitative HCV RNA assays has not been investigated. Therefore establishing accuracy of viral load measurements using the run control is not appropriate The manufacturers of the quantitative HCV RNA assays have prepared their internal calibrators based on different standards and this may cause systematic differences in quantitative results between methods. The accuracy of different quantitative assays in reporting in IU or copies/ml values could have been affected by the differences in calibration of the NAT systems and by heat inactivation of the BQC standard. Therefore laboratories should define their own geometric mean and 95% CI in the applied test system and interpret results according to the Westguard rules 18. P0063 ViraQ Ultrio HCV Check

13 References 1. Grabarczyk P, van Drimmelen H, Kopacz A, Gdowska J, Liszewski G, Piotrowski D, Górska J, Kuśmierczyk J, Candotti D, Lętowska M, Lelie N, Brojer E. Head-to-head comparison of two transcription-mediated amplification assay versions for detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus Type 1 in blood donors. Transfusion. 2013;53: Assal A, Barlet V, Deschaseaux M, Dupont I, Gallian P, Guitton C, Morel P, David B, and De Micco P. Comparison of the analytical and operational performance of two viral nucleic acid test blood screening systems: Procleix Tigris and cobas s 201. Transfusion 2009;49: Koppelman M, Assal A, Chudy M, Torres P, de Villaescusa RG, Reesink HW, Lelie PN, Cuypers HT. Multi-center performance evaluation of a transcription-mediated amplification assay for screening of human immunodeficiency virus-1 RNA, hepatitis C virus RNA, and hepatitis B virus DNA in blood donations. Transfusion 2005;45: Grabarczyk P, Koppelman M, Boland F, Sauleda S, Fabra C, Cambie G, O Riordan K, Van Drimmelen H, O Riordan J, Lelie N. Inclusion of human immunodeficiency virus type 2 (HIV-2) in a multiplex transcription mediated amplification assay does not affect detection of HCV and hepatitis B and C virus genotypes: A Multi-center performance evaluation study. Transfusion 2015 [Epub ahead of press]. 5. Saldanha J, Lelie N, Heath A. Establishment of the first international standard for nucleic acid amplification technology (NAT) assays for HCV RNA. WHO Collaborative Study Group.Vox Sang. 1999;76(3): Saldanha J, Heath A, Lelie N, Pisani G, Nübling M, Yu M. Calibration of HCV working reagents for NAT assays against the HCV international standard. 7. Collins ML, Zayati C, Detmer JJ, Daly B, Kolberg JA, Cha TA, Irvine BD, Tucker J, Urdea MS. Preparation and characterization of RNA standards for use in quantitative branched DNA hybridization assays. Anal Biochem ;226: Simmonds P, Smith DB, McOmish F, Yap PL, Kolberg J, Urdea MS, Holmes EC. Identification of genotypes of hepatitis C virus by sequence comparisons in the core, E1 and NS-5 regions. J Gen Virol May;75 ( Pt 5): Stephan W, Dichtelmüller H, Prince AM, Brotman B, Huima T. Inactivation of the Hutchinson strain of hepatitis non-a, non-b virus in intravenous immunoglobulin by beta-propiolactone. J Med Virol. 1988;26: Yoshizawa H, Itoh Y, Iwakiri S, Kitajima K, Noguchi Y, Tachibana K, Nakamura T, Miyakawa Y, Mayumi M. Beta-propiolactone for the inactivation of non-a/non-b type 1 hepatitis virus capable of inducing cytoplasmic tubular ultrastructures in chimpanzees. Vox Sang. 1984;46: Scheidler A, Rokos, K, Reuter T, Ebermann R and Pauli G. Inactivation of Viruses by beta-propriolactone in Human Cryo Poor Plasma and IgG concentrates. Biologicals 1998;26: Katayama K, Kumagai J, Komiya Y, Mizui M, Yugi H, Kishimoto S, Yamanaka R, Tamatsukuri S, Tomoguri T, Miyakawa Y, Tanaka J, Yoshizawa H. 13. Titration of hepatitis C virus in chimpanzees for determining the copy number required for transmission. Intervirology. 2004;47(1): El Ekiaby M, Moftah F, Goubran H, van Drimmelen H, LaPerche S, Kleinman S, Busch M, Lelie N. Viremia levels in hepatitis C infection among Egyptian blood donors and implications for transmission risk with different screening scenarios.transfusion Mar 13. P0063 ViraQ Ultrio HCV Check

14 15. Bruhn R, Lelie N, Busch M, Kleinman S and the International NAT Study Group. Relative efficacy of nucleic acid amplification testing and serologic screening in preventing hepatitis C virus transmission risk in seven international regions.transfusion Feb Van Drimmelen A.A.J., Lelie PN. Preparation of inactivated secondary viral standards: Safety assessment of quality control samples for viral serology and NAT assays in blood screening laboratories. BQC document number CE Weusten J, Vemeulen M, Van Drimmelen H, Lelie PN. Refinement of a viral transmission risk model for blood donations in serconversion window phase screened by nucleic acid testing in different pool sizes and repeat test algorithms. Transfusion 2011;51: Lelie N., Van Drimmelen H. and the International NAT Study Group. Calibration and stability of WHO and secondary viral standards. SoGAT XXIV 8-9 May 2013, Ljubljana, Slovenija 19. Centers for Disease Control (CDC). Update: Universal precautions for prevention of transmission of human immunodeficiency virus, hepatitis B virus, and other blood borne pathogens in health-care settings. MMWR 1988; 37: Centers for Disease Control (CDC). Guidelines for prevention of transmission of human immunodeficiency virus and hepatitis B virus to health-care and public-safety workers. MMWR 1989; 38(S-6): Westgard rules Van Drimmelen H., Bremer C, Gerlich W, Quint W, Ullum H, O Riordan J, Gdowska J, Grabarczyk P, Brojer E, Lelie N, Commutability of inactivated or lyophilised virus in external quality control (EQC) samples for NAT. SoGAT XXII April 2011, Rome, Italy P0063 ViraQ Ultrio HCV Check

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16 BioQControl B.V. Visseringlaan ER Rijswijk The Netherlands Tel: +31 (0) Fax: +31 (0) Internet: KI4059 v1.1 June 2015 P0063 ViraQ Ultrio HCV Check