November/ December 2016

Transcription

1 November/ December 2016 Pre-evaluation of the External Quality Assessment Schemes in Virus Diagnostics Prof. Dr. Heinz Zeichhardt Dr. Martin Kammel Issued by: INSTAND Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laborarien e.v. Düsseldorf/Berlin, Germany, Pre-evaluation Virology November December a.doc 1 of 16

2 INSTAND EQA Schemes in Virus Diagnostics in cooperation with: Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten e.v. (DVV) Gesellschaft für Virologie e.v. (GfV) Deutsche Gesellschaft für Hygiene und Mikrobiologie e.v. (DGHM) EQAS Adviser: Prof. i.r. Dr. Heinz Zeichhardt Professor of Virology Charité - University Medicine Berlin Correspondence address: Prof. Dr. Heinz Zeichhardt Institut für Qualitätssicherung in der Virusdiagnostik - IQVD Potsdamer Chaussee 80, D Berlin, Germany Tel.: +49-(0) ; Fax: +49-(0) Heinz.Zeichhardt@iqvd.de Assistant EQAS Adviser: Dr. Martin Kammel c/o INSTAND e.v. Ubierstr. 20, D Düsseldorf, Germany Tel.: +49-(0) ; Fax: +49-(0) m.kammel@iqvd.de Organisation and Logistics: INSTAND e.v. Ubierstr. 20 D Düsseldorf, Germany Tel.: +49 (0) Fax: +49 (0) instand@instand-ev.de Internet: Pre-evaluation Virology November December a.doc 2 of 16

3 Pre-Evaluation and Mailing of Participation Documents INSTAND External Quality Assessment Schemes November/December 2016 Virus Immunology Virus Genome Detection by PCR/NAT Dear colleagues, You have registered for one or several of the INSTAND external quality assessment (EQA) schemes in diagnostics in November/December Today you receive the pre-evaluation. By mail, you receive the following participation documents of those EQA schemes in which you have participated this time: certificate of successful participation statement of participation statement of individual results The EQA schemes having been performed in November/December 2016 are highlighted in bold in Tables 1 and 2. For these highlighted EQA schemes, the corresponding participation documents will be sent out by mail gether with this pre-evaluation. Please note: The participation documents of the following EQA schemes for drug resistance determination will be sent out later by mail: cymegalo (349) hepatitis B (397) hepatitis C (399) HIV-1 standard program (383) HIV-1 additional program (384) VIRUS IMMUNOLOGY: Cymegalo (351) Hepatitis A (343) Hepatitis B Prog. 1 (344) Hepatitis B Prog. 2 (345) Hepatitis C (346) HIV-1/HIV-2 (335) HIV-1 p24 Ag (337) Table 1: EQA schemes performed with a frequency of four times per year VIRUS GENOME DETECTION: Cymegalo (365) Hepatitis A (377) Hepatitis B (361) Hepatitis C (362) HIV-1 (360) Parvo B19 (367) The EQA schemes having been performed in November/December 2016 are highlighted in bold (Table 1). For these highlighted EQA schemes, the corresponding participation documents will be sent out by mail gether with this pre-evaluation. Pre-evaluation Virology November December a.doc 3 of 16

4 VIRUS IMMUNOLOGY: Table 2: EQA schemes performed twice per year or with lower frequency (EQA schemes having been performed in November/December 2016 are highlighted in bold) Chikungunya (402) Dengue es (Ab/NS1-Ag) (350) Epstein Barr (352) TBE (FSME) (358) Hantaes (355) Hepatitis D (347) Hepatitis E (348) Herpes simplex es (354) HTLV-1/HTLV-2 (339) Measles (357) Mumps (356) Parvo B19 (342) Rubella (341) Rabies (Tollwut) (336) Varicella zoster (353) Zika (338) VIRUS GENOME DETECTION: Adenoes (371) BK (364) Chikungunya (392) Coronaes (340) Cymegalo training program (368) Cymegalo resistance determination (349) Dengue es (369) Enteroes (372) RKI-Entero-Surveillance (every two years) (374) Epstein Barr (376) Hepatitis B training program (378) Hepatitis B genotyping (396) Hepatitis B resistance determination (397) Hepatitis C training program (379) Hepatitis C geno-/subtyping (375) Hepatitis C resistance determination (399) Hepatitis D (400) Hepatitis E (380) Herpes simplex type 1/2 (363) HIV-1 training program (382) HIV-1 drug resistance determ. (standard progr.) (383) HIV-1 drug resistance determ. (additional progr.) (384) HIV-2 (395) Human Metapneumo (385) Human Papilloma es (373) Human Rhinoes (393) Influenza es (genome/ag) (370) JC (394) Measles (386) Mumps (387) Noro (381) Parainfluenza es (388) Respirary syncytial (Ag/genome) (359) Rotaes (401) Rubella (389) Rabies (Tollwut) (390) Varicella zoster (366) West Nile (391) Zika (403) The EQA schemes having been performed in November/December 2016 are highlighted in bold (Table 2). For these highlighted EQA schemes, the corresponding participation documents will be sent out by mail gether with this pre-evaluation. EQA schemes in Table 2 marked in italics were not performed in November/December Please see the following Tables 3, 4 and 5 for details on sample properties and the expected target values for this EQA scheme November/December You received information on sample properties already per on The reports of all EQA schemes will be released on the INSTAND homepage immediately after completion. For details please see the INSTAND homepage under "EQAS Online / Service for EQA tests / EQA area (Virus immunology / Virus genome detection)" in English language: and in German language: Pre-evaluation Virology November December a.doc 4 of 16

5 Please note: RiliBÄK A compilation of the "Guidelines of the German Medical Association on quality assurance in medical laborary testing (Bundesärztekammer / RiliBÄK = Richtlinie der Bundesärztekammer zur Qualitätssicherung laborariumsmedizinischer Untersuchungen)" with all Sections including Section "Qualitative medical laborary testing = Qualitative laborariumsmedizinische Untersuchungen" and Section "Direct detection and characterisation of infectious agents = Direkter Nachweis und Charakterisierung von Infektionserregern" has recently been published (in German language: Deutsches Ärzteblatt, Jg. 111, Heft 38, 19. September 2014, A A 1618) (please see link). An English version of the guideline translated by INSTAND e.v. with the consent of the Executive Board of the German Medical Association has been published in "German Medical Science" [in English language: Bundesärztekammer (German Medical Association), Instand e.v., Guidelines of the German Medical Association on quality assurance in medical laborary testing. GMS Z Forder Qualitatssich Med Lab. 2015; 6] (please see link). Notice for German laboraries: The requirements laid down in Specified Section - effective since and with a transition period until should now be fulfilled. INSTAND EQA schemes in diagnostics and INSTAND ordering documents 2017 For details please see the INSTAND ordering documents 2017 incl. brochure and order form (please see link). Surplus samples of the current and previous EQA schemes in diagnostics are available for test assessment of your diagnostics. Please contact INSTAND for details. Thank you for your kind cooperation. Prof. Dr. H. Zeichhardt Pre-evaluation Virology November December a.doc 5 of 16

6 Table 3: EQA Schemes Virus Immunology - November/December 2016 Pre-evaluation Program Group RiliBÄK Analyte Sample Cymegalo Epstein Barr Tick-borne encephalitis (TBE = FSME) # Hepatitis A Hepatitis B (prog. 1) (HBsAg anti-hbs anti-hbc) mandary: mandary: mandary: anti-cmv-igg anti-cmv-igm anti-cmv-igg anti-cmv-igm anti-ebv-igg anti-ebv-igm anti-ebv-igg anti-ebv-igm anti-tbe-igg anti-tbe-igm anti-tbe-igg anti-tbe-igm Sample properties qualitative dilution sample source avidity: no avidity / no statement possible avidity: low = = anti-hav anti-hav The accepted results will be shown in the report mlu/ml (2 miu/ml target value) 50 miu/ml (60 miu/ml)* healthy blood donor (Pool) 1 : 4 acute CMV infection past EBV infection (two healthy blood donors) healthy blood three healthy blood donor with indication of a past TBE infection/vaccination healthy blood Pre-evaluation Virology November December a.doc 6 of 16 1 : 15 anti-hav-igg healthy blood donor anti-hav-igm : 10 acute hepatitis A anti-hav-igm healthy blood HBsAg IU/ml (1.16 IU/ml target (a) 1 : value) acute hepatitis B HBsAg IU/ml (17.38 IU/ml target (a) 1 : 500 value) HBsAg healthy blood IU/ml 0.00 IU/ml target value) HBsAg IU/ml (4.54 IU/ml target (a) 1 : acute hepatitis B value) anti-hbs IU/l (b) 1 : (57 IU/l target value) anti-hbs anti-hbs anti-hbs IU/l (28 IU/l target value) IU/l (112 IU/l target value) 0-9 IU/l (0 IU/l target value) a, b: Marked samples derive from corresponding sck materials diluted in consecutive steps. Non-marked samples derive from independent preparations. The samples and are identical. (b) 1 : (b) 1 : anti-hbs healthy blood donor healthy blood # FSME = Frühsommer-Meningoenzephalitis * For highly concentrated samples some commercial tests for the detection of anti-hav-igg or anti-hav-tal reveal values > 60 miu/ml, which are outside the linear measurement range of the respective test system. Therefore, a final target value derived from a consensus value from all results stated in miu/ml could not be assigned highly concentrated samples. In this case a lower limit value in miu/ml is indicated in order assess a reported result of a laborary as a "correct" result.

7 Table 3 (contd.): EQA Schemes Virus Immunology - November/December 2016 Pre-evaluation Sample properties Program Group RiliBÄK Analyte Sample qualitative dilution sample source Hepatitis B anti-hbc (c) 1 : 350 chronic hepatitis B ( for HBeAg, anti- (prog. 1) anti-hbc (c) 1 : 175 HBc-IgM ) mandary: 344 healthy blood anti-hbc (HBsAg anti-hbs anti-hbc) (continued) Hepatitis B (prog. 2) (anti-hbc-igm HBeAg anti-hbe) Hepatitis C (Ab and HCV-Ag) * ** Hepatitis D Hepatitis E Herpes simplex es HIV-1/ HIV-2 HIV-1 p24 Ag anti-hbc (c) 1 : 700 chronic hepatitis B ( for HBeAg, anti- HBc-IgM ) mandary: anti-hbc-igm : 150 acute hepatitis B healthy blood anti-hbc-igm mandary: healthy blood HBeAg HBeAg : 750 chronic hepatitis B mandary: ( for HBeAg) chronic hepatitis B anti-hbe : 170 healthy blood anti-hbe anti-hcv anti-hcv healthy blood * mandary: HCV antigen HCV Ag mandary: mandary: mandary: anti-hcv HCV antigen anti-hcv HCV antigen anti-hcv HCV antigen anti-hdv-igg anti-hdv-igm anti-hdv-igg anti-hdv-igm anti-hev-igg anti-hev-igm anti-hev-igg anti-hev-igm anti-hsv-igg anti-hsv-igm anti-hsv-igg anti-hsv-igm ** * ** & = & = not evaluated not evaluated 1 : 10 1: 10 1 : 50 chronic hepatitis C (subtype 3a) condition after chronic hepatitis C (successful therapy) chronic hepatitis C (subtype 1b) 1 : 350 chronic hepatitis D healthy blood donor past hepatitis E healthy blood donor past HSV-1/HSV-2 infection (one healthy blood donor) anti-hiv-1/ healthy blood anti-hiv : 100 HIV-1 infection anti-hiv : 3.6 HIV-2 infection anti-hiv : 75 HIV-1 infection p24 Ag : p24 Ag c: Marked samples derive from corresponding sck materials diluted in consecutive steps. Non-marked samples derive from independent preparations. & The samples and are identical. HIV-1 infection (spiked pool of blood donors; HIV-1 heat inactivated) healthy blood Pre-evaluation Virology November December a.doc 7 of 16

8 Table 3 (contd.): EQA Schemes Virus Immunology - November/December 2016 Pre-evaluation Sample properties Program Group RiliBÄK Analyte Sample qualitative dilution sample source HTLV-1/ healthy blood anti-htlv-1/ * HTLV-2 donor 339 anti-htlv ** 1 : 4 HTLV-2 infection * anti-htlv * 1 : 500 HTLV-1 infection ** Measles Mumps Parvo B19 * ** Rubella mandary: anti-htlv ** 1 : 500 HTLV-1 infection anti-measles-igg anti-measles-igm anti-measles-igg anti-measles-igm anti-mumps-igg anti-mumps-igm anti-mumps-igg anti-mumps-igm anti-parvo B19-IgG anti-parvo B19-IgM anti-parvo B19-IgG anti-parvo B19-IgM anti-parvo B19-IgG anti-parvo B19-IgM anti-parvo B19-IgG anti-parvo B19-IgM titer HI test / HiG anti-rubella-igg anti-rubella-igm titer HI test / HiG anti-rubella-igg anti-rubella-igm Non-marked samples derive from independent preparations ** * * * avidity: no avidity / no statement possible / no statement possible avidity: no avidity (64 target value) 50 IU/ml (131 target value) (256 target value) 100 IU/ml (271 target value) # one healthy blood donor with indication of a past measles infection/vaccination one healthy blood donor with indication of a past measles infection/vaccination healthy blood donor one healthy blood donor with indication of a past mumps infection/vaccination past parvo B19 infection (healthy blood donor) past parvo B19 infection (healthy blood donor) past parvo B19 infection (two healthy blood donors) healthy blood donor two healthy blood donors with indication of a past rubella infection or vaccination two healthy blood donors with indication of a past rubella infection or vaccination # Some commercial tests for the detection of anti-rubella-igg reveal for highly concentrated samples values > 400 IU/ml and > 500 IU/ml, respectively, which are outside the linear measurement range of the respective test system. Therefore, a final target value derived from a consensus value from all results stated in IU/ml could not be assigned highly concentrated samples. In this case a lower limit value in IU/ml is indicated in order assess a reported result of a laborary as a "correct" result. Pre-evaluation Virology November December a.doc 8 of 16

9 Table 3 (contd.): EQA Schemes Virus Immunology - November/December 2016 Pre-evaluation Program Group RiliBÄK Analyte Sample Varicella zoster Zika * * anti-vzv-igg anti-vzv-igm anti-vzv-igg anti-vzv-igm anti-zika-igg anti-zika-igm anti-zika-igg anti-zika-igm anti-zika-igg anti-zika-igm Non-marked samples derive from independent preparations Sample properties qualitative dilution sample source The results for anti-zika- IgM obtained by a test of one manufacturer (EuroImmun, Arbo- Fever-Mosaic 2) were inconsistent and have not been evaluated (without disadvantage for the certificate)., borderline past VZV infection (two healthy blood donors) past VZV infection (two healthy blood donors) sample and sample derive from the same patient Z3 sample is a follow-up of patient Z3 past Zika infection for anamnestic information see sample blood collected: approx. 4 months after onset of disease sample and sample derive from the same patient Z3 sample is the primarily derived from patient Z3 post-acute Zika infection, Zika RNA not detectable anymore stay in South America (Columbia, Peru, Chile, Bolivia and Argentina) Clinical signs: fever, headache, muscle pain, joint pain and rash blood collected: approx. 3 weeks after onset of disease healthy blood donor * The EQA program Virus Immunology - Zika Virus (338) is performed in cooperation with Bernhard-Nocht-Institut, Hamburg (Nationales Referenzzentrum für tropische Infektionserreger und WHO Collaborating Centre for Arbo and Haemorrhagic Fever Reference and Research; Prof. Dr. Stephan Günther, Dr. Petra Emmerich and Prof. Dr. Dr. Jonas Schmidt-Chanasit). Pre-evaluation Virology November December a.doc 9 of 16

10 EQA Schemes Virus Genome Detection by PCR/NAT November/December 2016 Pre-evaluation Notices Evaluation of results for quantitative genome detection of CMV 1) Notice for German and foreign participants of EQA scheme 365: For evaluation, "IU/ml" have primarily been considered as measurement units of the quantitative results for the analyte CMV. This is in accordance the "Guideline of the German Medical Association (Bundesärztekammer / RiliBÄK)", Specified RiliBÄK Section, Table B. 3-2a, When applying CE-marked tests, which not (yet) allow reporting of results in IU/ml, it should be continued report the results as stated by the manufacturer. Evaluation of results for quantitative genome detection of HBV and HCV 2) Notice for German participants of EQA schemes 361 and 362: For evaluation, "IU/ml" have been considered as measurement units of the quantitative results for the analytes HBV and HCV. This is in accordance the "Guideline of the German Medical Association (Bundesärztekammer / RiliBÄK)", Specified RiliBÄK Section, Table B. 3-2a. Statements in "copies/ml" will not be accepted anymore. 3) Notice for foreign participants of EQA schemes 361 and 362: Please note that quantitative results in "copies/ml" for the genome detection of HBV and HCV, respectively, have not been evaluated due the low number of analyses or missing analyses. Evaluation of results for quantitative genome detection of HIV-1 4) Notice for German participants of EQA scheme 360: For evaluation, "copies/ml" have been considered as measurement unit of the quantitative results for the analyte HIV-1. This is in accordance the "Guideline of the German Medical Association (Bundesärztekammer / RiliBÄK)", Specified RiliBÄK Section, Table B. 3-2a. Statements in "IU/ml" will not be accepted anymore. 5) Notice for foreign participants of EQA scheme 360: Please note that quantitative results in "IU/ml" for the genome detection of HIV-1 have not been evaluated due the low number of analyses or missing analyses. Pre-evaluation Virology November December a.doc 10 of 16

11 Table 4: EQA Schemes Virus Genome Detection - November/December 2016 Pre-evaluation Program Group RiliBÄK Sample CMV (DNA) EBV (DNA) HAV spiked HBV (DNA) HCV HEV * suspension of feces** HIV-1 spiked HIV-2 spiked HMPV mandary: mandary: mandary: mandary: mandary: mandary: Sample properties qualitative Target value of all methods (note on dilution (provisional data) geno-/subtype) copies/ml IU/ml For evaluation of results in copies/ml or IU/ml: see notice 1, page (d) 1 : (d) 1 : (d) 1 : (d) 1 : (e) 1 : (e) 1 : (e) 1 : : not evaluated # not evaluated # (f) 1 : not evaluated # not evaluated # (f) 1 : 500 not evaluated # not evaluated # not evaluated # not evaluated # (g) 1 : Results in copies/ml: (g) 1 : not accepted or 0.0 not evaluated (g) 1 : (see notices 2 and 3, page 10) (h) 1 : (subtype 4a) Results in copies/ml: (h) 1 : 40 not accepted (subtype 4a) or (h) 1 : 400 not evaluated (subtype 4a) (see notices 2 and 3, (h) 1 : 127 page 10) (subtype 4a) ** (subtype 3c) 1 : 62 not evaluated # not evaluated # ** (subtype 3e) (i) 1 : 31 not evaluated # not evaluated # ** 1 : 200 not evaluated # not evaluated # ** (subtype 3e) (i) 1 : 310 not evaluated # not evaluated # (group M/ subtype F) (group M/ subtype F) (group M/ subtype F) (group M/ subtype F) (j) 1 : (j) 1 : (j) 1 : (j) 1 : Results in IU/ml: not accepted or not evaluated (see notices 4 and 5, page 10) strain: EHO (k) 1 : 75 not evaluated # not evaluated # strain: EHO (k) 1 : 750 not evaluated # not evaluated # strain: EHO (k) 1 : 7.5 not evaluated # not evaluated # not evaluated # not evaluated # (subtype A) (l) 1 : 20 not evaluated # (subtype A) (l) 1 : 80 not evaluated # not evaluated # (subtype A) (l) 1 : 320 not evaluated # # The quantitative results are not evaluated due the low number of analysis (without disadvantage for the certificates). d, e, f, g, h, i, j, k, l: Marked samples derive from corresponding sck materials diluted in consecutive steps.. Non-marked samples derive from independent preparations. Pre-evaluation Virology November December a.doc 11 of 16

12 Table 4 (contd.): EQA Schemes Virus Genome Detection November/December 2016 Pre-evaluation Program Group RiliBÄK Sample Measles FTA cards Mumps FTA cards Parvo B19 (DNA) Respirary syncytial (antigen/ genome) Rubella FTA cards VZV (DNA) mandary: mandary: mandary: Sample properties qualitative Target value of all methods (note on dilution (provisional data) geno-/subtype) copies/ml IU/ml (genotype B3) undiluted not evaluated # (genotype H1) undiluted not evaluated # undiluted not evaluated # (genotype D8) undiluted not evaluated # (genotype H) undiluted not evaluated # (genotype G) undiluted not evaluated # (genotype F) undiluted not evaluated # undiluted not evaluated # (m) 1 : not evaluated # (m) 1 : not evaluated # (m) 1 : not evaluated # (m) 1 : not evaluated # RSV A (n) 1 : 200 not evaluated # RSV B (o) 1 : 33 not evaluated # RSV A (n) 1 : 100 not evaluated # / RSV B borderline (o) 1 : 66 not evaluated # (genotype 2B) undiluted not evaluated # undiluted not evaluated # (genotype 1E) undiluted not evaluated # (genotype 1A) undiluted not evaluated # (p) 1 : (p) 1 : : (p) 1 : # The quantitative results are not evaluated due the low number of analysis (without disadvantage for the certificates). m, n, o, p: Marked samples derive from corresponding sck materials diluted in consecutive steps. Non-marked samples derive from independent preparations. For sample , the reporting of "borderline" in test category 10 (Qualitative detection of RSV antigen) was accepted as additional correct result for rapid tests for antigen detection of RSV. Considering also the result "borderline" ensured that this sample would not have been misinterpreted as. Pre-evaluation Virology November December a.doc 12 of 16

13 Table 5: EQA Schemes Virus Genome Detection incl. Typing November/December 2016 Pre-evaluation Program Group RiliBÄK Sample Adenoes (DNA) mandary: Coronaes Enteroes HBV- Genotyping* HSV-1/ HSV-2 (DNA) * 363 mandary: mandary: qualitative Sample properties Target value of all methods copies/ml species Quantitative results D will be discussed in the final report. A C type (note on dilution) Adeno 2 1 : diluted Adeno 37 1 : diluted Adeno 31 1 : 300 diluted not evaluated # not evaluated # not evaluated # not evaluated # ---- CoV OC43 1 : diluted (q) MERS-CoV 1 : diluted (r) MERS-CoV 1 : diluted (r) CoV OC43 1 : diluted (q) not evaluated # not evaluated # ---- MERS-CoV 1 : diluted (r) Echo 30 1 : diluted (s) Quantitative results Coxsackie B will be discussed in 1 : diluted the final report Echo 30 1 : diluted (s) genotype B2 1 : diluted genotype D1 1 : 586 diluted genotype A1 1 : diluted genotype D3 1 : diluted $ = $ = HSV-2 1 : diluted (t) HSV-1 1 : diluted (u) HSV-2 1 : diluted (t) HSV-1 1 : diluted (u) HSV-2 1 : diluted (t) # The quantitative results are not evaluated due the low number of analysis (without disadvantage for the certificates). q, r, s, t, u: Marked samples derive from corresponding sck materials diluted in consecutive steps. Non-marked samples derive from independent preparations. $ The samples and are identical. * The EQA program Virus Genome Detection - HBV-Genotyping (396) is performed in cooperation with Paul-Ehrlich-Institut (WHO Collaborating Centre for Quality Assurance of Blood Products and in vitro Diagnostic Devices, Bundesinstitut für Impfsffe und biomedizinische Arzneimittel, Abteilung Virologie, PD Dr. Micha Nübling, Dr. Michael Chudy, Dr. Sally A. Baylis und Dr. Julia Kreß). Pre-evaluation Virology November December a.doc 13 of 16

14 Table 5 (contd.): EQA Schemes Virus Genome Detection incl. Typing November/December 2016 Pre-evaluation Program Group RiliBÄK Sample Human papilloma es (DNA) biopsy* ** Human Rhinoes Noro suspension of feces Rotaes suspension of feces Zika & & mandary: qualitative Sample properties Target value of all methods copies/ml species type (note on dilution) * Low Risk HPV 6 1 : 80 diluted ** ** High Risk HPV 18 1 : 20 diluted ** High Risk HPV 16 1 : 4 diluted ** High Risk HPV 18 1 : 40 diluted not evaluated # ---- HRV A type 30 1 : 500 diluted not evaluated # ---- HRV A type 49 1 : 50 diluted (v) not evaluated # ---- HRV A type 49 1 : 500 diluted (v) not evaluated # not evaluated # ---- genogroup II 1 : 440 diluted not evaluated # : 200 diluted not evaluated # not evaluated # not evaluated # not evaluated # not evaluated # not evaluated # ---- genogroup II 1 : 731 diluted genogroup II 1 : 794 diluted G2P[4] 1 : diluted G4P[8] 1 : diluted (w) G4P[8] 1 : 82 diluted (w) G4P[8] 1 : diluted (w) not evaluated # not evaluated # not evaluated # not evaluated # ---- African lineage (inactivated) 1 : 400 diluted (x) African lineage (inactivated) 1 : diluted (x) African lineage (inactivated) 1 : 40 diluted (x) # The quantitative results are not evaluated due the low number of analysis (without disadvantage for the certificates). v, w, x: Marked samples derive from corresponding sck materials diluted in consecutive steps.. Non-marked samples derive from independent preparations & The EQA program Virus Immunology - Zika Virus (338) is performed in cooperation with Bernhard-Nocht-Institut, Hamburg (Nationales Referenzzentrum für tropische Infektionserreger und WHO Collaborating Centre for Arbo and Haemorrhagic Fever Reference and Research; Prof. Dr. Stephan Günther, Prof. Dr. Dr. Jonas Schmidt-Chanasit and Dr. Petra Emmerich). Pre-evaluation Virology November December a.doc 14 of 16

15 Table 5 (contd.): EQA Schemes Virus Genome Detection incl. Typing November/December Pre-evaluation Program Group RiliBÄK Sample Influenza A-und B- es* inclusive influenza A(H1N1) pdm09 and avian influenza A (different subtypes) (genome/ antigen) 370* mandary: Sample properties and results considered as "correct" (target values) type/subtype strain origin for avian influenza A(H7N9) for seasonal influenza B for Influenza A(H1N1) pdm09 A/Anhui/1/2013 B/Brisbane/60/2008 (vaccine strain) A/California/7/2009 (vaccine strain) for seasonal influenza B for seasonal influenza A(H3N2) B/Phuket/3073/2013 (vaccine strain) A/Switzerland/ / 2013 (vaccine strain) allanic fluid (inactivated) (1 : 400 diluted) infected MDCKcells (lysate) (1 : 8 diluted) infected MDCKcells (lysate) (1 : 100 diluted) non-infected MDCK cells (lysate) infected MDCKcells (lysate) (1 : 150 diluted) infected MDCKcells (lysate) (1 : 250 diluted) * The EQA program for influenza A and B es, incl. influenza A(H1N1) pdm09 and avian influenza A (different subtypes), is performed in cooperation with Nationales Referenzzentrum für Influenza, Robert Koch-Institut, Berlin, Dr. Brunhilde Schweiger, and Nationales Referenzlabor für Aviäre Influenza, Bundesforschungsinstitut für Tiergesundheit, Friedrich-Loeffler-Institut, Insel Riems, PD Dr. Timm C. Harder. Pre-evaluation Virology November December a.doc 15 of 16

16 Table 6: EQA Schemes Virus Genome Detection for Drug Resistance Determination November/December Pre-evaluation Program Group RiliBÄK Sample CMV drug resistance 349 a) Sample properties and results considered as "correct" (target values) The EQA scheme (349) has been closed and is currently under evaluation. The target values will be specified in a separate pre-evaluation. You will be notified by . HBV drug resistance plasmid 397 b) The EQA scheme (397) has been closed and is currently under evaluation. The target values will be specified in a separate pre-evaluation. You will be notified by HCV drug resistance 399 c) The EQA scheme (399) has been closed and is currently under evaluation. The target values will be specified in a separate pre-evaluation. You will be notified by HIV-1 drug resistance standard program * plasmid** HIV-1 drug resistance additional program 383 d) 384 d) * * * ** Non-marked samples derive from independent preparations The EQA scheme (383) has been closed and is currently under evaluation. The target values will be specified in a separate pre-evaluation. You will be notified by . The EQA scheme (384) has been closed and is currently under evaluation. The target values will be specified in a separate pre-evaluation. You will be notified by . The above mentioned EQA schemes were performed in cooperation with: a) CMV drug resistance (349) Nationales Konsiliarlaborarium für Cymegalie (CMV) - (Schwerpunkt) CMV-Infektionen bei immunsupprimierten Personen Universitätsklinikum Ulm, Institut für Virologie; Prof. Dr. Thomas Mertens, Prof. Dr. Detlef Michel Nationales Konsiliarlaborarium für Cymegalie (CMV) - (Schwerpunkt) kongenitale/postnatale CMV-Infektionen Universitätsklinikum Tübingen, Institut für Medizinische Virologie; Prof. Dr. Gerhard Jahn, Prof. Dr. Klaus Hamprecht b) HBV drug resistance (397) Nationales Referenzzentrum für Hepatitis-B-Virus u. Hepatitis-D-Virus Justus-Liebig-Universität Gießen, Institut für Medizinische Virologie; Prof. Dr. Dieter Glebe, Dr. Christian Schüttler, Prof. Dr. Wolfram Gerlich, Prof. Dr. John Ziebuhr c) HCV drug resistance (399) Nationales Referenzzentrum für Hepatitis-C-Viren, Universitätsklinikum Essen, Institut für Virologie; Prof. Dr. Ulf Dittmer, Prof. Dr. Stefan Ross, Prof. Dr. Michael Roggendorf d) HIV-1 drug resistance - standard program (383) and additional program (384) Universitätsklinikum Erlangen, Institut für Klinische und Molekulare Virologie; Prof. Dr. Klaus Überla, Dr. Klaus Korn Ludwig-Maximilians-Universität München, Max-von-Pettenkofer Institut, Klinische Virologie; Prof. Dr. Oliver T. Keppler, Prof. Dr. Josef Eberle, Prof. Dr. Lutz Gürtler Nationales Referenzzentrum für Retroviren, Universitätsklinikum Frankfurt, Institut für Medizinische Virologie; Prof. Dr. Volkhard A.J. Kempf, Prof. Dr. Holger F. Rabenau, Prof. Dr. Annemarie Berger, PD Dr. Martin Stürmer Uniklinik Köln, Institut für Virologie; Prof. Dr. Herbert Pfister, Dr. Rolf Kaiser Pre-evaluation Virology November December a.doc 16 of 16