INSTAND e.V. · 346 Hepatitis C Virus September 2014 Report 20141116.doc Report about INSTAND e.V. EQAS 346 - September 2014 3 of 8 Notes to the evaluation Guideline of the German

Report External Quality Assessment Scheme

Group 346

Virus Immunology - Hepatitis C Virus

September 2014

INSTAND e.V. in cooperation with:

Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten (DVV)

Gesellschaft für Virologie (GfV) Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM)

Prof. Dr. Heinz Zeichhardt doc. Dr. Oliver Donoso Mantke Issued by:

INSTAND e.V. Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laboratorien e.V. Düsseldorf/Berlin, 16.11.2014

346 Hepatitis C Virus September 2014 Report 20141116.doc

Report about INSTAND e.V. EQAS 346 - September 2014 2 of 8

EQAS Adviser: Assistant EQAS Adviser: Prof. Dr. Heinz Zeichhardt doc. Dr. Oliver Donoso Mantke Charité - Universitätsmedizin Berlin c/o INSTAND e.V. Institut für Virologie, Campus Benjamin Franklin Ubierstr. 20, 40223 Düsseldorf Hindenburgdamm 27, 12203 Berlin Tel.: +49-(0)30-688197730; Fax: +49-(0)30-688197741 Tel.: +49-(0)30-84453625/23; Fax: +49-(0)30-84453626 Email: [email protected] Email: [email protected]

INSTAND Target Value Laboratories

Universität Duisburg-Essen, Universitätsklinikum Essen, Institut für Virologie, Nationales Referenzzentrum für Hepatitis-C-Viren, Nationales Konsiliarlaboratorium für Tollwut: Prof. Dr. U. Dittmer, Prof. Dr. S. Ross, Prof. Dr. M. Roggendorf

DRK Blutspendedienst Ost gGmbH, Institut f. Transfusionsmedizin Plauen: Dr. A. Karl, DBC K. Frank, Dr. K. Gubbe

Justus-Liebig-Universität Gießen, Institut für Medizinische Virologie, Nationales Referenzzentrum für Hepatitis-B-Virus und Hepatitis-D-Virus: PD Dr. D. Glebe, Dr. C. Schüttler, Prof. Dr. W. Gerlich, Prof. Dr. J. Ziebuhr

Labor Enders, Institut für Virologie, Infektiologie und Epidemiologie, Stuttgart: Prof. Dr. Gisela Enders & Partner

Paul-Ehrlich-Institut, Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel, Prüflabor für IVD, Langen: Dr. S. Nick, Dr. H. Scheiblauer

Universität Regensburg, Institut für Medizinische Mikrobiologie und Hygiene, Bereich Klinische Virologie und Infektionsimmunologie, Nationales Konsiliarlaboratorium für HAV und HEV: Prof. Dr. Dr. A. Gessner, Prof. Dr. B. Schmidt, Dr. J. Wenzel

Universitätsklinikum des Saarlandes, Institut für Virologie, Homburg/Saar: Prof. Dr. S. Smola, Prof. Dr. N. Müller-Lantzsch, Dr. J. Rissland

Universitätsklinikum Frankfurt, Institut für Medizinische Virologie, Frankfurt/Main, Nationales Referenzzentrum für Retroviren: Prof. Dr. O. T. Keppler, Prof. Dr. H. Rabenau, PD Dr. A. Berger, PD Dr. M. Stürmer

Universitätsklinikum Freiburg, Institut für Medizinische Mikrobiologie und Hygiene, Abteilung Virologie: Dr. D. Huzly, PD Dr. M. Panning, Prof. Dr. D. Neumann-Haefelin

Carried out by:

INSTAND e.V. Ubierstr. 20 40223 Düsseldorf Tel.: +49 (0)211 - 1592 13 0 Fax: +49 (0)211 - 1592 1330 Email: [email protected] Internet: www.instand-ev.de

mailto:[email protected]

mailto:[email protected]

http://www.instand-ev.de/



Notes to the evaluation

Guideline of the German Medical Association (RiliBÄK) The INSTAND External Quality Assessment (EQA) scheme "Virus Immunology - Hepatitis C Virus" (346) includes measurands / tests, which are subject to the new Guideline of the German Medical Association (Bundesärztekammer/ RiliBÄK = Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen).

Measurands / tests Specified RiliBÄK Section

Hepatitis C virus, antibodies against (anti-HCV)

B 2 "Qualitative determinations in laboratory medicine = Qualitative laboratoriumsmedizinische Untersuchungen"

Hepatits C virus, HCV antigen detection (HCV-Ag)

B 3 "Direct detection and characterization of infectious pathogens = Direkter Nachweis und Charakterisierung von Infektionserregern"

Information on changes as to the INSTAND External Quality Assessment (EQA) schemes in virus diagnostics have already been published in recent EQA scheme reports and postal mailing.

For details, please refer to

the information on the INSTAND EQA schemes in virus diagnostics and the new RiliBÄK (as of 24 January 2014)

Release of final reports of EQA schemes in virus diagnostics Each participant of this EQA scheme receives an email with a table allowing to directly open and/or save the report of the corresponding EQA scheme by clicking the respective download button.

Furthermore, each report of a defined EQA scheme will be released on the INSTAND homepage immediately after completion as PDF file under "EQAS / Reports / Year and Category (Virus immunology)" in English language (http://www.instandev.de/en/eqas/reports/) and in German language (http://www.instandev.de/ringversuche/kommentare/).

Certificate

Participation documents are sent out by post for this EQA scheme "Virus Immunology - Hepatitis C Virus" (346) as follows:

certificate of successful participation,

statement of participation,

statement of individual results.

The certificate of successful participation of this EQA scheme lists the respective measurands/tests, assigned to defined test categories, for which the requirements of the EQA scheme are met. Each test category is individually evaluated for the certificate of successful participation and separately listed in all participation and evaluation documents.

The EQA scheme "Virus Immunology - Hepatitis C Virus" (346) comprises the following test categories:

Test categories (10) Screening tests for the detection of anti-HCV and combined detection of anti-HCV and HCV antigen* (15) Tests for the isolated detection of HCV antigen** (20) Complementary tests for the detection of anti-HCV*

* measurand / test subject to RiliBÄK, Specified Section B 2 ** test subject to RiliBÄK, Specified Section B 3

http://www.instandev.de/uploads/tx_nfextinstandpdf/Info_virol_EQASs_-_new_RiliBAEK_and_organisation_as_of_24_January_2014_20140124a.pdf

http://www.instandev.de/en/eqas/reports/

http://www.instandev.de/ringversuche/kommentare/



Receiving a certificate of successful participation The evaluation criteria for the results of EQA schemes for the detection of virus specific antibodies follow the new Guideline of the German Medical Association, RiliBÄK, Specified Section E 2 (specific requirements on EQA schemes for qualitative laboratory medical analyses = Spezielle Anforderungen an Ringversuche bei qualitativen laboratoriumsmedizinischen Untersuchungen). For receiving a certificate of successful participation for a defined EQA scheme it is required that you analyzed all samples of the sample set correctly with the same method in the corresponding test categories (100% correct results according to the target values). Please note: A corresponding proceeding has been applied for tests for virus antigen and genome detection. Specifications will follow.

Example - Program "Virus Immunology - Hepatitis C Virus" (346): All 4 samples of the sample set have to be tested correctly with the same method in test category 10 "Screening tests for the detection of anti-HCV and combined detection of anti-HCV and HCV antigen". The same applies for test categories 15 and 20 of this EQA scheme.

Frequency of mandatory participation to this EQA scheme and validity of the certificates

The RiliBÄK defines the validity period of a certificate of successful participation for each of the EQA schemes stated in the Tables B 2-2 and B 3-2 (external quality assurance = Externe Qualitätssicherung/Ringversuche) of the Specified RiliBÄK Sections B 2 and B 3, respectively, as twice as long as the frequency for mandatory participation. This means that the validity period of the certificates of successful participation for this INSTAND EQA scheme will be one year. The validity of the certificates starts with the closing date of the EQA scheme (deadline for receipt of data). This date is printed on top of the certificates.

Tests which are subject to the RiliBÄK are indicated in the certificate of successful participation by "R" with reference to the corresponding Specified Section of the RiliBÄK.

Statement of individual results

For this EQA scheme "Virus Immunology - Hepatitis C Virus" (346) a statement of individual results is sent out by post together with the certificate of successful participation and statement of participation.

The statement of individual results lists for each measurand/test, assigned to defined test categories, the "correct result" with the target value as "valid result" as well as the reported result of the laboratory as "your results". This information is given line by line for each sample analyzed.

In addition a "+"-symbol indicates that a certificate of successful participation is issued for a given test category if the laboratory reached 100% correct results for all 4 samples according to the target values.

Overview of results

A summary of results is given for each of the samples in a table with a specification by test categories. A success rate is depicted for each of the samples reflecting the portion of "correct" results (expressed as "percent" correct results and as "number of correct results per number of total results reported"). In addition an overall success rate - based on the results for all samples of a sample set - is given for each of the test categories. See Table 2 of the annotation to this report.



Deployed EQA samples

Sera from patients with characteristic parameters of an acute or chronic or past hepatitis C are deployed in this EQA scheme "Virus Immunology - Hepatitis C Virus" (346). The positive samples are diluted in a negative serum pool of healthy blood donors. Negative samples are from a negative serum pool of healthy blood donors.

Target values

The evaluation of this EQA scheme is based on the determination of target values for each of the samples analyzed. Please note: Reference measurement methods for the determination of target values are not applicable for virus diagnostics.

The target value of a given EQA scheme sample - preset by the EQA scheme adviser - is confirmed by the INSTAND Target Value Laboratories prior to the distribution of the samples to the participants of this EQA scheme. The above mentioned INSTAND Target Value Laboratories test the samples for a second time during the course of the EQA scheme as regular participants. The final target value for a given sample is derived from the consensus value from all qualitative results. For this the results reported by the INSTAND Target Value Laboratories before and during the EQA scheme are considered.

Accepted statements of results according to the respective sample property

Qualitative results - "reactive/positive", "negative" or "borderline/indeterminate" (nominal characteristics) for anti-HCV and HCV-Ag The statement "not done" is allowed, when an analysis was not required for a given sample.

In case the results of a given EQA scheme deviate from the preset target value, it will be investigated whether the deviating results are due to the test performance in the laboratory or to test immanent problems of commercial or in-house-tests. This investigation is performed together with the INSTAND Target Value Laboratories under the auspices of the EQA scheme adviser and in cooperation with the Joint Diagnostic Council of DVV and GfV.

Determination of evaluation intervals

Not applicable



Annotation of the EQAS Adviser

Dear colleagues,

Below please find a detailed comment on this EQA scheme "Virus Immunology - Hepatitis C Virus" (346) September 2014 with:

Information about test categories, statement of results and evaluation criteria,

Summary of sample properties, target values, results and success rates,

Annex with detailed description of all reported qualitative results including differentiation according to test formats, manufacturers and names of test kits.

Number of participants in this EQA scheme: 400 laboratories 1 Test categories, statement of results and evaluation criteria for this EQA scheme The following statements of results were requested for each of the test categories in this EQA scheme which were the basis of evaluation (see Table 1):

Table 1: Test categories, statement of results and evaluation criteria

Test categories Statement of results

the following statements of results were requested

Evaluation criteria no. of correctly determined

samples for receiving a certificate of successful

participation

(10) Screening tests for the detection of anti-HCV or combined detection of anti-HCV and HCV antigen

reactive or

negative or

borderline

4 of 4 samples

(15) Tests for the isolated detection of HCV antigen

reactive or

negative or

borderline

4 of 4 samples

(20) Complementary tests for the detection of anti-HCV

positive or

negative or

indeterminate or

not done

4 of 4 samples

Reporting of results in the protocol sheets The simultaneous reporting of different results obtained with one and the same test cannot be accepted and will be evaluated as a missing value, e.g. the simultaneous reporting of a "reactive/positive" and "borderline/indeterminate" result for one and the same sample will not be accepted.

A result has not been considered for evaluation in case you had specified that this result should only be taken as additional information and ignored as valid result.

We ask you to report also the raw data of your test results (e.g. s/co, index etc.). We will start to show the evaluations of these raw data in due time. Please note for future EQA schemes that it is required to report complete results for all of the 4 samples for screening tests and complementary tests, respectively. In case of samples determined "negative" in screening tests please fill in at least "nd = not done", when you have not performed confirmation testing with such samples.



2 Summary of sample properties, target values, results and success rates

Table 2: Summary of sample properties, target values, results and success rates - testing for anti HCV and HCV-antigen

Sample No.

Sample properties Considered as

"correct" results (target values)

Success rates for all methods per sample

Sample source Dilutio

n

Screening tests

Test

category 10

HCV antigen

tests Test

category 15

Comple- mentary

tests Test

category 20

Scree-ningtests

Test

category 10

HCV antigen

tests Test

category 15

Comple-mentary

tests Test

category 20

346069* An anti-HCV positive serum of a patient with past hepatitis C (HCV PCR negative) was diluted with negative sera of healthy blood donors

1 : 130* reactive negative# positive 100%

(427/427) 100%#

(13/13)# 100%

(131/131)

346070* 1 : 65* reactive negative# positive 100%

(427/427) 100%

(13/13) 100%

(131/131)

346071 Pool serum; negative sera of healthy blood donors

---- negative negative/

nd§ negative/

nd§ 99.8%

(426/427) 100%#

(13/13)# 99.2%

(118/119)

346072

An anti-HCV positive serum of a patient with chronic hepatitis C (HCV PCR positive) was diluted with negative sera of healthy blood donors

1 : 20 reactive reactive# positive 100%

(427/427) 92.3%#

(12/13) # 99.2%

(130/131)

Success rates for all 4 samples in test categories 10, 15 and 20, respectively&

99.7%& (395/396)&

92.3%& (12/13)&

98.4%& (125/127)&

& The success rates for all 4 samples in test categories 10, 15 and 20, respectively, refer to the number of participating laboratories. Laboratories having reported results obtained by several methods in the corresponding test category are recorded only once.

* The samples 346069 and 346070 were the same dilutions of the same serum of the anti-HCV positive patient mentioned above. The dilution sera were identical.

# The anti-HCV positive samples 346069 and 346070 were confirmed as HCV RNA negative by quantitative HCV-PCR. The anti-HCV positive sample 346072 was confirmed as HCV RNA positive by quantitative HCV-PCR.

§ nd = not done



A detailed description of the results for all samples including a differentiation according to the test formats, manufacturers and names of test kits is given in the annex to this report: 3 Annex - Tables including differentiation according to test formats, manufacturers and names of test kits

3.1 Qualitative testing for anti-HCV and HCV-Ag (Test categories 10, 15 and 20)

We thank our colleagues of the above-mentioned INSTAND-Target Value Laboratories for their cooperation. Surplus samples of the current and previous EQA schemes in virus diagnostics are available for test assessment of your virus diagnostics. Please contact INSTAND e.V. for details. Thank you very much for your kind cooperation. Sincerely yours, Prof. Dr. H. Zeichhardt P.S. We would like to inform you about the new virological INSTAND EQA schemes that are performed on a regular basis starting in 2014 and 2015, respectively:

information on new virological EQA schemes (as of 10 November 2014)

http://www.instandev.de/uploads/tx_nfextinstandpdf/Information_new_virological_INSTAND_EQAS_2014_2015_20141110a.pdf

346 HCV Deckblatt qual EN.doc

INSTAND e. V., Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laboratorien e. V. (vormals Hämometerprüfstelle) - www.instandev.de in cooperation with Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) Gesellschaft für Virologie (GfV) Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM)

Annex

3.1 Qualitative testing for anti-HCV and HCV-Ag

Screening tests for the detection of anti-HCV and combined detection of anti-HCV and HCV antigen

(test category 10)

Tests for the exclusive detection of HCV antigen

(test category 15)

Complementary tests for the detection of anti-HCV

(test category 20)

Differentiation according to method, manufacturer and test name

Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laboratorien e. V. (INSTAND)in cooperation withDeutsche Vereinigung zur Bekämpfung der Viruskrankheiten e. V. (DVV)Gesellschaft für Virologie e. V. (GfV)Deutsche Gesellschaft für Hygiene und Mikrobiologie e. V. (DGHM)

EQAS Virology Sept. 2014

Virus immunology Hepatitis C (346)Qualitative results for sample 346069

10. Screening tests for the detection of anti-HCV and combined detection of anti-HCV and HCV antigen : reactive

Total test total reactive borderline negative Success rate

427 427 0 0 100.0%

Method / Manufacturer total reactive borderline negative Success rate

ELISA-anti-HCV (10) 26 26 0 0 100.0%

Siemens - Ezygnost Anti-HCV 4.0 11 11 100.0%Bio-Rad - Monolisa Anti-HCV PLUS 5 5 100.0%Ortho - Ortho HCV 3.0 ELISA-Test 5 5 100.0%Fujirebio - INNOTEST HCV Ab IV 3 3 100.0%Human - anti-HCV 1 1 100.0%DiaSorin - Murex anti-HCV (version 4.0) 1 1 100.0%

ELISA-anti-HCV+HCV Ag (11) 1 1 0 0 100.0%

Bio-Rad - Monolisa HCV Ag-Ab Ultra 1 1 100.0%

MEIA-anti-HCV AxSYM (20) 12 12 0 0 100.0%

Abbott - AxSYM HCV Version 3.0 12 12 100.0%

ChLIA-anti-HCV (30) 106 106 0 0 100.0%

Siemens - ADVIA Centaur HCV 60 60 100.0%Bio-Rad - Access HCV Ab plus 24 24 100.0%Abbott - PRISM HCV 8 8 100.0%DiaSorin - LIAISON XL Murex HCV Ab 7 7 100.0%Ortho - VITROS Anti-HCV 7 7 100.0%

ECLIA-anti-HCV (50) 129 129 0 0 100.0%

Roche - Elecsys Anti-HCV II 129 129 100.0%

CMIA-anti-HCV (60) 143 143 0 0 100.0%

Abbott - ARCHITECT Anti-HCV 143 143 100.0%

other anti-HCV (98) 10 10 0 0 100.0%

bioMerieux - VIDAS Anti-HCV 6 6 100.0%OraSure - OraQuick HCV Rapid Antibody Test 4 4 100.0%

CvirG / LgesQ Rv=1423 23.10.2014 14:18h �� Bl. 44

Grp. 346

Qualitative results for sample 346069

15. Tests for the isolated detection of HCV antigen : negative


13 0 0 13 100.0%


CMIA HCV Ag (33) 13 0 0 13 100.0%

Abbott - ARCHITECT HCV Ag 13 13 100.0%


20. Complementary tests for the detection of anti-HCV : positive

Total test total positive indet. negative Success rate

131 131 0 0 100.0%

Method / Manufacturer total positive indet. negative Success rate

Dot IA anti-HCV (20) 1 1 0 0 100.0%

Bio-Rad - Deciscan HCV plus 1 1 100.0%

Line IA (21) 129 129 0 0 100.0%

Fujirebio - INNO-LIA HCV Score 70 70 100.0%Mikrogen - recomLine HCV IgG 59 59 100.0%

Western Blot (30) 1 1 0 0 100.0%

MP Biomedicals - HCV BLOT Version 3.0 1 1 100.0%


Grp. 346




427 427 0 0 100.0%


ELISA-anti-HCV (10) 26 26 0 0 100.0%

Siemens - Ezygnost Anti-HCV 4.0 11 11 100.0%Bio-Rad - Monolisa Anti-HCV PLUS 5 5 100.0%Ortho - Ortho HCV 3.0 ELISA-Test 5 5 100.0%Fujirebio - INNOTEST HCV Ab IV 3 3 100.0%DiaSorin - Murex anti-HCV (version 4.0) 1 1 100.0%Human - anti-HCV 1 1 100.0%





ChLIA-anti-HCV (30) 106 106 0 0 100.0%

Siemens - ADVIA Centaur HCV 60 60 100.0%Bio-Rad - Access HCV Ab plus 24 24 100.0%Abbott - PRISM HCV 8 8 100.0%Ortho - VITROS Anti-HCV 7 7 100.0%DiaSorin - LIAISON XL Murex HCV Ab 7 7 100.0%

ECLIA-anti-HCV (50) 129 129 0 0 100.0%


CMIA-anti-HCV (60) 143 143 0 0 100.0%


other anti-HCV (98) 10 10 0 0 100.0%





13 0 0 13 100.0%


CMIA HCV Ag (33) 13 0 0 13 100.0%



Grp. 346




131 131 0 0 100.0%


Dot IA anti-HCV (20) 1 1 0 0 100.0%


Line IA (21) 129 129 0 0 100.0%


Western Blot (30) 1 1 0 0 100.0%



Grp. 346


10. Screening tests for the detection of anti-HCV and combined detection of anti-HCV and HCV antigen : negative


427 1 0 426 99.8%


ELISA-anti-HCV (10) 26 0 0 26 100.0%

Siemens - Ezygnost Anti-HCV 4.0 11 11 100.0%Ortho - Ortho HCV 3.0 ELISA-Test 5 5 100.0%Bio-Rad - Monolisa Anti-HCV PLUS 5 5 100.0%Fujirebio - INNOTEST HCV Ab IV 3 3 100.0%DiaSorin - Murex anti-HCV (version 4.0) 1 1 100.0%Human - anti-HCV 1 1 100.0%





ChLIA-anti-HCV (30) 106 0 0 106 100.0%


ECLIA-anti-HCV (50) 129 1 0 128 99.2%

Roche - Elecsys Anti-HCV II 129 1 128 99.2%

CMIA-anti-HCV (60) 143 0 0 143 100.0%


other anti-HCV (98) 10 0 0 10 100.0%





13 0 0 13 100.0%


CMIA HCV Ag (33) 13 0 0 13 100.0%



Grp. 346


20. Complementary tests for the detection of anti-HCV : negative


119 0 1 118 99.2%


Dot IA anti-HCV (20) 1 0 0 1 100.0%


Line IA (21) 117 0 1 116 99.1%

Fujirebio - INNO-LIA HCV Score 63 63 100.0%Mikrogen - recomLine HCV IgG 54 1 53 98.1%

Western Blot (30) 1 0 0 1 100.0%



Grp. 346




427 427 0 0 100.0%


ELISA-anti-HCV (10) 26 26 0 0 100.0%

Siemens - Ezygnost Anti-HCV 4.0 11 11 100.0%Ortho - Ortho HCV 3.0 ELISA-Test 5 5 100.0%Bio-Rad - Monolisa Anti-HCV PLUS 5 5 100.0%Fujirebio - INNOTEST HCV Ab IV 3 3 100.0%DiaSorin - Murex anti-HCV (version 4.0) 1 1 100.0%Human - anti-HCV 1 1 100.0%





ChLIA-anti-HCV (30) 106 106 0 0 100.0%


ECLIA-anti-HCV (50) 129 129 0 0 100.0%


CMIA-anti-HCV (60) 143 143 0 0 100.0%


other anti-HCV (98) 10 10 0 0 100.0%



15. Tests for the isolated detection of HCV antigen : reactive


13 12 1 0 92.3%


CMIA HCV Ag (33) 13 12 1 0 92.3%

Abbott - ARCHITECT HCV Ag 13 12 1 92.3%


Grp. 346




131 130 1 0 99.2%


Dot IA anti-HCV (20) 1 0 1 0 0.0%


Line IA (21) 129 129 0 0 100.0%


Western Blot (30) 1 1 0 0 100.0%



Documents

INSTAND e.V. · 346 Hepatitis C Virus September 2014 Report 20141116.doc Report about INSTAND e.V. EQAS 346 - September 2014 3 of 8 Notes to the evaluation Guideline of the German