EN    EN EN 
 EN    EN  COMMISSION OF THE E UROPEAN COMMUNITIES 
Brussels, 22.8.2008 
COM(2008) XXX final 
  
Draft 
COMMISSION DECISION 
of […] 
amending Commission Decision 2002/364/EC on  common technical sp ecifications for in 
vitro diagnostic medical devices 
(Text with EEA relevance) EN 2   EN Draft 
COMMISSION DECISION 
of  
amending Commission Decision 2002/364/EC on common technical specifications for in 
vitro  diagnostic medical devices 
(Text with EEA relevance) 
THE COMMISSION OF THE EUROPEAN COMMUNITIES, 
Having regard to the Treaty esta blishing the European Community, 
Having regard to Directive 98/79/EC of the European Parliament and of the Council of 
27 October 1998 on in vitro  diagnostic medical devices1, and in particular the second 
subparagraph of Article 5(3) thereof, 
Whereas: (1) The common technical specifications for in vitro  diagnostic medical devices are laid 
down in Commission Decision 2002/364/EC
2. 
(2) In the interest of public health and in or der to reflect technica l progress including the 
evolution in the performance and analytical sensitivity of devices, it is appropriate to 
revise the common technical specificati ons laid down in Decision 2002/364/EC. 
(3) The definition of rapid test should be refined in order for it to be more precise. For the 
sake of clarity further defi nitions should be included. 
(4) To bring the common technical specifications  in line with current scientific and 
technical practices it is nece ssary to update a number of  scientific and technical 
references. 
(5) The requirements for HIV screening assays shou ld be clarified. In order to ensure that 
the performance criteria appropriate to toda y’s technology is reflected in the common 
technical specifications it is  necessary to add requireme nts for HIV antibody/antigen 
combined tests and further specification of the sample requirements for certain assays. 
(6) The Annex to Decision 2002/364/EC should th erefore be amended accordingly and, 
for the purpose of clarity, be replaced. 
(7) Manufacturers whose devices are already on the market should be given a transition 
period in order to adapt to the new comm on technical specifications. On the other 
hand, in the interest of public health, manuf acturers who so wish should be able to 
apply the new common technical specifications before the expiry of the transition period.  
                                                
 
1 OJ L 331, 7.12.1998, p. 1. Directive as amended by Regulation (EC) No 1882/2003 (OJ L 284, 
31.10.2003, p. 1). 
2 OJ L 131, 16.5.2002, p. 17. EN 3   EN (8) The measures provided for in this Decision are in accordance with the opinion of the 
committee set up by Article 6(2) of Council Directive 90/385/EEC3. 
HAS ADOPTED THIS DECISION:  
Article 1 
The Annex to Decision 2002/364/EC is replaced by  the text in the Annex to this Decision. 
Article 2  
This Decision shall apply from 1 December 2010 for those devices first placed on the market 
prior to 1 December 2009. 
It shall apply from 1 December 2009 for all other devices. However, Member States shall allow manufacturers to apply th e requirements set out in the 
Annex before the dates set out in  the first and second paragraph. 
Article 3 
This Decision is addressed to the Member States. 
Done at Brussels,  
 For the Commission 
   Member of the Commission 
                                                
 
3 OJ L 189, 20.7.1990, p. 17. EN 4   EN ANNEX  
COMMON TECHNICAL SPECIFICATIONS (CTS) FOR IN VITRO -DIAGNOSTIC 
MEDICAL DEVICES 
1. SCOPE 
The common technical specificatio ns set out in this Annex sh all apply for the purposes of 
Annex II List A to Directive 98/79/EC. 
2. DEFINITIONS  AND  TERMS 
(Diagnostic) sensitivity 
The probability that the device gi ves a positive result in the presence of the target marker. 
True positive 
A specimen known to be positive for the target ma rker and correctly classified by the device. 
False negative 
A specimen known to be positive for the target marker and misclassified by the device. 
(Diagnostic) specificity 
The probability that the device gives a negative result in the absence of the target marker. 
False positive 
A specimen known to be negative for the target  marker and misclassified by the device. 
True negative 
A specimen known to be negative for the target ma rker and correctly classified by the device. 
Analytical sensitivity 
Analytical sensitivity may be e xpressed as the limit of detecti on, i.e. the sma llest amount of 
the target marker that ca n be precisely detected. 
Analytical specificity 
Analytical specificity means the ability of the method to determ ine solely the target marker. 
Nucleic acid amplification techniques (NAT) 
The term ‘NAT’ is used for tests for the detec tion and/or quantificatio n of nucleic acids by 
either amplification of a target sequence, by amplification of a signa l or by hybridisation. 
Rapid test 
‘Rapid test’ means qualitative or semi quantitative in vitro  diagnostic medical devices, used 
singly or in a small series, which involve non- automated procedures and have been designed 
to give a fast result. 
Robustness 
The robustness of an analytical  procedure means the capacity of  an analytical procedure to 
remain unaffected by small but deliberate vari ations in method parameters and provides an 
indication of its reliability during normal usage. 
Whole system failure rate EN 5   EN The whole system failure rate means the fre quency of failures when the entire process is 
performed as prescribed by the manufacturer. 
Confirmation assay  
Confirmation assay means an assay used for the confirmation of a reactive result from a 
screening assay. 
Virus typing assay 
Virus typing assay means an assay used for typing with already known positive samples, not 
used for primary diagnosis of infection or for screening. 
Sero-conversion HIV samples 
Sero-conversion HIV samples mean: 
– p24 antigen and/or HIV RNA positive and; 
– recognised by all of the antibody screening tests and; 
– positive or indeterminate confirmatory assays. 
Early sero-conversion HIV samples 
Early sero-conversion HIV samples mean: 
– p24 antigen and/or HIV RNA positive and; 
– not recognised by all of the antibody screening tests and; 
– indeterminate or negative confirmatory assays. 
3. COMMON TECHNICAL SPECIFICATIONS (CTS)  FOR PRODUCTS REFERRED TO IN 
ANNEX  II, LIST A OF DIRECTIVE 98/79/EC. 
3.1. CTS for performance evaluation of re agents and reagent products for the 
detection, confirmation and quantificat ion in human specimens of markers of 
HIV infection (HIV 1 and 2), HTLV I and II, and hepatitis B, C, D: 
General Principles: 
3.1.1.  Devices which detect virus infections placed on the market for use as either 
screening or diagnostic tests, shall m eet the requirements for sensitivity and 
specificity set out in Table 1. See also  principle 3.1.11 for screening assays. 
3.1.2.  Devices intended by the manufacturer for testing body fluids other than serum or 
plasma, e.g. urine, saliva, et c shall meet the same CTS re quirements for sensitivity 
and specificity as serum or plasma test s. The performance evaluation shall test 
samples from the same individuals in bot h the tests to be approved and in a 
respective serum or plasma assay. 
3.1.3.  Devices intended by the manufacturer for sel f-test, i.e. home use shall meet the same 
CTS requirements for sensitivity and specificity as respective devices for professional use. Relevant parts of the pe rformance evaluation shall be carried out 
(or repeated) by appropriate la y users to validate the opera tion of the device and the 
instructions for use. 
3.1.4.  All performance evaluations shall be carried out in di rect comparison with an 
established state of the art device. The device used for comparison shall be one 
bearing CE marking, if on the market at the time of the performance evaluation. EN 6   EN 3.1.5.  If discrepant test results are identified as part of an evaluation, these results shall be 
resolved as far as possible, for example: 
– by evaluation of the discrepant sa mple in further test systems; 
– by use of an alternat ive method or marker; 
– by a review of the clinic al status and diagnosis  of the patient; and 
– by the testing of follow-up-samples. 
3.1.6.  Performance evaluations shall be perf ormed on a population equivalent to the 
European population. 
3.1.7.  Positive specimens used in the performance evaluation shall be selected to reflect 
different stages of the respective diseas e(s), different antibody patterns, different 
genotypes, different subtypes, mutants etc. 
3.1.8.  Sensitivity with true positives and sero-c onversion samples shall be evaluated as 
follows: 
3.1.8.1.  Diagnostic test sensitivity during sero-conversio n has to represent th e state of the art. 
Whether further testing of the same or a dditional sero-conversion panels is conducted 
by the notified body or by the manufacturer the results shall c onfirm the initial 
performance evaluation data (see Table 1). Se roconversion panels should start with a 
negative bleed(s) and should ha ve narrow bleeding intervals. 
3.1.8.2.  For blood screening devices (with the excep tion of HBsAg and anti-HBc tests), all 
true positive samples shall be identified as  positive by the device  to be CE marked 
(Table 1). For HBsAg and anti-HBc test s the new device shall have an overall 
performance at least equivalent to that  of the established device (see 3.1.4). 
3.1.8.3.  Regarding HIV tests: 
– all sero-conversion HIV samples sha ll be identified as positive; and 
– at least 40 early sero-conversion HIV sa mples shall be tested. Results should 
conform to the state of the art. 
3.1.9.  Performance evaluation of screening assays shall include 25 positive (if available in 
the case of rare infections) “same day”  fresh serum and/or plasma samples ( ≤ 1 day 
after sampling). 
3.1.10.  Negative specimens used in a performance eval uation shall be defined so as to reflect 
the target population for which the te st is intended, for example blood donors, 
hospitalised patients, pregnant women etc. 
3.1.11.  For performance evaluations for screening assays (Table 1) blood donor populations 
shall be investigated from at least two blood donation centres and consist of 
consecutive blood donations, which have not been selected to exclude first time 
donors. 
3.1.12.  Devices shall have a specificity of at least 99.5% on blood donations, unless 
otherwise indicated in the accompanying tabl es. Specificity shall be calculated using 
the frequency of repeatedly reactive (i .e. false positive) results in blood donors 
negative for the target marker. 
3.1.13.  Devices shall be evaluated to establish the effect of potential in terfering substances, 
as part of the performance evaluation. Th e potential interfering substances to be 
evaluated will depend to some extent on the composition of the reagent and EN 7   EN configuration of the assay. Potential interferi ng substances shall be identified as part 
of the risk analysis required by the essential requirements for each new device but may include, for example: 
– specimens representing “related” infections; 
– specimens from multipara, i.e. women who have had more than one pregnancy, 
or rheumatoid factor positive patients; 
– for recombinant antigens, human antibodi es to components of  the expression 
system, for example anti E. coli, or anti yeast. 
3.1.14.  For devices intended by the manufacturer to be used with serum and plasma the 
performance evaluation must demonstrate se rum to plasma equivalency. This shall 
be demonstrated for at least 50 dona tions (25 positive and 25 negative). 
3.1.15.  For devices intended for use with plasma the performance evaluation shall verify the 
performance of the device us ing all anticoagulants which the manufacturer indicates 
for use with the device. This shall be demonstrated for at least 50 donations (25 
positive and 25 negative). 
3.1.16.  As part of the required risk analysis th e whole system failure rate leading to 
false-negative results shall be determined in repeat assays on low-positive specimens. 
3.1.17.  If a new in vitro  diagnostic medical device bel onging to Annex II List A is not 
specifically covered by the common techni cal specification, the common technical 
specification for a related device should be taken into account. Related devices may 
be identified on different grounds, e.g. by th e same or similar intended use or by 
similar risks. 
3.2. Additional Requirements for HIV an tibody/antigen combined tests 
3.2.1.  HIV antibody/antigen combined tests in tended for anti-HIV and p24 antigen 
detection which include claims for single p24  antigen detection shall follow Table 1 
and Table 5, including criteria for an alytical sensitivity for p24 antigen. 
3.2.2.  HIV antibody/antigen combined tests intende d for anti-HIV and p24 detection which 
do not include claims for single p24 dete ction shall follow Table 1 and Table 5, 
excluding criteria for analyt ical sensitivity for p24. 
3.3. Additional Requirements for Nucleic Ac id Amplification Techniques (NAT) 
The performance evaluation criteria for NAT assays can be found in Table 2. 
3.3.1.  For target sequence amplifica tion assays, a functionality co ntrol for each test sample 
(internal control) shall reflect the state of the art. This c ontrol shall as far as possible 
be used throughout the whole process, i.e.  extraction, amplifica tion/hybridisation, 
detection. 
3.3.2.  The analytical sensitivity or detection lim it for NAT assays shall be expressed by the 
95% positive cut-off value. This is the anal yte concentration where 95% of test runs 
give positive results following serial dilutio ns of an international reference material 
for example a WHO standard or calibrated reference material. 
3.3.3.  Genotype detection shall be demonstrated  by appropriate prim er or probe design 
validation and shall also be  validated by testing charac terised genotyped samples. 
3.3.4.  Results of quantitative NAT assays shall be  traceable to international standards or 
calibrated reference materials, if available, and be expressed in international units utilised in the specifi c field of application. EN 8   EN 3.3.5.  NAT assays may be used to detect  virus in antibody negative samples, 
i.e. pre-sero-conversion samples. Viruse s within immune-complexes may behave 
differently in comparison to free viruses, for example during a centrifugation step. It 
is therefore important that during r obustness studies, antibody-negative 
(pre-sero-conversion) samples are included. 
3.3.6.  For investigation of potential carry-over,  at least five runs with alternating 
high-positive and negative specimens sha ll be performed during robustness studies. 
The high positive samples shall comprise of samples with naturally occurring high virus titres. 
3.3.7.  The whole system failure rate leading to fa lse-negative results shall be determined by 
testing low-positive specimens. Low positive specimens shall contain a virus concentration equivalent to 3 times the 95% positive cut-off virus concentration. 
3.4. CTS for the manufacturer’s release testing of reagents and reagent products for 
the detection, confirmation and quantif ication in human sp ecimens of markers 
of HIV infection (HIV 1 and 2), HTLV  I and II, and hepatitis B, C, D 
(Immunological assays only) 
3.4.1.  The manufacturers release tes ting criteria shall ensure that every batch consistently 
identifies the relevant antig ens, epitopes, and antibodies. 
3.4.2.  The manufacturer’s batch release testing for screening assays shall include at least 
100 specimens negative for the relevant analyte. 
3.5. CTS for performance evaluation of reagents and reagent products for 
determining the following blood gro up antigens: ABO blood group system 
ABO1 (A), ABO2 (B), ABO3  (A,B); Rh blood group system RH1 (D), RH2 (C), 
RH3 (E), RH4 (c), RH5 (e); Kell blood group system KEL1 (K) 
Criteria for performance evaluation of reag ents and reagent products for determining 
the blood groups antigens: ABO blood group sy stem ABO1 (A), ABO2 (B), ABO3 
(A,B); Rh blood group system RH1 (D), RH2 (C), RH3 (E), RH4 (c), RH5 (e); Kell 
blood group system KEL1 (K) can be found in Table 9. 
3.5.1.  All performance evaluations shall be carried out in di rect comparison with an 
established state of the art device. The device used for comparison shall be one 
bearing CE marking, if on the market at the time of the performance evaluation. 
3.5.2.  If discrepant test results are identified as part of an evaluation, these results shall be 
resolved as far as possible, for example: 
– by evaluation of the discrepant sa mple in further test systems; 
– by use of an alternative method. 
3.5.3.  Performance evaluations shall be perf ormed on a population equivalent to the 
European population. 
3.5.4.  Positive specimens used in the performance evaluation shall be selected to reflect 
variant and weak antigen expression. 
3.5.5.  Devices shall be evaluated to establish the effect of potential in terfering substances, 
as part of the performance evaluation. Th e potential interfering substances to be 
evaluated will depend to some extent on the composition of the reagent and configuration of the assay. Potential interferi ng substances shall be identified as part 
of the risk analysis required by the es sential requirements for each new device. EN 9   EN 3.5.6.  For devices intended for use with plasma the performance evaluation shall verify the 
performance of the device us ing all anticoagulants which the manufacturer indicates 
for use with the device. This shall be  demonstrated for at least 50 donations. 
3.6. CTS for the manufacturers release testing of reagents and reagent products for 
determining the blood group antigens: ABO blood group system ABO1 (A), 
ABO2 (B), ABO3 (A,B); Rh blood group system RH1 (D), RH2 (C), RH3 (E), 
RH4 (c), RH5 (e); Kell bl ood group system KEL1 (K) 
3.6.1.  The manufacturer’s release testing criteria sh all ensure that ever y batch consistently 
identifies the relevant antig ens, epitopes, and antibodies. 
3.6.2.  Requirements for manufacturers batch re lease testing are outlined in Table 10.  
EN 10   EN Table 1 : “screening” assays: anti-HIV 1 and 2, anti-HTLV I and II, anti-HCV, HBsAg, anti-HBc 
 
  anti-HIV-1/2 anti-HTLV-I/II anti-HCV HBsAg anti-HBc 
Diagnostic sensitivity Positive specimens 400 HIV-1 
100 HIV-2 
including 40 non-B-subtypes, all available 
HIV/1 subtypes should be 
represented by at least 3 samples per subtype 300 HTLV-I 
100 HTLV-II 400 (positive samples) 
Including samples from 
different stages of infection and reflecting different 
antibody patterns. 
Genotype 1-4: > 20 samples per genotype (including 
non-a sub-types of 
genotype 4); 5: > 5 samples; 
6 : if available
 400 Including subtype-
consideration 400 
Including evaluation of 
other HBV-markers 
 Sero-conversion panels 20 panels 10 further panels 
(at Notified Body or 
manufacturer)) To be defined when 
available 20 panels 
10 further panels (at 
Notified Body or manufacturer)  20 panels 
10 further panels (at 
Notified Body or manufacturer .) To be defined when 
available 
Analytical sensitivity Standards    0.130 IU/ml (Second 
International Standard for 
HBsAg, subtype adw2, genotype A, NIBSC code: 
00/588)  
Specificity Unselected donors 
(including 1st time donors) 5000 5000 5000 5000 5000 
 Hospitalized patients 200 200 200 200 200 
 Potentially cross-reacting 
blood-specimens (RF+, 
related viruses, pregnant women, etc) 100 100 100 100 100  
EN 11   EN Table 2 : NAT assays for HIV1, HCV, HBV, HTLV I/II (qua litative and quantitative; not molecular typing) 
HIV1 HCV HBV HTLV I/II 
quantitative quantitative quantitative 
NAT qualitative quantitative qualitative 
As for HIV 
quantitative qualitative 
As for HIV 
quantitative qualitative 
As for HIV 
quantitative Acceptance 
criteria 
Sensitivity 
Detection limit Detection of 
analytical sensitivity 
(IU/ml; defined on WHO standards or 
calibrated reference 
materials) According to EP 
validation guideline (
1): several dilution 
series into borderline 
concentration; statistical analysis 
(e.g. Probit analysis) 
on the basis of at least 24 replicates; 
calculation of 95 % 
cut-off value Detection limit: as 
for qualitative tests; Quantification limit: 
dilutions (half-log10 
or less) of calibrated reference 
preparations, 
definition of lower, upper quantification 
limit, precision, 
accuracy, "linear" measuring range, 
"dynamic range". 
Reproducibility at different 
concentration levels 
to be shown According to EP 
validation guideline (
1): several dilution 
series into borderline 
concentration; statistical analysis 
(e.g. Probit analysis) 
on the basis of at least 24 replicates; 
calculation of 95 % 
cut-off value  According to EP 
validation guideline (
1): several dilution 
series into borderline 
concentration; statistical analysis 
(e.g. Probit analysis) 
on the basis of at least 24 replicates; 
calculation of 95 % 
cut-off value  According to EP 
validation guideline (
1): several dilution 
series into borderline 
concentration; statistical analysis 
(e.g. Probit analysis) 
on the basis of at least 24 replicates; 
calculation of 95 % 
cut-off value   
Genotype/subtype 
detection/quantification efficiency At least 10 samples 
per subtype (as far as available) Dilution series of all 
relevant genotypes/subtypes, 
preferably of 
reference materials, as far as available At least 10 samples 
per genotype (as far as available)  As far as calibrated 
genotype reference materials are 
available  As far as calibrated 
genotype reference materials are 
available   
 Cell culture 
supernatants ( could substitute for rare 
HIV-1 subtypes) Transcripts or 
plasmids quantified by appropriate 
methods may be 
used.        
 According to EP 
validation guideline 
(1) as far as 
calibrated subtype 
reference materials 
are available; in vitro  
transcripts could be 
an option  According to EP 
validation guideline 
(1) as far as 
calibrated subtype 
reference materials 
are available; in vitro
transcripts could be 
an option  According to EP 
validation guideline 
(1) as far as 
calibrated subtype 
reference materials 
are available; in vitro
transcripts could be 
an option  According to EP 
validation guideline 
(1) as far as 
calibrated subtype 
reference materials 
are available; in vitro
transcripts could be 
an option    
EN 12   EN HIV1 HCV HBV HTLV I/II 
quantitative quantitative quantitative 
NAT qualitative quantitative qualitative 
As for HIV 
quantitative qualitative 
As for HIV 
quantitative qualitative 
As for HIV 
quantitative Acceptance 
criteria 
Diagnostic 
specificity negative 
samples 500 blood donors 100 blood donors 500 blood donor s  500 blood donors  500 individual blood 
donations   
Potential cross 
reactive markers By suitable assay 
design evidence (e.g. sequence 
comparison) and/or 
testing of at least 10 human retrovirus 
(e.g. HTLV)-positive 
samples As for qualitative 
tests By assays design 
and/or testing of at least 10 human 
flavivirus (e.g. HGV, 
YFV) positive samples  By assays design 
and/or testing of at least 10 other DNA-
virus positive 
samples  By assay design 
and/or testing of at least 10 human 
retrovirus (e.g. HIV-) 
positive samples   
Robustness  As for qualitative 
tests        
Cross-contamination At least 5 runs using 
alternating high positive (known to 
occur naturally) and 
negative samples  At least 5 runs using 
alternating high positive (known to 
occur naturally) and 
negative samples  At least 5 runs using 
alternating high positive (known to 
occur naturally) and 
negative samples  At least 5 runs using 
alternating high positive (known to 
occur naturally) and 
negative samples   
Inhibition Internal control 
preferably to go through the whole 
NAT procedure  Internal control 
preferably to go through the whole 
NAT procedure  Internal control 
preferably to go through the whole 
NAT procedure  Internal control 
preferably to go through the whole 
NAT procedure   
Whole system failure 
rate leading to false-
neg results At least 100 samples 
virus-spiked with 3 x 
the 95 % pos cut-off 
concentration  At least 100 samples 
virus-spiked with 3 x 
the 95 % pos cut-off 
concentration  At least 100 samples 
virus-spiked with 3 x 
the 95 % pos cut-off 
concentration  At least 100 samples 
virus-spiked with 3 x 
the 95 % pos cut-off 
concentration  99 / 100 assays 
positive 
(1) European Pharmacopoeia guideline 
Note: Acceptance criteria for ‘whole system failure rate leading to false-neg results’ is 99/100 assays positive. 
For quantitative NATs a study shall be performed on at least 100 positive specimens reflecting the routine conditions of users (e.g. no pre-selection of specimens). Compara tive results with another NAT test system 
shall be generated in parallel. 
For qualitative NATs a study on diagnostic sensitivity shall be pe rformed using at least 10 sero-conversion panels. Comparative  results with another NAT test system shall be generated in parallel .  
EN 13   EN Table 3 : Rapid tests: anti-HIV 1 and 2, anti-H CV, HBsAg, anti-HBc, anti-HTLV I and II 
  anti-HIV 1/2 anti-HCV HBsAg anti-HB c anti-HTLV I/II Acceptance criteria 
Diagnostic sensitivity Positive specimens Same criteria as for 
screening assays Same criteria as for 
screening assays Same criteria as for 
screening assays Same criteria as for 
screening assays Same criteria as for 
screening assays Same criteria as for 
screening assays 
 Sero-conversion 
panels Same criteria as for 
screening assays Same criteria as for 
screening assays Same criteria as for 
screening assays Same criteria as for 
screening assays Same criteria as for 
screening assays Same criteria as for 
screening assays 
1000 blood donations 1000 blood donations 1000 blood d onations 1000 blood donations 1000 blood donations 
200 clinical specimens 200 clinical specimens 200 clinical specimens 200 clinical specimens 200 clinical specimens 
200 samples from 
pregnant women 200 samples from 
pregnant women 200 samples from 
pregnant women  200 samples from 
pregnant women Diagnostic specificity Negative specimens 
100 potentially 
interfering samples 100 potentially 
interfering samples 100 potentially 
interfering samples 100 potentially 
interfering samples 100 potentially 
interfering samples > 99 % (anti-HBc: >  96 %) 
  
EN 14   EN Table 4 : Confirmatory/supplementary assa ys for anti-HIV 1 and 2, anti-HTLV I and II, anti-HCV, HBsAg 
  anti-HIV Confirmatory A ssay anti-HTLV Confirmatory 
Assay HCV Supplementary Assay HBsAg Conf irmatory Assay Acceptance criteria 
Diagnostic sensitivity Positive specimens 200 HIV-1 and 100 HIV-2 200 H TLV-I and 100 HTLV-II 300 HCV (positive samples) 300 HBs Ag Correct identification as 
positive (or indeterminate), not negative 
  Including samples from 
different stages of infection and 
reflecting different antibody patterns  Including samples from 
different stages of infection and 
reflecting different antibody patterns. Genotypes 1 – 4: > 20 
samples (including non-a sub-
types of genotype 4); 5: > 5 samples; 6: if available Including samples from 
different stages of infection 
20 “high pos” samples (> 26 
IU/ml); 20 samples in the 
cut-off range  
 Sero-conversion 
panels 15 seroconversion panels/ low 
titre panels  15 seroconversion panels/ low 
titre panels 15 seroconversion panels/ low 
titre panels  
Analytical sensitivity Standards    Second International Standard 
for HBsAg, subtype adw2, 
genotype A, NIBSC code: 
00/588  
Diagnostic specificity Negative specimens 200 blood donations 200 blood donation 200 blood donations 10 false positives as avai lable 
from the performance 
evaluation of the screening 
assay. (1) No false-positive results/ (1) no 
neutralisation 
  200 clinical samples including pregnant women 200 clinical samples including 
pregnant women 200 clinical samples including 
pregnant women  
 
  50 potentially interfering 
samples, including samples with indeterminate results in 
other confirmatory assays
 50 potentially interfering 
samples including samples with indeterminate results in other 
confirmatory assays
 50 potentially interfering 
samples including samples with indeterminate results in other 
supplementary assays
 50 potentially interfering 
samples  
(1) Acceptance criteria no neutralisation for HBsAg confirmatory assay  
EN 15   EN Table 5 : HIV 1 Antigen 
  HIV-1 Antigen Assay Acceptance criteria 
Diagnostic sensitivity Positive specimens 50 HIV-1 Ag-positive 
50 cell culture supernatants including different 
HIV-1 subtypes and HIV-2 Correct identification (after neutralisation) 
 Sero-conversion panels 20 sero-c onversion panels/low titre panels  
Analytical sensitivity Standards HIV-1 p24 Antigen, 1st International Reference 
Reagent, NIBSC code: 90/636 ≤ 2 IU/ml  
Diagnostic specificity  200 blood donations 
200 clinical samples 
50 potentially interfering samples >99.5% after neutralisation 
 
Table 6 : Serotyping and Genotyping Assay: HCV 
  HCV Serotyping and Genotyping Assay Acceptance criteria 
Diagnostic sensitivity Positive specimens 200 (positive samples) 
Including samples from different stages of 
infection and reflecting different antibody patterns. 
Genotypes 1 – 4: > 20 samples (including non-a sub-types of genotype 4); 
5:> 
5 samples; 
6: if available > 95% agreement between serotyping and 
genotyping  
> 95% agreement between genotyping and 
sequencing 
Diagnostic specificity Negative specimens 100   
EN 16   EN Table 7 : HBV Markers: anti-HBs, anti HBc IgM, anti-HBe, HBeAg 
  anti-HBs anti-HBc IgM anti- HBe HBeAg Acceptance criteria 
Diagnostic sensitivity Positive specimens 100 vaccinees 
100 naturally infected 
persons 200 
Including samples from 
different stages of infection (acute/chronic etc.)  
The acceptance criteria 
should only be applied on samples from acute 
infection stage. 200  
Including samples from 
different stages of infection (acute/chronic etc.) 200  
Including samples from 
different stages of infection (acute/chronic etc.) >
 98 % 
 Sero-con-version panels 10 follow-ups or anti-HBs 
sero-conversions When available    
Analytical sensitivity Standards WHO 1st International 
Reference Preparation 1977; NIBSC, United 
Kingdom   HBe - Referenzantigen 82; 
PEI Germany Anti-HBs: <10 mIU/ml 
Diagnostic specificity Negative specimens 500 
Including clinical samples  
50 potentially interfering 
samples 200 blood donations 
200 clinical samples 
50 potentially interfering 
samples 200 blood donation 
200 clinical samples 
50 potentially interfering 
samples 200 blood donations 
200 clinical samples 
50 potentially interfering 
samples >98%  
EN 17   EN Table 8 : HDV markers: anti-HDV, anti-HDV IgM, Delta Antigen 
  anti-HDV anti-HDV IgM Delta Antigen  Acceptance criteria 
Diagnostic sensitivity Positive specimens 100 
Specifying HBV-markers 50 
Specifying HBV-markers 10 
Specifying HBV-markers > 98 % 
Diagnostic specificity Negative specimens 200 
Including clinical samples 50 potentially interfering 
samples 200 
Including clinical samples 50 potentially interfering 
samples 200 
Including clinical samples 50 potentially interfering 
samples >
 98 %  
EN 18   EN Table 9 : Blood group antigens in the ABO, Rh and Kell blood group systems 
 1 2 3 
Specificity Number of tests per recommended method To tal number of samples to be tested for a launch 
product Total number of samples to be tested for a new 
formulation, or use of well-characterized reagents 
Anti-ABO1 (anti-A), an ti-ABO2 (anti-B), anti-
ABO3 (anti-A,B)  500 3000 1000 
Anti-RH1 (anti-D) 500 3000 1000 
Anti-RH2 (anti-C ), anti- RH4 (anti-c), anti-RH3 
(anti-E) 100 1000 200 
Anti-RH5 (anti-e) 100 500 200 
Anti-KEL1 (anti-K) 100 500 200 
Acceptance criteria: 
All of the above reagents shall show comparable test results w ith established reagents with accep table performance with regard to claimed reactivity of the device. For esta blished reagents, where the application or 
use has been changed or extended, further testing should be carried out in accordance with the requirements outlined in column 1 (above). 
Performance evaluation of anti-D-reagents sh all include tests against a range of weak RH1 (D) and partial RH 1 (D) samples, depe nding on the intended use of the product. 
Qualifications: 
Clinical samples: 10% of the test population Neonatal specimens: > 2 % of the test population 
ABO samples: > 40% A, B positives 
‘weak D’: > 2% of RH1 (D) positives  
EN 19   EN Table 10 : Batch release criteria for reagents and reagent products to de termine blood group antigens in  the ABO, Rh and Kell blood 
group systems 
Specificity Testing Requirements on each reagent 
1. TEST REAGENTS  
Blood Group Reagents Minimum number of control cells to be tested 
 Positive reactions  Negative reactions 
 A1 A2B Ax   B 0  
Anti-ABO1 (anti-A) 2 2 2*   2 2  
 B A1B    A1 0  
Anti-ABO2 (anti-B) 2 2    2 2  
 A1 A2 Ax B  0   
Anti-ABO3 (anti-A,B) 2 2 2 2  4   
         
 R1r R2r WeakD   r’r r”r rr 
Anti-RH1 (anti-D) 2 2 2*   1 1 1 
 R1R2 R1r r’r   R2R2 r”r rr 
Anti-RH2 (anti-C) 2 1 1   1 1 1 
 R1R2 R1r r’r   R1R1   
Anti-RH4 (anti-c) 1 2 1   3   
 R1R2 R2r r”r   R1R1 r’r rr 
Anti-RH 3 (anti-E) 2 1 1   1 1 1 
 R1R2 R2r r”r   R2R2   
Anti-RH5 (anti-e) 2 1 1   3   
 Kk     kk   
Anti-KEL1 (anti-K) 4     3   
(*) Only by recommended techniques where r eactivity against these antigens is claimed  
Note: Polyclonal reagents must be tested against a wider panel of cells to confirm specificity and exclude presence of unwanted  
contaminating antibodies. 
Acceptance Criteria: 
Each batch of reagent must exhibit unequi vocal positive or negative results by all recommended techniques in accordance with th e results 
obtained from the performance evaluation data. 
2. CONTROL MATERIALS (RED CELLS ) 
The phenotype of red cells used in the control of blood typing reagents listed above should be confirmed using established devi ce.”