EN   EN 
 
 
 EUROPEAN  
COMMISSION   
Brussels, XXX   
[…](2019) XXX  draft  
ANNEX  
 
ANNEX  
to the  
Commission Implementing Decision  
amending Decision 2002/364/EC as regards definitions of first –line assays and 
confirmatory assays, requirements for devices for self -testing and requirements for HIV 
and HCV rapid tests, confirmatory and supplementary assays  
   
EN 2  EN ANNEX  
The Annex  to Decision 2002/364/EC  is amended as follows:  
(1) Section 2 is amended as follows:  
(a) the following definition of "First line assay" is inserted between the definition 
of "Whole system failure rate " and the definition of "Confirmation assay":  
‘First -line assay  
First-line assay means an assay used to detect a marker or analyte, and which may be 
followed by a confirmatory assay. D evices intended solely to be used to monitor a previously 
determined marker or analyte are not considered first -line assays. ’; 
(b) the definition of "Confirmation assay" is replaced by the following:  
‘Confirmatory assay  
Confirmatory assay means an assay used for the confirmation of  a reactive result from a first -
line assay.’;  
(2) Section 3 is amended as follows:  
(a) Sub-section 3.1.1. is replaced by the following:  
‘3.1.1 . Devices which detect virus infections shall meet the requirements for sensitivity and 
specif icity set out in Table 1 , Table 3, Table 4  and Table 5 , which apply to them taking 
account of the intended purpose  of the devices concerned , virus type and entities to be 
detected (antigen and/or antibody) . See also principle 3.1.11 for first -line assays.’ ; 
 
(b) Sub-section 3.1.3. is replaced by the following:  
‘3.1.3. Devices for self -testing shall meet the same CTS requirements for sensitivity and 
specificity as respective devices for professional use. Relevant parts of the performance 
evaluation shall be carr ied out (or repeated) by appropriate lay users to validate the operation 
of the device and the instructions for use . The lay users  selected  for the performance 
evaluation shall be representative of  the intended users groups.  
Performance evaluation of a device for self -testing  shall include, for each body fluid claimed 
for use with the  device , e.g. whole blood, urine, saliva, etc., at least 200 lay users that are 
known positive for the infection and at least 400 lay users that do not know their status, of 
which at least 200 are at high risk of acquiring the infection. The sensitivity and specificity of 
the device  for self -testing  in the hands of lay users shall  be defined against the confirmed 
patient infectious status. ’; 
(c) Sub-section 3.1.9. is replaced by th e following:  
‘3.1.9. Performance evaluation of first line assays shall include 25 positive (if available in the 
case of rare infections) ‘same day’ fresh serum samples (≤ 1 day after sampling). ’; 
(d) Sub-section 3.1.11. is replaced by the following:   
EN 3  EN ‘3.1.11. For performance evaluations for first line assays (Table 1 and Table 3) blood donor 
populations shall be investigated from at least two blood donation centers and consist of 
consecutive blood donations, which have not been selected to exclude first time  donors. ’; 
(e) Sub-section 3.4.2. is replaced by the following:  
‘3.4.2. The manufacturer’s batch release testing for first line assays shall include at least 100 
specimens negative for the relevant analyte. ’. 
(3) Table 1 is replaced by the following:  
EN 4  EN  
‘Table 1:  
First -line assays, excluding rapid tests: anti -HIV 1/2, HIV 1/2 Ag/Ab, anti -HTLV I/II, anti -HCV, HCV Ag/Ab, HBsAg, anti -HBc 
  anti-HIV 1/2, HIV 1/2 Ag/Ab  Anti -HTLV -I/II anti-HCV, HCV Ag/Ab  HBsAg  Anti -HBc  
Diagnostic 
sensitivity  Positive specimens  400 HIV -1 
100 HIV -2 
including 40 non -B-subtypes, all 
available HIV/1 subtypes shall 
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 subtypes 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 ( WHO 
International Standard:  
Third International 
Standard for HBsAg, 
subtypes ayw1/adw2, HBV 
genotype B4, NIBSC code: 
12/226)   
Specificity  Unselected donors (including 
first-time donors)  5 000 5 000 5 000 5 000 5 000 
Hospitalized patients  200 200 200 200 200 
Potentially cross -reacting 
blood -specimens (RF+, 
related viruses, pregnant 
women, etc)  100 100 100 100 100’  
EN 5  EN (4) Table 3 is replaced by the following:  
  
‘Rapid tests: anti -HIV 1/2, HIV 1/2 Ag/Ab,  anti -HCV, HCV Ag/Ab, HBsAg, anti -HBc, anti -HTLV I and II  
  anti-HIV 1/2, HIV 1/2 
Ag/Ab  anti-HCV, HCV Ag/Ab   HBsAg  anti-HBc anti-HTLV I and II  Acceptance criteria  
Diagnostic 
sensitivity  Positive specimens  Same criteria as in Table 
1 Same criteria as in Table 
1 Same criteria as in Table 
1 Same criteria as in Table 
1 Same criteria as in Table 
1 Same criteria as in Table  1 
Sero-conversion 
panels Same criteria as in Table 
1 Same criteria as in Table 
1 Same criteria as in Table 
1 Same criteria as in Table 
1 Same criteria as in Table 
1 Same criteria as in Table  1 
Diagnostic 
specificity  Negative 
specimens  1 000 blood donations  
200 clinical specimens  
200 samples from 
pregnant women  
100 potentially 
interfering samples  1 000 blood donations  
200 clinical specimens  
200 samples from 
pregnant women  
100 potentially 
interfering samples  1 000 blood donations  
200 clinical specimens  
200 samples from 
pregnant women  
100 potentially  
interfering samples  1 000 blood donations  
200 clinical specimens  
 
 
100 potentially 
interfering samples  1 000 blood donations  
200 clinical specimens  
200 samples from 
pregnant women  
100 potentially 
interfering samples  ≥ 99 %  
(anti-HBc: ≥ 96 %) ’ 
 
(5) Table 4 is replaced by the following:  
‘Confirmatory  and supplementary  assays for anti -HIV 1 / 2, HIV 1/2 Ag/Ab,  anti-HTLV I and II, anti -HCV,  HCV Ag/Ab, HBsAg  
  anti-HIV 1/2, HIV 1/2 Ag/Ab 
confirmatory assays  anti-HTLV I and II  
confirmatory assays  anti-HCV, HCV Ag/Ab 
supplementary assay s HBsAg  confirmatory assays  Acceptance criteria  
Diagnostic 
sensitivity  Positive 
specimens  200 HIV -1 and 100 HIV -2 
Including samples from different 
stages of infection and reflecting 
different antibody patterns  200 HTLV -I and 100 HTLV -
II 300 HCV (positive samples)  
Including samples from different 
stages of infection and reflecting 
different antibody patterns.  
Genotypes 1 – 4: > 20 samples 300 HBsAg  
Including samples from different 
stages of infection  
20 ‘high pos’ samples (>26 IU/ml); Correct identification as 
positive (or indeterminate), 
not negative   
EN 6  EN (including non -a subtypes of 
genotype 4;  
5: > 5 samples;  
6: if available   20 samples in the cut -off range  
Sero-conversion 
panels 15 sero -conversion panels/low 
titre panels  15 sero -conversion panels/low 
titre panels  15 sero -conversion panels/low titre 
panels  
Analytical 
sensitivity  Standards     Third International Standard for 
HBsAg, subtypes ayw1/adw2, HBV 
genotype B4, NIBSC code: 12/226   
Diagnostic 
specificity  Negative 
specimens  200 blood donations  
200 clinical samples including 
pregnant women  
50 potentially interfering 
samples, including samples with 
indeterminate results in other 
confirmatory assays  200 blood donations  
200 clinical samples 
including pregnant women  
50 potentially interfering 
samples, including samples 
with indeterminate results in 
other confirmatory assays  200 blood donations  
200 clinical samples including 
pregnant women  
50 potentially interfering samples, 
including samples with 
indeterminate results in other 
supplementary  assays  10 false positives as available from 
the performance evaluation of the 
first line  assay (1). 
50 potentially interfering samples  No false -positive results/ 
(1) no neutralisation ’ 
(1) Acceptance criteria : no neutralisation for HBsAg confirmatory assay.