The Annex to Decision 2002/364/EC is amended as follows:
Section 2 is amended as follows:
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. Devices intended solely to be used to monitor a previously determined marker or analyte are not considered first-line assays.’;
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.’;
Section 3 is amended as follows:
Sub-section 3.1.1 is replaced by the following:
Devices which detect virus infections shall meet the requirements for sensitivity and specificity 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.’;
Sub-section 3.1.3 is replaced by the following:
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 carried 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.’;
Sub-section 3.1.9 is replaced by the following:
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).’;
Sub-section 3.1.11 is replaced by the following:
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.’;
Sub-section 3.4.2 is replaced by the following:
The manufacturer’s batch release testing for first line assays shall include at least 100 specimens negative for the relevant analyte.’.
Table 1 is replaced by the following:
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’ |
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 | 21 000 blood donations | 1 000 blood donations | 1 000 blood donations | 1 000 blood donations | 1 000 blood donations | ≥ 99 % (anti-HBc: ≥ 96 %) |
| 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 | ||||
| 100 potentially interfering samples | 100 potentially interfering samples | 100 potentially interfering samples | 100 potentially interfering samples | 100 potentially interfering samples’ |
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
| a Acceptance criteria: no neutralisation for HBsAg confirmatory assay.’ | ||||||
| anti-HIV 1/2, HIV 1/2 Ag/Ab confirmatory assays | anti-HTLV I and II confirmatory assays | anti-HCV, HCV Ag/Ab supplementary assays | 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 (including non-a subtypes of genotype 4; Genotype 5: > 5 samples; Genotype 6: if available | 300 HBsAg Including samples from different stages of infection 20 ‘high pos’ samples (>26 IU/ml); 20 samples in the cut-off range | Correct identification as positive (or indeterminate), not negative |
| 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 blood donations | 200 blood donations | 10 false positives as available from the performance evaluation of the first line assaya. | No false-positive results/a 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 | |||