2002/364/EC: Commission Decision of 7 May 2002 on common technical specifications for in vitro-diagnostic medical devices (Text with EEA relevance) (notified under document number C(2002) 1344)
Date: 2002-05-07
Institutions: European Commission
Subjects: marketing standard, medical device, medical diagnosis, technical specification, test tube fertilisation

16.5.2002

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Official Journal of the European Communities

L 131/17

COMMISSION

COMMISSION DECISION

of 7 May 2002

on common technical specifications for in vitro-diagnostic medical devices

(notified under document number C(2002) 1344)

(Text with EEA relevance)

(2002/364/EC)

THE COMMISSION OF THE EUROPEAN COMMUNITIES,

Having regard to the Treaty establishing the European
Community,

Having regard to Directive 98/79/EC of the European Parlia-
ment and of the Council of 27 October 1998 on in vitro
diagnostic medical devices (1), and in particular the second
subparagraph of Article 5(3) thereof,

Whereas:

(1)

(2)

(3)

(4)

Directive 98/79/EC sets out the essential requirements
that in vitro diagnostic medical devices must meet when
they are placed on the market and conformity with
harmonised standards provides
a presumption of
conformity with the relevant essential requirements.

By way of exception to these general principles, the
drawing up of common technical specifications takes
account of a current practice in some Member States
whereby for selected devices mainly used for the evalu-
ation of the safety of blood supply and of organ dona-
tion, such specifications are adopted by the public
authorities. These common technical specifications can
be used for performance evaluation and re-evaluation.

Scientific experts from various interested parties have
been involved in the drafting of the common technical
specifications.

Directive 98/79/EC provides that Member States are to
presume compliance with the essential requirements in
respect of devices designed and manufactured in
conformity with common technical specifications drawn
up for certain devices in the highest risk category. These
specifications are to establish appropriate performance

(5)

(6)

evaluation and re-evaluation criteria, batch release
criteria, reference methods and reference materials.

Manufacturers are, as a general rule, to be required to
comply with the common technical specifications. If, for
duly justified reasons, manufacturers do not comply
with those specifications they must adopt solutions of a
level at least equivalent thereto.

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/EEC (2),

HAS ADOPTED THIS DECISION:

Article 1

The technical specifications set out
in the Annex to this
Decision are adopted as common technical specifications for in
vitro diagnostic medical devices in list A of Annex II
to
Directive 98/79/EC.

This Decision is addressed to the Member States.

Article 2

Done at Brussels, 7 May 2002.

For the Commission

Erkki LIIKANEN

Member of the Commission

(1) OJ L 331, 7.12.1998, p. 1.

(2) OJ L 189, 20.7.1990, p. 17.

L 131/18

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Official Journal of the European Communities

16.5.2002

CTS — COMMON TECHNICAL SPECIFICATIONS FOR IN VITRO-DIAGNOSTIC MEDICAL DEVICES

ANNEX

1.

SCOPE

These Common Technical Specifications are for the list of devices referred to in Annex II,

list A:

— reagents and reagent products,

including related calibrators and control materials,

for determining the

following blood groups: ABO system, Rhesus (C, c, D, E, e) anti-Kell,

— reagents and reagent products, including related calibrators and control materials, for the detection, confirma-
tion and quantification in human specimens of markers of HIV infection (HIV 1 and 2), HTLV I and II, and
hepatitis B, C and D.

2.

DEFINITIONS

(Diagnostic) sensitivity

The probability that the device gives a positive result in the presence of the target marker.

True positive

A specimen known to be positive for the target marker 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 marker and correctly classified by the device.

Analytical sensitivity

In the context of the CTS it may be expressed as the limit of detection: i.e. the smallest amount of the target
marker that can be precisely detected.

Analytical specificity

The ability of the method to determine solely the target marker.

Nucleic acid ampification techniques (NAT)

In the context of this document the term ‘NAT’ is used for tests for the detection and/or quantification of nucleic
acids by either amplification of a target sequence, by amplification of a signal or by hybridisation.

Rapid test

In this context the term ‘rapid test’ is understood to mean those tests which can only be used singly or in a small
series and which have been designed to give a rapid result for near patient testing.

Robustness

The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small but deliberate
variations in method parameters and provides an indication of its reliability during normal usage.

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L 131/19

Whole system failure rate

The whole system failure rate is the frequency of failures when the entire process is performed as prescribed by
the manufacturer.

3.

COMMON TECHNICAL SPECIFICATIONS (CTS) FOR PRODUCTS DEFINED IN ANNEX II, LIST A OF DIRECTIVE
98/79/EC.

3.1.

CTS for performance evaluation of reagents and reagent products for the detection, confirmation and
quantification 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 and/or diagnostic tests,

shall meet the same requirements for sensitivity and specificity (see Table 1).

3.1.2. Devices intended by the manufacturer for testing body fluids other than serum or plasma, e.g. urine, saliva, etc.
shall meet the same CTS requirements for sensitivity and specificity as serum or plasma tests. The performance
evaluation shall test samples from the same individuals in both the tests to be approved and in a respective serum
or plasma assay.

3.1.3. Devices intended by the manufacturer for self-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 performance evaluation
shall be carried out (or repeated) by appropriate lay users to validate the operation of the device and the
instructions for use.

3.1.4. All performance evaluations shall be carried out in direct comparison with an established device with acceptable
performance. Once the CE marking of IVDs is established, the device used for comparison shall be CE marked, if
on the market at the time of the performance evaluation.

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 sample in further test systems,

— by use of an alternative method or marker,

— by a review of the clinical status and diagnosis of the patient, and

— by the testing of follow-up-samples.

3.1.6.

Performance evaluations shall be performed 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
disease(s), different antibody patterns, different genotypes, different subtypes etc.

3.1.8.

For blood screening devices (with the exception of HBsAg tests), all true positive samples shall be identified as
positive by the device to be CE marked (Table 1). For HbsAg tests the new device shall have an overall
performance at least equivalent to that of the established device (see principle 3.1.4). Diagnostic test sensitivity
during the early infection phase (sero-conversion) has to represent the state of the art. Whether further testing of
the same or additional sero-conversion panels is conducted by the notified body or by the manufacturer the
results shall confirm the initial performance evaluation data (see Table 1).

3.1.9. Negative specimens used in a performance evaluation shall be defined so as to reflect the target population for
which the test is intended, for example blood donors, hospitalised patients, pregnant women etc.

3.1.10. 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.

3.1.11. Devices shall have a specificity of at least 99,5 % on blood donations, unless otherwise indicated in the
accompanying tables. Specificity shall be calculated using the frequency of repeatedly reactive (i.e. false positive)
results in blood donors negative for the target marker.

3.1.12. Devices shall be evaluated to establish the effect of potential interfering substances, as part of the performance
evaluation. The potential interfering substances to be evaluated will depend to some extent on the composition of
the reagent and configuration of the assay. Potential interfering 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;

L 131/20

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16.5.2002

— specimens from multipara, i.e. women who have had more than one pregnancy, or rheumatoid factor positive

patients,

— for recombinant antigens, human antibodies to components of the expression system, for example anti–E.

coli, or anti–yeast.

3.1.13. For devices intended by the manufacturer to be used with serum and plasma the performance evaluation must

demonstrate serum to plasma equivalency. This shall be demonstrated for at least 50 donations.

3.1.14. For devices intended for use with plasma the performance evaluation shall verify the performance of the device
using all anticoagulants which the manufacturer indicates for use with the device. This shall be demonstrated for
at least 50 donations.

3.1.15. As part of the required risk analysis the whole system failure rate leading to false-negative results shall be

determined in repeat assays on low-positive specimens.

3.2.

Additional requirements for nucleic acid amplification techniques (NAT)

The performance evaluation criteria for NAT assays can be found in Table 2.

3.2.1.

For target sequence amplification assays, a functionality control for each test sample (internal control) shall reflect
the state of the art. This control shall as far as possible be used throughout the whole process, i.e. extraction,
amplification/hybridisation, detection.

3.2.2. The analytical sensitivity or detection limit for NAT assays shall be expressed by the 95 % positive cut-off value.
This is the analyte concentration where 95 % of test runs give positive results following serial dilutions of an
international reference material for example a WHO standard or calibrated reference materials.

3.2.3. Genotype detection shall be demonstrated by appropriate primer or probe design validation and shall also be

validated by testing characterised genotyped samples.

3.2.4. 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 specific field of application.

3.2.5. NAT assays may be used to detect virus in antibody negative samples, i.e. pre-sero-conversion samples. Viruses
within immune –complexes may behave differently in comparison to free viruses,
for example during a
centrifugation step. It is therefore important that during robustness studies, antibody-negative (pre-sero-conver-
sion) samples are included.

3.2.6.

For investigation of potential carry-over, at least five runs with alternating high-positive and negative specimens
shall be performed during robustness studies. The high positive samples shall comprise of samples with naturally
occurring high virus titres.

3.2.7. The whole system failure rate leading to false-negative results shall be determined by testing low-positive
specimens. Low positive specimens shall contain a virus concentration equivalent to 3 x the 95 % positive cut-off
virus concentration.

3.3.

CTS for the manufacturer's release testing of reagents and reagent products for the detection, confirma-
tion and quantification in human specimens of markers of HIV infection (HIV 1 and 2), HTLV I and II,
and hepatitis B, C, D (immunological assays only)

3.3.1. The manufacturer's release testing criteria shall ensure that every batch consistently identifies the relevant

antigens, epitopes, and antibodies.

3.3.2. The manufacturer's batch release testing shall include at least 100 specimens negative for the relevant analyte.

3.4.

CTS for performance evaluation of reagents and reagent products for determining the blood group
antigens: ABO system (A, B), Rhesus (C, c, D, E, e) and Kell (K)

Criteria for performance evaluation of reagents and reagent products for determining the blood groups: ABO
system (A,B), Rhesus (C, c, D, E, e) and Kell (K) can be found in Table 9.

3.4.1. All performance evaluations shall be carried out in direct comparison with an established device with acceptable
performance. Once the CE marking of IVDs is established, the device used for comparison shall be CE marked, if
on the market at the time of the performance evaluation.

3.4.2.

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 sample in further test systems,

— by use of an alternative method.

3.4.3.

Performance evaluations shall be performed on a population equivalent to the European population.

16.5.2002

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3.4.4.

Positive specimens used in the performance evaluation shall be selected to reflect variant and weak antigen
expression.

3.4.5. Devices shall be evaluated to establish the effect of potential interfering substances, as part of the performance
evaluation. The potential interfering substances to be evaluated will depend to some extent on the composition of
the reagent and configuration of the assay. Potential interfering substances shall be identified as part of the risk
analysis required by the essential requirements for each new device.

3.4.6.

For devices intended for use with plasma the performance evaluation shall verify the performance of the device
using all anticoagulants which the manufacturer indicates for use with the device. This shall be demonstrated for
at least 50 donations.

3.5.

CTS for the manufacturer's release testing of reagents and reagent products for determining the blood
group antigens: ABO system (A, B), Rhesus (C, c, D, E, e), and Kell (K)

3.5.1. The manufacturer's release testing criteria shall ensure that every batch consistently identifies the relevant

antigens, epitopes, and antibodies.

3.5.2. Requirements for manufacturer's batch release testing are outlined in Table 10.

Diagnostic sensitivity

Positive specimens

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

40

non-B-

400 HIV 1
100 HIV 2
including
subtypes,
all available HIV 1 subtypes
should be represented by at
least
samples per
subtype

three

300 HTLV I
100 HTLV II

400
including genotypes 1a-4a:
at
least 20 samples/geno-
type genotypes 4 non-a
and 5:
at
type

least 10 samples/geno-

400
including
eration

subtype-consid-

400
including evaluation of other
HBV-markers

Sero-conversion panels

20 panels
10 further panels (at Noti-
fied Body or manufacturer)

To be defined when avail-
able

20 panels
10 further panels (at Noti-
fied Body or manufacturer)

20 panels
10 further panels (at Noti-
fied Body or manufacturer)

To be defined when available

Analytical sensitivity

Standards

Specificity

Unselected donors
(including 1st time donors)

Hospitalised patients

Potentially
blood-specimens
related
women etc.)

cross-reacting
(RF+,
viruses, pregnant

5 000

200

100

ng/ml

0,5
(French/UK
standard until WHO avail-
able)

5 000

200

100

5 000

200

100

5 000

200

100

5 000

200

100

L

1
3
1
/
2
2

E
N

O

f
f
i
c
i
a
l

J
o
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n
a
l

o
f

t
h
e

E
u
r
o
p
e
a
n
C
o
m
m
u
n
i
t
i
e
s

.

.

1
6
5
2
0
0
2

Table 2: NAT assays for HIV1, HCV, HBV, HTLV I/II (qualitative and quantitative; not molecular typing)

.

.

1
6
5
2
0
0
2

HIV 1

HCV

HBV

HTLV I/II

NAT

qualitative

quantitative

qualitative

quantitative

As for HIV
quantitative

qualitative

quantitative

As for HIV
quantitative

qualitative

quantitative Acceptance

criteria

E
N

As for HIV
quantitative

Sensitivity
Detection limit
Detection of
analytical
sensitivity (IU/ml; defined
on WHO standards or
calibrated reference mate-
rials)

series

According to EP valida-
tion guideline (1): several
dilution
into
borderline
concentra-
tion;
statistical analysis
(e.g.
Probit analysis) on the
basis of
least 24
at
replicates; calculation of
95 % cut-off value

Detection limit:
as for qualitative tests;
Quantification limit:
dilutions (half-log 10 or
less) of calibrated refer-
ence preparations, defi-
lower, upper
nition of
quantification
limit,
accuracy,
precision,
‘measuring
‘linear’,
‘dynamic range’
range’
Reproducibility
at
concentration
different
levels to be shown

series

According to EP valida-
tion guideline (1): several
into
dilution
borderline
concentra-
tion; statistical analysis
(e.g. Probit analysis) on
the basis of at least 24
replicates; calculation of
95 % cut-off value

series

According to EP valida-
tion guideline (1): several
into
dilution
borderline
concentra-
tion; statistical analysis
(e.g. Probit analysis) on
the basis of at least 24
replicates; calculation of
95 % cut-off value

series

According to EP valida-
tion guideline (1): several
dilution
into
borderline
concentra-
tion; statistical analysis
(e.g. Probit analysis) on
the basis of at least 24
replicates; calculation of
95 % cut-off value

Genotype/subtype detec-
tion/quantification
effi-
ciency

At least 10 samples per
genotype
as
(as
available)

far

At least 10 samples per
subtype (as far as avail-
able)
superna-
culture
Cell
tants
(could substitute
for rare HIV 1 subtypes)

all
Dilution series of
relevant
genotypes/
subtypes, preferably of
reference materials, as
far as available
Transcripts or plasmids
quantified
appro-
priate methods may be
used

by

calibrated

According to EP valida-
tion guideline (1) As far
as
subtype
reference materials are
in vitro tran-
available;
scripts
an
be
option

could

calibrated

According to EP valida-
tion guideline (1) as far
as
subtype
reference materials are
in vitro tran-
available;
scripts
an
be
option

could

as

far

As
genotype
materials are available

calibrated
reference

as

far

As
genotype
materials are available

calibrated
reference

calibrated

According to EP valida-
tion guideline (1) as far
as
subtype
reference materials are
in vitro tran-
available;
scripts
an
be
option

could

calibrated

According to EP valida-
tion guideline (1) as far
as
subtype
reference materials are
in vitro tran-
available;
scripts
an
be
option

could

O

f
f
i
c
i
a
l

J
o
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n
a
l

o
f

t
h
e

E
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p
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a
n
C
o
m
m
u
n
i
t
i
e
s

L

1
3
1
/
2
3

HIV 1

HCV

HBV

HTLV I/II

NAT

qualitative

quantitative

qualitative

quantitative

As for HIV
quantitative

qualitative

quantitative

As for HIV
quantitative

qualitative

quantitative Acceptance

criteria

As for HIV
quantitative

Diagnostic
negative samples

specificity

Potential
markers

cross

reactive

500 blood donors

100 blood donors

500 blood donors

500 blood donors

By suitable assay design
evidence (e.g. sequence
and/or
comparison)
least 10
testing of at
human retrovirus
(e.g.
HTLV) positive samples

As for qualitative tests

By assays design and/or
least 10
testing of at
(e.g.
human flavivirus
HGV,
positive
samples

YFV)

By assays design and/or
testing of at
least 10
other DNA-virus posi-
tive samples

Robustness

As for qualitative tests

Cross-contamination

Inhibition

At
least 5 runs using
alternating high positive
(known to occur natu-
negative
rally)
samples

and

Internal control prefer-
ably to go through the
whole NAT procedure

Whole system failure rate
leading
false-neg
to
results

At
least 100 samples
virus-spiked with 3 ×
the 95 % pos cut-off
concentration

(1) European Pharmacopoeia guideline.

At
least 5 runs using
alternating high positive
(known to occur natu-
negative
rally)
samples

and

Internal control prefer-
ably to go through the
whole NAT procedure

At
least 100 samples
virus-spiked with 3 ×
the 95 % pos cut-off
concentration

At
least 5 runs using
alternating high positive
(known to occur natu-
negative
rally)
samples

and

Internal control prefer-
ably to go through the
whole NAT procedure

At
least 100 samples
virus-spiked with 3 ×
the 95 % pos cut-off
concentration

Nota: Acceptance criteria for ‘whole system failure rate leading to false-neg results’

is 99/100 assays positive.

500 individual blood
donations

By assays design and/or
least 10
testing of at
(e.g.
human retrovirus
HIV) positive samples

At
least 5 runs using
alternating high positive
(known to occur natu-
negative
rally)
samples

and

Internal control prefer-
ably to go through the
whlole NAT procedure

At
least 100 samples
virus-spiked with 3 ×
the 95 % pos cut-off
concentration

99/100
assays
positive

L

1
3
1
/
2
4

E
N

O

f
f
i
c
i
a
l

J
o
u
r
n
a
l

o
f

t
h
e

E
u
r
o
p
e
a
n
C
o
m
m
u
n
i
t
i
e
s

.

.

1
6
5
2
0
0
2

Table 3: Rapid tests: anti HIV 1 and 2, anti HCV, HBsAg, anti HBc, anti HTLV I and II

Anti-HIV 1/2

Anti-HCV

HBsAg

Anti-HBc

Anti-HTLV I/III

Acceptance criteria

Diagnostic sensitivity

Positive specimens

criteria

Same
screening assays

as

for

criteria

Same
screening assays

as

for

criteria

Same
screening assays

as

for

criteria

Same
screening assays

as

for

criteria

Same
screening assays

as

for

criteria

Same
screening

as

for
assays

Diagnostic specificity

Negative
mens

speci-

1 000 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 preg-
nant women

200 samples from preg-
nant women

200 samples from preg-
nant women

200 samples from preg-
nant women

100 potentially
fering samples

inter-

100 potentially
fering samples

inter-

100 potentially
fering samples

inter-

100 potentially
fering samples

inter-

100 potentially
fering samples

inter-

.

.

1
6
5
2
0
0
2

E
N

O

f
f
i
c
i
a
l

J
o
u
r
n
a
l

o
f

t
h
e

E
u
r
o
p
e
a
n
C
o
m
m
u
n
i
t
i
e
s

L

1
3
1
/
2
5

Table 4: Confirmatory/supplementary assays for anti-HIV 1 and 2, anti-HTLV I and II, anti-HCV, HBsAg

Anti-HIV confirmatory assay

Anti-HTLV confirmatory assay

HCV supplementary assay

HbsAg confirmatory assay

Acceptance criteria

Diagnostic sensitivity

Positive specimens

200 HIV 1 and 100 HIV 2 200 HTLV I and 100 HTLV

300 HCV

300 HBsAG

II

samples

from
Including
different stages of infection
and reflecting different anti-
body patterns

samples

from
Including
different stages of infection
and reflecting different anti-
body patterns genotypes 1
- 4a: 15 samples; genotypes
4 (non a), 5: five samples;
six:

if available

samples

from
Including
different stages of infection
20 ‘high pos’ samples (> 50
ng HBsAg/ml); 20 samples
in the cut-off range

Correct
positive (or
not negative

identification

as
indeterminate),

Sero-conversion panels

15 seroconversion panels/
low titre panels

15 seroconversion panels/
low titre panels

15 seroconversion panels/
low titre panels

Analytical sensitivity

Standards

Diagnostic specificty

Negative specimens

200 blood donations

200 blood donations

200 blood donations

clinical

200
samples
including pregnant women

clinical

200
samples
including pregnant women

clinical

200
samples
including pregnant women

50 potentially interfering
samples, including samples
with indeterminate results
in
confirmatory
assays

other

50 pontentially interfering
samples including samples
with indeterminate results
in
confirmatory
assays

other

50 potentially interfering
samples including samples
with indeterminate results
in
supplementary
assays

other

(1) Acceptance criteria no neutralisation for HBsAg confirmatory assay.

HBsAg
NIBSC, WHO)

standards

(AdM,

20 false-positives
corresponding
assay (1)

in the
screening

50 potentially interfering
samples

No false-positive results/ (1)
no neutralisation

L

1
3
1
/
2
6

E
N

O

f
f
i
c
i
a
l

J
o
u
r
n
a
l

o
f

t
h
e

E
u
r
o
p
e
a
n
C
o
m
m
u
n
i
t
i
e
s

.

.

1
6
5
2
0
0
2

Diagnostic sensitivity

Positive specimens

Table 5: HIV 1 Antigen

HIV 1 antigen assay

Acceptance criteria

50 HIV 1 Ag-positive
50 cell culture supernatants including different
HIV 1 subtypes and HIV 2

Correct

identification

(after

neutralisation)

Diagnostic specificity

Diagnostic specificity

Sero-conversion panels

20 sero-conversion panels/low titre panels

Standards

ADM or 1st

international reference

< 50 pg/ml

200 blood donations
200 clinical samples
50 potentially interfering samples

≥ 99,5 % after neutralisation

Table 6: Serotyping Assay: HCV

Diagnostic sensitivity

Positive specimens

HCV 1 serotyping assay

Acceptance criteria

200
incl. genotypes 1-4a: > 20 samples.
4 (non a);
5: > 10 samples,
if available
6:

≥ 95 % agreement between serotyping and geno-
typing

Diagnostic specificity

Negative specimens

100

.

.

1
6
5
2
0
0
2

E
N

O

f
f
i
c
i
a
l

J
o
u
r
n
a
l

o
f

t
h
e

E
u
r
o
p
e
a
n
C
o
m
m
u
n
i
t
i
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s

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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
persons

naturally

infected

200
including
from
different stages of infection
(acute/chronic etc.)

samples

200
including
from
different stages of infection
(acute/chronic etc.)

samples

200
including
from
different stages of infection
(acute/chronic etc.)

samples

≥ 98 %

Sero-con-version panels

10 follow-ups or anti/HBs
sero-conversions

When available

Analytical sensitivity

Standards

WHO standard

PEI standard

Anti-HBs: < 10 mIU/ml

Diagnostic specificity

Negative specimens

500
including clinical samples

200 blood donations

200 blood donations

200 blood donations

≥ 98 %

200 clinical samples

200 clinical samples

200 clinical samples

50 potentially interfering
samples

50 potentially interfering
samples

50 potentially interfering
samples

50 potentially interfering
samples

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

Diagnostic specificity

Negative specimens

200
including clinical samples
50
potentially
samples

interfering

200
including clinical samples
50
potentially
samples

interfering

200
including clinical samples
50
potentially
samples

interfering

≥ 98 %

≥ 98 %

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E
N

O

f
f
i
c
i
a
l

J
o
u
r
n
a
l

o
f

t
h
e

E
u
r
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p
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a
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C
o
m
m
u
n
i
t
i
e
s

.

.

1
6
5
2
0
0
2

Table 9: Blood Groups ABO, Rhesus (C, c, D, E, e) and Kell

1

2

3

Specificity

Number of tests per recommended method

Total 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-characterised reagents

Anti-A, B and AB

Anti-D

Anti-C, c, E

Anti-e

Anti-K

500

500

100

100

100

3 000

3 000

1 000

500

500

1 000

1 000

200

200

200

Acceptance criteria:
all of the above reagents shall show comparable test results with established reagents with acceptable performance with regard to claimed reactivity of the device. For established 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 shall

include tests against a range of week RhD and partial Rh samples, depending on the intended use of the product.

Qualifications:
clinical samples:
Neonatal specimens:
ABO samples:
‘weak D’:

10 % of the test population
> 2 % of the test population
> 40 % A, B positives
> 2 % of Rhesus positives

.

.

1
6
5
2
0
0
2

E
N

O

f
f
i
c
i
a
l

J
o
u
r
n
a
l

o
f

t
h
e

E
u
r
o
p
e
a
n
C
o
m
m
u
n
i
t
i
e
s

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L 131/30

EN

Official Journal of the European Communities

16.5.2002

Table 10: Batch release criteria for Blood Groups ABO, Rhesus (C, c, D, E, e), and Kell

Specificity Testing Requirements on each reagent

1. Test reagents

Acceptance Criteria:

Each batch of reagent must exhibit unequivocal positive or negative results by all recommended techniques in accordance
with the 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 device.