Regulations, 2010 (ln_2010_21) | MT

Malta Government Gazette — Legal Notice 2010 21 — Regulations, 2010

Preamble — Regulations, 2010 Open official source

Suppliment tal-Gazzetta tal-Gvern ta’ Malta Nru. 18,531, 8 ta’Jannar, 2010

Taqsima B

L.N. 21 of 2010

PRODUCT SAFETY ACT

(CAP. 427)

In Vitro Diagnostic Medical Devices (Amendment)

Regulations, 2010

IN exercise of the powers conferred by article 38 of the Product

Safety Act, the Minister of Finance, the Economy and Investment, on

the advice of the Malta Standards Authority, has made the following

regulations

Malta Government Gazette — Legal Notice 2010 21 — Regulations, 2010

Reg. 1 — Regulations, 2010 Open official source

(1) The title of these regulations is the In Vitro Citation, scope

Diagnostic Medical Devices (Amendment) Regulations, 2010, and and

commencement.

they shall be read and construed as one with the In Vitro Diagnostic S.L. 427.16.

Medical Devices Regulations, hereinafter referred to as "the principal

regulations".

(2) These regulations transpose Commission Decision

2009/ 108/EC * amending Decision 2002/364/EC ** on common

technical specifications for in vitro diagnostic medical devices.

(3) These regulations shall apply to in vitro diagnostic medical

devices falling under the scope of the principal regulations.

(4) These regulations shall enter into force on 1st

December 2009. For devices placed on the market prior to this

date, these regulations shall apply from 1st December 2010.

Manufacturers are allowed to apply the requirements set out in these

regulations before such dates.

Malta Government Gazette — Legal Notice 2010 21 — Regulations, 2010

Reg. 2 — Regulations, 2010 Open official source

Schedule XI to the principal regulations shall be Substitutes

Schedule XI to

substituted by the following

the principal

regulations.

* OJ L.39, 10-02-2009, p.34.

** OJ L.131, 16-05-2002, p.17.

"Schedule XI

Based on Annex I of Commission Decision 2009/108/EC of 3 February 2009 on

common technical specifications (CTS) for in vitro diagnostic medical devices

1. SCOPE

The common technical specifications set out in this Schedule shall apply

for the purposes of Schedule II, List A.

2. DEFINITIONS AND TERMS

(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

Analytical sensitivity may be expressed as the limit of detection, i.e. the

smallest amount of the target marker that can be precisely detected.

Analytical specificity

Analytical specificity means the ability of the method to determine

solely the target marker.

Nucleic acid amplification techniques (NAT)

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

‘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 variations in method

parameters and provides an indication of its reliability during normal usage.

Whole system failure rate

The whole system failure rate means the frequency 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.

Malta Government Gazette — Legal Notice 2010 21 — Regulations, 2010

Reg. 3 — Regulations, 2010 Open official source

COMMON TECHNICAL SPECIFICATIONS

(CTS)

FOR

PRODUCTS REFERRED TO IN SCHEDULE II, LIST A.

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 or diagnostic tests, shall meet 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, for example 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 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.

3.1.5 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, mutants, etc.

3.1.8 Sensitivity with true positives and sero-conversion samples shall

be evaluated as follows

3.1.8.1 Diagnostic test sensitivity during 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). Seroconversion panels should start with a negative bleed(s) and should have

narrow bleeding intervals.

3.1.8.2 For blood screening devices (with the exception 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 tests 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 shall be identified as positive;

and

-

at least 40 early sero-conversion HIV samples 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 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.

3.1.11 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 tables. Specificity

shall be calculated using the frequency of repeatedly reactive (i.e. false

positive) results in blood donors negative for the target marker.

3.1.13 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;

- 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.

3.1.14 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 (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 using 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 the 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 belonging to Schedule II,

List A is not specifically covered by the common technical specification, the

common technical specification for a related device should be taken into

account. Related devices may be identified on different grounds, for example

by the same or similar intended use or by similar risks.

3.2 Additional Requirements for HIV antibody/antigen combined tests

3.2.1 HIV antibody/antigen combined tests intended 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 analytical sensitivity for p24

antigen.

3.2.2 HIV antibody/antigen combined tests intended for anti-HIV and

p24 detection which do not include claims for single p24 detection shall

follow Table 1 and Table 5, excluding criteria for analytical sensitivity for

p24.

3.3 Additional Requirements for Nucleic Acid Amplification Techniques

(NAT)

The performance evaluation criteria for NAT assays can be found in

Table 2.

3.3.1 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.

3.3.2 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 material.

3.3.3 Genotype detection shall be demonstrated by appropriate primer or

probe design validation and shall also be validated by testing characterised

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 specific field of application.

3.3.5 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-conversion) samples are included.

3.3.6 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.

3.3.7 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 times the 95% positive cut-off

virus concentration.

3.4 CTS for the manufacturer’s release testing of reagents and eagent

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

(Immunological assays only).

3.4.1 The manufacturer’s release testing criteria shall ensure that every

batch consistently identifies the relevant antigens, 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 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 blood group system KEL1 (K).

Criteria for performance evaluation of reagents and reagent products for

determining the blood groups antigens: ABO blood group system ABO1 (A),

ABO2 (B), ABO3 (A,B); Rh blood group B 9 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 direct 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 sample in further test systems;

-

by use of an alternative method.

3.5.3 Performance evaluations shall be performed

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

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.

3.5.6 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.

3.6. 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 blood group system KEL1 (K).

3.6.1 The manufacturer’s release testing criteria shall ensure that every

batch consistently identifies the relevant antigens, epitopes, and antibodies.

3.6.2 Requirements for manufacturers batch release testing are outlined in

Table 10.

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-

anti-HCV

HBsAg

anti-HBc

I/II

Diagnostic Positive

400 HIV-1

300 HTLV-I

400 (positive

400 Including 400

sensitivity specimens

100 HIV-2

100 HTLV-

samples)

subtype-

Including

including 40

II

consideration evaluation of

Including

non-B-

other HBV-

samples from

subtypes, all

markers

different stages of

available

infection and

HIV/1

reflecting

subtypes

different

should be

antibody patterns.

represented

by at least 3

Genotype 1-4: >

samples per

20 samples - per

subtype

genotype

(including non-a

sub-types of

genotype 4);

5: > 5 samples;

6: if available

Sero-

20 panels

To be

20 panels

To be defined

conversion

10 further

defined

10 further panels

10 further

when

panels

panels (at

when

(at Notified Body

panels (at

available

Notified Body

available

or manufacturer)

Notified Body

or

manufacturer)

Analytical

Standards

0.130 IU/ml

sensitivity

(Second

International

Standard for

HBsAg,

subtype adw2,

genotype A,

NIBSC code

00/588)

Specificity

Unselected

donors

(including1 st

time donors)

Hospitalized

patients

Potentially

cross-

reacting

blood-

specimens

(RF+, related

viruses,

pregnant

women, etc)

Table 2: NAT assays for HIV1, HCV, HBV, HTLV I/II (qualitative and

quantitative; not molecular typing)

HIV1

HCV

HBV

HTLV I/II

Acceptanc

e criteria

NAT

qualitative

quantitative

qualitative

quantitative

qualitative

quantitative

As for HIV

quantitative

Sensitivity

According

Detection

According

According to

Detection

to EP

limit: as for

to EP

EP

limit

validation

qualitative

validation

Detection

guideline

tests;

guideline

( 1 ): several

of

(1)

Quantific-

analytical

several

ation limit

dilution

sensitivity

dilution

dilutions

series into

(IU/ml;

series into

(half-log10

borderline

defined on

borderline

or less) of

concentra-

concentr-

WHO

concentra-

calibrated

tion;

ation;

standards or

tion;

reference

statistical

calibrated

statistical

prepara-

analysis

reference

analysis

tions,

(e.g. Probit

materials)

(e.g.

definition of

analysis)

analysis) on

Probit

lower, upper

on the

the basis of

analysis)

quantifi-

basis of at

at least 24

on the

cation limit,

least 24

replicates;

basis of at

precision,

replicates;

calculation

least 24

accuracy,

calculation

of 95% cut-

replicates;

"linear"mea

of 95%

off value

calculatio

suring

cut-off

n of 95%

range,

value

cut-off

"dynamic

value

range".

Reproduci-

bility at

different

concentra-

tion levels

to be shown

Genotype/

At least 10

Dilution

At least 10

As far as

subtype

samples per

series of all

samples

calibrated

detection/

subtype (as

relevant

per

genotype

quantific-

far as

genotypes/

genotype

reference

ation

available)

subtypes,

(as far as

materials

efficiency

preferably

available)

are

of

available

reference

materials,

as far as

available

Cell culture

Transcripts

supernatant

or plasmids

s (could

quantified

substitute

by

for rare

appropriate

HIV-1

meethods

subtypes)

may be

According

used

to EP

According

validation

to EP

guideline

validation

( 1 ) as far as

guideline ( 1 )

guideline

calibrated

( 1 ) as far as

as far as

subtype

calibrated

reference

subtype

materials

reference

are

materials

available;

are

in vitro

available;

available; in

transcripts

in vitro

vitro

could be an

transcripts

option

could be an

option

Diagnostic

500 blood

100 blood

500 blood

specificity

donors

negative

samples

HIV1

HCV

HBV

HTLV I/II

Acceptanc

e criteria

qualitative

quantitative

qualitative

quantitative

qualitative

quantitative

As for HIV

quantitative

By

As for

By assays

suitable

qualitative

design and/

assay

tests

or testing

or testing of

design

of at least

at least 10

evidence

10 human

other DNA-

human

(e.g.

flavivirus

virus

retrivirus

sequence

(e.g. HGV,

positive

(e.g. HIV-)

compari-

YFV)

samples

positive

son) and/

positive

samples

or testing

samples

of at least

10 human

retrovirus

(e.g.

HTLV)-

positive

samples

As for

qualitative

tests

At least 5

runs using

alternating

high

positive

(known to

occur

naturally)

and

negative

samples

Internal

control

preferably

to go

through the

whole

whole NAT

NAT

procedure

At least

99 / 100

assays

samples

positive

virus-

spiked with

spiked

spiked with

3 x the 95%

with 3 x

3 x the 95

pos cut-off

the 95%

% pos cut-

concentra-

pos cut-off

off

tion

concentra-

concentr-

tion

ation

( 1 ) European Pharmacopoeia guideline

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). Comparative results with

another NAT test system shall be generated in parallel.

For qualitative NATs a study on diagnostic sensitivity shall be performed using at least 10 sero-

conversion panels.

Comparative results with another NAT test system shall be generated in parallel.

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/II

Acceptance

criteria

Diagnostic Positive

Same criteria

Same criteria as

sensitivity specimens

as for

for screening

screening

assays

Sero-

Same criteria

Same criteria as

conversion

as for

for screening

panels

screening

assays

> 99 % (anti-

Negative

1000 blood

HBc: > 96 %)

specimens

donations 200

donations

clinical

200 clinical

specimens

specimens 200

specimens

specimens 200

200 samples

samples from

200 samples

samples from

from pregnant

pregnant

from pregnant

pregnant

women

100 potentially 100

100 potentially 100 potentially

interfering

potentially

interfering

samples

interfering

samples

Table 4: Confirmatory/supplementary assays for anti-HIV 1 and 2,

anti-HTLV I and II, anti-HCV, HBsAg

anti-HIV

anti-HTLV

HCV

HBsAg

Acceptance

Confirmatory Confirmatory Supplementary Confirmatory

criteria

Assay

Diagnostic

Positive

200 HIV-1

200 HTLV-I

300 HCV

300 HBsAg

Correct

sensitivity

specimens

and 100 HIV- and 100

(positive

identificationas

HTLV-II

samples)

positive (or

indeterminate),

not negative

Including

samples from

different

different stages

stages of

of infection and

of infection 20

infection and

reflecting

“high pos”

reflecting

different

samples (> 26

different

antibody

IU/ml); 20

antibody

patterns.

samples in the

patterns

Genotypes 1 -

cut-off range

4: > 20 samples

(including non-

a sub-types of

genotype 4);

5: > 5 samples;

6: if available

Sero-con-

15 sero-

version

conversion

seroconversion

panels

panels/ low

titre panels

anti-HIV

anti-HTLV

HCV

HBsAg

Acceptance

Confirmatory

Supplementary

Confirmatory

criteria

Assay

Analytical

Standards

Second

sensitivity

International

Standard for

HBsAg,

subtype adw2,

genotype A,

NIBSC code

00/588

Diagnostic

Negative

200 blood

10 false

No false-

specificity

specimens

donations

positives as

positive

available from

results/ (1) no

the

neutralisation

performance

evaluation of

the screening

assay. (1)

200 clinical

samples

including

pregnant

women

50 potentially

potentially

interfering

samples,

samples

samples,

including

samples with

indeterminate

indetermin-

results in

results in other

ate results in

other

confirmatory

other

confirmatory

assays

confirmatory

assays

Table 5: HIV 1 Antigen

HIV-1 Antigen Assay

Acceptance criteria

Diagnostic

Positive specimens

50 HIV-1 Ag-positive

Correct identification (after

sensitivity

50 cell culture supernatants

neutralisation)

including different HIV-1

subtypes and HIV-2

Sero-conversion panels

20 sero-conversion panels/

low titre panels

Analytical

Standards

HIV-1 p24 Antigen, 1st

≤ 2 IU/ml

sensitivity

International Reference

Reagent, NIBSC code: 90/

Diagnostic

200 blood donations 200

>99.5% after neutralisation

specificity

clinical samples 50

potentially interfering

samples

Table 6: Serotyping and Genotyping Assay: HCV

HCV Serotyping and Genotyping

Acceptance criteria

Assay

Diagnostic

Positive specimens

200 (positive samples) Including

> 95% agreement between

sensitivity

samples from different stages of

serotyping and genotyping

infection and reflecting different

> 95% agreement between

antibody patterns. Genotypes 1 -

genotyping and sequencing

4: > 20 samples (including non-a

sub-types of genotype 4);

5: > 5 samples;

6: if available

Diagnostic

Negative specimens

specificity

Table 7: HBV Markers: anti-HBs, anti HBc IgM, anti-HBe, HBeAg

anti-HBs

anti-HBc IgM

anti-HBe

HBeAg

Acceptance

criteria

Diagnostic

Positive

100 vaccinees

200 Including

> 98%

sensitivity

specimens 100 naturally

samples from

infected

different stages

different

persons

of

infection

of

infection

stages

of

(acute/chronic

infection

etc.)

(acute/chronic

etc.)

The

acceptance

criteria should

only

be

applied

on

samples from

acute infection

stage

Sero-con-

10 follow-ups When availa-

version

or

anti-HBs

ble

panels

sero-

conversions

Analytical

Standards

WHO

1st

HBe

- Anti-HBs

sensitivity

International

Referenzan-

<10 mIU/ml

Reference

tigen 82; PEI

Preparation

Germany

1977; NIBSC,

United

Kingdom

Diagnostic No

500 Including 200

blood

blood 200

blood

>98%

specificity negative

clinical

donations

specimens

samples

clinical

200 clinical

samples

50 potentially 50 potentially

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

Positive

>98%

sensitivity

specimens

Specifying

HBV- Specifying HBV-

markers

Diagnostic

Negative

>98%

specificity

specimens

Including

clinical Including clinical Including

clinical

samples

potentially 50

potentially

interfering samples interfering samples interfering samples

Table 9: Blood group antigens in the ABO, Rh and Kell blood group systems

Specificity

Number of tests per

Total number of samples

recommended method

to be tested for a launch

to be tested for a new

product

formulation, or use of

well-characterized

reagents

Anti-ABO1(anti-A),anti-

Anti-ABO2 (anti-B), Anti-

ABO3 (anti-A,B)

Anti-RH1 (anti-D)

Anti-RH2

(anti-C

),

anti-RH4

(anti-c),

anti-RH3 (anti-E)

Anti-RH5 (anti-e)

Anti-KEL1 (anti-K)

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 weak RH1 (D) and partial RH1 (D) samples, depending 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

Table 10: Batch release criteria for reagents and reagent products to

determine 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

A2B

Ax

B

Anti-ABO1 (anti-A)

2*

B

A1B

Anti-ABO2 (anti-B)

Ax

B

Anti-ABO3 (anti-A,B)

R1r

R2r

Weak

r’r

r’’r

rr

D

Anti-RH1 (anti-D)

2*

R1R2

R1r

r’r

R2R2 r’’r

rr

Anti-RH2 (anti-C)

R1R2

R1r

r’r

R1R1

Anti-RH4 (anti-c)

R1R2

R2r

r”r

R1R1 r’r

rr

Anti-RH 3 (anti-E)

R1R2

R2r

r”r

R2R2

Anti-RH5 (anti-e)

Kk

kk

Anti-KEL1 (anti-K)

(*) Only by recommended techniques where reactivity 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 unequivocal positive or negative results by all recommended

techniquesin 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.".

Regulations, 2010

Statutory Text (4 Articles)

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