|
|
Home
| Databases
| WorldLII
| Search
| Feedback
Maltese Laws |
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:
1. (1) The title of these regulations is the In Vitro Diagnostic Medical Devices (Amendment) Regulations, 2010, and they shall be read and construed as one with the In Vitro Diagnostic 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.
Citation, scope and commencement.
S.L. 427.16.
Substitutes Schedule XI to the principal regulations.
* OJ L.39, 10-02-2009, p.34.
** OJ L.131, 16-05-2002, p.17.
B 154
"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
B 155
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.
B 156
3. 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.
B 157
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:
and
- all sero-conversion HIV samples shall be identified as positive;
- 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:
B 158
- 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
B 159
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).
B 160
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.
B 161
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 |
Diagnostic sensitivity | 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 (including1st 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 |
B 162
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 | quantitative | qualitative | quantitative | Acceptanc e criteria | |
NAT | qualitative | quantitative | qualitative | As for HIV quantitative | As for HIV quantitative | qualitative | As for HIV quantitative | Acceptanc e 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 concentra- tion; statistical analysis (e.g. Probit analysis) on the basis of at least 24 replicates; calculatio n of 95% cut-off value | Detection limit: as for qualitative tests; Quantific- ation limit: dilutions (half-log10 or less) of calibrated reference prepara- tions, definition of lower, upper quantifi- cation limit, precision, accuracy, "linear"mea suring range, "dynamic range". Reproduci- bility at different concentra- tion levels to be shown | According to EP validation guideline (1): several dilution series into borderline concentra- tion; 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 concentr- ation; 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 concentr- ation; statistical analysis (e.g. Probit analysis) on the basis of at least 24 replicates; calculation of 95% cut- off value | ||||
Genotype/ subtype detection/ quantific- ation 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 supernatant s (could substitute for rare HIV-1 subtypes) According to EP validation guideline (1) as far as calibrated subtype reference materials are available; in vitro transcripts could be an option | Transcripts or plasmids quantified by appropriate meethods may be used | ||||||||
Cell culture supernatant s (could substitute for rare HIV-1 subtypes) 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 | ||||||
Diagnostic specificity negative samples | 500 blood donors | 100 blood donors | 500 blood donors | 500 blood donors | 500 blood donors |
B 163
HIV1 | HCV | HBV | HTLV I/II | Acceptanc e criteria | |||||
NAT | qualitative | quantitative | qualitative | quantitative | quantitative | qualitative | quantitative | Acceptanc e criteria | |
NAT | qualitative | quantitative | qualitative | As for HIV quantitative | As for HIV quantitative | qualitative | As for HIV quantitative | Acceptanc e criteria | |
Potential cross reactive markers | By suitable assay design evidence (e.g. sequence compari- son) 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 assays design and/ or testing of at least 10 human retrivirus (e.g. HIV-) positive samples | ||||
Robustness | As for qualitative tests | ||||||||
Cross- contami- nation | 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 concentra- tion | At least 100 samples virus- spiked with 3 x the 95% pos cut-off concentra- tion | At least 100 samples virus- spiked with 3 x the 95 % pos cut- off concentra- tion | At least 100 samples virus- spiked with 3 x the 95 % pos cut- off concentr- ation | 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). 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.
B 164
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 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 |
Diagnostic sensitivity | 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 |
Negative specimens | 1000 blood donations 200 clinical specimens 200 samples from pregnant women 100 potentially interfering samples | 1000 blood donations 200 clinical specimens 200 samples from pregnant women 100 potentially interfering samples | 1000 blood donations 200 clinical specimens 200 samples from pregnant women 100 potentially interfering samples | 1000 blood donations 200 clinical specimens 100 potentially interfering samples | 1000 blood donations 200 clinical specimens 200 samples from pregnant women 100 potentially interfering samples | 99 % (anti- HBc: 96 %) |
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-II | 300 HCV (positive samples) | 300 HBsAg | Correct identificationas positive (or indeterminate), not negative |
Diagnostic sensitivity | Positive specimens | 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 | ||
Diagnostic sensitivity | Sero-con- version panels | 15 sero- conversion panels/ low titre panels | 15 seroconversion panels/ low titre panels | 15 seroconversion panels/ low titre panels |
B 165
anti-HIV Confirmatory Assay | anti-HTLV Confirmatory Assay | HCV Supplementary Assay | HBsAg Confirmatory Assay | Acceptance criteria | ||
Analytical sensitivity | Standards | Second International Standard for HBsAg, subtype adw2, genotype A, NIBSC code: 00/588 | ||||
Diagnostic specificity | Negative specimens | 200 blood donations 200 clinical samples including pregnant women 50 potentially interfering samples, including samples with indetermin- ate 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 confirmatory assays | 10 false positives as available from the performance evaluation of the screening assay. (1) 50 potentially interfering samples | No false- positive results/ (1) no neutralisation |
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) |
Diagnostic sensitivity | Sero-conversion panels | 20 sero-conversion 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 |
B 166
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 |
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% |
Diagnostic sensitivity | Sero-con- version panels | 10 follow-ups or anti-HBs sero- conversions | When availa- ble | 200 Including samples from different stages of infection (acute/chronic etc.) | 200 Including samples from different stages of infection (acute/chronic etc.) | > 98% |
Analytical sensitivity | Standards | WHO 1st International Reference Preparation 1977; NIBSC, United Kingdom | HBe - Referenzan- tigen 82; PEI Germany | Anti-HBs: <10 mIU/ml | ||
Diagnostic specificity | No negative specimens | 500 Including clinical samples 50 potentially interfering samples | 200 blood donations 200 clinical samples 50 potentially interfering samples | 200 blood donations 200 clinical samples 50 potentially interfering samples | 200 blood donations 200 clinical samples | >98% |
B 167
Table 8: HDV markers: anti-HDV, anti-HDV IgM, Delta Antigen
anti-HDV anti-HDV IgM Delta Antigen Acceptance criteria
Diagnostic sensitivity
Diagnostic specificity
Positive specimens
Negative specimens
100
Specifying HBV- markers
200
Including clinical samples
50 potentially
50
Specifying HBV- markers
200
Including clinical samples
50 potentially
200
Including clinical samples
50 potentially
>98%
>98%
interfering samples
interfering samples interfering samples
Table 9: Blood group antigens in the ABO, Rh and Kell blood group systems
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-characterized reagents |
Anti-ABO1(anti-A),anti- Anti-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 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
B 168
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 | |||||||
A1 | A2B | Ax | B | 0 | ||||
Anti-ABO1 (anti-A) | 2 | 2 | 2* | 2 | 2 | |||
B | A1B | 1 | 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 | Weak D | 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) | 2 | 1 | 1 | 1 | 1 | 1 | ||
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 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.".
WorldLII:
Copyright Policy
|
Disclaimers
|
Privacy Policy
|
Feedback
URL: http://www.worldlii.org/mt/legis/laws/psa427ivdmdr201021o2010742