{
  "url": "https://openlegislation.uk/eu-decision-2002-364/annex/division-3",
  "json_url": "https://openlegislation.uk/eu-decision-2002-364/annex/division-3.json",
  "legislation": "eudn/2002/364",
  "legislation_title": "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)",
  "legislation_url": "https://openlegislation.uk/eu-decision-2002-364",
  "path": "annex/division/3",
  "kind": "division",
  "number": "3",
  "heading": "COMMON TECHNICAL SPECIFICATIONS (CTS) FOR PRODUCTS REFERRED TO IN ANNEX II, LIST A OF DIRECTIVE 98/79/EC",
  "text": "Table 1\nScreening assays: anti-HIV 1/2, HIV 1/2 Ag/Ab, anti-HTLV I/II, anti-HCV, HCV Ag/Ab, HBsAg, anti-HBc\nanti-HIV 1/2, HIV 1/2 Ag/Ab\nAnti-HTLV-I/II\nanti-HCV, HCV Ag/Ab\nHBsAg\nAnti-HBc\nDiagnostic sensitivity\nPositive specimens\n400 HIV-1\n100 HIV-2\nincluding 40 non-B-subtypes, all available HIV/1 subtypes shall be represented by at least 3 samples per subtype\n300 HTLV-I\n100 HTLV-II\n400 (positive samples)\nIncluding samples from different stages of infection and reflecting different antibody patterns.\nGenotype 1-4: > 20 samples per genotype (including non-a subtypes of genotype 4);\n5: > 5 samples;\n6: if available\n400\nincluding subtype-consideration\n400\nincluding evaluation of other HBV-markers\nSero-conversion panels\n20 panels\n10 further panels (at Approved Body or manufacturer)\nTo be defined when available\n20 panels\n10 further panels (at Approved Body or manufacturer)\n20 panels\n10 further panels (at Approved Body or manufacturer)\nTo be defined when available\nAnalytical sensitivity\nStandards\n0,130 IU/ml (WHO International Standard: Third International Standard for HBsAg, subtypes ayw1/adw2, HBV genotype B4, NIBSC code: 12/226)\nSpecificity\nUnselected donors (including first-time donors)\n5 000\n5 000\n5 000\n5 000\n5 000\nHospitalized patients\n200\n200\n200\n200\n200\nPotentially cross-reacting blood-specimens (RF+, related viruses, pregnant women, etc.)\n100\n100\n100\n100\n100\nTable 2\nNAT assays for HIV1, HCV, HBV, HTLV I/II (qualitative and quantitative; not molecular typing)\nEuropean Pharmacopoeia guideline.\nNotes: Acceptance criteria for ‘whole system failure rate leading to false-neg results’ is 99/100 assays positive.\nFor 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.\nFor 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.\nHIV1\nHCV\nHBV\nHTLV I/II\nAcceptance criteria\nNAT\nqualitative\nquantitative\nqualitative\nquantitative\nqualitative\nquantitative\nqualitative\nquantitative\nAs for HIV quantitative\nAs for HIV quantitative\nAs for HIV quantitative\nSensitivity\nDetection limit\nDetection of analytical sensitivity (IU/ml; defined on WHO standards or calibrated reference materials)\nAccording to EP validation guideline : several dilution series into borderline concentration; statistical analysis (e.g. Probit analysis) on the basis of at least 24 replicates; calculation of 95 % cut-off value\nDetection limit: as for qualitative tests; Quantification limit: dilutions (half-log10 or less) of calibrated reference preparations, definition of lower, upper quantification limit, precision, accuracy, ‘ linear ’ measuring range, ‘ dynamic range ’ . Reproducibility at different concentration levels to be shown\nAccording to EP validation guideline : several dilution series into borderline concentration; statistical analysis (e.g. Probit analysis) on the basis of at least 24 replicates; calculation of 95 % cut-off value\nAccording to EP validation guideline : several dilution series into borderline concentration; statistical analysis (e.g. Probit analysis) on the basis of at least 24 replicates; calculation of 95 % cut-off value\nAccording to EP validation guideline : several dilution series into borderline concentration; statistical analysis (e.g. Probit analysis) on the basis of at least 24 replicates; calculation of 95 % cut-off value\nGenotype/subtype detection/quantification efficiency\nAt least 10 samples per subtype (as far as available)\nDilution series of all relevant genotypes/subtypes, preferably of reference materials, as far as available\nAt least 10 samples per genotype (as far as available)\nAs far as calibrated genotype reference materials are available\nAs far as calibrated genotype reference materials are available\nCell culture supernatants (could substitute for rare HIV-1 subtypes)\nTranscripts or plasmids quantified by appropriate methods may be used.\nAccording to EP validation guideline as far as calibrated subtype reference materials are available; in vitro transcripts could be an option\nAccording to EP validation guideline as far as calibrated subtype reference materials are available; in vitro transcripts could be an option\nAccording to EP validation guideline as far as calibrated subtype reference materials are available; in vitro transcripts could be an option\nAccording to EP validation guideline as far as calibrated subtype reference materials are available; in vitro transcripts could be an option\nDiagnostic specificity negative samples\n500 blood donors\n100 blood donors\n500 blood donors\n500 blood donors\n500 individual blood donations\nPotential cross-reactive markers\nBy suitable assay design evidence (e.g. sequence comparison) and/or testing of at least 10 human retrovirus (e.g. HTLV)-positive samples\nAs for qualitative tests\nBy assays design and/or testing of at least 10 human flavivirus (e.g. HGV, YFV) positive samples\nBy assays design and/or testing of at least 10 other DNA-virus positive samples\nBy assay design and/or testing of at least 10 human retrovirus (e.g. HIV-) positive samples\nRobustness\nAs for qualitative tests\nCross-contamination\nAt least 5 runs using alternating high positive (known to occur naturally) and negative samples\nAt least 5 runs using alternating high positive (known to occur naturally) and negative samples\nAt least 5 runs using alternating high positive (known to occur naturally) and negative samples\nAt least 5 runs using alternating high positive (known to occur naturally) and negative samples\nInhibition\nInternal control preferably to go through the whole NAT procedure\nInternal control preferably to go through the whole NAT procedure\nInternal control preferably to go through the whole NAT procedure\nInternal control preferably to go through the whole NAT procedure\nWhole system failure rate leading to false-neg results\nAt least 100 samples virus-spiked with 3 × the 95 % pos cut-off concentration\nAt least 100 samples virus-spiked with 3 × the 95 % pos cut-off concentration\nAt least 100 samples virus-spiked with 3 × the 95 % pos cut-off concentration\nAt least 100 samples virus-spiked with 3 × the 95 % pos cut-off concentration\n99/100 assays positive\nTable 3\nRapid tests: anti-HIV 1 and 2, anti-HCV, HBsAg, anti-HBc, anti-HTLV I and II\nAnti-HIV 1/2\nAnti-HCV\nHBsAg\nAnti-HBc\nAnti-HTLV I/II\nAcceptance criteria\nDiagnostic sensitivity\nPositive specimens\nSame criteria as for screening assays\nSame criteria as for screening assays\nSame criteria as for screening assays\nSame criteria as for screening assays\nSame criteria as for screening assays\nSame criteria as for screening assays\nSero-conversion panels\nSame criteria as for screening assays\nSame criteria as for screening assays\nSame criteria as for screening assays\nSame criteria as for screening assays\nSame criteria as for screening assays\nSame criteria as for screening assays\nDiagnostic specificity\nNegative specimens\n1 000 blood donations\n1 000 blood donations\n1 000 blood donations\n1 000 blood donations\n1 000 blood donations\n≥ 99 % (anti-HBc: ≥ 96 %)\n200 clinical specimens\n200 clinical specimens\n200 clinical specimens\n200 clinical specimens\n200 clinical specimens\n200 samples from pregnant women\n200 samples from pregnant women\n200 samples from pregnant women\n200 samples from pregnant women\n100 potentially interfering samples\n100 potentially interfering samples\n100 potentially interfering samples\n100 potentially interfering samples\n100 potentially interfering samples\nTable 4\nConfirmatory/supplementary assays for anti-HIV 1 and 2, anti-HTLV I and II, anti-HCV, HBsAg\nAcceptance criteria no neutralisation for HBsAg confirmatory assay.\nAnti-HIV confirmatory assay\nAnti-HTLV confirmatory assay\nHCV supplementary assay\nHBsAg confirmatory assay\nAcceptance criteria\nDiagnostic sensitivity\nPositive specimens\n200 HIV-1 and 100 HIV-2\n200 HTLV-I and 100 HTLV-II\n300 HCV (positive samples)\n300 HBsAg\nCorrect identification as positive (or indeterminate), not negative\nIncluding samples from different stages of infection and reflecting different antibody patterns\nIncluding samples from different stages of infection and reflecting different antibody patterns.\nGenotypes 1 – 4: > 20 samples (including non-a subtypes of genotype 4);\n5: > 5 samples;\n6: if available\nIncluding samples from different stages of infection\n20 ‘high pos’ samples (> 26 IU/ml); 20 samples in the cut-off range\nSero-conversion panels\n15 sero-conversion panels/low titre panels\n15 sero-conversion panels/low titre panels\n15 sero-conversion panels/low titre panels\nAnalytical sensitivity\nStandards\nSecond International Standard for HBsAg, subtype adw2, genotype A, NIBSC code: 00/588\nDiagnostic specificity\nNegative specimens\n200 blood donations\n200 blood donation\n200 blood donations\n10 false positives as available from the performance evaluation of the screening assay .\nNo false-positive results/ no neutralisation\n200 clinical samples including pregnant women\n200 clinical samples including pregnant women\n200 clinical samples including pregnant women\n50 potentially interfering samples, including samples with indeterminate results in other confirmatory assays\n50 potentially interfering samples including samples with indeterminate results in other confirmatory assays\n50 potentially interfering samples including samples with indeterminate results in other supplementary assays\n50 potentially interfering samples\nTable 5\nHIV 1 antigen, HIV Ag/Ab, HCV antigen, HCV Ag/Ab\nThe total number of seroconversion panels for combined Ag/Ab assays (from tables 1 and 5) need not be greater than 30.\nHIV-1 antigen and HIV Ag/Ab assays\nHCV antigen and HCV Ag/Ab assays\nAcceptance criteria\nDiagnostic sensitivity\nPositive specimens\n50 HIV-1 antigen positive\n50 cell culture supernatants including different HIV-1 subtypes and HIV-2\n25 HCV core antigen and/or HCV RNA positive but anti-HCV negative samples, comprising HCV genotypes 1-6 (if a genotype is not available, a justification shall be made)\nSee general principle in § 3.1.8\nSero-conversion panels\n20 sero-conversion panels/low titre panels\n20 sero-conversion panels/low titre panels\nAnalytical sensitivity\nStandards\nHIV-1 p24 Antigen, First International Reference Reagent, NIBSC code: 90/636\nHCV core antigen detection limit shall be investigated using dilutions of the WHO International HCV core antigen Standard: (HCV core Ag product code: PEI 129096/12)\nFor HIV-1 p24 antigen: ≤ 2 IU/ml\nDiagnostic specificity\n200 blood donations\n200 clinical samples\n50 potentially interfering samples\n200 blood donations, 200 clinical samples, 50 potentially interfering samples\n≥ 99,5 % after neutralisation or, if no neutralisation test available, after resolution of the sample status according to general principles in § 3.1.5\nTable 6\nSerotyping and genotyping assay: HCV\nHCV serotyping and genotyping assay\nAcceptance criteria\nDiagnostic sensitivity\nPositive specimens\n200 (positive samples)\nIncluding samples from different stages of infection and reflecting different antibody patterns.\nGenotypes 1 – 4: > 20 samples (including non-a subtypes of genotype 4);\n5: > 5 samples;\n6: if available\n≥ 95 % agreement between serotyping and genotyping\n> 95 % agreement between genotyping and sequencing\nDiagnostic specificity\nNegative specimens\n100\nTable 7\nHBV markers: anti-HBs, anti HBc IgM, anti-HBe, HBeAg\nAnti-HBs\nAnti-HBc IgM\nAnti-HBe\nHBeAg\nAcceptance criteria\nDiagnostic sensitivity\nPositive specimens\n100 vaccinees\n200\n200\n200\n≥ 98 %\n100 naturally infected persons\nIncluding samples from different stages of infection (acute/chronic, etc.)\nThe acceptance criteria should only be applied on samples from acute infection stage.\nIncluding samples from different stages of infection (acute/chronic, etc.)\nIncluding samples from different stages of infection (acute/chronic, etc.)\nSero-conversion panels\n10 follow-ups or anti-HBs sero-conversions\nWhen available\nAnalytical sensitivity\nStandards\nWHO First International Reference Preparation 1977; NIBSC, United Kingdom\nHBe — Referenzantigen 82; PEI Germany\nAnti-HBs: < 10 mIU/ml\nDiagnostic specificity\nNegative specimens\n500\n200 blood donations\n200 blood donation\n200 blood donations\n≥ 98 %\nIncluding clinical samples\n200 clinical samples\n200 clinical samples\n200 clinical samples\n50 potentially interfering samples\n50 potentially interfering samples\n50 potentially interfering samples\n50 potentially interfering samples\nTable 8\nHDV markers: anti-HDV, anti-HDV IgM, delta antigen\nAnti-HDV\nAnti-HDV IgM\nDelta antigen\nAcceptance criteria\nDiagnostic sensitivity\nPositive specimens\n100\n50\n10\n≥ 98 %\nSpecifying HBV markers\nSpecifying HBV markers\nSpecifying HBV markers\nDiagnostic specificity\nNegative specimens\n200\n200\n200\n≥ 98 %\nIncluding clinical samples\nIncluding clinical samples\nIncluding clinical samples\n50 potentially interfering samples\n50 potentially interfering samples\n50 potentially interfering samples\nTable 9\nBlood group antigens in the ABO, Rh and Kell blood group systems\n1\n2\n3\nSpecificity\nNumber of tests per recommended method\nTotal number of samples to be tested for a launch product\nTotal number of samples to be tested for a new formulation, or use of well-characterised reagents\nAnti-ABO1 (anti-A), anti-ABO2 (anti-B), anti-ABO3 (anti-A,B)\n500\n3 000\n1 000\nAnti-RH1 (anti-D)\n500\n3 000\n1 000\nAnti-RH2 (anti-C), anti-RH4 (anti-c), anti-RH3 (anti-E)\n100\n1 000\n200\nAnti-RH5 (anti-e)\n100\n500\n200\nAnti-KEL1 (anti-K)\n100\n500\n200\nTable 11\nVariant Creutzfeldt-Jakob disease (vCJD) assays for blood screening\nMaterial\nNumber of specimens\nAcceptance Criteria\nAnalytical sensitivity\nvCJD brain spikes in human plasma (WHO reference number NHBY0/0003)\n24 replicates of each of three dilutions of the material WHO number NHBY0/0003\n(1×10 4 , 1×10 5 , 1×10 6 )\n23 of the 24 replicates detected at\n1×10 4\nvCJD spleen spikes in human plasma (10 % spleen homogenate — NIBSC reference number NHSY0/0009)\n24 replicates of each of three dilutions of the material NIBSC number NHSY0/0009\n(1×10, 1×10 2 , 1×10 3 )\n23 of the 24 replicates detected at\n1×10\nDiagnostic sensitivity\nA)\nSpecimen from appropriate animal models\nAs many specimen as reasonably possible and available, and at least 10 specimens\n90 %\nB)\nSpecimen from humans with known clinical vCJD\nAs many specimen as reasonably possible and available, and at least 10 specimens\n90 %\nOnly in case where 10 specimens are not available:\nthe number of specimens tested shall be comprised between 6 and 9\nall available specimens shall be tested\nno more than one false negative result\nAnalytical specificity\nPotentially cross-reacting blood-specimens\n100\nDiagnostic specificity\nNormal human plasma samples from area of low BSE exposure\n5 000\nAt least 99,5 %",
  "extent": "E+W+S+N.I.",
  "status": null,
  "version": "current",
  "annotations": [
    {
      "type": "F",
      "label": "F1",
      "text": "Substituted by Commission Decision of 27 November 2009 amending Decision 2002/364/EC on common technical specifications for in vitro diagnostic medical devices (notified under document C(2009) 9464) (Text with EEA relevance) (2009/886/EC)."
    },
    {
      "type": "F",
      "label": "F2",
      "text": "Substituted by Commission Implementing Decision (EU) 2019/1244 of 1 July 2019 amending Decision 2002/364/EC as regards requirements for HIV and HCV antigen and antibody combined tests and as regards requirements for nucleic acid amplification techniques with respect to reference materials and qualitative HIV assays (notified under document C(2019) 4632) (Text with EEA relevance)."
    },
    {
      "type": "F",
      "label": "F3",
      "text": "Words in Annex Table 1 substituted (E.W.S.) (11.8.2021) by The Medical Devices (Amendment) (EU Exit) Regulations 2021 (S.I. 2021/873), reg. 1(1), Sch. 2 para. 3(d)"
    },
    {
      "type": "F",
      "label": "F4",
      "text": "Inserted by Commission Decision of 20 December 2011 amending Decision 2002/364/EC on common technical specifications for in vitro diagnostic medical devices (notified under document C(2011) 9398) (Text with EEA relevance) (2011/869/EU)."
    },
    {
      "type": "X",
      "label": "X1",
      "text": "Substituted by Corrigendum to Commission Decision 2009/886/EC of 27 November 2009 amending Decision 2002/364/EC on common technical specifications for in vitro diagnostic medical devices (Official Journal of the European Union L 318 of 4 December 2009)."
    },
    {
      "type": "footnote",
      "label": "f1",
      "text": "European Pharmacopoeia guideline."
    },
    {
      "type": "footnote",
      "label": "f2",
      "text": "Acceptance criteria no neutralisation for HBsAg confirmatory assay."
    },
    {
      "type": "footnote",
      "label": "f3",
      "text": "The total number of seroconversion panels for combined Ag/Ab assays (from tables 1 and 5) need not be greater than 30."
    }
  ],
  "outstanding_effects": [],
  "provenance": {
    "source": "legislation.gov.uk",
    "source_url": "https://www.legislation.gov.uk/eudn/2002/364/annex/division/3",
    "retrieved_at": "2026-11-01T15:18:33.780237+00:00"
  },
  "licence": "Open Government Licence v3.0",
  "licence_url": "https://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/",
  "attribution": "Contains public sector information licensed under the Open Government Licence v3.0. Source: legislation.gov.uk, The National Archives."
}