If you are preparing a CE marking submission for a Class D IVD — an HIV, HBV or HCV diagnostic — you will quickly find that the Common Technical Specifications (CTS 2009/108/EC) define not just what performance you need to demonstrate, but exactly which samples you need to demonstrate it with. This post breaks down the requirements by Annex and table, so you know what to source before you start your study.
Why Class D is different
IVDR Class D covers the highest-risk in vitro diagnostics — devices used to detect life-threatening transmissible agents in blood, blood components, cells, tissues or organs intended for transfusion or transplantation, where a false negative result poses a high individual or public health risk. For practical purposes, this means: HIV-1/2, HBV (HBsAg, anti-HBc, anti-HBs, DNA), HCV (antibody, RNA), HTLV-I/II, and Treponema pallidum.
Unlike Class B and C devices, Class D requires mandatory Notified Body involvement in the conformity assessment — and batch release testing by a national reference laboratory (OMCL) before each production batch is placed on the market. The performance data must be generated against the specific requirements of the CTS, not just against any set of samples you have available.
The CTS — what it actually specifies
The Common Technical Specifications (Commission Decision 2009/108/EC, referenced in IVDR Annex IX) define minimum performance requirements for Class D IVDs. Each Annex covers a specific pathogen group, and each Annex contains multiple tables specifying different study types. The critical point: each table specifies not just the number of samples but their exact composition — and “native human biomaterial with no additives” is the implicit requirement throughout.
HBV — what you need (Annex VI)
Hepatitis B is the most complex CTS panel requirement because it covers multiple markers (HBsAg, anti-HBc, anti-HBs, HBV DNA) and multiple study types.
| Study type | CTS Reference | Required samples | Anmerkungen |
|---|---|---|---|
| Diagnostic sensitivity — comprehensive | Annex VI, table 1 | 400 positive, including 25 same-day fresh | Most demanding — fresh samples require advance coordination |
| Diagnostic sensitivity — standard | Annex VI, table 2 | 400 anti-HBc + HBsAg positive | For combined marker assays |
| Diagnostic sensitivity — HBsAg only | Annex VI, table 3 | 300 HBsAg positive | For HBsAg-specific assays |
| Diagnostic sensitivity — anti-HBs | Annex VI, table 4 | 100–200 positive + vaccinated donors | Vaccinated donors require separate panel |
| Diagnostic sensitivity — HBV DNA | Annex VI, table 5 | 100 DNA positive | Molecular assays only |
| Diagnostic specificity | Annex VI, table 1–5 | 200–5,000 blood donors + 200 hospitalised | Unselected blood donors — random population sample |
| Self-test validation | Annex VI, table 6 | 200–400 lay participants | For lay-use (home test) devices only |
| Matrix equivalence | Annex I | 25 positive + 25 negative per matrix | Required when device claims multiple sample types |
HCV — what you need (Annex V)
| Study type | CTS Reference | Required samples |
|---|---|---|
| Diagnostic sensitivity — comprehensive | Annex V, table 1 | 400 HCV positive, including 25 same-day fresh |
| Diagnostic sensitivity — standard | Annex V, table 2 | 400 HCV antibody positive |
| Diagnostic sensitivity — reduced | Annex V, table 3 | 300 HCV antibody positive |
| Diagnostic sensitivity — minimal | Annex V, table 5 | 100 HCV positive |
| Diagnostic specificity | Annex V, table 1–5 | 200–5,000 blood donors |
| Self-test validation | Annex V, table 6 | 200–400 lay participants |
HIV — what you need (Annex III)
| Study type | CTS Reference | Required samples | Anmerkungen |
|---|---|---|---|
| Diagnostic sensitivity — comprehensive | Annex III, table 1 | 400 HIV-1 + 100 HIV-2 positive | Both subtypes required |
| Diagnostic sensitivity — standard | Annex III, table 2 | 400 HIV-1 positive | HIV-1 focused assays |
| Diagnostic sensitivity — HIV-1 Ag | Annex III, table 4 | 50 HIV-1 antigen positive | For combination Ag/Ab assays |
| Diagnostic sensitivity — reduced | Annex III, table 3 | 200 HIV-1 positive | |
| Diagnostic sensitivity — minimal | Annex III, table 5 | 100 HIV-1 + 100 HIV-2 positive | |
| Diagnostic specificity | Annex III, table 1–5 | 200–5,000 blood donors | Unselected + hospitalised |
| Self-test validation | Annex III, table 6 | 200–400 lay participants |
Cross-reactivity and interference — what is required alongside sensitivity panels
The CTS does not only specify sensitivity and specificity panels. For a complete Class D submission, you also need interference and cross-reactivity data demonstrating that the device does not produce false positives in the presence of:
- General interference panel: 16 standard interferents — typical components include rheumatoid factor, antinuclear antibodies, lipemic serum, icteric serum, haemolytic serum, polyclonal hypergammaglobulinaemia, pregnancy serum
- Vaccination panel: donors vaccinated against common pathogens — hepatitis B vaccine, influenza, MMR — to rule out vaccine cross-reactivity
- Cross-reacting conditions: HIV-positive donors for HBV assays and vice versa; malaria, syphilis, toxoplasma, CMV, EBV positive — depending on the intended use population
- Pregnant donors: 100–200 pregnant donors for assays used in antenatal screening
The three most common mistakes in Class D panel sourcing
1. Sourcing spiked or diluted positive material instead of native donors. The CTS implicitly requires native human biomaterial — real patients with confirmed positive results, not healthy donor serum spiked with recombinant antigen or diluted high-positive samples. Notified Bodies will scrutinise the sample documentation and reject spiked material for sensitivity panels.
2. Underestimating the specificity panel requirement. Five thousand unselected blood donors is a large logistics challenge. Many manufacturers underestimate the lead time for large specificity panels — planning 8–12 weeks in advance is realistic.
3. Missing the fresh sample requirement. The table 1 panels for HBV, HCV and HIV require 25 same-day fresh samples collected and processed within hours of donation. This requires a standing arrangement with a collection centre — it cannot be sourced from a frozen biobank. Plan this as early as possible in your study timeline.
What to do next
The fastest path to a complete Class D panel package is to work with a supplier who has assembled CTS-referenced panels before and understands the specificity of each table’s requirements — not just the total sample count.
SeamlessBio supplies IVDR Class D sample sets for HBV, HCV and HIV — referenced to the specific CTS Annex and table numbers, with full IRB documentation, donor screening results, and IVDR documentation package on request. Panels are available from stock and on custom order.
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