How do you bring an NGS-based or genomic IVD through the IVDR, including its bioinformatics?
We prepare NGS-based and genomic IVDs for the IVDR, with the bioinformatics pipeline as part of the device. That covers the performance evaluation with its reference databases and every later change to algorithm or database.
Overview
Where does an NGS test differ from other IVDs under the IVDR?
NGS-based and genomic IVD · IVDR Annex I Sections 9 and 16, Annex II, Annex VIII Rule 3, Annex XIII · MDCG 2019-11, 2020-16, 2020-1, 2022-6 · IEC 62304
Last updated: October 31, 2026
An NGS test is reagents, sequencer and software working together, and the result comes from the software. The IVDR counts software as an IVD (Art. 2(2)) and sets requirements for it in Annex I Section 16 and Annex XIII that do not arise for a purely chemical assay.
- The bioinformatics is part of the device. MDCG 2019-11 Rev. 1 qualifies software that analyzes NGS raw data from tumor genomes and detects somatic alterations as IVD medical device software. If it renders the raw data of a specific IVD readable, it drives that device and takes its class (Annex VIII Section 1.4).
- Reference databases belong in the performance evaluation plan. For software qualified as a device, Annex XIII Part A Section 1.1 requires the identification and specification of the reference databases and other data sources used as the basis for decision making.
- Many genomic tests are class C. Rule 3 covers companion diagnostics, devices for screening, diagnosis or staging of cancer, and devices for human genetic testing; MDCG 2020-16 Rev. 5 lists a targeted NGS test for (haemato)-oncology as an example. A sequencer for NGS applications is class A, but the class of the test follows its intended purpose.
- Changes to the algorithm or database are design changes. Where the device holds an EU technical documentation assessment certificate, changes that could affect safety and performance require approval by the notified body (Annex IX Section 4.11). Under Annex VI Part C Section 6.2.2, new or modified algorithms and database structures that change performance or the interpretation of data require a new UDI-DI.
Services
How we support you
Reference databases under control
Inventory of the databases the software uses for annotation, classification or comparison of variants, with version, source and role in the result, as required for the performance evaluation plan. For every planned update, an assessment of whether it changes performance or the interpretation of data.
Assessment of changes to pipeline and database
Assessment of planned changes to algorithm, pipeline version, sequencer chemistry or reference database against Annex IX Section 4.11 and the UDI rules for software in Annex VI Part C Section 6.2. For devices still placed on the market under Art. 110(3) IVDR, the assessment follows MDCG 2022-6.
How we work together
What it comes down to
An NGS-based IVD delivers its result only after several steps: library preparation, sequencing, and a bioinformatics pipeline that aligns the reads, calls variants and compares them with reference databases. The IVDR treats the whole chain as a device question. Software is expressly part of the IVD definition in Art. 2(2), and Annex I Section 16 requires it to be developed according to the state of the art.
Much of the regulatory work therefore sits in the software and the data it relies on. The algorithm is described in the technical documentation, the software is validated as it is used in the finished device, and the reference databases are specified in the performance evaluation plan.
| Component | IVDR anchor | Guidance |
|---|---|---|
| Bioinformatics software | Art. 2(2), Annex VIII Section 1.4, Annex I Section 16 | MDCG 2019-11 Rev. 1, Figure 2, Example 4 |
| Algorithm | Annex II Section 3.1(d) | MDCG 2020-1 |
| Software validation | Annex II Section 6.4 | IEC 62304:2006+AMD1:2015 |
| Reference databases | Annex XIII Part A Section 1.1 | MDCG 2020-1 (curated databases) |
| Class of the test | Annex VIII Rule 3(f), (h), (i) | MDCG 2020-16 Rev. 5 |
| Sequencer, general reagents | Annex VIII Rule 5 | MDCG 2020-16 Rev. 5 |
| Changes after certification | Annex IX Section 4.11, Annex VI Part C Section 6.2 | MDCG 2022-6 (legacy devices) |
Performance follows the three pillars of Annex XIII: scientific validity of the marker, analytical performance with the parameters of Annex I Section 9.1(a), and clinical performance. For software, MDCG 2020-1 accepts evidence from verification and validation as well as from curated databases and reference databases.
After certification, the pipeline can still change: a new software version, an updated annotation database, a new sequencer chemistry. Each change is assessed for its effect on performance and on the interpretation of results, because that decides whether the notified body has to approve it and whether a new UDI-DI is needed.
Outside the scope of this page are the detailed classification, the performance evaluation plan and report in general, the planning of performance studies, software development to IEC 62304, IVDR implementation for a whole portfolio, and in-house devices of health institutions under Art. 5(5) IVDR.
Our approach
Our approach
Step
Result
Define intended purpose and system boundary
An intended purpose that names analytes, variant types, specimen and target population, and a system description that assigns reagents, instrument and software to the device or to its environment.
Qualify and classify
Status and class for each component, with the rules applied and the MDCG examples used for comparison.
Plan the performance evaluation
A performance evaluation plan that specifies the reference databases and other data sources, the parameters of Annex I Section 9.1 and the acceptance criteria.
Document and set up change control
Technical documentation with algorithm description and software validation, and a change procedure that assesses each pipeline or database update for performance, UDI and notified body.
Common pitfalls
Where projects commonly fail
The pipeline is run as an internal laboratory tool and kept out of the technical documentation.
If the software renders the raw data of the IVD readable and is intended for use with it, it drives the device (MDCG 2019-11 Rev. 1, Annex I, example f.3) and is part of its conformity assessment.
A reference database is updated without an assessment.
Under Annex VI Part C Section 6.2.2, a change of database structure that affects performance or the interpretation of data requires a new UDI-DI, and for legacy devices under Art. 110(3) IVDR, MDCG 2022-6 counts adding a new database with new content for comparing genetic results as a significant change.
The test's class is taken from the sequencer.
Under MDCG 2020-16 Rev. 5 the sequencer is class A, and the performance of the reagent on the instrument is part of the reagent's conformity assessment; the class of the test itself follows its intended purpose, often Rule 3.
Trueness is planned against reference material that does not exist for the marker.
Annex XIII Part A Section 1.2.2 provides for this case: comparison with other well-documented methods or a composite reference standard, failing which a clinical performance study against current clinical practice.
Product Development & Regulatory Strategy
Do any of these pitfalls apply to you?
In a first call we assess your situation and say what needs clarifying first in your case. Without obligation, reply usually within one working day.
FAQ
Frequently asked questions
Sources
- Regulation (EU) 2017/746 (IVDR), consolidated version CELEX 02017R0746-20250110: Art. 2, 4, 5, 48, 110, Annex I Sections 9 and 16, Annex II Sections 3.1 and 6.4, Annex VI Part C Section 6.2, Annex VIII, Annex IX Sections 2.4, 4.11 and 5.2, Annex XIII Part A
- IEC 62304:2006+AMD1:2015 CSV, Medical device software, Software life cycle processes, Edition 1.1 (June 26, 2015): https://webstore.iec.ch/en/publication/22794
- MDCG 2019-11 Rev. 1, Guidance on Qualification and Classification of Software in Regulation (EU) 2017/745 and Regulation (EU) 2017/746 (June 2025): https://health.ec.europa.eu/document/download/b45335c5-1679-4c71-a91c-fc7a4d37f12b_en?filename=mdcg_2019_11_en.pdf
- MDCG 2020-16 Rev. 5, Guidance on Classification Rules for in vitro Diagnostic Medical Devices under Regulation (EU) 2017/746 (September 2026): https://health.ec.europa.eu/document/download/12f9756a-1e0d-4aed-9783-d948553f1705_en?filename=md_mdcg_2020_guidance_classification_ivd-md_en.pdf
- MDCG 2020-1, Guidance on Clinical Evaluation (MDR) / Performance Evaluation (IVDR) of Medical Device Software (March 2020): https://health.ec.europa.eu/document/download/19d9e24f-2808-4e00-bfeb-75892047407d_en?filename=md_mdcg_2020_1_guidance_clinic_eva_md_software_en.pdf
- MDCG 2022-6, Guidance on significant changes regarding the transitional provision under Article 110(3) of the IVDR (May 2022): https://health.ec.europa.eu/document/download/14c2d8dd-8489-4db5-b035-1c174f17fb54_en?filename=mdcg_2022-6.pdf
Image notice: The images on this page were generated using artificial intelligence. They do not depict real people, places, or events.
Projects from this industry
What we have worked on in this industry
Latest insights
All insights →Regulations & standards considered
- EU 2017/746 (IVDR), Art. 2(2) (in vitro diagnostic medical device, including software)
- EU 2017/746 (IVDR), Annex I Section 9.1 (analytical and clinical performance) and Section 16 (electronic programmable systems and software)
- EU 2017/746 (IVDR), Annex II Section 3.1(d) (description of the algorithm) and Section 6.4 (software verification and validation)
- EU 2017/746 (IVDR), Annex VIII Section 1.4 (software) and Rule 3(f), (h) and (i) (companion diagnostics, cancer, human genetic testing)
- EU 2017/746 (IVDR), Annex XIII Part A Section 1.1 (performance evaluation plan, reference databases for software) and Section 1.2 (scientific validity, analytical and clinical performance)
- EU 2017/746 (IVDR), Annex IX Section 4.11 (changes to the approved device) and Annex VI Part C Section 6.2 (UDI for software)
- EU 2017/746 (IVDR), Art. 4 (genetic information, counseling and informed consent)
- IEC 62304:2006+AMD1:2015 (medical device software, software life cycle processes, Edition 1.1)
- MDCG 2019-11 Rev. 1 (qualification and classification of software, June 2025)
- MDCG 2020-16 Rev. 5 (classification rules for IVD, September 2026)
- MDCG 2020-1 (clinical evaluation and performance evaluation of medical device software, March 2020)
- MDCG 2022-6 (significant changes under Art. 110(3) IVDR, May 2022)
Related topics
Qualification & Classification →
Qualification of software and classification under Annex VIII of the IVDR, including Rule 3
Performance Evaluation Plan & Report →
Plan and report of the performance evaluation under Art. 56 and Annex XIII
Software as a Medical Device →
Development to IEC 62304, cybersecurity and approval of software as a medical device
IVD Performance Studies →
Analytical and clinical performance studies for in vitro diagnostics under the IVDR
IVD Consulting & IVDR Readiness →
IVDR implementation for a whole IVD portfolio, from classification to certification
In-house IVDs & Laboratory-Developed Tests →
In-house IVDs and laboratory-developed tests of health institutions under Art. 5(5) IVDR
Have a concrete project?
Briefly outline your situation. We'll respond with an initial assessment, usually within one business day.
Prefer direct? info@theentourage.us
- Reply usually within one working day
- 4 locations: DE · CH · IT · US
- 100% life sciences