In vitro diagnostic medical devices (IVDs) have been an integral part of healthcare for many years. However, their use has seen a significant surge in recent times. The rapid spread of the coronavirus clearly showed us how critical it is for diagnostic tests to deliver accurate results—especially considering that a false-negative outcome can have serious public health implications. The same holds true for many other IVDs, where incorrect results could lead to harmful consequences. Therefore, it has become extremely important to regulate IVD’s worldwide.
Given the wide range of products that fall under the definition of an IVD, it was extremely complicated to apply the same regulatory requirements to all of them. To address this, IVDs are categorized into four different risk-based classes as below. This forms the foundation of the in-vitro diagnostic classification system:
- Class A – Low patient and public health risk
- Class B – Moderate patient risk and/or low public health risk
- Class C – High patient risk and/or moderate public health risk
- Class D – High patient risk and high public health risk
What are In Vitro Diagnostic Medical Devices or IVDs?
“In-vitro diagnostic medical device” means ‘any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:
- concerning a physiological or pathological process or state,
- concerning congenital physical or mental impairments,
- concerning the predisposition to a medical condition or a disease,
- to determine the safety and compatibility with potential recipients,
- to predict treatment response or reactions,
- To define or monitor therapeutic measures.
What is IVDD to IVDR? And Why is it Important?
It wasn’t until May 2017 that a unified European regulation specifically governing IVDs was introduced—Regulation (EU) 2017/746, commonly known as the In Vitro Diagnostic Regulation. This new framework builds upon the earlier In Vitro Diagnostic Directive (IVDD 98/79/EC), by adding new requirements while retaining the previous ones. To allow manufacturers time to adjust, a transition period of five years was granted, with the IVDR officially becoming applicable from May 26, 2022.
Unlike the IVDD, which relied on national legislation to enforce its provisions, the eu ivdr regulation is directly applicable across all EU member states, promoting harmonization of standards. However, individual countries may still impose additional conditions for specific IVDs. A key change introduced by the In Vitro Diagnostic Regulation is the adoption of a risk-based classification system, similar to that used for non-IVDs. This system not only determines the regulatory pathway for CE marking but also influences how “legacy” IVDs transition under the new rules.
This guide outlines the in-vitro diagnostic classification system process in a stepwise format, closely aligned with the regulatory text in ivdr annex viii and intended for direct application. Understanding the ivdr risk classification process is essential for regulatory compliance.
Step 1: Is the Product an IVDR-Regulated Device?
Initial Question – Is the product a reagent, calibrator, control, kit, instrument, software, specimen receptacle, or an accessory intended by the manufacturer for in vitro examination of specimens derived from the human body?
- No → Not an IVD under IVDR (classification ends here).
- Yes → Proceed to classification rules.
Step 2: IVDR Classification Tree (Rules 1–7)
The IVDR applies seven classification rules. Devices must be assigned to the highest applicable class (A to D).
Rule 1: This rule states that if the device helps detect/quantify then they fall under Class D. Else, the manufacturer must proceed to checking Rule 2. Examples include-
- Transmissible agents in blood, tissues, cells, or organs for transfusion/transplantation
- Life-threatening transmissible agents with high propagation risk
Rule 2: This rule first checks if the device is used for blood grouping or tissue typing for immunological compatibility. If so, the manufacturers need to check if the marker is limited to ABO, Rh (D, C, E, c, e), Kell (K), Kidd (Jka/Jkb), or Duffy (Fya/Fyb). If yes, then they fall under Class D, else they fall under ivdr class c. Else, the manufacturer must proceed to checking Rule 3.
Rule 3: This rule states that if the device is used for any of the following then they fall under ivdr class c, else manufacturer must proceed to checking Rule 4.
- Detect sexually transmitted agent.
- Detect infectious agent in CSF/blood (no high propagation risk) – Companion diagnostic.
- Cancer screening/diagnosis/staging.
- Human genetic testing – Prenatal/neonatal/congenital disorder screening.
- Disease staging or therapeutic drug monitoring where error could be life-threatening.
Rule 4: This rule asks the manufacturer to first check if the device is a self-test or near-patient test. If yes, it is a ivdr class b if it is a self-test for pregnancy, fertility, cholesterol, or for detecting glucose/erythrocytes/leukocytes/bacteria in urine. Otherwise, it would come under Class C. If not, manufacturer must proceed to checking Rule 5.
Rule 5: This rule states that if the device is used for general laboratory use, IVD instrument, buffer/wash solution, general culture medium, or a specimen receptacle, it would fall under Class A, else the manufacturer proceeds to check Rule 6.
Rule 6 & Rule 7: This rule states that the device is a ivdr class b if it is a control without an assigned value. If not, it would be a Class B irrespective (default catch-all).
Step 3: Conformity Assessment Overview:
Each class has a defined conformity route and level of Notified Body (NB) involvement:
Class | Conformity Route | Notified Body Involvement |
A | Annex II & III (self-declaration) | None |
B | Annex IX (QMS + TD) or Annex XI (Production QA) | Design dossier sampling |
C | Annex IX (QMS + TD on representative samples) or Annex XI + X (type examination) | NB review + surveillance |
D | Annex IX + EU Reference Lab testing & batch verification or IX + X + XI combo | Highest scrutiny incl. Ref-Lab + unannounced audits |
Additional Notes |
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Highest Class Prevails: If a product meets criteria for multiple rules, assign it to the highest applicable class. |
This decision flow is designed for regulatory and quality teams to quickly and accurately assign IVDR risk classification and prepare for the appropriate conformity assessment route.
Conclusion
The introduction of the In Vitro Diagnostic Regulation has brought consistency to how the wide spectrum of IVDs is regulated, enhancing safety for both patients and the broader public throughout Europe. With the rollout of a more detailed, rules-based classification system under the In Vitro Diagnostic Regulation, around 80% of IVDs will now require assessment by a notified body—significantly higher than the previous figure of approximately under 10%. This shift has led to the need for many IVDs to undergo reclassification, as well as new certification or recertification processes.
Understanding the IVDR risk classification process is essential for IVD manufacturers to comply with eu ivdr regulation and plan their regulatory pathway. By following the step-by-step flow—from confirming if the product falls under ivdr annex viii to applying the classification rules—manufacturers can determine the correct risk class and the level of Notified Body involvement needed. Using this structured approach helps regulatory teams classify devices accurately and prepare for the required documentation and assessments under the in-vitro diagnostic classification system.
At Morulaa, our consultants help IVD manufacturers classify their devices under IVDR (Class A–D) based on intended use and risk rules through our flexible staffing model. Whether it’s the preparation of core technical documentation—like intended use, risk classification rationale, or performance evaluation—our team steps in to fill the gap. We conduct gap analyses to align existing files with IVDR requirements. Essentially, we provide outsourced experts who support your urgent documentation needs—work that might otherwise take ages in-house.