Structure of the IVDD 98/79/EC

The IVDD is one of the most complex of the EU’s “new approach” directives. It has 24 Articles and 10 Annexes. The Articles cover general items such as scope and definitions, placing devices on the market and putting them into service, free movement of CE marked goods in the European Economic Area, reference to harmonized standards, vigilance and incident reporting, conformity assessment procedures, registration responsibilities, appointment of an Authorized Representative, consequences of wrongly affixed CE marking, confidentiality, etc.

In-Vitro Diagnostic Medical Devices are classified into three main groups:

1. General IVD Medical Devices
2. IVD Medical Devices from Annex II - List A and List B of the In-Vitro Diagnostic Medical Device Directive
3. IVD Medical Devices for ‘self-test’ intended to be used by a lay person in the home environment

Annex I- lists the Essential Requirements. All devices must comply with these requirements (where applicable). Manufacturers are required to check each device type or model against each requirement, determine whether the requirement is applicable, acquire documented evidence of compliance and keep this evidence available in the Technical File of the device. There are good reasons to say that Annex I is the real core of the directive.

Annex II - lists devices of high or moderate risk, and is divided into two lists:
List A: Reagents and reagent devices, including related calibrators and control materials for determining the following blood groups: ABO system, rhesus (C,c,D,E,e) anti-Kell; the detection, confirmation and quantification in human specimens of markers of HIV 1 and 2, HTLV 1 and II and Hepatitis B, C and D.
List B: Reagents and reagent devices, including related calibrators and control materials for determining the blood groups Anti-Duffy and Anti-Kidd; determining irregular and antierythrocytic antibodies; detection and quantification of the infectious rubella and toxoplasmosis; diagnosing phenylketonuria; determining the infectious cytomegalovirus and chlamydia; HLA tissue groups DR,A,B; tumor marker PSA; evaluating the risk of trisomy 21(including software). Devices for self-diagnosis and measurement of blood sugar (glucose).
Annex III - EC Declaration of Conformity. A procedure in which the manufacturer declares conformity of his devices with the IVDD. Applicable to all devices except those listed in Annex II or devices for performance evaluation. All “ordinary” IVD devices can be CE marked using this “self-certification” route. Additionally, for devices for self-testing, a Notified Body shall carry out an examination of the design.
Annex IV - Full Quality Assurance System. Applicable to all devices listed in Annex II and may be applied for devices for self-testing. Sections 4 and 6 of this Annex require that design examination and batch release by a Notified Body shall be carried out for Annex II/List A devices.
Annex V - EC Type - examination. A procedure which involves examination and testing of representative samples of the device by the Notified Body and certification that the device meets the applicable essential requirements. Annex V can only be used in combination with Annex VI (batch verification) or Annex VII (quality assurance system approval).
Annex VI - EC Verification. A procedure in which the Notified Body examines and tests every individual device or sample taken from a batch on a statistical basis.
Annex VII - Production Quality Assurance. The Notified Body shall audit and certify the manufacture’s production quality system (which is usually based on EN46002 or ISO 13488 standards).
Annex VIII - Devices for performance evaluation. This Annex describes procedures concerning devices for performance evaluation, i.e. devices intended by the manufacturer to be subject to performance evaluation studies in clinical laboratories or in other environments outside his own premises.
Annex IX - Criteria for the designation of Notified Bodies.
Annex X - Appearance of the CE mark.

The specific function of an In-Vitro Diagnostic Medical Device and whether or not it is listed in Annex II will determine its classification.

Devices listed in Annex II List A are considered the highest risk devices. They are then followed by those in Annex II list B, then self-tested and finally the ‘general’ IVD Medical Devices.

ANNEX II: List of Devices referred to in Article 9(2) (3)

List A

Reagents and reagent devices, including related calibrators and control materials, for determining the following blood groups: ABO system, rhesus (C, c, D, E, e) anti-Kell, reagents and reagent devices, including related calibrators and control materials, 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 and D.

List B

1. Reagents and reagent devices, including related calibrators and control materials, for determining the following blood groups: Anti-Duffy and Anti-Kidd
2. Reagents and reagent devices, including related calibrators and control materials, for determining irregular anti-erythrocytic antibodies
3. Reagents and reagent devices, including related calibrators and control materials, for the detection and quantification in human samples of the following congenital infections: rubella, toxoplasmosis
4. Reagents and reagent devices, including related calibrators and control materials, for diagnosing the following hereditary disease: phenylketonuria
5. Reagents and reagent devices, including related calibrators and control materials, for determining the following human infections: cytomegalovirus, chlamydia
6. Reagents and reagent devices, including related calibrators and control materials, for determining the following HLA tissue groups: DR, A, B
7. Reagents and reagent devices, including related calibrators and control materials, for determining the following tumoral marker: PSA
8. Reagents and reagent devices, including related calibrators, control materials and software, designed specifically for evaluating the risk of trisomy 21, the following device for self-diagnosis, including its related calibrators and control materials: device for the measurement of blood sugar