There are currently three key European Directives governing the requirements manufacturers must meet before they can market medical devices. These are the active implantable medical devices directive, the general medical devices directive and the in vitro diagnostic medical devices directive.
We looked at obtaining CE mark approval under the general medical devices directive here. In a follow-up to that article, we consider the procedure for obtaining a CE mark for an in vitrodiagnostic medical device (IVD). An IVD can only be freely marketed or put into service in the EEA if the manufacturer complies with the in vitro diagnostic medical devices Directive.
What is an IVD?
In assessing whether a device is an IVD or not, a key consideration will be the manufacturer's intention. The Directive defines an IVD as any medical device that is:
- a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, or system (whether used alone or in combination), that is
- 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:
- concerning a physiological or pathological state, or
- concerning a congenital abnormality, or
- to determine the safety and compatibility with potential recipients, or
- to monitor therapeutic measures.
Note that specimen receptacles (whether vacuum-type or not) and accessories are also captured by the Directive if they are specifically intended by their manufacturer (in the case of specimen receptacles) for the primary containment and preservation of specimens derived from the human body, for the purpose ofin vitro diagnostic examination, or (in the case of accessories) to be used together with an IVD to enable that IVD to be used for its intended purpose.
However, products for general laboratory use are not, generally speaking, IVDs unless those products, in view of their characteristics, are specifically intended by their manufacturer to be used for in vitro diagnostic examination.
First steps – classification and choosing the Conformity Assessment Route
As for manufacturers of general medical devices, an IVD manufacturer must follow one of four Conformity Assessment Routes in order to obtain CE mark approval for their device. The particular route will depend upon the categorisation of the IVD. An IVD may be categorised as follows:
- General: All devices, except Annex II devices, Self-test devices and devices for performance evaluation, e.g. bacteriological media, blood gas analysers and cell cultures for virus isolation.
- Self-test: All devices, except Annex II devices and devices intended for performance evaluation, intended by the manufacturer to be used by lay persons in a home environment, e.g. pregnancy testing kits.
- Annex II, list A: (other than devices intended for performance evaluation) e.g. reagents including related calibrators and controls for use in HIV and hepatitis assays.
- Annex II, list B: (other than devices intended for performance evaluation) e.g. reagents including related calibrators and controls for use in rubella, toxoplasma, cytomegalovirus and chlamydia assays.
Conformity Assessment Routes
For General IVDs, the manufacturer can self-declare the device's conformity with the essential requirements of the Directive. A Notified Body (an independent entity that has been designated by the national regulatory body) will not be involved.
Manufacturers of Self-test IVDs must also declare the device's conformity with the Directive. In addition, however, they will need to submit details of the IVD design to a Notified Body. The Notified Body will then assess the design of the IVD in terms of its suitability for non-professional users. Alternatively, the manufacturer may follow the conformity assessment routes for Annex II devices.
For Annex II, List A devices, the manufacturer must submit for assessment to the Notified Body a device or batch of devices, as well as requesting the Notified Body to undertake either:
- an audit of the manufacturer's quality system, together with a review of the IVD design dossier; or
- an EC-type examination (whereby the Notified Body will assess whether or not a representative sample of the production satisfies the Directive), together with an audit of the manufacturer's quality system.
For Annex II, list B devices, the manufacturer may follow either of the assessment routes for Annex II, List A devices, or request that a Notified Body undertakes an EC-type examination, and an EC Verification. For the EC Verification, the manufacturer will need to, among other requirements, ensure and declare that their products conform to the type described in the EC type-examination certificate.
Finally - notwithstanding that their device may otherwise be categorised as either a General, Self-test, Annex II List A, or Annex II List B device - manufacturers of devices for performance evaluation must instead make a statement in accordance with particular requirements set out in the Directive. These requirements include identifying the device, and listing the laboratories taking part in the evaluation study.
Final steps to CE mark
Manufacturers of IVDs, including devices for performance evaluation, must register with the MHRA. Where a Notified Body has been involved in the assessment of the IVD, manufacturers must also wait to receive the appropriate certificate from the Notified Body.
For all devices, once the relevant assessment has been successfully completed (and the certificate received, as applicable) the manufacturer may place the CE mark on their medical device. The CE mark must be easily visible, readable and permanent. If a Notified Body has been involved in the assessment procedure then the Notified Body's number must also be shown alongside the CE mark.
Note on exemptions
Where a health institution manufactures an IVD in-house and then uses that IVD on the premises of the manufacture, then an exception to the requirements under the Directive may apply. However, other conditions will need to be met.
In certain circumstances, non-compliant IVDs may be shown at trade fairs, for example.