Post-marketing phase

After receiving a positive opinion (and certification) for a medical device, a variation can be submitted or side effects or calamities reported at a later stage in the life cycle, if necessary.

Variations

Variations are changes towards the dossier as known at the MEB related to the ancillary substance of the device. This means changes relating to the quality, safety or benefit/risk of the substance which forms an integral part of the medical device, but which would be a medicinal product when used separately and whereby a consultation with a competent authority in the EU has already taken place for this substance and the product is certified.

Variations under MDD continue to be possible provided the 'minor' change requirement is met, see MDCG 2020-3 (Guidance on significant changes regarding the transitional provision under Article 120 of the MDR with regard to devices covered by certificates according to MDD or AIMDD March 2020),

As regards submitting details for a variation, you are kindly requested to submit the dossier in accordance with the EC/1234/2008 variation regulation for medicinal products. With the MDR coming into effect, the procedure will, for the time being, consist of a round of 40 days and if necessary a 2nd round of 20 days (excluding clock stop). As far as variations are concerned, the MDR does not make any distinction in degree of complexity and assessment time (see MDR, Annex IX, Chapter II, 5.2 f). The variation regulation for medicinal products, there are four different types of variations, namely IA, IB, II and line extensions.

Please note, that certain changes with a significant effect on the quality, safety or efficacy of the ancillary medicinal substance cannot be handled within a variation procedure, because the device is considered to be a ‘new’ device. In these circumstances, a new initial consultation procedure should be followed. Please see below at ‘New consultation procedures’.

  • A type IA variation relates to a change which only has a minimal impact or no impact at all on the quality, safety or efficacy of the active substance. A Type IA variation is only validated without the MEB assessing its content. The MEB must be informed within a year of the implementation of an IA variation. It is possible to combine a number of type IA variations in an annual report, in line with EC/1234/2008. An annual report like this will be processed like a variation, consisting of 2 rounds.
  • Type IB variations are all changes which have not been defined as type IA or type II variation, or as a line extension, and which do not have any significant impact on quality, safety or efficacy of the active substance. A Type IB variation is validated and assessed.
  • A type II variation is a change which is not a so-called line extension and which can have a significant impact on the quality, safety or efficacy of the medicinal product in question. A Type II variation is validated and assessed.
  • A line extension is a recommendation for a medical device in the name of the same company, whereby only the strength differs from other medical devices for which the company already has a certificate, or has applied for one. With a different strength also changes in the total amount of the medicinal substance are meant, for example with the addition of a different length of a coated stent for which the concentration with each surface remains the same, but the total exposure towards the medicinal product changes.  A new consultation procedure (CP) sub-number will always be assigned. For example, CP 100 has an existing certificate. The line extension will be assigned the number: CP 100.2 and the existing CP 100 will be CP 100.1.

New consultation procedures

Several complex changes cannot be implemented via a variation procedure and the product will be assessed as a new medical device. If in these cases no additional ancillary substance is integrated, the fee corresponding to an initial consultation procedure with known active substance is charged.  . If a substance is added, the fee will depend on whether the substance is new or known.

Below examples are given of such complex changes which can not be handled via a variation procedure:

Changes relating to the integral substance

  • The addition of one or more integral substances
  • The omission of one or more integral substances
  • A quantitative change to the integral substance
  • The replacement of the integral substance with a different salt/ester complex/derivative
  • The replacement with a different isomer, different mixture of isomers, or a mixture with an isolated isomer (for example a racemate by a single enantiomer)
  • The replacement of a substance which has been prepared using biology or biotechnology with one with a different molecular structure, or for which a modification of a vector used to prepare the antigen/source material (including a master cell bank from a different source) has been implemented
  • A new ligand or binding mechanism of a radiopharmacon.

Changes relating to the use of the medical device

  • The addition of a medical ground in a different therapeutic field
  • A change to a medical ground in a different therapeutic field
  • The addition of a new route of administration
  • A change to the route of administration.

Changes relating to the medical device

As a result of which the pattern and the degree of local and systemic release of the medicinal product could change, for example: Addition of a foil towards a plaster/wounddressing which results in administration under occlusion.

Reports of adverse reactions and calamities

The competent authority for all medical devices in the Netherlands is the Health and Youth Care Inspectorate (IGJ). Adverse reactions and calamities must be reported to the IGJ (in addition to the notified body that granted the certificate). You can find information on this on the IGJ website. The MEB only needs to receive a copy if the report concerns a medical device with an added pharmaceutical substance. You can do this using the contact form.

On the other hand, the MEB will advise the notified body as soon as it receives information about the ancillary substance which may affect the previously determined risks or benefits of the incorporation of the substance in the device. In that case the MEB will advise the notified body as to whether this information may or may not affect the previously determined risks or benefits of the incorporation of the substance in the device. The notified body must take account of this advice from the MEB when reviewing its assessment of the conformity assessment procedure. The MEB will only give the above advice if the MEB issued an opinion earlier in the consultation procedure, issued an opinion in a reconsultation procedure, or adopted the role of an earlier medicines agency via a transfer.