procedure & dossier requirements

If a Notified Body wants to seek advice (Consultation Procedure) from the MEB with regard to a substance that is an integral part of a medical device but that is a medicinal product when used separately, the MEB follows the procedure described below.

1. The MEB asks for written notification that advice (Consultation Procedure) will be sought, preferably one to two months before submission of the dossier. At this stage the Notified Body can, if it wishes, also indicate that it would like to have a pre-submission meeting. If prior Scientific Advice (or Regulatory Advice) is being sought, then as with applications for medicinal products this should normally have been requested at an earlier stage. The MEB then proposes a timetable and assigns a consultation number. This timetable indicates when the assessment can begin (and where appropriate when the pre-submission meeting would take place) and what the assessment period is (see also point 3). As the capacity for assessment in the context of the consultation procedure is not unlimited, the MEB might sometimes set a starting date a few weeks or months after the announced dossier submission date. If the Notified Body decides to waive consultation in view of the proposed timetable or for other reasons, the MEB would like to be informed of this as soon as possible. If the dossier is not received until more than one or two weeks after the announced submission date, then the timetable previously announced may have to be revised.

2. The dossier is validated on receipt. This includes ascertaining whether all the documents mentioned are actually present and whether the dossier meets the requirements set out below (see points 8 to 10). The MEB also decides whether the product can in fact be regarded as a medical device containing as an integral component a substance that is a medicinal product when used separately and that merely supports the operation of the medical device.
The Notified Body will be informed as to whether the dossier is valid within two weeks. Dossiers that are invalid will not be processed. Notified Bodies will be given the opportunity to submit additional documentation and information as rapidly as possible. The dossier may then be declared valid. The timetable might be revised as a result.
If the dossier is declared valid, an invoice for payment will be sent to the Notified Body (for details of fees, see the document Consultation procedure for medical devices: Fees). If the fee due has not been received by 30 days after the invoice date, the assessment will be stopped and will not resume until the amount owed has been received. This might also mean that the deadlines previously set out in the timetable are not met.

3. The assessment periods are:

  * New substances are defined as substances that at the time of the request for consultation were not included as active ingredients in any medicinal product authorised in the Netherlands.
Known substances on the other hand are substances that at the time of the request for consultation were included as active ingredients in one or more medicinal products authorised in the Netherlands. If the indication to which the consultation procedure relates is for a therapeutic area different from the indications for which the aforementioned medicinal products are authorised, then this is regarded as a new application of a known substance.

** Variations are all changes relating to the quality, safety or usefulness of the substance which is an integral component of the medical device but which is a medicinal product when used separately, and where a consultation with a competent authority has already taken place with regard to this substance, which resulted in the product’s certification. Some changes are so far-reaching that the product has to be regarded as a new medical device (for more information see: Fees).

4. Once the procedure has begun (once the dossier has been declared valid), the Notified Body may at any time withdraw its request to consult the MEB and ask a different competent authority for advice. It is requested to notify the MEB of the name of the new competent authority in this event. The MEB must be notified in writing without delay of the withdrawal of consultation requests. Any fees that have already been paid will not be reimbursed. Any outstanding payments still have to be paid.

5. The advice requested will be provided in writing. It will comprise one or more (sub) reports and a covering letter with a recommendation arising from the attached (sub) report(s). The recommendation may be:

• a positive opinion that the quality, safety and usefulness of the substance has been sufficiently demonstrated in accordance with the standards applied by law for the marketing authorisation of medicinal products;
• a request for more information;
• a negative opinion that the quality, safety and usefulness of the substance has not been sufficiently demonstrated in accordance with the standards applied by law for the marketing authorisation of medicinal products.

If either a positive or negative opinion is issued, the consultation is regarded as terminated.
If the MEB asks for more information, the Notified Body should submit the data requested preferably within four months or within another timescale set by the MEB. The Notified Body may ask for this deadline to be extended. Such requests will always be answered in writing, and a new date may be set if deemed appropriate. The MEB normally reaches a final decision after two assessment rounds at the most. An additional (third) assessment round may be needed in exceptional cases in the light of new information brought to the MEB’s attention (during a hearing, for example). The MEB decides whether a third round is necessary.
If the additional information is not received within the agreed time, the 'quality, safety and usefulness' of the substance is regarded as insufficient and the consultation is considered terminated.

6. Once the consultation procedure has been completed, the Notified Body is asked to inform the MEB of its decision on the medical device in question, and to state whether its decision diverges from the advice given by the MEB. If the Notified Body receives a negative opinion from the MEB, it is asked to consult the Health Care Inspectorate (Chief Inspector for Pharmacy and Medical Technology) before granting a certificate.

7. The MEB does not consider itself to be under any obligation to file the data submitted in the context of the consultation procedure. Of course, data submitted will be treated confidentially.

8. The following documentation is required, presented clearly and with a table of contents:

• A fully completed and signed Consultation request form. N.B. when requesting advice on a series of products, a separate form must be completed for each presentation.
• A provisional opinion of the Notified Body on the suitability of the medical device with the supporting medicinal substance.
  If the Notified Body has not yet completed its assessment, it is requested to submit a provisional opinion on the parts that have already been assessed and a summary of the aspects that have yet to be evaluated (e.g. biocompatibility investigation). N.B. this provisional opinion should be stated on the Consultation request form.
• The documentation as described in "Commission Guidance Document: Medical Devices (MEDDEV 2.1/3 Rev 3)" ( Dec 2009)
  See under C.3 "Documentation to be provided by the Notified Body to the competent authority.
  The format (section headings and structure) of the MEDDEV document can be used.
• the MEB would much prefer to receive the entire dossier on an electronic data carrier (CD-Rom). However, the signed cover letter from the Notified Body accompanying the dossier should be submitted on paper.
• The summary of the risk analysis - referred to in C.3. 1) “General Information” of the MEDDEV document - should be attached as an appendix to Module 5 rather than Module 1. If it is impossible to submit all the data requested, arguments should be presented for each section as to why this is not thought necessary.
• As far as the chemical-pharmaceutical and biological data are concerned, the requirements for human medicinal products are set out in considerable detail in Directives, Regulations, Decrees and Guidelines. The data for Module 3 should comply with these documents as far as possible.

N.B. In the case of substances of animal origin, attention must be paid to viral safety and the risk of transfer of transmissible spongiform encephalopathies (TSE) to humans.

• Where possible, all clinical data submitted by the manufacturer of the medical device to the Notified Body should be provided. Clinical data that is not directly relevant for supporting the medicinal substance’s safety and usefulness can be included as an appendix to Module 5.
• Only data relevant to the consultation should be submitted.

9. As already mentioned under point 8, the MEB would much prefer to receive the entire dossier on an electronic data carrier (CD-Rom). For electronic submissions, please refer to the MEB website also. However, in case the dossier is submitted on paper, submission of a single copy will be sufficient.

10. The Modules 3, 4 and 5 should preferably be written in Dutch or English, but German and French are also acceptable.
The other documents should be written in Dutch or English. For more information regarding the Consultation Procedure, please contact the Pharmacotherapeutical Groups.