Consultation process for medical devices incorporating a medicinal substance

This information is intended as clarification of the consultation process to a Notified Body when consulting the Swedish Medical Products Agency

The Swedish Medical Products Agency (MPA), as an EU Competent Authority, may be consulted by a Notified Body for verification of the quality, safety and usefulness of a medicinal substance in a medical device. The opinion given by the Competent Authority is to be taken into account by the Notified Body in the overall assessment of the medical device.

Scope

The products concerned are medical devices that incorporate a medicinal substance as an integral part (e.g. implantable drug eluting stents, bone cements containing antibiotic, blood bags containing anticoagulant etc.).
When a medical device incorporates a medicinal substance (as defined in Directive 2001/83/EC) which is liable to act upon the body with action ancillary to the device; the safety, quality and usefulness of the substance must be verified by analogy with the relevant medicinal products legislation as required by Annex I section 7.4 of the Medical Devices Directive (93/42/EEC). The Notified Body has the ultimate responsibility to decide whether the pertinent legal requirements for the product are met. To be able to make this decision a consultation process, such as that defined in Annex II section 4.3 of the Medical Device Directive (93/42/EEC), involving a Competent Authority to verify the quality, safety and usefulness of the medicinal substance when this is an integral part of the medical device, is necessary. The opinion given by the Competent Authority should be taken into account in the overall assessment made by the Notified Body.

The borderline between a medical device and a medicinal product together with the process for consultation is described in a guideline (Guidelines relating to the application of: The council directive 90/385/EEC on active implantable medical devices; the council directive 93/42/EEC on medical devices).

Step 1 - Actions to initiate consultation process

A request for consultation is made by a Notified Body by completing the Request form (to the right on this page) and submitting the completed form by e-mail to registrator@mpa.se. The Request form is applicable both for consultations on New applications and Variation applications*). If a pre-submissionmeeting or a teleconference is requested, this should be specified in the form together with issues for discussion. The MPA will respond by e-mail whether the request can be accepted (based on the availability of required expertise).  The response will also include information on when the MPA is prepared to receive the documentation, estimated assessment time, classification of application including fee and meeting arrangements, if applicable.

The time table is valid provided the documentation is submitted according to the agreed date. In case of delay, a revised time table should be discussed with the MPA, otherwise a new request must be made.

*) Concerning some variations where it is not clear to the Notified Body whether or not a consultation is necessary the request form may be applied in order to ask for the MPA advice on  this matter. Some guidance related to variations for drug eluting stents are given below.

Step 2 - The consultation process

An Application form should be completed, in order for the MPA to register the application properly, and be attached to the scientific documentation for consultation. The application including documentation, preferably as electronic-only submission in the CTD format, should be submitted to RIC@mpa.se.

Please note that there are separate Application forms for new applications and variation applications (to the right on this page).

After registration of the application, a coordinator for the consultation procedure will be appointed by the MPA. A new reference number (ASP-no) will be assigned and communicated to the Notified Body. In subsequent correspondence concerning the consultation process, this reference number should be specified.

The MPA will evaluate the submitted documentation, applying an estimated primary assessment time of 120 days (new applications and major variations). In case of concerns or issues for clarification identified during the assessment, those will be sent as part of the assessment report to the Notified Body. A 210 day procedure is normally applied for new applications and after finalised assessment the MPA opinion will be sent to the Notified Body. For minor variations a 60 day procedure is applied.

The Notified Body will, shortly after registration of the application for consultation, receive an invoice specifying the fee in accordance with the information in the table below.

Drug /Device combination products – Consulation fees (SEK)

ClassificationFee1) (SEK)Remark
New active substance (NCE) in SE 400 000 e.g. NCE in a new or established therapeutic area
Known active substance in a new therapeutic area 250 000  
Known active substance in an established therapeutic area 150 000 e.g. a new stent with an active substance incorporated for which the MPA has previously been consulted
Variation - major 30 000 Major change which may affect quality of the active substance, safety or usefulness (e.g. new clinical data, new manufacturer of medicinal substance, change outside approved specification limits)
Variation - minor 10 000 Minor change which may affect quality of the active substance, safety or usefulness (e.g. new test method for the medicinal substance, tightening of specification limits)

1)only one fee will apply to multiple applications made at the same time for a range of similar drug/device combination products (e.g. a range of catheters made of identical material incorporating the same active substance in the same amount according to the same principle)

Guidance on changes related to drug eluting coronary stent consultations previously evaluated by the Swedish Medical Products Agency (MPA)

The Examples below will give some guidance on types of changes which should trigger a consultation. Examples are also given of changes which generally not require a consultation.

1. Examples of changes classified as major and where a consultation should be requested.

  • Change of the drug release profile of the coated coronary stent, resulting in a change of the accepted specification limits for drug release
  • New manufacturer of the drug substance, i.e. change or addition of a drug substance manufacturer

2. Examples of changes classified as minor and where a consultation should be requested.

  • Extension of shelf life of the stent
  • Reduced sample size for specification testing.
  • Minor change in specification parameter, for example, reduced testing frequency.
  • Test method optimization.

3. Examples of changes generally not requiring a variation application or a notification.

  • Extension of shelf life for a new strength of the stent up to the shelf life of the already assessed/approved strengths. changes to the developmental section, change in characterization tests (note: not to mix up with specification test.
  • Changes concerning the excipients relating to e.g. change of or addition of vendor, tightened specification limits, test method modification/optimization, inclusion of alternate storage conditions or extension of a retest period.
  • Changes of the manufacturing process of the coated stent which do not affect the quality of the drug substance.
  • Changes in the drug substance specification in order to be in compliance with the current specification for the substance (from the same manufacturer) that is used in a medicinal product on the EU market. (it is assumed that the manufacturer of the medical device  applies the currently approved drug substance specification which is applied by the manufacturer of the medicinal product).
 
 
 

Swedish Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, SWEDEN | +46 18 17 46 00 | registrator@lakemedelsverket.se | Contact information