Circular No. 635 of 4 May 2018 details the approval procedure for risk minimisation activities (RMA). Certain paragraphs of this circular could be misinterpreted and specific situations were not considered. Therefore, the FAMHP would like to provide details on the RMA material included in the medicine package and on the addition / modification of RMA material for a medicine that is already available on the market.
Implementation period: basic rule
RMA must be implemented within 90 days after approval, unless the Minister or his delegate defines another deadline.
Additional time for implementation
Pharmaceutical companies may need more time in the particular situation where the approved RMA material consists of material included in the medicine package (e.g. a patient card placed in or attached to the medicine package).
For such implementation to take place within a reasonable period of time that takes not too long either, the FAMHP decided that this period could be aligned with the six-month legal period that is provided for the introduction of the new leaflets in accordance with article 35, § 4 of the Royal Decree of 14 December 2016.
This derogation implies that the QP (Qualified Person - GMP) will no longer release batches without RMA or with an old version of it, six months after the date of approval or after the date defined by the Minister or his delegate.
The measure also ensures that the RMA material and the package leaflet contain similar information.
Addition of RMA material after commercialisation : correction of incorrect interpretation of the circular
For a medicinal product that is already on the market and to which RMA material is added post-marketing, the circular does specify a deadline for the submission of the RMA file, neither a deadline for implementing the approved RMA material.
The RMA file should be submitted within the specified period and in according to the agreed conditions. In case of non-compliance, the commercialisation of the medicine may be suspended. RMA material must always be approved prior to its release.
In order to limit the time between the decision to add RMA material and its implementation, the FAMHP requests that this RMA material is implemented within six months after the decision to add it, unless another deadline is specified by the authorities.
Amendments to the circular
1. Section "1. Approval procedure": introduction
The introduction of section "1. Approval procedure" is completed by a third paragraph, as follows (additions are in bold):
The RMA file must be:
- submitted after the MA has been granted or after the EMA's Committee for Medicinal Products for Human Use (CHMP) has given a positive opinion on the evaluation procedure;
- approved prior to marketing unless an existing RMA program has varied or a new RMA program is added to an already marketed medicine.
In case of variations impacting RMA material, the application to update the material must be submitted either before the deadline specified by the authorities or, if no deadline is specified, within six months after approval of these variations .
In case of adding RMA material to an already marketed medicine without RMA, the RMA material must be implemented either before the deadline specified by the authorities or, if no deadline is specified, within six months after adding RMA material.
In order to meet the deadline, the MAH must submit the application for approval of the material as soon as possible, taking into account the deadlines inherent in the RMA approval process.
Please note that RMA material must be approved prior to its release.
2. Section "1. Approval procedure": point "f) Implementation"
In point f), the first paragraph is completed and a second one is added, worded as follows (additions are in bold):
Approved RMA must be implemented:
- Either when the medicine is placed on the market if RMA is imposed when the MA is granted
- Either within 90 days after the approval date if RMA is imposed after the MA has been granted or if RMA is added or if an already approved RMA file is impacted by variations, unless the Minister or his delegate sets another deadline.
- In the very particular case where the RMA is included in the package, its implementation will be aligned with the legislation foreseen for introduction of new leaflets (art. 35, § 4, of the R.D. of 14.12.2006). This derogation implies that the QP will no longer release batches without RMA or with an old version, six months after the date of approval or after the date defined by the Minister or his delegate.
If the RMA file is not submitted within the specified period or if the approval procedure has not resulted in an approval of the material, the commercialisation of the medicinal product may be suspended.
The MAH is responsible for implementing the RMA and their compliance with the approved file.