V.B.10. RMP part VII “Annexes to the risk management plan”

The RMP should contain the annexes listed below (if applicable). If the RMP applies to more than one medicinal product, usually it would be expected that the annexes will be relevant for all products. Particular aspects not applicable to all medicinal products in the RMP should be highlighted (e.g. a follow-up form in annex 4 might only be applicable to the products containing the active substance that is causally linked to the event).

V.B.10.1. RMP annex 1

Annex 1 of the RMP is the structured electronic representation of the EU risk management plan. It is not required to be submitted in eCTD, the electronic file should be submitted in accordance to V.C.2. and the applicable guidance (8) . This annex can be left empty in the RMP document.

V.B.10.2. RMP annex 2: Tabulated summary of planned, on-going, and completed pharmacovigilance study programme

This annex should include a tabulation of studies included in the pharmacovigilance plan (current or in previous RMP versions; category 1, 2 and 3 studies), as follows:

• Planned and ongoing studies, including objectives, safety concern addressed, and the planned dates of submission of intermediate and final results.
• Completed studies, including objectives, safety concern addressed, and the date of submission of results to the competent authorities (effective, planned, or state the reason for not submitting the results).

V.B.10.3. RMP annex 3: Protocols for proposed, on-going, and completed studies in the pharmacovigilance plan

Annex 3 should not include protocols of studies not imposed nor requested by the competent authority (i.e. not in the pharmacovigilance plan). This annex may include the electronic links or references to other modules of the eCTD dossier where the protocols are included, instead of the full protocol documents.

V.B.10.3.1. RMP annex 3 – part A: Requested protocols of studies in the pharmacovigilance plan, submitted for regulatory review with this updated version of the RMP

If protocols have been requested to be submitted for review by the competent authority, and the marketing authorisation holder choses to submit for assessment a study protocol within the same procedure as the RMP submission, part A should include this protocol; alternatively the protocol might be reviewed in a stand-alone procedure, and once agreed, included in the RMP annex 3 – part C. The regulatory pathway for the protocol submission should be agreed with the competent authority.

V.B.10.3.2. RMP annex 3 – part B: Requested amendments of previously approved protocols of studies in the pharmacovigilance plan, submitted for regulatory review with this updated version of the RMP

If protocols amendments have been requested to be submitted for review by the competent authority, and the marketing authorisation holder choses to submit for assessment the study protocol amendment within the same procedure as the RMP submission, part B should include the updated protocol; alternatively the protocol amendment might be reviewed in a stand-alone procedure, and once agreed, included in the RMP annex 3 – part C. The regulatory pathway for the protocol submission should be agreed with the competent authority. Once approved, protocols from parts A or B should be moved to part C, with the next warranted RMP update.

V.B.10.3.3. RMP annex 3 – part C: Previously agreed protocols for on-going studies and final protocols not reviewed by the competent authority

Previously agreed protocols for on-going studies and final protocols not reviewed by the competent authority should be included in this part C of RMP annex 3, as follows:

• The full protocols that have been previously assessed by the competent authority and agreed (i.e. no protocol resubmission was requested). The protocols should be accompanied by the name of the procedure when the protocol was approved and date of the outcome. This may include the electronic link or reference to other modules of the eCTD dossier where the protocols have been previously submitted, instead of the full protocol documents.
• The final protocols of other category 3 studies: protocols that were not requested to be reviewed by the competent authorities and are submitted by the marketing authorisation holder for information only.

Protocols of completed studies should be removed from this annex once the final study reports are submitted to the competent authority for assessment.

V.B.10.4. RMP annex 4: Specific adverse event follow-up forms

This annex should include all follow-up forms used by the marketing authorisation holder to collect additional data on specific safety concerns. The usage of follow-up forms included in this annex should be detailed in the pharmacovigilance plan in the RMP, as routine pharmacovigilance activities.

The forms that should be included in this annex are sometimes known as “event follow-up questionnaire”, “adverse event data capture/collection aid” or “adverse reaction follow-up form”.

V.B.10.5. RMP annex 5: Protocols for proposed and on-going studies in RMP part IV

This annex should include links or reference to other parts of the eCTD dossier, where the protocols for an imposed efficacy study are already included, for studies included in RMP part IV.

V.B.10.6. RMP annex 6: Details of proposed additional risk minimisation activities

If applicable, this annex should include the proposed draft (and approved, if applicable) key messages of the additional risk minimisation activities.

V.B.10.7. RMP annex 7: Other supporting data (including referenced material)

When applicable, to avoid duplication of the materials presented as references, this annex should include eCTD links or reference to other documents included in other modules of the dossier.

V.B.10.8. RMP annex 8: “Summary of changes to the risk management plan over time”

A list of all significant changes to the RMP in chronological order should be provided in this annex. This should include a brief description of the changes and the date and version number of the RMPs when:

• safety concerns were added, removed or reclassified;
• studies were added or removed from the pharmacovigilance plan;
• risk minimisation activities recommending specific clinical measures to address the risks or additional risk minimisation activities were modified in the risk minimisation plan.