You are here

Risk management plans for medicines and biologicals

Australian requirements and recommendations

29 March 2019

Book pagination

Evaluation process for Risk Management Plans

RMPs are evaluated during the prescription medicines registration and biological inclusion processes.

Who is responsible for evaluating the RMP?

The Risk Management Plan Evaluation Section is primarily responsible for evaluating the RMP. The clinical and non-clinical evaluators provide advice to the RMP evaluator about the adequacy of the summary of safety concerns in the RMP.

What is considered in the evaluation?

In evaluating the RMP, we will consider:

  • the adequacy of the summary of safety concerns at the time of application
  • identification of additional safety concerns during the course of our evaluation of other modules included in the application (which may result in recommendations to amend the summary of safety concerns originally submitted)
  • the adequacy and appropriateness of the proposed product vigilance and risk minimisation activities for the specified safety concerns

RMP Evaluation process for medicines and biologicals

Table 3 below describes the RMP evaluation process for prescription medicines and biologicals. For medicines, the process reflects the standard application pathway. Refer to other TGA guidance for information about RMP evaluation during the priority or provisional or comparable overseas regulator pathways.

Table 3: RMP evaluation process steps for prescription medicines and biologicals
Step Prescription medicine process Biologicals process

Round 1 evaluation

Recommendations for amendments:

  • Summary of safety concerns
  • Consumer Medicine Information
  • Product Information
  • Risk minimisation plan
  • Pharmacovigilance plan

If available, advice from the clinical and nonclinical evaluations will be incorporated at this stage.

The report is provided at Milestone 3.

Recommendations for amendments:

  • Summary of safety concerns
  • Patient information leaflet
  • Product Information
  • Risk minimisation plan
  • Biovigilance plan

Round 1 report

Response to request for information (s31)

Response to request for information (s32JA)

Round 2 evaluation

Reconciliation of s31 response to issues raised in round 1 report.

Incorporation of further advice from:

  • clinical evaluator
  • non-clinical evaluator

Questions for expert advisory committee determined, if advice required

Note: the report is usually issued two weeks after Milestone 5 to allow for incorporation of final clinical and non-clinical advice.

Reconciliation of s32JA response to issues raised in round 1 report.

Incorporation of advice from:

  • clinical evaluator
  • non-clinical evaluator

Questions for expert advisory committee determined, if advice required

Post-Round 2 evaluation

Consider pre-ACM/ACV response

Consider pre-ACB response

Expert advisory review (if required)

Advisory Committee on Medicines (ACM) or Advisory Committee on Vaccines (ACV)

If required, committee advice will normally be sought at Milestone 6

Advisory Committee on Biologicals (ACB)

Final reconciliation

Final RMP negotiation, considering any ACM/ACV advice, the post-ACM/ACV response and final PI and CMI modifications

Final RMP negotiation, considering any ACB advice, the post-ACB response and final PI and CMI modifications

Decision to approve

Implementation of the RMP is imposed as a condition of registration at the decision date (Milestone 7)

Implementation of the RMP is imposed as a condition of inclusion

Post-approval

Ongoing pharmacovigilance and risk-minimisation:

  • Periodic Safety Update Report (PSUR) submission for a specified period of time
  • RMP updates submitted as per guidelines for the life cycle of the product

Ongoing biovigilance and risk-minimisation:

  • Periodic Safety Update Report (PSUR) submission for a specified period of time RMP updates submitted as per guidelines for the life cycle of the product

The roles of the Advisory Committees

In some cases, we will seek advice from one (or more) of our advisory committees on the adequacy and appropriateness of the safety specifications, and product vigilance and risk minimisation activities, detailed in the RMP.

We notify the sponsor in the RMP report when a product is to be referred to one or more of these committees.

If advice is required

We will provide the questions to the sponsor prior to the committee meeting. However, in accordance with the prescription medicines registration process and the biologicals inclusion process, there is no opportunity to submit additional or supplementary data at this stage prior to committee review.

Medicines

We would usually seek expert advice on the risk management plan at the committee advice phase (Milestone 6 of the prescription medicines registration process). In some cases we may seek advice between Milestone 3 and Milestone 4 of the prescription medicines registration process.

Biologicals

In some cases we may seek advice between the first and second rounds of RMP evaluation for biologicals.

When does the TGA provide feedback on the evaluation of an RMP?

Medicines

We will issue a full RMP evaluation report, and any recommendations and questions on the RMP, via the single round s31 information requests at Milestone 3, except for applications assessed under the priority pathway, for which the RMP evaluation report will be issued at the conclusion of the evaluation phase.

The relevant recommendations from the clinical and non‐clinical evaluation reports, and the sponsor's response to the RMP evaluation report, will be incorporated into the RMP evaluation when available. This may be after Milestone 5 for medicines.

This advice will be provided to the Delegate and sent to the sponsor.

The RMP may be subject to review or consideration by TGA's advisory committees and, in this case, the relevant minutes from the ACM or ACV meeting(s) will be provided to the sponsor.

If there are outstanding issues after the round 2 RMP evaluation, we will conduct further rounds of RMP evaluation as needed. After each round of evaluation, we will send the updated RMP evaluation report to the sponsor. We may also contact the sponsor directly to discuss the outstanding issues.

Biologicals

We will issue a full RMP evaluation report, and any recommendations and questions on the RMP, via the s32JA information request after the first round of RMP evaluation.

The relevant recommendations from the clinical and non‐clinical evaluation reports, and the sponsor's response to the RMP evaluation report, will be incorporated into the RMP evaluation when available. This may be after the second round of RMP evaluation.

This final report will be provided to the Delegate, and then sent to the sponsor before any regulatory decision.

The RMP may be subject to review or consideration by the TGA's advisory committees and, in this case, the relevant minutes from the ACB meeting(s) will be provided to the sponsor.

If there are outstanding issues after the round 2 RMP evaluation, we will conduct further rounds of RMP evaluation. After each round of evaluation, we will send the updated RMP evaluation report to the sponsor.

RMP updates during the evaluation process

An updated EU RMP may become available during the evaluation process, either due to sponosr-initiated changes, or changes required as part of the evaluation process in the EU. If you anticipate that this will occur, please advise us in your submission (for example, by including the due date for the updated RMP in your ASA, or including a note to the reviewer).

We may ask you to submit an updated RMP to reflect required changes identified during the evaluation.

Any updated RMP submission requires a:

  • summary table of changes between the updated RMP and the last RMP submitted to the TGA
  • cover letter stating the reason for submission

It is acceptable to submit an updated version of the RMP with tracked changes or annotated changes, in addition to a clean version.

Maintaining records

Maintain records, in Section 1.1 of the revised ASA template, of:

  • when RMPs were submitted to us, and
  • the significant changes between each version of the RMP.

Other requirements

  • Ensure you reflect any updates to the Product Information (PI), Consumer Medicine Information (CMI) or Patient Information Leaflet that result from the evaluation process in the subsequent version of the ASA. If available, this may be provided with the closing sequence that contains the approved PI and CMI, or at a later date as post-approval RMP update.
  • For changes that have no impact on the EU RMP, but affect the ASA, providing an updated ASA is sufficient, with a reference to the current EU RMP version (for example: changes to Australian PI/CMI documents).
  • On completion of the evaluation process, you should ensure that a final version of the RMP confirming the agreed pharmacovigilance and risk minimisation activities has been submitted. This may require submission of a revised version that addresses any recommendations made in the round 2 or subsequent evaluation reports.
  • We may ask you to provide hard copies of final additional risk minimisation materials and passwords to access electronic materials, when available, for our records.

The RMP in the Australian Public Assessment Report (AusPAR)

The AusPAR will contain a section on pharmacovigilance findings, which will include the summary of the RMP evaluation, including the following key elements:

  • the agreed summary of safety concerns
  • a summary of the associated pharmacovigilance and risk minimisation activities, including whether additional activities are being conducted to address particular safety concerns

The AusPAR may include:

  • timelines for planned activities, such as:
    • reporting dates for key ongoing or planned studies
    • communication program milestones
  • any differences between the risk minimisation activities undertaken in Australia compared to the EU

It may also include the key safety messages and outcomes of additional risk minimisation activities.

How is the RMP referred to in the conditions of registration or inclusion?

The latest versions of the RMP and ASA that have been evaluated by the TGA will be included in the conditions of registration or inclusion (taking into account any updates provided during the evaluation process). In some circumstances we may apply a version of the RMP and ASA evaluated as part of a concurrent submission as a condition of registration.

In addition, your written agreements to the RMP evaluator's recommendations during the s31 process or s32JA process (which are not explicitly stated in the RMP document), as well as any further requirements determined by the Delegate, may be included in the conditions of registration or inclusion.

Book pagination