Risk management plans for medicines and biologicals

12 December 2017

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Evaluation process for Risk Management Plans

The process used to evaluate the RMP (as a component of the application) is in accordance with the prescription medicines registration and biological inclusion processes.

Who is responsible for evaluating the RMP?

Several areas of the TGA will undertake evaluation of the RMP, including the Risk Management Plan Evaluation Section.

What is considered in the evaluation?

In evaluating the RMP, we will consider:

  • safety specifications identified (by the sponsor) at the time of application
  • additional safety concerns identified during the course of our evaluation of other modules included in the application (which may result in amendments to the safety specifications originally submitted)
  • adequacy and appropriateness of the proposed product vigilance and risk minimisation plans for the specified safety concerns

RMP Evaluation process for medicines

Step Description
Round 1 evaluation (Milestone 3)

Recommendations for amendments:
Summary of safety concerns
Consumer Medicine Information document
Product Information document
Risk minimisation plan
Pharmacovigilance plan
If available, advice from the clinical and nonclinical evaluations will be incorporated at this stage

Round 1 report Response to request for information (s31)
Round 2 evaluation (Milestone 5)

Reconciliation of s31 response to issues raised in Round 1 report.
Incorporation of further advice from:
ACM/ACV (if sought after milestone 3)
Clinical
Nonclinical

Post-Round 2 evaluation Consider pre-ACM/ACV response
Expert advisory review (Milestone 6)                  (if required) Advisory Committee on Medicines (ACM) or Advisory Committee on Vaccines (ACV
Final reconciliation Final RMP negotiation, considering any ACM/ACV advice, the post-ACM/ACV response and final PI and CMI modifications
Decision to approve (Milestone 7) Delegate
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

RMP Evaluation process for biologicals

Step Description
Round 1 Evaluation

Recommendations for amendments:
Table of ongoing safety concerns
Patient information leaflet
Product Information document
Risk minimisation
Biovigilance

Round 1 report Response to request for information (s32JA)
Round 2 Evaluation

Reconciliation of s32JA response to issues raised in Round 1 report.
Incorporation of advice:
ACB (if sought after round 1 evaluation)
Clinical
Nonclinical

Post-Round 2 evaluation Consider pre-ACB response
Expert advisory review (Milestone 6)(if required) Advisory Committee on Biologicals (ACB)
Final reconciliation Final RMP negotiation, considering any ACB advice, the post-ACB response and final PI and CMI modifications
Post-Round 2 evaluation Delegate
Post-approval

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 role 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, 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 may seek expert advice on the risk management plan either:

  • between Milestone 3 and Milestone 4 of the prescription medicines registration process, and between the first and second rounds of RMP evaluation for biologicals

OR

  • at the committee advice phase (Milestone 6 of the prescription medicines registration process)

We will endeavour to 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.

When does the TGA provide feedback on the RMP evaluation?

Medicines

We will issue a full RMP evaluation report and any recommendations and/or questions on the RMP via the single round s31 information requests at Milestone 3.

The relevant recommendations from the clinical and nonclinical evaluation reports and the sponsor's response to the RMP evaluation report will be incorporated into the RMP advice document after Milestone 5.

This advice will be provided to the Delegate, and then sent to the sponsor with the Delegate's overview (if there is no Delegate's overview, this will happen soon after Milestone 5).

The RMP may be subject to review or consideration by the TGA 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. After each round of evaluation, we will send the updated RMP evaluation report to the sponsor.

Biologicals

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

The relevant recommendations from the clinical and nonclinical evaluation reports and the sponsor's response to the RMP evaluation report will be incorporated into the RMP advice document after the second round of RMP evaluation.

This final report will be provided to the Delegate and sent to the sponsor before any regulatory decision.
The RMP may be subject to review or consideration by the TGA 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

You may submit an updated RMP with your response to the consolidated s31 questions or s32JA request and the RMP evaluation report. If you anticipate an updated RMP will be available during the evaluation process, please identify this in the RMP documentation (for example, by including the due date for the updated RMP).

Summary table

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

Maintaining records

Ensure you maintain records of:

  • when RMPs were submitted to us

AND

  • the significant changes between each version of the RMP

Other requirements

  • Ensure you reflect in the RMP 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
  • For changes that have no impact on the EU RMP, but impact 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)
  • We recommend that, on completion of the evaluation process, sponsors submit a final version of the RMP confirming the risk management activities for monitoring purposes

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