Risk management plan (RMP)

  1. Overview on RMP

Overview on RMP

Understand the components of an RMP and their role in addressing risks associated with a product.

What is an RMP?

An RMP is a detailed description of the risk management system that is put in place to identify, characterise, prevent, and minimise risks relating to a product.

The RMP comprises the product’s:

  • Safety concerns, which include the product’s important identified risks or potential risks, and missing information
  • Proposed pharmacovigilance (PV) activities to identify and characterise safety signals and clinically relevant risks
  • Proposed risk minimisation activities (RMA) to reduce the probability or severity of adverse events

Pharmacovigilance (PV) activities

Routine PV activities include:

  • Monitoring the safety profile of registered products, including signal detection and evaluation
  • Reporting local serious adverse events to HSA in accordance with the stipulated timeline
  • Providing timely notifications to HSA on significant safety issues that may influence the overall benefit-risk profile of the product (see Post-registration RMP obligations)
  • Preparing the product's Periodic Benefit-Risk Evaluation Reports (PBRER). HSA may request for the submission of PBRER for selected products on a routine or ad hoc basis (see Post-registration RMP obligations)

Additional PV activities can include:

  • Conducting and submitting the results of post-market safety studies e.g. monitoring of long-term safety from clinical studies
  • Conducting active surveillance programmes
  • Regular review and submission of data from established local or overseas patient registries

For CTGTP, in particular gene therapy products that may present long-term risks to patients, the proposed plan for long-term follow-up observations of delayed adverse events should be discussed in the RMP. The discussion may include the following:

  • Objective(s) of the long-term follow-up (e.g. to monitor for insertional mutagenesis and secondary malignancy)
  • Safety endpoint(s)
  • Proposed long-term follow-up plan (e.g. conduct of observational studies and/or randomised controlled trials, leveraging existing registries)
  • Patient population
  • Data source (e.g. clinical studies, patient registries)
  • Duration of follow-up (e.g. 15 years for products using integrating vectors, or products with potential for reactivation from latency)
  • Frequency of submission of the long-term follow-up reports

Risk minimisation activities (RMA)

Routine RMA include:

  • Provision of warnings and precautions in the package insert
  • Timely safety updates to labelling and packaging

Additional RMA can include:

Provision of physician and/or patient educational materials

Educational materials may be developed to provide the necessary information to help physicians and/or patients mitigate or manage safety concerns that may be significantly reduced through tighter patient selection, closer monitoring, or earlier detection and management of adverse events.

Issuance of Dear Healthcare Professional Letter (DHCPL)

A DHCPL is a communication tool intended to alert healthcare professionals about important new or updated safety information regarding a product and any actions they may need to take. A DHCPL may be initiated by the product registrant or HSA.

Implementation of controlled access programme

A controlled access programme may be required for products with significant safety concerns when used by the general population, but have a place in therapy for certain patient populations (e.g. treatment of conditions without alternative therapies). Under this programme, supply of the product may be restricted to selected physicians/specialists/pharmacies, and patient access is contingent on fulfilment of one or more requirements.

Implementation of pregnancy prevention programme

A pregnancy prevention programme may be required for products with known or potential teratogenic effects. It lays out a set of interventions that aim to minimise the likelihood of pregnancy during treatment and drug exposure during pregnancy.

Next RMP submission for product registration