Risk management plan (RMP)

  3. Post-registration RMP obligations

Post-registration RMP obligations

Understand your RMP obligations as registrants of therapeutic products and CTGTP.

Implementation of RMP requirements

Registrants are responsible for the implementation and continued compliance with the RMP requirements to characterise or minimise the risks associated with their products. These include routine PV activities and RMA, as well as additional PV activities and RMA stipulated in the product registration conditions. Other information, such as data on local product utilisation, may also be requested by HSA on an ad hoc basis.

Safety notification to HSA

The registrant must notify HSA of actions taken by HSA's reference drug regulatory agencies or the registrant to address significant safety issues which may influence the overall benefit-risk profile of the product as soon as possible.

Examples of such actions include:

  • Update to warnings or safety information in the overseas product labelling requested by HSA's reference drug regulatory agencies, including removal of approved indications
  • Company-initiated risk minimisation measures related to newly emerging safety issues that were not mandated by HSA, e.g. dissemination of local Dear Healthcare Professional Letter
  • Product withdrawal/suspension due to safety concerns
  • Failure to obtain a product registration renewal due to safety reasons

The safety notification should describe the safety-related reasons that led to the actions being taken, with supporting documents where appropriate. Each notification should be accompanied by the registrant's assessment on the significance of the safety issue in the local context and recommendation(s) on follow-up action(s) to be undertaken locally. If the assessment by the reference agency or registrant is still ongoing, the anticipated timelines for the assessment outcomes should be provided in the interim, followed by the final outcomes when available.

Any intention of voluntary local withdrawal/discontinuation of a registered product from the market by the registrant arising from safety issues should be discussed with HSA at an early stage.

Submission of PBRER upon HSA's request

The Periodic Benefit-Risk Evaluation Report (PBRER) provides a comprehensive, concise and critical analysis of new or emerging information on the product’s benefit-risk profile in its approved indications.

HSA may request for the routine submission of PBRER for specific products (see How to submit). The registrant will be informed accordingly through the product’s registration conditions.

The registrant must submit the PBRER:

a) at intervals of 6 months commencing from the date of registration of the product for an initial period of 2 years; and

b) annually, for the next 3 years.

The first PBRER submitted should include data from the date of local product registration. For example, if the product was approved locally in July and the data lock period of the latest available PBRER was from January to June, this PBRER does not need to be submitted. Instead, the next PBRER with a data lock period of July to December will be considered as the first PBRER submission to fulfil the post-approval conditions for the product.

Each subsequent PBRER should cover the period since the last updated report and should be submitted within 70 days (for PBRER covering up to 12 months) or 90 days (for PBRER covering more than 12 months) from the data lock point.

After the initial 5 years of registration approval, HSA may request for PBRER to be continued to be submitted if there are reasons to continue the safety monitoring of the product in the market.

How to submit

  • CTGTP – SHARE (Fulfilment of Approval Condition)

Please indicate the purpose of the submission. For example, “PBRER submission for [Product Name], Data lock period DD-MM-YYYY to DD-MM-YYYY”

HSA-approved educational materials

Distribution

Publication and distribution of educational materials

Following HSA’s approval of the educational materials, the registrant should submit the finalised artwork (i.e. version for local distribution) to HSA for publication on the HSA website when available (see How to submit).

The registrant must also ensure that all healthcare professionals (HCP) who will be prescribing the product are provided with the latest copy of the HSA-approved physician educational materials. Copies of the latest approved patient medication guides and/or patient alert cards must also be made available to HCP for distribution to their patients who are supplied with the product.

Registrants are to keep the records of the distribution of these educational materials to the HCP and submit these records to HSA upon request. The distribution records must include the following information:

  • Names of the healthcare institutions/clinics/pharmacies receiving the educational material(s)
  • Date of distribution of the educational material(s)

HSA does not dictate the mode of distribution of the educational materials (i.e. hardcopy or softcopy), as long as the materials are disseminated in accordance with the product’s registration conditions. Companies who are planning to host educational materials on digital platforms are encouraged to notify HSA of their intention to implement an electronic RMP.

How to submit

Finalised artwork of HSA-approved educational materials should be submitted via:

  • Therapeutic products

– Approved within NDA or GDA application – Online form

– Administrative changes to approved materials – Online form

– Approved safety or clinical revisions to existing materials – HSA will inform registrants of the method of submission

  • CTGTP – SHARE (Fulfilment of Approval Condition)

Please indicate the purpose of the submission. For example, “Finalised artwork for [Product Name]”

 

Revision

Submission of revised educational materials

All post-approval revisions to the educational materials are to be submitted to HSA for approval or notification (see How to submit).

  • For approval – Revisions affecting the clinical use and/or safety content of the educational materials must be reviewed and approved by HSA prior to distribution to the HCP.
  • For notification – Revisions that do not affect the clinical use and/or safety content of the educational materials (e.g. editorial updates, artwork changes, version number or company logo changes, corrections of typographical errors, changes in address, and other administrative changes) do not require HSA’s approval and may be distributed following their submission to HSA.

Following HSA’s approval of the revised educational materials, the registrant should submit the finalised artwork to HSA when available. The revised materials will replace the existing version published on the HSA website.

How to Submit

Both draft and clean copies of the proposed revised educational materials should be submitted via: 

  • CTGTP – SHARE (Fulfilment of Approval Condition)

 

Discontinuation

Request for discontinuation of existing educational materials

For educational materials that have been implemented locally for at least 5 years, the registrant can review the need for continuation of these educational materials and provide justifications to HSA should the registrant wish to propose discontinuing the existing materials (see How to submit).

The justifications should include:

  • Summary status of safety concerns highlighted in the educational materials to support the discontinuation of the materials (e.g. changes in adverse event reporting rates or trends since implementation of the educational materials)
  • New and/or emerging safety concerns associated with the product (if any) and the actions taken to manage these safety concerns over the past 5 years
  • Whether educational materials were requested by HSA’s reference drug regulatory agencies, including an elaboration on the type of materials requested and whether these materials are still being implemented or have been discontinued
  • Local annual sales data for the past 5 years
  • Registrant’s proposed local education action plan for new and/or emerging safety concerns as well as those highlighted in the educational materials upon discontinuation of the materials
  • Any other relevant information

How to Submit

Requests for discontinuation of HSA-approved materials should be submitted via:

  • CTGTP – SHARE (Fulfilment of Approval Condition)

Please indicate the purpose of the submission. For example, “Discontinuation of PEM for [Product Name]"

HSA-approved controlled access programme or pregnancy prevention programme

Registrants should have a system in place such that the following information can be provided to HSA upon request:

  • List of authorised prescribers/pharmacies that supplied the product to patients
  • Number of patients prescribed with the product

  • Distribution records of the educational materials, including

- Name and address of the healthcare institutions/clinics/pharmacies where the materials are distributed

- Date and distribution of educational materials

The distribution records of the educational materials must be retained for two years from the date of distribution.

  • Number of potential pregnancy exposures in patients and pregnancy outcomes with congenital malformations (only applicable to pregnancy prevention programmes)

New or updated forms used in the controlled access programme or pregnancy prevention programme should be provided for updating of HSA’s document records when available.

How to submit

HSA will inform registrants of the method of submission

Other HSA-requested RMP documents

HSA may request for the submission of other RMP documents in the post-registration setting. Examples include:

  • Clinical safety study reports to further characterise any potential and identified risks associated with the product or to evaluate the safety of the product in selected patient populations
  • Data on local product utilisation, such as the product sales data or cumulative data on number of patients exposed to the product

How to submit

HSA will inform registrants of the method of submission

Previous RMP submission for product registration