Risk management plan (RMP)

  2. RMP submission for product registration

RMP submission for product registration

Find out when an RMP submission is required and the documents to be submitted

Requirements for RMP submission

An RMP must be submitted for all New Drug Applications type 1 (NDA-1) for therapeutic products or CTGTP. This requirement will also apply to products with a long history in the international market. Companies may propose to implement only routine PV activities and RMA if the product has been shown to have an acceptable and well-established safety profile.

For other application types, including NDA-2/3, variation applications or generic drug application (GDA), an RMP is to be submitted only upon HSA’s request during application review.

RMP documents for NDA-1 applications

The following RMP documents are to be submitted as part of the NDA-1 application dossier.

1. Singapore-Specific Annex (SSA)

  Singapore-Specific Annex (SSA)2110 KB

You should use the above SSA to submit the product’s proposed RMP for Singapore and include the following information:

  • Product information e.g. product name and active ingredient(s)
  • Safety concerns  i.e. important identified risks, potential risks and missing information
  • Proposed local PV activities and RMA
  • Supporting documents e.g. the list of RMP documents that have been submitted in the application

2. Reference RMP (e.g. EU-RMP, US REMS, Core RMP)

For products that are registered in the EU or USA, the latest approved EU-RMP and/or US REMS should be included in the application dossier. If the product does not have an EU-RMP or US REMS, an alternative reference RMP may be submitted, such as the company's core RMP or RMP(s) approved by other overseas regulators (translated into English, where applicable).

If an updated version of the reference RMP(s) becomes available during HSA's application review, applicants should submit it as soon as possible to facilitate the timely review of the application. The relevant updates to the RMP(s) and an impact assessment of these updates on the proposed local RMP should be highlighted in a cover letter. An updated SSA should also be submitted if there are any changes to the proposed local RMP.

To submit an updated EU-RMP, US REMS and/or alternative RMP during application review:

  • Therapeutic products – Upload in PRISM, Section 7 (Supporting Attachments) under Other Supporting Documents. The applicant may contact the evaluator of the application to request for the issuance of an Input Request to submit the updated reference RMP
  • CTGTP – Upload in SHARE under Module 5.5 (ICH CTD Format) or Part IV (ASEAN CTD Format). The applicant may contact the evaluator of the application or email HSA_CTGTP@hsa.gov.sg to request for the issuance of an Input Request to submit the updated reference RMP

3. Other RMP documents, where relevant

If additional PV activities or RMA are proposed for the product, all relevant RMP documents should be included in the NDA-1 application dossier as part of the product’s proposed local RMP. This may include the following:

Educational materials for physicians and/or patients

Educational materials for physicians and/or patients may be proposed to highlight specific safety concerns associated with therapeutic products and CTGTP, and provide advice on the actions required to optimise their safe and effective use.

Key information in educational materials include the product’s local approved indication(s), contraindications and the important adverse events to note. Educational materials may also highlight important information such as:

 Physician Educational Material

Patient Medication Guide or 

Patient Alert Card
  • Risks in certain patient population(s), allowing physicians to make informed decisions when selecting patients who may benefit most from the therapy
  • Recommended dosing information and advisories to adhere closely to
  • Need for regular monitoring and/or laboratory testing that could affect the decision to continue or modify the patient therapy
  • Any monitoring parameters to manage the adverse events
  • Need to monitor for early signs of adverse events that could require discontinuation or modification of patient therapy
  • Potential risk for medication error
  • Need to conduct long-term safety monitoring for delayed adverse events
  • Information to aid patient counselling
  • Need to closely adhere to the directions for use of the prescribed medication
  • Early signs of adverse events and when to seek medical attention
  • Important food-drug interactions or lifestyle modifications required while on the medication (e.g. drugs that are associated with teratogenicity)

The proposed educational materials should be submitted in the application dossier. HSA will review the submitted draft material(s) during application evaluation in conjunction with the dossier to determine the additional activities required for implementation in the local RMP.

The HSA-approved educational materials will be published on the HSA website (see Post-registration RMP obligations).

Controlled access programme

A controlled access programme may be proposed for a product where the benefit has been assessed to outweigh the risks for a selected group of patients.

The RMP documents to be submitted for HSA’s review should comprise:

  • A description of the objectives and requirements of the programme, including the conditions to be fulfilled before the product is prescribed and/or dispensed
  • The proposed educational materials to be distributed under the programme

Forms to be used in the programme should also be submitted for documentation purposes. These may include:

  • Letter of undertaking from prescribing physicians
  • Letter of undertaking from dispensing pharmacists
  • Patient informed consent form

Pregnancy prevention programme

A pregnancy prevention programme may be considered for products with known or potential teratogenic effects.

The RMP documents to be submitted for HSA’s review should comprise the proposed conditions of the programme, such as:

  • Exclusion of pregnancy before starting treatment and during treatment
  • Mandatory patient counselling prior to treatment initiation about the risk of teratogenicity and the need for effective contraception throughout treatment
  • Acknowledgement by physicians/pharmacists regarding their understanding of the programme
  • Acknowledgement by patients that the appropriate advice regarding risk of teratogenicity has been given and understood
  • Provision of educational materials for physicians and/or patients

Submission of RMP documents

The RMP documents should be submitted in softcopy as part of the product registration application dossier:

  • Therapeutic products – Upload in PRISM, Section 7 (Supporting Attachments) under Other Supporting Documents
  • CTGTP – Upload in SHARE under Module 5.5 (ICH CTD Format) or Part IV (ASEAN CTD Format). More information on the submission of CTGTP applications is available here

For therapeutic products, if the complete set of RMP documents is not available at the point of application submission, they must be submitted within the following time frame:

  • Applications submitted via the full or abridged route – The application must be accompanied by a letter of commitment to provide the complete set of RMP documents within 40 working days from the date of application acceptance for evaluation. A stop-clock may be imposed on an application under evaluation if the documents are not submitted to HSA
  • Applications submitted via the verification route – The complete set of RMP documents must be submitted for the application to be accepted for evaluation
For CTGTP, all RMP documents required in support of NDA-1 applications should be provided as part of the application dossier at the point of application submission. 
 

Points to note after submitting your application

HSA will review the submitted RMP documents together with the application dossier.

HSA may discuss with the applicant or request for additional PV activities or RMA to be implemented in Singapore. Applicants should submit all the requested additional RMP materials and supporting documents as soon as possible to prevent unnecessary delays in the product application process.

The additional PV activities or RMA to be implemented as part of the local RMP will be stipulated in the product registration conditions upon application approval.

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