Regulatory Updates for Therapeutic Product Registration (effective 1 Aug 2024)

As part of HSA’s ongoing initiative to improve regulatory efficiency and enhance clarity in our regulatory requirements and processes, the Therapeutic Products Branch (TPB), Health Products Regulation Group, is pleased to update industry on the following:

1. Guidance updates with effect from 1 Aug 2024

i. New tool for estimating key evaluation milestones for NDA, GDA and MAV-1 full and abridged applications

To improve transparency and predictability in our regulatory processes, industry can expect to receive the first evaluation Input Request (IR) for NDA, GDA and MAV-1 product applications at the following timepoints:

Note: excluding any stop-clock time between acceptance and issuance of first evaluation Input Request.

Industry can also use the webtool ↗ (opens in new tab) to estimate the key application milestone timelines for NDA, GDA and MAV-1 applications.

The following guidance documents have been revised:

• Guidance on Therapeutic Product Registration

• Appendix 5

ii. New cloud-based platform for submission of application dossier and DMF “EasiShare”

Companies now have a new option of submitting their dossiers via a cloud-based file exchange software (EasiShare) in addition to the existing submission modes via electronic media (CDs/DVDs) or PRISM.

Applicants may refer to the Key Points to Note when Preparing Documents for Therapeutic Product Application Dossier Submission via EasiShare on our website for important information on how to use EasiShare.

The following guidance documents have been revised:

• Guidance on Therapeutic Product Registration

• Appendix 11

iii. Guidelines on post-approval changes that do not require notification to HSA

A list of post-approval changes which do not require notification to HSA has been published in Section 4 of Appendices 13 and 14 to provide transparency on such changes. Some changes previously categorised as MIV-2 Do-and-Tell (D&T) now fall under this category. For example, notification of product labelling changes related to machine readable codes (e.g. QR code) for e-labelling is no longer required.

Other changes to the current variation checklists include deletion of checklist for renewal of CEP due to CEP 2.0 implementation in September 2023, consolidation of product labelling D&T changes related to product registrant, as well as editorial updates.

The following guidance documents have been revised:

• Guidance on Therapeutic Product Registration

• Appendix 7A

• Appendices 13 and 14

• Appendix 13B Checklists C17, C18 and C30

• Appendix 13C Checklists D5, D7, D9 (obsolete), D12, D14, D22, D27, D28 and D29 (obsolete)

• Appendix 14B Checklists C8, C13 and C14

• Appendix 14C Checklists D4, D6, D11, D13, D15, D16 and D17 (obsolete)

iv. Implementation of the Health Products (Therapeutic Products) (Amendment) Regulations 2024

Following the public consultation on the proposed amendments to regulation 23 of the Health Products (Therapeutic Products) Regulations 2016 [“TPR”] for the implementation of restraining patents held from 1 March to 12 April 2024, HSA has published a summary of responses to the feedback received on our website, including information detailing the scope of patents and the patent declaration process under the revised regulation 23 to provide the necessary clarity.

The Health Products (Therapeutic Products) (Amendment) Regulations 2024 has been published on the Government Gazette ↗ (opens in new tab) and will come into effect on 1 August 2024. Accordingly, the patent declaration forms specified under regulations 23(2) and 23(5) of the TPR, and regulation 23(8)(b)(iii) of the Amendment Regulations have been updated and published on the HSA website, and should be used with effect from 1 August 2024.

The following guidance documents have been revised:

• Guidance on Therapeutic Product Registration

• Appendix 1

v. Introduction of Swissmedic as HSA’s reference agency

Swissmedic will be added as one of HSA’s reference agencies, along with EMA, FDA, Health Canada, MHRA and TGA.

The guidance documents have been updated accordingly with above information.

 vi. Editorial amendments

The following guidance documents have been updated with editorial changes and minor amendments:

• Guidance on Therapeutic Product Registration

• Appendices 2A and 3A

• Appendix 6

• Appendix 17

2. Status update on implementation of GMP requirements for chemical DS manufacturers with effect from 1 Oct 2024

The requirement for Evidence of Good Manufacturing Practice (GMP) Compliance for manufacturers of chemical drug substance (DS) will be fully implemented on 1 October 2024. This follows a one-year transition period which commenced in September 2023 for companies to comply with the requirement. Accordingly, NDAs, GDAs, and MIV-1 applications (for addition of new chemical DS manufacturers) submitted on or after 1 October 2024 must be accompanied by the required GMP Compliance Evidence for DS manufacturers.

For more information, please refer to the Guidance on the Implementation of DS GMP evidence for Chemical DS manufacturers with FAQ [PDF, 138 KB] ↗ (opens in new tab)

The following guidance documents have been revised:

• Guidance on Therapeutic Product Registration

• Appendices 2A and 3A

3. Other updates

i) Status update on eCTD implementation

The timeline for releasing the eCTD specification package (version 1.0) has been adjusted to Q3 2024 according to the system testing schedules. Additional testing is required to ensure the functionality and smooth transition to the eCTD platform. To allow sufficient time for industry to familiarise with version 1.0, the eCTD implementation date will be adjusted accordingly.

HSA will provide regular updates on the progress of eCTD implementation, and we seek your understanding on the unforeseen delay. We will work closely with industry stakeholders to ensure a successful deployment of the eCTD system.

ii) Streamlining of RMP requirements for biosimilar applications 

As of April 2024, the submission of RMP documents, including the Singapore-Specific Annex (SSA), is no longer mandatory for biosimilar (NDA-2) applications, unless requested by HSA. The submission of RMP documents is still required for NDA-1 applications.

Applicants are also reminded to use the updated SSA form as part of the RMP documentary requirements for NDA-1 applications. Appendices 16/16A of the Guidance on Therapeutic Product Registration are no longer applicable.

The following guidance documents have been revised:

• Guidance on Therapeutic Product Registration

• Removal of Appendices 16 and 16A

• Appendices 2A and 3A