Regulatory Updates for Therapeutic Product Registration (30 June 2023)

As part of HSA’s ongoing initiatives 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 changes:

1.    Update of guidance documents for therapeutic product registration

·       Guidance on Therapeutic Product Registration in Singapore

The guidance has been updated as of 30 June 2023 and is available for download here.

i) Biosimilar labelling requirements

Chapter H has been updated to remove the mandatory requirement for inclusion of a warning statement on the risks associated with the switching of products during treatment.

The change in the labelling requirement takes into consideration that biosimilarity is established based on demonstration of comparability which include physicochemical, structural, and in vitro functional testing complemented by clinical equivalency to rule out clinically significant differences in efficacy between the biosimilar and reference products. Based on the extensive real-world data available, switching between biosimilar and reference products did not show evidence of increased safety or immunogenicity risks.

ii) Annotation of proposed labelling changes for variation applications

Sections 24.2.1 and 27 have been updated to specify the requirement for annotation of any proposed labelling changes submitted in post-approval variation applications.

Product registrants are reminded of their duty and obligations to provide accurate information and comply with sub-regulations 42(2)(a) and (c) of the Health Products (Therapeutic Products) Regulations when submitting variation applications to HSA. All changes made to the current approved label must be appropriately annotated using the current approved version. Omission of annotation of changes or inappropriately annotated labelling would render the submission false and misleading, which may require application withdrawal if such lapses are not adequately addressed.

iii) Patent declaration

Section 3 and the patent declaration form (Form 1) (Appendix 1) have been enhanced to clarify the pre-specified condition for a Category A3 application. A Category A3 declaration is applicable only to an application that is made within 18 months of the patent expiry from the point of application submission.

In addition, Form 2 (Appendix 1) has been updated to require the names of the applicant company and the authorised person to be stated for clarity.

The new forms will take effect from 31 July 2023.

iv) Notification form to submit Drug Master File (DMF)

Appendix 11A has been replaced by a new online form for DMF Holders to notify HSA on the submission of a DMF. The replacement of the PDF form with the online form is expected to enhance efficiency and reduce administrative burden on the DMF holders.

DMF holders are to submit the online form prior to furnishing the DMF documents to HSA. Submission of a Letter of Access to an existing DMF version (where there are no changes to the DMF) can also be made via the form.

The new online form will take effect from 31 July 2023. Please also refer to Appendix 11 of the Guidance on Therapeutic Product Registration in Singapore.

v) MIV-1 (biological) checklists for variation of strain(s) for SARS-CoV-2 vaccine and variation of strain(s) for seasonal influenza vaccine

Appendix 14A (Guideline on Minor Variation Applications for Biological Therapeutic Products) has been revised to include a new checklist (B19) for variation of strain(s) for SARS-CoV-2 vaccine as well as editorial changes to checklist (B13) for variation of strain(s) for seasonal influenza vaccine.

vi) Administrative and editorial changes

The following sections of the guidance have been revised with administrative updates:

• Section 2
• Sections 6.2.1 and 23.2.1
• Sections 15.1, 18.1, 20.1, 24.1, 24.2, 25.3 and 25.4

Appendices 2A, 2B, 3A and 3B have been revised to align with the respective changes.

·       Import and Supply of Registered Therapeutic Product on Consignment Basis

The guidance document for the Special Access Route (SAR) for import and supply of a registered drug on consignment basis has been updated to provide clarity on the conditions and documentary requirements for using this SAR. 

Based on the feedback from industry stakeholders, the requirement for certificates of analysis (CoA) has been revised to include CoAs issued by an overseas testing laboratory that is accredited by the International Laboratory Accreditation Cooperation (ILAC) to perform the specific test(s) in accordance with the accreditation scope.

Please also refer to the updated Guidance for Application to Import a Therapeutic Product on Consignment Basis.

2. PRISM Application Form - changes to the drop-down list of manufacturing operations for finished product manufacturers

Section 5 - Manufacturer’s Particulars of the PRISM application form has been revised to enable the following options of manufacturing operations:

• Bulk Production
• Primary Packaging
• Secondary Packaging
• Bulk Production (Solvent/Diluent)
• Bulk Production (Drug Product Intermediate)
• Quality Control Testing

The new manufacturing operations selection is applicable to new and variation applications effective as of 30 June 2023. This change does not affect current registered therapeutic product registrations, except where a variation application affecting section 5 of the PRISM application form is submitted.

More information is described in Appendix 17 of the Guidance on Therapeutic Product Registration in Singapore.

 

Published: 30 Jun 2023

Regulatory Updates