Singapore’s Health Sciences Authority (HSA) is driving forward the transition to eCTD to enable full electronic submissions, minimizing the need for submitting documents using storage media like CD/DVD ROMs with the following approach:
HSA will adopt a phased approach, and the use of eCTD for dossier submissions will be voluntary based on ICH (International Council for Harmonisation) eCTD specification 3.2.2. The initial phase will allow New Drug Applications (NDA), Generic Drug Applications (GDA), and their corresponding Drug Master File (DMF) submissions in eCTD format. The industry consultation phase ended in June 2023 and the final version of the eCTD implementation package will be released in the 2nd Quarter of 2024, according to the most recent update published on 11 December, 2023. (ref: Post Consultation Update).
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Contents of Singapore's v.0.9 Draft
HSA issued a notice to the industry regarding eCTD implementation and published an eCTD v0.9 draft consultation package on 2nd May 2023. This package holds the Specification, eCTD validation criteria with Document Matrix / Submission Type Matrix, the technical files like defined value lists in Extensible Markup Language (XML) format, XML Schema Definition (XSD) as well as sample eCTD sequences and a Questions and Answers document.
Singapore Goes eCTD - The Technical Details
- Only in the case of a Baseline eCTD submission, the sequence number should be 0000.
- The first submission of a new marketing authorization application should be 0001 (see validation criteria 2.1.8), like the criteria by the US Food and Drug Administration.
- The use of STFs (Study Tagging Files) is optional for Studies (see validation criteria 1.2).
- A maximum file size of 200 Megabytes (MB) is defined; the only exceptions are XPT files, which can be up to 5 Gigabytes (GB).
- The maximum allowed path length is 180 characters.
- The naming conventions for files and folders are not part of the validation criteria → For detailed information, see specification chapter 4.6.1.
- The docx files representing the source files are allowed in section 1.2.3.
The Business Details
Certain sections in Module 1 allow a maximum of one document. In addition, in Module 1, there are sections that allow only specific lifecycle operations. A Document Matrix lists the mandatory and optional documents to be provided per submission type. Submission grouping is possible for Singapore and the Submission Matrix informs about the possible groupings of submission types.
An eCTD baseline should always be submitted for products previously registered in a different format. Each product should have its own unique eCTD application number. Applicants need to provide a summary of missing content in sections 3.2.P and 3.2.S of Module 3 (see validation criteria 3.6.1 and 3.6.2). All clinical studies should have node extensions (warning; see validation criteria 3.4.8).
The lifecycle operation "Append" should not be used normally, as this would result in an ERROR in validation criteria. However, there is only one exception for the above criteria in the form of allowance for append operation in the STF (Study Tagging Files) files. Replaced documents must have different content than their originals (see validation criteria 3.5.10). Lifecycle operation for PDF and source (docx or rtf) must always be reflected for both, i.e., PDF and the source. Working documents (where needed) must have the same lifecycle as their PDF renditions. Special conventions for node extension names must be followed in section 3.2.R of Module 3 (see validation criteria 3.4.11). For DMF and Pharmacovigilance (PV) submissions, the eCTD format should be used as well.
Interim update on key changes
After public consultation of v0.9, the HSA communicated their plans to include the following changes in v1.0:
The Health Authority will issue a unique e-identifier via the portal to be used as the application folder name. It is planned that companies will not need to generate Universally Unique Identifier (UUIDs) themselves. HSA will also update the specification document to clarify the order of submission in the Pharmaceutical Regulatory Information System (PRISM) and eCTD portal. Regarding baseline submissions, HSA will include illustrations of business workflow for baseline and transfer submissions. Applicants could include multiple dosage forms/strengths in a single application or submit as separate applications as part of changes HSA would incorporate in the final version of eCTD v1.0. In the final version, HSA will also provide a regional stylesheet for viewing the XML files. The validation criteria will be fine-tuned to allow electronic signatures in PDF documents.
The following content will be a part of Singapore's eCTD v1.0 package update:
- Summary of changes
- Updated specification and validation criteria documents
- Updated technical package (sample submissions, validation matrices, stylesheets)
- Updated Q&A
- Training and test submission schedules
About the writers:
Michael Faust
Michael Faust is a Business Consultant in EXTEDO’s Regulatory Competence Center with over seven years of experience in the regulatory field, supporting EXTEDO and customers with regulatory courses and updates, software training, support, and projects.
Priya Krishnan
Priya is a Regulatory Publishing Services Business Consultant at EXTEDO with four years of industry experience in Scientific Publishing and Regulatory Affairs. She has a double master's degree in microbiology and MBA&E Life science Management, focusing on Regulatory Affairs.
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