Singapore’s Health Sciences Authority (HSA) has a structured framework for the submission and management of Drug Master Files (DMFs) to support the registration of therapeutic products. Under the DMF system, manufacturers can submit confidential information on drug components while enabling drug product applicants to reference this information in their registration dossiers.

Overview of the DMF System in Singapore

A DMF is a technical dossier typically used to provide data on active pharmaceutical ingredients (APIs), excipients, or drug packaging materials that support a finished drug product application.

In Singapore, there are two main components in a DMF:

Open (Applicant) Part: This part contains information that can be shared with the finished product applicant and submitted as part of the finished product registration dossier. It contains general information about the drug substance and manufacturer, and some quality information.
Closed (Restricted) Part: This part includes confidential information, such as proprietary manufacturing processes, that are not disclosed to the finished product applicant. Only the HSA has access to this confidential information. The closed part contains a description of the manufacturing process and process controls, control of materials, controls of critical steps and intermediates, process validation and/or evaluation, and manufacturing process development.

This separation of information (open/closed) allows the DMF holder to protect confidential know-how while making it possible for the HSA to assess the quality and safety of the finished drug product.

Notably, a DMF cannot be approved as a standalone submission. Instead, the HSA evaluates a DMF only when it is referenced in a therapeutic product application. Therefore, the DMF functions as a supporting dossier rather than an independent finished drug registration submission.

Responsibilities of DMF Holders and Applicants

Both DMF holders and finished product applicants have ongoing obligations to maintain the accuracy of the DMF and the related finished product dossier. The DMF holder must make sure that all relevant information is kept up-to-date and must notify product registrants of any changes that could affect the quality, safety, or performance of the finished drug as soon as possible.

When such changes occur, the product registrant is responsible for making the appropriate post-approval submissions to the HSA. This coordinated approach ensures that any updates to manufacturing or component information are properly reflected in the registered product’s regulatory file.

Notification Process Before Submission

Before submitting a DMF or related documents, the DMF holder must complete an online Notification of DMF Submission Form. This notification is required upon submission of a new DMF, a new Letter of Access (also known as Letter of Authorization), and a DMF update.

The notification form must include supporting documents such as a Letter of Access and, if applicable, a summary table outlining updates to the DMF.

The Letter of Access is a critical document that authorizes the HSA and the product applicant to reference the DMF. It must include:

The product name, dosage form, and strength
Basic information about the applicant
A declaration confirming that both the HSA and applicant will be informed of any changes that may affect the finished product quality or safety

After the notification is submitted, the HSA will assign a unique DMF number to the file. The DMF holder and the applicant are typically informed of this number within around 20 working days. This reference number must be used in subsequent submissions and correspondence.

Submission Requirements

After receiving confirmation from the HSA, the DMF holder may proceed with the formal submission. The required documentation depends on the type of submission.

For a new DMF, the DMF holder must submit a cover letter indicating the response ID from the notification form and the assigned DMF number. The open and closed parts of the DMF must be in machine-readable PDF format.

For a DMF update, in addition to a cover letter referencing the response ID and DMF number, updated open and closed parts of the DMF are required in machine-readable PDF format

For a new Letter of Access without updates, if a product application references an existing version of a DMF, only the Letter of Access and notification form are required. The DMF itself does not need to be resubmitted.

Once the HSA receives a complete DMF submission, it will notify both the DMF holder and the applicant. The applicant may then submit the open part of the DMF and a copy of the Letter of Access as part of the therapeutic product registration dossier.

Submission Formats and Channels

All submissions must reference the HSA-assigned DMF number. File folders should include both the name of the drug component and the DMF number (for example, “[Name of the API/Excipient]_1234”).

There are two electronic submission channels – PRISM and EasiShare. While PRISM is only available to the finished product applicants, EasiShare can be used by both DMF holders and product applicants. In addition, submissions may be sent to the office of the Therapeutic Products Branch of the HSA in Singapore.

Key Takeways for Manufacturers

Foreign manufacturers preparing a Singapore DMF should ensure that open and closed sections are clearly organized and aligned with international Common Technical Document (CTD) standards, where applicable. The Letter of Access needs to be properly drafted and consistent with the referenced product application. To avoid delays and confusion, the assigned DMF number should be used consistently in all submissions and correspondence. Most importantly, to ensure compliance and the validity of the DMF, any changes that may affect the safety and efficacy of the product need to be reported to the finished drug applicant.

Because the HSA evaluates DMFs only alongside product applications, coordination between DMF holders and product applicants is essential to avoid delays in the review process.

Conclusion

Singapore’s DMF system provides a structured and confidential mechanism for submitting detailed component information to support therapeutic product registration. By requiring prior notification, assigning unique DMF numbers, and reviewing DMFs only in connection with product applications, the HSA ensures that proprietary information is protected while maintaining regulatory oversight of product quality and safety. For API and excipient manufacturers seeking to enter the Singapore market, careful planning of DMF submissions, clear communication between stakeholders, and timely updates to the dossier are key to ensuring a smooth regulatory process.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)
Mr. Gross founded PBM in 1988 and has helped hundreds of medical companies with regulatory and business development issues in Asia. He is recognized nationally and internationally as a leader in the Asian medical markets. Mr. Gross has a BA degree, Phi Beta Kappa, from the University of Pennsylvania and an MBA from Columbia University.