Singapore has a well-structured and rigorous regulatory framework for drug registration, which is overseen by the Health Sciences Authority (HSA) under the Health Products Act (HPA). The HSA is responsible for evaluating, approving, and regulating therapeutic products before they can be supplied in the country. Companies that intend to engage in the manufacturing, importing, or wholesaling of pharmaceutical products must obtain the relevant licenses to legally operate within Singapore. The entire registration process is designed to ensure that only high-quality, effective, and safe pharmaceutical products reach the market, thereby protecting public health.
Key Regulatory Framework for Drug Registration in Singapore
The Health Products Act (HPA) mandates that all therapeutic products must be registered before they can be legally supplied within Singapore. In addition to the mandatory product registration, companies involved in the pharmaceutical supply chain may also need to obtain one or more of the following licenses, depending on their specific business activities:
- Manufacturer’s Licence (ML): Required for companies that manufacture therapeutic products within Singapore.
- Importer’s Licence (IL): Required for companies that import therapeutic products into Singapore from other countries.
- Wholesaler’s Licence (WL): Required for companies that engage in the wholesale distribution of therapeutic products in Singapore.
The regulatory requirements established by the HSA aim to ensure the quality, safety, and efficacy of all pharmaceutical products available in the Singaporean market.
Categories of Product Registration Applications
Companies seeking to register a therapeutic product in Singapore must determine the appropriate product registration application category based on the nature of their product. The HSA classifies registration applications into the following categories:
- New Drug Application (NDA)
New Drug Applications (NDAs) apply to pharmaceutical products that contain new active ingredients, new combinations of active ingredients, or new formulations. NDAs are further classified into three subcategories:
- NDA-1: This category applies to the first strength of a product that contains a new chemical or biological entity that has never been registered before.
- NDA-2: This category applies to products that contain a new combination of registered chemical or biological entities, products that involve a new dosage form or new route of administration, or products that are intended for a new indication or patient population.
- NDA-3: This category applies to subsequent strengths of a product that has already been registered or submitted under NDA-1 or NDA-2.
- Generic Drug Application (GDA)
Generic Drug Applications (GDAs) apply to products that are bioequivalent to an already registered reference product. These applications are divided into two subcategories:
- GDA-1: This category applies to the first strength of a generic chemical product that is identical in composition to a currently registered product.
- GDA-2: This category applies to subsequent strengths of a registered generic product, provided that the product name and dosage form remain identical to the registered GDA-1 product.
Documents Required for Drug Registration in Singapore
The documentation required for a drug registration application depends on the type of product being registered and whether it has already been approved by other regulatory agencies. The HSA requires applicants to submit one of the following types of evaluation dossiers:
- Full Evaluation Dossier: Required for new drugs that have not been evaluated or approved by any other regulatory agency.
- Abridged Evaluation Dossier: Required for drugs that have already been approved by at least one major regulatory agency.
- Verification Evaluation Dossier: Required for drugs that have been approved by a stringent regulatory authority and have no significant differences from the approved product.
Step-by-Step Registration Process
Step 1: Pre-Submission Preparations
Before submitting an application, companies must ensure that they have compiled all necessary documents required for the registration process. At this stage, applicants are strongly encouraged to seek clarifications from the HSA through a pre-submission inquiry or by requesting a pre-submission consultation.
Step 2: Application Submission
Once the pre-submission preparations are complete, applicants must:
- Complete the application form using the HSA’s online Pharmaceutical Regulatory and Information System (PRISM). Before accessing PRISM, companies must have an active Company Registration for e-Services account.
- Submit the complete evaluation dossier to the HSA within two working days after submitting the PRISM application, if it has not already been submitted electronically.
Step 3: Application Screening
After submission, the HSA conducts an initial screening to identify any deficiencies in the application. If additional information is required, the applicant must provide the necessary documents within 20 working days. Failure to respond within this timeframe will result in the application being rejected, and a new application must be submitted.
Step 4: Application Evaluation and Decision
Once the application dossier passes the screening stage, it proceeds to the evaluation stage, where the HSA conducts a thorough review to determine if the product meets the necessary regulatory standards. A regulatory decision is then made based on the outcome of this evaluation.
Processing Timelines for Drug Registration in Singapore
The target processing timelines for drug registration in Singapore are as follows:
- Full evaluation dossiers: Processed within 270 working days.
- Abridged evaluation dossiers: Processed within 120-240 working days.
- Verification evaluation dossiers: Processed within 60-120 working days.
It is important to note that these timelines do not account for any delays caused by the need for additional information from the applicant. Depending on the number of input requests made by the HSA and the response time of the applicant, the actual evaluation period may extend beyond the stated timelines.
In exceptional cases, priority review may be granted for life-saving drugs that address critical unmet medical needs.
Registration Exclusivity and Patent Linkage System
Under the Health Products (Therapeutic Products) Regulations 2016, the efficacy and safety data used to register a product are granted 5 years of registration exclusivity. During this exclusivity period, a competitor cannot register a similar product using the same data unless explicit consent is obtained from the original registrant.
In addition, Singapore has implemented a patent linkage system as part of its obligations under the US-Singapore Free Trade Agreement. Applicants must declare whether a patent exists for the therapeutic product being registered. If the product is patented, the application will fall under one of the following categories:
- Category A1: The applicant owns the patent or has obtained consent from the patent owner.
- Category A2: The applicant seeks registration upon the expiry of the patent (applications cannot be made more than 18 months before patent expiry).
- Category B: The applicant believes the patent is invalid or that the drug does not infringe on the patent.
For Category B applications, the HSA requires notification to be sent to the patent holder, providing them an opportunity to take legal action if necessary.
Recent Regulatory Updates
Expedited Minor Variation Applications
The HSA has introduced a new framework to expedite the review of minor variations for certain pharmaceutical products. To qualify for an expedited review, a drug must meet specific eligibility criteria:
- There must be no alternative medicine available in Singapore.
- The drug must be required for national procurement.
- There must be an urgent need for the product.
To assist applicants, the HSA will launch an online form to guide them in determining eligibility for this expedited review program. If an applicant submits the required documentation for an expedited review, the HSA will evaluate the request and determine within five working days whether the application qualifies.
Updates to Appendix 7 for Drug Registration
The HSA has implemented revisions to Appendix 7 of the drug registration guidelines. The following changes have been introduced:
- The requirement to include the date of manufacture on the outer packaging or inner label has been removed.
- The warning statement regarding alternative uses of biosimilar products is no longer mandatory on package labels.
- There is now greater flexibility regarding the inclusion of the product owner’s name, drug manufacturer’s name, or registrant’s name and address on the outer drug carton or package insert.
Faster Evaluation Timelines for New Drug Applications
Singapore’s Therapeutic Products Branch, Health Products Regulation Group has improved its evaluation process for New Drug Applications (NDAs), Generic Drug Applications (GDAs), and Major Variation Applications (MAV-1). Companies can expect to receive their first-round evaluation feedback earlier than before. Additionally, a new web tool has been introduced to provide clearer timelines for drug approval.
Implementation of the eCTD Portal
In late September 2024, the HSA announced the launch of an eCTD (electronic Common Technical Document) portal program, which will begin in early 2025. The eCTD portal version 1.0 is an improvement over the previous version 0.9 and will initially be in a voluntary test phase from March to September 2025. This phase will allow companies to submit new drug applications, generic drug applications, and Drug Master File (DMF) applications electronically. While the eCTD format is widely used by Western pharmaceutical companies, it remains uncertain whether its use will become mandatory in Singapore in the future.
Project Orbis Information Now Available
The HSA website now includes dedicated information about Project Orbis, a US FDA initiative that involves multiple international regulatory agencies, including Singapore, working together on the accelerated approval of cancer treatments. This provides transparency and guidance for pharmaceutical companies looking to participate in Project Orbis.
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.