A company seeking to market a therapeutic product in Singapore must obtain marketing approval from the HSA through making an application for product registration.
A therapeutic product registered under the Health Products Act is specific to the product with respect to its:
- proprietary or brand name;
- pharmaceutical formulation;
- pharmaceutical dosage form (ie, physical presentation) and strength; and
- indication(s) and dosing regimen.
Different formulations, dosage forms and strengths of the same chemical or biologic entity are considered as different products and will require separate registrations for the individual product.
Upon satisfying the regulatory requirements for quality, safety and efficacy, a therapeutic product may be registered under one of the following forensic classifications, which determines the level of control for access:
- prescription-only medicine (POM);
- pharmacy-only medicine (P); or
- general sale list medicine (GSL).
An applicant making an application for the registration of a therapeutic product must ensure that all information contained in the application is truthful and is not misleading. An applicant must inform the HSA of any emerging information that may affect the benefit-versus-risk assessment of the therapeutic product to which the application relates, as soon as the applicant becomes aware of such information. The HSA may require a statutory declaration by the applicant verifying any information contained in or relating to the application.
Based on the HSA’s Guidance on Therapeutic Product Registration in Singapore (2018), the registration process involves the following steps:
- pre-submission preparation;
- application submission;
- application screening;
- application evaluation;
- regulatory decision; and
- post-approval changes.
In respect of new product registration, an application can either be in respect of a new drug application or a generic drug application.
A generic drug application applies to a therapeutic product that contains one or more chemical entities, and that is essentially the same with a current registered product with respect to its qualitative and quantitative composition of active ingredients, pharmaceutical dosage form and clinical indication.
There are four types of evaluation routes for registering a new therapeutic product, namely the full route, the abridged route, the verification route and the verification-CECA route. The full route applies to any new product that has not been approved by any drug regulatory agency at the time of submission. The abridged route applies to any new or generic product that has been evaluated by at least one drug regulatory agency. The verification route applies to any new or generic product that has been evaluated and approved by one of the HSA’s reference drug regulatory agency, which includes Australia’s Therapeutics Goods Administration, the European Medicines Agency, Health Canada, the UK Medicines and Healthcare Products Regulatory Agency and the US Food and Drug Administration. The verification-CECA route applies to any generic product manufactured in India that has been evaluated and approved by one of the HSA’s reference drug regulatory agency, which includes Australia’s Therapeutics Goods Administration, the European Medicines Agency, Health Canada, the UK Medicines and Healthcare Products Regulatory Agency and the US Food and Drug Administration.
Applicants are encouraged to contact the HSA by submitting an enquiry via the online feedback form on the HSA’s website or request a meeting or notification prior to the submission of an application if questions arise or clarification is required.
All applications are to be made in two parts: through an online submission through the HSA’s PRISM web portal and a hard-copy submission of the registration dossier, which is to be submitted within two working days from the PRISM submission. The registration dossier is to be in the common technical document format, based on the ‘Common Technical Document for Registration of Pharmaceuticals for Human Use’ as promulgated by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
After submission, the HSA will screen the application to ensure that the correct application type has been chosen and that there are no deficiencies that would delay the process. The HSA puts in place a stop-clock whenever it raises any queries in relation to the application. The stop-clock ends when a complete and satisfactory response is received by the HSA.
Once the application is accepted, evaluation by the HSA commences. A stop-clock is again put in place in respect of any queries raised.
Once the application has been evaluated, the HSA will issue a regulatory decision of ‘approval’, ‘approvable’, ‘non-approvable’ or ‘rejection’.
Approval and rejection are final decisions issued by the HSA. If an approvable regulatory decision has been reached, the conditions for approval will be stated in writing and the applicant will be required to fulfil these conditions within the stipulated time frame. If a non-approvable regulatory decision has been reached, the applicant will be informed of the non-approvable issues in writing, and a reply should be made within the specified time frame if the applicant wishes to continue with the application. The reply should be based on the original data set as submitted to the HSA; additional data that require evaluation will not be accepted.
An application will be considered withdrawn if the applicant fails to reply within the stipulated time frame subsequent to an approvable or a non-approvable decision. Once an application is withdrawn, it is considered closed and the applicant will be required to submit a new application according to prevailing submission requirements if the applicant wishes to pursue the regulatory approval for the product concerned. Upon an approval regulatory decision, the product will be added to the Register of Therapeutic Products.
The HSA may register the product subject to post-approval commitments and the applicant will be required to furnish a letter of commitment stating the undertakings concerned.
Upon the registration of a product, product registrants are responsible for ensuring the product’s quality, efficacy and safety to the end of its life cycle. The HSA must be notified of any changes to the product’s quality, efficacy and safety.
Pursuant to Regulations 26 and 29 of the Health Products (Therapeutic Products) Regulations 2016, confidential information received in support of the registration of an innovative therapeutic product is protected for a period of five years from the date of receipt, during which the HSA will not use the information to determine whether to grant any other registration applications. Confidential supporting information refers to trade secrets and information that has commercial value that would be, or would likely be, diminished by disclosure. A five-year period of exclusivity is granted for a therapeutic product for which safety and efficacy data has been generated in support of its registration. During the exclusivity period, a subsequent similar therapeutic product will not be able to rely on such data generated for the earlier therapeutic product to obtain registration.
Pursuant to Regulation 23 of the Health Products (Therapeutic Products) Regulations 2016, an application for the registration of a therapeutic product is required to make a declaration on whether the therapeutic product for which registration is sought is subject to a subsisting patent. A person who makes any statement or furnishes any document which the person knows or has reason to believe is false in a material particular or intentionally suppresses any material fact, furnishes information which is misleading and shall be guilty of an offence under Regulation 25 of the Health Products (Therapeutic Products) Regulations 2016 and shall be liable to a fine up to S$20,000 or to imprisonment for a term up to 12 months or to both.
Medicinal products (excluding therapeutic products)
All applications to obtain a product licence in respect of a medicinal product (that is not a therapeutic product) must be in compliance with the Medicines Act, the Poisons Act and the Misuse of Drugs Regulations (subsidiary legislation promulgated under the Misuse of Drugs Act).
The considerations that the HSA would take into particular consideration in determining whether to grant a product licence as set out in section 12 of the Medicines Act include:
- quality, according to the specification and the method or proposed method of manufacture, and provisions proposed for securing that the products sold or supplied would be of that quality; and
- whether the grant of the product licence would be in the public interest.
Pursuant to section 19A of the Medicines Act (introduced in 1998 to enable Singapore to comply with its obligations under article 39 of the World Trade Organization TRIPS Agreement), the HSA is obliged to maintain the confidentiality of information received in respect of innovative medicinal products, subject to the exclusions set out in section 19B of the Medicines Act (which include disclosing the confidential information if, in the opinion of the HSA, it is necessary to protect the health or safety of members of the public; disclosing the confidential information to another governmental department or statutory body, if the HSA is of the opinion that such department or body would take reasonable steps to protect the confidentiality of such information; and disclosing the confidential information to any specific international bodies, such as the World Health Organization (WHO)).
Pursuant to section 12A of the Medicines Act, all applications for new product licences must be accompanied by patent declarations in the form set out in Part I of the Sixth Schedule of the Medicines (Licensing, Standard Provisions and Fees) Regulations. Such patent declaration forms must be submitted at the time of application submission, and at any other time as the HSA may require. Generally, a confirmatory declaration will be requested when an approvable regulatory decision is issued. The applicant is required to furnish the confirmatory declaration within the time frame stipulated by the HSA.
Such an application may not be made earlier than 18 months before the expiry of the patent if:
- there is a patent in force in respect of the medicinal product to which the application relates;
- the applicant is not the proprietor of the patent;
- the proprietor has not consented to or acquiesced in the grant of the product licence; and
- the applicant is requesting the grant of a product licence after the expiry of the patent (ie, a Category A3 patent declaration).
A company that wishes to register a medical device on the Singapore Medical Device Register may make an application to the HSA via the HSA’s MEDICS web portal.
The HSA classifies medical devices based on a series of factors, including:
- how long the device is in contact with the body;
- the degree of invasiveness;
- whether the device delivers medicinal products or energy to the patient; and
- whether the device is intended to have a biological effect on the patent.
The HSA applies the following risk level classifications for medical devices:
Hypodermic needles/suction equipment
Ventilator/bone fixation plate
Heart valves/implantable defibrillator
The HSA has adopted the guidance developed by the Global Harmonization Task Force in developing Singapore’s risk classification model.
All Class A medical devices are exempted from product registration. While the product registration requirements previously applied to Class A medical devices that are supplied in sterile state, these requirements were removed from 1 June 2018. However, importers and manufacturers are still required to list all their Class A medical devices on the Class A Medical Device Register, to ensure safety and facilitate post-market surveillance and monitoring.
All information and documents submitted in support of the registration of Class B, C and D medical devices must be compiled in the ASEAN Common Submission Dossier Template (CSDT) format.
Since 1 September 2012, the registration process for Class B medical devices has been expedited. For instance, a Class B medical device may be immediately registered where it has already been approved by any two of the following independence reference agencies specified by the HSA - the US Food and Drug Administration, the European Union Therapeutic Goods Administration, Australia’s Therapeutic Goods Administration, Canada’s Medical Devices Bureau and Japan’s Ministry of Health Labour and Welfare - and has been marketed for at least three years without safety concerns. From 1 June 2018, the requirements were further streamlined such that Class B medical devices with no safety issues globally and the approval of two independent reference agencies, or the approval of one reference agency in addition to three years of marketing history, are also eligible for immediate market access. Additionally, also with effect from 1 June 2018, Class B and C standalone mobile medical applications with no safety issues globally and the approval of one reference agency are eligible for immediate market access.
With effect from 15 August 2017, the HSA may, upon an application for the registration of a medical device either immediately register the medical device or evaluate the medical device under:
- an abridged evaluation process;
- an expedited abridged evaluation process;
- a full evaluation process; or
- a priority full evaluation process.
A medical device may qualify for evaluation under an abridged evaluation process if any competent regulatory agency of a foreign jurisdiction has granted approval for the supply of the medical device in that jurisdiction; the approval by the competent regulatory agency is of a type accepted by the HSA and identified on the HSA’s website at the time of the application for the registration of the medical device; and the medical device complies with all other conditions specified on the HSA’s website.
With effect from 15 August 2017, a medical device is to be evaluated under a full evaluation process where either:
- the medical device does not qualify for evaluation under an abridged, expedited abridged evaluation process or immediate registration; or
- the applicant chooses to subject the medical device to a full evaluation process.
A Class B, C, or D medical device may qualify for evaluation under a priority full evaluation process if the medical device is to be evaluated under a full evaluation process and is considered by the HSA to be a novel medical device.
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