Pharmaceutical Regulations and Registration in Singapore

Pharmaceuticals known as therapeutic products in Singapore have proven their healthcare innovation in recent years. This possesses a great scope for global manufacturers to enter the Singapore market. Along with the huge opportunity, also comes the stringent regulations which require compliance.

This blog aims to comprehend all the key requirements of pharmaceutical regulations in Singapore.

Pharmaceutical Products Market in Singapore

Singapore stands on 6th position in healthcare system worldwide and is one of the leading pharmaceutical or biomedical hubs in Asia since they took the initiative of government’s Biomedical Sciences (BMS) launched in 2000. Singapore spends its 4.7% of GDP on healthcare. The healthcare industry in Singapore is expected to grow at 6.40% of CAGR till 2030.

6% of World’s total OCT Drugs are produced in Singapore and it is expecting a 48% of revenue share in pharmaceutical market by 2024. Growth of Singapore’s pharmaceutical industry is contributed by several factors such as adopting modern technology and development of reliable and cost effective medical services. The industry has significantly benefited through the funding support by government in Research and development on biomedical and related sciences. Singapore’s pharmaceutical exports supersede the import and continue to grow.

Drug Classification in Singapore

Based on products:

• Generics
• Over-the-Counter (OTC Drugs)
• Patented drugs

Based on therapeutics:

• Infectious diseases
• Cardiovascular diseases
• CNS Disorders
• Oncology
• Respiratory Diseases
• Diabetes
• Gastro-intestinal diseases
• Dermatology, Rheumatology and other diseases

Based on regulatory classification:

• Prescription only medicine (POM)- Sold only by prescription
• Pharmacy only medicine, 1st Schedule (P)- sold in pharmacy under the pharmacist supervision
  Pharmacy only medicine, 2nd Schedule (P+)- sold in pharmacy under the pharmacist supervision but under certain conditions given in schedule.
• General sales list (G)- Sold to the consumer without any restrictions
• Regulatory Overview Of Pharmaceuticals In Singapore:

How are Drugs Regulated and Approved in Singapore?

Let us understand the main regulatory authorities and the guidelines for registration of pharmaceutical products:

• Health Science Authority (HSA): HSA is the main regulatory body responsible for the smooth regulation of therapeutic products in Singapore. This HSA regulates these pharmaceuticals through the Health Products Acts (HPA) and Health Products (Therapeutic Product) Regulation 2016.
• Ministry of Health (MoH): MoH is responsible for amending healthcare regulations and policies. It ensures that all healthcare bodies comply with the healthcare regulations.

Pharmaceutical Regulations Process in Singapore

Clinical Trials:

The clinical trials for all the pharmaceutical registration are regulated by the HSA, whereas medical devices and Class 1 CTGPs (Cell, Tissue, Gene Therapy Products) need to comply with the Human Biomedical Act requirements.

All the therapeutic products, medical devices, and CTGPs used as clinical research material should comply with the regulatory controls for clinical research materials.

Product Types And Their Key Regulations:

To know more about how to submit an application for CTA, CTN, and CTC click here.

Pharmaceutical (Therapeutic) Product Registration In Singapore:

It is extremely important to find the type of application of the drug which is to be registered via registration guides. There are two types of applications which are-

I. New Drug Application (NDA)

II. Genetic Drug Application (GDA)

HSA regulates the generic drugs and handles the registration of pharmaceutical products. The importer should have a person as registrant from Singapore which will be responsible for safety, efficacy and the quality of the product and applicant needs to have a local company in Singapore which is registered with Accounting and Corporate Regulatory Authority (ACRA).

PRISM– The drug application in the ICH CTD format is registered through the online/electronic/e-service platform which is generally known as PRISM (Pharmaceutical Regulatory and Information System). E-service gives convenience to customers and authority.

The following are the steps for HSA pharmaceutical product registration:

Pre-submission:

During the pre-submission phase of Therapeutic Drug Registration in Singapore, the correct application type, evaluation route, and dossier format should be selected according to the type of drug.

Application Type:

The following are the types of applications:

New drug applications (NDA-1, NDA-2, NDA-3).

Generic drug applications (GDA-1, GDA-2).

Evaluation Route for Drug Registration :

Then the evaluation route is decided based on the type of therapeutic product and its approval in the reference country. Drug registration in Singapore can only be done after the evaluation of the drugs. Below are the types of evaluation routes available:

• Full (NDA only): For new product approval with no approval in the reference country.
• Abridged: New or generic product which is approved by at least one regulatory agency.
• Verification: New or generic product that is approved by reference regulatory agencies.
• Verification-CECA (GDA only): Generic products manufactured in India and approved by reference regulatory agencies.

Dossier Format:

The applicant may decide to submit the dossier format in one of the following dossier formats:

• International Council for Harmonization Common Technical Document (ICH CTD).
• ASEAN Common Technical Document (ACTD)

Application Submission:

Before the submission of the application the applicant must have access to the following e-services:

• CRIS account
• Corppass or HSA PIN

If the applicant has already access to these e-services, he can apply for product registration through the PRISM portal.

For detailed guidance on how to apply through PRISM, click here.

The application for therapeutic product registration should be submitted under one of the following Forensic classifications:

• Prescription Only Medicine (POM): Sold only upon doctor’s prescription for serious disease conditions.
• Pharmacy Only Medicine (P): Sold by the pharmacist for minor diseases without prescription.
• General Sale List (GSL): Therapeutic products that can be freely obtained under any store.

Screening and Acceptance:

The screening and evaluation process involves screening the application along with the attested documents by the HSA. If the application is authentic in all aspects, the application is forwarded for evaluation and decision stage, or else the application is rejected.

Following is the list of documents required to be submitted before the screening process:

• Drug Master File (DMF) if applicable
• Copy of email acknowledgment from HSA
• Application supporting DMF if applicable
• Application Checklist
• Assessment reports

The NDA as well as the GDA takes a Turn Out Time (TOT) of 50 days from the date of receipt of the application dossier

Evaluation and Decision:

If the application clears out the screening stage, it moves forward to the evaluation stage. The following are the stages of evaluation for therapeutic application:

• Stage 1: Acceptance for evaluation
• Stage 2: Active evaluation in progress
• Stage 3: Evaluation at midway
• Stage 4: Completed evaluation

The evaluation process requires 120-160 working days from the date of acceptance. And once your application satisfies all the evaluation stages, your product gets registration approval.

If your application is declared non-approved, the deficiencies are specified in the reason, which needs to be addressed immediately.

If the application is declared rejected, it is the final decision, and nothing can be done about it.

Post-Approval Changes:

It involves updates to the HSA, and changes made to the product label, specification, concentration, etc. after it has been approved.

Therapeutic Product Licensing:

• Once the product is registered, the applicant needs to apply for a license according to his use of therapeutic products.
• The manufacturer will need a dealer’s license for the import and wholesale of therapeutic products.
• For manufacturing therapeutic products, the manufacturer’s license for therapeutic products (TPML).
• The company must comply with the GMP before applying for TPML.

Licensing Types And Their Purpose:

• TPIL allows restricted licenses for one-time use at a lower cost
• Bundling both the licenses, TPIL and TPWL, can be done for a discounted fee.

Labeling Requirements for Pharmaceutical Products in Singapore:

The following information must be written on the label of pharmaceutical products:

1. 1. 1. All the information on the label must be written in English language.
      2. The outer packaging label should include the following aspects on its label:
         • • Product name with its strength.
           • List all the ingredients with their concentration.
           • Batch.no
           • Manufacturing and Expiry date
           • Storage conditions
           • Administration instructions
           • Precautions if any
           • Product registration number
           • Name of the manufacturer
      3. All the information written on the outer packaging should be written on the inner package also, but if space does not permit include atleast the given information on the inner package:
         1. • Product name
            • Ingredients with their concentration
            • Batch number
            • Manufacture date
            • Expiry date
            • Route of administration
            • Registrant name
      4. The product must contain an information leaflet and should cover all the manufacturing details and consumption instructions in detail.

Generic Drug Application(GDA)

This application applies to the therapeutic product which consists of one or more chemicals. The GDA Application can only be registered if the drug meets the criteria which should be according to Singapore reference products. There are 2 types of GDA Application to register and market the drugs in Singapore;

• GDA 1 – First strength of generic chemical product submission.
• GDA 2- Subsequent strength of generic product which is already submitted as GDA-1 and the product and dosage should be same as first strength product.

Post-Approval Activities:

Variation Applications:

A variation application is submitted when there is a minor change in the approved therapeutic product in terms of product quality, safety, and efficacy.

There are two types of variation applications, they are as follows:

• MAV: For major variation application
  (MAV-1, MAV-2)
• MIV: For minor variation application
  (MIV-1, MIV-2 Notification, MIV-2 Do and Tell)

For more details regarding the type of variation types, click here.

Advertisement Of Therapeutic Products:

• There is no need for approval from the HSA for advertising therapeutic products.
• However, they should comply with the required regulations.
• Prescription medicines (POM) are banned from being advertised.
• Pharmacy-only (P) medicines require a reminder as a part of advertisement, to consult your doctor if symptoms persist.

Adverse Event Reporting:

• Adverse events can be reported through the CIOMS I form, online, or through email.
• It is compulsory to report serious adverse events (SAEs) of the therapeutic products from the importers, manufacturers, distributors, etc.
• A SAE must be reported within the first 15 days, and detailed information should be submitted in another 15 days to the HSA.

Product Defect Reporting And Recalls:

• Any defects found in the product must be informed to the HSA regarding the quality, safety, or efficacy.
• Defects are classified as critical which should be reported within 48 hours, while non-critical category of defects should be reported within 15 days.
• In case of adverse events, product defects, etc., the manufacturer recalls the products.
• The manufacturer needs to inform the HSA 24 hours before the recall, and the recall should be completed within 1-3 weeks.
• The recalls may be of class 1 (high risk) or Class 2 (moderate risk) categories.

Conclusion:

The compliance of therapeutic products in Singapore is handled by the HSA. The manufacturer must thus ensure compliance with the HSA regulations for a successful therapeutic product in Singapore. By these stringent regulations, HSA ensures that the safety, efficacy, and quality standards are not compromised so as to always maintain patient safety.

For a smooth registration of your therapeutic product with the HSA in Singapore, partner with Artixio. We, with our experienced localized team members, ease your regulatory journey achieving timely compliance and making your product successful.

Contact today at info@artixio.com

FAQs:

1. Do generic drugs require registration in Singapore?

Yes, generic products do require registration in Singapore with the HSA authority, before they are marketed.

2. What is the fast-track process of approval in Singapore for drugs that require immediate approval in case of rare disease treatment?

HSA has a special expedited process for the approval of medicines for the treatment of rare diseases or any serious conditions that require medications on an urgent basis. This fast-track process is known as the PRIME scheme and within this scheme, the drug is approved within 120-180 days.

3. What is a special access route (SAR) In Singapore?

The special access route (SAR) in Singapore allows unregistered medicines to be used for special clinical cases. This scheme allows both imported and local unregistered drugs to be used in Singapore.

4. How frequently should the product license be renewed in Singapore?

The product license should be renewed once every 5 years as the validity of the product license is 5 years in Singapore.