Pharmaceutical Regulations and Registration process in Singapore
Selling and exporting of the New or Generic drugs can be only done after obtaining a valid product license through registration. The application for license needs to be submitted to the Singapore Health Sciences Authority (HSA) and requires common technical document (CTD) format which is designed by ICH (International Conference on Harmonization). The manufacturer or import should have ICH designed Association of Southeast Asian Nations (ASEAN).
Pharmaceutical Market Overview 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 continues to grow.
Pharmaceutical Registration and Registration in Singapore
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
How are Drugs Regulated and Approved in Singapore?
Selling and exporting of the New or Generic drugs can be only done after obtaining a valid product license. The application for license needs to be submitted to the Singapore Health Sciences Authority (HSA) and requires common technical document (CTD) format which is designed by ICH (International Conference on Harmonization). The manufacturer or import should have ICH designed Association of Southeast Asian Nations (ASEAN).
The Applicant should know the type of product application and route for the evaluation of the drug in case of therapeutic products and the applicant need to attend HSA pre-submission consultation which helps in differentiating the drug between chemical and biological therapeutic products. In Singapore classifies the application into two categories which are NDA (New drug Application) and GDA (Generic Drug Application). GDA Applies to the chemical and does not apply to the biosimilar drugs (Submitted via NDA).
Which Authorities Regulate Drugs?
Ministry of Health
Association of southeast Asian Nations (ASEAN)
Health Products Act – It regulates the registration, supply, import, manufacture, storage, packaging and advertising of the products including therapeutics, cosmetics and medical devices in Singapore.
Health Sciences Authority (HSA) – The key authority and multi-disciplinary agency in Singapore which regulates the drugs jurisdiction of medical and biological drugs.
Pre-registration Requirements:
To register a pharmaceutical product in Singapore, manufacturers must fulfill specific pre-registration requirements:
1. Pharmaceutical Manufacturing License: Manufacturers must hold a valid pharmaceutical manufacturing license granted by either the Health Sciences Authority (HSA) or a comparable foreign regulatory body.
2. Qualified Person: A Qualified Person (QP) must be designated to guarantee adherence to regulatory obligations during the entire manufacturing process.
List of Documents Required:
During the registration process, the following documents may be required:
Product information, including composition, manufacturing process, and specifications.
Stability data.
Clinical trial data (if applicable).
Bioequivalence data (for generics).
Quality testing data.
Packaging and labelling information.
Process of Drug Registration
Therapeutic Drug Registration:
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.
They can only be registered after the evaluation of the drugs. There are 3 routes of evaluation which are-
I. Verification route
II. Abridged route
III. Verification evaluation route (CECA Scheme)
Notification process
After the approval of the application, if the HSA finds that the application is satisfying the requirements of quality, efficacy and safety, the product is included in the therapeutic products register by the authorities.
CPP (Certificate of Pharmaceutical product) is issued for registered or un-registered products which are to be exported or evaluated. The therapeutic product needs to be manufactured under the quality compliance according to the GMP Standards mandated by WHO.
New Drug Application (NDA)
These drugs are composed of new chemical and biological entities. NDA covers therapeutic products under 3 categories;
NDA 1- First strength of new chemical or biological entity which are currently not existed or registered in Singapore.
NDA 2- Products which does not fall in NDA-1,NDA-3 OR GDA products and first strength products, or the products which are registered by the new route of administration or patient population, new indication and dosage recommendation.
NDA 3- Subsequent strength of products which are already registered and the product name, dosage and patient population should be same as NDA-1 and NDA-2 submission.
Biosimilar Products-
They are the therapeutic products which are very similar to existing biological products in physicochemical characteristics, safety, biological activity and efficacy. These products are submitted via NDA-2 or NDA-3.
Generic Drug Application(GDA)
This application applies on 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.
Timeline for registration of drugs-
NDA: It takes 50 days for screening application for all the evaluation routes but the evaluation time for different routes is between 60- 270 days.
60 days- verification evaluation routes
180 days- Abridged evaluation
270 days- Full evaluation time
GDA: It takes about 50 days for the screening of the application which starts from the day when the registrant receive the receipt for the application dossier and the screening time can be increases if the applicant needs to provide any clarification or additional document. Given below are the time taken for the evaluation of drugs.
120 days- Verification evaluation route
90 days – Verification evaluation route (CECA scheme),
14 days - Verification evaluation route first communication.
240 days - Abridged evaluation route.
Labeling Requirements for Pharmaceutical Products in Singapore:
To ensure patient safety and appropriate usage, pharmaceutical products in Singapore must comply with rigorous labeling requirements. These key requirements encompass:
1. Product Identification: The label should prominently display the product name, strength, dosage form, and batch number.
2. Directions for Use: Clear and concise instructions on how to properly utilize the product, including dosage guidelines and recommended duration of use.
3. Precautions and Warnings: Any contraindications, warnings, precautions, or specific storage conditions should be clearly communicated.
4. Ingredients: A comprehensive listing of both active and inactive ingredients contained within the product.
5. Expiry Date: An expiration date indicating the shelf life of the product.
Clinical Trial Requirements:
In Singapore, clinical trials must adhere to regulatory guidelines established by HSA (Health Sciences Authority). These guidelines lay out key requirements, which include:
1. Clinical Trial Application: Researchers are required to submit a comprehensive clinical trial application to HSA. This application should include detailed information about the trial protocol, investigational product, and study objectives.
2. Ethics Committee Approval: Prior to commencing a clinical trial, approval from an accredited ethics committee is mandatory. The ethics committee carefully reviews the trial protocol to ensure compliance with ethical guidelines.
3. Good Clinical Practice (GCP): Clinical trials conducted in Singapore must comply with internationally recognized standards of Good Clinical Practice. These standards ensure the ethical conduct of trials, uphold data integrity and prioritize the protection of participants.
Testing Requirements in Singapore:
Pharmaceutical products undergo thorough testing to evaluate their safety, quality, and effectiveness. Essential testing requirements include:
1. Quality Testing: Products are subjected to comprehensive testing to ensure they meet stringent quality standards. This encompasses examinations for impurities, stability, and dissolution.
2. Bioequivalence Studies: Generic pharmaceutical products must substantiate their bioequivalence to the reference product using comparative studies. This ensures that the generic product performs equivalently to the original.
3. Pharmacokinetic Studies: Some products may necessitate pharmacokinetic studies to assess their absorption, distribution, metabolism, and excretion within the body. These studies provide valuable insights into how the product behaves in the human system.
Foreign Testing:
Singapore acknowledges and accepts testing conducted by respected regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). In certain instances, foreign testing data from these authorities may be considered valid, as long as it adheres to the applicable standards and requirements.
In cases where products have already been approved in the EU or US:
The registration process in Singapore can be streamlined if the pharmaceutical products have received approval from esteemed regulatory authorities such as the FDA or EMA. HSA acknowledges the assessments and evaluations conducted by these reputable authorities, which may expedite the review and approval process.
Import and Distribution Requirements:
To import and distribute pharmaceutical products in Singapore, it is imperative to meet the following requirements:
1. Import License: Importers are required to procure an import license from HSA prior to importing any pharmaceutical products into Singapore.
2. Good Distribution Practices (GDP): Distributors must strictly comply with GDP guidelines, which encompass appropriate storage, handling, and distribution practices for pharmaceutical products.
GMP Inspection Requirements:
In order to guarantee adherence to Good Manufacturing Practices, HSA carries out inspections of pharmaceutical manufacturing facilities. These inspections evaluate the quality management systems, manufacturing processes, and compliance with regulatory standards.
Post-Marketing Activities in Singapore:
Following the registration of a product, pharmaceutical companies are obligated to fulfil a range of post-marketing responsibilities, which include:
Pharmacovigilance: Manufacturers and distributors must establish a pharmacovigilance system to monitor and document any adverse events associated with their products.
Variations: Any modifications made to the registered product must be promptly reported to HSA via variation applications, ensuring continual compliance and safety.
Renewal: Product registrations typically have a specified validity period, and renewal must be conducted within the designated timeframe.
Audits and Inspections: HSA conducts audits and inspections to verify ongoing adherence to regulatory requirements and quality standards.
References-
1. https://www.hsa.gov.sg/therapeutic-products/register
2. https://www.hsa.gov.sg/therapeutic-products/cpp-sls/certificate-pharmaceutical-product
3. https://www.hsa.gov.sg/e-services/prism/therapeutic-products
4. https://www.hsa.gov.sg/therapeutic-products/register/guides/new-drug
https://www.hsa.gov.sg/therapeutic-products/register/overview/overview