The regulatory controls for therapeutic products (i.e. pharmaceutical products) were transferred from the Medicines Act to the Health Products Act on 1 Nov 2016. The regulatory controls for other types of medicinal products (such as cell, tissue and gene therapy products and complementary health products) remain under the Medicines Act (see Figure 1).
Figure 1: Transfer of Regulatory Controls for Pharmaceutical Products from the Medicines Act to the Health Products Act
As a result, clinical trials of therapeutic products are regulated under the subsidiary legislation of the Health Products Act, the Health Products (Clinical Trials) Regulations. Clinical trials of medicinal products continue to be regulated under the Medicines (Clinical Trials) Regulations, which have been revised to align with the regulatory controls in the Health Products (Clinical Trials) Regulations.
Figure 2 summarises the applicable regulations for clinical trials of therapeutic products and medicinal products.
Figure 2: Applicable Regulations for Clinical Trials of Therapeutic Products and Medicinal Products
(click to access the regulations)
Clinical Trials of Therapeutic Products
Under the Health Products Act and the Health Products (Clinical Trials) Regulations, HSA adopts a risk-based Clinical Trial Authorisation-Clinical Trial Notification (CTA-CTN) system to the regulation of clinical trials of therapeutic products. Under this system, the requirements and the extent of regulatory review are risk-stratified according to the local registration status of the investigational therapeutic product used in the clinical trial.
The CTA is intended for “higher-risk” clinical trials in that they involve locally unregistered therapeutic products or unapproved use of a registered therapeutic product. The CTN submission route is for clinical trials that are considered to be of “low risk” in comparison to normal medical practice, since they involve only therapeutic products used in accordance with its approved label (Figure 3). As such registered products would already have been reviewed by HSA for product registration, CTN submissions will be subjected only to a simplified regulatory screening and verification process that leverages on review by the Institutional Review Board (IRB). In most instances, this is expected to shorten clinical trial start-up timelines as compared to clinical trials that require authorisation.
Figure 3: Clinical Trial Authorisation-Clinical Trial Notification (CTA-CTN) system
Figure 4 summarises the key differences between CTA and CTN.
Figure 4: Summary of Key Differences between CTA and CTN
|Clinical Trial Authorisation (CTA)||Clinical Trial Notification (CTN)|
|Target Processing Timeline (excluding stop-clock time)||30 working days
(Some Phase 1 studies:
15 working days)
|5 working days|
Informed Consent Form
Principal Investigator's CV
CMC documents, if requested
Informed Consent Form
Approved Product Label
IRB approval letter
Addition of Trial Site
Change of Principal Investigator
|Need to comply with clinical trial regulations and GCP||
|Subject to GCP Inspections||Yes||Yes|
|Regulatory Outcome||Authorisation||Acceptance of Notification|
|Authorisation / Acceptance validity period||Duration of the trial||Duration of the trial|
Clinical Trials of Medicinal Products
Clinical trials of medicinal products (e.g. cell, tissue and gene therapy products or complementary health products) are regulated under the Medicines Act and Medicines (Clinical Trials) Regulations. Such clinical trials require a Clinical Trial Certificate (CTC) issued by HSA before the trial can be conducted (Figure 5).
Figure 5: Regulation of Clinical Trials of Medicinal Products
Observational Clinical Trials
Observational clinical trials are excluded from the regulatory controls under the Health Products Act and the Medicines Act. This is in consideration that the decision to prescribe the therapeutic product or medicinal product is not dictated by the clinical trial protocol, and any risk relating to the use of the product in the observational clinical trial would be no different from the use of the product in the clinical practice setting. The exclusion of observational clinical trials from the regulatory controls reduces compliance costs and resources which, even if invested, may not necessarily result in enhanced subject safety.
Clinical Trials of Medical Devices
Clinical trials of medical devices are currently not regulated by HSA. Please refer to the Health Products (Medical Device) Regulations for regulatory controls on the use of medical devices in clinical trials.
Guideline for Good Clinical Practice
Clinical trials of therapeutic products and medicinal products must be conducted in accordance with the applicable clinical trial regulations, Good Clinical Practice (GCP) guidelines (ICH E6), protocol and standard operating procedures. As clinical trials have evolved tremendously in terms of scale and complexity over the past 20 years, the ICH E6 GCP Guidelines have been amended to encourage sponsors to implement quality management systems whilst continuing to ensure protection of human subjects participating in trials and clinical trial data integrity.
Please refer to the ICH website to download a copy of the ICH E6(R2) Guideline for Good Clinical Practice.
Clinical Research Materials
Regulation of Clinical Research Materials
New regulations were implemented on 1 Nov 2016 to streamline and simplify the regulatory approach for the import and supply of therapeutic products (TP), medicinal products (MP) and medical devices (MD) for use in clinical research, including regulated clinical trials. These products are referred to as “Clinical Research Materials*” (CRM).
The regulatory controls, which are in the respective subsidiary legislation based on the 3 product categories (TP, MP, MD), are similar (Figure 6).
Figure 6: Applicable Regulations for Clinical Research Materials*
(click to access the regulations)
For the purpose of streamlining the implementation of the CRM regulations, the term “Clinical Research Materials”, will be used operationally to refer to:
- TP, MP or placebo that meets the definition of “Clinical Research Material” under the Health Products (Therapeutic Products as Clinical Research Materials) Regulations or the Medicines (Medicinal Products as Clinical Research Materials) Regulations
- MD that is referred to in the Health Products (Medical Devices) Regulations as a “medical device whose planned use is for a clinical purpose in any clinical research”, or other similar expression
Objectives of the CRM regulations
The CRM regulations are intended to:
- facilitate access to CRM for use in clinical research, through a simplified and harmonised regulatory notification system (“CRM notification”)
- require imported/locally-manufactured CRM to be of sufficient quality
- restrict supply of imported/locally-manufactured CRM to regulated trials or IRB-approved clinical research
- require traceability and accountability of CRM through record-keeping
- require disposal/export of imported/locally-manufactured CRM after the research/trial ends
- require appropriate CRM labelling
- require reporting of unexpected serious adverse drug reactions (USADRs), or medical device adverse events (or potential adverse event) related to the use of CRM
Please refer to the Regulatory Guidance section for more information on the CRM notification process and other regulatory requirements pertaining to CRM.