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This application is a service of the Singapore Government.

Health Sciences Authority

FAQs

Unless stated otherwise, these FAQs apply to clinical trials of therapeutic products or medicinal products.

[A] GENERAL REGULATORY REQUIREMENTS FOR CLINICAL TRIALS

[A1] What are the regulatory requirements for clinical trials in Singapore?

[A2] How can I determine if my clinical trial requires Clinical Trial Authorisation (CTA), Clinical Trial Notification (CTN) or a Clinical Trial Certificate (CTC)?

[A3] Can I submit my clinical trial application to HSA and the IRB concurrently?

[A4] What are the documents that must be submitted to HSA to support the clinical trial application?

[A5] For how long is a Clinical Trial Authorisation (CTA), Clinical Trial Notification (CTN) or Clinical Trial Certificate (CTC) valid?

[A6] What are the subsequent applications required to be submitted to HSA following receipt of the authorisation (for CTA), acceptance of notification (for CTN) or approval (for CTC) by HSA?

[A7] What are the regulatory timelines for subsequent submissions to HSA?

[A8] How is study completion defined?

[A9] If a clinical trial was approved by HSA before 1 Nov 2016, how will it be affected by the revised clinical trial regulations?

[A10] If a clinical trial of a therapeutic product was an observational clinical trial approved by HSA before 1 Nov 2016, would the trial be excluded from the clinical trials regulations from 1 Nov 2016?

[A11] Are there any fees for the submission of clinical trial application to HSA?

[B] SPECIFIC REGULATORY REQUIREMENTS FOR CLINICAL TRIALS

[B1] What are the regulatory requirements on First-in-Human (FIH) trials of therapeutic products?

[B2] Are non-clinical safety/toxicology studies required to be conducted in compliance to GLP standards?

[B3] Are there any regulatory requirements for clinical trials involving radiopharmaceuticals?

[B4] What kind of preclinical data is required to support clinical trials of cell, tissue and gene therapy products (CTGTP)?

[B5] Are there any additional dossier requirements for submission of cell, tissue and gene therapy product (CTGTP) clinical trials?

[B6] What are the regulatory requirements for conducting clinical trials on health supplements?

[B7] What are the applicable ICH guidelines that the Health Sciences Authority adopts for clinical trials?

[C] CLINICAL TRIALS ON MEDICAL DEVICES

[C1] What are the current regulatory requirements for clinical trials of medical devices?

[D] PRINCIPAL INVESTIGATOR

[D1] What are the regulatory obligations of a Principal Investigator (PI)?

[D2] Who can be a Principal Investigator (PI) of a clinical trial?

[D3] Can a doctor who has a conditional registration with Singapore Medical Council (SMC) be a Principal Investigator (PI) of a clinical trial?

[D4] What is the minimum training required for Principal Investigators (PIs)?

[D5] What should be done when the Principal Investigator (PI) is on extended leave?

[D6] If the Principal Investigator (PI) of a suspended / terminated / completed clinical trial has resigned, is there a need to submit an amendment application for Change of PI to HSA?

[E] STUDY STAFF

[E1] What types of study specific responsibilities require trial-related medical / dental decisions to be made by an investigator?

[E2] What are the minimum training requirements for study staff?

[E3] If the study staff has been trained in the Singapore Guideline for Good Clinical Practice (SGGCP), do they need to be re-trained in the ICH E6 GCP after the port over of the clinical trials regulations?

[E4] If there is a change of Principal Investigator (PI) for a clinical trial, how can this change be documented on the Signature Sheet?

[F] SPONSOR

[F1] What are the regulatory obligations of a sponsor of a regulated clinical trial?

[F2] What are the additional sponsor responsibilities for investigator-initiated clinical trials where more than one local trial site is involved in conducting the clinical trial on a single protocol (i.e. multi-sponsor IITs)?

[F3] What should the sponsor do if there is a transfer of local sponsorship for an ongoing clinical trial?

[F4] What should the sponsor do when there is a change in the contact person?

[F5] What should the local sponsor do when there is a change in company address?

[G] PROTOCOL

[G1] What kind of study amendments should be submitted to HSA?

[G2] Although it is the sponsor’s responsibility to assess whether an amendment is regarded as a substantial amendment, does a lead sponsor need to consult the participating sponsors on the assessment for multi-sponsor Investigator-initiated trials (MS IITs)?

[G3] Are there any guidelines for reporting Protocol Deviations to HSA?

[G4] Does HSA approve Protocol Waivers?

[H] INFORMED CONSENT FORM (ICF)

[H1] What are the basic principles of an informed consent process?

[H2] What are the regulatory requirements for informed consent?

[H3] What are the regulatory requirements for informed consent in vulnerable subjects?

[H4] For clinical trials in minors, must the minor give consent prior to participating in the clinical trial?

[H5] For clinical trials in minors, if the mother of the minor is below 21 years of age and is not / never was married, can the mother give informed consent for the minor?

[H6] For clinical trials in adults lacking capacity where there is a donee for the adult lacking capacity, does the investigator need to ascertain whether the donee has been authorised to give consent for clinical trial participation?

[H7] For clinical trials in adults lacking capacity where it has been established that the adult child of the adult lacking capacity is the legal representative, is there an order of priority amongst the adult children if the adult lacking capacity has more than one adult child?

[H8] For clinical trials in adults lacking capacity where it has been established that the adult sibling of the adult lacking capacity is the legal representative, is there an order of priority amongst the adult siblings if the adult lacking capacity has more than one adult sibling?

[H9] For clinical trials in adults lacking capacity where it has been established that the adult child is the legal representative, would the adult child be considered as ‘not available’ if the adult child is located overseas?

[H10] What are the elements of an informed consent form?

[H11] What are the required approvals for the informed consent form prior to use?

[H12] Who can obtain informed consent?

[H13] When should informed consent be obtained from the subject or legal representative (if applicable)?

[H14] Which version of the informed consent form should be used to consent the subject or legal representative (if applicable)?

[H15] Where should informed consent be obtained from the subject or legal representative (if applicable)?

[H16] How should the informed consent form be explained to the subject or legal representative (if applicable)?

[H17] How should the informed consent form be completed?

[H18] Are signature stamps and date stamps acceptable means of signing and dating the informed consent form?

[H19] If a clinical trial involves recruiting subjects who are mentally competent, but unable to sign or date the informed consent form, how can consent be obtained from such a subject?

[H20] How can informed consent be obtained from a subject or legal representative (if applicable) who is unable to read the informed consent form?

[H21] Who can act as an impartial witness?

[H22] How can informed consent be obtained from a subject or legal representative by an investigator who is not conversant with the subject or legal representative’s language?

[H23] Who can act as a translator?

[H24] Is there a summary table available to help determine whether an impartial witness or a translator is required during an informed consent process?

[H25] How many copies of the informed consent form should be signed?

[H26] Should the subject or legal representative (if applicable) be re-consented if new information becomes available during the clinical trial?

[H27] Does the subject need to be re-consented if there is a change of Principal Investigator (PI) for the clinical trial?

[H28] How should informed consent be documented in the subject’s medical records?

[H29] Do Assent Forms for clinical trials in minors need to be submitted to HSA?

[H30] Can Short Form Consents be used for clinical trials regulated by HSA?

[I] INVESTIGATIONAL PRODUCTS (IP)

[I1] What are investigational products (IP) and auxiliary products (AP)?

[I2] What are the labelling requirements for therapeutic products or medicinal products used in clinical trials regulated by HSA or clinical research not regulated by HSA?

[I3] How should the IP/AP be labelled prior to delivery to the local trial site?

[I4] Do the labelling requirements apply to locally registered therapeutic products and medicinal products used in clinical trials?

[I5] The IP labelling for registered products depends on whether the registered product is used in accordance with all of the following conditions:
(i) is not used in a clinical trial in a blinded fashion,
(ii) is not repackaged for use in the trial,
(iii) is used in accordance with the terms of its product registration/licence.
How is ‘repackaging’ defined in this context?

[I6] If the investigational product (IP) or auxiliary product (AP) is to be administered to the subject at the trial site via a syringe, infusion bag or plastic cup (e.g. for oral formulations), would the syringe, infusion bag or plastic cup be required to be labelled in accordance with the applicable regulations?

[I7] Are IP documentation required to be maintained for clinical trials of locally registered therapeutic products or medicinal products?

[I8] Is temperature monitoring required to monitor the storage of the IP?

[I9] What are the required procedures if the site is involved in re-packaging of the IP?

[I10] Is the import of therapeutic product into Singapore for pre-clinical studies (e.g. cell lines for in vitro or in vivo studies) subjected to regulatory control in Singapore?

[I11] What are the regulatory controls for conducting clinical trials on controlled drugs or psychotropic substances?

[I12] What are the regulatory considerations for destruction of investigational products in Singapore?

[I13] Are there any guidelines for Investigational Product management for investigator-initiated clinical trials (IITs)?

[J] BIOLOGICAL SAMPLES

[J1] Is an export licence required for sending biological samples to overseas for testing?

[K] SAFETY REPORTING

[K1] What are the regulatory requirements for safety reporting in clinical trials?

[K2] What are the regulatory requirements for safety reporting of registered drugs used in clinical trials?

[K3] What safety reporting requirements apply for an investigational product whose active ingredient is registered in Singapore, but for which the registered route of administration or formulation is different from that of the registered product?

[K4] When should the sponsor start to submit reports of unexpected serious adverse drug reactions (USADR) to HSA?

[K5] When may the sponsor cease submission of USADR reports to HSA?

[K6] In the event of trial termination, does HSA have any requirements on when to cease submission of safety reports?

[K7] Does the sponsor need to submit safety reports from Named Patient Programme or for compassionate use of unregistered drugs?

[K8] Does the sponsor need to submit periodic line listings, DSURs, annual or periodic safety reports to HSA?

[K9] If the serious adverse event was causally-related to a study procedure in a clinical trial, is there a need to report this event?

[K10] Are there any instances whereby serious and expected reactions are to be reported?

[K11] When does the reporting timeline for reporting of an unexpected serious adverse drug reaction (USADR) start?

[K12] Can the sponsor do a batch submission of reports of unexpected serious adverse drug reactions (USADR)?

[K13] Who should assume responsibility when the sponsor company does not have a local party performing safety reporting submissions?

[K14] How can one gain access to Expedited Safety Reports (ESR) module in PRISM?

[K15] In cases where safety reporting is done by the pharmacovigilance department of the sponsor company located overseas, can the reporting be done via ESR?

[K16] If the local sponsor outsources the safety reporting to a CRO, how may the CRO use the online ESR module?

[K17] What are the current regulatory requirements for safety reporting in clinical trials involving medical devices?

[L] CLINICAL RESEARCH MATERIALS (CRM)

[L1] What are Clinical Research Materials (CRM)?

[L2] What are the regulatory requirements for Clinical Research Materials (CRM) in Singapore?

[L3] What are the differences between the CRM regulations and the clinical trial (CT) regulations?

[L4] When must CRM notification be submitted to HSA?

[L5] Is CRM notification required if the product is locally-registered and obtained from a pharmacy or sourced from an authorised local distributor?

[L6] Are dealers of CRM required to obtain dealers licences (e.g. manufacturer’s licence, importer’s licence, wholesaler’s licence)?

[L7] If a company is the authorised importer for a locally-registered therapeutic product as reflected in the full-scope importer’s licence, would CRM notification be required prior to import of the registered product for use in local clinical research?

[L8] If a company has a full scope importer’s licence but is not the authorised importer for a locally-registered therapeutic product, would CRM notification be required prior to import of the locally-registered therapeutic product for use in local clinical research?

[L9] Is CRM notification required before supply of IP that was compounded at the local trial site?

[L10] Is CRM notification required for the import of unused Investigational Products from overseas trial sites into Singapore for destruction?

[L11] Does the CRM notification need to be amended for a change in Principal Investigator (PI)?

[L12] Is it possible to make amendments to the CRM notification?

[L13] If CRM notification was previously made to facilitate the import of a medical device (e.g., ECG machine) for a particular clinical trial, would it be possible to use the ECG machine for another clinical trial and not return it to the overseas manufacturer?

[L14] Is there a difference in “import route” for importing CRM for local research vs. overseas research?

[L15] What are the records that must be maintained for CRM?

[M] OTHERS

[M1] How does the Personal Data Protection Act 2012 (PDPA) apply to the collection and usage of subjects' data in clinical trials conducted in Singapore?

[M2] How may the site archive essential study documents electronically?

Last updated: 9 Oct 2017


[A] GENERAL REGULATORY REQUIREMENTS FOR CLINICAL TRIALS

[A1] What are the regulatory requirements for clinical trials in Singapore?

With effect from 1 Nov 2016:

Clinical trials of therapeutic products (e.g. pharmaceutical drugs and biologics) require clinical trial authorisation (CTA) or acceptance of clinical trial notification (CTN) before the trial can be initiated or conducted. Such clinical trials must be conducted in compliance with the Health Products (Clinical Trials) Regulations and the ICH E6 Good Clinical Practice guidelines.

Clinical trials of medicinal products (e.g. cell, tissue and gene therapy products or complementary health products) require a clinical trial certificate (CTC) before the trial can be initiated or conducted. Such clinical trials must be conducted in compliance with the Medicines (Clinical Trials) Regulations and the ICH E6 Good Clinical Practice guidelines.

Observational clinical trials of therapeutic products and medicinal products, and clinical trials of medical devices, are not regulated by HSA.

Please refer to the Regulatory Framework page for an overview of the regulatory requirements for clinical trials in Singapore.

Note: Regardless of whether the clinical trial is regulated by HSA, the import and supply of therapeutic products, medicinal products and medical devices for use in local clinical research may be subject to regulatory control under the Health Products (Therapeutic Products as Clinical Research Materials) Regulations, the Medicines (Medicinal Products as Clinical Research Materials) Regulations or the Health Products (Medical Devices) Regulations. Please refer to Section [L] for FAQ on the regulation of Clinical Research Materials in Singapore.

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[A2] How can I determine if my clinical trial requires Clinical Trial Authorisation (CTA), Clinical Trial Notification (CTN) or a Clinical Trial Certificate (CTC)?

Please refer to the Guidance on Determination of Whether a Clinical Trial Requires a Clinical Trial Authorisation (CTA), Clinical Trial Notification (CTN) or Clinical Trial Certificate (CTC).

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[A3] Can I submit my clinical trial application to HSA and the IRB concurrently?

For clinical trials that require clinical trial authorisation (CTA) or a clinical trial certificate (CTC), the clinical trial application may be submitted concurrently to HSA and the relevant IRB.

For clinical trials that require clinical trial notification (CTN) to HSA, the submission should be made only after having received IRB approval for the clinical trial.

Please refer to the Guidance on Regulatory Requirements for New Applications and Subsequent Submissions for further details.

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[A4] What are the documents that must be submitted to HSA to support the clinical trial application?

Please refer to the Guidance on Regulatory Requirements for New Applications and Subsequent Submissions.

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[A5] For how long is a Clinical Trial Authorisation (CTA), Clinical Trial Notification (CTN) or Clinical Trial Certificate (CTC) valid?

The CTA, CTN or CTC is valid for the duration of the clinical trial.

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[A6] What are the subsequent applications required to be submitted to HSA following receipt of the authorisation (for CTA), acceptance of notification (for CTN) or approval (for CTC) by HSA?

Please refer to the Guidance on Regulatory Requirements for New Applications and Subsequent Submissions for further details.

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[A7] What are the regulatory timelines for subsequent submissions to HSA?

The regulatory timelines for subsequent submissions include:

Subsequent Submission to HSA Submission Timeline
Substantial amendments Prior to implementation
Serious Breaches As soon as possible, but no later than 7 calendar days
Urgent Safety Measures  As soon as possible, but no later than 7 calendar days
Trial Status Reports 6 monthly (+ 14 calendar days)
Unexpected Serious Adverse Drug Reactions (USADR)

- Fatal or life threatening events
Initial report: As soon as possible, and not later than 7 calendar days from sponsor’s first awareness of the USADR;

Follow-up report: As soon as possible, and not later than 8 calendar days following the initial report.
Unexpected Serious Adverse Drug Reactions

- Non-fatal or non-life threatening events
Initial report: As soon as possible, and not later than 15 calendar days from sponsor’s first awareness of the USADR;

Follow-up report: As soon as available
Updates to the Investigator’s Brochure (IB) or new safety information As soon as available
Suspension of clinical trial 15 calendar days from date of trial suspension
Termination of clinical trial 15 calendar days from date of trial termination
Completion of clinical trial 30 calendar days from date of trial completion
Final Report 1 year from date of trial completion

Please refer to the Guidance on Regulatory Requirements for New Applications and Subsequent Submissions for further details.

If the sponsor is unable to comply with the above regulatory timelines, the sponsor should notify HSA in writing of the reason(s) for the delay and corrective and preventive actions implemented to prevent a recurrence.

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[A8] How is study completion defined?

Study completion is defined as ‘Last Patient Last Visit (LPLV)’ for the clinical trial. For clinical trials where subjects are followed up remotely after LPLV (e.g. survival follow-up via telephone calls or safety follow-up etc.), study completion is defined as the end of remote follow-up. For multi-national clinical trials, study completion applies to the LPLV for the local trial sites.

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[A9] If a clinical trial was approved by HSA before 1 Nov 2016, how will it be affected by the revised clinical trial regulations?

Clinical trials of pharmaceutical products and biologics (known as therapeutic products from 1 Nov 2016) that had been granted a Clinical Trial Certificate before 1 Nov 2016 will become regulated under the Health Products (Therapeutic Products) Regulations from 1 Nov 2016. The clinical trial will be regarded as a clinical trial with Clinical Trial Authorisation (CTA) if the trial status is indicated as ongoing on PRISM on 1 Nov 2016.

Clinical trials of medicinal products (cell, tissue and gene therapy products and complementary health products) approved by HSA before 1 Nov 2016 will remain regulated under the Medicines (Clinical Trials) Regulations. The clinical trial will continue to require a Clinical Trial Certificate (CTC).

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[A10] If a clinical trial of a therapeutic product was an observational clinical trial approved by HSA before 1 Nov 2016, would the trial be excluded from the clinical trials regulations from 1 Nov 2016?

Observational clinical trials of therapeutic products that were granted a Clinical Trial Certificate (CTC) before 1 Nov 2016 will be regarded as a clinical trial with a Clinical Trial Authorisation from 1 Nov 2016. Such observational trials will be subject to the regulatory controls under the Health Products (Clinical Trials) Regulations.

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[A11] Are there any fees for the submission of clinical trial application to HSA?

There are currently no fees imposed for the submission of clinical trial application to HSA.

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[B] SPECIFIC REGULATORY REQUIREMENTS FOR CLINICAL TRIALS

[B1] What are the regulatory requirements on First-in-Human (FIH) trials of therapeutic products?

In general the documentation requirement to support FIH applications is not significantly different to that for later phase studies. The therapeutic product need not be approved in other countries before the FIH trial can be conducted in Singapore. As with all clinical trials, the sponsor applicant must be a locally registered company.

For guidance on non-clinical and clinical requirements, companies may refer to applicable ICH guidelines and relevant guidelines issued by the major agencies (FDA, EMA).

The following are examples of such guidance, which the pharmaceutical industry should be familiar with.

  • M3(R2) Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals
  • S6(R1) Preclinical safety evaluation of biotechnology-derived pharmaceuticals
  • FDA CDER guidance for industry: Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers
  • Guideline on Strategies to Identify and Mitigate Risks for First-In-Human Clinical Trials with Investigational Medicinal Products (EMA/CHMP/SWP/28367/07)

If the investigational product is of a novel therapeutic class or mechanism of action, we would encourage a pre-submission meeting with the sponsor.

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[B2] Are non-clinical safety/toxicology studies required to be conducted in compliance to GLP standards?

Non-clinical studies providing toxicology information to support clinical trials should be conducted in compliance with Good Laboratory Practice (GLP), which is a quality system on the organisation process and conditions under which the non-clinical studies are planned, recorded, archived and reported. The basis to accept studies conducted in compliance to GLP will help assure regulatory agencies that the non-clinical safety data are accurate and reliable for the purpose of risk evaluation.

For more information on GLP, please refer to the GLP Compliance Programme administered by Singapore Accreditation Council.

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[B3] Are there any regulatory requirements for clinical trials involving radiopharmaceuticals?

The regulation of radiopharmaceutical clinical trials is similar to that for the conventional medicinal products. HSA generally takes reference to applicable international guidelines from FDA and EMA guidelines for the use of radiopharmaceuticals in clinical trials.

The import, export, possession, use, transport, disposal etc. of radioactive material is subject to control under the Radiation Protection Act, which is regulated by the National Environment Agency (NEA). Please refer to NEA website > Anti-Pollution & Radiation Protection > Radiation Protection for more information including the adequacy of the facility.

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[B4] What kind of preclinical data is required to support clinical trials of cell, tissue and gene therapy products (CTGTP)?

Relevant preclinical data include:

(i) Nonclinical proof of concept to provide the scientific basis for conducting clinical trial:

  • Potential mechanism of action
  • Establish pharmacologically effective doses
  • Optimize route of administration and dosing regimen
  • Rationale for species/model selection

(ii) Toxicity studies in relevant animal species to provide useful information about the safety of the product

  • Identify, characterize, quantify potential local and systemic toxicities
  • Safety data for recommendation of initial dose and dose escalation scheme in humans

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[B5] Are there any additional dossier requirements for submission of cell, tissue and gene therapy product (CTGTP) clinical trials?

Yes. In addition to the standard supporting documentation required of all clinical trial applications (refer to Guidance on Regulatory Requirements for New Applications and Subsequent Submissions), the submission dossier for a CTGTP clinical trial should also include Chemistry, Manufacturing, and Control (CMC) Information:

  • consistent control of cell source, reagents, facility, personnel and equipment
  • validation of manufacturing process, aseptic processing and test methods
  • Confirm safety and quality of each lot by product testing
  • Quality Overall Summary on Equipment and Facility – this refers to the list of equipments and qualification pertaining to the manufacturing or processing of the CTT product, and a description of the heating, ventilation and air-conditioning system (HVAC)

For regulatory guidance on a CTGTP clinical trial, companies may refer to applicable guidelines issued by major regulatory agencies (FDA, EMA). The following are examples of such guidance, which trial sponsors should be familiar with.

  • FDA Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)
  • FDA Final Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products
  • FDA Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy
  • EMA Guideline on Human Cell-Based Medicinal Products
  • EMA Guideline on Potency Testing of Cell Based Immunotherapy Medicinal Products for the Treatment of Cancer

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[B6] What are the regulatory requirements for conducting clinical trials on health supplements?

Clinical trials on health supplements do not, in general, require regulatory approval from HSA.  However, if the aim of the trial is to evaluate the health supplement for a medicinal purpose e.g., treatment or prevention of a specific disease, then the trial may be regulated under the Medicines Act and require a Clinical Trial Certificate (CTC). The team may enquire with HSA if unsure as to whether a study involving a health supplement will require a CTC.

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[B7] What are the applicable ICH guidelines that the Health Sciences Authority adopts for clinical trials?

The Health Sciences Authority adopts the following ICH guidelines for clinical trials, where applicable:

  1. E2A: Pharmacovigilance
  2. E6(R2): Good Clinical Practice
  3. M3: Nonclinical Safety Studies
  4. S1A-S1C: Carcinogenecity Studies
  5. S2: Genotoxicity Studies
  6. S3A-S3B: Toxicokinetics and Pharmacokinetics
  7. S4: Toxicity Testing
  8. S5: Reproductive Toxicology
  9. S6: Biotechnology Products
  10. S7A-S7B: Pharmacology Studies
  11. S8: Immunotoxicology Studies
  12. S9: Nonclinical Evaluation for Anticancer Pharmaceuticals
  13. S10: Photosafety Evaluation
  14. S11: Nonclinical Safety Testing


Please refer to the ICH website for the updated ICH guidelines.

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[C] CLINICAL TRIALS OF MEDICAL DEVICES

[C1] What are the current regulatory requirements for clinical trials of medical devices? 

All manufacturers, importers, wholesalers and suppliers of medical devices, including medical practitioners who supply medical devices to patients as part of clinical practice or clinical trials, have legal responsibilities in accordance with the Health Products (Medical Devices) Regulations. This includes the need to ensure compliance with labelling requirements, reporting of product defects and adverse effects to HSA, as well as proper record keeping. 

Unlike clinical trials of therapeutic products or medicinal products that require a CTA, CTN or CTC, clinical trials of medical devices are not currently regulated by HSA.  The clinical investigator may proceed with the trial after obtaining relevant ethics approval, keeping in view the duties and obligations of all dealers of medical devices as outlined in the table below:

Duties and Obligations Parties
Local Manufacturer Importer Supplier* Sponsor
All CRM (including locally-registered products)
Ensure the CRM (MD) complies with “Safety and Performance Requirements for Medical Devices” in the First Schedule of the Health Products (Medical Devices) Regulations

(Ref: GN-16: Guidance on Essential Principles for Safety and Performance of Medical Devices)
   
Maintain records of manufacture, assembly and testing      
Maintain records of receipt (new) and supply

(Ref: Section 5.2.1 of Guidance on CRM; and GN-06: Guidance on Distribution Records for Medical Devices)
√* √* √*
Ensure compliance with labelling requirements

(Ref: GN-23: Guidance on Labelling for Medical Devices)
√*
Report MD defects and adverse effects to HSA

(Ref: GN-05: Guidance on Reporting of Adverse Events for Medical Devices)
√*
Maintain records of complaints

(Ref: GN-07: Guidance on Complaint Handling of Medical Devices)
√*
Notify HSA concerning recall

(Ref: GN-04: Guidance on Medical Device Recall)
√*
Notify HSA concerning field safety corrective actions (FSCAs)

(Ref: GN-10: Guidance on Medical Devices Field Safety Corrective Action)
√*
Additional requirements for locally-manufactured or imported CRM
Ensure CRM supply/use only for clinical research purpose (new) √* √* √*
Ensure CRM use only in IRB-approved clinical research (new)      
Ensure disposal/export of CRM within 6 months of research completion/termination (new)      
Maintain records of disposal/export (new)

(Ref: Section 5.2.1 of Guidance on CRM)
     

* Responsibility as “Supplier”. Supplier includes local manufacturer, importer, wholesaler, sponsor, investigator, where applicable, if the party is involved in the activity of supplying a MD for clinical research.

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[D] PRINCIPAL INVESTIGATOR

[D1] What are the regulatory obligations of a Principal Investigator (PI)?

The regulatory obligations of a Principal Investigator (PI) conducting a clinical trial include the following:

  • Conduct trial in accordance with protocol, regulatory conditions, the Regulations and principles of GCP;
  • Conduct trial at specified place(s);
  • Responsible for medical care/decisions relating to subject;
  • Consent and provision of information;
  • Keep adequate trial-related documents;
  • Declare financial interest to IRB;
  • Report serious breach of GCP/protocol to IRB, if required; and
  • Report serious adverse events (SAEs) to sponsor, and IRB if required, within stipulated timelines.

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[D2] Who can be a Principal Investigator (PI) of a clinical trial?

A Principal Investigator (PI) is a qualified practitioner, who is qualified by training and experience; and has adequate resources to conduct a clinical trial [Ref: Health Products (Clinical Trial) Regulation 5(1) and Medicines (Clinical Trial) Regulation 5(1)]. A qualified practitioner is a registered medical practitioner under the Medical Registration Act or a registered dentist under the Dental Registration Act. Section 4.1.1 of ICH E6 GCP requires the Investigator to be qualified by education, training and experience to conduct the clinical trial.

For clinical trials assessing investigational products in specialised therapeutic areas, the PI should be at least an Associate Consultant (AC) or above in the specialised therapeutic area. This is because clinical trials in such therapeutic areas usually involve complex diagnostic evaluation of the disease condition, or study procedures that require specialized skills. Suitably qualified ACs and above would have sufficient training and experience to conduct such clinical trials properly, as well as handle unforeseen adverse events or difficulties arising from the conduct of the clinical trial.

For clinical trials assessing registered therapeutic products or licensed medicinal products, the PI may be general practitioner where in clinical practice, he/she would be using the product.

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[D3] Can a doctor who has a conditional registration with Singapore Medical Council (SMC) be a Principal Investigator (PI) of a clinical trial?

A PI should have a level of authority to supervise the clinical trial in addition to being able to make independent medical decisions during the trial. The level of supervision should be appropriate to the  nature of the trial and the subject population. If the registration condition requires the doctor to "work under supervision", the doctor would be required to submit a statement from the doctor's supervisor indicating support for the doctor's involvement as the PI of the study, along with the clinical trial application to HSA. 

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[D4] What is the minimum training required for Principal Investigators (PIs)?

PIs should fulfil the training requirements specified by the respective Institutional Review Board (IRB), unless a waiver of has been granted by the IRB. Training documentation (e.g. GCP certificate, Collaborative IRB Training Initiative, study-specific training) or supporting documents for waiver (if applicable) should be maintained in the study files. It is not necessary to submit training documentation to HSA. 

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[D5] What should be done when the Principal Investigator (PI) is on extended leave?

The PI should have sufficient time to properly conduct and supervise the clinical trial. It is recommended that an amendment application for Change of PI be submitted to HSA in the following situations if the PI is away on extended leave for more than 4 months:

  • The PI is also conducting multiple studies concurrently;
  • The clinical trial is a complex clinical trial;
  • A large number of subjects have been enrolled into the clinical trial;
  • The clinical trial involves a subject population that is critically ill; or
  • The clinical trial is conducted by inexperienced site study staff.

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[D6] If the Principal Investigator (PI) of a suspended / terminated / completed clinical trial has resigned, is there a need to submit an amendment application for Change of PI to HSA?

An amendment application for Change of PI must be submitted if the PI of a suspended clinical trial has resigned. However, this is not required if the PI of a terminated / completed clinical trial has resigned.

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[E] STUDY STAFF

[E1] What types of study specific responsibilities require trial-related medical / dental decisions to be made by an investigator?

Section 4.3.1 of ICH E6 GCP requires an investigator, who is a qualified physician, to make trial-related medical / dental decisions. This would imply that the investigator should be a locally registered doctor or dentist to make trial-related medical / dental decisions respectively. Examples of trial-related medical / dental decisions would include the following, where applicable:

  • Obtaining informed consent
  • Confirming subject eligibility
  • Performing physical examinations
  • Reviewing laboratory results
  • Reviewing ECG results
  • Signing off case report forms
  • Signing off data queries
  • Safety reporting

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[E2] What are the minimum training requirements for study staff?

Study staff should be adequately qualified (by education, training and experience) and informed about the protocol, investigational product and their trial related roles and responsibilities [Ref: ICH E6 GCP 4.2.3 and 4.2.4]. Please refer to the relevant IRB for minimum training requirements for Principal Investigators. Additionally, all study staff should be provided with study-specific training and all relevant training documentation should be maintained on file.

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[E3] If the study staff has been trained in the Singapore Guideline for Good Clinical Practice (SGGCP), do they need to be re-trained in the ICH E6 GCP after the port over of the clinical trials regulations?

The principles of Good Clinical Practice (GCP) outlined in the ICH E6 GCP and SGGCP are the same, and the guidelines by and large similar. It is thus not required for study staff trained in SGGCP to be re-trained in ICH E6 GCP.

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[E4] If there is a change of Principal Investigator (PI) for a clinical trial, how can this change be documented on the Signature Sheet?

It would be recommended to complete an end date for all study staff on the current Signature Sheet; and complete a new Signature Sheet for all study staff to be authorised by the new PI.

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[F] SPONSOR

[F1] What are the regulatory obligations of a sponsor of a regulated clinical trial?

The regulatory obligations of a sponsor of a regulated clinical trial include the following:

  • Obtain authorisation (for CTA), acceptance of notification (for CTN) or approval (for CTC) for the clinical trial;
  • Obtain approval for substantial trial amendments;
  • Notify HSA of trial status, suspension, termination and/or conclusion, and submit final report within stipulated timelines;
  • Ensure information in the Investigator’s Brochure (IB) is concise, objective and kept up to date;
  • Ensure that the clinical trial is conducted under supervision of qualified principal investigator;
  • Ensure that the clinical trial is conducted at specified place(s);
  • Carry out functions of the sponsor in accordance with principles of GCP;
  • Put and keep in place arrangements to ensure compliance with principles of GCP
  • Notify HSA of serious breach of GCP/protocol and urgent safety measures taken to protect subjects against immediate hazard within stipulated timelines;
  • Keep adequate trial-related documents;
  • Ensure appropriate investigational and auxiliary product labelling; and
  • Report unexpected serious adverse drug reactions (USADRs) to HSA within stipulated timelines.

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[F2] What are the additional sponsor responsibilities for investigator-initiated clinical trials where more than one local trial site is involved in conducting the clinical trial on a single protocol (i.e. multi-sponsor IITs)?

For investigator-initiated clinical trials where more than one local trial site is involved in conducting a clinical trial on a single protocol (i.e. multi-sponsor IITs), the following are additional responsibilities for the lead sponsor and participating site sponsor:

Additional responsibilities for the lead sponsor:

  • Regulatory submissions and notifications to HSA (e.g. CTC/CTA/CTN applications, amendments, serious breaches, trial status reports, final trial reports, etc);
  • Ongoing safety evaluation of study drug(s) administered to subject;
  • Prompt notification to all participating site investigators/institutions of findings that could adversely affect subject safety or impact conduct of trial; and
  • Notification of unexpected serious adverse drug reactions, and serious breaches of GCP/protocol, to HSA.

Additional responsibilities for the participating site sponsor(s):

  • Report immediately to lead sponsor any Serious Adverse Event (SAE) at the participating site, or any finding that could adversely affect subject safety or impact conduct of trial; and
  • Provide all relevant information to lead sponsor that is necessary for the lead sponsor to perform trial-related regulatory submissions and notifications to HSA

Please refer to the Guidance on Multi-sponsor Investigator-initiated Trials for further details.

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[F3] What should the sponsor do if there is a transfer of local sponsorship for an ongoing clinical trial?

For transfer of local sponsorship for an ongoing clinical trial to another locally registered company, the new local sponsor should submit a new clinical trial application to HSA. The new clinical trial application should contain the following:

  • All currently-approved study documents as required for a new clinical trial application; and
  • Letter from the current local sponsor indicating transfer of local sponsorship to the new local sponsor. This letter should be copied to the new local sponsor and the respective trial site PI(s) and IRB(s).

Upon receipt of the clinical trial authorisation (CTA), acceptance of notification (CTN) or approval of (CTC) the clinical trial, the current local sponsor should submit a Trial Status Report to indicate the change of local sponsor. This can be done by indicating the trial status as “Premature site closure” and providing the reason as change of local sponsor.

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[F4] What should the sponsor do when there is a change in the contact person?

The contact person of the local sponsor is deemed to be the applicant who had submitted the most recent PRISM application for that clinical trial (excluding safety reports). E-mail reminders for submission of Trial Status Report are sent to this contact person. Hence, it is essential to inform HSA when there is a change in the contact person.

The change of local sponsor contact person can be effected through the submission of a Trial Status Report or any other application (excluding safety reports). Subsequent regulatory correspondences would thereafter be directed to the new local sponsor contact person after the submission has been processed by HSA. 

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[F5] What should the local sponsor do when there is a change in company address?

The local sponsor should inform HSA via e-mail. Our contact information is on this page.

To update the company address in PRISM, please go to PRISM e-Services for Clinical Trials > Amend Company Information.

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[G] PROTOCOL

[G1] What kind of study amendments should be submitted to HSA?

Substantial amendments must be submitted to HSA.

Non-substantial amendments need not be submitted to HSA unless otherwise specified or requested by HSA. For example, all updated investigator’s brochures should be submitted, regardless of whether the change(s) are substantial amendments or not.

Please refer to the Guidance on Determining Whether an Amendment to a Clinical Trial is a Substantial Amendment for further details.

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[G2] Although it is the sponsor’s responsibility to assess whether an amendment is regarded as a substantial amendment, does a lead sponsor need to consult the participating sponsors on the assessment for multi-sponsor Investigator-initiated trials (MS IITs)?

For MS IITs, the lead sponsor (who is involved in protocol development) should assess whether an amendment is substantial. It would be recommended for the lead sponsor to consult other participating sponsors on the assessment. There should ideally be a consensus amongst the lead sponsor and participating sponsors on the assessment. In addition, the participating sponsors should always be informed of the assessment, and such communication should be documented on file. This is to ensure that all the sponsors involved in the MS IIT are aware of the nature of the protocol amendment. In the event that the sponsors are not able to ascertain whether the amendment is substantial or not, the lead sponsor may write to HSA for advice.

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[G3] Are there any guidelines for reporting Protocol Deviations to HSA?

Sponsors should notify HSA of any serious breach which is likely to affect to a significant degree:

  • The safety or physical or mental integrity of any subjects in a clinical trial; or
  • The scientific value of the clinical trial.

Please refer to the Guidance on Notification of Serious Breaches.

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[G4] Does HSA approve Protocol Waivers?

The practice of enrolling subjects into a study based on "Protocol Waiver" is discouraged. The protocol's eligibility criteria should be amended to reflect the clinical practice. For industry-sponsored studies, there are implications to the validity of the data presuming that the enrollment of the subject, who has not fulfilled the eligibility criteria has been permitted, is not compromised.

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[H] INFORMED CONSENT FORM (ICF)

[H1] What are the basic principles of an informed consent process?

The basic principles of an informed consent are information, comprehension and voluntariness, in accordance with the Belmont Report.

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[H2] What are the regulatory requirements for informed consent?

The regulatory requirements for informed consent are outlined in Regulations 16 to 20 of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and Section 4.8 of ICH E6 GCP guidelines.

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[H3] What are the regulatory requirements for informed consent in vulnerable subjects?

Please refer to the Guidance on Safeguards and Consent Requirements in Vulnerable Subjects for regulatory requirements for informed consent in vulnerable subjects (i.e. minors, adults lacking capacity and clinical trials in emergency situations).

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[H4] For clinical trials in minors, must the minor give consent prior to participating in the clinical trial?

For clinical trials in minors, the investigator should determine if the minor has sufficient capacity or understanding and intelligence to give consent.

If the minor has sufficient capacity or understanding and intelligence to give consent, the minor’s legal representative and the minor must give consent for the minor to participate in the clinical trial.

If the minor has does not have sufficient capacity or understanding and intelligence to give consent, the minor’s legal representative must give consent for the minor to participate in the clinical trial. If the minor subsequently is deemed to have the capacity or understanding and intelligence to give consent during the clinical trial, the minor must be re-consented accordingly.  

Please refer to the Guidance on Safeguards and Consent Requirements in Vulnerable Subjects for further details.

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[H5] For clinical trials in minors, if the mother of the minor is below 21 years of age and is not / never was married, can the mother give informed consent for the minor?

For clinical trials in minors, if the mother of the minor is below 21 years of age and is not / never was married, the mother cannot give informed consent for the minor since she is not an adult parent. The father of the minor could give consent if he is > 21 yrs. Otherwise, the legal guardian of the minor must give consent.

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[H6] For clinical trials in adults lacking capacity where there is a donee for the adult lacking capacity, does the investigator need to ascertain whether the donee has been authorised to give consent for clinical trial participation?

For clinical trials in adults lacking capacity where there is a donee for the adult lacking capacity, the investigator should ascertain whether the donee has been authorised to give consent for clinical trial participation by verifying the section entitled ‘Powers Granted to the Donee’ on the Lasting Power of Attorney Form 1. If the donee has been granted the power to decide on clinical trial participation, the donee may give consent for the adult lacking capacity. If the donee has not been granted the power to decide on clinical trial participation, the donee should not give consent for the adult lacking capacity.

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[H7] For clinical trials in adults lacking capacity where it has been established that the adult child of the adult lacking capacity is the legal representative, is there an order of priority amongst the adult children if the adult lacking capacity has more than one adult child?

For clinical trials in adults lacking capacity where it has been established that the adult child of the adult lacking capacity is the legal representative, there is no order of priority amongst the adult children if the adult lacking capacity has more than one adult child. However, there should be no objections from the other adult children and any individual(s) of higher priority to the enrollment of the adult lacking capacity into the clinical trial. It would be recommended to give the family of the adult lacking capacity ample time to consider enrollment of the adult lacking capacity into the clinical trial.

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[H8] For clinical trials in adults lacking capacity where it has been established that the adult sibling of the adult lacking capacity is the legal representative, is there an order of priority amongst the adult siblings if the adult lacking capacity has more than one adult sibling?

For clinical trials in adults lacking capacity where it has been established that the adult sibling of the adult lacking capacity is the legal representative, there is no order of priority amongst the adult siblings if the adult lacking capacity has more than one adult sibling. However, there should be no objections from the other adult siblings and any individual(s) of higher priority to the enrollment of the adult lacking capacity into the clinical trial. It would be recommended to give the family of the adult lacking capacity ample time to consider enrollment of the adult lacking capacity into the clinical trial.

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[H9] For clinical trials in adults lacking capacity where it has been established that the adult child is the legal representative, would the adult child be considered as ‘not available’ if the adult child is located overseas?

The adult child may be considered as ‘not available’ if the adult child is located overseas. Where feasible, the decision from that adult child should be obtained and documented.

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[H10] What are the elements of an informed consent form?

The elements of an informed consent form are outlined in Regulations 19(1) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and Section 4.8.10 of ICH E6 GCP guidelines.

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[H11] What are the required approvals for the informed consent form prior to use?

The English informed consent form must be approved by the relevant Institutional Review Board (IRB) and HSA prior to use. Please refer to Regulations 18(2) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and Section 4.8.1 of ICH E6 GCP guidelines.

Translated informed consent forms need not be submitted to HSA, but should be submitted to the relevant IRBs prior to use, in accordance with IRB guidelines.

All amendments to the informed consent forms must be submitted to the relevant IRBs prior to use. Substantial amendments to the informed consent forms must be submitted to HSA for review and approval prior to use. Please refer to the Guidance on Determining Whether an Amendment to a Clinical Trial is a Substantial Amendment.

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[H12] Who can obtain informed consent?

Informed consent must be obtained by an investigator who is a qualified practitioner and delegated by the Principal Investigator to obtain informed consent. A qualified practitioner is a registered medical practitioner under the Medical Registration Act or a registered dentist under the Dental Registration Act. Please refer to Regulations 18(1) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and Section 4.8.8 of ICH E6 GCP guidelines.

It is not acceptable for an investigator who is not a qualified practitioner and other non-investigators (e.g. Clinical Research Coordinators, Research Assistants, Study Pharmacists etc.) to obtain informed consent.

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[H13] When should informed consent be obtained from the subject or legal representative (if applicable)?

Informed consent must be obtained from the subject or legal representative (if applicable) prior to any study procedures. Please refer to Regulations 16(1 and 2) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and Section 4.8.8 of ICH E6 GCP guidelines.

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[H14] Which version of the informed consent form should be used to consent the subject or legal representative (if applicable)?

The version of the informed consent form that has been approved by the IRB and HSA (except for administrative changes) should be used to consent the subject or legal representative.

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[H15] Where should informed consent be obtained from the subject or legal representative (if applicable)?

Informed consent should be obtained from the subject or legal representative (if applicable) in a conducive environment without any coercion, duress or undue influence. Please refer to Regulation 20 of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and Section 4.8.3 of ICH E6 GCP guidelines.

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[H16] How should the informed consent form be explained to the subject or legal representative (if applicable)?

The language of the informed consent form should be non-exculpatory, non-technical, practical and understandable by the subject or legal representative (if applicable). The subject or legal representative (if applicable) should be given ample time and opportunity to ask questions to consider participation. Please refer to Sections 4.8.4, 4.8.6 and 4.8.7 of ICH E6 GCP guidelines.

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[H17] How should the informed consent form be completed?

The informed consent form should be personally signed and dated by the investigator obtaining informed consent, the subject or legal representative, and the impartial witness (if applicable). Please refer to Regulation 18(2) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and Section 4.8.8 of ICH E6 GCP.

If there are checkboxes to be completed in the informed consent form, it would be recommended that the checkboxes are personally completed by the subject or legal representative (if applicable).

The signature of the investigator obtaining informed consent should be consistent with the Signature Sheet.

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[H18] Are signature stamps and date stamps acceptable means of signing and dating the informed consent form?

No, Regulations 18(2) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and Section 4.8.8 of ICH E6 GCP require the person giving consent to personally sign and date the informed consent form. Hence, it would not be acceptable for signature stamps and date stamps to be used as a means of signing and dating the informed consent form.

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[H19] If a clinical trial involves recruiting subjects who are mentally competent, but unable to sign or date the informed consent form, how can consent be obtained from such a subject?

An impartial witness would be required to observe the informed consent process if the subject is mentally competent but unable to sign or date the informed consent form. It would be recommended to develop an informed consent process for such a scenario and submit it to the IRB for review and approval. Please refer to Regulation 18(2) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations for further details.

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[H20] How can informed consent be obtained from a subject or legal representative (if applicable) who is unable to read the informed consent form?

If the subject or legal representative is unable to read the informed consent form, an impartial witness would be required to be present during the informed consent process. By signing the informed consent form, the impartial witness attests that the informed consent had been accurately explained to, apparently understood by, and informed consent freely given by the subject or legal representative (if applicable). The subject or legal representative (if applicable) should sign and personally date the informed consent form, if capable of doing so. Please note that the role of an impartial witness is different from a translator, since the translator does not need to attest to the above-mentioned clauses. Please refer to Regulation 18(5) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and ICH E6 GCP 4.8.9 for further details.

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[H21] Who can act as an impartial witness?

Section 1.26 of ICH E6 GCP defines an impartial witness as ‘A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject of the subject’s legally acceptable representative cannot read, and who read the informed consent form and any other written information supplied to the subject’.

The role of an impartial witness is to attest that the informed consent has been accurately explained to the subject or legal representative, the informed consent has been apparently understood by the subject or legal representative, and the subject or legal representative has voluntarily agreed to participate in the clinical trial.

There is no regulatory provision regarding who can act as the impartial witness. One should consider whether the person who acts as an impartial witness is independent of the clinical trial and is not influenced by people involved in the clinical trial. The possible choices would be either a family member, friend, clinic staff (who is not a part of the study team), or a layperson. Whilst it is impractical to get a layperson, the viable options would either be the family member, friend, clinic staff (who is not a part of the study team). The choice of an impartial witness should be made in the best interest of the subject.

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[H22] How can informed consent be obtained from a subject or legal representative by an investigator who is not conversant with the subject or legal representative’s language?

If the subject or legal representative is able to read the informed consent form, a translator would be required to be present during the informed consent process.

If the subject or legal representative is unable to read the informed consent form, a translator and an impartial witness would be required to be present during the informed consent process.

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[H23] Who can act as a translator?

Section 4.8.6 of ICH E6 GCP guidelines requires the language used in the oral and written information about the trial should be non-technical, practical and easily understood by the subject or legal representative and impartial witness (if applicable).

An individual who is adequately qualified or certified in the local language may act as a translator. The translator differs from the impartial witness in that the translator’s role is to translate one language to another and the translator may be part of the study team unlike an impartial witness. Information on the translator should be completed in the informed consent form or subject medical records. 

It is acceptable for an impartial witness to act as a translator if the impartial witness is able to fulfil the role of a translator.

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[H24] Is there a summary table available to help determine whether an impartial witness or a translator is required during an informed consent process?

The following table summarizes when an impartial witness or translator is required during an informed consent process:

Subject or Subject's legal representative Investigator Language of written ICF Translator required? Impartial Witness required? Comments
Literate in English Literate in English English No No  
Literate in a local language Literate in a local language Local Language No No  
Literate in a local language Literate in English and unable to communicate with subject or subject's LAR Local Language Yes No  
Literate in a local language Literate in English and unable to communicate with subject or subject's LAR English Yes Yes

It is strongly recommended that the ICF in local language be made available.

The impartial witness may act as a translator if he/she is able to fulfill this role. Alternatively, the English ICF and a Short Form Consent (in a local language that the subject or the subject’s LAR is literate in) could be signed by all parties involved in the informed consent process.

Illiterate or unable to read due to visual impairment Literate in English only and unable to communicate with subject or subject's LAR English Yes Yes The impartial witness may act as a translator if he/she is able to fulfill this role.
Illiterate or unable to read due to visual impairment Literate in English and a local language and able to communicate with subject or subject's LAR English or Local Language No Yes The choice of language of the written ICF depends on whether the impartial witness is literate in that language

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[H25] How many copies of the informed consent form should be signed?

There is no regulatory provision regarding the number of copies of informed consent forms that should be signed. The signed and dated informed consent form should also be provided to the subject or legal representative and also filed in the Investigator Site File [Ref: ICH E6 GCP 4.8.11 and 8.3.12].

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[H26] Should the subject or legal representative (if applicable) be re-consented if new information becomes available during the clinical trial?

If new information becomes available during the clinical trial which may affect the subject’s or legal representative’s (if applicable) to continue participation in the clinical trial, the subject or legal representative (if applicable) must be re-consented with the amended informed consent form at the earliest feasible opportunity. Please refer to Regulation 19(2) of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations, and ICH E6 GCP 4.8.2 for further details. The amended informed consent form must be approved by the relevant IRB and HSA prior to use.

It would be recommended that the sponsor provide details of the re-consent process in writing to the relevant IRB and HSA prior to implementation.

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[H27] Does the subject need to be re-consented if there is a change of Principal Investigator (PI) for the clinical trial?

If there is a change of PI for a clinical trial, the informed consent form should be amended and submitted to the IRB and HSA for review and approval. The subject should then be re-consented with the amended informed consent form accordingly.

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[H28] How should informed consent be documented in the subject’s medical records?

It would be recommended that the person obtaining informed consent from the subject or the legal representative (if applicable) document the following in the subject’s medical records:

  • Protocol Reference
  • Date of informed consent
  • Informed Consent Process (e.g. for use of legal representative / impartial witness / translator)
  • Signed copy provided to subject

For example:

  • Informed consent for a minor
    The informed consent version dated dd/mm/yyyy was explained to Mr ABC on DD/MM/YYYY for participation in Protocol DEF. Mr ABC is the subject’s deputy / parent / legal guardian. The risks and benefits of the clinical trial were explained and questions answered (if any). He understood the informed consent form and voluntarily agreed to allow his child / ward to participate in the clinical trial. A signed copy of the informed consent form was provided to him.

  • Informed consent for an adult lacking capacity
    The informed consent version dated dd/mm/yyyy was explained to Mr ABC on DD/MM/YYYY for participation in Protocol DEF. Mr ABC is the subject’s donee / deputy / spouse / adult child / parent / guardian / adult sibling / person nominated by Mr ABC before he lost capacity. The risks and benefits of the clinical trial were explained and questions answered (if any). He understood the informed consent form and voluntarily agreed to allow the subject to participate in the clinical trial. Dr GHK was the independent doctor who assessed the subject’s capacity. A signed copy of the informed consent form was provided to him.

  • Use of Impartial witness
    The informed consent version dated dd/mm/yyyy was explained to the subject on DD/MM/YYYY for participation in Protocol DEF. As the subject was unable to read the informed consent form, Mr ABC acted as the impartial witness during the informed consent process. Mr ABC is a family member / friend / clinic staff / lay person. The risks and benefits of the clinical trial were explained and questions answered (if any). Mr ABC confirmed that the subject was accurately explained, understood and voluntarily agreed to participate in the clinical trial.

  • Use of Translator
    The informed consent version dated dd/mm/yyyy was explained to the subject on DD/MM/YYYY for participation in Protocol DEF. As the subject preferred to use the translated informed consent form as reference, Mr ABC acted as the translator during the informed consent process. The risks and benefits of the clinical trial were explained and questions answered (if any). The subject understood the informed consent form and voluntarily agreed to participate in the clinical trial. A signed copy of the informed consent form was provided to him.

  • Routine
    The informed consent form version dated dd/mm/yyyy was explained to the subject on DD/MM/YYYY for participation in Protocol DEF. The risks and benefits of the clinical trial were explained and questions answered (if any). The subject understood the informed consent form and voluntarily agreed to participate in the clinical trial. A signed copy of the informed consent form was provided to the subject.

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[H29] Do Assent Forms for clinical trials in minors need to be submitted to HSA?

Assent Forms for clinical trials in minors do not need to be submitted to HSA. Please check with your Institutional Review Board about the requirements for Assent Forms.

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[H30] Can Short Form Consents be used for clinical trials regulated by HSA?

There is no regulatory provision for the use of Short Form Consents for clinical trials regulated by HSA. The subject or legal representative (if applicable) must sign the full informed consent form that has been approved by the IRB and HSA (except for administrative changes). Please refer to the relevant IRB for further information on the use of Short Form Consents.

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[I] INVESTIGATIONAL PRODUCTS (IP)

[I1] What are investigational products (IP) and auxiliary products (AP)?

An investigational product (IP) is defined as a Therapeutic Product/ Medicinal Product or a placebo that is to be tested or used as a reference in a clinical trial.

An auxiliary product (AP) is defined as a Therapeutic Product/ Medicinal Product used for the needs of a clinical trial as described in the protocol, but not as an investigational product.

The table below provides some examples of investigational products and auxiliary products.

Purpose of CRM (TP/MP) Type of CRM
Test Investigational Product
Reference (e.g., active comparator or placebo) Investigational Product
Background treatment or standard of care required by the protocol, which is administered for the study indication and relevant to the design of the study Auxiliary Product
Challenge agents Auxiliary Product
Rescue medications (unregistered) Auxiliary Product


Note: The following types of products will not be subject to regulatory requirements (e.g., labelling requirements) for an auxiliary product, since they are typically used in accordance with standard of care:
> Locally registered Therapeutic Product/ Medicinal Product used as pre-medications
> Locally registered rescue medications
> Locally registered treatment for trial-related adverse events
> Locally registered concomitant medication for co-morbidities

Please refer to the Guidance on Labelling of Therapeutic Products and Medicinal Products Used in Clinical Trials for further details.

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[I2] What are the labelling requirements for therapeutic products or medicinal products used in clinical trials regulated by HSA or clinical research not regulated by HSA?

Please refer to the Guidance on Labelling of Therapeutic Products and Medicinal Products Used in Clinical Trials for further details.

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[I3] How should the IP/AP be labelled prior to delivery to the local trial site?

The supply of the IP/AP to the local trial site would be regarded as wholesale supply. The IP/AP supplied to the local trial site must be labelled in accordance with Regulation 13 of the Health Products (Therapeutic Products as Clinical Research Materials) Regulations or Medicines (Medicinal Products as Clinical Research Materials) Regulations, as applicable. It would be the responsibility of the sponsor, importer and supplier (if applicable) to ensure that the IP/AP is labelled in accordance with the applicable regulations.

Please refer to the Guidance on Labelling of Therapeutic Products and Medicinal Products Used in Clinical Trials for further details.

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[I4] Do the labelling requirements apply to locally registered therapeutic products and medicinal products used in clinical trials?

Yes, the labelling requirements apply to locally registered therapeutic products and medicinal products used in clinical trials.

Please refer to the Guidance on Labelling of Therapeutic Products and Medicinal Products Used in Clinical Trials for further details.

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[I5] The IP labelling for registered investigational products depends on whether the registered product is used in accordance with all of the following conditions:
(i) is not used in a clinical trial in a blinded fashion
(ii) is not repackaged for use in the trial;
(iii) is used in accordance with the terms of its product registration/licence

How is ‘repackaging’ defined in this context?

Repackaging refers to removing the product from the container in which it is originally supplied by its manufacturer and
 (a) placing it in a different container; or
 (b) changing the outer packaging or other packaging in which the container is further enclosed.

The reference made to ‘repackaged for use in the trial’ for registered investigational products may apply to any of the following scenarios:

  • For blinded clinical trials where the registered investigational product would have to be placed in a different container, or have the outer packaging or other packaging changed in order for the test and reference to be identical; or
  • Transferring the registered investigational product from a bulk container to another container (e.g. box, Ziploc bag / bottle / cup etc.).

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[I6] If the investigational product (IP) or auxiliary product (AP) is to be administered to the subject at the trial site via a syringe, infusion bag or plastic cup (e.g. for oral formulations), would the syringe, infusion bag or plastic cup be required to be labelled in accordance with the applicable regulations?

If the IP/AP is required to be administered to the subject at the trial site through a syringe, infusion bag or plastic cup, the following labelling requirements will apply*:

  • Syringe or plastic cup for immediate administration to the subject at the trial site: The syringe or plastic cup should be labelled in accordance with clinical practice.
  • Infusion bag for immediate administration to the subject at the trial site: The infusion bag should be labelled in accordance with clinical practice and the words ‘For Clinical Trial Use Only’. For registered AP, the infusion bag should be labelled in accordance with clinical practice.
  • Syringe or infusion bag for delayed administration to the subject at the trial site: The syringe or infusion bag should be labelled in accordance with clinical practice and the words ‘For Clinical Trial Use Only’. For registered AP, the syringe or infusion bag should be labelled in accordance with clinical practice.

*NB: These recommendations do not apply to IP/AP that is brought home by the subject.

Additionally, there should be measures in place to ensure that the principles of labelling are complied with:
 (a)  to ensure protection of the subject and traceability;
 (b)  to enable identification of the product and the clinical trial;
 (c)  to facilitate proper use and storage of the product;
 (d)  to ensure the reliability and robustness of data generated in the clinical trial.

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[I7] Are IP documentation required to be maintained for clinical trials of locally registered therapeutic products or medicinal products?

Please refer to the Guidance on Alternative Measures for Investigational Product Management for Locally Registered Therapeutic Products or Medicinal Products.

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[I8] Is temperature monitoring required to monitor the storage of the IP?

Yes, temperature is required to provide assurance that the IP has been stored as per Sponsor requirements as per Sections 4.6.4 and 5.14.5 of ICH E6 GCP guidelines. The Sponsor should provide written instructions for handling and storage of IP as per Section 5.14.3 of ICH E6 GCP guidelines. The temperature monitoring devices should be calibrated and maintained as per Sections 8.2.12 and 8.3.7 of ICH E6 GCP guidelines. Further, it would be recommended that there should be traceability between various temperature monitoring devices, temperature logs and calibration and maintenance certificates.

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[I9] What are the required procedures if the site is involved in re-packaging of the IP?

Please refer to the Guidance for Investigational Product (IP) Repackaging on Site.

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[I10] Is the import of therapeutic product into Singapore for pre-clinical studies (e.g. cell lines for in vitro or in vivo studies) subjected to regulatory control in Singapore?

This will not require an import permit from HSA. However, if you are dealing with radiolabelled substances, you may wish to enquire with Centre for Radiation Protection and Nuclear Science, National Environment Agency, to ascertain if there are regulatory requirements to be met with regard to radiolabelled substances.

Gazetted poisons should be imported by a Form A Licence Holder. However, even if the product is not a gazetted poison, the principles of Good Distribution Practice should still apply.

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[I11] What are the regulatory controls for conducting clinical trials on controlled drugs or psychotropic substances?

Compliance with the Health Products (Clinical Trials) Regulations, the Medicines (Export Licence for Psychotropic Substances) and the Misuse of Drugs Regulations must be observed with conducting clinical trials on psychotropic substances or controlled drugs.

For the purpose of the clinical trial involving the use of controlled substance, additional approval administered by the HSA’s Licensing and Certification Branch is required. Following receipt of the authorisation (CTA) / acceptance of notification (CTN) / approval (CTC) for the clinical trial and acknowledgement of CRM notification by HSA,  copies of the CTA / CTN / CTC and the CRM-notification should be submitted to the HSA Licensing and Certification Branch, which will then process the application and issue the Import Licence and Wholesale Licence for the controlled drug.

The company making the application for Controlled Drug Wholesale Licence would subject to audit by HSA Licensing and Certification Branch. The Controlled Drug Wholesale Licence can only be issued to a company having a registered pharmacist who holds a valid Form A licence. The applicant for the import licence for Controlled Drugs should also be a licensed Form A Poison Licence holder to whom the import licence may be issued. The consignment of imported drugs can only be used for its designated purpose and must not be distributed or sold outside of this trial.

Once the trial has been completed, any leftover stock must be destroyed and the destruction procedure should be witnessed by a HSA inspector. If the clinical research material containing controlled drugs or psychotropic substances are to be exported out of Singapore, a corresponding export licence shall be applied and issued before the export is made.

General information on this process is available at this website:

Authorizations to import and export Restricted/Psychotropic Substances, Licence to import/export Controlled Drugs and Licence to sell Controlled Drugs by way of wholesale

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[I12] What are the regulatory considerations for destruction of investigational products in Singapore?

It is not necessary to obtain prior approval from (or notify) HSA for destruction of Investigational Products. As per Sections 4.6 and 5.14 of ICH E6 GCP guidelines, it is the Sponsor's and Principal Investigator's responsibilities to ensure proper documentation are maintained for receipt, storage, dispensing, accountability and return and / or destruction.

If the Investigational Products are to be destroyed locally, it is important to comply with the National Environment Agency (NEA) guidelines for disposal of drugs (particularly for cytotoxic or biohazardous items). General information on toxic wastes control, including pharmaceutical waste disposal management is outlined at NEA's website > Anti-Pollution & Radiation Protection > Chemical Safety > Toxic Industrial Waste > Toxic Waste > Control of Biohazardous Waste. Please contact NEA for further information.

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[I13] Are there any guidelines for Investigational Product management for investigator-initiated clinical trials (IITs)?

Please refer to Guidance on Alternative Measures for Investigational Product Management for Investigator-initiated Trials if you are conducting an investigator-initiated clinical trial on a locally registered medicinal product whereby the hospital pharmacy is utilized to manage the Investigational Product for further details.

Please also refer to Template Forms - Investigational Product (IP) Templates for IP management forms.

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[J] BIOLOGICAL SAMPLES

[J1] Is an export licence required for sending biological samples to overseas for testing?

An export licence is not required from HSA for shipping of biological samples to overseas for testing.

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[K] SAFETY REPORTING

[K1] What are the regulatory requirements for safety reporting in clinical trials?

Please refer to regulation 25 of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations. All unexpected serious adverse drug reactions (USADR)  must be reported to HSA by the sponsor as soon as possible, and not later than the stipulated timelines.

Please also refer to the Guidance on Expedited Safety Reporting Requirements for Therapeutic Products and Medicinal Products Used in Clinical Trials for further details

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[K2] What are the regulatory requirements for safety reporting of registered drugs used in clinical trials?

Registered therapeutic products and medicinal products may be used in clinical trials in one of the following ways:

  • As the investigational product being tested;
  • As the comparator product; or
  • As an auxiliary product

For registered therapeutic products and medicinal products in general, reports of unexpected serious adverse drug reactions (USADR) arising from protocols ongoing in Singapore should be reported to HSA. In addition, the following table summarises the types of report (local or overseas) that should be submitted to HSA:

  Local Reports arising from ongoing trial protocols Overseas Reports arising from ongoing trial protocols
Investigational TP or MP (Test)
Investigational TP or MP (Comparator/ Reference) X
Auxiliary TP or MP   X

Key:
√= USADR report to be submitted to HSA in an expedited manner within stipulated timelines);
X = USADR report is not subject to expedited reporting requirements

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[K3] What safety reporting requirements apply for an investigational product whose active ingredient is registered in Singapore, but for which the registered route of administration or formulation is different from that the registered product?

Generally, the safety reporting requirements for registered drugs will apply for such products, unless the risk profile of the investigational product is expected to be higher than that of its registered counterpart (e.g. registered oral dosage form vs. investigational IV formulation). In such an instance, the safety reporting requirements for unregistered drugs will apply.

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[K4] When should the sponsor start to submit reports of unexpected serious adverse drug reactions (USADR) to HSA?

Reporting of USADR should commence immediately upon clinical trial authorisation, acceptance of notification or issuance of a clinical trial certificate.

However, should any new safety concern surface from individual reports or aggregate analysis of USADR during the clinical trial application review period, the sponsor should ensure that the new safety information is promptly communicated to HSA by email so that the information can be considered in the benefit-risk assessment of the clinical trial.

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[K5] When may the sponsor cease submission of USADR reports to HSA?

Submission of USADR reports may stop when the Last Patient Last Visit is achieved in Singapore. However, HSA should continue to be informed of any new safety information that emerges after "Last Patient Last Visit" in Singapore, particularly if the information were of relevance or potential significance even to previously-treated patients.   

Safety reporting to HSA may stop when the Last Patient Last Visit is achieved in Singapore, unless indicated otherwise in the study protocol.

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[K6] In the event of trial termination, does HSA have any requirements on when to cease submission of safety reports?

Safety reporting to HSA may stop when the Last Patient Last Visit is achieved in Singapore, unless indicated otherwise in the study protocol.

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[K7] Does the sponsor need to submit safety reports from Named Patient Programme or for compassionate use of unregistered drugs?

If the compassionate use programme takes the form of a long-term clinical trial extension protocol for which a Clinical Trial Authorisation (CTA) or Clinical Trial Certificate (CTC) has been granted, reports of unexpected serious adverse drug reactions (USADR) should be submitted to the Clinical Trials Branch, in accordance with clinical trial regulations and guidance.

All local reports of serious adverse drug reactions (regardless of expectedness) arising from the use of unregistered drugs in other types of compassionate use programmes (i.e., those without a CTA or CTC) should be submitted to the Vigilance and Compliance Branch of HSA. Please refer to Guidance for Industry - Post-Marketing Vigilance Requirements for Therapeutic Products.

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[K8] Does the sponsor need to submit periodic line listings, DSURs, annual or periodic safety reports to HSA?

There is currently no requirement for submission of such documents. These documents may be submitted to HSA at the sponsor’s discretion. However, HSA may request for these reports to be submitted when deemed necessary.

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[K9] If the serious adverse event was causally-related to a study procedure in a clinical trial, is there a need to report this event?

In general, procedure-related serious adverse events need not be reported to HSA. However, the procedure also involves a drug or medical device, and it is plausible that the use of the drug or medical device as part of the procedure might have contributed to the adverse outcome, then the adverse event should be reported.

In addition, if the event has potential to affect the safety and welfare of other subjects, and preventive actions can be taken at local trial sites to prevent a similar occurrence, we would suggest that HSA be informed by email since such an event might warrant a protocol or informed consent form amendment.

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[K10] Are there any instances whereby serious and expected reactions are to be reported?

Expected reactions can be reported when the information may materially influence

(a) the benefit-risk assessment of a medicinal product, or
(b) the overall conduct of a clinical trial

An increase in the rate of occurrence of a serious and expected ADR, which is judged to be clinically important, would fit these criteria.

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[K11] When does the reporting timeline for reporting of an unexpected serious adverse drug reaction (USADR) start?

The reporting timeline starts upon first receipt by the sponsor, regardless of physical location.

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[K12] Can the sponsor do a batch submission of reports of unexpected serious adverse drug reactions (USADR)?

The regulations require sponsors to submit every USADR report to HSA as soon as possible (i.e., without undue delay). Therefore, batch reporting should be considered only if the sponsor is able to ensure that the legal obligation is not compromised.

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[K13] Who should assume responsibility when the sponsor company does not have a local party performing safety reporting submissions?

All clinical trials conducted in Singapore require a local sponsor. The local sponsor assumes responsibility for ensuring that safety reporting in clinical trials is in accordance with local regulatory requirements. Although the function of safety reporting submissions may be contractually delegated to a contract research organisation, the local sponsor assumes overall responsibility for ensuring that safety reporting submissions are performed in accordance with local regulatory requirements.

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[K14] How can one gain access to Expedited Safety Reports (ESR) module in PRISM?

The CRIS administrator of your company must assign either drafter or submitter rights for the ESR module to you. Please note that if drafter role was assigned, the CRIS administrator will need to map the necessary protocols to the drafter for access. Please refer to our guidelines for mapping of ESR function.

The PRISM ESR module can be accessed from Clinical Trials E-Services & Forms > amend@prism > Submission of Expedited Safety Report.

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[K15] In cases where safety reporting is done by the pharmacovigilance department of the sponsor company located overseas, can the reporting be done via ESR?

The overseas staff may gain access to ESR module by applying for a HSA PIN. Please note that only drafter rights can be assigned to a HSA PIN holder. Submission must still be performed by a SingPass holder. Information on how to apply for HSA PIN is available here.

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[K16] If the local sponsor outsources the safety reporting to a CRO, how may the CRO use the online ESR module?

The local sponsor may provide drafter rights for ESR module to the CRO, who would then be able to draft ESR applications. The drafter may then notify the local sponsor to proceed with the submission.

Please note that the implication of providing submitter rights to a CRO is that the CRO will be able to view and access all clinical trial applications filed under the sponsor company.

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[K17] What are the current regulatory requirements for safety reporting in clinical trials involving medical devices?

Please refer to the following:

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[L] CLINICAL RESEARCH MATERIALS (CRM)

[L1] What are Clinical Research Materials (CRM)?

CRM includes any of the following product types that are manufactured, imported or supplied for the purpose of being used in any clinical research accordance with a research protocol. The clinical research may either be a regulated clinical trial (i.e. clinical trial requiring a CTA / CTN / CTC) or a clinical research that is not regulated by HSA.

  • Registered or unregistered therapeutic products;
  • Licensed or unlicensed medicinal products;
  • Placebo; or
  • Medical devices

Please refer to the Guidance on Clinical Research Materials for further details.

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[L2] What are the regulatory requirements for Clinical Research Materials (CRM) in Singapore?

The regulatory requirements for CRMs are outlined in the following regulations:

Please refer to the Guidance on Clinical Research Materials for further details.

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[L3] What are the differences between the CRM regulations and the clinical trial (CT) regulations?

The CRM regulations and the CT regulations have different regulatory intent. The table below summarises the key differences:

  CRM regulations CT regulations

Regulatory intent

  • To facilitate access to CRM;
  • To regulate the import and  supply of CRM;
  • To ensure traceability and accountability of CRM;
  • To impose duties on dealers of CRM.
  • To regulate the conduct of clinical trials (i.e. clinical trials of therapeutic products or medicinal products).
Regulated parties
  • Manufacturers
  • Importers
  • Wholesalers
  • Suppliers
  • Sponsors
  • Sponsors
  • Investigators
  • Study team members

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[L4] When must CRM notification be submitted to HSA?

CRM notification should be submitted to HSA prior to import of CRM, or prior to supply of CRM by the local manufacturer.

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[L5] Is CRM notification required if the product is locally-registered and obtained from a pharmacy or sourced from an authorised local distributor?

CRM notification is not required if the locally-registered CRM is obtained from local commercial sources.

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[L6] Are dealers of CRM required to obtain dealers licences (e.g. manufacturer’s licence, importer’s licence, wholesaler’s licence)?

Dealers of CRM are not required to obtain dealers licences (e.g. manufacturer’s licence, importer’s licence, wholesaler’s licence), provided that CRM notification is made prior to import of CRM by the importer, or prior to supply of CRM by the local manufacturer.

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[L7] If a company is the authorised importer for a locally-registered therapeutic product as reflected in the full-scope importer’s licence, would CRM notification be required prior to import of the registered product by the authorised importer for use in local clinical research?

CRM notification will not be required as the authorised importer may legitimately import the locally-registered therapeutic product with the valid importer’s licence.

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[L8] If a company has a full scope importer’s licence but is not the authorised importer for a locally-registered therapeutic product, would CRM notification be required prior to import of the locally-registered therapeutic product for use in local clinical research?

CRM notification will be required as the company, even though in possession of a full scope importer’s licence is not the authorised importer for the locally-registered therapeutic product.

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[L9] Is CRM notification required before supply of IP that was compounded at the local trial site?

Compounding of IP at the local trial site is considered to be a manufacturing activity. Hence, CRM notification would be required prior to supply of the compounded IP.

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[L10] Is CRM notification required for the import of unused Investigational Products from overseas trial sites into Singapore for destruction?

CRM notification is not required for the import of unused Investigational Products from overseas trial sites for local disposal. However, the company will require a Therapeutic Products Importer’s Licence (TPIL) - Limited Scope for Restricted Activity for import TP for non-clinical use. In addition, the company must comply with duties and obligations outlined in the Health Products (Therapeutic Products) Regulations, such as record-keeping and ensuring that the product is not supplied to the public The National Environment Agency (NEA) should continue to be notified of the import and an acknowledgement obtained.

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[L11] Does the CRM notification need to be amended for a change in Principal Investigator (PI)?

The CRM Notification need not be amended for a change in PI, since details pertaining to change of PI will be automatically updated in PRISM following HSA approval of the application for change of PI.

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[L12] Is it possible to make amendments to the CRM notification?

Yes. Amendments (e.g., change in quantity of CRM to be imported) may be made to the CRM notification. For regulated clinical trials, the amendment  may be made as part of an amendment to a CT application

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[L13] If CRM notification was previously made to facilitate the import of a medical device (e.g., ECG machine) for a particular clinical trial, would it be possible to use the ECG machine for another clinical trial and not return it to the overseas manufacturer?

Generally, any imported CRM imported (with prior CRM notification) should be disposed of within 6 months after study completion. If there is intention to use the MD for another clinical trial, the sponsor should write to HSA to seek approval accordingly.

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[L14] Is there a difference in “import route” for importing CRM for local research vs. overseas research?

The table below summarises various “import routes” for importing therapeutic products and medical devices for local research use vs. overseas research use.

Purpose of Import Location of Clinical Trial Site Regulatory Import Route

Clinical Research

Local Clinical Research Site

TP/MD: CRM Notification

Overseas Clinical Research Site (Import for Re-export)

TP: Importer’s Licence (Restricted Activity)

MD: GN-28 Authorisation Route for Export of Unregistered Medical Devices

Laboratory Analysis of Human Biological Samples from Clinical Research Participants Local Clinical Research Site (i.e., biological samples are from local subjects) MD: CRM Notification
Overseas Clinical Research Site (i.e., biological samples are from overseas subjects)

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[L15] What are the records that must be maintained for CRM?

The table below summarises the record keeping requirements for CRMs that are therapeutic products or medicinal products:

  Type of Records
  Manufacture

(aligned to TP regs)
Receipt / Supply Disposal (or export or putting to other use)
Applies to Locally-manufactured CRM All CRM Imported or Locally-manufactured CRM
Party responsible Manufacturer Any person who supplies CRM, including local manufacturer, importer, wholesaler, sponsor, investigator Sponsor
Required elements in the record

(aligned to TP regs)

 

 
  • Proprietary name (brand name) or other description
  • Identification no. of the CRM (e.g., batch no., lot no.)
  • Details of receipt, supply, putting to other use, disposal or export:
  1. date of receipt, supply, putting to other use, disposal, export
  2. quantity of CRM received, supplied, put to other use, disposed, exported
  3. name/address of person the CRM was received from, supplied to, or of the person responsible for putting to other use, disposal or export of CRM
Duration of record-keeping
  • 1 year after CRM expiry date or
  • 5 years after date of manufacture, assembly, testing

(whichever is longer)

TP/MP in regulated clinical trial (aligned/refers to CT regs):

  • No more pending or planned application for TP/MP registration
  • 2 years after the last of such registrations has been granted
  • 2 years after informing HSA of termination of clinical trial

(whichever is latest)

TP/MP in other clinical research (records of receipt/supply aligned to TP regs):

  • 2 years after the supply, putting to other use, disposal or export


The table below summarises the record keeping requirements for CRMs which are medical devices:

  Type of Records
  Manufacture

(existing MD regs)

 

Receipt / Supply Disposal (or export or putting to other use)
Applies to Locally-manufactured CRM All CRM Imported or Locally Manufactured CRM
Party responsible Manufacturer Any person who supplies CRM, including local manufacturer, importer, wholesaler, sponsor, investigator Sponsor
Required elements in the record

(aligned to TP regs)
 
  • Proprietary name (brand name) or description of the CRM
  • Identification no. or mark of the CRM (e.g., batch no., serial no.)
  • Details of receipt, supply, putting to other use, disposal or export:
  1. date of receipt, supply, putting to other use, disposal, export
  2. quantity of CRM received, supplied, put to other use, disposed, exported
  3. name/address of person the CRM was received from, supplied to, or of the person responsible for putting to other use, disposal or export of CRM
Duration of record-keeping
  • Projected useful life of the MD or
  • 2 years after the MD is supplied

(whichever is longer)

Unregistered MD used in regulated TP/MP clinical trial (CT):

  • No more pending or planned application for TP/MP registration
  • 2 years after the last of such registrations has been granted
  • 2 years after informing HSA of termination of clinical trial
  • 6 years after the completion of the trial

(whichever is latest)

Registered MD used in regulated CT, or any MD in other CR:

  • Projected useful life of the MD (not applicable to records of disposal...), or
  • 2 years after the supply, putting to other use, disposal or export

(whichever is longer)

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[M] OTHERS

[M1] How does the Personal Data Protection Act 2012 (PDPA) apply to the collection and usage of subjects' data in clinical trials conducted in Singapore?

The collection and usage of subjects’ data in clinical trials must be protected in order to ensure subject privacy and data confidentiality. The regulatory provisions for confidentiality are outlined in Paragraph 11 of the First Schedule of the Health Products (Clinical Trials) Regulations and the Medicines (Clinical Trials) Regulations. Please also refer to ICH E6 GCP Sections 2.11, 4.8.10(n, o), 8.3.21 and 8.4.3.

In addition, the Sponsor should be aware of PDPA requirements and ensure that the Informed Consent Form (ICF) is consistent with those requirements. You may wish to consult the relevant IRB on the inclusion of the PDPA clause in the informed consent form.

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[M2] How may the site archive essential study documents electronically?

Source data is defined as “original or certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial” as per ICH E6 GCP 1.51. Essential documents may be archived by electronic means, microfilm or other suitable archiving technology.

It would be important to adhere to the following 3 principles of ICH E6 GCP guidelines when scanning essential documents:

  • Section 2.10 : All clinical trial information should be recorded, handled and stored in a way that allows its accurate reporting, interpretation and verification.
  • Section 2.11: The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with applicable regulatory requirements.
  • Section 2.13: Systems with procedures that assure quality of every aspect of the trial should be implemented.

The site may wish to refer to European Medicines Agency (EMA) Guidance on Trial Master Files (Feb 2013) for further guidance on electronic trial master files. In this reflection paper, EMA considers destroying original essential documents with wet signatures (e.g. contracts and ICDs) risky and careful considerations should be made as to which original essential documents can be destroyed.

It would thus be advisable for the sites to consult their hospital IT departments on how IT can be embraced for electronic archiving without compromising the ICH E6 GCP principles.
 

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