5. Investigator and Investigational Product

5.1 Does local regulation require PI/CI to be approved/registered by any health authority (e.g., RA/EC)?  

Yes. For any Interventional Clinical Research that involves drugs, the principal investigator has to register with the National Medical Research Register (NMRR).

5.2 Does local regulation require any specific documents if PI/CI is based outside the country?

No specific regulations have been found on this matter.

5.3 Does local authority allow electronic ICF administration, including electronic signatures?

Yes. Electronic signature of the ICF is permitted.

5.4 Does local regulation require ICF to be administered as audio/visual and do these need to be recorded?

No. There is no specific requirement other than in the event that a subject is not able to sign.

If a subject is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. After the written informed consent form and any other written information to be provided to subjects, is read and explained to the subject or the subject’s legally acceptable representative, and after the subject or the subject’s legally acceptable representative has orally consented to the subject’s participation in the trial and, if capable of doing so, has signed and/or thumb printed and dated the informed consent form, the witness should sign and personally date the consent form. 

By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and appropriately understood by, the subject or the subject’s legally acceptable representative and that informed consent was freely given by the subject or the subject’s legally acceptable representative.

5.5 Is there any specific information/requirement on data capture/management (e.g., privacy regulations, etc.)?

All clinical trials must comply with the Malaysian Personal Data Protection Act 2010 which came into effect on 15 November 2013.

5.6 If a clinical study involves the study product as OTC and this is provided via pharmacy/amazon, etc., are there any specific regulations for IP management that need to be followed?

There is no specific guidance on this matter.

5.7 For a marketed study product/OTC, can a participant be compensated after confirmation of the purchased study product, or upfront prior to product acquisition? Does compensation in any way impact how the study is viewed (i.e., RWE vs. Interventional Study)? 

There is no specific guidance on this matter.

5.8 Is it permitted to pay participant stipends (i.e., is it permitted to pay the patients for their participation in the clinical trial)? If so, what is the average range? 

Yes. Stipends may be paid for reasonable expenses, subject to EC approval. "Reasonable" usually refers to all research-related costs and any special testing.

The policy on paying trial subjects, and the amount, must be stated in the subject information leaflet and be approved by the IRB/IEC.

5.9 Specific labeling requirements for clinical study product

The Malaysia GCP Guidelines state that:

"5.13.1 The sponsor should ensure that the investigational product(s) (including active comparator(s) and placebo, (if applicable) is characterized as appropriate to the stage of development of the product(s), is manufactured in accordance with any applicable GCP, and is coded and labeled in a manner that protects the blinding, if applicable. In addition, the labeling should comply with applicable regulatory requirements.

5.13.2 The sponsor should determine, for the investigational product(s), acceptable storage temperature, storage conditions (e.g. protection from light), storage times, reconstitution fluids and procedures, and devices for product infusion, if any. The sponsor should inform all involved parties (e.g. monitors, investigators, pharmacists, storage managers) of these determinations.

5.13.3 The investigational product(s) should be packaged to prevent contamination and unacceptable deterioration during transport and storage.

5.13.4 In blinded trials, the coding system for the investigational product(s) should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency but does not permit undetectable breaks of the blinding.

5.13.5 If significant formulation changes are made in the investigational or comparator product(s) during the course of clinical development, the results of any additional studies of the formulated product(s) (e.g.stability, dissolution rate, bioavailability) needed to assess whether these changes would significantly alter the pharmacokinetic profile of the product should be available prior to the use of the new Malaysian Guideline for Good Clinical Practice, 4th Ed Page 44 formulation in clinical trials."

5.10 What documents need to be submitted (including relevant fee if any), and to whom, if a permit is needed for an investigational/study product being shipped from outside the country? Are there any specific requirements for biologics? 

The Malaysian Guideline for Application of Clinical Trial Import License and Clinical Trial Exemption provides detailed guidance: 

Note: All references made in section 5.10 will be to the document: The Malaysian Guideline for Application of Clinical Trial Import License and Clinical Trial exemption - unless stated otherwise. 

Prior to the importation/manufacturing product locally, the Principal Investigator or sponsor is required to apply for CTIL/CTX from the Drug Control Authority (DCA). 

The following products will require a CTIL/CTX:

1. Products including placebo which are not registered with the DCA and are intended to be imported for clinical trial purposes.
2. A product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form and when used for unapproved indication / when used to gain further information about an approved use for clinical trial purposes.
3. An unregistered product including a placebo manufactured locally for the purpose of the clinical trial.

Documents required in a new application for CTIL/CTX:

1. Table of Content (Appendix A provides a format for the table of content required for a new application.)
2. Cover Letter
3. A complete application form with NMRR Registration ID signed by the applicant
4. Application form for
   1. Clinical Trial Import Licence (Current Borang BPFK 442) or
   2. Clinical Trial Exemption (Current Borang BPFK 443)
5. Two copies of Application Submission Form, ‘Borang Penyerahan Permohonan’ (current Borang BPFK 001)
6. Two copies of Submission Checklist, ‘Senerai Semak untuk Penyerahan Permohonan Lesen Mengimport/Permit Bagi Percubaan Klinikal’ (current Borang BPFK 002)
7. Receipt for Processing Fee
8. A copy of the Company Registration Certificate
9. A copy of License A of the applicant (in the case where a product contains a poison/drug)
10. Good Clinical Practices Certificate for Principal Investigator
11. Letter of Authorization / Agreement (the structure for the letter can be found in Appendix B)- it should be submitted to DCA in cases where:
    1. sponsor or a PI decides to use a service of CRO for the conduct of a clinical trial; or
    2. the applicant is not the sponsor or product owner. 
12. Approval Letter by Ethics Committee of the Institution(s) where the clinical trial is to be conducted.
13. A current copy of the certificate of Good Manufacturing Practices (GMP) or a statement on GMP from the manufacturer and repacker.
    1. A certificate of GMP must be issued by an authority recognized by the DCA (i.e. the authorities listed in the WHO ‘Certificate Scheme on The Quality of Pharmaceutical Product Moving In International Commerce’).
    2. A statement on GMP can be issued by the Quality Assurance department where the product is manufactured.
    3. For local products, a manufacturing license is required.
       1. For comparator product, the following is required:
          1. Certificate of GMP. If a GMP certificate is not available, one of the following documents can be submitted:
             1. Approval letter from the regulatory authority
             2. Annual Registration of Drug Establishment
             3. Package Insert
       2. For repacked product: 
          1. Certificate of GMP
          2. If the certificate of GMP is not available, a statement of GMP must be submitted by the repacker.
14. Clinical Trial Protocol and Protocol Amendments - The clinical trial protocol shall be in the format provided by Section 6, Malaysian Guideline for GCP, and include the definition of the end of the trial.
15. Declaration by Investigator/PI - Structure for Format of Declaration by Investigator/Principal Investigation can be found in Appendix C. 
16. Informed Consent form (initial version only)
17. Pharmaceutical Data (Appendices D1 – D6 outline the pharmaceutical data format for different types of IP)
    1. Certificate of Analysis (CoA) of the recent, representative batch for the product.
    2. A sample of the label(s) for the imported products.
    3. Applicant must ensure labels of the products for clinical trial meet the Labeling Requirements, which can be found in Appendix E.
    4. For Biosimilars products, these should comply with our Guidance Document and Guidelines for Registration of Biosimilars in Malaysia for Biosimilar Products 2008 which can be downloaded from our website.
    5. For Biological/Biotechnology products, these should comply with our Guidelines for Application for Registration of Biological/Biotechnology products which can be downloaded from our website.
18. Investigator's Brochure
    1. For content and format of the IB, reference is made to section 7, in the current version of the Malaysian Guideline for GCP.
    2. Product particulars, data, and supporting documentation sufficient to establish the safety, efficacy, and quality of the Investigator Brochure (IB).
    3. For Biosimilars products, these should comply with our Guidance Document and Guidelines for Registration of Biosimilars in Malaysia for Biosimilar Products 2008 which can be downloaded from our website.
    4. For Biological/Biotechnology products, these should comply with our Guidelines for Application for Registration of Biological/Biotechnology products which can be downloaded from our website.
19. Overall risk and benefit assessment
20. A copy of scientific advice from other regulatory agencies, if available 
21. Evidence of Phase 1 Unit Accreditation by NPRA 
22. Proof of Insurance Cover
23. Declaration by the sponsor for CTIL/ CTX Application Involving FIH Clinical Trial (a format for Declaration by Sponsor can be found in Appendix F).

5.11 What is the turn-around time to get an import permit?

Under normal circumstances, all CTIL/CTX applications will be assessed within the following timeline:

• 45 working days for phase I trial, including FIH clinical trials, clinical trials involving biological/ biotechnological, cell therapy products, and gene therapy products as well as herbal/natural products with therapeutic claims.
• 30 working days for all products except those products mentioned above.

For CTX applications, Day 0 is the day of receipt of a complete CTX application dossier. For CTIL applications, Day 0 is the day a complete CTIL application dossier AND the official receipt of payment is received. 

During the evaluation phase, the evaluator may have a query raised related to the application. The clock will stop on the day the query is e-mailed to the applicant. The applicant is expected to respond to the query within 30 working days. CTIL/CTX application will be rejected if NPRA does not receive adequate response/ reply for the queries or information requested by the evaluator.

The timeline for FIH clinical trials of 45 working days only accounts for CTIL/CTX evaluation by NPRA; it does not include the review time taken by the external Panel of Experts.

Fast-track reviews can be considered for the application of new IP used for treatment/ prevention in pandemic/ epidemic situations in the interest of public health except for FIH clinical trials.

Fast-track CTIL/CTX application will be assessed within the following timeline:

• 22 working days for phase I trial, the clinical trial involves biological/biotechnological, cell therapy products, and gene therapy products as well as herbal/natural products with therapeutic claims.
• 14 working days for all products except those products mentioned above.

5.12 Does local authority allow the destruction of clinical supplies at an off-site location (e.g. third-party vendor in or outside the country) after study completion? Are certificates of destruction required? 

According to the Malaysia GCP Guidelines:

Disposal / Return of Unused Investigational Product

• Confirmation of the local drug disposal or return of unused drug supplies to the country of origin or regional depot.
• For local disposal, all investigational products should be disposed of by authorized bodies/authorities and documented. A destruction certificate should be provided as evidence of destruction.