2. General Questions

2.1 Name of Regulatory Authority

National Pharmaceutical Regulatory Agency (NPRA), an agency under the Malaysian Ministry of Health (MOH). The Drug Control Authority specifically looks after the regulation of drugs (including biologics). The National Pharmaceutical Control Bureau (NPCB) is the group within NPRA that manages clinical trial applications.

https://npra.gov.my/index.php/en/

2.2 Name of Ethics Committee

Following on from a 2007 Directive, all ethics committees are required to register with the DCA. Both public and private ethics committees are available.

The committees to whom the application should be submitted will depend on the type of clinical trial site:

A. For government health facilities managed by the MOH

The Malaysian National Institute of Health (NIH) issued the Guidelines for Conducting Research in MOH Institutions and Facilities (“NIH Guidelines”) in October 2015. According to the NIH Guidelines, all clinical trials involving MOH facilities must register with the NMRR and obtain prior approval from the MOH, as follows:

• The government employee intending to act as an investigator for the clinical trial must sign an investigator agreement and obtain approval from the head of his or her department and the organizational or institutional director of the relevant government department.
• Obtain permission to conduct research at the respective facilities/institutions.
• Where a private institution undertakes collaborative research with the MOH, a formal letter of agreement between the related MOH institution or division and the private institution is required.

The NMRR will review the documents submitted. If satisfied with the registration application, the NMRR will forward it to the Medical Research and Ethics Committee (MREC) for their review and approval.

B. For universities or private institutions

Applications are to be submitted to the respective IRB/IEC of the university or institution, which will review and approve the trial proposal as per the functions of the MREC.

If the university or institution concerned does not have its own IRB/IEC, applications can be submitted to the MREC or such committees of other universities or private institutions.

For a list of all registered ethics committees, see this link.

2.3 Clinical Trial Application Language

The application form must be completed in English or Bahasa Melayu.

2.4 Is regulatory approval required from both regulatory authorities and/or EC?

Yes.

2.5 Can regulatory authority and EC submission be done in parallel?

Yes, submissions to the Ethics Committee and National Pharmaceutical Control Bureau (NPCB) can be made in parallel.

2.6 Requirement of any import permit/license before investigational product/study product is shipped from point of origin

For all unapproved products, a clinical trial import license must be obtained from the DCA. 

A Licence in Form 4 in the schedule of the Control of Drugs and Cosmetics Regulations of 1984, authorizing the licensee to import any product for purposes of clinical trials, notwithstanding that the product is not a registered product.

2.7 Biological Specimen Export Requirements

The Division of Disease Control - Ministry of Health deals with Biological Import/Export Permit applications through BLESS. 

Governing Acts and Regulations

1. Prevention and Control of Infectious Disease Act 1988.
2. Prevention and Control of Infectious Diseases (Importation and Exportation of Human Remains, Human tissues, and Pathogenic Organisms or Substances) Regulations 2006.

The applicant needs to complete the online application form and provision the following documents:

1. A copy of the NRIC or passport of the applicant
2. Certification or documentation from the importing or exporting country
3. Information or documentation on the method of disposal

There are fees to be paid for the private sector and the amount depends on the risk group category for the specimens that are being exported.

An import/export permit for the year will be issued upon approval. A copy of the permit needs to be provided together with the specimens at the time of import/export. 

The import/export permit needs to be renewed annually.

2.8 Are studies of GMOs permitted (e.g., GMOs used in vaccines/vaccine manufacture and other modified products)?

Yes. Cell and Gene Therapy products are regulated in Malaysia under the “Guidance Document and Guidelines for Registration of Cell and Gene Therapy Products (CGTPs) - December 2015.”

2.9 Is in-country sponsor presence/representation required?

No, there is no requirement for the sponsor to be located or based in Malaysia. However, as an application for the Import License or Exemption must be made by an entity that is registered with the Companies Commission of Malaysia, the sponsor may appoint a CRO incorporated in Malaysia to assume its duties and functions.

2.10 Is there any mandatory requirement to identify a local PI or can a PI be based in a foreign country?

No. According to the Malaysian Guideline for Good Clinical Practice (4th Edition), investigators need to be suitably qualified and meet the requirements of the Regulatory Body/Ethics Committee but there is no specific requirement around the residency of the PI.

2.11 Is there any mandatory requirement to identify a local chief or coordinating investigator?

Yes. If the trial is a multicentre trial, then a Coordinating Investigator should be assigned.

The Malaysian Guideline for GCP defines the Coordinating Investigator as ‘an investigator assigned the responsibility for the coordination of investigators at different centers participating in a multicentre trial’.

2.12 If the applicant is CRO or a third party, does regulatory authority need any authorization or transfer of obligations from the sponsor? Does the authorization letter need to be notarized and/or apostilled?

There are no specific requirements for the delegation of the role of the sponsor.

Change of Sponsor 

The applicant shall notify the DCA if there is any change of sponsor for the clinical trial. The following documents shall be included in the notification:

1. a cover letter that includes the date of transfer of responsibilities;
2. a letter on a headed company paper from the current sponsor confirming the transfer of the study; and
3. a letter on headed company paper from the new sponsor confirming that they accept the role of sponsor for this study.

Other company documents (e.g. protocol) should NOT be submitted as part of this submission.

2.13 Is there a requirement to register clinical trials on a local registry or database?

Yes. All clinical trials that require a CTIL (Clinical Trial Import Licence)/CTX (Clinical Trial Exemption) online application must be registered with the National Medical Research Register (NMRR). Reference is made to the Directive of DPS CT1-2009. Before submitting the CTIL/CTX application to NPRA, the applicant should obtain a unique full NMRR Registration Number from the NMRR website. An applicant who fails to register his/her clinical trial with NMRR shall result in non-acceptance of the CTIL/CTX application.

https://npra.gov.my/easyarticles/images/users/1140/Malaysian-Guideline-for-Application-of-CTIL-and-CTX-8th-Ed-Final.pdf

The applicant is required to quote the NMRR Registration Number in all communication with NPRA. 

https://nmrr.gov.my/

2.14 What is the local requirement for clinical study documents archival; minimum of years for the archival, specific format followed (electronic/paper and/or both)?

Retention of essential documents

The Application Guidelines require the sponsor and the investigator to archive all trial-related documents safely and to inform the DCA prior to the destruction of any such documents.

Section 8 of the GCP Guidelines outlines the details of all records that must be maintained in relation to a trial.

https://www.crc.gov.my/wp-content/uploads/2018/03/Malaysian_gcp_4th_Edition28Final_29.pdf

Section 5.5.11 of the GCP Guidelines states that essential documents should be retained by the sponsor for either of the following:

1. At least 2 years after the last approval of a marketing application in an ICH region (member country of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) and until there are no pending or intended marketing applications in an ICH region.
2. At least 2 years from the formal discontinuation of clinical development of the study drug.

The sponsor should inform the investigator of the need for the retention of records and inform the investigator in writing when such records are no longer required.

2.15 Requirements around periodic safety reporting and timelines on SAEs/AEs/ADRs/SUSARs/DSURs.

SAEs do not need to be reported to the NPRA but should be reported to the ethics committee within 7 days.

The event must fulfill all the following criteria before reporting to NPRA:

1. The event is an adverse drug reaction (ADR). Please read FAQ #3.
2. The suspected drug is the investigational product, which requires CTIL/CTX, not the comparator or placebo.
3. The ADR is serious. Please read FAQ #4.
4. The ADR is unexpected. Please read FAQ #5.
5. The source of the report can be either local or overseas. In the case of overseas reports, they must come from the same clinical trial protocol as in Malaysia.
6. The report must contain the minimum information for expedited reporting. Please read FAQ #9.

Reporting of SUSARs to NPRA is mandatory. The timelines for reporting are as follows:

• Fatal or Life-threatening Unexpected ADRs: The NPCB should be notified as soon as possible but no later than 7 calendar days after first knowledge by the sponsor of a qualifying case, followed by a report as complete as possible within 8 additional calendar days.
• All Other Serious, Unexpected ADRs: The NPCB should be notified as soon as possible but no later than 15 calendar days after first knowledge by the sponsor that a case meets the minimum criteria for expedited reporting.

2.16 Requirement on any periodic clinical study update, specific template, and its frequency (e.g., interim or annual progress report and final report, etc.)?

In cases of trials lasting for more than 6 months, an interim report shall be submitted annually no later than one year after the initial approval date until the completion/termination of the clinical trial. It is acceptable for a report to be submitted within the month that it is due. An interim report should be submitted for each trial site. Please refer to Appendix H of the Malaysian Guideline for Application of Clinical Trial Import Licence and Clinical Trial Exemption.

https://npra.gov.my/easyarticles/images/users/1140/Malaysian-Guideline-for-Application-of-CTIL-and-CTX-8th-Ed-Final.pdf

2.17 Does the local regulation require notification of “serious breaches” of GCP or the trial protocol? 

Yes. Noncompliance with the protocol, SOPs, GCP, and/or applicable regulatory requirement(s) by an investigator/institution, or by a member(s) of the sponsor’s staff should lead to prompt action by the sponsor to secure compliance.

If the monitoring and/or auditing identify serious and/or persistent noncompliance on the part of an investigator/institution, the sponsor should terminate the investigator’s/institution’s participation in the trial. When an investigator’s/institution’s participation is terminated because of noncompliance, the sponsor should notify promptly the regulatory authority(ies).

The DCA will enforce the rules and punitive action will be decided by the DCA.

2.18 Does RA/CA require insurance and indemnity to cover the sponsor and investigator’s potential liability?

Yes. Sponsors must have insurance in place prior to the commencement of a study to indemnify investigators and subjects against any loss or injury.