Managing Clinical Trials during COVID-19 Pandemic in Malaysia
(Updated 22 Mac 2023)
General Questions
1. Do we need to notify NPRA if we were to delay Site Initiation Visit (SIV) and/or Pause Recruitment for our studies? Notification for each individual study or can we just provide a general notification?
Notification to NPRA is required for delayed SIV and/or pause recruitment especially during COVID-19 pandemic.
Due to anticipated increase in workload to the industry during this COVID-19 emergency, general notification for all studies via e-mail are acceptable. However, these notifications need to be followed by hardcopy submission to NPRA.
2. Is there a general email address where notification/submissions can be directed to, or these can be directed to any officers?
Investigational Product (IP) Direct to Patients (DTP)
3. Do we need to obtain Clinical Trial Import License (CTIL) or any special approval from NPRA when importing study drug from Singapore for the Malaysian patient who is participating in a trial in Singapore?
Every Clinical Trial Import License (CTIL) approvals from NPRA are under the presumption that the Investigational Product (IP) will be administered or dispensed to Malaysian patients at a clinical trial site in Malaysia since the respective clinical trial was approved by the Malaysian ethics committee. Therefore to maintain the trial’s integrity, IP sharing between countries is not recommended.
However, there is another option in which you can apply for exemption under Regulation 15(6) Control of Drugs and Cosmetics Regulation 1984, an exemption to import unregistered products for life-threatening diseases under Pharmacy Enforcement Division.
You can also contact the following officers in the Pharmacy Enforcement Division for further information:
1. Pn Astrina Bt Abdul Salam (astrina@moh.gov.my) – Legislation Branch
2. Pn Nursyila Roziana Binti Mohd Radzi (nursyila@moh.gov.my) – Licensing Branch
Below are additional comments from Good Clinical Practice (GCP) and Good Laboratory Practice (GLP) Section for further consideration:
NPRA recognise that the supply of IP to trial subjects may be disrupted during COVID-19 crisis due to quarantine, travel limitation, cancellation on the site visits or other considerations if site personnel or trial subjects become infected with COVID-19.
• Sponsor has a valid Clinical Trial Import License (CTIL) / Clinical Trial Exemption (CTX) with an approved import quantity.
• Sponsor shall only distribute the IP on Malaysian sites to trial subjects.
• The direct-to-patient (DTP) delivery of IP shall not raise any new safety risks.
• Sponsor shall ensure the conduct of appropriate alternative safety monitoring specifically if trial participants are not be able to come to the investigational site.
• Prior to direct distribution to the subject, sponsor should investigate the viability of the distribution via investigator or hospital pharmacy.
• If courier service is used. The sponsor need to ensure that the shortest route of transportation used during transportation and storage requirements are met. These have to be documented.
• Sponsor has to ensure that the standard operation procedure (SOP) is in place for delivery of IP to trial subject or their relative. In other words, the sponsor need to deliver the IP to the subject personally and not deliver to neighbor or placed outside the door. In addition, sponsor need to ensure the subject received adequate training for self-administration of the investigational product. All of these have to be documented.
• Sponsor is required to ensure that the subject will store the IP in a suitable way.
• Dispatch of the IP to the subject has to be done after agreement with the investigator and on the basis of the investigator prescription. Procedure for accountability must be in place.
• Sponsor may not store the personal data of the trial subject for a longer period than is required for the purpose of dispatching the medicine to the subject. Sponsor may only authorise a limited number of employees to process the personal data in order to dispatch the medicine. This has to be documented.
• Sponsor must ensure that trial subjects understand and provide consent that the trial medicine will be delivered directly to their homes.
However, there is another option in which you can apply for exemption under Regulation 15(6) Control of Drugs and Cosmetics Regulation 1984, an exemption to import unregistered products for life-threatening diseases under Pharmacy Enforcement Division.
You can also contact the following officers in the Pharmacy Enforcement Division for further information:
1. Pn Astrina Bt Abdul Salam (astrina@moh.gov.my) – Legislation Branch
2. Pn Nursyila Roziana Binti Mohd Radzi (nursyila@moh.gov.my) – Licensing Branch
Below are additional comments from Good Clinical Practice (GCP) and Good Laboratory Practice (GLP) Section for further consideration:
NPRA recognise that the supply of IP to trial subjects may be disrupted during COVID-19 crisis due to quarantine, travel limitation, cancellation on the site visits or other considerations if site personnel or trial subjects become infected with COVID-19.
• Sponsor has a valid Clinical Trial Import License (CTIL) / Clinical Trial Exemption (CTX) with an approved import quantity.
• Sponsor shall only distribute the IP on Malaysian sites to trial subjects.
• The direct-to-patient (DTP) delivery of IP shall not raise any new safety risks.
• Sponsor shall ensure the conduct of appropriate alternative safety monitoring specifically if trial participants are not be able to come to the investigational site.
• Prior to direct distribution to the subject, sponsor should investigate the viability of the distribution via investigator or hospital pharmacy.
• If courier service is used. The sponsor need to ensure that the shortest route of transportation used during transportation and storage requirements are met. These have to be documented.
• Sponsor has to ensure that the standard operation procedure (SOP) is in place for delivery of IP to trial subject or their relative. In other words, the sponsor need to deliver the IP to the subject personally and not deliver to neighbor or placed outside the door. In addition, sponsor need to ensure the subject received adequate training for self-administration of the investigational product. All of these have to be documented.
• Sponsor is required to ensure that the subject will store the IP in a suitable way.
• Dispatch of the IP to the subject has to be done after agreement with the investigator and on the basis of the investigator prescription. Procedure for accountability must be in place.
• Sponsor may not store the personal data of the trial subject for a longer period than is required for the purpose of dispatching the medicine to the subject. Sponsor may only authorise a limited number of employees to process the personal data in order to dispatch the medicine. This has to be documented.
• Sponsor must ensure that trial subjects understand and provide consent that the trial medicine will be delivered directly to their homes.
4. Is it required to notify NPRA at each instance when Investigational Product (IP) is to be shipped from depot (sponsor) or investigator site directly to the patient?
5. How will Investigational Product (IP) accountability be tracked (or linked back to the Site-Specific Approval of IP quantity) as the proforma invoice will no longer state the site name, instead it will be the address of the patient. In this case, sponsor/CROs are not allowed to keep a copy on the proforma invoice for submission to NPRA at the end of the study (patient confidentiality will be compromised), so should accountability per NPRA’s requirement be performed?
COVID-19 Trials
6. For COVID-19 trials, it is imperative that we move as fast as possible to complete submissions to NPRA for their review, so that study start-up can be as quick as possible (due to the nature of this pandemic).
Effective from 1st April 2023, to streamline with the amendment on the requirements for Conditional Registration of Pharmaceutical Products During Disaster dated 20th June 2022 (Section 5b: Eligibility Conditions), for Investigational Products (IP) in COVID-19 Trials with the following characteristics can be considered for Fast Track Reviews:
Therapeutic product with new active ingredient(s) and a different mechanism of action or a new vaccine with a different platform that has not been registered in Malaysia (either via full registration or via conditional registration). In addition, the said product should have as good as or compelling efficacy and/or safety profiles compared to current existing registered products.
7. During the Movement Control Order (MCO) period, how is submission for COVID-19 trials performed? Do we need to submit hardcopy dossier and face-to-face with NPRA officer?
Submissions to NPRA
8. If the Movement Control Order (MCO) is extended and a variation application is needed (for example, Clinical Trial Import License (CTIL) Renewal/ Additional Quantity) would it be acceptable to submit it via email? Are the below following approaches acceptable by NPRA?
Since MCO has been fully lifted, all variation application need to be submitted via hardcopy submission.
a) Official Company chop won’t be available in such case, but company name will be reflected on the digital signature. Is this acceptable?
No. Official Company Chop/ Stamp is now required since MCO has been fully lifted.
b) The forms will be electronically signed, and the stamp will be typed. Is this acceptable?
No. The digital signature/ e-signature is acceptable however the Official Company Chop/ Stamp is required.
c) Would NPRA accepts e-signature for submission without the company stamp?
No. Both digital signature/ e-signature and the Official Company Chop/ Stamp are required.
9. Can notifications of Protocol Amendments and updated Investigator's Brochure (IB) be submitted by email during Movement Control Order (MCO) period?
10. During Movement Control Order (MCO) period, what are the submissions allowed to be performed via email and what are the submission would require a face to face meeting with NPRA officer?
11. Post Movement Control Order (MCO), do we need to submit all submissions made via email to NPRA again in paper format?
Approval Timeline
12. For Clinical Trial Import License (CTIL) submission that was accepted prior to Movement Control Order (MCO), how would NPRA manage the review and approval in terms of timeline?
The approval timeline is not affected.
13. Per Malaysian Guideline for Clinical Trial Import License (CTIL) / Clinical Trial Exemption (CTX) Edition 7.1, End of Study report is needed to be submitted within 3 months from the site closure. If the 3 months falls within the Movement Control Order (MCO) period, can the submission be delayed till MCO is lifted or there is an alternative channel for submission?
