Managing Clinical Trials during COVID-19 Pandemic in Malaysia
General Questions
1. Do we need to notify NPRA if we were to delay 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 COVID19 pandemic.
Due to anticipated increase in workload to the industry during this COVID19 emergency, general notification for all studies via e-mail are acceptable.
2. Is there a general email address where notification/submissions can be directed to, or these can be directed to any officers?
Investigational Product Direct to Patients
3. Do we need to obtain 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 CTIL approvals from NPRA are under the presumption that the 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
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Below are the additional comments from GCP and GLP Section’s for further consideration:
NPRA recognise that the supply of IMP 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 .
Considering these highly unusual circumstances, the sponsors or researcher may distribute investigational products directly to the trial subjects without involving the investigator or site personnel. Such decisions will depend on specific circumstances, including the nature of the investigational product, the ability to conduct appropriate safety monitoring and the nature of the disease under study in the trial.
Sponsor shall consider the following when implementing the home delivery option:
• Sponsor has a valid CTIL/CTX with an approved import quantity.
• Sponsor shall only distribute the investigational product on Malaysian sites to trial subjects.
• The direct-to-patient delivery of investigational product 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 investigational product to trial subject or their relative. In other words, the sponsor need to deliver the investigational product 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 investigational product in a suitable way.
• Dispatch of the investigational product 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
Page
Below are the additional comments from GCP and GLP Section’s for further consideration:
NPRA recognise that the supply of IMP 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 .
Considering these highly unusual circumstances, the sponsors or researcher may distribute investigational products directly to the trial subjects without involving the investigator or site personnel. Such decisions will depend on specific circumstances, including the nature of the investigational product, the ability to conduct appropriate safety monitoring and the nature of the disease under study in the trial.
Sponsor shall consider the following when implementing the home delivery option:
• Sponsor has a valid CTIL/CTX with an approved import quantity.
• Sponsor shall only distribute the investigational product on Malaysian sites to trial subjects.
• The direct-to-patient delivery of investigational product 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 investigational product to trial subject or their relative. In other words, the sponsor need to deliver the investigational product 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 investigational product in a suitable way.
• Dispatch of the investigational product 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 IP is to be shipped from depot (sponsor) or investigator site directly to the patient?
5. How will 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 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). If we need to wait for NMRR ID prior to submission to NPRA, there may be long delay as we need to have a complete EC package submitted first (i.e. translations, IAHODIA forms etc). Are there any options to expedite this administrative step?
Expedited pathway is available for COVID19 related trial’s product. Expedited pathway shortens our evaluation timeline, however, other regulatory requirement remains.
7. During the MCO period, how is submission for COVID trials performed? Do we need to submit hardcopy dossier and face-to-face with NPRA officer?
Submissions to NPRA
8. If the MCO is extended and a variation application is needed (for example, CTIL renewal/additional quantity) would it be acceptable to submit it via email? Are below approached acceptable by NPRA?
Yes. All variation application can be submitted via e-mail.
a) Official Company chop won’t be available in such case, but company name will be reflected on the digital signature. Is this acceptable?
Yes.
b) The forms will be electronically signed, and the stamp will be typed. Is this acceptable?
Yes.
c) Would NPRA accepts e-signature for submission without the company stamp?
Yes.
Note: For variation applications that involve payment i.e., CTIL renewal, Additional IP. The following procedures apply:
- Send the variation application via email to zaril@npra.gov.my.
- The evaluator will verify the amount to pay via email. The applicant will receive the verification of amount via email.
- The applicant is required to submit the following document via courier:
- Bank draft/money order/wang pos
- Borang BPFK-001.3 – Borang penyerahan yuran pemprosesan lesen import percubaan klinikal.
- Payment amount verification email (from no. 2)
- Cover letter
Please submit the documents to:
Unit Hasil
National Pharmaceutical Regulatory Agency
Lot 36, Jalan Universiti
46200 Petaling Jaya
Selangor
Alternatively, the payment can be made using credit card/bank draft/money order/wang pos physically at the Unit Hasil’s counter every Wednesdays 8.00 am to 10.00 am
- The applicant is required to submit the official receipt via email to the evaluator (refer no. 2).
9. Can notifications of protocol amendments and updated IB to be submitted by email during MCO period?
10. During MCO, 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 MCO, do we need to submit all submissions made via email to NPRA again in paper format?
Approval Timeline
12. For CTIL submission that was accepted prior to MCO, how would NPRA manage the review and approval in terms of timeline?
The approval timeline is not affected.
13. Some local ECs are impacted by the COVID-19 outbreak and will meetings have postponed to a later date, potentially up to June 2020. NPRA approval was already granted, However, by the time we receive EC approval letter should be around June/early Jul 2020. Will NPRA hold the approval letter and CTILs for us until that time?
14. Per CTIL guideline, end of study report is needed to be submitted within 3 months from the site closure. If the 3 months falls within the MCO period, can the submission be delayed till MCO is lifted or there is an alternative channel for submission?
