Pharmacovigilance – Product Registration Holders
Important notice:
This FAQ should be read together with the Malaysian Guidelines on Good Pharmacovigilance Practices (GVP) for Product Registration Holders, First Edition, August 2021, the current Drug Registration Guidance Document (DRGD), and other applicable NPRA requirements. Where there is any inconsistency, the applicable legislation, directives, registration conditions and current NPRA guidance prevail.
The 2021 GVP Guideline is under revision. This FAQ will be reviewed again when the next edition is issued.
1. Must the Responsible Person for Pharmacovigilance (RPPV) be based in Malaysia?
Answer: The RPPV should preferably be based in Malaysia. If the RPPV is based outside Malaysia (e.g. Singapore), the PRH must appoint a local contact person based in Malaysia. The local contact person must be contactable by the Authority at all times, be able to contact the RPPV, and have sufficient pharmacovigilance experience or training to understand the role. If the RPPV or local contact person is not a healthcare professional, access to a medically qualified person should be available. The details of the RPPV and local contact person must be provided to the Authority.
Guideline reference: P2.1.2 and P6.1.3.
2. Must a PRH obtain the reporter’s consent before processing and submitting an ADR/AEFI report?
Answer: PRHs must process safety information in accordance with applicable Malaysian data-protection and confidentiality requirements. The Authority maintains strict confidentiality regarding the identities of patients and reporters. ADR/AEFI reports submitted to NPRA must contain an identifiable patient and an identifiable reporter, but the information should be limited to what is relevant for pharmacovigilance and handled securely.
Guideline reference: P1.3, P1.7.2 and P3.2.1.
3. For a PRH that has already submitted a Pharmacovigilance System Summary (PVSS) while developing its Pharmacovigilance System Master File (PSMF), what is the Authority’s expectation on PVSS resubmission? Is the PVSS no longer applicable once the PSMF is in place?
Answer: At present, NPRA requests the Pharmacovigilance System Summary (PVSS) only from PRHs participating in the voluntary phase of the Good Pharmacovigilance Practice (GVP) Inspection Programme and from PRHs submitting applications for the Conditional Registration of Pharmaceutical Products during a Disaster. The PVSS is not currently required from all PRHs.
For the PRHs mentioned above, the PVSS is generally required as a one-time submission and does not need to be resubmitted once the PSMF has been established, unless otherwise requested by NPRA.
The PVSS serves as a summary of the PRH's pharmacovigilance system at the time of submission, whereas the PSMF is a living document that must be maintained and kept up to date to accurately reflect the current pharmacovigilance system.
Until further announcement, the preparation and submission requirements for PVSS and PSMF do not apply to traditional medicines and health supplements, although their pharmacovigilance activities must continue to be maintained and monitored.
Guideline reference: P6.1.2(a)–(e).
4. What are the ADR reporting requirements to the Authority when the Country of Adverse Event (AE) occurrence is Malaysia but the medicinal products is not from Malaysia. (e.g. the patient bought the product overseas)?
Answer: This ADR is not mandatory to be reported as the medicinal product is not registered in Malaysia. However, the NPRA would encourage the reporting of this ADR as it occurred in Malaysia.
5. Where should ADR/AEFI reports involving products supplied under compassionate use, named-patient use, exemption or a special import permit in Malaysia be submitted?
Answer: Products which are unregistered in Malaysia but supplied under an exemption, compassionate-use, named-patient, or special import approval technically fall outside of NPRA regulatory oversight. Nevertheless, NPRA continues to accept and record ADR reports in the interest of monitoring these products on behalf of the Pharmaceutical Services Programme. Hence, ADRs should be reported to NPRA Pharmacovigilance Section through the standard ADR/AEFI reporting route and following the stipulated reporting timeline of registered products. The organisation supplying the product must ensure that the applicable protocol clearly assigns responsibility for reporting suspected ADRs/AEFIs.
Guideline reference: P1.9.1 and P3.3.2.1.
6. With regards to Compassionate use/ Named patient use. “The protocol should encourage the prescriber to report any adverse reactions suspected of being related to use of the medicinal product to the Authority.”
a) Who holds the ultimate responsibility of ADR reporting under compassionate use/named patient use?
b) Can the protocol be exempted for “named patient use” requested by one doctor for one patient OR a request that is initiated by hospital on regular and larger quantity basis?
Answer:
a) The prescriber is ultimately responsible for the ADR reporting under compassionate use/named patient use because the approval of use is granted to the prescriber. However, if the ADR has come to the knowledge of the PRH and the ADR has not yet been reported to the Authority, then the PRH holds the responsibility to report to the Authority.
b) The protocol is not exempted for the given situations.
7. In a scenario of cumulative cases which involved non-specific patient numbers, e.g. Reporter shared that two or three of his patients experienced diarrhoea after taking product A, OR Reporter commented that a few of his patients experienced bleeding after taking product B. Is this reportable?
Answer: Each ADR report should involve only one patient to fulfil the validity of an ADR report (contain an identifiable reporter, identifiable patient, suspected reaction and suspected medicinal product.). Therefore, for the scenarios mentioned above, separate reports need to be submitted for each patient involved. The reporter should make reasonable follow-up attempts to obtain patient-specific information.
Guideline reference: P1.7.2, P3.2.1 and P3.2.3.
8. How should a PRH monitor suspected ADRs/AEFIs reported through mass media, the internet or digital media?
Answer: PRH-sponsored websites and programmes must be screened regularly. A non-PRH-sponsored website or programme should be included in screening once the PRH becomes aware that it relates to the PRH’s registered product. Screening frequency must allow potential valid cases to be submitted within the stipulated timeline. Eligible unsolicited cases should be managed as spontaneous reports. Reports that do not meet reporting criteria should be documented and retained for future reference.
Guideline reference: P3.3.1.3.
9. Are serious expected and unexpected ADRs/AEFIs from organised data-collection systems or post-registration studies reportable?
Answer: Solicited reports should be treated as study reports and require an appropriate causality assessment by a healthcare professional or the PRH. For PRH-sponsored studies subject to post-market reporting requirements (e.g. phase IV studies), ADRs/AEFIs—especially serious expected and unexpected reactions, including unusual lack of efficacy for new drugs—should be reported to the PRH by investigators so that reportable cases can be submitted to the Authority.
Guideline reference: P3.3.2 and P3.3.2.2.
10. What should a PRH do if it becomes aware of a signal of a possible teratogenic effect?
Answer: The Authority must be informed in writing no later than three calendar days after the PRH first becomes aware of the signal. Such a signal is also an example of an emerging safety issue. It should be notified as an emerging safety issue rather than submitted only as an individual case report.
Guideline reference: P3.4.1.1(v), P7.1 and Appendix 2.
11. When must an overseas withdrawal or suspension be notified to NPRA?
Answer: A withdrawal or suspension of registration or availability in another country due to an emerging safety issue must be notified to the Authority within 24 hours after first knowledge by the PRH. Only an action that has taken place—not one that is merely contemplated—needs to be notified under this requirement. A withdrawal or suspension solely for business reasons is not an emerging safety issue under this provision.
Guideline reference: P7.1 and Appendix 2.
12. Must a PRH prepare an annual summary report for every registered product?
Answer: The summary report is to be prepared only upon request by the Authority. NPRA may request an Issue-Related Summary Report for a specified safety issue and will set the submission period, generally 30 calendar days or less depending on urgency. Separate annual safety-report requirements may apply to particular categories or registration conditions, such as orphan medicines. PRHs must also comply with applicable PBRER requirements.
Guideline reference: P4.3.2, Appendix 4 and Appendix 5.
13. What RMP format is acceptable for submission to NPRA?
Answer: An RMP prepared in the European Union RMP format is acceptable. Every RMP submission must be accompanied by a Malaysia-Specific Annex (MSA) using the NPRA template. The MSA must explain the product overview and safety concerns in Malaysia and describe the local pharmacovigilance and risk-minimisation plans. The RMP must remain proportionate to the product’s risks and be updated throughout its life cycle when required.
Guideline reference: P5.5, P5.6 and P5.6.7; Appendix 6.
14. Which parts of an RMP require Malaysia-specific information?
Answer: Malaysia-specific information must be provided in the MSA submitted with each RMP. This includes the Malaysian product overview; changes from earlier versions; safety concerns relevant to the Malaysian indication; local pharmacovigilance activities; local risk-minimisation measures; and applicable Malaysian product information, educational materials, study information and other supporting data.
Guideline reference: P5.6.7 and Appendix 6.
15. Would there be any requirements to conduct any local studies? If yes, please advise under what circumstances? Also, please advise if this will be a pre-requisite to approval of the product?
Answer: Yes. Additional pharmacovigilance activities, including post-registration studies, may be required when necessary to characterise or manage a safety concern or to support evaluation of the product’s benefit-risk balance. The requirement may be imposed as part of the RMP, a registration condition or a specific direction from the Authority. The need, design and timeline are determined case by case.
Guideline reference: P5.2, P5.3, P5.5 and P5.6.3.
16. What are the consequences of non-compliance with the GVP Guideline?
Answer: The Guideline is issued under Regulation 29 of the Control of Drugs and Cosmetics Regulations 1984. A person who contravenes directives or guidelines issued under Regulation 29 commits an offence. Non-compliance may also lead to regulatory action under applicable legislation, directives or product-registration conditions.
Guideline reference: P1.2.