9. GUIDELINES FOR REGISTRATION HOLDERS
9.1 REPORTING OBLIGATIONS
The legal provisions regarding the conduct of pharmacovigilance is set out in the Sales of Drug Act, Control of Drug and Cosmetic Regulation 1984, Section 28 which states that:
"A licensed manufacturer, a licensed wholesaler, a licensed importer or the holder of a registration certificate in respect of any product shall inform the Authority of any adverse reactions arising from the use of the registered product immediately after he receives notice of such adverse reactions".
9.2 RESPONSIBILITIES OF THE REGISTRATION HOLDER
All registration holders must ensure that an appropriate system of pharmacovigilance is in place in the company in order to accept responsibility and liability for its products on the market and to ensure that appropriate action can be taken, when necessary. It is recommended that the registration holder have permanently and continuously at its disposal in Malaysia, a qualified person responsible for pharmacovigilance. This person should have experience in all aspects of pharmacovigilance. If the identified person is not a health care professional, he/she should have access to a medically qualified person.
Registration holders should inform the Surveillance Pharmacovigilance Division, National Pharmaceutical Control Bureau, in writing of the contact person(s) responsible for all matters pertaining to pharmacovigilance. The postal address, email address, telephone and fax numbers of this person should be submitted in this correspondence as well.
The role of the qualified person responsible for pharmacovigilance are as follows.
- To establish a system for monitoring ADRs encountered by health professionals associated with the use of products marketed by the company
- To ensure that information pertaining to suspected adverse reactions which are reported to the staff of the company or organisation, including medical representatives, is collected and collated so that it is accessible at a single point
- To ensure that all local adverse drug reaction reports are submitted to the DCA in a timely manner
- To submit Periodic Safety Updated Reports (PSUR), company-sponsored post-registration study reports, etc to the DCA
- To ensure that any request for additional risk-benefit information from the DCA is reported to the DCA promptly and fully.
9.3 REPORTING ADRS TO THE DCA
9.3.1 Adverse Drug Reactions Occurring Within Malaysia
- ALL reports of adverse reactions associated with the use of registered products occurring in Malaysia must be reported to the DCA within the stipulated timelines as outlined in Appendix 2.
- New Chemical Entities
Registration holders of New Chemical Entities are required to actively monitor for adverse reactions occurring as a result of the use of the compounds registered. Registration holders are required to report all ADRs in accordance to the stipulated timeliness. The registration holder is also obliged to submit a "NULL" report at six-monthly intervals for the first two years should there be no ADR reports submitted to them.
9.3.2 Adverse Drug Reactions Occurring Outside Malaysia
- Foreign individual case reports need not be forwarded to the DCA on a routine basis, but should be reported in the context of a specific safety issue or on specific request by the DCA.
- The DCA should be advised of any significant safety issue or action which has been taken by a foreign agency, including the basis for such action, no later than 3 days of first knowledge by the applicant.
- Information on withdrawal of the registration status in any country must be notified to the DCA within 24 hours of first knowledge by the registration holder.
9.4 PERIODIC SAFETY UPDATE REVIEWS (PSUR)
- Registration holders who have registered a product containing a new chemical entity after 1 January 2002 must routinely submit PSURs on that product 6 monthly for the first 2 years after approval in Malaysia and annually for the subsequent 3 years.
- This time frame may be varied in order to harmonize periodic safety updates internationally. However, the periodic safety update should be submitted no later than 6 months after the date of approval.
- The registration holders should inform the DCA of any steps which are to be taken with regards to safety concerns raised in the PSUR.
- A copy of the most updated relevant package insert/s should be submitted together with the PSUR.
- The registration holder should submit any consequential variations (e.g. package insert changes) simultaneously with the PSUR at the time of its submission, in order to prevent any unnecessary duplication of effort.
- Registration holders may, in addition, be requested to submit PSURs in the following circumstance - new indications, dosage form, routes of administration or use in populations beyond the registration for the active ingredient.
9.5 CASE REPORTS FROM PUBLISHED SCIENTIFIC LITERATURE
- Registration holders should report published suspected adverse drug reactions related to the active substance(s) of its registered products, as relevant. A copy of the relevant published article should be provided to the DCA.
- If multiple drug products are mentioned in the literature report, only the registration holder whose drug is the suspect drug is required to submit a report. The suspect drug is usually that mentioned as such by the author or stated in the article's title.
9.6 REPORTS FROM POST-REGISTRATION STUDIES
- All adverse reactions from post-registration studies taking place in Malaysia must be reported to the DCA in accordance to the timelines given in Appendix 2 based on the seriousness of the adverse reactions. This applies to reports from any type of clinical or epidemiological investigation, independent of design or purpose.
- Investigators involved in post-registration studies should be aware of the definition of what constitutes a serious adverse drug reaction as well as the distinction between 'reactions' and 'events'.
- In the case of post-marketing studies, adverse "events" are usually systematically solicited. In cases where there is uncertainly as to whether or not an event is a reaction, it is better to report the case as an adverse reaction. Events that are clearly unrelated to the product should not be reported.
- If the registration holder receives a report of a serious adverse drug reaction from the investigator who is blinded to individual patient treatment, the guidelines outlined in Section 10.3 below should be adhered to. Blinded cases should not be routinely submitted.
9.7 ON-GOING PHARMACOVIGILANCE EVALUATION
- Registration holders must inform the DCA within 3 calendar days of first knowledge by the registration holder, whether new evidence becomes available which may significantly impact on the benefit/risk assessment of a product or which would be sufficient to consider changes in the conditions of registration of the product.
- Additional pharmacovigilance data such as actual case reports, drug usage figures, the regulatory status of the product in other countries, independent pharmacoepidemiology studies, pre-clinical studies or significant product quality data may be requested by the DCA as the situation warrants. This must be submitted within a time period specified by the DCA.