Current Reporting System for Adverse Drug Reactions National Pharmaceutical Control Bureau Ministry of Health Malaysia www.bpfk.gov.my WHO Collaborating Centre For Regulatory Control of Pharmaceuticals Member of Pharmaceutical Inspection Cooperation Scheme MS ISO 9001:2000 Certified
Feedback given to registration holders receive ADR report report ADR Pharmaceutical company ADR form National ADR centre Health professionals WHO recommendations Malaysian ADR Advisory Committee (MADRAC) Drug Control Authority (DCA) ADR MONITORING SYSTEM IN MALAYSIA
THE SPONTANEOUS REPORTING SYSTEM Malaysia like most other countries uses a spontaneous reporting system for ADR Passive surveillance system Health professionals are encouraged to report adverse reactions which they believe to be drug-related directly to the regulatory authority or the company marketing the suspected product on a voluntary basis.
The spontaneous reporting system processes 1. data acquisition which depends largely on the input of information derived from reports submitted by the health professionals who have encountered what they suspect is an ADR The spontaneous reporting system 1.data acquisition 2.data assessment 3.data interpretation
The spontaneous reporting system 1.data acquisition 2.data assessment 3.data interpretation The spontaneous reporting system processes:- 2. data assessment which involves assessment of the individual case reports and assessment of pooled data obtained from various sources such as the international database of the WHO
The spontaneous reporting system 1.data acquisition 2.data assessment 3.data interpretation The spontaneous reporting system processes:- 3. data interpretation based on the available data and the assessments made, a signal related to the adverse reaction may be generated
Malaysia Adverse Drug Reactions Advisory Committee (MADRAC) • As part of the regulatory process, a system to ensure the safety of the public consuming registered products was established through the monitoring of adverse drug reactions • MADRAC was established under the Drug Control Authority (DCA) to perform the function of monitoring safety profiles of drugs registered for use in Malaysia
MADRAC provides the DCA with information pertaining to drug safety issues which occur locally and internationally • The National Drug Safety Monitoring Centre, which is the secretariat to MADRAC, was accepted as the 30th member of the World Health Drug (WHO) Safety Monitoring Program in 1990. • Under the monitoring programme, all ADR reports which have been received and screened by MADRAC are submitted to the Uppsala Monitoring Centre in Sweden for inclusion into the WHO database
MADRAC Mission To ensure the safety of Malaysians through the continuous assessment of the safety profiles of drugs registeredfor use in this country.
What MADRAC do? Functions • Promote ADR reporting in Malaysia • Provide information and advice to the DCA in order that regulatory action can be taken based on the ADRs received (local & foreign). • Provide information to doctors, pharmacist and other health care professionals on ADRs. • Participate in the WHO ADR monitoring programme.
Outcome of ADR reporting • Suggest labeling changes to be made to the product insert/packaging e.g. warnings, boxed warnings, precautions, drug interactions, etc. • Recommend restrictions on usage e.g. not recommended for children, contraindicated in pregnancy, patients with certain risk factors. • Advocate control on sale of particular products • Implement drug recalls/withdrawal based on safety issues
Receive ADR report/information FROM ADR REPORT TO DRUG POLICY Verify information Assessment WHO Discuss at MADRAC meeting Requires regulatory action? Prepare policy paper for DCA IMPLEMENT POLICY
ADULTERATED PRODUCT BAIKE WAN • BPFK received ADR/complaint from consumer stating that this product can relieve nerves and joint pain. • Product has been tested by BPFK and found to contain caffein and niacinamide and the registration of the product has been cancelled. • Although the registration of the product has been cancelled, BPFK still receives complaint that the product is available in the market.
ADULTERATED PRODUCT BAIKE WAN • These reports were forwarded to the enforcement unit for further action since the product is an unregistered product. • BPFK also received complaint from other regulatory authorities stating that they have tested the product and found to be adulterated with scheduled poisons ie chlorpheniramine, frusemide and piroxicam. • Since the registration of the product has been cancelled and adulterated product is still available in the market and for the safety to the consumers, a press statement is made on this product
TO BE FAIR IS TO BE BEAUTIFUL • 1997:A young Malay lady called in to complain that she had used a whitening cream which initially was very effective • On continuous usage, her skin started to get hyperpigmented instead • Her face looked so terrible she did not even want to venture out of her house
Information on product used and where it was purchased was provided • Sample taken for testing and was found to contain 25% hydroquinone • Actions taken: • GMP audit done of manufacturing premise • Found gross violation of GMP principles • Manufacturer instructed to shut down • Total product recall • Decision made not to allow use of hydroquinone in Over-The-Counter products
WHO – Uppsala Monitoring Centre • WHO International Drug Monitoring Programme carried out by Uppsala Monitoring Centre (UMC) in Sweden. • UMC – responsible to collect ADR data from all over the world especially from countries that are members and the generation of signals of drugs which might possibly have problematic side-effects.
Overview - areas of work of the Uppsala Monitoring Centre • Receipt, analysis and recording of worldwide adverse event data • Maintenance and screening of international database (currently over 3.9 million records) • Publication of previously unknown adverse events in SIGNAL • Editing, updating and publishing the WHO Drug Dictionary • Maintaining and publishing the Adverse Reaction Terminology (WHO-ART) • Carrying out special searches of the database by request • Publishing a range of special reports
Assistance to potential members of the Programme in developing their pharmacovigilance systems • Running training courses in pharmacovigilance • Organising the annual meeting for member and associate member countries • Publishing scientific articles • Contributing to international conferences. • WHO Drug Dictionary • WHO Adverse Drug Reaction Terminology • VigiFlow: A validated case management system for pharmacovigilance centres and companies • Data – mining and signaling • Monitoring Herbal Medicine and Herbal ATC Classification
WHO definition of “SIGNAL” “Reported information on a possible causal relationship between and adverse event and a drug, the relationship being unknown or incompletely documentedpreviously” Additional note : Usually more than 1 report is required to generate a signal, depending on the seriousness of the event and the quality of information.
How Signals can be detected? • Manual investigation + clinical judgement - Clinical review - Search for and review - Look at total number of reports • Quantitative Signal detection - Proportional Reporting Ratio - Reporting Odds Ratio - Bayesian Confidence Propagation Neural Network (BCPNN) – a combination between Bayesian Statistic and a neural network implementation
INTERNATIONAL DRUG SAFETY PROGRAM • Initiated in 1964 at the request of the World Health Assembly • Coordinated by the WHO • Started with 10 countries • To become a member, must have a national centre responsible for coordinating the program • Malaysia became the 34th member in 1990 • Up to this date – 82 member countries 18 associate members
Functions of the WHO Programme for International Drug Monitoring include • Identification and analysis of new adverse reaction signals from the case report • Provision of the WHO database as a reference source for signal strengthening and ad hoc investigations. • Information exchange between WHO and National Centres, mainly through 'Vigimed', an e-mail information exchange system • Publication of periodical newsletters, (WHO Pharmaceuticals Newsletter and Uppsala Reports), guidelines and books in the pharmacovigilance and risk management area
Supply of tools for management of clinical information including adverse drug reaction case reports • Provision of training and consultancy support to National Centres and countries • Computer software for case report management designed to suit the needs of National Centres (VigiFlow) • Annual meetings for representatives of National Centres at which scientific and organizational matters are discussed • Methodological research for the development of pharmacovigilance as a science.
Measures taken to promote ADR reporting • Distribution of Manual on ADR reporting to all medical practitioners and pharmacists • ADR reporting forms with prepaid postage given free to doctors and pharmacists • Talks by MADRAC committee members to public and private sector doctors and pharmacists • Articles on ADR reports in local newsletter
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