Current Reporting System for Adverse Drug Reactions

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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 90012000 Certified
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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
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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.
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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
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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
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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
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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

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• 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

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MADRAC Mission

• To ensure the safety of Malaysians through the
  continuous assessment of the safety profiles of
  drugs registeredfor use in this country.

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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.

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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

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FROM ADR REPORT TO DRUG POLICY
Receive ADR report/information
Verify information
Assessment
Discuss at MADRAC meeting
WHO
Requires regulatory action?
Prepare policy paper for DCA
IMPLEMENT POLICY
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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.

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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

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TO BE FAIR IS TO BE BEAUTIFUL

• 1997A 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

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• 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

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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.

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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

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• 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

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WHO definition of SIGNAL

• Reported information on a possible causal
  relationship between and adverse event and a
  drug, the relationship being unknown or
  incompletely documented previously
• 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.

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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

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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

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WHO International Drug Monitoring Programme
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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

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• 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.

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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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THANK YOU FOR YOUR ATTENTION