Medicines Act: Pharmacovigilance and the Medical Profession

Medicines Regulatory Unit - Malta  Set-up more than one year ago  Currently employs 12 pharmacists  Headed by Ms. L. Wismayer, Director, MRU  Will establish the Medicines Authority (MA) in Malta  Preparation of Medicines Act

MRU - Legislation & Structure  Future Structure of Medicines Authority: Inspectorate (incl. Pharmacies, Distribution, Manufacturing) Pre-licensing (incl. Launch of Marketing Authorisation Project) Post-licensing (incl. Pharmacovigilance & Advertising)  Legislation: Main legislation: Role of Medicines Authority to deal with all pharmacovigilance issues Subsidiary legislation i.e. regulations which transpose relevant parts of EU directives/regulations

Relationships between MA and others LICENSING AUTHORITY MEDICINES REVIEW BOARD (Appeals) MEDICINES AUTHORITY (a scientific body carrying out its functions in accordance with scientific evidence) EXPERTS (to be consulted on various issues as required) MEDICINES ADVISORY BOARD (Mainly dealing with safety issues but also any other issues which require expert consultation)

Some Functions of Licensing Authority  To establish standards to ensure the quality, safety and efficacy of medicinal products  To establish standards for the reporting of adverse reactions, serious adverse reactions or suspected unexpected adverse reactions and make provisions for the collection or submission of related information from any person or activity by or under this act  To withdraw or recall medicinal products from the market in the interest of public health or as a measure of precaution

PHARMACOVIGILANCE  DISASTER!  1961  Thalidomide  WHO Project  1968  International Drug Monitoring

PHARMACOVIGILANCE UK - Yellow Card Scheme  Since more than 30 years (1964)  Also recently as electronic reporting CIOMS  Council International Organisation of Medical Science  Common format for reporting of ADR’s European Union  Directive2001/83/EC  TITLE IX, Articles

Some Definitions from 2001/83/EC  Adverse reaction: A response to a medicinal product which is noxious and unintended and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease or for the restoration, correction or modification of physiological function.  Serious adverse reaction: An adverse reaction which results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect.  Unexpected adverse reaction: An adverse reaction, the nature, severity or outcome of which is not consistent with the summary of product characteristics.

Legislation & Pharmacovigilance Draft Regulations: “The Medicines Authority shall establish a pharmacovigilance system. This system shall be used to collect information useful in the surveillance of medicinal products, with particular reference to adverse reactions in human beings, and to evaluate such information scientifically.” MRU Projects:  Design of ADR report form  Launching of form during Seminar for HCP  Setting up of Medicines Advisory Board

Legislation & Pharmacovigilance Draft Regulation: “This system shall also take into account any available information on misuse and abuse of medicinal products which may have an impact on the evaluation of their benefits and risks.” Definition: Abuse of medicinal products: “Persistent or sporadic, intentional excessive use of Medicinal products which is accompanied by harmful physical or psychological effects.”

Legislation & Pharmacovigilance Draft Regulation: “The Medicines Authority shall take all appropriate measures to encourage doctors and other health care professionals to report suspected adverse reactions to the Medicines Authority.” MRU projects:  Seminar/Workshops to reinforce use of ADR reporting system  Newsletter published at regular intervals throughout the year  Education in Pharmacy Curriculum for Undergraduates

Effects of Adverse Drug Reactions ADR’s cause admissions to:  Hospitals (2% - 6% of all admissions)  Attendance to Primary Care Complicate hospital in-patient stay  10% - 20% cases Responsible for deaths  Possibly as high as the 4th common cause

Effects of Adverse Drug Reactions  Increase the length of hospital stay  Increase the cost of patient care  Adversely affect patient quality of life  Cause patients to lose confidence in doctors  Occurrence of toxicity in a minority of patients will preclude use of the drug in the majority of patients  Mimic disease and result in unnecessary investigations and/or delay in treatment  Major economic burden on the pharmaceutical industry

Design of ADR Report Form  In Confidence  Patient Details  Suspected Drugs  Suspected Reactions  Other Drugs  Seriousness  Outcome  Reporter Details

What to report  Reports on all suspected adverse reactions known or not, serious or not, are welcome and useful  Established drugs - Serious or unusual reactions are of particular importance  Known and minor reactions are of less interest  If an increased frequency of a given reaction is suspected this is also a reason for reporting

Causality Categories  Category A: ‘Good reasons and sufficient documentation to assume a causal relationship, in the sense of plausible, conceivable, likely, but not necessarily highly probable’  Category B: ‘Reports containing sufficient information to accept the possibility of a causal relationship, in the sense of not impossible and not unlikely, although the connection is uncertain and may even be doubtful, e.g. because of missing data, insufficient evidence or the possibility of another explanation’  Category 0: ‘Reports where causality is, for one or another reason, not assessable, e.g. because of missing or conflicting data’

“Reporting Culture” Raising HCP’s awareness  All medicines can cause adverse drug reactions  Responsibility to participate in national pharmacovigilance system Advantages of Spontaneous ADR Reporting:  Operates for all drugs throughout the whole of their lifetime  Only affordable method of detecting really rare ADR’s Main weaknesses  Under-reporting (not more than 10%)  “numerator” data (the number of reports of each suspected reaction)

Under-reporting Reporting of ADR’s needs continuous stimulation:  To achieve a positive attitude towards reporting  To make reporting an accepted and understood routine The following may stimulate reporting:  Easy access to pre-paid ADR reporting forms  Acknowledgement of receipt of ADR forms  Feedback in the form of bulletin/newsletter  Participation in education and scientific meetings  Collaboration with professional associations and committees  Pharmacovigilance in clinical pharmacy

Pharmacovigilance & Market Authorisation Draft Regulations: “The marketing authorization holder shall be required to record and report all other suspected serious adverse reactions which are brought to his attention by a health care professional immediately to the competent authority... and in no case later than 15 calendar days following the receipt of the information.” “Where, as a result of the evaluation of pharmacovigilance data, the Medicines Authority considers that a marketing authorisation should be suspended, withdrawn or varied…” “In case of urgency, the Medicines Authority may suspend the marketing authorisation of a medicinal product….”

Medicines Advisory Board and Experts MAB: Physician, Pharmacologist,Toxicologist Experts: All specialist areas  Anatomy, Physiology, Pharmaceutics etc…  Medicine, Surgery, Cardiology, Dermatology etc...  Paediatrics, Geriatrics, Diabetes, Vaccines etc..  Intensive care, Anaesthesiology, Dentistry etc...  Biotechnology, Genetics, Medical Devices etc…  Nutrition, Pharmacognosy, Herbals, Homeopathics etc...

Work to be carried out by MAB  Review of data and advice given leading to Variations, Suspension or Withdrawals of Marketing Authorisations of Medicinal Products Example: Aspirin - association with Reye’s Syndrome - UK  CSM advised that children less than 12 years should not receive aspirin except on medical advice  Relevant data for children aged 12 and over reviewed  New proposed warning: “Do not give to children aged under 16 years, unless on the advice of a doctor”

In Conclusion the Aims of PhVG are to:  Improve patient care and safety  Improve public health and safety  Contribute to the assessment of benefit, harm, effectiveness and risk of medicines  Promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public

Summary of Pharmacovigilance Plan  Design of ADR reporting card  Launching of new ADR reporting system (Seminar, Workshops)  Launching of market authorisation project  Seminar (NtMAHs, obligations of MAHs, HCPs and regulatory authority, as well as reinforcing use of ADR reporting card)  Launch of newsletter on drug safety issues targeting HCPs, scientific institutions & patient groups  Academia – regulatory affairs education

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