pharmacovigilance.pptx

Introduction to Pharmacovigilance
 History and development of Pharmacovigilance
 Importance of safety monitoring of Medicine
 WHO international drug monitoring programme
 Pharmacovigilance Program of India(PvPI)

1. Pharmacovigilance Miss. Gayatri K. Bahatkar Assistant Professor P. R. Patil Institute of Pharmacy, Talegaon SP.

2. Definition of pharmacovigilance According to WHO, pharmacovigilance is the science of collecting, monitoring, researching assessing and evaluating information from healthcare provider and patient of the adverse effect of medication. Prior identification of adverse drug reactions is most important for safety of a patient taking medicine. The information received from health care providers, pharmaceutical companies and patients should be evaluated in order to assess the risk and benefits involved with respect to a particular drug. A careful monitoring of drug usage at every step such as pharmacovigilance inspection, reporting of ADR, periodic collection of safety report, post-authorization safety studies is required.

3. Aim of pharmacovigilance Patient safety- improve patients safely with Ips IP efficacy- see if IP is effective SAEs- track serious adverse events Population- improve public health Risk benefit- review risk, benefit, efficacy for rationalized use of IP Educate- educate on IP safely.

4. The important purpose of pharmacovigilance programmes are To improve patient care To provide medicines and all medical and paramedical services safe . To improve public health services To assess benefit, risk, and effectiveness of medicines To encourage safe, rational, therapeutically effective and cost-effective use of medicines To promote understanding, educating and clinical training in pharmacovigilance, and To support effective communication to health care professionals and the public.

5. Pharmacovigilance Benefit risk assessment of drugs Patient safety Education and training Public health Rational use of drug WHO /Uppsala monitoring center Pharmaceutical companies Hospitals / academic Healthcare worker Patients Nationals / regionals pv centres Acting to protect public health

6. History and development of pharmacovigilance In more recent times, serious adverse reactions associated with medical products resulted in the evolution of regulatory changes and an effort to discover drug safety issues as early as possible. Pharmacovigilance is the practice used by sponsors and regulatory bodies to detect harmful effects associated with medical products to identify potential risks and enable warnings to reach physicians in a timely manner. 1847- chloroform- James young simpson - chloroform induced syncope 1893- lancet setup commission for death due to anaesthesia 1897- diacetylmorphine – felix hoffmen - Bayer lab 1937- Domagk – prontosil red- sulphonamide derivative- sulphonilamide

7. 1938- federal food drug and cosmetic act was passed under which pharmaceutical product manufacturers would have to show scientific evidences Many children in the 1960’s 1954- stalinon diioddiethyl – neurotoxicity 1959- visa legislation 1961- thalidomide disaster- chemie gruenthal company. McBride began to associate this so-called harmless compound with severe birth defects in the babies he delivered. The drug interfered with the babies’ normal development, causing many of them to be born with phocomelia, resulting in shortened, absent, or flipper-like limbs. A German newspaper soon reported 161 babies were adversely affected by thalidomide, leading the makers of the drug- who had ignored reports of the birth defects associated with the it to finally stop distribution within Germany. Other countries. Followed suit and, by March of 1962, the drug was banned in most countries where it was previously sold.

8. 1962- kafouvers - harris amendment act legislators tightened restrictions surrounding the surveillance and approval process for drugs to be sold in the U.S., requiring that manufacturers prove they are both safe and 1963- resolution WHA 16;36 1964- UK started yellow card system 1965- European union issue EC directive 65/65 1968- WHO started pilot project for the purpose of pool ADR 1970-Diehtyl stillbestrol drug- induced viginal carcinoma(1.6 lakh cases) 1989- antiarrhythmic drug used in CAST study- PVC killer ( premature ventricular contraction )

9. 1997- ICH E2 adopted electronic reporting 1999- revised medwatch ,draft medDRA by USFDA released 2001- post marketing safety reporting guideline issue 2002- PDUFA lll ( prescription drug user fee act) 2005- final risk management guideline issued 2007- FDA amendment act. 2010- new IND reporting and European pv legislation 2012 –European pv legislation effective 2014-MHRA good Pv practice for medicine

10. Importance of safety monitoring of medicine The clinical development process of medicine .Till a medicine not approved for sale its remains protected under scientific environment of clinical trials. Before release for sale , a medicine is tested using a limited population ranging from 500 to 5000, once the medicine into the market. Once the medicine comes into the market, it becomes legally available for consumption by the general population. The population may be children's , pregnant women ,patients suffering from other diseases and the elderly. It may be given separately or in combination with other medicine It is therefore very much necessary to observe and record the effectiveness and safety of the medicine under real life condition , In fact adverse effect interaction with food or with other medicine and risk factor are to be noticed only during its real use over the year.

11. Pre-clinical animal experiments Animal experiments for acute toxicity , organ damage , dose dependence, metabolism, kinetics, carcinogenicity, mutagenicity/ teratogenicity Clinical studies Phase l 20-50 healthy volunteers to collect preliminary data Phase ll 150- 350 subjects with diseases- to determine safety and dosage recommendation Phase lll 250-4000 more varied patient groups- to determine short-term safety and efficacy Phase- lV Post- approval studies to determine specific safety issues Spontaneous reporting

12. Year Drug Adverse reactions Remarks 1950 Chloramphenicol Aplastic anaemia Still being used 1961 Thalidomide Phocomelia National disaster 1970 Clioquinol Smon After 30 years of use 1970 Diethylstillbesterol Adenocarcinoma In utero expouser 1975 Practolol Oculo-mucocutaneous syndrome 5 years after marketing 1976 Zomepirac Anaphylaxis Withdrawn 1978 Phenformin Lactic acidosis Withdrawn

13. Year Drug Adverse reaction Remarks 1978 Phenformin Lactic acidosis Withdrawn 1980 Ticrynafen Death from liver disease Detected after 5 years of suspection 1982 Ticrynafen Hepatitis Withdrawn 1990 Etretinate Birth defect high risk of birth defect narrow therapeutic index 1999 Astimizole Arrhythmias Because of interaction with other drugs 2004 Rofecoxib Myocardial infraction Withdrawn 2007 Inhaled insulin Long term safety ,high cost Withdrawn in UK due to poor sales caused by national restriction on prescribing , doubts over long term safety.

14. Thus closed and effective monitoring is required to asses the risk associated with the use of medicine. This is possible when all the stakeholder extend their hand in the field of PV to meet the challenges . To make such collaboration saucerful the effective and comprehensive system are required. The typical limitation include lack of training, recourses ,political support and scientific infrastructure for the future development of the science and practice of pv .

15. In general, the stakeholders who need to collaboratively work are 1. Government 2. Industry 3. Hospitals and academia 4. Medical and pharmaceutical associations 5. Poisons and medicines information centers 6. Health professionals 7. Patients 8. Consumers 9. The media 10. World Health Organization

16. WHO international drug monitoring programme During the 16th World Assembly in 1968, the 16.36 resolution was called for "a systematic collection of information on serious adverse drug reactions during the development and particularly after medicines have been made available for public use". This finally appeared as the WHO Programme for International Drug Monitoring (PIDM). The WHO encourages pharmacovigilance at country level. Initially, the WHO PIDM was formed with members of 10 countries. Till May 2016, 124 countries have joined the WHO PIDM and 29 associate members are waiting for full membership. Reports on adverse reactions associated with medicinal products are to be submitted by WHO PIDM Member States. This is known as Individual Case Safety Reports (ICSRs) and it is recorded as the WHO global database. The WHO Programme for International Drug Monitoring offers a forum for WHO member states to work together in pharmacovigilance, VigiBase™.

17. VigiBase is managed and maintained by the WHO Collaborating Centre for International Drug Monitoring, known as the Uppsala Monitoring Centre. There were over 10 million reports of adverse drug reactions in VigiBase till October 2014. Data in VigiBase are recorded in a structured and comprehensive manner to allow the detection of potential medicinal safety hazards. The objectives of pharmacovigilance are: To improve patient care and patient safety with respect to the use of medicines; and To support public health programmes by supplying reliable, balanced information to assess the risk-benefit profile of medicines. History – established in 1968 with 10 country IDMC –WHO Geneva- who collaborating center of international drug monitoring – Upssala

18. UMC- non profit organization = WHO + Swedish govt. Vision and goal of UMC In science and concept of pharmacovigilance Prevent harm to human from medicine Gather and share objective intelligence and opinion for drug safety by transparent communication Support and promote of rational used of medicine so improved patient therapy And public health. Global education and communication in benefit, harm, effectiveness and risk of medicine Activity of UMC Developing leading edge system and science to identify and communication of safety hazard from drugs

19. Carryout research within ethical , intellectual and scientific boundary of theory and practice of PV Pursuing active collaboration and communication with all sketch holders Pursuing goal of single global database for drug safety Ensure to never miss signal of potential hazards All stakeholder ensure to evaluate and learn for decision Encourage growth of PV Promote existing centres and stakeholders Share info openly and transparently Stimulate harmonized sys worldwide for Pv Maintain and develop useful products and tools and services in pursuit = vision and goal programme

20. Communication about safety of medicines Methods of communication Issued by Letters to the Doctors Pharmaceutical Manufacturer Medicine alerts National health authorities Media statements National health authorities/Pharmacovigilance centres Leaflets for information To the patients Pharmaceutical Manufacturer/National Health Authorities/Pharmacovigilance centres News letters National Pharmacovigilance centres and WHO Personal feedback to Reporters National Pharmacovigilance centres

21. The collaborating center is responsible for maintaining the global ADR database, VigiBase. At present the database contains more than three million ADR reports. The WHO Collaborating Centre analyses the reports in the database to: Identify early warning signals of serious adverse reactions to medicines; Evaluate the hazard; Undertake research into the mechanisms of action to support the development of safer and more effective medicines. Through an advisory committee, the WHO plays an important role in the provision of expert advice on all matters relating to the safety of medicines. The Committee also assists consistently for implementation of the policies and actions among the member countries and advises those who are concerned about the action taken in another country.

22. Pharmacovigilance in India The concept of pharmacovigilance is not new to India. It is in its earlier stage. In about 1986 a formal ADR monitoring system consisting of 12 regional centers was proposed for India. Each center would cover a population of 50 million. In the year 1989, six regional centers in Mumbai, New Delhi, Kolkata, Lucknow, Pondicherry and Chandigarh were set up under the guidance and support of the Drug Controller of India. India joined the WHO Programmed in 1997 for International Drug Safety Monitoring. The programmed was managed Pharmacology, AIIMS) was considered as the National Centre. The center in Mumbai (at KEM by the Uppsala Monitoring Centre, Sweden. The center in New Delhi (at Dept of Hospital) was considered as the WHO Special Centre. Out of the six centers, only the centers in Mumbai and New Delhi were actively working. However, spontaneous reporting of ADRs.

23. National Pharmacovigilance Advisory Committee based in the Central Drugs Standard Control Organization (CDSCO), New Delhi started supervising the NPVP. Two zonal centers. The South-West zonal centre and the North-East zonal center, had been collecting information from all over the country and sending the information to the Committee as wel as to the Uppsala Monitoring Centre in Sweden. Mission of this program Safe guard health of Indians Ensuring benefit of medicine Out weight the risk associated with drug

24. Vision of pv program of India improve patient safety welfare of Indians health Objective of pv program of India create nationwide system for patient safety reporting Identify and analyzed new ADR from reported cases Analyzed risk benefit ratio of marketed drug. Support regulatory agency in decision making Communicate safety info of medicine

25. Goal of PV program of India they are devided into to type Short term Long term Short term Develop and implement pv system Enroll all MCI approved medical colleges Encourage healthcare professional to report ADR of drug vaccine medical devices and biological products Collection of case report and data

26. Long term Expand PV program to all govt. and privet hospitals Develop electronic reporting system Develop self-reporting culture among health professional To make ADR reporting mandatory for health professional Causes of failure of implementation of PV program in India PV system not well funded and systematic for big country like India Data obtain from zonal to peripheral center are often poor and not well analyzed Motivation for PV in healthcare professional in urban and ruler negligible Paitent not well educated to directly report ADR to regulatory bodies.

27. Although clinical trials in India has been started in and around 1996. In global market the landmark year for the industry was 2005. The studies of the clinical trials have been structured, supervised where the safety and efficacy of a new drug or therapy are to be tested to develop new treatments. This would help those badly affected with the targeted condition. For conducting global clinical trials, India is considered as a better choice for its Large patient populations, Highly educated talent, Wide spectrum of disease, Lower costs of operations, Favorable economic and intellectual property environment.

28. Presently around the world the clinical research industry has grown at an excellent rate with pharmaceutical industry. The major survival amount of the pharmaceutical companies is innovation and introducing new drugs in the market. For approval, well organized, properly supervised and well-structured clinical trials have to be conducted as per ICH GCP guidelines and in accordance with defined rules of the country wherein the trial is planned to be conducted. It should be mentioned here that the conditions under which patients are studied during the pre-marketing phase do not necessarily reflect on how these medicines will be used in the hospitals or in general practice once it is marketed .

29. year Events 1747 First reported clinical trials by james lind , proving the effectiveness of lemon juice in preventing survey 1937 Death of 107 children's due to sulfanilamide toxicity 1950 Aplastic anemia reported due to chloramphenicol 1961 Global disaster due to thalidomide toxicity 1963 16th World Health Assembly recognized importance to rapid action on ADR's. 1968 WHO pilot research project for international drug monitoring. 1996 Clinical trials of global standards started in India.

30. 1997 India joined WHO Adverse Drug Reaction Monitoring Programme 1998 Pharmacovigilance initiated in India. 2002 67th National Pharmacovigilance Center established in India 2004-05 National Pharmacovigilance Programme launched in India 2005 Conduct of structured clinical trials in India. 2009-10 PVPI was initiated

31. Pharmacovigilance is also beneficial to the patients in the following means: It Increases the savings to the patient by cutting the cost, It helps the health care institution and other health care practitioners, It helps regulatory authority with respect to scrutiny or even the withdrawal of drugs that do not show a favorable risk-benefit ratio. It can prevent from or reduces the readmissions of the patients.

32. INTRODUCTION TO ADVERSE DRUG REACTIONS Adverse drug reactions (ADRs) is an unwanted, undesirable effect of a medicine that occurs during usual clinical application. It occurs almost daily in health care institutions and can adversely affect a patient’s quality of life; sometimes may lead to considerable morbidity and mortality. Much attention has been given to identify The patient populations most at risk, The drugs most commonly responsible, and The potential causes of ADRs. The factors responsible for the prevalence of ADRs worldwide are: Increase in the number of drugs in the market, An aging population, and An upward trend in polypharmacy.

33. The difference between ADRS and ADES is that ADRs can occur even after appropriate prescription and correct dosing. ADES are generally associated with inappropriate use of the drug that usually occurs during drug therapy. It may not be related to the pharmacology o the drug itself. Adverse drug events (ADES) may occur due to medication errors. The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) has defined the medication errors as: “any preventable event that may cause or lead inappropriate medication use or patient harm while the medication is in the control of the Health care professional, patient, or consumer.

34. Objectives of ADRs Monitoring (A) To help the drug regulatory authority, public health programmes , scientists and consumers for taking appropriate action to reduce the risks of ADRs. It is also necessary to find out the nature and frequency of ADRs with periodical check of the benefit-risk ratio of medicinal products. The benefit-risk ratio of medicinal products can be re for evaluated by: Providing updated drug safety information to health care professionals and other stakeholders including WHO ADRs Monitoring Centers. Updating information in package and disseminating information which may result recall or withdrawal of the product in the market or restrictions for marketing. Propagating information for designing proper education programme to consumers and other users. Taking initiative to study the effect of a for further education. For example benefit of the drug especially in long term for prevention of relapse or study of new indication, overuse, possible mechanism underlying the adverse reaction observed or misuse.

35. (B) To identify the risk factors that may affect, induce or influence the development, severity and incidence of adverse reactions in the population; for example, 1 Patient factors such as genetics, racial differences, diets, diseases, prescribing Practices, pattern of drug use and food habits (high carbohydrate, fat diet etc.). 2. Drug interactions, drug distribution, storage and use including indications, dose. Availability and other underlying conditions. Due to adverse drug reactions the patients may lose confidence in the therapy or may show negative towards their physicians and may look for self-treatment options. As a result additional ADRS may not be observed. About 5% of the hospital admissions are the result of an ADR, and at least one ADR would be found in about 10%-20% of inpatients during their stay in hospitals. The actual frequency of ADRS may be even greater than the above values. Because some ADRS imitate natural disease states and thus, remain undetected and/or unreported

36. Some ADRs present minor symptoms, others are serious and cause death in as many as 0.1%-0.3% of hospitalized patients. Adverse drug reactions should be identified and managed as early as possible to reduce their harmful effects on the patients. The cost of managing ADRs can be high, whether they occur in the inpatients or the outpatients. The clinical diagnosis of an ADR is not always observable. Practitioners often advise Additional laboratory tests or procedures to investigate the cause of a patient’s symptoms. Practitioners may also prescribe pharmacotherapy for conditions caused by an unrecognized ADR. This increases the cost of treatment as well as the risk of additional ADRs. If the ADR occurs when the patient is hospitalized, the duration of stay can be increased and overall cost of treatment may also increase. Due to ADRs the anxiety or depression and loss of working days for the Patient and/or Caregiver may take place, as a result additional indirect cost may increase.

37. The study of drug-related injuries and making warning or withdrawal recommendations for pharmaceutical agents are the major activities of pharmacovigilance; however, it includes assessment, understanding, and prevention of ADRs. Pharmacists play a vital role in each step of the pharmacovigilance activity; so that the Patients need not require unnecessary procedures or take unnecessary drugs so that safety And quality of life for the patient can be preserved.

38. Thank you