HISTORY AND DEVELOPMENT OF PHARMACOVIGILANCE DR, RAMESH BHANDARI ASST. PROFESSOR DEPARTMENT OF PHARMACY PRACTICE KLE COLLEGE OF PHARMACY, BELAGAVIJ History of Pharmacovigilance In 1901, in USA: 13 children died from contaminated diphtheria antitoxin due to which passed Biological Control Act 1902 — ensure purity and safety of serum, vaccines and other products. “In 1937 in USA: 105 people died including 35 children due to new liquid formulation (raspberry flavoured elixir) of anti-infective sulphanilamide. (Tablets and powder was used before for —streptococeal _ infections) due to which The federal food, drug and cosmetics act (FDCA) was enacted in 1938 which began to examine the risk-benefit profile of medicinal products. (required proof of safety through NDA)a History of Pharmacovigilance “Gradual increase in regulatory authority: *Durham-Humphrey Amendment of 1951 (FDCA amendment 1951) — separation of drugs into 2 types — drugs could be used without the physician assistance (named over the counter drugs) and drugs needing physician assistance.I History of Pharmacovigilance THALIDOMIDE TRAGEDY; » Late 1950s and early 1960s — changed focus of drug safety from reactive to proactive (mandates safety surveillance before marketing as well as post marketing pharmacovigilance.) » 1956-1961 used thalidomide in 20 different countries as sleeping pill (hypnotic) and antiemetic in pregnant women. (but not approved for use in USA because of its delayed NDA) » Late 1961 and early 1962 reports of various limb deformities (Phocomelia) from Europe began.a History of Pharmacovigilance “POST THALIDOMIDE EVOLUTION: ~ Necessity to monitor drag products for efficacy and safety increases. ~ Regulatory changes following thalidomide tragedy: fauver-Harris Amendments: Required affirmative approval from the FDA before a praduet could be marketed. (21 CFR Part 314) * Mandatory IND pracess permitting FDA monitoring of testing, transportation, and distribution (21 CFR part 312) * Mandate registration aifsubjeckt exposed during pre-clinical and clinical testing (21. CFR pari 50)a History of Pharmacovigilance Kefauver-Harris Amendments: * Established 3 separate phases of clinical trial to prove efficacy (21 CFR part 312) * Required uniformly formatted drug labelling (21 CFR part 201.57) * Established good manufacturing practices (21 CFR part 210) * Regular post marketing communication with FDA on experience with the drugs (all spontaneous reporting, analysis of medical literature on product)a Origin of Pharmacovigilance Pharmakon — Drugs Vigilare — to watch or to see Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine/vaccine related problem.= Origin of Pharmacovigilance nal tumours in girls and young men Phenformin | 1978 Lactie acide Phenolphthalein 1997 reinogenicity Troglitazone 2000 Hepatotoxicity Rofecoxib 2004 Risk of Myocardial Infarction 2010 isk of heart aac and dealsWHO INTERNATIONAL DRUG MONITORING PROGRAMME~y KEE WHO INTERNATIONAL DRUG MONITORING PROGRAMME >Under the auspices of |() countries, a 3 year feasibility study of a collaborative international program of pharmacovigilance was begun by Professor Jan Venulet in 1968 funded by USA. Professor Venulet and the FDA’s Drug safety group developed _a_thesaurus DART, to describe_spontaneous report in uniform body system based terminology.= WHO INTERNATIONAL DRUG om MONITORING PROGRAMME »Later in FDA, DART evolved into COSTART (Coding symbols for thesaurus of adverse reaction terms). > COSTART used until MedDRA (Medical terminology for drug regulatory authorities) was adopted in later 1990s by the European commission as a part of ICH.=” WHO INTERNATIONAL DRUG a MONITORING PROGRAMME »Venulet developed a program agreed to by members states for recording. storing, and retrieving incoming spontaneous reports into a database, as well as methodologies for analysing the data received. » This is known as International Drug Monitoring Programme which then moved to WHO headquarters in Geneva, Switzerland. >In 1978, the program was moved to Uppsala. Sweden.= WHO INTERNATIONAL DRUG = MONITORING PROGRAMME + Uppsala Monitoring centre’s mission is to Safeguard patients and to: “Lead the research and development tools and_ methodologies for pharmacovigilance and patient safety © Lead and support global pharmacovigilance activities Develop effective networks and sustainable pharmacovigilance system ¥ Apply best practices in communication and networking with stakeholders ¥ Provide high quality and cost effective tools, services and international dictionaries, classification and terminologies for pharmacovigilance and patient safety ¥ Build an effective organization for the future sey]~ KLE WHO INTERNATIONAL DRUG MONITORING PROGRAMME >This monitoring program now serves over 80 countries with annual meeting exchange practices, provide training, and serve as a database of adverse events from member countries.4 FUNCTIONS OF WHO INTERNATIONAL see DRUG MONITORING PROGRAMME > Identification and analysis of new adverse reaction signals from the case report information submitted to the national centers, > Information exchange between WHO and national centers through “Vigimed” » Publication of periodical newsletters > Supply of tools for management of clinical information (WHO drug dictionary and the WHO adverse reaction terminology).74 FUNCTIONS OF WHO INTERNATIONAL sep DRUG MONITORING PROGRAMME Training and consulting support to national centers and countries establishing pharmacovigilance system >» Computer software for case report management » Annual meeting for representatives of national centers74 FUNCTIONS OF WHO INTERNATIONAL sep DRUG MONITORING PROGRAMME »Methodological research for the development of pharmacovigilance scientific articles in Publication of various pharmacovigilance.PHARMACOVIGILANCE PROGRAM OF INDIA (PVPI)ma PHARMACOVIGILANCE PROGRAM OF INDIA (PvPI) In 1986 — Proposed ADR monitoring system for India (12 Regional Centres) In 1997 — India joined WHO-ADR monitoring programme (3 centres i.e. AIIMS, KEM and AMU} In 2004 — National pharmacovigilance program (2 zonal, 5 Roenr eee ee kena In 20: — Pharmacovigilance programme of India (PvP!) By Dr. Rar h BhandariNATIONAL PHARMACOVIGILANCE PROGRAM ZONES IN INDIA= PHARMACOVIGILANCE PROGRAM OF INDIA — (PvPI) = PyPI was initiated by CDSCO, New Delhi in July 2010 with AIIMS New Delhi being the National Coordinating Centre (NCC) for monitoring ADRs. Then later the National coordinating centre was shifted to the Indian Pharmacopoeia Commission (IPC), Ghaziabad, (U.P.) in 15" April, 2011.= ee eM OF INDIA — PvPI Mission: =Safeguard the health of the Indian population by ensuring that the benefits of use of medicine outweighs the risks associated with its use,PHARMACOVIGILANCE PROGRAM OF INDIA (PvPI) * Develop and implement pharmacovigilance system in india * Encourage health care professionals in reporting of adverse reaction to drugs, vaccines, medical devices * Collection of adverse reactions reports Lo rays term ae + To develop and implement e-reporting system. * To make ADR reporting mandatory for health care [-{oy-] iS Nckealenae= nici pee OF INDIA — PvPI Objecti: *To create a nation-wide system for patient safety reporting. *To identify and analyse new signals from the reported cases. *To analyse the benefit-risk ratio of marketed drug products. To generate evidence based information on drug safety. =To promote rational use of medicines.COMMUNICATIONS UNDER PvP! ~ KLE J €DSCO Zonal Offices 4 Zone | — — ADR Monitoring Centres COSCO, Headquarter, New Dethi | NCC, IPC, Ghaziabad ‘Uppsala Monitoring Centre, Sweden= a eM OF INDIA — PvPI *This program is monitored by different committees under NCC: ¥ Steering Committee ¥ Strategic Advisory Committee =Technical support will be provided by: v Signal Review Panel ¥ Core Training Panel ¥ Quality Review Panel= PHARMACOVIGILANCE PROGRAM OF INDIA pa (PvPl) *ADR Will be collected from: ¥ Medical council of India (MCI) approved medical colleges and hospitals ¥ Private hospitals ¥ Public health programs ¥ Autonomous institutions (ICMR)Steering Committee g Signal Review Quality Review Panel GOVERNANCE OF PvPI PvPl—Headquarters Government of India National Pharmacovigilance Coordinating Centre Indian Pharmacopoeia Commission Ghaziabad, UP Central Drugs Standards Control Organisation Ministry of Health and Family Welfare (MoHFW) "COSCO Zanal and Subzonal Centres= aidan eM OF INDIA = PvPI ¥ The PvPI Programme had been planned to be implemented in 3 phases: 1. Phase I: To set up 40 ADR Monitoring centres (AMC) would be rolled out in 2010. 2. Phase I: To set up 140 MCI recognized medical colleges by 2011. 3. Phase III: Programme would ultimately cover the healthcare system by 2013. ¥ AMCs operates with logistic support from their respective Zonal CDSCO centres situated at Ghaziabad, Kolkata, Mumbai and Chennai. ¥CDSCO Headquarters at New Delhi controls the Zonal Centres.DEVELOPMENT OF PHARMACOVIGILANCE IN INDIA 1848 Girl child death due to chloroform anaesthesia 1901 Contaminated Diphtheria antitoxin toxicity 1937 Sulfanilamide elixir toxicity 1961 Thalidomide Tragedy 1968 WHO international Drug Monitoring Programme 1986 India Proposed ADR Monitoring System 1997 India Joined WHO ADR Monitoring Programme 2004 National Pharmacovigilance Programme launched in India 2010 Pharmacovigilance programme of India InitiatednN REFERENCE Elizabeth B. Andrews, Nicholas Moore. Mann’s Pharmacovigilance. 3™ Edition. Wiley Blackwell. 2014. Borton Cobert, Cobert’s Manual of Drug Safety and Pharmacovigilance, 2" Edition. Jones and Bartlett Learning, 2012. S. K. Gupta. Textbook of Pharmacovigilance. 2"! Edition. Jaypee Brothers Medical Publishers. 2019.THANK YOU