Pharmacovigilance Program of India: Recent Developments and Future Perspectives PDF

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/311161823 Pharmacovigilance Programme of India: Recent developments and future perspectives Article in Indian Journal of Pharmacology · November 2016 DOI: 10.4103/0253-7613.194855 CITATIO...

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/311161823 Pharmacovigilance Programme of India: Recent developments and future perspectives Article in Indian Journal of Pharmacology · November 2016 DOI: 10.4103/0253-7613.194855 CITATIONS READS 103 5,939 3 authors, including: Vivekanandan Kalaiselvan Prasad Thota Indian Pharmacopoeia Commission Ministry of Health & Family Welfare Government… Indian Pharmacopoeia Commission 140 PUBLICATIONS 1,479 CITATIONS 56 PUBLICATIONS 579 CITATIONS SEE PROFILE SEE PROFILE All content following this page was uploaded by Prasad Thota on 03 September 2019. The user has requested enhancement of the downloaded file. [Downloaded free from http://www.ijp-online.com on Tuesday, September 3, 2019, IP: 117.247.233.180] Educational Forum Access this article online Quick Response Code: Pharmacovigilance Programme of India: Recent developments and future perspectives Vivekanandan Kalaiselvan, Prasad Thota, Gyanendra Nath Singh1 Website: www.ijp‑online.com Abstract: DOI: 10.4103/0253-7613.194855 Promoting safe use of medicines is a priority of Indian Pharmacopoeia Commission that functions as the National Coordination Center (NCC) for Pharmacovigilance Programme of India (PvPI). One hundred and seventy‑nine adverse drug reactions (ADRs) monitoring centers currently report ADRs to NCC. Current India contribution to global safety database reaches 3% and the completeness score is 0.93 out of 1. NCC is taking several measures to enhance patient safety including capacity building for monitoring, surveillance, collaboration with national health programs and other organizations to increase ADR reporting and to ensure that PvPI is a vital knowledge database for Indian regulators. The Central Drugs Standard Control Organization has notified important safety label changes on drugs such as carbamazepine and piperacillin + tazobactam in the year 2015, other drugs are under monitoring for regulatory interventions. Key words: Adverse drug reaction reporting, patient safety, Pharmacovigilance Programme of India T he burden of adverse drug reactions (ADRs) in the global scenario is high and accounts for considerable morbidity, mortality, and monitoring of medicines as an integral part of clinical practice, the Ministry of Health and Family Welfare (MoHFW), Government of India extra‑cost to the patients.[1‑3] In England, 0.9% of launched the nationwide Pharmacovigilance the total hospital admissions were due to ADRs Programme of India (PvPI) in the year 2010 to during the year 1999–2008. ADRs are common inspire confidence and trust among patients in Australian healthcare system also and they and healthcare professionals with respect contribute to 1% of hospital admissions. In to medicines safety. Indian Pharmacopoeia the United States of America, ADRs contribute Commission (IPC) under the MoHFW has 3.4%–7% of hospital admissions. The percentage been functioning as the National Coordination of hospital admissions due to ADRs in certain Centre (NCC) for PvPI since April 2011. There countries is 10% or more.[7,8] India, with a current has been rapid progress in reporting of ADRs by National population of 1.27 billion, is the fourth largest the healthcare professionals in the past 5 years. Coordination Centre, producers of pharmaceuticals in the world Pharmacovigilance with more than 6000 licensed manufacturers Establishing the Culture of Adverse Programme of India, and over 60,000 branded formulations in the Drug Reaction Reporting Indian Pharmacopoeia market. Studies revealed that ADRs are leading Commission, to hospitalization and constitute a significant Currently, 179 Medical Council of India approved Ministry of Health economic burden on patients in India.[10‑12] A teaching hospitals and corporate hospitals and Family Welfare, study showed that hospital admissions due to have been identified as ADRs Monitoring 1 Pharmacovigilance ADRs accounted for 0.7% of total admissions Centers (AMCs) across the country. These centers Programme of India, and deaths due to ADRs accounted for 1.8% of are covered in four zonal offices of Central Indian Pharmacopoeia total admissions in a territory referral center in Drugs Standard Control Organization (CDSCO) Commission, Ministry South India. for administrative and logistic purpose. These of Health and Family AMCs are connected with international Welfare, Ghaziabad, Therefore, medicines safety monitoring networking (reporting through VigiFlow; Uttar Pradesh, India is an essential element of healthcare and WHO‑Uppsala Monitoring Centre [UMC] for high‑quality medical care. Since safety software). These AMCs report ADRs to NCC Address for correspondence: This is an open access article distributed under the terms of the Dr. Vivekanandan Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, Kalaiselvan, which allows others to remix, tweak, and build upon the work non- How to cite this article: Kalaiselvan V, Thota P, E‑mail: [email protected] commercially, as long as the author is credited and the new creations Singh GN. Pharmacovigilance Programme of India: are licensed under the identical terms. Recent developments and future perspectives. Indian Submission: 25‑01‑2016 J Pharmacol 2016;48:624-8. Accepted: 10‑11‑2016 For reprints contact: [email protected] 624 © 2016 Indian Journal of Pharmacology Published by Wolters Kluwer - Medknow [Downloaded free from http://www.ijp-online.com on Tuesday, September 3, 2019, IP: 117.247.233.180] Kalaiselvan, et al.: Pharmacovigilance Programme of India: Recent developments and future perspectives through VigiFlow, the software owned by WHO‑UMC, The cornerstones of pharmacovigilance apply equally to TB as (Sweden). The reluctance in reporting is now changing as to any other disease amenable to medication. Events linked to the PvPI has launched a complete roadmap for a proactive medications, particularly novel medicines or new combinations pharmacovigilance system which increases the awareness thereof, need to be recognized in a timely fashion if the events about the benefits of ADRs reporting. Over 5 years, the NCC are to provide benefit to the individual patient and the public. has played a significant role in creating awareness among Appropriate measures need to be put in place to ensure that harm healthcare professionals about reporting ADRs that saw more is reduced and symptoms relieved. Healthcare workers need to than 1,49,000 ADRs reported till December 2015 [Figure 1]. be informed and trained about the methodology and routes for Currently, the contribution of India to the WHO global reporting ADRs. Keeping this in view and to improve patient Individual Case Safety Reports (ICSRs) database is 3%. The care and safety in relation to the use of anti‑tubercular drugs, healthcare professionals are encouraged to report through RNTCP formally entered into collaboration with the PvPI on feedback and Newsletters. October 11, 2013. As a consequence, RNTCP staffs have attended IPC‑WHO national workshops on pharmacovigilance held in Completeness Score for Indian Individual Case the country. These programs are keen to customize trainings Safety Reports for RNTCP and take these activities further. UMC communicates the result of the documentation grading Integration of Pharmacovigilance Programme of for the ICSRs to the national centers. The report completeness India and National AIDS Control Organization score is a score from 0 to 1 on an ICSR, calculated from the information provided in a structured format. The score depends India has the third largest number of people living with HIV on the required information of the field in the ADR report in the world, 2.1 million at the end of 2013 and accounts for such as type of report, primary source, gender, and time to about 4 out of 10 people living with HIV in the region, in India, onset, age at onset, outcome, indication, and free text. Average the numbers of new HIV infections declined by 19%, yet it still completeness score for Indian ICSRs for the period of 2011–2015 accounted for 38% of all new HIV infections in the region. India is illustrated in Figure 2. recorded a 38% decline in AIDS‑related deaths between 2005 and 2013. During this period, there was a major scale‑up of Integration of Pharmacovigilance Programme of access to HIV treatment. At the end of 2013, more than 700,000 India and Revised National Tuberculosis Control people were on antiretroviral therapy (ART), the second largest Program number of people on treatment in any single country. During last 5 years, there were 11 ART fixed drug combination were The monitoring of safety of medicines used in national health approved for manufacturing in India. To ensure the safety programs has been identified as a matter of concern. The safety of antiretroviral (ARV) medicines used in the program, IPC, issues are apparent in the use of medicines for the treatment NCC‑PvPI, and National AIDS Control Organization formally of malaria, tuberculosis (TB), HIV, etc., Since inception, the agreed to collaborate on September 15, 2014, for setting up Revised National Tuberculosis Programme (RNTCP), one systems and processes for reporting, analysis, and monitoring of the largest public health programs in India, has evaluated of ADRs due to ARV medicines used in NACP. over 70 million persons of TB and initiated treatment for over 17 million TB patients. A diagnosed TB patient on Collaboration with Adverse Events Following treatment under RNTCP takes more than one anti‑tubercular Immunization drug simultaneously with regimens lasting from 6 months to 2 years or more. This increases the likelihood of ADRs, some of NCC‑PvPI is assisting with adverse events following which may be severe. The overall burden of adversity directly immunization (AEFI) at Immunization Technical Support attributable to anti‑TB medicines, that is, mortality, morbidity, and reduced quality of life, is poorly documented in published literature and by the national program. 1 0.9 No. of Individual Case Safety Reports 0.8 160000 Completeness Score 0.7 140000 149607 0.6 Quarter1 120000 0.5 Quarter2 No. of ICSRs 100000 109638 Quarter3 0.4 80000 Quarter4 0.3 60000 68680 0.2 40000 40809 0.1 20000 17880 0 0 3215 2011 2012 2013 2014 2015 2010 2011 2012 2013 2014 2015 Figure 1: Growth of database of Individual Case Safety Reports since the inception Figure 2: WHO‑Uppsala Monitoring Centre completeness score for Indian of the Pharmacovigilance Programme of India Individual Case Safety Reports from the year 2011‑2015 Indian Journal of Pharmacology ‑ Vol 48, Issue 6, December 2016 625 [Downloaded free from http://www.ijp-online.com on Tuesday, September 3, 2019, IP: 117.247.233.180] Kalaiselvan, et al.: Pharmacovigilance Programme of India: Recent developments and future perspectives Unit (ITSU) which has been set up by MoHFW with Public PvPI. The role of NCC in collaboration with other national Health Foundation of India to ensure the vaccine safety. AEFI and international organizations to promote patients safety is cases which are reported to NCC are shared with ITSU on illustrated in Figure 3. regular basis for further necessary action. To bridge the gap among PvPI, AEFI, CDSCO, and other stakeholders NCC Education and Training on Pharmacovigilance at published an exclusive issue of “PvPI Newsletter (volume Regional Training Centers 3; issue 5 2013).” The NCC officials/coordinators at AMCs participated in all AEFI workshops. A primary objective of NCC‑PvPI is to promote the safest use of medicines through contributing to appropriate education in Collaborations with Central Drugs Standard Control pharmacovigilance and training activities across the country. Organization The NCC identified nine Regional Training Centers (RTCs) such as JSS Medical College, Mysore; Seth GS Medical ADR monitoring and reporting to national regulatory College and KEM Hospital, Mumbai; Postgraduate Institute authority are put in place in many countries. In India, PvPI of Medical Education and Research, Chandigarh; Institute is closely working with CDSCO, drug regulatory authority of Post Graduate Medical Education and Research, Kolkata; of India. CDSCO understands that pharmacovigilance plays All India Institute of Medical Sciences, Bhopal; B. J. Medical a specialized and pivotal role in ensuring ongoing safety of College, Ahmedabad; Silchar Medical College and Hospital; medicinal products in India and it seeks inputs from NCC All India Institute of Medical Sciences, Rishikesh; and Nizam’s before taking any kind of regulatory decisions. NCC‑PvPI is Institute of Medical Sciences, Hyderabad. These centers working in close coordination with CDSCO zonal offices also provide continual training to the personnel at AMC of their for technical, administrative, and logistics matters related to respective regions.  Take appropriate regulatory decision and actions on the basis of recommendations made by NCC.  Propagate medicine safety related decisions to stakeholders.  PvPI launched  Provide administrative support to run PVPI. under MoHFW, Govt of India and provide financial support to run the programme effectively. CDSCO  To ensure the safety of Headquarter, vaccines. New Delhi  To monitor safety AEFI and MoHFW, ITSU, of medicines used Government MoHFW in these programs of India  To promote and establish Cohort Event Monitoring and Target Spontaneous Reporting in India. Indian NIB, Pharmacopoeia MoHFW, National Commission Noida Health NCC-PvPI, Programs  To track adverse reactions and incidences  To organise training associated programs for stakeholders. Uppsala with blood and Monitoring blood WHO-India Centre, products. (Country Sweden Adverse Office) Drug Reaction Monitoring Centres  To participate in International Drug Monitoring Programme  Monitoring and and contributing in reporting ADRs. global safety database. Figure 3: Coordination of Indian Pharmacopoeia Commission with other organizations 626 Indian Journal of Pharmacology ‑ Vol 48, Issue 6, December 2016 [Downloaded free from http://www.ijp-online.com on Tuesday, September 3, 2019, IP: 117.247.233.180] Kalaiselvan, et al.: Pharmacovigilance Programme of India: Recent developments and future perspectives Communications facilitator for promoting public health. India is cementing its place IT sector through mobile connections to reach every NCC is committed to communicate the findings of PvPI to individual in a population of 1.27 billion where approximately stakeholders and public with respect to importance of ADRs 77.58% population is already using mobile phones. Hence, it is and reporting them, information about benefit‑harm and more rationale to introduce the concept of PvPI to stakeholders effectiveness‑risk, rational use of medicines, etc. A variety of through mobile phones. NCC‑PvPI in technical collaboration methods for PvPI communication is used by NCC as follows. with NSCB Medical College, Jabalpur, developed a mobile application for the healthcare professionals to promote easy Website and instant reporting of ADR. This facility was launched by The websites of CDSCO (www.cdsco.nic.in) and NCC (www. Secretary Health, MoHFW, Government of India, on May 22, ipc.gov.in) are important tools for communication to the 2015. stakeholders and public seeking specific information. PvPI documents on these websites can be searched by navigating Utilization of Periodic Safety Update Reports from the home page. Examples of documents on these websites Reporting include list of AMCs, how, what, and where to report ADRs, newsletters, training module, guidance document, etc. Periodic safety update reports (PSURs) are a tool to monitor the safety of ongoing medicines in the market. In India, marketing Media authorization holders (MAHs) are required to prepare PSURs Since medicines safety communications with healthcare and to submit them to CDSCO twice in a year for 2 years and professionals, patients, and the general public must be focused annually for another 2 years. Since PSURs are not directly on joint responsibility for safe and rational therapy, NCC linked with PvPI, NCC has taken the initiatives in collaboration communicates the findings in national newspapers, electronic with CDSCO to utilize the data for PvPI. The first interactive media, etc., on regular basis. session on “Review of Periodic Safety Update Report/Post Marketing Surveillance Data and Pharmacovigilance Planning Newsletter of Marketed Products” was held on December 18 and 19, 2013 PvPI Newsletter is unique among healthcare professionals at New Delhi. Representatives from MAHs, CDSCO, and because it focuses on the ADRs‑related informations. Three NCC‑PvPI were participated and discussed the issues and issues per year guides how to take a leading role in monitoring, roadmap for better coordination and participation of MAHs reporting, and preventing ADRs. It is available in a convenient in PvPI. electronic format and printed version is circulated to AMCs, corporate hospitals, academic institutions, health departments, Availability of Medicine Side Effect Reporting Form etc. for Consumers in Different Vernacular Languages Scientific Journals Patients or consumers are the end users of pharmaceutical NCC publishes original and review articles on PvPI in national products, to ensure the safe use of them is the ultimate goal and international journals.[14‑25] of pharmacovigilance activities. In an increasing number of countries, patients are now allowed to report ADRs to Helpline Facility to Provide Assistance in Adverse the spontaneous reporting system.[18-20,26,27] Option of ADRs Drug Reaction Reporting reporting by patients to PvPI was started at NCC‑PvPI on August 1, 2014. Patient or his/her representative (relative) are To enhance the participation of patients, healthcare encouraged to report ADRs either directly to the NCC‑PvPI professionals, and the pharmaceutical industry in enhancing through toll free helpline number: 1800‑180‑3024 or E‑mail medicines safety by reporting suspected ADRs to the id: [email protected] or to their nearest AMC under PvPI, NCC recently launched a helpline number (toll free), PvPI by submitting “Medicines Side Effect Reporting form i.e., 1800 180 3024 facility for reporting adverse events. This for Consumers” (blue form) which can be downloaded from facility was dedicated to the nation on October 11, 2013. This the official website of IPC www.ipc.gov.in and by the end of may be one of the innovative methods to create awareness and 2015, this form is available in ten vernacular languages such as to reach every corner of the country for the pharmacovigilance Hindi, Kannada, Malayalam, Assamese, Bengali, Odiya, Tamil, activity. This facility will be useful for the healthcare Telugu, Gujarati, and Marathi. professionals those who are working in tertiary healthcare system to report ADRs. Adverse events‑related information Future Perspectives which received at NCC will be communicated to nearest AMCs for validating the reports. Since sending timely feedback or NCC has mandated the RTCs to organize advance level training acknowledgement will build public confidence recently this for the personnel’s of all AMCs under their respective regions facility has been upgraded by sending short message service and one CME in pharmacovigilance at an AMC under their feedback/acknowledgment to the ADRs reporters. region to increase the awareness of healthcare professionals about the ADR reporting. In near future, all Medical Council Android Mobile Application for Adverse Drug of India approved institutions will be enrolled under the PvPI. Reaction Reporting As IPC was recognized as the WHO Collaborating Center for medicines and vaccine safety in the South East Asia region In developing countries such as India, under‑reporting of during 38th Annual Meeting of National Pharmacovigilance ADR remains serious concern. In India, IT is becoming a great Centers participating in the WHO program for international Indian Journal of Pharmacology ‑ Vol 48, Issue 6, December 2016 627 [Downloaded free from http://www.ijp-online.com on Tuesday, September 3, 2019, IP: 117.247.233.180] Kalaiselvan, et al.: Pharmacovigilance Programme of India: Recent developments and future perspectives drug monitoring, plan to initiate, and coordinate with countries Gogtay NJ. Evaluation of the prevalence and economic burden in South East Asia region for potential signals from the built of adverse drug reactions presenting to the medical emergency safety database. NCC is in a process of developing and department of a tertiary referral centre: A prospective study. BMC promoting an effective channel for ADRs reporting such as Clin Pharmacol 2007;7:8. online reporting system. 11. Raut A, Diwan A, Patel C, Patel P, Pawar A. Incidence, severity and financial burden associated with adverse drug reactions in medicine inpatients. Asian J Pharm Clin Res 2011;4:103‑11. Conclusion 12. Khan FA, Nizamuddin S, Najmul H, Mishra H. A prospective study on prevalence of adverse drug reactions due to antibiotics ADRs reporting through PvPI improved with the measures usage in otolaryngology department of a tertiary care hospital in such as education, training, and provision of technical North India. Int J Basic Clin Pharmacol 2013;2:548‑53. assistance. The PvPI is a vital knowledge databases for Indian 13. Ramesh M, Pandit J, Parthasarathi G. Adverse drug reactions drug regulation. The CDSCO has notified important safety label in a south Indian hospital – Their severity and cost involved. changes for carbamazepine and piperacillin + tazobactam in Pharmacoepidemiol Drug Saf 2003;12:687‑92. the year 2015. The PvPI plans to expand its scope of activities 14. Kalaiselvan V, Prakash J, Singh GN. Pharmacovigilance to widen its reach to other healthcare professionals and to programme of India. Arch Pharm Pract 2012;3:229‑32. strengthen measures for capacity building. 15. Prasad T, Kalaiselvan V, Jai P, Suinder S, Gyanendra Nath S. Weight gain in association with insulin use‑an analysis of Individual Case Acknowledgment Safety Reports in Indian database. J Pharmacovigil 2014;2:119. We are thankful to MoHFW, Government of India, for the 16. Iftekar H, Kalaiselvan V, Gyanendra NS. Efficacy and safety of vildagliptin in the management of type 2 diabetes mellitus. Indian administrative and financial support. We are also thankful to J Pharm Pract 2012;5:8‑15. all the stakeholders of PvPI for their contributions. 17. Sainul Abideen P, Chandrasekaran K, Maheshwaran U, Vijayakumar A, Kalaiselvan V, Mishra P, et al. Implementation Financial Support and Sponsorship of self reporting pharmacovigilance in anti tubercular therapy Nil. using knowledge based approach. J Pharmacovigil 2013;1:1‑5. 18. Kalaiselvan V, Prasad T, Bisht A, Singh S, Singh GN. Adverse drug Conflicts of Interest reactions reporting culture in Pharmacovigilance Programme of There are no conflicts of interest. India. Indian J Med Res 2014;140:563‑4. 19. Kalaiselvan V, Prasad T, Singh A. Current status of adverse References drug reactions monitoring centres under pharmacovigilance programme of India. Indian J Pharm Pract 2014;7:19‑22. 1. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, 20. Kalaiselvan V, Sharma S, Singh GN. Adverse reactions to contrast et al. Adverse drug reactions as cause of admission to hospital: media: An analysis of spontaneous reports in the database of the Prospective analysis of 18 820 patients. BMJ 2004;329:15‑9. pharmacovigilance programme of India. Drug Saf 2014;37:703‑10. 2. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, 21. Kalaiselvan V, Gakhar S, Prasad T, Gupta SK, Singh GN. Pirmohamed M. 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