Though the Pharmacovigilance Programme of India (PvPI) has come a long way in bringing the pharmacovigilance to the forefront of drug safety in the country, lack of clarity of regulations, absence of quality metrics and limited guidance availability are affecting pharma industry's compliance to PvPI, according to experts.
Although there is sufficient pharmacovigilance expertise in the country, only a very little of it is being utilized for Indian pharmacovigilance. Existing expertise is limited to collection and networking of data. Developing PV expertise in signal generation, system management along with capacity building at all levels in line with global standards should be focused upon to improve PvPI outcome, said Dr J Vijay Venkatraman, managing director & CEO, Oviya MedSafe – a pharmacovigilance consulting firm.
“This approach will help do away with the excessive dependence on Uppsala Monitoring Centre's database. Besides this, a slew of steps need to be adopted to strengthen PvPI including collaboration with global regulatory agencies viz. PMDA, US FDA, EMA, clearly defined responsibilities among governmental agencies, encouraging ADR reporting through social media, providing enforcement powers to IPC to ensure PV compliance and so on”, he added.
Though pharma industry has been encouraged to submit ADRs due to their pharmaceutical products to Indian Pharmacopoeia Commission (IPC), NCC-PvPI in xml-E2B format since 2015, there is hardly any mechanism for PvPI to provide feedback to the industry on their adverse drug reaction (ADR) data. The PvPI received encouraging response from the industry whose contribution to it was around 19 per cent of the total reports received by PvPI.
The PvPI also needs to come out with a framework to do away with ambiguity in ADR reporting by industry. At present it is not clear if a system exists within PvPI to rein in duplication of ADR reports related to a pharmaceutical product coming from a pharma company as well as healthcare professionals.
Evolution of regulations
Till March 2016 India did not have any regulation making it compulsory for pharma company to put in place pharmacovigilance system. Taking advantage of it, most of the drug makers have not set up pharmacovigilance unit.
On March 8, 2016, Union health ministry issued the draft notification on post marketing surveillance of pharmaceutical products in India. The ministry notified that the companies shall have a PV system in place for collecting, processing and forwarding the report to the licensing authority for information on ADRs emerging from the use of drug manufactured or marketed by the pharmaceutical companies in India.
The notification lacked clarity to make it implementable by the pharma industry.
Hence a 15-member committee representing 60 pharmaceutical companies was set up with Dr Jamal Anwar Baig, country head, pharmacovigilance, Merck Sharp & Dohme as point of contact to suggest measures to be adopted to ensure smooth implementation of regulation of post marketing surveillance of pharmaceutical products.
The committee submitted its suggestions to IPC in November 2016. The committee's suggestions were forwarded to CDSCO by IPC to look into it.
The panel in its report recommended for setting of pharmacovigilance system at each pharma manufacturing unit which will collect, process and forward report to the licensing authority for information on adverse drug reactions (ADRs) emerging from the use of the drug manufactured or marketed by the company in the country.
It further suggested appointing trained medical officer, pharmacist to handle pharmacovigilance system who will be responsible for collection and analysis of ADR report. It also suggested training module to educate field force i.e. medical representatives to report ADRs.
Besides this, the committee suggested making it compulsory for pharma industry to conduct third party audit of pharmacovigilance system. It also proposed that it should be made compulsory for marketing authorisation holders and license holders manufacturing products in India to submit risk management plan to ensure drug safety at par with EU, USA.
“Our recommendations are aligned with draft regulation of post marketing pharmacovigilance issued in March 2016”, said Dr Baig.
Once CDSCO comes out with new guidelines, pharma companies will be forced to put in place pharmacovilance system thereby increasing ADR reporting in the country, he added.
The government needs to make it mandatory for pharmaceutical companies to have pharmacovigilance (PV) audit to ensure patient safety and good pharmacovigilance practices (GPvP), stated Moin Don, a leading pharmacovigilance expert and chief executive officer & founder of PVCON Consulting Services.
PV audit is a critical review and analysis of the compliance with global and local regulation, internal Standard Operating Procedures (SOPs), contracts/agreements of the systems supporting the monitoring of adverse events and signal detection. The aim of the audit is to provide assurance that the internal PV and related systems are robust to protect patient safety. PV audit has become legal requirement in European Union, USA and other regulated markets. Pharma companies exporting products to these markets are required to conduct audit of pharmacovigilance system regularly, said Don, who is closely associated with government of India’s National Pharmacovigilance Programme as Advisor and Trainer for DCGI & PVPI staff and has also been a trainer for Uppasala Monitoring Centre’s PV Workshop in Asia Pacific region.
As of now India does not have such requirements. However Indian drug regulatory agency CDSCO, IPC have drafted good pharmacovigilance practice guidelines mandating PV inspection of stakeholders especially market authorisation holders, responsible for marketing drugs in India by drug regulatory agency. The good pharmacovigilance practice guidelines are yet to be implemented, he said.
In the absence of binding requirements, it's very difficult to ensure industry compliance with good pharmacovigilance practices, he opined.
Currently PV audits are conducted by big pharma companies. They have quality and assurance department conducting internal PV audit. Other pharma companies lacking quality and assurance function, generally outsource PV audit to consultants who are PV auditors.
Once the GPvP guidelines are implemented, there would be a big leap forward in implementing and practising pharmacovigilance activities in India.
When asked small and mid size companies facing challenges in implementing PV activities, he said “Small companies can start with PV activity with 2-3 persons without a database. It's essential to have SOPs and to train your people in SOPs especially marketing support. The companies can then start getting ADRs from doctors, prescribers, medical representatives. Gradually companies can develop robust pharmacovigilance system.”
IPC initiatives
IPC is taking several measures to enhance patient safety including capacity building for monitoring, surveillance, collaboration with national health programmes and other organizations to increase ADR reporting and to ensure that PvPI is a vital knowledge database for Indian regulators. The CDSCO 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.
IPC has launched a toll free number facility, mobile application for the healthcare professionals and public to report ADRs. It also launched consumer reporting forms in 10 regional languages to promote consumer involvement in reporting ADR.
In order to get pan India ADR information, government is planning to roll out the pharmacovigilance programme at district level hospitals in a couple of months time. IPC is in the process of identifying 20 new adverse drug monitoring centres (AMCs) under PvPI at district level healthcare institutions.
Special thrust will be given to identify AMCs that had no ADR centres from the existing set of 210 AMCs in the country.
To further widen the scope of PvPI and strengthen evidence based information, government had also upgraded 10 per cent of its technical data associates (TDA) last year to the cadre of senior technical data associates working in over 100 AMCs across the country under PvPI.
So far 210 ADR monitoring centres have been inducted under the PvPI which have reported 2.5 lakh adverse drug reaction cases to WHO monitoring centre at Uppsala.
ADR data vital for drug safety
India has a vast population that exhibits genetic and ethnic variability, there also exists a vast variation in disease prevalence. The ADR data so generated will help to make vital policy decisions regarding safe use of medicines in Indian population.
A vast population in the country is yet to be covered under the drug safety programme which was initiated in July 2010 by Central Drugs Standard Control Organization (CDSCO) under the aegis of Ministry of Health & Family Welfare (MoHFW), at the All India Institute of Medical Sciences (AIIMS), New Delhi as the National Coordinating Centre (NCC) to safeguard health of Indian population. On April 15, 2011, the NCC was shifted from AIIMS to Indian Pharmacopoeia Commission (IPC) which has gained recognition as the first WHO collaborating centre for safety of medicines and vaccines in South East Asia region.
ADR monitoring centres comprising of Revised National Tuberculosis Control Programme (RNTCP) centres, Antiretroviral therapy (ART) and Bedaquiline centres, ADR centres at medical colleges, public and private hospitals are mostly located in urban areas covering only 20 per cent of the target population. Technical associates (TAs) at ADRs monitoring centres (AMCs) collect information from the patients, perform follow-up with them, enter information in the prescribed format and send them to the headquarters.
Medical colleges and health facilities in rural areas need to be encouraged to have ADR monitoring centres for patient safety reporting which helps identify and analyse risk benefit ratio of marketed medicines, generate evidence on safety of medicines and support regulatory agencies in decision making, said Prof C Ramesh of IIHMR University, Jaipur.
In a bid to sensitise budding pharmacists about ADR reporting, pharmacovigilance will be made part of final year curriculum of B Pharm course and M Pharm course by academic year 2018-19.
It will improve ADR reporting by pharmacists in PvPI and will lead to better patient care.
Pharmacy Council of India (PCI) has included pharmacovigilance subject in B Pharm and M Pharm syllabus, put on its website last August. It will be conducted by PCI approved pharmacy colleges from academic year 2018-19, said PCI president B Suresh.
Though pharmacovigilance is part of semester VIII of B Pharma course, it deals with basics of pharmacovigilance. Thorough approach of pharmacists towards pharmacovigilance needs to be developed to encourage ADR reporting. The latest move by PCI to include pharmacovigilance as a subject in B Pharm and M Pharm courses will increase pharmacy students' understanding of pharmacovigilance and subsequently improve their perception on ADR reporting.