Pharmacovigilance - Opportunity to Differentiate
The journey of drugs from molecule to shelf is a long one indeed. This highly regulated process is designed to both foster innovation and also minimize risks. The journey does not end after clinical trials are complete and the drug approved. Drug manufacturers have a legal duty to track and report adverse events throughout the drug lifecycle. This process has two key components – to collect and manage data from various touch points on medicine safety and then to analyze this data to detect signals of potential risks or manufacturing issues with the drugs. Based on this information, appropriate decisions, recalls, regulatory notifications, etc. need to be issued.
While responsible drug manufacturers and pharma companies will provide spontaneous reporting of adverse events, and in fact, the global pharmacovigilance framework relies on this principle, applying Occam’s Razor, it is still important for national and international regulatory bodies to frame guidelines and mandatory reporting requirements for effective pharmacovigilance. The World Health Organization (WHO) runs a global International Drug Monitoring Programme, spanning 90 nations and recording adverse events, safety reports, etc., in the WHO International Database.
The European Union has recently adopted some legislative proposals to improve existing pharmacovigilance practices. While Regulation (EC) No 726/2004 currently governs pharmacovigilance, and existing guidelines in the ICH series detail out the conduct of pharmacovigilance procedures, this is a constantly evolving process. With increased healthcare costs and the need to ensure safe & effective medicines, there is a global push to improve stakeholder involvement in the pharmacovigilance process. It is estimated that adverse drug reactions cause 197,000 deaths each year in the EU.
The existing EudraVigilance network, managed by the European Medicines Agency (EMEA), is used to record adverse events during development and post-marketing of drugs. This system has been in existence since 2001, and there is a general consensus among stakeholders that the system, coupled with the complex existing regulations, does not facilitate the process of pharmacovigilance. There are many redundancies in the process and data accuracy is questionable. The roles of stakeholders are not well-defined, and there is insufficient focus on analysis of the risk profile data gathered.
At a high level, the proposals centre around centralizing all adverse reporting into Eudravigilance, enabling better access to this information, and to tackle counterfeiting of medicines. The proposals define clear roles and responsibilities for all stakeholders, ensure proper risk management and quality assurance throughout the drug lifecycle, and provide accurate, transparent communication.
These proposals are still to be legislated by the European Parliament and member states, but pharmaceutical companies should begin preparations for their implementation by taking a fresh look at their pharmacovigilance processes and systems. They will need to provide relevant information through a pharmacovigilance master file as part of new drug applications. They will also need to ensure risk management processes span the entire drug lifecycle and maintain a risk profile of drugs post-marketing approval. From a reporting perspective, the proposals greatly simplify the process by requiring only a single submission of adverse event reports to Eudravigilance rather than to agencies in individual member states. On the other hand, existing adverse event reporting systems are not engineered to collect reports directly from patients, relying more on intermediaries and service providers. Thus, companies can proactively establish convenient web portals or contact centers where patients can file reports that are then collated, validated, and processed through the same process as for more formal channels.
The cost of preventable ADRs within the EU is estimated to be €23.7 billion[i] and thus regulatory agencies like the EMEA are mandating proactive pharmacovigilance through Signal Detection, Pharmacovigilance plan in protocols and Product risk management plan. Pharma companies will need to move from their current focus on entry and capture of adverse events and shift to more proactive risk management & more “value-added”, efficient approach to data entry. Given that pharmacovigilance spends can be about 13% of total R&D spend[ii], optimal adverse event processing can be a cost driver and maximize efficiency.
Another innovative approach can be to outsource parts of the adverse event processing. While this is still subject to regulatory reviews and approvals, it can be an efficient way of allowing the company to focus on value added activities. In an internal survey, 30% of pharma companies were either considering or had begun outsourcing parts of their pharmacovigilance activities.
This space will see significant focus and innovation in coming years. Given its impact on internal and external stakeholders, it cannot be ignored and must be given strategic focus for a competitive edge, besides ensuring regulatory compliance.
