Magazine Article | September 29, 2011

5 Key Questions & Answers Regarding Pharmacovigilance

Source: Life Science Leader

A Q&A with Sanket Agrawal, executive director, global regulatory affairs and safety, at Amgen, and Nagaraja Srivatsan, senior VP, head of life sciences, North America, Cognizant Technology Solutions.

1. What are the key challenges concerning global regulatory/drug safety operations and the near-term policy changes/guidelines expected from THE FDA and other agencies?

Sanket Agrawal, Amgen: The industry’s key challenges in pharmacovigilance, in some ways, remain unchanged yet significantly more acute. We must remain focused on patient safety while dealing with evolving regulations, evolving science and understanding of disease and treatment, ever fewer resources, and ever more data. To exemplify, we must align with the changing regulatory focus on risk management plans (RMPs) and risk evaluation and mitigation strategies (REMS) while running transactional safety operations at the same level, retool/rehire to improve our collective understanding of disease biology and mechanisms of action to better anticipate safety outcomes, plan for rapid digitization and public availability of health data and social media content, and reduce budgetary spend in the PV (pharmacovigilance) departments. The PV function will respond, but it will also change more in the next few years than it has in the past three decades.

In terms of most impactful near-term regulatory changes, the recent FDA IND (investigational new drug) guidance materially affects the processes for ADR (acute drug reaction) reporting, but without greater international harmonization may divert resources away from analysis of data toward transactional reporting. The upcoming EU PV legislation also aims to shift greater emphasis toward generation and analysis of benefit/risk information rather than operations. However, this expectation, while welcome, is largely additive (i.e. current activities may not reduce materially). Reducing industry burden usually is a low priority, but we must not forget, additive requirements create the same resource gaps in regulatory agencies. We must allocate our combined yet finite resources effectively.

Nagaraja Srivatsan, Cognizant: The key industry challenges relate to the three fundamental components of drug safety:

  • detection of risks — comprehensive and continuous detection of risks
  • analysis and evaluation of risks — proactive analysis and evaluation of risks
  • management of risks, including risk communication — clear management and communication of risks.


The FDA and other regulatory agencies are working hard to ensure the safety and effectiveness of drugs and other medical products. The regulatory agencies’ objective is to strengthen existing pre- and postmarket drug safety processes and procedures. In order to achieve this, the pre- and postmarket components of drug safety must work together, creating a seamless flow and integration of information gathered during the discovery, preclinical, clinical, regulatory submission, and postmarketing process. Regulatory agencies are reevaluating their overall approach to risk management. The goal for the future is to ingrain safety throughout a drug’s entire period of use including the clinical phase. Ultimately it is the intent of the manufacturers and regulatory agencies to ensure that appropriate safety information specific to the products/classes are communicated to physicians and patients in a timely manner.

2. What are some best practices in developing a risk and compliance plan complete with clinical safety and postmarketing Pharmacovigilance information to meet regulatory requirements in an evolving global environment?

Sanket Agrawal, Amgen: I do not think there are “best” practices, only good practices. PV is not an island; it functions within a larger R&D and commercial ecosystem and hence, is innately tailored to each company’s products, pipeline, regulatory commitments, and culture. Of course, maintaining a single company database of all AE (adverse effects) data is a minimum beginning for completeness of safety data, both clinical and postmarketing. Other good practices include maintaining a common repository of PV regulatory requirements across the product life cycle. Given the criticality of this function and the high cost of failure, a comprehensive QMS (quality management system) is essential — quality plans, inspection readiness, accountable business process owners, and robust documentation and training. In the era of risk management, it is essential for the PV function to have clear traceability of global safety commitments and effectiveness of implemented risk minimization measures. An RMP is only the beginning.

Nagaraja Srivatsan, Cognizant: Drug safety and pharmacovigilance processes and systems have routinely been reactive rather than proactive. Now, however, consumers, physicians, payers, and regulators are demanding safer products and faster responses from the industry to address safety concerns. Additionally, regulators are requiring surveillance programs throughout a product’s life cycle. Some of the best practices are:

  • global process harmonization — ability to develop similar processes to help track, process, and report on drug safety issues from multiple geographies to multiple regulatory agencies
  • integrated PV/safety organizations, processes, and systems encompassing clinical operations and development, biostats, regulatory affairs, PR, and QA to manage all the above needs
  • governance to ensure seamless coordination with third parties such as CROs and other global partners
  • integration of clinical development and PV departments into executive management and reporting to ensure safety profiles/REMS are fed back to the clinical development design/protocol
  • reporting into the board level to ensure that strategic policies and procedures facilitate the oversight and management of the safety of products (ensure “License to operate”) and allow escalation of issues quickly and effectively, if required
  • oversight of the entire PV system (e.g. by an EU-qualified person or a global safety review committee with international leaders on board)
  • plans to implement the DSUR (development safety update report) to harmonize clinical safety reporting across ICH (International Conference On Harmonization) regions.


3. What are some of the key challenges to Developing proactive drug safety and pharmacovigilance programs, and what are your solutions?

Sanket Agrawal, Amgen: As an industry, our cost levers are few — simplification of processes, automation (tools), and using outsourcing/offshoring to reduce labor costs. The objectives, regulatory compliance, and patient safety remain unchanged. Thus, primarily we attempt ongoing reduction of cost-per-transaction in operations. For the most part, this rarely reduces overall cost, since savings are used to fund increased activities in areas such as risk management, REMS, and compliance. Technology continues to challenge us and remains an opportunity to unlock efficiency, but as an industry, our technology needs far exceed supplier offerings. Quite simply, it is a myth that we can increase efficiency, reduce cost, maintain quality, and improve compliance across the overall PV function.

Nagaraja Srivatsan, Cognizant:Key challenges continue to be that multiple regulatory agencies require different types of information to be tracked and reported within varying timelines. The processes are increasingly becoming divergent and complex. Systems and information silos proliferate across life sciences organizational functions and through the life cycle of the drug itself.

Some of the initiatives that organizations are embarking on include:

  • defining core versus context to select appropriate pharmacovigilance partners to outsource either end-to-end or selected activities across “case intake,” “case processing,” and “case reporting” functions
  • process standardization and harmonization — As the above functions are used to support not just the FDA, EMEA (European Medicines Agency), and MHS (military health system), drug safety operations need to be global where they process cases in a uniform manner, while at the same time accommodating minor variations to address local regulatory requirements, irrespective of where they originated for submission to multiple global agencies. This requires global templates that can be leveraged to standardize and harmonize processes.
  • global centers — leveraging the availability of qualified resources across the globe to truly have a nonstop processing of cases to ensure compliance with strict reporting timelines and safety exchange agreements with global licensing partners
  • build integrated systems — Currently all life sciences organizations have safety systems of record. Leading organizations are building safety repositories that combine current safety information with historical clinical and preclinical information and extend them to bring in information from claims processors as well as leverage market information to have a comprehensive set of information about the drug and its safety.
  • signal detection — organizations are leveraging these above integrated repositories to detect signals proactively
  • safety as copartner in clinical development — Finally, organizations are leveraging pharmacovigilance teams during protocol design to help enable design trials that are better suited for specific patient populations based on safety profiles.


4. Social media, global consortiums, etc. are being discussed as potential ways for communicating the policy changes, riskMAPs (risk minimization action plans), any drug groups related to safety recommendations, etc. Are you seeing an impact of these in the way operations are being managed?

Sanket Agrawal, Amgen: Not extensively yet. Social media channels, and regulatory guidance surrounding them are very nascent. Purely from a PV perspective, the “data” exhibits very high noise ratio and unclear relative value, compared to potential effort in finding actionable nuggets. I know many believe that high-quality data is sitting in these channels, just waiting to be plucked. I suspect otherwise. We have to be very mindful of any perception of promotional activity if the interaction were to be more than passive data mining. There is perhaps some value in incorporating some of these channels to better communicate with healthcare professionals who could, in turn, disseminate info to patients. For instance, product information, package insert, label, and new safety information may be reasonably communicated to HCPs (healthcare professionals) via mobile devices through a company’s MedInfo function or using a third-party service.

Nagaraja Srivatsan, Cognizant: A key aspect of drug safety is risk communication. Clear management and communication of risks is a key priority for regulatory agencies. Expanding safety communication and information flows is a major undertaking of the FDA. The agency is conducting a comprehensive review of current public communication tools, posting reviews of new drug applications, supplements, and assessments of postmarket safety studies. These emerging channels in the future can become ways of communicating drug safety information.

The current guidance from regulatory agencies and its interpretation by life sciences organizations are more conservative. Only approved information is communicated and discussed in these forums. In the future, the FDA and other agencies will have to modify their current policies and mandates to better leverage these new channels.

Even though these forums have brought similar disease patients together for some disease states and helped create a platform to exchange and discuss treatment regiments and safety, by and large the information discussed in these channels for medication is not yet reliable for a larger population.

With social media, DTC (direct-to-consumer) channels access, and availability of a plethora of information from so many sources, it is critical for patients to be proactive and rely on their physicians “right” information to ensure safety. The more complicated the disease and treatment, the more critical is the onus on patients to understand the communication channels and discriminate on the value of the information based on those channels.

5. What is the role of technology in providing better information, improving outcomes, and effective management of drug safety operations, especially the heightened need for real-time data analytics and insights?

Sanket Agrawal, Amgen: As I stated, technology has an important role in improving efficiency and capability, but reality lags behind promise and opportunity. For example, real-time analytics would be only as good as the data these systems could aggregate. The traditional silo approach to commercial life sciences software and general lack of interoperability standards make the task of safety operations difficult and cross-data analytics nearly pointless. I think innovation is sometimes hard to find or to get excited about because the industry is focused on making technology functional and cost-effective to operate. A simple business need, for example, is to be able to easily move or virtually integrate safety-related data between our various systems (e.g. clinical, toxicology, pharmacovigilance, observational, market research) so that we may generate or test novel hypotheses. This is nearly impossible to achieve today or even five years from now.

Nagaraja Srivatsan, Cognizant: Real-time data analytics and insights can help life sciences organizations use drug safety as a competitive differentiator. There is also an increasing need to prove comparative effectiveness of a drug. The need for having real-time data all through the drug life cycle is driven by the imperative to design drugs for specific patient populations, thus increasing their effectiveness and safety, leading to quicker approval and increased market share.

Innovative organizations are looking at the data continuum across the value chain, including not only premarket and postmarket, but also global. This enables them to view/connect signals early on and make appropriate decisions. Major organizations are reorganizing to ensure safety and clinical functions are reporting to a single leader to ensure that insight from drug safety is incorporated into future trial design on the safety analysis.

The industry is clearly evolving. There are leaders who are being proactive and strategic and some who are clearly burdened with just supporting the reporting requirements. In the coming years, there will be a difference between the leading life sciences organizations and those who have a more tactical approach in pharmacovigilance.