Pharmacovigilance is all about identifying, assessing, understanding and preventing adverse drug reactions. To do that effectively, biopharma companies need to screen the signals that could lead to an adverse reaction. Signal management relates to the safety information we gather from variety of sources, including spontaneous reports, clinical studies and scientific literature, which are potentially caused by a medicine and warrant further investigation, to confirm new adverse reactions or changes to known risks causally associated to this medicine. 

Proactively detecting signals for the identification of risks related to a drug is essential for the patients’ safety and can have significant impact on the drug’s marketing status. Approximately 40 percent of the confirmed signals managed by the European Medicine Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) in 2014 resulted in changes to the product information, including distribution of Direct Healthcare Professional Communications (DHPCs). And in 2013, 50 percent of all signals reviewed resulted in changes in labeling. In the EU, transparency, compliance and quality are critical elements of the pharmacovigilance (PV) legislation. In the U.S., the Food and Drug Administration continues to expect strong and swift signal detection and analysis throughout a product’s lifecycle.

We are also seeing an increasing focus by inspectors on the way companies are organized around signal management, which means the requirement to properly plan, track and manage, and take action upon signals has never been greater. Whether a company holds one or more product licenses, a fit-for-purpose clear and transparent safety signal management system that is fully integrated in an IT solution is core to the success of any PV program.

Yet biopharma companies may fall short with their current signal management systems, usually for one of three reasons:

  1. They lack the resources, especially those which PV expertise, and/or time to perform regular and periodic signal detection activities for all of the products in their portfolio. These issues puts biopharma companies at risk of non-compliance towards health authority regulations, as well as creates opportunities for delay in the detection of signals, which ultimately puts the patients’ safety at risk.

  2. Companies lack a validated, audit-trailed tracking system for their signal management activities, instead relying on manual tracking and spreadsheets. Not having a reliable system puts biopharma at risk of non-compliance with health authority regulations. It also makes it more complicated to keep track of safety issues, and to compile data for inspections, audits, and Periodic Safety Update Report (PSUR) preparation.

  3. Companies forget to perform signal detection on multiple sources. Often, signal detection includes only the review of data coming from the company’s safety database. However, other sources should be included in the review for this process to be thorough, including weekly literature screening, review of data from Health Authority websites (e.g. PRAC, FDA, MHRA), Eudravigilance and external data sources like FAERS and Vigibase. This is especially important for generic products when the primary safety data often comes from the public domain (e.g.. literature, innovation label, health authority requests for products in the same drug class).

Biopharma companies need to have the right tools, processes, and leadership in place to make sure their signal management processes are consistent and effective. Here’s what that looks like:

  • Technology: Regardless of whether a product has an established safety profile or requires more risk management planning, companies will maximize their compliance by implementing an automated IT-validated signal management system. An ideal system will include an audit trail and systematic tracking capabilities, scheduling of signal detection runs, tracking of signal detection outcomes (including documentation and link to source documents), tracking of signals (decisions, status, due dates, risk minimization measures, implementation), and report generation capabilities.

  • Processes: PV regulations for signal management are stringent but well defined across guidelines. While a signal management process will always include uniform steps for signal detection, validation, evaluation and recommendation for action, the approach towards each of these steps may differ among companies and products. It is important that the company allows this flexibility (e.g., signaling strategy) without needing to deviate from its standard operating procedures.

  • Leadership: Because safety issues may compromise marketing authorization of products that are not well managed, it is of the utmost important that the right stakeholders are included and consulted in signal management decision-making. Depending on the size of the company, the decision-making body may be unique for all products, or there may be a dedicated safety management team for each product. As signal management has implications across departments, the governance body would ideally be a cross-functional team that includes PV, medics, epidemiologists, biostatisticians, regulatory, and labeling.
Topics in this blog post: Biopharma, EMA, FDA, Regulatory Environment