Status: Final
Date: March 2005
Target Audience: Drug sponsors and applicants
This document provides guidance to the industry on good pharmacovigilance practices and pharmacoepidemiologic assessment of observational data regarding drugs, including biological drug products (excluding blood and blood components). Specifically, it provides guidance on safety signal identification, pharmacoepidemiologic assessment and safety signal interpretation, and pharmacovigilance plan development.
Risk assessment and risk minimization form what FDA calls risk management. Risk management is the process of assessing a product’s benefit-risk balance, developing and implementing tools to minimize its risks while preserving its benefits, evaluating tool effectiveness and reassessing the benefit-risk balance, and making adjustments, as appropriate, to the risk minimization tools to further improve the benefit-risk balance. This four part process should be continuous throughout a product’s life-cycle, with the results informing the sponsor’s decisions regarding risk minimization.
Risk assessment during product development should be conducted thoroughly; however, it is impossible to identify all safety concerns during clinical trials. Once a product is marketed, there is generally a large increase in the number of patients exposed, including those with co-morbid conditions and those being treated with concomitant medical products. Therefore, post-marketing safety data collection and risk assessment based on observational data are critical for evaluating and characterizing a product’s risk and for making informed decisions on risk minimization.
This guidance focuses on pharmacovigilance activities in the post-approval period. The term pharmacovigilance here means all scientific and data gathering activities relating to the detection, assessment, and understanding of adverse events, including the use of pharmacoepidemiologic studies. The goal is to identify adverse events and understanding, where possible, their nature, frequency, and potential risk factors.
Pharmacovigilance involves the identification and evaluation of safety signals. Here, safety signal refers to a concern about an excess of adverse events compared to what would be expected to be associated with a product’s use.
Safety signals warranting additional investigation can be further evaluated through carefully designed non-randomized observational studies of the product’s use in the “real world.” Pharmacoepidemiologic studies are often initiated when a safety signal has been identified after approval. The results of these studies may be used to characterize one or more safety signals associated with a product, or may examine the natural history of a disease or drug utilization patterns. Sponsors can initiate pharmacoepidemiologic studies at any time.
Resulting Recommendations:
(Developing a Pharmacovigilance Plan)
In certain limited instances, unusual safety risks may become evident after a product is marketed that could suggest that consideration by the sponsor of a pharmacovigilance plan may be appropriate. A pharmacovigilance plan is a plan developed by a sponsor that is focused on detecting new safety risks and/or evaluating already identified safety risks. The development of such a plan may be useful at the time of product launch or when a safety risk is identified during product marketing.
Pharmacovigilance plans have proven appropriate for products with which serious safety risks have been identified pre or post approval, or for at-risk populations that have not been adequately studied.
For more information on this issue, contact the Kulkarni Law Firm.