Risk Management Guidances

RISK MANAGEMENT GUIDANCES

The Prescription Drug User Fee Act of 2003 (PDUFA III )specifically addressed risk management, noting that efficient risk management as one of FDA’s five strategic goals, including both the new drug review process and oversight after approval. Acknowledg-ing that it is impossible at the time of approval to know everything about a medicine’s safety, PDUFA III mandated that there be increased surveillance of the safety of medicines during their first 2 years on the market (or first 3 years for drugs with potentially seri-ous safety concerns identified at the time of approval). The FDA also agreed to develop regulatory strategies and guidance documents on risk management. Three guidance documents were developed with input from the public and industry. These guidances, summa-rized below, were published as final documents in March 2005.

Due to its relevance to this chapter, the ‘Guidance on Good Pharmacovigilance Practices and Pharma-coepidemiologic Assessment’ is provided in full at the end of this chapter.

GUIDANCE ON PRE-MARKETING RISK ASSESSMENT

This regulatory guidance focuses on approaches a industry might consider throughout all stages of the clinical development of products. Some key compo-nents of the guidance include specific recommendations to industry for improv-ing the assessment and reporting of safety during drug development trials;

·   improving the assessment of important safety issues during registration trials and to provide best practices for analyzing and reporting data that are developed as a result of a careful pre-approval safety evaluation and

·   building on (but not superceding) a number of existing FDA and ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) guidances related to pre-approval safety assessments.

GUIDANCE ON DEVELOPMENT AND USE OF RISK MINIMIZATION ACTION PLANS

This guidance provides a conceptual framework on the development, implementation and evaluation of risk minimization action plans for prescription drug and biological products. It focuses on (1) initiating and designing plans called risk minimization action plans or RiskMAPs to minimize identified product risks, (2) selecting and developing tools to minimize those risks, (3) evaluating RiskMAPs and monitoring tools, (4) communicating with FDA about RiskMAPs, and (5) the recommended components of a RiskMAP submission to FDA. Table 43.1 provides recent exam-ples of drug RiskMAPs and tools to minimize risks.

GUIDANCE ON GOOD PHARMACOVIGILANCE PRACTICES AND PHARMACOEPIDEMIOLOGIC ASSESSMENT

This guidance document focuses on pharmacovig-ilance activities in the post-approval period. Phar-macovigilance is defined to mean all scientific and data gathering activities relating to the detection, assessment and understanding of adverse events. This includes the use of pharmacoepidemiologic studies. These activities are undertaken with the goal of identi-fying adverse events and understanding, to the extent possible, their nature, frequency and potential risk factors.

CONCLUSIONS

Pharmaceutical risk management faces important challenges in addressing innovative therapies, public expectations of product safety and optimizing patient selection to better minimize adverse outcomes. Regu-latory pharmacovigilence activities have a criti-cal role in assuring product safety by means of proactively designing and implementing interven-tions to minimize a product’s risks. Pharmacovig-ilence also provides a framework for evaluating these interventions in light of new knowledge that is acquired over time and revising interventions when appropriate.