Director, Regulatory Affairs Gilead Sciences, Inc. Foster City, California, United States
Toxicology data and principles are utilized by Industry to derive safe, allowable levels for impurities in drug substances and drug products. While the process for deriving certain allowable levels remains poorly described in regulatory guidance (i.e. nitrosamines) other classes of impurities have generally accepted methodologies (structurally-related and potentially mutagenic impurities) which are routinely implemented and described in regulatory guidance(s). This presentation will explore how impurity control strategies are developed based on manufacturing process understanding and knowledge of safe allowable levels for impurities, and how control strategies may differ based on impurity type (nitrosamines, structurally-related, or potentially mutagenic impurities). This presentation will elaborate on how the derived safe allowable levels for impurities inform the justification of specifications for drug substances and products. The impact of changes to dosing regimes on impurity control strategies with respect to acceptable levels for impurities will be described. Strategies for the appropriate timing of key toxicology assessments and in vitro/in vivo testing and their impact to CMC strategy will be highlighted through case studies.
