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Safety concerns regarding known or suspected genotoxic impurities in pharmaceutical products have become more prominent in the last decade. When regulators identified concerns, delays often occurred in pharmaceutical development programs, at least partially due to the lack of consistent regulatory guidance. The Committee for Medicinal Products for Human Use (CHMP) of the EMEA and the Center for Drug Evaluation and Research (CDER) of the US FDA subsequently released guidance (final and draft, respectively) on how best to deal with these impurities in 2006 and 2008. The recommendations include the use of toxicological thresholds as one acceptable approach for setting acceptable daily exposure levels. The recommended thresholds are based on a previous Threshold of Regulation approach developed by US FDA’s Center for Food Safety and Nutrition for food contact materials set on the determination of a virtually safe dose derived from a carcinogenic potency data base. This session will discuss the derivation of the TTC by the CHMP and CDER and will describe how the TTC is applied to the regulation of genotoxic impurites in pharmaceutical products. [ABSTRACT FROM AUTHOR]

The requirements regarding the safety characterization of impurities in drug substances and products are more formalized and better understood than those for excipient-related impurities even though excipients can often comprise the majority of the overall drug product formulation. Impurities in drug substances and products have been regulated over the previous decade and a half through the International Conference for Harmonization (ICH) Guidances Q3A(R2) and Q3B(R2). More recently, the Committee for Medicinal Products for Human Use (CHMP) of the EMEA and the Center for Drug Evaluation and Research (CDER) of the US FDA released guidance (final and draft, respectively) on how best to deal with genotoxic impurities in drug products. Although ICH Guidance Q3B addresses impurities in new drug products classified as reaction products of the drug substance with an excipient, the guidances currently available specifically exclude impurities arising from excipients. The control of excipient-related impurities is often managed by the manufacturer of the excipient. This session will discuss the regulatory aspects of safety characterization of impurities in drug substances and products and contrast them with the regulations regarding impurities in excipients. [ABSTRACT FROM AUTHOR]