Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities; Guidance for Industry; Availability

Issuing agencies

Abstract

The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a final guidance for industry entitled "Recommended Acceptable Intake Limits for Nitrosamine Drug Substance- Related Impurities (NDSRIs)." This guidance provides applicants and manufacturers of drugs, including prescription and over-the-counter (OTC) drug products, with a recommended framework for predicting the mutagenic and carcinogenic potential of NDSRIs that could be present in drug products and recommends acceptable intake (AI) limits for NDSRIs. NDSRIs, which are a subcategory of nitrosamine impurities that share structural similarity to the active pharmaceutical ingredient (API) in drug products, typically lack compound-specific mutagenicity and carcinogenicity data to inform safety assessments. This guidance provides a recommended methodology for AI determination that uses structural features of NDSRIs to generate a predicted carcinogenic potency categorization and corresponding recommended AI limit that manufacturers and applicants can apply, in the absence of other FDA- recommended AI limits, in their evaluation of potential impurities in their drug products.