This guidance is intended to assist applicants preparing to submit to the Food and Drug Administration (FDA) abbreviated new drug applications (ANDAs) and prior approval supplements (PASs) to ANDAs for which the applicant is seeking approval of a new strength of the drug product. The guidance highlights deficiencies in relation to information about impurities that may cause FDA to refuse to receive an ANDA. A refuse-to-receive decision indicates that FDA determined that an ANDA is not sufficiently complete to permit a substantive
Typical deficiencies leading to a refuse-to-receive decision include: (1) failing to provide adequate justification for proposed limits in drug substances and drug products for specified identified impurities that are above qualification thresholds; (2) failing to provide adequate justification for proposed limits for specified unidentified impurities that are above identification thresholds; and (3) proposing limits for unspecified impurities (e.g., any unknown impurity) that are above identification thresholds.
This guidance is not meant to be a comprehensive list of deficiencies in relation to impurity information that may or will lead to a refuse-to-receive determination by FDA. Instead, this guidance clarifies that a failure to provide proper justification for proposed impurity limits may lead FDA to refuse to receive an ANDA. It also makes recommendations to ensure that appropriate justification for impurities are submitted in ANDAs. This guidance is being issued concurrently with the guidance for industry ANDA Submissions – Refuse to Receive Standards.