The US Food and Drug Administration (FDA) has issued final guidance on refuse-to-receive standards for abbreviated new drug applications (ANDA) submissions and concurrently draft guidance on refuse-to-receive standards for ANDA submissions due to a lack of proper justification of impurity limits, The FDA also issued draft guidance for electronic submissions of lot distribution reports.
The final guidance, ANDA Submissions―Refuse-to-Receive Standards, is intended to assist applicants preparing to submit to the FDA 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 that may cause FDA to refuse-to-receive an ANDA. A refuse-to-receive decision indicates that the FDA determined that an ANDA is not sufficiently complete to permit a substantive review. This guidance is not meant to be a comprehensive list of the deficiencies that may or will lead to a refuse-to-receive determination by the FDA. Instead, this guidance identifies certain deficiencies and certain recurrent deficiencies that in the FDA’s experience have led the FDA to refuse-to-receive an ANDA. This guidance also describes how the FDA will assess deficiencies identified during FDA’s filing review to determine whether an ANDA should be received. In the guidance, the FDA said that the industry is aware of many of the standards described in the guidance because FDA has historically applied many of them.
Concurrent to the issuance of the final guidance, FDA issued draft guidance, ANDA Submissions—Refuse to Receive for Lack of Proper Justification of Impurity Limits. This guidance is intended to assist applicants preparing to submit to the FDA ANDAs and prior approval supplements (PASs) to ANDAs for which the applicant is seeking approval of a new strength of the drug product.2 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 review.
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 aboveidentification 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 the FDA to refuse to receive an ANDA. It also makes recommendations to ensure that appropriate justification for impurities are submitted in ANDAs.
The FDA also issued draft guidance, Electronic Submission of Lot Distribution Reports, to provide licensed manufacturers of products distributed under an approved biologics license application with recommendations on how to submit lot distribution reports (LDRs) for biological products in an electronic format that the FDA can process, review, and archive.