{"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.","action":"Notice of availability.","agencies":[{"raw_name":"DEPARTMENT OF HEALTH AND HUMAN SERVICES","name":"Health and Human Services Department","id":221,"url":"https://www.federalregister.gov/agencies/health-and-human-services-department","json_url":"https://www.federalregister.gov/api/v1/agencies/221","parent_id":null,"slug":"health-and-human-services-department"},{"raw_name":"Food and Drug Administration","name":"Food and Drug Administration","id":199,"url":"https://www.federalregister.gov/agencies/food-and-drug-administration","json_url":"https://www.federalregister.gov/api/v1/agencies/199","parent_id":221,"slug":"food-and-drug-administration"}],"body_html_url":"https://www.federalregister.gov/documents/full_text/html/2023/08/07/2023-16814.html","cfr_references":[],"citation":"88 FR 52183","comment_url":null,"comments_close_on":null,"correction_of":null,"corrections":[],"dates":"The announcement of the guidance is published in the Federal Register on August 7, 2023.","disposition_notes":null,"docket_ids":["Docket No. FDA-2020-D-1530"],"dockets":[{"supporting_documents":[],"agency_name":"FDA","documents":[{"comment_count":null,"comment_start_date":null,"updated_at":"2024-09-05T09:56:31.376-04:00","comment_url":"https://www.regulations.gov/commenton/FDA-2020-D-1530-0031","allow_late_comments":false,"id":"FDA-2020-D-1530-0031","comment_end_date":null,"regulations_dot_gov_open_for_comment":false}],"supporting_documents_count":0,"id":"FDA-2020-D-1530","title":"Control of Nitrosamine Impurities in Human Drugs; Guidance for Industry; Availability"}],"document_number":"2023-16814","effective_on":null,"end_page":52185,"executive_order_notes":null,"executive_order_number":null,"explanation":null,"full_text_xml_url":"https://www.federalregister.gov/documents/full_text/xml/2023/08/07/2023-16814.xml","html_url":"https://www.federalregister.gov/documents/2023/08/07/2023-16814/recommended-acceptable-intake-limits-for-nitrosamine-drug-substance-related-impurities-guidance-for","images":{},"images_metadata":{},"json_url":"https://www.federalregister.gov/api/v1/documents/2023-16814?publication_date=2023-08-07","mods_url":"https://www.govinfo.gov/metadata/granule/FR-2023-08-07/2023-16814/mods.xml","not_received_for_publication":null,"page_length":3,"page_views":{"count":1700,"last_updated":"2026-04-04 12:15:04 -0400"},"pdf_url":"https://www.govinfo.gov/content/pkg/FR-2023-08-07/pdf/2023-16814.pdf","presidential_document_number":null,"proclamation_number":null,"public_inspection_pdf_url":"https://public-inspection.federalregister.gov/2023-16814.pdf?1691153135","publication_date":"2023-08-07","raw_text_url":"https://www.federalregister.gov/documents/full_text/text/2023/08/07/2023-16814.txt","regulation_id_number_info":{},"regulation_id_numbers":[],"regulations_dot_gov_info":{"supporting_documents":[],"comments_count":0,"agency_id":"FDA","comments_url":"https://www.regulations.gov/docketBrowser?rpp=50&so=DESC&sb=postedDate&po=0&dct=PS&D=FDA-2020-D-1530","supporting_documents_count":0,"docket_id":"FDA-2020-D-1530","document_id":"FDA-2020-D-1530-0031","regulation_id_number":null,"title":"Control of Nitrosamine Impurities in Human Drugs; Guidance for Industry; Availability","checked_regulationsdotgov_at":"2024-09-06T13:00:16Z"},"regulations_dot_gov_url":null,"significant":null,"signing_date":null,"start_page":52183,"subtype":null,"title":"Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities; Guidance for Industry; Availability","toc_doc":"Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities","toc_subject":"Guidance:\n","topics":[],"type":"Notice","volume":88}