The guidance can help both applicants and manufacturers limit the mutagenic and carcinogenic potential of NDSRIs.
Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - stock.adobe.com
On Aug. 4, 2023, FDA released a guidance document, Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs). The guidance gives both applicants and manufacturers of drugs recommendations for estimating the mutagenic and carcinogenic potential of NDSRIs that could be in drug products and gives acceptable intake (AI) limits for NDSRIs.
NDSRIs are a subcategory of nitrosamine impurities that share structural similarity to the API in drug products; NDSRIs often lack the compound-specific mutagenicity and carcinogenicity data necessary for informed safety assessments. FDA wrote in the guidance document that 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.”
FDA wrote that it will provide updated NDSRI-specific information on its website to be viewed in tandem with the guidance. The updated information will include suggested AI limits for specific NDSRIs based on “compound-data or read-across analysis from a surrogate”, suggested interim AI limits for NDSRIs, suggested testing methods for corroborative testing of specific NDSRIs, and suggested safety testing methods for NDSRIs. It will also include suggested AI limits for specific NDSRIs based on “predicted carcinogenicity potency categorization listed by APIs that hypothetically could be at risk of forming such NDSRIs.”
Source: FDA
Trump Directs FDA, EPA to Reduce Regulatory Barriers to Domestic Pharma Manufacturing
May 7th 2025The White House is instructing FDA to increase fees for and inspections of foreign drug manufacturing plants and reduce the time required to approve such sites that will be newly constructed in the US.
New Cancer Research and Treatment Center in Development in London
May 1st 2025Aviva Capital Partners and developer Socius are investing £1 billion in a 12-acre site to be located at the London Cancer Hub next to The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust’s Sutton site.
Regeneron Treatment for Multiple Myeloma Gets Conditional Marketing Approval from EC
April 29th 2025The indication is specific to patients who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy.
Trump Directs FDA, EPA to Reduce Regulatory Barriers to Domestic Pharma Manufacturing
May 7th 2025The White House is instructing FDA to increase fees for and inspections of foreign drug manufacturing plants and reduce the time required to approve such sites that will be newly constructed in the US.
New Cancer Research and Treatment Center in Development in London
May 1st 2025Aviva Capital Partners and developer Socius are investing £1 billion in a 12-acre site to be located at the London Cancer Hub next to The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust’s Sutton site.
Regeneron Treatment for Multiple Myeloma Gets Conditional Marketing Approval from EC
April 29th 2025The indication is specific to patients who have received at least three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy.
2 Commerce Drive
Cranbury, NJ 08512