Drugs

Nitrosamine Acceptable Intake Limits Guide

FDA has posted a final guidance entitled “Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs).” The document provides manufacturers and applicants of drugs, including prescription and over-the-counter (OTC) drug products, with a recommended framework for predicting the mutagenic and carcinogenic potential NDSRIs that could be present in drug products and recommends acceptable intake (AI) limits for such.

NDSRIs are described as a class of nitrosamine impurities that have been identified in many drug products and also could be present in active pharmaceutical ingredients (APIs). “These impurities share structural similarity to the API (having the API or API fragment in the chemical structure) and are therefore unique to each API,” the guidance says. “NDSRIs generally form in the drug product through nitrosation of APIs (or API fragments) that have secondary or tertiary amines when exposed to nitrosating agents such as residual nitrites in excipients used to formulate the drug product. NDSRIs often lack carcinogenicity and mutagenicity study data (typically from animal studies) from which an AI limit can be determined.”

This guidance also provides a recommended methodology for AI limit determination that uses NDSRI structural features to produce a predicted carcinogenic potency categorization and corresponding recommended AI limit that manufacturers and applicants can use, in the absence of other agency-recommended AI limits, in their evaluations of approved and marketed drug products as well as products in development.

FDA notes that past uncertainty about NDSRI presence in drug products raised regulatory challenges and has led to some applicants conducting unnecessary studies or, in some cases, discontinuing drug products from the market. “Because nitrosamine impurities have been identified in many drug products, disruptions in supply and access have increased, sometimes resulting in drug shortages,” it says. “This guidance recommends a risk-based safety assessment of NDSRIs and can be used by manufacturers and applicants to identify AI limits for NDSRIs in their drug products and APIs in conjunction with the recommendations in the guidance for industry Control of Nitrosamine Impurities in Human Drugs (February 2021).”

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

Overton Confirmation Remains Uncertain After Senate Hearing

FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA has classified Boston Scientific's recall of its Imager II Angiographic Catheters as Class I because a manufacturing problem could cause catheter tips to degrade and detach, potentially resulting in life-threatening complications. The agency announced the Class I classification 9/25, updating an Early Alert it issued

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

Read more

Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome