RA/QA News Roll: Mid August 2023

Here's what's happening at FDA and across the broader life science RA/QA space.

This is our biweekly recap of news and industry happenings curated for our paid subscribers. Our goal is to bring you the headline news as well as the stories, research, and insights that might be harder to find.

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Here are some key items from the past couple of weeks.

FDA Guidances

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• The FDA has issued a draft guidance for sponsors conducting clinical trials of medical devices to treat opioid use disorder (OUD). The agency acknowledges the complex challenges faced in these trials, including high rates of missing data, confounding effects of concomitant drug treatments, and measuring the durability of the treatment effect. To address these challenges, the FDA recommends well-defined study populations, appropriate monitoring of drug use, control for biases, and inclusion of an appropriate follow-up period. The guidance also emphasizes the importance of accurately representing the intended treatment population and tracking drug use during the trial. Stakeholders can provide comments on the draft guidance until October 25th.

• The FDA has issued a new final guidance outlining recommended acceptable intake limits for nitrosamine drug substance-related impurities. A few key takeaways: The guidance provides a 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 share structural similarities to the API and are unique to each API. They generally form in the drug product through nitrosation of APIs exposed to nitrosating agents.) The guidance recommends a risk-based safety assessment of NDSRIs and introduces a predicted carcinogenic potency categorization approach. An AI limit represents a daily exposure to a compound that approximates a 1:100,000 cancer risk after 70 years of exposure. The guidance complements the approach recommended in ICH M7(R2) (see FDA guidance here) and is based on structure-activity relationship (SAR) concepts to assess and classify the mutagenic and carcinogenic risk of impurities.

• The FDA has released a new draft guidance document regarding QTc information in the labeling of human prescription drugs and biological products.

• The FDA has released a new draft guidance document that pertains to the methods used after marketing approval to gather data about under-represented populations in clinical trials.

• There are two recently introduced draft guidance documents that center around the Biosimilar User Fee Amendments (BsUFA) of 2022. Within this user fee program, the FDA has specific responsibilities to fulfill in exchange for the funding allocated for particular activities. These activities include tasks like receiving and reviewing Biologics License Applications (BLAs) for biosimilars. The first guidance outlines the categorization (A-F) of BLA supplements, detailing the approach the FDA will take in managing these submissions along with its associated obligations. The second guidance focuses on the FDA's procedures for conducting Formal Meetings with sponsors of biosimilar products.

FDA General

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• In a clear sign that the FDA is taking steps to collaborate with global agencies for inspections, it recently signed an inspection agreement with the Swiss Agency for Therapeutic Products (Swissmedic). The agreement allows for exchanging official documents and using each other's inspection resources for manufacturer oversight. The agreement with the Swiss agency applies to pre- and post-approval inspections and regular GMP inspections of manufacturing facilities conducted within either party’s territory. The FDA is also exploring further international collaboration through joint assessments with agencies like the European Medicines Agency (EMA) and participating in pilot programs to conduct inspections more efficiently and expedite drug application reviews across borders. However, specific timelines for implementing these actions permanently have not been provided.