Yesterday, the FDA quietly posted another update to the CDER Nitrosamine Impurity Acceptable Intake Limits webpage. The latest update is not an extended timeline for submitting changes or new acceptable intake (AI) limits as might be expected but instead because CDER has become aware of an emerging issue related to small-molecule nitrosamine impurities such as N-nitroso-dibutylamine (NDBA) possibly leaching into drug products that are packaged in infusion bags.

The update to the website was made to add a link to a link to a document titled “August 18, 2025: Emerging Scientific and Technical Information on Leachable NDBA and Other Small-Molecule Nitrosamines in Infusion Bags” to the section “Other Emerging Scientific and Technical Issues” (between tables 4 and 5). The link takes you to a document on FDA letterhead that the Agency refers to as a statement, but it reads like a guidance document. Due to the limited data that the FDA has received on this topic to date, the Agency is requesting that manufacturers and applicants test their products and report the data to their applications.

Testing should be performed on at least three batches within expiry, and the strength (or strengths) of greatest risk should be selected for testing. The Agency asks for testing to be shared with CDER, including test results and method validation information to be sent to the application as general correspondence, within ninety days of the date on this “emerging issues” statement, which equates to a due date of November 16, 2025.

Other than the fact that this is another call to action with little to no accompanying notice or publicity, the other surprising part of the statement is that CDER is acknowledging the unique nature of products packaged in infusion bags and is recommending an adjustment factor for the lifetime AI limit! Unlike other health authorities, in the past, the FDA has appeared to be firmly opposed to any adjustments to account for less than lifetime exposure in relation to other drug products so it is remarkable that the Agency is now proposing such an adjustment in this notice.

The posting of this “emerging issues” statement certainly confirms that the nitrosamine saga will continue and new potential issues will continue to emerge as more data is gathered. With this latest webpage update, like the update from earlier in June, CDER is asking for information from manufacturers and providing a short timeframe for action.

If you have questions about nitrosamine impurities or testing your infusion products, or need assistance with other nitrosamine impurity issues, Lachman can help! Send us an email at LCS@LachmanConsultants.com to schedule a consultation.