Lachman has blogged many times on the topic of nitrosamines over the last several years as the FDA has issued and revised guidances providing its recommendations for assessment and control of nitrosamine impurities. The published deadline for compliance with these recommendations is quickly approaching; it’s just over three months until the August 1, 2025 compliance date listed in both Control of Nitrosamine Impurities in Human Drugs: Guidance for Industry and Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs): Guidance for Industry for completion of confirmatory testing, submission of required changes in drug applications, and ensuring that any NDSRIs in drug products meet the FDA-recommended Acceptable Intake (AI) limit. The countdown has begun, the last candle has been lit, we’re in the home stretch, or… insert your own favorite concluding phrase here.

During the Thursday morning Q&A session at the Generic Drugs Forum (GDF) held on April 9-10, 2025, after the presentations on nitrosamine impurities, the FDA speakers confirmed that the August 1st compliance date is the date by which products on the market need to comply with published limits. They also noted that some consideration will be made for additional data and information provided to them, especially in relation to averting a potential shortage, but they were not aware of any other planned actions or extensions beyond that date.

The other unknown factor as the compliance date approaches is the potential impact of the recent reductions in force of FDA staff and the possible reorganization of remaining staff. These stories have dominated the news recently and have injected a high degree of uncertainty into the future regarding immediate impacts on the FDA’s ability to review applications and manage submissions as well as issue external communications, such as guidance updates. The approaching deadline is expected to potentially increase the number of supplements submitted to the FDA and may also increase the number of Field Alert Reports and calls to the Drug Shortage Staff regarding high nitrosamine impurity levels for products for which mitigation strategies haven’t yet been implemented while they remain under review with the FDA. The hope is that enough staff remains to receive and respond to such a potential increase in activity and that they can react in a timely manner to support industry through this transition, but the fear is that some products may have to cease production until mitigation strategies are approved and implemented, which could increase drug shortages.

Dr. Reynolds Cantave (Senior Regulatory Business Process Manager, Office of Quality Assurance, Office of Pharmaceutical Quality, CDER) gave a presentation at the GDF that included a good reminder of the FDA’s expectations for industry regarding nitrosamine impurities:

  • observe the Agency’s guidance recommendations;
  • be transparent in reporting and addressing issues;
  • continually commit to patient safety through rigorous quality control; and
  • collaborate with the FDA on improving nitrosamine control measures
    (watch his presentation here: Nitrosamine Related Guidance – GDF 2025 – Day 2).

Transparent communication and collaboration have also been requested of the FDA by industry, but with many of the communications and policy staff let go recently (as discussed in this blog), transparent communications may be harder for the FDA to support in the near future and the Agency’s ability to react in a timely manner may be impacted, unfortunately.

As mentioned above, the Agency has no plans to delay the compliance date for nitrosamine impurities. If you have questions on navigating the nitrosamine impurities guidances or preparing for the upcoming compliance date, Lachman can help! Please contact us at LCS@LachmanConsultants.com.