Type of Notice: General Announcement
Posting Date: 26-Sep-2025
Introduction:
This General Announcement is intended to promote awareness in the pharmaceutical and regulatory communities regarding USP’s on-going efforts to create compendial solutions to address the presence of Mutagenic Impurities in the commercial drug supply.
Background:
In September 2022, USP published in PF 48(5) a Stimuli article entitled “Mutagenic Impurities and Potentially Mutagenic Impurities in the USP-NF.” USP received and assessed stakeholder feedback on this Stimuli article.
In March 2024, USP proposed in PF 50(2) several revisions to General Notices and Requirements, section 5.60. Specifically, the subsection 5.60.10, Other Impurities in USP and NF Articles was proposed to be deleted and replaced with a new subsection 5.60.10, entitled Impurities That Are Unusually Toxic and/or Mutagenic. This new subsection explicitly references The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guidance M7: “Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.” This new subsection 5.60.10 became official in the USP-NF 2025 Issue 2 on August 1, 2025.
Evolution of the MICF:
USP intends to develop compendial solutions to address the potential presence of Mutagenic Impurities in Official Articles, which will collectively be termed the “Mutagenic Impurity Compendial Framework” (MICF). Based on information received by USP, as well as potential risks to public health and safety of the medicine supply, USP considers the development of the MICF a high organizational priority.
One potential approach to the MICF could involve coupling a given Official Monograph with a mandatory General Chapter numbered <1000, when a particular Mutagenic Impurity is likely to be present in a given Official Article and therefore requires a control strategy.
This General Announcement is being published for awareness only. Additionally, the strategy and implementation time frame for these efforts are expected to evolve over the next few years. USP intends to continue engaging stakeholders and regulatory bodies about our efforts to develop and implement the MICF. Conventional USP Stakeholder Engagement mechanisms are expected to be employed in the near future which could include but not be limited to workshops and/or roundtables, as well as other potential engagement options.
For more information, contact us at MICF@usp.org.