USP Proposes New Standards for Organic Impurities in Medicines

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USP releases new and revised standards for organic impurities in medicines for public comment.

The U.S. Pharmacopeial Convention (USP) has proposed new and revised standards for organic impurities in drug substances and drug products. Drafts of the new and revised standards appear in the May–June 2014 issue of Pharmacopeial Forum (PF). The publication of the drafts initiates a 90-day public comment period ending on July 31, 2014. Organic impurities include process impurities and degradation products in drug substances as well as degradation products found in drug products.

The two drafts that appear in PF are revisions to General Chapter <1086> Impurities in Drug Substances and Drug Products and the proposal of new General Chapter <476> Organic Impurities in Drug Substances and Drug Products. While stakeholder input to the proposed changes are expected to trigger subsequent revisions, the chapters, once official, will be included in USP’s compendia of monograph and general chapter standards, U.S. Pharmacopeia—National Formulary (USP–NF).

A stimuli article also appears in the May–June PF issue, detailing the rationale behind these proposals. This includes details of a June 2013 survey conducted to obtain feedback on USP’s modernization initiative overall and stakeholder input on current USP standards related to organic impurities. The stimuli article also addresses the scope of chapters <1086> and <476> and a strategy for their implementation.

For medicines marketed in the US, drug substances and drug products covered by proposed General Chapter <476> can generally be placed in one of two categories: those covered by FDA approvals (most New Drug Application, Abbreviated New Drug Application, and Biologic License Application products); and those not requiring FDA pre-approval for marketing, such as products covered by the FDA OTC monograph system.


The proposed changes to General Chapter <1086> are intended to align it with current scientific and regulatory standards. They also include new definitions, threshold tables, and a decision tree for use when impurities associated with drug substances and drug products need to be addressed or reported. Based on stakeholder input from the June 2013 survey, both chapters <1086> and <476> are aligned with the regulatory approaches and scientific concepts of International Conference on Harmonization (ICH) Q3A and Q3B guidelines for impurities.

Also noted in the stimuli article is that General Chapter <476> is not intended to replace General Chapter <466> Ordinary Impurities. USP’s ongoing effort to modernize monographs in USP–NF includes the elimination of references to General Chapter <466>, a process independent from the revision of <1086> and the creation of <476>. Over time, General Chapter <466> will become obsolete and will be omitted from USP–NF. New monographs are expected to refer to General Chapter <476>, as appropriate.

Source: U.S. Pharmacopeial Convention