USP: Proposals for Extractables & Leachables

The USP is expanding the Extractables and Leachables (E&Ls) chapter series <1664>. Following the previously published draft chapter for E&Ls in parenteral drug products (<1664.2>) three new drafts of USP's E&L chapters were just published in Pharmacopoeial Forum (PF) 51(6) . The comment deadline is 31 January 2026.

The USP E&L chapter series <1664> thus now includes the following subsections:

• <1664.1> Assessment of Leachables in Orally Inhaled and Nasal Drug Products (Revision)
• <1664.2> Parenteral Drug Products (Intramuscular, Intravenous, and Subcutaneous) (New)
• <1664.3> Assessment of Leachables in Topical Ophthalmic Drug Products (New)
• <1664.4> Assessment of Leachables in Topical and Transdermal Drug Products (New)

Background and Updates

USP chapter <1664> Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems and its subsections addresses leachables derived from two primary sources: process equipment used to produce the dosage form and container closure systems used to package the drug product. The discussion in the subsections is primarily devoted to organic leachables. For consideration of inorganic (i.e., elemental) leachables, general chapter <1664> is applicable.

The proposal for <1664.1> is based on the version of the chapter official as of 1 August 2015. The revision addresses specific considerations for leachables in orally inhaled and nasal drug products, including metered-dose inhalers, nasal sprays, inhalation solutions, suspensions, sprays, and dry powder inhalers. The updates include sections on elemental impurities, nitrosamines, and testing of additional leachable time points over the shelf life.

The new proposed chapter <1664.3> contains specific considerations for leachables in topical ophthalmic drug products, including solutions, suspensions, emulsions, and ointments. Chapter <1664.4> specifically addresses the unique considerations for leachables in topical and transdermal drug products, including patches, creams, gels, ointments, pastes, suspensions, lotions, foams, sprays, aerosols, and solutions.

More information is available online in the Pharmacopeial Forum (PF).