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?467? ORGANIC VOLATILE IMPURITIES RESIDUAL SOLVENTS LIMITS For pharmacopeial purposes, residual solvents in pharmaceuticals are defined as organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. The residual solvents are not completely removed by practical manufacturing techniques. Appropriate selection of the solvent for the synthesis of a drug substance or an excipient may enhance the yield, or determine characteristics such as crystal form, purity, and solubility. Therefore, the solvent may sometimes be a critical element in the synthetic process. This General Chapter does not address solvents deliberately used as excipients nor does it address solvates. However, the content of solvents in such products should be evaluated and justified. Because residual solvents do not provide therapeutic benefit, they should be removed, to the extent possible, to meet ingredient and product specifications, good manufacturing practices, or other quality-based requirements. Drug products should contain no higher levels of residual solvents than can be supported by safety data. Solvents that are known to cause unacceptable toxicities (Class 1, HYPERLINK 13/USP28/v28230/usp28nf23s0_c467.htm \l usp28nf23s0_c467-t1 Table 1) should be avoided in the production of drug substances, excipients, or drug products unless their use can be strongly justified in a risk-benefit assessment. Solvents associated with less severe toxicity (Class 2, HYPERLINK 13/USP28/v28230/usp28nf23s0_c467.htm \l usp28nf23s0_c467-t2 Table 2) should be limited in order to protect patients from potential adverse effects. Ideally, less toxic solvents (Class 3, HYPERLINK 13/USP28/v28230/usp28nf23s0_c467.htm \l usp28nf23s0_c467-t3 Table 3) should be used where practical. The complete list of solvents included in this General Chapter is given in Appendix 1. These tables and the list are not exhaustive. Where other solvents ha