This guidance is being published with the objective to recommend acceptable amount of residual solvents in pharmaceuticals forthe safety of target animals as well of the safety of residuals in products derived from treated food producing animals.
There are no therapeutic benefits from residual solvents, all residual solvent should be removed to the extent possible to meet product specifications. The list of solvents and their acceptable levels is not exhaustive and other solvent will be added to this list as it develops.
excerpt from guideline
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The objective of this guideline is to recommend acceptable amounts for residual solvents in pharmaceuticals for the safety of the target animal as well as for the safety of residues in products derived from treated food producing animals. The guideline recommends use of less toxic solvents and describes levels considered to be toxicologically acceptable for some residual solvents.
Residual solvents in pharmaceuticals are defined here as organic volatile chemicals that are used or produced in the manufacture of active substances or excipients, or in the preparation of veterinary medicinal products. The solvents are not completely removed by practical manufacturing techniques. Appropriate selection of the solvent for the synthesis of active substance may enhance the yield, or determine characteristics such as crystal form, purity, and solubility. Therefore, the solvent may sometimes be a critical parameter in the synthetic process. This guideline 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.
Since there is no therapeutic benefit from residual solvents, all residual solvents should be removed to the extent possible to meet product specifications, good manufacturing practices, or other quality-based requirements. Veterinary medicinal products should contain no higher levels of residual solvents than can be supported by safety data. Some solvents that are known to cause unacceptable toxicities (Class 1, Table 1) should be avoided in the production of active substances, excipients, or veterinary medicinal products unless their use can be strongly justified in a risk-benefit assessment. Some solvents associated with less severe toxicity (Class 2, Table 2) should be limited in order to protect target animals and human consumers from potential adverse effects. Ideally, less toxic solvents (Class 3, Table 3) should be used where practical. The complete list of solvents included in this guideline is given in Appendix 1.
The lists are not exhaustive and other solvents can be used and later added to the lists. Recommended limits of Class 1 and 2 solvents or classification of solvents may change, as new safety data becomes available. Supporting safety data in a marketing application for a new veterinary medicinal product containing a new solvent may be based on concepts in this guideline or the concept of qualification of impurities as expressed in the guideline for active substance (VICH GL 10, Impurities in New Veterinary Drug Substances) or veterinary medicinal product (VICH GL 11, Impurities in New Veterinary Medicinal Products), or all three guidelines.
