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The practice of recovering and using solvents in the pharmaceutical industry has implications for the quality of active pharmaceutical ingredients (APIs) in finished pharmaceutical products. Various recovery processes and installations are currently being utilized. This article attempts to present the latest developments and collective provisions related to the topic and has been compiled based on experience gained as part of activities related to the WHO Prequalification of Medicines Programme. Importantly, it presents typical questions that should be addressed when an API manufacturing site is being inspected. Of particular relevance is the reproducibility of the given recovery process and, by implication, the quality of the recovered solvent. Such considerations are crucial to the quality of the final product. Comments on this article are welcome and should be forwarded to [email protected].
Solvent recovery is a routine practice in the pharmaceutical industry when it is technically and economically viable for the particular waste stream. Organic solvents are ubiquitous in the reaction and separation steps of pharmaceutical processes. The replacement of organic solvents appears to be difficult owing to the strong influence on the outcome of the reaction and /or quality of the separation (e.g., crystallization). The use of multiple solvents and reagents for different purposes within a process frequently leads to the formation of solvent mixtures.
It is hard and often impossible to recover solvent in pure form from such a waste stream consisting of multiple solvents and reagents used in the reaction and separation process. Therefore, the use of recovered solvents and the pooling of solvents must be appropriately qualified to assure product quality and avoid cross contamination during active pharmaceutical ingrethent (API) production.
The use of recovered solvents can generate problems from a product purity stand point. For example, a recovered solvent can be of an azeotropic composition that may become the solvent during a reaction. This change of solvent may cause changes in the spectrum of impurities present in the final product. On the other hand, intermediate and product isolation via crystallization can be...