Control of drug substance impurities

In theory, all impurities should be eliminated. In practice, it is generally not economically feasible to totally eliminate all impurities. However, the levels of all impurities should be controlled to provide a consistent product. In most cases, only low levels of impurities should be allowed, but in rare cases, even quite high levels of impurities are tolerated. In some cases, for example, biotechnology derived products such as macrocyclic antibiotics, or extracts of a botanical source such as some dietary supplements, the drug substance or active component contains multiple compounds, all of which have biological activity. However, only organic impurities, which include residual solvents in the drug substance, are addressed in this chapter. 

For each dmg substance, the maximum acceptable levels of the various impurities are described in the drug substance monograph or the specification included in the submissions to the regulatory authorities. In this chapter, the ICH Q6A [4] and Q6B [5] definition of specification is used. A specification consists of three parts the test (e.g. moisture content, impurities), references to the analytical procedure (e.g. high-performance liquid chromatography [HPLC], gas chromatography [GC]), and the acceptance criterion (e.g. not more than 0.50%). 

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