Qualification threshold

Qualification Threshold A limit above (>) which an impurity should be qualified. 

Maximum daily dose (g/day) Reporting threshold (%) Identification threshold Qualification threshold... 

Attempts at structural identification of the compound are expected for impurities above the identification threshold. The evaluation of biological safety is expected above the qualification threshold. 

Impurities are generally toxicologically qualified when the drug is first approved for marketing, but changes in the synthetic process that lead to an existing or new impurity being routinely produced at a level above the qualification threshold... 

Table 8.1 ICH guidelines for reporting, identification, and qualification thresholds for impurities in drug substances and drug products [7, 8]...

Maximum Daily Dose Reporting Threshold Identification Threshold Qualification Threshold ... 

The profile of impurities in a new drug substance may change for a variety of reasons, such as process scale-up changes, synthetic route changes, and changes made to key intermediates. ICH decision trees help classify, qualify, and select limits for new molecular entities (NMEs). If an impurity exceeds the qualification threshold listed below in Table 3 (ICFI Q3A(R)), studies are needed to qualify that impurity in drug substances. 

If data are unavailable to qualify the proposed acceptance criterion of an impurity, studies to obtain such data can be appropriate when the usual qualification thresholds given are exceeded. 

The setting of impurity limits in the specification should take into account both the quality of the drug substance, i.e. the actual levels of related substances found in batch analysis, and also the safety of an individual impurity or given impurity profile at the specified levels. The acquisition and evaluation of data which establishes this safety is referred to as qualification. An impurity or impurity profile is considered qualified if it has been adequately tested in pre-clinical or clinical studies and such studies are needed for impurities present above the dose-dependent qualification thresholds prescribed in the note for guidance. 

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