Identification threshold

Identification Threshold A limit above (>) which an impurity should be identified. 

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. 

However, analytical procedures should be developed for those potential impurities that are expected to be unusually potent, producing toxic or pharmacological effects at a level not more than the identification threshold. (From Refs. 55 and 56.)... 

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

Table 2 ICH Q3B(R) reporting and identification thresholds for impurities in drug product...

Degradation products observed in stability studies conducted at recommended storage conditions should be identified when present at a level greater than the identification thresholds (1% for a maximum daily dose of 2g). 

The studies conducted to characterize the structure of actual impurities present in the new drug substance at a level greater than 0.1% (depending on the daily dose, calculated using the response factor of the drug substance) should be described. Note that all specified impurities at a level greater than the identification threshold in batches manufactured by the proposed commercial process should be identified. 

A rationale for the inclusion or exclusion of impurities in a specification should be presented. The rationale should include a discussion of the impurity profiles observed in the safety and clinical development batches, together with a consideration of the impurity profile of batches manufactured by the proposed commercial process. Specified, identified impurities should be included along with specified, unidentified impurities estimated to be present at a level greater than the identification threshold given. For impurities known to be tmu-sually potent or that produce toxic or unexpected pharmacological effects, the quantification/detection limit of the analytical procedures should be commensurate with the level at which the impurities should be controlled. For unidentified impurities, the procedure used and assumptions made in establishing the level of the impurity should be clearly stated. Specified, unidentified impurities should be referred to by an appropriate qualitative analytical descriptive label (e.g., "unidentified A," "unidentified with relative retention of 0.9"). A general acceptance criterion of not more than the identification threshold for any unspecified impurity and an acceptance criterion for total impurities should be included. 

Qualitatively, these may be quickly detected by the Beilstein test for halogens a copper wire is heated in a gas burner until no color can be seen and the coil plunged into the acetic acid, then brought into the gas flame again. Any trace of green or blue-green flame shows the presence of halogen. The lower identification threshold is about 0.7 ppm for chloride, about 0.65 ppm for bromide, and about 0.55 for iodide. 

There are several definitions of threshold. The detection threshold is defined as the lowest stimulus eliciting a sensorial response, even though no identification can be reached. The recognition threshold or identification threshold is the level of stimulus at which the specific stimulus can be identified. The differential threshold or just noticeable difference, is the minimum increase in a stimulus required to detect a difference in the perception. 

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