ANALYSIS OF CHROMAMETER RESULTS OBTAINED FROM CORTICOSTEROID-INDUCED SKIN BLANCHING - I - MANIPULATION OF DATA

Purpose. One of the unresolved issues in the FDA Guidance document for topical corticosteroid bioequivalence testing is the method of manipu lation suggested for the chromameter data. The purpose of this study w as to manipulate the instrumental data from a typical blanching study in a number of ways to investigate the appropriateness of these proced ures for comparison with the subjective visually-assessed results. Met hods. The human skin blanching assay methodology routinely practiced i n our laboratories was utilised and the vasoconstriction produced by t wo corticosteroid formulations of different potency was assessed visua lly and instrumentally by use of a Minolta chromameter. The instrument al data were corrected for zero-time and unmedicated site readings. In addition, Euclidean distances were calculated using all data generate d by the instrument. Results, Individually the a-, b- and L-scale chro mameter values are imprecise and there is negligible vasoconstriction response recorded for the moderately potent formulation. Arithmetical manipulation of the data as suggested by the FDA does not appear to im prove the quality of the data in any way. Euclidean distance analysis more closely resembles the visual data and appears to have better prec ision. Conclusions, It is clear that mathematical correction of chroma meter data is unnecessary, especially since the instrumental data are extremely imprecise. Furthermore, the assessment of each individual ch romameter index does not adequately characterise the blanching respons e profile. It is therefore suggested that Euclidean distance may be a better measure on which to base an analysis of bioequivalence than the truncated data set methodology currently suggested by the FDA.