Drug development specificity validation

Predictive validity is the ability of a model to predict the effect that pharmacological or other manipulations will have on the condition being modeled. This criterion can present a real difficulty, in that drug development is often dictated by animal models. For example, if a given model only detects a subset of effective compounds (i.e. those belonging to a specific chemical class), then useful candidates will be discarded long before clinical trials, and the flaw in the model s predictive validity will not be discovered. Thus, the possibility that a model will yield false negatives cannot be ruled out. 

The ability to provide accurate and reliable data is central to the role of analytical chemists, not only in areas like the development and manufacture of drugs, food control or drinking water analysis, but also in the field of environmental chemistry, where there is an increasing need for certified laboratories (ISO 9000 standards). The quality of analytical data is a key factor in successfully identifying and monitoring contamination of environmental compartments. In this context, a large collection of methods applied to the routine analysis of prime environmental pollutants has been developed and validated, and adapted in nationally or internationally harmonised protocols (DIN, EPA). Information on method performance generally provides data on specificity, accuracy, precision (repeatability and reproducibility), limit of detection, sensitivity, applicability and practicability, as appropriate. 

Gardner N, Haresign W, Spiller R, Farraj N, Wiseman J, Norbury H, Ilium L (1996) Development and validation of a pig model for colon-specific drug delivery. J. Pharm. Pharmacol 48 pp 689-693. 

A final caveat in the RPAIA field that limits biomarker discovery as well as other uses in drug development is the somewhat limited panel of antibodies that have been validated to date for the platform. Many antibodies that work on western blots have the potential to work with RPMAs as well, because in both platforms proteins are in a denatured state. However, because the molecular weight of analytes detected by RPMA cannot be known, it is imperative to demonstrate the specificity of antibodies, usually measured by the absence of nonspecific reactive bands on western blots developed under similar blocking conditions. A second requirement for antibody validation is proof of principle that an antibody detects quantitative changes in the expected target on an... 

Impurities in API. Treatment of the impurities in the API is similar to that for the new drug product. Impurities in the API include organic impurities (process and drug related), inorganic impurities, and residual solvents. Quality control analytical procedures are developed and validated to ensure appropriate detection and quantitation of the impurities. Specification limits for impurities are set based on data from stability studies and chemical development studies. A rationale for the inclusion or exclusion of impurities is set at this stage. The limits set should not be above the safety level or below the limit of the manufacturing process and analytical capability. 

A highly sensitive and specific ELISA for the determination, in different types of water samples, of diclofenac, a commonly used nonsteroidal anti-inflammatory drug (NSAID), has been developed by Deng et al.357 This analyte belongs to the most frequently detected, pharmaceutically active compounds in the water cycle. The immunoassay was able to measure tap water samples directly— respective LOD and IC50 values were 6 and 60 ng E. On the other hand, surface water samples required fivefold dilution and the wastewater samples 10-fold dilution in buffer to be analyzed correctly the LODs were then 20 and 60 ng E, respectively. Recently, the development and validation of a highly sensitive and specific ELISA for the detection of pharmaceutical indomethacin in... 

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