Accuracy potency

A number of oral solution or suspension products are included in the EPARs. Apart from the usual points of consideration for active ingredients and excipients, particular mention is made of possible precipitation of active ingredient when a solution is in use, the inclusion of excipients having a major impact on bioavailability, the need for flavoring to mask the taste of the active ingredient, relative potency compared with other routes of administration, preservation issues, dosing devices and the precision and accuracy of the dose delivered, and bioequivalence where formulations have been modified during the development process. 

The near-IR technique has been used very successfully for moisture determination, whole tablet assay, and blending validation [23]. These methods are typically easy to develop and validate, and far easier to run than more traditional assay methods. Using the overtone and combination bands of water, it was possible to develop near-IR methods whose accuracy was equivalent to that obtained using Karl-Fischer titration. The distinction among tablets of differing potencies could be performed very easily and, unlike HPLC methods, did not require destruction of the analyte materials to obtain a result. 

In these tests, EA 3580 produced somewhat more impairment in performance of Track Tracing Accuracy (Fig. 34) than in Track Tracing Speed (Fig. 35), suggesting that physical competence may be more resistant than cognitive functions to the effects of anticholinergic drugs with high relative central potency. 

Contrary to the practical results reviewed above, statistics from correlation work revealed a serious deficiency in the accuracy with which Phase I Equations 3 and 4 predicted -for the Phase II dataset r for Equation 3 predictions for the 103 compound Phase II data was only 0.45 r for Equation 4 predictions for the Phase II dataset was only 0.44. An analysis of the residuals for the Phase II dataset [Potency(observed)-Potency(predicted by Phase I models)] immediately Identified the source of the problem of the 26 Phase II compounds having DICARB >4, 17 had potency for adult observed more than one log unit better than predicted 15 had egg potency observed more than one log unit better than predicted. As schematically shown in Figure 2B, the parabolic functions for DICARB for the Phase I models underpredict at values of DICARB extrapolated beyond those represented in the Phase I dataset. 

It is an essential condition of biological assay methods that the tests on the standard preparation and on the sample whose potency is being determined should be carried out at the same time and, in all other respects, under strictly comparable conditions. The validation of microbiological assay method includes performance criteria (analytical parameters) such as linearity, range, accuracy, precision, specificity, etc. 

ICH Q2A suggested validation of the characteristics of accuracy, precision, specificity, linearity, and range for potency and content uniformity assay. A detailed discussion of each of these parameters is presented later in this chapter. Some examples of validation data are presented along with a brief critical discussion of the data. 

The goal of being able to predict with greater accuracy the potency and spectrum of compounds before they are synthesized awaits three developments the structures of more HRVs and compounds, the ability to more accurately model hydrophobic interactions, and probably the most difficult, the ability to predict changes in the HRVs that occur due to drug binding. 

Potency, yield, physical parameters Method, instrumentation, calibration, traceability, precision, accuracy... 

Many compounds may interact and cause unexpected toxic effects which could not be expected from the known toxicity of the individual components. Often one of three principles applies for assessment of the interactions between compounds in a mixed exposure. These are (i) independent action or no interaction between the components (ii) interaction between the compounds (which in some cases may be dealt with by adding the expected effects of the individual compounds using a weight factor expressing the relative potency of the compounds) and (iii) no assessment is possible because the interaction mechanisms are too complex for normal toxicological evaluation. It should be noted that different types of health effects may require different types of assessments of the interactions and that these assessments have different accuracy. These interactions are the main causes of the slow process of establishing official guidelines of IAQ. Further information is found in Cochet et al., (2006). 

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