Pharmaceutical data, modeling

The Clinical Data Interchange Standards Consortium (CDISC) is a non-profit group that defines clinical data standards for the pharmaceutical industry. CDISC has developed numerous data models that you should familiarize yourself with. Four of these models are of particular importance to you ... 

The largest commercially available datasets are the Physical Properties (PHYSPROP) and AQUASOL databases ca. 6000 compounds in each database). The AQUASOL database has been published as a book. Furthermore, two relatively large sets of aqueous solubility data models were used in many other studies.Data from the AQUASOL database had an interlaboratory variation of about a = 0.49 log-units (as estimated for A=1031 molecules).Moreover, large inter-laboratory errors mask the influence of temperature, and differences as large as AT = 30 °C do not increase this error. In-house models developed at pharmaceutical companies could be based on similar or even larger numbers of measurements. For example, about 5000 molecules were used to develop a model at Bayer Healthcare AG. " ... 

Thus, all the error is assumed to be with the dependent variable. Therefore, it is important that the independent variables are carefully measured or controlled. For example, when time is the independent variable, actual times should be recorded and used in the data analyses rather than scheduled times. Although most modeling of pharmaceutical data has confined the error to the y term, there have been attempts to include error in the x value during the fitting process. ... 

Process Economics. Relative economics of various ceU culture processes depend heavily on the performance of the ceU line in a system and on the cost of raw materials, particularly the medium. Models are usuaUy developed for the various processes using productivity data obtained from smaU-scale experiments (see Pilot AND MiCROPLANTs). Often, for high value products, the process which ensures the shortest time to market may be the process of choice because of other economic criteria. This is especially tme for pharmaceuticals (qv). RehabUity concerns also often outweigh economic considerations in choosing a process for a high value product. 

Step 1 of the parametrization process is the selection of the appropriate model compounds. In the case of small molecules, such as compounds of pharmaceutical interest, the model compound may be the desired molecule itself. In other cases it is desirable to select several small model compounds that can then be connected to create the final, desired molecule. Model compounds should be selected for which adequate experimental data exist, as listed in Table 1. Since in almost all cases QM data can be substimted when experimental data are absent (see comments on the use of QM data, above), the model compounds should be of a size that is accessible to QM calculations using a level of theory no lower than HE/6-31G. This ensures that geometries, vibrational spectra, conformational energetics, and model compound-water interaction energies can all be performed at a level of theory such that the data obtained are of high enough quality to accurately replace and... 

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