Drug assessment process

The first issue lies in the whole realm of the human disease process itself. Many adverse drug events mimic diseases and vice versa. Is an adverse event really an adverse event, or is it merely a natural occurrence of a disease process that is entirely independent of drug exposure The science of drug safety is often complicated by the lack of objective markers of drug toxicity that can systematically separate a disease process from an adverse drug event process [2]. Clinical trials, often viewed as the gold standard to assess efficacy, are simply too limited in scope to answer safety questions in a systematic way. 

Table 8.1 Drug assessment and registration structures and processes... 

The emphasis at this stage of the drug development process is upon assessing safety. Satisfactory pharmacological, and particularly toxicological, results must be obtained before any regulatory authority will permit commencement of human trials... 

The criteria used by the CBER and CDER regulators in assessing product performance during the drug development process are similar, i.e. safety, quality and efficacy. However, the administrative details can vary in both name and content. Upon concluding preclinical trials, all... 

From the above we conclude that in silico absorption models are very useful tools in assessing the development potential of compounds in the drug discovery process, and their use in discovery projects could help to reduce the attrition rate due to poor pharmacokinetic properties in later phases. The... 

The impact of the in vitro screens applied to each stage in the drug discovery process will be different. The optimal set of assays at the early stages should assess drug activity against a small number of targets that play a key role in the function of core physiological systems. 

An NDA submitted to the MHLW is reviewed by the PMDA. PMDA personnel have the authority to inspect the drug manufacturing facility and clinical trial sites to assess comphance. In the process, the PMDA consults the Pharmaceutical Affairs and Food Sanitation Council (PAFSC). Results of the review are forwarded to the Pharmaceutical and Food Safety Bureau (PFSB), which prepares the final approval through the Minister of the MHLW. Figure 8.10 shows the drug approval process in Japan. The procedure for manufacturing and distribution of drugs for overseas manufacturers is presented in Fig. 8.11. 

Advances in chemical synthesis have enabled considerable sophistication in the construction of diverse compound libraries to probe protein function [61, 62). However, few general techniques exist that can directly assess binding mechanisms and evaluate ligand afEnities in a multiplexed format. To realize the full potential of combinatorial chemistry in the drug discovery process, generic and efficient tools must be applied that combine mixture-based techniques to characterize protein-ligand interactions with the strengths of diversity-oriented chemical synthesis. 

Bertrand, M. Jackson, P. Walther, B. Rapid assessment of drug metabolism in the drug discovery process. Eur J Pharm Sci 2000, 11 [Suppl 2], S61-S72. 

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