Exploratory development drug substance

The term exploratory development (ED) can be defined as the first part of clinical drug development in which tolerability, pharmacokinetics and pharmacodynamic activity are defined in man and in which an early indication of therapeutic efficacy is often obtained . A new active substance (NAS) can be defined as an unlicensed new chemical or biological entity with activity in biological systems whose therapeutic potential is under investigation . The overall aim of ED should be to select appropriate NASs for full development (ED) and to reject those that will not make useful medicines, as early as possible. 

The first step in the product development process is establishing specifications after exploratory research to bring a product to market. Specifications are the quality definition of an article (dosage forms or the related materials for production) upon which acceptance for eventual market distribution is based. The data for establishing pharmaceutical product specifications for both drug substances and dosage forms are defined by identity, purity, strength, and quality, derived from the preformulation study. 

The product development process in the pharmaceutical industry is not unlike that of other industries, in which exploratory materials are researched and developed into products, and where problems arise the analytical laboratory is called upon to provide solutions. The characterization of the physical properties of pharmaceutical solids is one of the disciplines utilized early in the drug development process. The characterization of these properties is vital to determining whether the compound under investigation is a candidate for continued development as a drug product. To facilitate the characterization of pharmaceutical solids in laboratories, a conceptual approach for this characterization has been developed (66) that uses decision trees to guide the analyst in the characterization of drug substances. 

Reductive [ CJmethylation procedures have found broad application in the rapid labeling of investigational drug substances for in vitro studies where metabolism does not occur, in early exploratory in vivo investigations in drug research and development, and in peptide and protein mapping. However, because A -dealkylation reactions are common metabolic events, compounds labeled by Af-[ C]methylation are usually not suitable for registration studies. 

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