Safety pharmacology development

Whitebread, S., Hamon, J., Bojanic, D., and Urban, L. (2005). In vitro safety pharmacology profiling An essential tool for successful drug development. Drug Disc. Today 10 1421-1433. 

In the EU, the CPMP issued a draft Note for Guidance on Safety Pharmacology Studies in Medicinal Product Development in 1998, but it has not yet been finalized or put in force, and as of the middle of 2001, USFDA has remained mute on guidelines. 

The initiative to add mandated safety pharmacology studies to the drug development process is overdue in arriving. However, its actual implementation and the use of the resulting data in risk/benefit decision will take some time to be worked out. During the year 2001, many small companies were put in a difficult position when the... 

CPMP (1998). Note for Guidance on Safety Pharmacology Studies in Medicinal Product Development. 

Fujimori, K. (1999). The role of general pharmacological studies and pharmacokinetics in the evolution of drugs (1) The role of general/safety pharmacology studies in the development of pharmaceuticals International harmonization guidelines. Folia Pharmacologica Japo-... 

Martin, L.I., Horvath, C.J. and Wyand, M.S. (1997). Safety pharmacology screening practical problems in drug development. Int. J. Toxicol. 16 41-65. 

Olejiniczak, K. (1999). Development of a safety pharmacology guideline. Human Exper. Toxicol. 18 502. 

Provides guidance on the timing of safety pharmacology Anon.24 studies in relation to clinical development. Establishes that safety pharmacology studies should be conducted prior to first administration to humans... 

Timing of Safety Pharmacology Studies in Relation to Clinical Development... 

The safety pharmacology "core battery" studies should be available prior to first administration in humans. Furthermore, "follow-up" and "supplemental" studies should also be available prior to first administration in humans if there are specific cause for concerns. During clinical development, additional studies may be warranted to clarify observed or suspected adverse effects in animals or humans. Finally, prior to product approval, effects on organ systems that are defined as part of "follow-up" and "supplemental" studies should be assessed, unless not warranted. Available information from toxicology or clinical studies can support this assessment and replace the need for stand-alone safety pharmacology studies. 

The future of safety pharmacology will depend, in part, upon the scientific and technological advances and regulatory challenges that envelop pharmaceutical development. 

There is a considerable interest in computational models to predict the safety of NCEs in the drug discovery and development phases. Insight into the safety pharmacological potential of a scaffold or series of structures early in the drug discovery process could help the medicinal chemists to prioritize particular scaffolds or hits or alternatively can contribute halting the discovery process for a given research project. The main safety... 

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