Stands clinical studies

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. 

In summary, biogenerics are best defined as copies of therapeutic proteins, launched after patent expiry of the active pharmaceutical ingredient, and sold with a moderate price reduction. They have to be approved via the route of the centralized procedure in Europe and currently require a complete stand-alone dossier including clinical studies proving efficacy and safety. 

The potential benefits of the use of adhesive monomers both in free-standing dentin-enamel adhesives and in self-adhesive formulations are still somewhat areas of debate. Current restorative resin/dentin adhesive systems have demonstrated outstanding long-term clinical performance in prospective clinical studies [49-53]. 

Extensive biotransformation studies have been conducted with the As-pidosperma alkaloid vindoline, but much less work has been done with monomeric Iboga and dimeric alkaloids from this plant. The long-standing interest in this group of compounds stems from the clinical importance of the dimeric alkaloids vincristine and vinblastine, both of which have been used for more than 2 decades in the treatment of cancer. Few mammalian metabolites of dimeric Catharanthus alkaloids have been characterized. Thus the potential role of alkaloid metabolism in mechanism of action or dose-limiting toxicities remains unknown. The fact that little information existed about the metabolic fate of representative Aspidosperma and Iboga alkaloids and Vinca dimers prompted detailed microbial, mammalian enzymatic, and chemical studies with such compounds as vindoline, cleavamine, catharanthine, and their derivatives. Patterns of metabolism observed with the monomeric alkaloids would be expected to occur with the dimeric compounds. 

Clinical research can target the needs of those in economically developing nations and those who are medically underserved in the United States. Yet we must be cautious in the design and implementation of research studies to ensure that those who are the most vulnerable, whether locally or abroad, are offered the most protections and stand to gain proportionately from the studies in which they participate. Research must satisfy the needs of the population in which it is undertaken, and the products developed during the course of the research must subsequently be made reasonably available. 

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