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| Tasks in Preclinical Development |
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| Safety evaluation |
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Toxicology |
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Multiple dose oral or i.v. studies on one rodent and one other species of 2 weeks' to 3 months' duration |
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| Mutagenicity tests |
| Reproduction toxicology |
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Safety pharmacology |
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Effects on hematology, hemodynamics, respiratory, gastrointestinal, and CNS systems |
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Pharmacokinetics |
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Basic kinetics and single dose ADME in two species; autoradiographic distribution pattern; protein binding |
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| Metabolism in vitro; toxicokinetics |
| Production |
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Drug substance scale-up |
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Scale-up from laboratory to pilot scale to produce necessary amounts for phase I under GMP conditions; last chemical conversion step should preferably be finalized |
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Formulation development |
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Formulation with suitable stability and acceptable bioavailability for phase I studies |
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