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Drug discovery:Backgrouand processes

Across
development of an existing, previously evaluated but unapproved active pharmaceutical ingredient for the treatment of a different disease
•Clinical proof of concept POC = right target plus right drug •Evaluate target and confirm role in the disease state
Investigational new drug application FDA must approve prior to first in human(FIH) clinical trial Contains: •Acute toxicity of drug substance in at least two species of animals • sufficient data and safety and efficacy •Implication on human pharmacology •Protocol describing clinical studies in detail •Manufacture and analysis of chemical composition •Describe the qualification of personnel
•First in human dosing to healthy volunteers •Administration of single escalating doses of drug to a small number of subjects •Short term multiple doses 10 to 15 volunteers Assess safety and PK
New potential drag intervention points that is identified as disease biology is understood (receptors, enzymes, iron channels, circulating agonists)
•First dosing to patience •Fewer dosages studied then in phase 1 •First evaluation of efficacy Safety profile and pharmacokinetics monitored •20 to 100 subject Assess proof of concept
Therapeutic index Toxic dose TD50/ dose for therapeutic response ED50
Down
use of existing approved drugs for new indications
Basic material properties In vitro cell testing In vivo animal testing
•Post marketing approval studies •Additional information about effectiveness and safety •300 to 3000 volunteers
Chemical related series that survive initial screening and their safety and efficacy is improved Structure activity relationship with chemicals structure of a current drug
Regulates pharmaceutical market Ensures human safety and efficacy
High throughput screening Competitor information Literature Academia Computer assisted drug design CADD
New drug application • proposed labelling details for the product • results and safety and efficacy of the drag • results from clinical trials • details on long-term studies and post marketing surveillance • method of manufacture of drug quality control analysis
•Test effectiveness of drug for particular indications in patients •Common effects documented and larger population •> 1000 subjects Finalise prescribing label