Drug development

• botanical/zoological
  • investigation of herbal remedies
  • plants, moulds and derived animal products
• serendipity
  • random discovery (e.g. penicillin)
  • unexpected properties of cuurent drugs (e.g. sulphonamide abs> sulphonylureas for DM)
• analogues of existing compounds
  • e.g. L-DOPA or insulin
  • beware of differences in pharmacokinetics and phatrmodynamics
• screening
  • "***** and hope"
  • lengthy, high risk, fewer than 1 in 100 compounds make it to market
• targeted drug design
  • new approach
• Also:
  • Gene therapy, stem cell, immunopharmacology etc

• phase I - human pharmacology (~50 ppl)
  • check toxicity and find effective dose
  • pharmacokinetic, pharmacodynamic and early metabolic studies
  • receive clinical trials exemption certificate
• phase II - therapeutic exploration (~250 ppl)
  • assess efficacy and safey on carefully monitored pt with limited numbers and scope
• phase II - therapeutic confirmation (~2000 ppl)
  • expand controlled trials
  • receive marketing authorisation ("the licence) 
• phase IV - therapeutic use
  • post-marketing trials

In total cost ~1billion Euro, takes 15 years+

• toxic ADRs (i.e. due to dose) seen Pase I-III
• idiosyncratic (non-dose related) ADRs seen as phase IV progresses

• pharmaceutical company synthesises, evaluates and trials teh drug
• licensing authority is advised based on:
  • quality
  • efficacy
  • safety
• licence granted to market the drug:
  • for specific condition
  • in a sprecific preparation
  • over a specified dose range

• commission on human medicines (CHM)
  • advises on applications for marketing authorisation
  • promotes "yellow card scheme"
  • provides advice about new safety issues
  • expert advisory groups (e.g. for paediaric drugs)
• Yellow car scheme
  • record ADRs
• black triangle
  • inverted black triangle placed on new drugs/vaccines under specific monitoring for safety, record all suspected ADRs for these drugs