Q. When is a drug not a drug? A. When it is a generic. Although most critics of the pharmaceutical industry can taste the difference between brands of coffee, many assume that generic and innovator pharmaceuticals are always equivalent: claims to the contrary can be dismissed as the squabbles between fat cats and copy cats. There is more, however, to making a drug than knowing what molecules go into it: developing a pharmaceutical formulation is a delicate business involving excipients, coatings, and perhaps devices, and scale-up to manufacture is often difficult. As most sponsors know to their cost from failed “bridging studies”, substituting one formulation for another is not always straightforward. However, it seems plausible that, in most cases, if two equally pure formulations show identical concentrationagainst-time profiles of the active ingredient in the blood, they must be equivalent. Since requiring generic companies to go through the same costly development as innovator companies would restrict their ability to compete on price, regulatory agencies have generally accepted that an in-vivo “bioequivalence” study of a generic bolstered by suitable in-vitro tests can provide proof of equivalence. The standard bioequivalence study is a pharmacokinetic clinical trial in which 12 to 40 healthy volunteers are given test and reference products on separate days in an AB/BA crossover. Blood samples are taken at regular intervals and the area under the concentration-time curve (AUC), and perhaps the concentration maximum (C max ), and occasionally the time to reach a maximum (t max ) are compared. 25 years ago, failure to find a significant difference would have been accepted as proof of equivalence. However, just as an acquittal for childmolesting is not an adequate reference for a job as a babysitter, so failure to find a difference cannot be regarded as a proof of equivalence. Of course, exact equality is impossible to prove. If two drugs cannot be shown to be identical twins, they may still be blood relatives. There is now international regulatory agreement that, if the 90%