OPEN QUESTIONS IN BIOEQUIVALENCE

Bioequivalence studies are mainly required to demonstrate the intercha ngeability of multisource pharmaceutical products, usually called gene rics. A pivotal investigation projected and conducted in compliance wi th specific guidelines allows a replicative company to register a gene ric drug via an ANDA (abbreviated new drug application) procedure. Ser ious problems are often encountered in planning and conducting these s tudies, which are not covered by operating guidelines, and call for pr otocols to be set up on a case-by-case basis. The main problems involv e the high variability of some active ingredients, how to manage basel ine with endogenous substances, drugs with a long terminal half-life, drugs under genetic polymorphic metabolism, drugs possessing stereogen ic centre(s), and drugs which cannot ethically be given to healthy vol unteers. These problems are extensively covered in this paper and, whe re appropriate, possible solutions are suggested. (C) 1995 The Italian Pharmacological Society