[Original brands and generic preparations]

Abstract

Background: Modern guidelines of drug approval aim at interchangeability of drugs containing the same active ingredients. Therapeutic equivalence of original and generic drugs is assumed as soon as bioequivalence is documented. For this to be accepted, first, pharmaceutical equivalence must prevail (the same amount of active substances in the same dosage forms) and, second, differences in bioavailabilities must not exceed certain limits. Drastic deviations from the original--not infrequent in the past--have become rare under the new sets of rules.

Current relevance: However, there is still room for sometimes stunning discrepancies between approved drugs, since the current procedures--mainly for economic reasons--do not cover some potentially relevant aspects: Usually, studies are performed on young, healthy, mostly male volunteers; possible effects of meals on bioavailability are not investigated and, after approval of a drug, maintenance of attested quality--as with all manufacturers--is not monitored. Moreover, the tolerated deviations from the bioavailability of the original drug are quite large; with certain substances, a change from the generic drug with the lowest bioavailability to that with the highest could mean transition from low efficacy to a toxic dose level. Documented examples include carbamazepine, phenytoin, levothyroxin, verapamil, and aspirin.

Conclusions: In conclusion, even today's sophisticated rules do not suffice to cover all eventualities. In particular, drugs with a narrow therapeutic range require close scrutiny in product selection. Pertinent are drug documentation as well as the distinguishing features of the respective manufacturers, mainly scientific support and record of product reliability. Besides the sometimes insufficient official documentation, the internet has been gaining importance as a source of information.